PRACTICE CHANGER
Early-morning testosterone tests are necessary only for men younger than 45. Because the natural diurnal variation in testosterone levels tends to diminish with age, it is acceptable to test men ages 45 and older before 2 pm.¹

STRENGTH OF RECOMMENDATION
B: Based on a retrospective cohort study.¹

ILLUSTRATIVE CASE
You are finishing up a visit with a 62-year-old man who has erectile dysfunction (ED), and you want to evaluate for androgen deficiency. It’s already noon. Should you ask him to return for an early-morning visit so you can test his testosterone level?

Increasing public awareness of androgen deficiency has led to more men being tested for testosterone levels. Current Endocrine Society guidelines recommend against routine screening for androgen deficiency in men who do not have symptoms.² However, for men with classic symptoms of androgen deficiency—such as decreased libido, ED, infertility, depression, osteoporosis, loss of secondary sexual characteristics, or reduced muscle bulk or strength—measurement of total testosterone level is recommended.²

Due to the natural diurnal variation in serum testosterone levels, the guidelines recommend collecting the sample in the early morning.² This recommendation is based on small observational studies that included mostly men younger than 45, which found a significant difference in testosterone levels between samples drawn early in the morning and in the afternoon.^3-5

In recent years, several studies have indicated that this variation declines as men age.^4-6 Recently, researchers evaluated the effects of age and time of testing on men’s total testosterone levels.

STUDY SUMMARY
Differences in testosterone levels are significant only in younger men
Welliver et al¹ performed a retrospective review of charts from a Minneapolis Veterans Affairs hospital. They identified 2,569 men seen for ED who had total testosterone levels measured between 7 AM and 2 PM in a 15-year period. Men whose total testosterone levels were outside the normal range (> 1,000 or < 50 ng/dL) or who had total testosterone drawn after 2 PM were excluded.

The authors analyzed the results based on age, creating one group for men younger than 40 and five-year age-groups for all other men. Using scatterplot techniques, they separated each age-group into two subgroups based on draw times—7 AM to 9 AM, or 9 AM to 2 PM—and compared the mean total testosterone level for each age and time.

Participants’ mean age was 63. Younger men (< 45) had the largest variation in serum total testosterone, with a large and significant decrease after 9 AM. Only the two youngest groups (ages < 40 and 40 to 44) showed a large decrease in total testosterone in specimens collected after 9 am, compared to those drawn earlier (mean difference, 207 and 149 ng/dL, respectively). This variation was not observed in patients older than 45. Although there was a statistically significant difference between early and later testosterone levels in men ages 70 to 74, the absolute difference—34 ng/dL (452 vs 418 ng/dL)—was unlikely to be clinically significant.

WHAT’S NEW
For older men, later testing will not affect results
This study confirms previous ­research indicating that the diurnal effect on testosterone levels becomes blunted with increasing age, at least in this group of men with ED. Allowing older men to have their total testosterone levels drawn until 2 PM would allow for greater patient flexibility in draw times, with little change in results.

CAVEATS
Study’s methodology cannot account for several potential confounders
This retrospective study analyzed a single random testosterone measurement from each participant, rather than repeat testosterone levels over the course of a day. However, the study was large (2,569 men) and used mean values, which should at least partially mitigate the effect of having only a single measurement from each participant.

The study measured total testosterone and did not account for potential confounding factors—such as obesity or use of testosterone replacement therapy or androgen deprivation therapy—that could affect sex hormone binding globulin, thus potentially altering total testosterone level. However, the authors estimated that less than 2% of the entire cohort was likely to have unrecognized hormonal manipulation with exogenous gonadotropins.

All of the men in the study were seen for ED, and it is possible that men with ED have more flattening of the diurnal variation than men without ED. However, we are unaware of other data that support this.

Up to 30% of men who have a low early-morning testosterone level may have a normal result when testing is repeated.^2,5 Therefore, for all men who have low testosterone level test results, draw a repeat total testosterone level before 9 am to confirm the diagnosis. Also, this study did not evaluate the course of testosterone levels throughout the later afternoon and evening, and it remains unclear whether levels can be drawn even later in the day.

CHALLENGES TO IMPLEMENTATION
Your lab’s policies might require early-morning draws
There will probably be few barriers to implementing this change, unless local laboratory policies are inflexible regarding the timing of testosterone draws. 

REFERENCES
1. Welliver RC Jr, Wiser HJ, Brannigan RE, et al. Validity of midday total testosterone levels in older men with erectile dysfunction. J Urol. 2014;192:165-169.
2. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536-2559.
3. Cooke RR, McIntosh JE, McIntosh RP. Circadian variation in serum free and non-SHBG-bound testosterone in normal men: measurements, and simulation using a mass action model. Clin Endocrinol (Oxf). 1993;39:163-171.
4. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab. 1983;56:1278-1281.
5. Brambilla DJ, Matsumoto AM, Araujo AB, et al. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab. 2009;94:907-913.
6. Crawford ED, Barqawi AB, O’Donnell C, et al. The association of time of day and serum testosterone concentration in a large screening population. BJU Int. 2007;100:509-513.

ACKNOWLEDGEMENT 
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved. 

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(7):418-419. 

PRACTICE CHANGER
Early-morning testosterone tests are necessary only for men younger than 45. Because the natural diurnal variation in testosterone levels tends to diminish with age, it is acceptable to test men ages 45 and older before 2 pm.¹

STRENGTH OF RECOMMENDATION
B: Based on a retrospective cohort study.¹

ILLUSTRATIVE CASE
You are finishing up a visit with a 62-year-old man who has erectile dysfunction (ED), and you want to evaluate for androgen deficiency. It’s already noon. Should you ask him to return for an early-morning visit so you can test his testosterone level?

Increasing public awareness of androgen deficiency has led to more men being tested for testosterone levels. Current Endocrine Society guidelines recommend against routine screening for androgen deficiency in men who do not have symptoms.² However, for men with classic symptoms of androgen deficiency—such as decreased libido, ED, infertility, depression, osteoporosis, loss of secondary sexual characteristics, or reduced muscle bulk or strength—measurement of total testosterone level is recommended.²

Due to the natural diurnal variation in serum testosterone levels, the guidelines recommend collecting the sample in the early morning.² This recommendation is based on small observational studies that included mostly men younger than 45, which found a significant difference in testosterone levels between samples drawn early in the morning and in the afternoon.^3-5

In recent years, several studies have indicated that this variation declines as men age.^4-6 Recently, researchers evaluated the effects of age and time of testing on men’s total testosterone levels.

STUDY SUMMARY
Differences in testosterone levels are significant only in younger men
Welliver et al¹ performed a retrospective review of charts from a Minneapolis Veterans Affairs hospital. They identified 2,569 men seen for ED who had total testosterone levels measured between 7 AM and 2 PM in a 15-year period. Men whose total testosterone levels were outside the normal range (> 1,000 or < 50 ng/dL) or who had total testosterone drawn after 2 PM were excluded.

The authors analyzed the results based on age, creating one group for men younger than 40 and five-year age-groups for all other men. Using scatterplot techniques, they separated each age-group into two subgroups based on draw times—7 AM to 9 AM, or 9 AM to 2 PM—and compared the mean total testosterone level for each age and time.

Participants’ mean age was 63. Younger men (< 45) had the largest variation in serum total testosterone, with a large and significant decrease after 9 AM. Only the two youngest groups (ages < 40 and 40 to 44) showed a large decrease in total testosterone in specimens collected after 9 am, compared to those drawn earlier (mean difference, 207 and 149 ng/dL, respectively). This variation was not observed in patients older than 45. Although there was a statistically significant difference between early and later testosterone levels in men ages 70 to 74, the absolute difference—34 ng/dL (452 vs 418 ng/dL)—was unlikely to be clinically significant.

WHAT’S NEW
For older men, later testing will not affect results
This study confirms previous ­research indicating that the diurnal effect on testosterone levels becomes blunted with increasing age, at least in this group of men with ED. Allowing older men to have their total testosterone levels drawn until 2 PM would allow for greater patient flexibility in draw times, with little change in results.

CAVEATS
Study’s methodology cannot account for several potential confounders
This retrospective study analyzed a single random testosterone measurement from each participant, rather than repeat testosterone levels over the course of a day. However, the study was large (2,569 men) and used mean values, which should at least partially mitigate the effect of having only a single measurement from each participant.

The study measured total testosterone and did not account for potential confounding factors—such as obesity or use of testosterone replacement therapy or androgen deprivation therapy—that could affect sex hormone binding globulin, thus potentially altering total testosterone level. However, the authors estimated that less than 2% of the entire cohort was likely to have unrecognized hormonal manipulation with exogenous gonadotropins.

All of the men in the study were seen for ED, and it is possible that men with ED have more flattening of the diurnal variation than men without ED. However, we are unaware of other data that support this.

Up to 30% of men who have a low early-morning testosterone level may have a normal result when testing is repeated.^2,5 Therefore, for all men who have low testosterone level test results, draw a repeat total testosterone level before 9 am to confirm the diagnosis. Also, this study did not evaluate the course of testosterone levels throughout the later afternoon and evening, and it remains unclear whether levels can be drawn even later in the day.

CHALLENGES TO IMPLEMENTATION
Your lab’s policies might require early-morning draws
There will probably be few barriers to implementing this change, unless local laboratory policies are inflexible regarding the timing of testosterone draws. 

REFERENCES
1. Welliver RC Jr, Wiser HJ, Brannigan RE, et al. Validity of midday total testosterone levels in older men with erectile dysfunction. J Urol. 2014;192:165-169.
2. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536-2559.
3. Cooke RR, McIntosh JE, McIntosh RP. Circadian variation in serum free and non-SHBG-bound testosterone in normal men: measurements, and simulation using a mass action model. Clin Endocrinol (Oxf). 1993;39:163-171.
4. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab. 1983;56:1278-1281.
5. Brambilla DJ, Matsumoto AM, Araujo AB, et al. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab. 2009;94:907-913.
6. Crawford ED, Barqawi AB, O’Donnell C, et al. The association of time of day and serum testosterone concentration in a large screening population. BJU Int. 2007;100:509-513.

ACKNOWLEDGEMENT 
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved. 

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(7):418-419. 

PRACTICE CHANGER
Early-morning testosterone tests are necessary only for men younger than 45. Because the natural diurnal variation in testosterone levels tends to diminish with age, it is acceptable to test men ages 45 and older before 2 pm.¹

STRENGTH OF RECOMMENDATION
B: Based on a retrospective cohort study.¹

ILLUSTRATIVE CASE
You are finishing up a visit with a 62-year-old man who has erectile dysfunction (ED), and you want to evaluate for androgen deficiency. It’s already noon. Should you ask him to return for an early-morning visit so you can test his testosterone level?

Increasing public awareness of androgen deficiency has led to more men being tested for testosterone levels. Current Endocrine Society guidelines recommend against routine screening for androgen deficiency in men who do not have symptoms.² However, for men with classic symptoms of androgen deficiency—such as decreased libido, ED, infertility, depression, osteoporosis, loss of secondary sexual characteristics, or reduced muscle bulk or strength—measurement of total testosterone level is recommended.²

Due to the natural diurnal variation in serum testosterone levels, the guidelines recommend collecting the sample in the early morning.² This recommendation is based on small observational studies that included mostly men younger than 45, which found a significant difference in testosterone levels between samples drawn early in the morning and in the afternoon.^3-5

In recent years, several studies have indicated that this variation declines as men age.^4-6 Recently, researchers evaluated the effects of age and time of testing on men’s total testosterone levels.

STUDY SUMMARY
Differences in testosterone levels are significant only in younger men
Welliver et al¹ performed a retrospective review of charts from a Minneapolis Veterans Affairs hospital. They identified 2,569 men seen for ED who had total testosterone levels measured between 7 AM and 2 PM in a 15-year period. Men whose total testosterone levels were outside the normal range (> 1,000 or < 50 ng/dL) or who had total testosterone drawn after 2 PM were excluded.

The authors analyzed the results based on age, creating one group for men younger than 40 and five-year age-groups for all other men. Using scatterplot techniques, they separated each age-group into two subgroups based on draw times—7 AM to 9 AM, or 9 AM to 2 PM—and compared the mean total testosterone level for each age and time.

Participants’ mean age was 63. Younger men (< 45) had the largest variation in serum total testosterone, with a large and significant decrease after 9 AM. Only the two youngest groups (ages < 40 and 40 to 44) showed a large decrease in total testosterone in specimens collected after 9 am, compared to those drawn earlier (mean difference, 207 and 149 ng/dL, respectively). This variation was not observed in patients older than 45. Although there was a statistically significant difference between early and later testosterone levels in men ages 70 to 74, the absolute difference—34 ng/dL (452 vs 418 ng/dL)—was unlikely to be clinically significant.

WHAT’S NEW
For older men, later testing will not affect results
This study confirms previous ­research indicating that the diurnal effect on testosterone levels becomes blunted with increasing age, at least in this group of men with ED. Allowing older men to have their total testosterone levels drawn until 2 PM would allow for greater patient flexibility in draw times, with little change in results.

CAVEATS
Study’s methodology cannot account for several potential confounders
This retrospective study analyzed a single random testosterone measurement from each participant, rather than repeat testosterone levels over the course of a day. However, the study was large (2,569 men) and used mean values, which should at least partially mitigate the effect of having only a single measurement from each participant.

The study measured total testosterone and did not account for potential confounding factors—such as obesity or use of testosterone replacement therapy or androgen deprivation therapy—that could affect sex hormone binding globulin, thus potentially altering total testosterone level. However, the authors estimated that less than 2% of the entire cohort was likely to have unrecognized hormonal manipulation with exogenous gonadotropins.

All of the men in the study were seen for ED, and it is possible that men with ED have more flattening of the diurnal variation than men without ED. However, we are unaware of other data that support this.

Up to 30% of men who have a low early-morning testosterone level may have a normal result when testing is repeated.^2,5 Therefore, for all men who have low testosterone level test results, draw a repeat total testosterone level before 9 am to confirm the diagnosis. Also, this study did not evaluate the course of testosterone levels throughout the later afternoon and evening, and it remains unclear whether levels can be drawn even later in the day.

CHALLENGES TO IMPLEMENTATION
Your lab’s policies might require early-morning draws
There will probably be few barriers to implementing this change, unless local laboratory policies are inflexible regarding the timing of testosterone draws. 

REFERENCES
1. Welliver RC Jr, Wiser HJ, Brannigan RE, et al. Validity of midday total testosterone levels in older men with erectile dysfunction. J Urol. 2014;192:165-169.
2. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536-2559.
3. Cooke RR, McIntosh JE, McIntosh RP. Circadian variation in serum free and non-SHBG-bound testosterone in normal men: measurements, and simulation using a mass action model. Clin Endocrinol (Oxf). 1993;39:163-171.
4. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab. 1983;56:1278-1281.
5. Brambilla DJ, Matsumoto AM, Araujo AB, et al. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab. 2009;94:907-913.
6. Crawford ED, Barqawi AB, O’Donnell C, et al. The association of time of day and serum testosterone concentration in a large screening population. BJU Int. 2007;100:509-513.

ACKNOWLEDGEMENT 
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved. 

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(7):418-419. 

In this issue, Dr. Onysko discusses “alternative” pharmacologic approaches to painful peripheral neuropathy. (See “Targeting neuropathic pain: Consider these alternatives.”) Because so many of our patients use alternative therapies, I contend that alternative therapies are no longer “alternative.” Even the federal government has officially recognized the widespread use of alternative therapies by changing the name of the National Center for Complementary and Alternative Medicine in December 2014 to the National Center for Complementary and Integrative Health.

Alternative medicine had a bad name in mainstream medicine until 1991, when the National Institutes of Health established the Office of Alternative Medicine, officially recognizing that some alternative treatments might have a scientific basis and true therapeutic effects beyond the placebo effect. Over the years, hundreds of randomized controlled trials (RCTs) have emerged to investigate the value of various herbal treatments, vitamin therapies, magnet therapy, acupuncture, tai chi, aromatherapy, and other physical medicine and medicinal treatment modalities.

Last spring, as I prepared an evidence-based medicine talk, I was struck by the solid evidence supporting numerous therapies we used to consider alternative. Many trials of acupuncture, for instance, have shown positive effects for various musculoskeletal problems. But acupuncture is also effective for functional dyspepsia, according to a well-designed RCT.¹ In addition, it can relieve symptoms of irritable bowel syndrome (IBS), according to a Cochrane meta-analysis of 17 RCTs.²

We can now count acupuncture among the evidence-based treatment options for conditions such as functional dyspepsia and IBS.

One of the new kids on the block in alternative medicine is functional medicine, founded by nutritionist/biochemist Jeff Bland. According to the Institute of Functional Medicine Web site, functional medicine is a combination of holistic medicine principles and a belief that we can treat a wide variety of ailments with various dietary treatments, including supplements.³ Although research on the interaction between gut flora and human health is burgeoning, I’m wary of claims of effectiveness until we see evidence of improved patient-oriented outcomes from well-executed RCTs.

I’m keeping an open mind, however, about all forms of complementary and integrative therapies. After all, who would have guessed 30 years ago that peptic ulcer disease could be cured with antibiotics?

In this issue, Dr. Onysko discusses “alternative” pharmacologic approaches to painful peripheral neuropathy. (See “Targeting neuropathic pain: Consider these alternatives.”) Because so many of our patients use alternative therapies, I contend that alternative therapies are no longer “alternative.” Even the federal government has officially recognized the widespread use of alternative therapies by changing the name of the National Center for Complementary and Alternative Medicine in December 2014 to the National Center for Complementary and Integrative Health.

Alternative medicine had a bad name in mainstream medicine until 1991, when the National Institutes of Health established the Office of Alternative Medicine, officially recognizing that some alternative treatments might have a scientific basis and true therapeutic effects beyond the placebo effect. Over the years, hundreds of randomized controlled trials (RCTs) have emerged to investigate the value of various herbal treatments, vitamin therapies, magnet therapy, acupuncture, tai chi, aromatherapy, and other physical medicine and medicinal treatment modalities.

Last spring, as I prepared an evidence-based medicine talk, I was struck by the solid evidence supporting numerous therapies we used to consider alternative. Many trials of acupuncture, for instance, have shown positive effects for various musculoskeletal problems. But acupuncture is also effective for functional dyspepsia, according to a well-designed RCT.¹ In addition, it can relieve symptoms of irritable bowel syndrome (IBS), according to a Cochrane meta-analysis of 17 RCTs.²

We can now count acupuncture among the evidence-based treatment options for conditions such as functional dyspepsia and IBS.

One of the new kids on the block in alternative medicine is functional medicine, founded by nutritionist/biochemist Jeff Bland. According to the Institute of Functional Medicine Web site, functional medicine is a combination of holistic medicine principles and a belief that we can treat a wide variety of ailments with various dietary treatments, including supplements.³ Although research on the interaction between gut flora and human health is burgeoning, I’m wary of claims of effectiveness until we see evidence of improved patient-oriented outcomes from well-executed RCTs.

I’m keeping an open mind, however, about all forms of complementary and integrative therapies. After all, who would have guessed 30 years ago that peptic ulcer disease could be cured with antibiotics?

In this issue, Dr. Onysko discusses “alternative” pharmacologic approaches to painful peripheral neuropathy. (See “Targeting neuropathic pain: Consider these alternatives.”) Because so many of our patients use alternative therapies, I contend that alternative therapies are no longer “alternative.” Even the federal government has officially recognized the widespread use of alternative therapies by changing the name of the National Center for Complementary and Alternative Medicine in December 2014 to the National Center for Complementary and Integrative Health.

Alternative medicine had a bad name in mainstream medicine until 1991, when the National Institutes of Health established the Office of Alternative Medicine, officially recognizing that some alternative treatments might have a scientific basis and true therapeutic effects beyond the placebo effect. Over the years, hundreds of randomized controlled trials (RCTs) have emerged to investigate the value of various herbal treatments, vitamin therapies, magnet therapy, acupuncture, tai chi, aromatherapy, and other physical medicine and medicinal treatment modalities.

Last spring, as I prepared an evidence-based medicine talk, I was struck by the solid evidence supporting numerous therapies we used to consider alternative. Many trials of acupuncture, for instance, have shown positive effects for various musculoskeletal problems. But acupuncture is also effective for functional dyspepsia, according to a well-designed RCT.¹ In addition, it can relieve symptoms of irritable bowel syndrome (IBS), according to a Cochrane meta-analysis of 17 RCTs.²

We can now count acupuncture among the evidence-based treatment options for conditions such as functional dyspepsia and IBS.

One of the new kids on the block in alternative medicine is functional medicine, founded by nutritionist/biochemist Jeff Bland. According to the Institute of Functional Medicine Web site, functional medicine is a combination of holistic medicine principles and a belief that we can treat a wide variety of ailments with various dietary treatments, including supplements.³ Although research on the interaction between gut flora and human health is burgeoning, I’m wary of claims of effectiveness until we see evidence of improved patient-oriented outcomes from well-executed RCTs.

I’m keeping an open mind, however, about all forms of complementary and integrative therapies. After all, who would have guessed 30 years ago that peptic ulcer disease could be cured with antibiotics?

1. The patient has a long-standing pruritic rash. Flat, slightly elevated, greasy brown papules are scattered on the chest, abdomen, and ­upper back, with mild surrounding erythema. The fingernails are deformed, with longitudinal red streaks and ridges and v-shaped notching of the free margin.
Reprinted with permission from Cutis. 2003;72:124-126.

Diagnosis: Darier disease (DD) or Darier-White disease is a rare genetic skin disorder caused by mutations of the ATP2A2 gene, located on the long arm of chromosome 12 at position 24,11.^1,2 This genetic mutation is inherited as an autosomal dominant trait with complete penetrance. DD affects men and women equally, with progressive skin signs of interfamilial and intrafamilial variability.³ Skin manifestations occur from late childhood to early adulthood and are typical during adolescence.³ Acute flare-ups can be triggered by heat, perspiration, sunlight, ultraviolet B exposure, stress, or certain medications (in particular, lithium).² DD is not contagious.²

1. Creamer D, Barker J, Kerdel FA. Papular and papulosquamous dermatoses. In: Acute Adult Dermatology: Diagnosis and Management (A Colour Handbook). London, UK: Manson Publishing Ltd; 2011:48.

2. Kelly EB. Darier disease (DAR). In: Encyclopedia of Human Genetics and Disease. Santa Barbara, CA: ABC-CLIO; 2013:186-187.

3. Ringpfeil F. Dermatologic disorders. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:101.

For more information on this case, see “Man, 45, With Greasy Rash and Deformed Nails.” Clin Rev. 2014;24(1):38,40-41

For the next photograph, proceed to the next page >>

2. Six months ago, this 36-year-old man’s left fourth finger began to bother him. He’s tried topical antibiotics, colloidal silver solution, and two different oral antibiotics. None have relieved the pain, which is severe enough to interfere with daily activity—particularly his job, which requires extensive computer time.

Diagnosis: “Infection” is only one potential cause of redness, swelling, increased warmth, and localized pain. Classically termed rubor, tumor, calor, and dolor, these are indicators of inflammation, which can occur in many conditions besides “infection.” In the case described, a simple hangnail was incompletely removed, leaving a shard of nail that then dug into the perionychial skin as it grew out. This set into motion a healing process that could not proceed to resolution, because the tissue was re-injured every time the finger struck the computer keyboard. This not only caused the wound to get stuck in a certain phase of healing (angioneogenesis) but also prevented completion of the process.

For more information on this case, see “Red and Swollen Doesn’t Mean “Infection.” Clin Rev. 2014;24(6):W1.

For the next photograph, proceed to the next page >>

3. A 25-year-old man presents with what he describes as a “fungal infection” of the fingernails that he’s had since birth. The nails are uniformly thickened and dystrophic, without significant discoloration. The patient’s palms and soles are hyperkeratotic, and the upper anterior legs are covered by a folliculocentric papular hyperkeratosis reminiscent of a coarse keratosis pilaris.

Diagnosis: Pachyonychia congenita (PC) is a rare condition that represents a mutation of keratin genes and is usually of autosomal dominant inheritance. First described by Muller in 1904, it was eventually categorized into one of two types: type I, MIM 167200, also known as Jadassohn-Lewandowsky, the most common type, and type II, MIM 167210, also known as Jackson-Lawler, with slightly different features. Today, a more common view is that no such divisions exist—only variations of PC that exhibit overlapping features.

For more information on this case, see “A fingernail "infection" present since birth.” Clin Rev. 2013;23(4):W6.

For the next photograph, proceed to the next page >>

4. Usually apparent at birth, this disorder may manifest with abnormal or missing nails. Characteristic nail changes include triangular lunulae and, most prominently on the thumb and index fingers, hypoplasia. Also apparent are orthopedic changes (particularly affecting the knees and elbows), renal disease, and glaucoma.

Reprinted with permission from Cutis. 2000;66:71, 75-76.

Diagnosis: The osteo-onychodysplasia, or nail-patella syndrome, is an autosomal dominant disorder. Studies have linked the syndrome to chromosome 9q34 and identified point mutations in the LMX1B gene.⁴ Other kindreds have been linked to chromosome 17q21-22.⁵ Prenatal diagnosis is possible, including noninvasive prenatal diagnosis using ultrasonography. Because of the risk for glaucoma, all family members should be screened by an ophthalmologist.⁶

4. Seri M, Melchionda S, Dreyer S, et al. Identification of LMX1B gene point mutations in Italian patients affected with nail-patella syndrome. Int J Mol Med. 1999;4:285-290.

5. Mangino M, Sanchez O, Torrente I, et al. Localization of a gene for familial patella aplasia-hypoplasia (PTLAH) to chromosome 17q21-22. Am J Hum Genetics. 1999;65:441-447.

6. Lichter PR, Richards JE, Downs CA, et al. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol. 1997;124:506-515.

For more information on this case, see “What Is Your Diagnosis? Nail-Patella Syndrome.” Cutis. 2000;66:71, 75-76.

1. The patient has a long-standing pruritic rash. Flat, slightly elevated, greasy brown papules are scattered on the chest, abdomen, and ­upper back, with mild surrounding erythema. The fingernails are deformed, with longitudinal red streaks and ridges and v-shaped notching of the free margin.
Reprinted with permission from Cutis. 2003;72:124-126.

Diagnosis: Darier disease (DD) or Darier-White disease is a rare genetic skin disorder caused by mutations of the ATP2A2 gene, located on the long arm of chromosome 12 at position 24,11.^1,2 This genetic mutation is inherited as an autosomal dominant trait with complete penetrance. DD affects men and women equally, with progressive skin signs of interfamilial and intrafamilial variability.³ Skin manifestations occur from late childhood to early adulthood and are typical during adolescence.³ Acute flare-ups can be triggered by heat, perspiration, sunlight, ultraviolet B exposure, stress, or certain medications (in particular, lithium).² DD is not contagious.²

1. Creamer D, Barker J, Kerdel FA. Papular and papulosquamous dermatoses. In: Acute Adult Dermatology: Diagnosis and Management (A Colour Handbook). London, UK: Manson Publishing Ltd; 2011:48.

2. Kelly EB. Darier disease (DAR). In: Encyclopedia of Human Genetics and Disease. Santa Barbara, CA: ABC-CLIO; 2013:186-187.

3. Ringpfeil F. Dermatologic disorders. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:101.

For more information on this case, see “Man, 45, With Greasy Rash and Deformed Nails.” Clin Rev. 2014;24(1):38,40-41

For the next photograph, proceed to the next page >>

2. Six months ago, this 36-year-old man’s left fourth finger began to bother him. He’s tried topical antibiotics, colloidal silver solution, and two different oral antibiotics. None have relieved the pain, which is severe enough to interfere with daily activity—particularly his job, which requires extensive computer time.

Diagnosis: “Infection” is only one potential cause of redness, swelling, increased warmth, and localized pain. Classically termed rubor, tumor, calor, and dolor, these are indicators of inflammation, which can occur in many conditions besides “infection.” In the case described, a simple hangnail was incompletely removed, leaving a shard of nail that then dug into the perionychial skin as it grew out. This set into motion a healing process that could not proceed to resolution, because the tissue was re-injured every time the finger struck the computer keyboard. This not only caused the wound to get stuck in a certain phase of healing (angioneogenesis) but also prevented completion of the process.

For more information on this case, see “Red and Swollen Doesn’t Mean “Infection.” Clin Rev. 2014;24(6):W1.

For the next photograph, proceed to the next page >>

3. A 25-year-old man presents with what he describes as a “fungal infection” of the fingernails that he’s had since birth. The nails are uniformly thickened and dystrophic, without significant discoloration. The patient’s palms and soles are hyperkeratotic, and the upper anterior legs are covered by a folliculocentric papular hyperkeratosis reminiscent of a coarse keratosis pilaris.

Diagnosis: Pachyonychia congenita (PC) is a rare condition that represents a mutation of keratin genes and is usually of autosomal dominant inheritance. First described by Muller in 1904, it was eventually categorized into one of two types: type I, MIM 167200, also known as Jadassohn-Lewandowsky, the most common type, and type II, MIM 167210, also known as Jackson-Lawler, with slightly different features. Today, a more common view is that no such divisions exist—only variations of PC that exhibit overlapping features.

For more information on this case, see “A fingernail "infection" present since birth.” Clin Rev. 2013;23(4):W6.

For the next photograph, proceed to the next page >>

4. Usually apparent at birth, this disorder may manifest with abnormal or missing nails. Characteristic nail changes include triangular lunulae and, most prominently on the thumb and index fingers, hypoplasia. Also apparent are orthopedic changes (particularly affecting the knees and elbows), renal disease, and glaucoma.

Reprinted with permission from Cutis. 2000;66:71, 75-76.

Diagnosis: The osteo-onychodysplasia, or nail-patella syndrome, is an autosomal dominant disorder. Studies have linked the syndrome to chromosome 9q34 and identified point mutations in the LMX1B gene.⁴ Other kindreds have been linked to chromosome 17q21-22.⁵ Prenatal diagnosis is possible, including noninvasive prenatal diagnosis using ultrasonography. Because of the risk for glaucoma, all family members should be screened by an ophthalmologist.⁶

4. Seri M, Melchionda S, Dreyer S, et al. Identification of LMX1B gene point mutations in Italian patients affected with nail-patella syndrome. Int J Mol Med. 1999;4:285-290.

5. Mangino M, Sanchez O, Torrente I, et al. Localization of a gene for familial patella aplasia-hypoplasia (PTLAH) to chromosome 17q21-22. Am J Hum Genetics. 1999;65:441-447.

6. Lichter PR, Richards JE, Downs CA, et al. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol. 1997;124:506-515.

For more information on this case, see “What Is Your Diagnosis? Nail-Patella Syndrome.” Cutis. 2000;66:71, 75-76.

1. The patient has a long-standing pruritic rash. Flat, slightly elevated, greasy brown papules are scattered on the chest, abdomen, and ­upper back, with mild surrounding erythema. The fingernails are deformed, with longitudinal red streaks and ridges and v-shaped notching of the free margin.
Reprinted with permission from Cutis. 2003;72:124-126.

Diagnosis: Darier disease (DD) or Darier-White disease is a rare genetic skin disorder caused by mutations of the ATP2A2 gene, located on the long arm of chromosome 12 at position 24,11.^1,2 This genetic mutation is inherited as an autosomal dominant trait with complete penetrance. DD affects men and women equally, with progressive skin signs of interfamilial and intrafamilial variability.³ Skin manifestations occur from late childhood to early adulthood and are typical during adolescence.³ Acute flare-ups can be triggered by heat, perspiration, sunlight, ultraviolet B exposure, stress, or certain medications (in particular, lithium).² DD is not contagious.²

1. Creamer D, Barker J, Kerdel FA. Papular and papulosquamous dermatoses. In: Acute Adult Dermatology: Diagnosis and Management (A Colour Handbook). London, UK: Manson Publishing Ltd; 2011:48.

2. Kelly EB. Darier disease (DAR). In: Encyclopedia of Human Genetics and Disease. Santa Barbara, CA: ABC-CLIO; 2013:186-187.

3. Ringpfeil F. Dermatologic disorders. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:101.

For more information on this case, see “Man, 45, With Greasy Rash and Deformed Nails.” Clin Rev. 2014;24(1):38,40-41

For the next photograph, proceed to the next page >>

2. Six months ago, this 36-year-old man’s left fourth finger began to bother him. He’s tried topical antibiotics, colloidal silver solution, and two different oral antibiotics. None have relieved the pain, which is severe enough to interfere with daily activity—particularly his job, which requires extensive computer time.

Diagnosis: “Infection” is only one potential cause of redness, swelling, increased warmth, and localized pain. Classically termed rubor, tumor, calor, and dolor, these are indicators of inflammation, which can occur in many conditions besides “infection.” In the case described, a simple hangnail was incompletely removed, leaving a shard of nail that then dug into the perionychial skin as it grew out. This set into motion a healing process that could not proceed to resolution, because the tissue was re-injured every time the finger struck the computer keyboard. This not only caused the wound to get stuck in a certain phase of healing (angioneogenesis) but also prevented completion of the process.

For more information on this case, see “Red and Swollen Doesn’t Mean “Infection.” Clin Rev. 2014;24(6):W1.

For the next photograph, proceed to the next page >>

3. A 25-year-old man presents with what he describes as a “fungal infection” of the fingernails that he’s had since birth. The nails are uniformly thickened and dystrophic, without significant discoloration. The patient’s palms and soles are hyperkeratotic, and the upper anterior legs are covered by a folliculocentric papular hyperkeratosis reminiscent of a coarse keratosis pilaris.

Diagnosis: Pachyonychia congenita (PC) is a rare condition that represents a mutation of keratin genes and is usually of autosomal dominant inheritance. First described by Muller in 1904, it was eventually categorized into one of two types: type I, MIM 167200, also known as Jadassohn-Lewandowsky, the most common type, and type II, MIM 167210, also known as Jackson-Lawler, with slightly different features. Today, a more common view is that no such divisions exist—only variations of PC that exhibit overlapping features.

For more information on this case, see “A fingernail "infection" present since birth.” Clin Rev. 2013;23(4):W6.

For the next photograph, proceed to the next page >>

4. Usually apparent at birth, this disorder may manifest with abnormal or missing nails. Characteristic nail changes include triangular lunulae and, most prominently on the thumb and index fingers, hypoplasia. Also apparent are orthopedic changes (particularly affecting the knees and elbows), renal disease, and glaucoma.

Reprinted with permission from Cutis. 2000;66:71, 75-76.

Diagnosis: The osteo-onychodysplasia, or nail-patella syndrome, is an autosomal dominant disorder. Studies have linked the syndrome to chromosome 9q34 and identified point mutations in the LMX1B gene.⁴ Other kindreds have been linked to chromosome 17q21-22.⁵ Prenatal diagnosis is possible, including noninvasive prenatal diagnosis using ultrasonography. Because of the risk for glaucoma, all family members should be screened by an ophthalmologist.⁶

4. Seri M, Melchionda S, Dreyer S, et al. Identification of LMX1B gene point mutations in Italian patients affected with nail-patella syndrome. Int J Mol Med. 1999;4:285-290.

5. Mangino M, Sanchez O, Torrente I, et al. Localization of a gene for familial patella aplasia-hypoplasia (PTLAH) to chromosome 17q21-22. Am J Hum Genetics. 1999;65:441-447.

6. Lichter PR, Richards JE, Downs CA, et al. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol. 1997;124:506-515.

For more information on this case, see “What Is Your Diagnosis? Nail-Patella Syndrome.” Cutis. 2000;66:71, 75-76.

ANSWER
The correct answer is lichen striatus (choice “d”), a rare, self-limited condition usually seen on the extremities of children. It will be discussed further in the next  section.

The differential for lichen striatus includes psoriasis (choice “a”). However, typical psoriatic lesions would not assume this configuration and would likely manifest with other corroborative areas of involvement.

Eczema (choice “b”) is certainly common in children, but it is unlikely to be relegated to one linear area. The same can be said of pityriasis rosea (choice “c”).

DISCUSSION 
Lichen striatus, also known as Blaschko linear acquired skin inflammation, is an unusual self-limited condition of unknown etiology seen mostly on the extremities of children ages 3 to 10. More common on legs than on arms, it can occasionally appear on the face.

Its linear configuration is instantly diagnostic: The lesion typically follows the Blaschko lines, which represent a segmental clone of cutaneous cells deposited at an embryonic stage of development.

As seen in this case, post­inflammatory hypopigmentation is common. In a minority of cases, the condition can involve the entire length of the extremity—even the digits, where it can lead to dystrophy of the affected nail. It almost always resolves within a few weeks to months, with or without treatment (which is limited to symptom relief).

Several potential causes of lichen striatus have been posited. The most convincing theory is a possible connection with human herpesviruses 6 and 7, which are also triggers for pityriasis rosea. There have been cases in which both conditions are present, ­producing somewhat similar microscopic changes in the skin (and both resolving without ­treatment). Additional items in the differential include lichen planus, lichen nitidus, and warts.

TREATMENT
For most cases of lichen striatus, treatment is supportive: topical steroids for the itching, which is seldom severe. Given the self-limited but prolonged nature of the problem, patient education is the more important component; these days, there are web-based sources to which you can direct your patients for reliable information, including the Mayo Clinic and the American Academy of Dermatology.

ANSWER
The correct answer is lichen striatus (choice “d”), a rare, self-limited condition usually seen on the extremities of children. It will be discussed further in the next  section.

The differential for lichen striatus includes psoriasis (choice “a”). However, typical psoriatic lesions would not assume this configuration and would likely manifest with other corroborative areas of involvement.

Eczema (choice “b”) is certainly common in children, but it is unlikely to be relegated to one linear area. The same can be said of pityriasis rosea (choice “c”).

DISCUSSION 
Lichen striatus, also known as Blaschko linear acquired skin inflammation, is an unusual self-limited condition of unknown etiology seen mostly on the extremities of children ages 3 to 10. More common on legs than on arms, it can occasionally appear on the face.

Its linear configuration is instantly diagnostic: The lesion typically follows the Blaschko lines, which represent a segmental clone of cutaneous cells deposited at an embryonic stage of development.

As seen in this case, post­inflammatory hypopigmentation is common. In a minority of cases, the condition can involve the entire length of the extremity—even the digits, where it can lead to dystrophy of the affected nail. It almost always resolves within a few weeks to months, with or without treatment (which is limited to symptom relief).

Several potential causes of lichen striatus have been posited. The most convincing theory is a possible connection with human herpesviruses 6 and 7, which are also triggers for pityriasis rosea. There have been cases in which both conditions are present, ­producing somewhat similar microscopic changes in the skin (and both resolving without ­treatment). Additional items in the differential include lichen planus, lichen nitidus, and warts.

TREATMENT
For most cases of lichen striatus, treatment is supportive: topical steroids for the itching, which is seldom severe. Given the self-limited but prolonged nature of the problem, patient education is the more important component; these days, there are web-based sources to which you can direct your patients for reliable information, including the Mayo Clinic and the American Academy of Dermatology.

ANSWER
The correct answer is lichen striatus (choice “d”), a rare, self-limited condition usually seen on the extremities of children. It will be discussed further in the next  section.

The differential for lichen striatus includes psoriasis (choice “a”). However, typical psoriatic lesions would not assume this configuration and would likely manifest with other corroborative areas of involvement.

Eczema (choice “b”) is certainly common in children, but it is unlikely to be relegated to one linear area. The same can be said of pityriasis rosea (choice “c”).

DISCUSSION 
Lichen striatus, also known as Blaschko linear acquired skin inflammation, is an unusual self-limited condition of unknown etiology seen mostly on the extremities of children ages 3 to 10. More common on legs than on arms, it can occasionally appear on the face.

Its linear configuration is instantly diagnostic: The lesion typically follows the Blaschko lines, which represent a segmental clone of cutaneous cells deposited at an embryonic stage of development.

As seen in this case, post­inflammatory hypopigmentation is common. In a minority of cases, the condition can involve the entire length of the extremity—even the digits, where it can lead to dystrophy of the affected nail. It almost always resolves within a few weeks to months, with or without treatment (which is limited to symptom relief).

Several potential causes of lichen striatus have been posited. The most convincing theory is a possible connection with human herpesviruses 6 and 7, which are also triggers for pityriasis rosea. There have been cases in which both conditions are present, ­producing somewhat similar microscopic changes in the skin (and both resolving without ­treatment). Additional items in the differential include lichen planus, lichen nitidus, and warts.

TREATMENT
For most cases of lichen striatus, treatment is supportive: topical steroids for the itching, which is seldom severe. Given the self-limited but prolonged nature of the problem, patient education is the more important component; these days, there are web-based sources to which you can direct your patients for reliable information, including the Mayo Clinic and the American Academy of Dermatology.

ANSWER
The correct interpretation of this ECG is atrial fibrillation with a rapid ventricular response and aberrantly conducted QRS complexes. The latter were misinterpreted as ventricular tachycardia. Although they represent a wide complex at a rate of more than 100 beats/min, the rhythm is irregular and the intrinsic (initial) inflection of normally conducted and aberrant beats is the same. (See lead I rhythm strip at bottom.)

What is unusual (and doesn’t make sense) regarding this ECG is the machine’s reading of the PR interval (128 ms) and the QRS duration (88 ms). For one thing, there is no measurable PR interval. And for another, the measured QRS duration accounts for the normally conducted complex and not the aberrantly conducted ones.

The technician was reassured, and the patient underwent successful cardioversion back to normal sinus rhythm. 

ANSWER
The correct interpretation of this ECG is atrial fibrillation with a rapid ventricular response and aberrantly conducted QRS complexes. The latter were misinterpreted as ventricular tachycardia. Although they represent a wide complex at a rate of more than 100 beats/min, the rhythm is irregular and the intrinsic (initial) inflection of normally conducted and aberrant beats is the same. (See lead I rhythm strip at bottom.)

What is unusual (and doesn’t make sense) regarding this ECG is the machine’s reading of the PR interval (128 ms) and the QRS duration (88 ms). For one thing, there is no measurable PR interval. And for another, the measured QRS duration accounts for the normally conducted complex and not the aberrantly conducted ones.

The technician was reassured, and the patient underwent successful cardioversion back to normal sinus rhythm. 

ANSWER
The correct interpretation of this ECG is atrial fibrillation with a rapid ventricular response and aberrantly conducted QRS complexes. The latter were misinterpreted as ventricular tachycardia. Although they represent a wide complex at a rate of more than 100 beats/min, the rhythm is irregular and the intrinsic (initial) inflection of normally conducted and aberrant beats is the same. (See lead I rhythm strip at bottom.)

What is unusual (and doesn’t make sense) regarding this ECG is the machine’s reading of the PR interval (128 ms) and the QRS duration (88 ms). For one thing, there is no measurable PR interval. And for another, the measured QRS duration accounts for the normally conducted complex and not the aberrantly conducted ones.

The technician was reassured, and the patient underwent successful cardioversion back to normal sinus rhythm. 

ANSWER
The radiograph shows complete opacification of the left hemithorax. The differential includes total atelectasis of the lung, mucus plug within the left bronchus, or possible blood or fluid collection. Of note, the patient has a catheter within the left subclavian vein, the distal tip of which appears to be in an unusual location. In this case, it was determined that the displaced catheter tip, resulting in hemothorax, was the etiology. The line was removed, and urgent cardiothoracic consultation was obtained. A left chest tube was promptly placed, with a resultant 2 L of immediate output. The patient improved clinically as well.

ANSWER
The radiograph shows complete opacification of the left hemithorax. The differential includes total atelectasis of the lung, mucus plug within the left bronchus, or possible blood or fluid collection. Of note, the patient has a catheter within the left subclavian vein, the distal tip of which appears to be in an unusual location. In this case, it was determined that the displaced catheter tip, resulting in hemothorax, was the etiology. The line was removed, and urgent cardiothoracic consultation was obtained. A left chest tube was promptly placed, with a resultant 2 L of immediate output. The patient improved clinically as well.

ANSWER
The radiograph shows complete opacification of the left hemithorax. The differential includes total atelectasis of the lung, mucus plug within the left bronchus, or possible blood or fluid collection. Of note, the patient has a catheter within the left subclavian vein, the distal tip of which appears to be in an unusual location. In this case, it was determined that the displaced catheter tip, resulting in hemothorax, was the etiology. The line was removed, and urgent cardiothoracic consultation was obtained. A left chest tube was promptly placed, with a resultant 2 L of immediate output. The patient improved clinically as well.

A 63-year-old Hispanic wom­an was referred to endocrinology by her primary care provider for uncontrolled type 2 diabetes mellitus (T2DM), which was diagnosed 16 years ago. Her antidiabetic medications included insulin glargine (55 U bid), metformin (1,000 mg bid), and glipizide (10 mg bid). She also had known dyslipidemia, hypertension, and depression. There was a history of poorly controlled glucose (A1C between 9% and 13% in the past three years).

This was a relatively common new patient consult in our endocrine clinic. Upon entering the room, I was greeted by the patient and two family members. I quickly noticed the patient’s facial plethora and central obesity with comparatively thin extremities. Further inquiry revealed that the greatest challenge for the patient and her family was her bouts of severe depression, during which she would stop caring and cease to take her medications.

During the physical exam, mild but not significant supraclavicular and dorsocervical fat pads were appreciated. The exam was otherwise unremarkable, with no purple striae on the torso, abdomen, breasts, and extremities.

In addition to routine diabetes lab tests (ie, A1C, chemistry panel, lipid panel, urine microalbumin-to-creatinine ratio), an overnight 1-mg oral dexamethasone suppression test was ordered. Results of the latter were abnormal, and further workup confirmed Cushing disease (see Table 1 for results). The patient was referred for neurosurgery.

Continue for Discussion >>

DISCUSSION: SECONDARY DIABETES
It is well known that the prevalence of diabetes is skyrocketing, and medical offices are filled with affected patients. According to a 2011 report from the CDC, 90% to 95% of all diabetes cases are type 2, 5% are type 1 (autoimmune), and the rest (about 1% to 5%) are “other types” of diabetes.³ Due to these disproportionate statistics, clinicians often overlook the possibility of uncommon etiologies and assume all patients with diabetes have type 2—especially when the patient is overweight or obese.

Table 2 lists conditions and medications that may contribute to significant hyperglycemia.⁴ Some contributors are rather obvious (eg, status post pancreatectomy) or have no impact on treatment strategy (eg, chromosomal defects such as Down or Turner syndrome). However, certain conditions, such as Cushing syndrome, acromegaly, and hemochromatosis, can be relatively hard to recognize due to the variable rate of clinical manifestation, especially in the earlier stages of the disease. Experts have raised concerns that the prevalence of secondary diabetes (1% to 5%) may actually be underestimated due to “misdiagnosis” as T2DM. 

Early detection of the underlying disorder, followed by initiation of appropriate treatment, is critical. It will not only improve but also may resolve the patient’s hyperglycemia, and it may also reverse or stop the damage to other vital organs.

The case patient had an unfortunate situation in which her Cushing syndrome was masked by commonly encountered diagnoses of hypertension, T2DM, obesity, and depression. Cushing is an easy diagnosis to miss, since it has an insidious onset and it can take more than five years for some of the physical findings to become evident.

Pancreatic cancer is another uncommon but critical disease worth mentioning. Pancreatic cancer should be in the differential diagnosis for previously eu­glycemic patients who experience abrupt elevation of glucose or previously well-managed patients whose glucose values quickly get out of control without obvious cause (eg, medication cessation, addition of glucocorticoid therapy, uncontrolled diet).

In our practice, we have encountered three patients with pancreatic cancer in this setting. The only sign was a sudden rise in glucose (300 to 500 mg/dL throughout the day) in patients whose A1C had been low (in the 6% range) with one or two oral medications. Thorough history taking did not reveal any potential causes for sudden hyperglycemia. Only one patient had a palpable mass on abdominal exam and elevated liver enzymes and bilirubin. Unfortunately, that patient died eight months later. The other two had favorable outcomes from surgery and chemotherapy. Early detection was the key for those two patients.

Next page: Conclusion >>

CONCLUSION 
Since the majority of patients with diabetes have T2DM, it is easy to “default” and start treating all patients as such, especially if they are overweight or obese. However, up to 5% of patients actually have underlying disease that may cause or worsen their diabetic status. Overlooking these rare conditions can be detrimental to the patient, as it will adversely affect not only glycemic control but more importantly, overall health. Identifying the underlying disease will allow the patient to receive appropriate treatment, which may offload a significant burden on glycemic control and in some cases, cure the hyper­glycemia.

REFERENCES
1. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540.
2. Nieman LK. Establishing the cause of Cushing’s syndrome. Up-to-Date. www.uptodate.com/contents/establishing-the-cause-of-cushings-syndrome. Accessed June 24, 2015.
3. CDC. National Diabetes Fact Sheet, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed June 24, 2015.
4. Ganda OP. Prevalence and incidence of secondary and other types of diabetes. In: Diabetes in America. 2nd ed. Bethesda, MD: National Institutes of Health; 1995:69-84.

A 63-year-old Hispanic wom­an was referred to endocrinology by her primary care provider for uncontrolled type 2 diabetes mellitus (T2DM), which was diagnosed 16 years ago. Her antidiabetic medications included insulin glargine (55 U bid), metformin (1,000 mg bid), and glipizide (10 mg bid). She also had known dyslipidemia, hypertension, and depression. There was a history of poorly controlled glucose (A1C between 9% and 13% in the past three years).

This was a relatively common new patient consult in our endocrine clinic. Upon entering the room, I was greeted by the patient and two family members. I quickly noticed the patient’s facial plethora and central obesity with comparatively thin extremities. Further inquiry revealed that the greatest challenge for the patient and her family was her bouts of severe depression, during which she would stop caring and cease to take her medications.

During the physical exam, mild but not significant supraclavicular and dorsocervical fat pads were appreciated. The exam was otherwise unremarkable, with no purple striae on the torso, abdomen, breasts, and extremities.

In addition to routine diabetes lab tests (ie, A1C, chemistry panel, lipid panel, urine microalbumin-to-creatinine ratio), an overnight 1-mg oral dexamethasone suppression test was ordered. Results of the latter were abnormal, and further workup confirmed Cushing disease (see Table 1 for results). The patient was referred for neurosurgery.

Continue for Discussion >>

DISCUSSION: SECONDARY DIABETES
It is well known that the prevalence of diabetes is skyrocketing, and medical offices are filled with affected patients. According to a 2011 report from the CDC, 90% to 95% of all diabetes cases are type 2, 5% are type 1 (autoimmune), and the rest (about 1% to 5%) are “other types” of diabetes.³ Due to these disproportionate statistics, clinicians often overlook the possibility of uncommon etiologies and assume all patients with diabetes have type 2—especially when the patient is overweight or obese.

Table 2 lists conditions and medications that may contribute to significant hyperglycemia.⁴ Some contributors are rather obvious (eg, status post pancreatectomy) or have no impact on treatment strategy (eg, chromosomal defects such as Down or Turner syndrome). However, certain conditions, such as Cushing syndrome, acromegaly, and hemochromatosis, can be relatively hard to recognize due to the variable rate of clinical manifestation, especially in the earlier stages of the disease. Experts have raised concerns that the prevalence of secondary diabetes (1% to 5%) may actually be underestimated due to “misdiagnosis” as T2DM. 

Early detection of the underlying disorder, followed by initiation of appropriate treatment, is critical. It will not only improve but also may resolve the patient’s hyperglycemia, and it may also reverse or stop the damage to other vital organs.

The case patient had an unfortunate situation in which her Cushing syndrome was masked by commonly encountered diagnoses of hypertension, T2DM, obesity, and depression. Cushing is an easy diagnosis to miss, since it has an insidious onset and it can take more than five years for some of the physical findings to become evident.

Pancreatic cancer is another uncommon but critical disease worth mentioning. Pancreatic cancer should be in the differential diagnosis for previously eu­glycemic patients who experience abrupt elevation of glucose or previously well-managed patients whose glucose values quickly get out of control without obvious cause (eg, medication cessation, addition of glucocorticoid therapy, uncontrolled diet).

In our practice, we have encountered three patients with pancreatic cancer in this setting. The only sign was a sudden rise in glucose (300 to 500 mg/dL throughout the day) in patients whose A1C had been low (in the 6% range) with one or two oral medications. Thorough history taking did not reveal any potential causes for sudden hyperglycemia. Only one patient had a palpable mass on abdominal exam and elevated liver enzymes and bilirubin. Unfortunately, that patient died eight months later. The other two had favorable outcomes from surgery and chemotherapy. Early detection was the key for those two patients.

Next page: Conclusion >>

CONCLUSION 
Since the majority of patients with diabetes have T2DM, it is easy to “default” and start treating all patients as such, especially if they are overweight or obese. However, up to 5% of patients actually have underlying disease that may cause or worsen their diabetic status. Overlooking these rare conditions can be detrimental to the patient, as it will adversely affect not only glycemic control but more importantly, overall health. Identifying the underlying disease will allow the patient to receive appropriate treatment, which may offload a significant burden on glycemic control and in some cases, cure the hyper­glycemia.

REFERENCES
1. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540.
2. Nieman LK. Establishing the cause of Cushing’s syndrome. Up-to-Date. www.uptodate.com/contents/establishing-the-cause-of-cushings-syndrome. Accessed June 24, 2015.
3. CDC. National Diabetes Fact Sheet, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed June 24, 2015.
4. Ganda OP. Prevalence and incidence of secondary and other types of diabetes. In: Diabetes in America. 2nd ed. Bethesda, MD: National Institutes of Health; 1995:69-84.

A 63-year-old Hispanic wom­an was referred to endocrinology by her primary care provider for uncontrolled type 2 diabetes mellitus (T2DM), which was diagnosed 16 years ago. Her antidiabetic medications included insulin glargine (55 U bid), metformin (1,000 mg bid), and glipizide (10 mg bid). She also had known dyslipidemia, hypertension, and depression. There was a history of poorly controlled glucose (A1C between 9% and 13% in the past three years).

This was a relatively common new patient consult in our endocrine clinic. Upon entering the room, I was greeted by the patient and two family members. I quickly noticed the patient’s facial plethora and central obesity with comparatively thin extremities. Further inquiry revealed that the greatest challenge for the patient and her family was her bouts of severe depression, during which she would stop caring and cease to take her medications.

During the physical exam, mild but not significant supraclavicular and dorsocervical fat pads were appreciated. The exam was otherwise unremarkable, with no purple striae on the torso, abdomen, breasts, and extremities.

In addition to routine diabetes lab tests (ie, A1C, chemistry panel, lipid panel, urine microalbumin-to-creatinine ratio), an overnight 1-mg oral dexamethasone suppression test was ordered. Results of the latter were abnormal, and further workup confirmed Cushing disease (see Table 1 for results). The patient was referred for neurosurgery.

Continue for Discussion >>

DISCUSSION: SECONDARY DIABETES
It is well known that the prevalence of diabetes is skyrocketing, and medical offices are filled with affected patients. According to a 2011 report from the CDC, 90% to 95% of all diabetes cases are type 2, 5% are type 1 (autoimmune), and the rest (about 1% to 5%) are “other types” of diabetes.³ Due to these disproportionate statistics, clinicians often overlook the possibility of uncommon etiologies and assume all patients with diabetes have type 2—especially when the patient is overweight or obese.

Table 2 lists conditions and medications that may contribute to significant hyperglycemia.⁴ Some contributors are rather obvious (eg, status post pancreatectomy) or have no impact on treatment strategy (eg, chromosomal defects such as Down or Turner syndrome). However, certain conditions, such as Cushing syndrome, acromegaly, and hemochromatosis, can be relatively hard to recognize due to the variable rate of clinical manifestation, especially in the earlier stages of the disease. Experts have raised concerns that the prevalence of secondary diabetes (1% to 5%) may actually be underestimated due to “misdiagnosis” as T2DM. 

Early detection of the underlying disorder, followed by initiation of appropriate treatment, is critical. It will not only improve but also may resolve the patient’s hyperglycemia, and it may also reverse or stop the damage to other vital organs.

The case patient had an unfortunate situation in which her Cushing syndrome was masked by commonly encountered diagnoses of hypertension, T2DM, obesity, and depression. Cushing is an easy diagnosis to miss, since it has an insidious onset and it can take more than five years for some of the physical findings to become evident.

Pancreatic cancer is another uncommon but critical disease worth mentioning. Pancreatic cancer should be in the differential diagnosis for previously eu­glycemic patients who experience abrupt elevation of glucose or previously well-managed patients whose glucose values quickly get out of control without obvious cause (eg, medication cessation, addition of glucocorticoid therapy, uncontrolled diet).

In our practice, we have encountered three patients with pancreatic cancer in this setting. The only sign was a sudden rise in glucose (300 to 500 mg/dL throughout the day) in patients whose A1C had been low (in the 6% range) with one or two oral medications. Thorough history taking did not reveal any potential causes for sudden hyperglycemia. Only one patient had a palpable mass on abdominal exam and elevated liver enzymes and bilirubin. Unfortunately, that patient died eight months later. The other two had favorable outcomes from surgery and chemotherapy. Early detection was the key for those two patients.

Next page: Conclusion >>

CONCLUSION 
Since the majority of patients with diabetes have T2DM, it is easy to “default” and start treating all patients as such, especially if they are overweight or obese. However, up to 5% of patients actually have underlying disease that may cause or worsen their diabetic status. Overlooking these rare conditions can be detrimental to the patient, as it will adversely affect not only glycemic control but more importantly, overall health. Identifying the underlying disease will allow the patient to receive appropriate treatment, which may offload a significant burden on glycemic control and in some cases, cure the hyper­glycemia.

REFERENCES
1. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540.
2. Nieman LK. Establishing the cause of Cushing’s syndrome. Up-to-Date. www.uptodate.com/contents/establishing-the-cause-of-cushings-syndrome. Accessed June 24, 2015.
3. CDC. National Diabetes Fact Sheet, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed June 24, 2015.
4. Ganda OP. Prevalence and incidence of secondary and other types of diabetes. In: Diabetes in America. 2nd ed. Bethesda, MD: National Institutes of Health; 1995:69-84.

In March 2009, a 63-year-old man was diagnosed with stage IV gastric carcinoma with metastasis to the liver. His treating oncologist gave him a prognosis of about 10 months’ life expectancy with chemotherapy. The patient’s family searched for alternative treatment options and found a natural alternative treatment center claiming the ability to cure the patient.

The patient and his family decided to defer chemotherapy, and he was admitted to the alternative treatment center for three to four weeks of inpatient care. The treatment consisted of “colonic hydrotherapy,” supplements designed to cleanse the body, and a diet restricted to seed milk, vegetable juice, and spinach soup. 

After six days, the patient developed severe diarrhea, confusion, and profound weakness. He was taken to a local hospital and admitted with a diagnosis of acute renal failure. Dialysis attempts were unsuccessful, and the man died of respiratory distress secondary to acute renal failure a week later.

The plaintiff claimed that the treatment provided by the defendants was contraindicated and caused acute renal failure, noting that the patient’s kidney function had been relatively normal when he entered the treatment facility. The plaintiff claimed that defendant Dr N., a chiropractor, never reviewed any of the decedent’s medical records, did not discuss the proposed treatment plan with his treating physicians, and failed to properly monitor the patient’s condition, notice his deterioration, and provide timely transfer to a hospital.

The defendant claimed that the treatment given had no adverse effects on the decedent and that the acute renal failure was due to hepatorenal syndrome due to his advanced metastatic liver cancer.

What was the outcome? >>

OUTCOME 
A $2.5 million verdict was returned. An appeal was pending.

COMMENT 
This is a case against a chiropractor, so why discuss it in a journal dedicated to NP and PA practice? Because it involves scope of practice, alternative medicine, the safety of “natural” treatments, and the ethical and legal problems of making unsupportable promises to patients.

Know your scope of practice, and don’t overextend. Clinicians trained as specialists (eg, in pediatrics, midwifery, or anesthesia) should use caution departing from that area. Those trained as “generalists” need to be careful as well; even if you were trained in a family practice program, if you are a PA who  has worked in dermatology for the past 10 years, think twice about giving treatment or advice to your friend with a neurologic complaint. In the event of a lawsuit, the plaintiff will spend a great deal of time building your resume as an expert in your discipline, only to attack you as inexperienced and unqualified in the case in which you extended yourself.

Here a chiropractor, without ever examining the patient, directed the treatment of a very sick man in an area in which he was not qualified. While chiropractors may claim the ability to treat outside their traditional scope, the jury’s verdict in this case proves that they were not persuaded he was right to do so. The chiropractor, Dr N., eventually lost his license, based in part on the false promises he made about his ability to cure patients of “any and all diseases, including cancer, by restoring the body to its natural state ….” This opportunistic preying upon the most ill and vulnerable in our society likely irked the jurors, who returned a substantial award, considering that the patient’s short life expectancy was uncontested.

Handle alternative medicine with particular care, because an alternative treatment may not qualify as “medicine” at all. If we define medicine as the application of scientific principles to health care, an alternative that is unproven, unstudied, and unknown does not qualify. Rather, it is guesswork—with potentially devastating consequences.

In this case, through his company, the chiropractor based his treatment plan on guesswork that colonic hydrotherapy and severe dietary restrictions would help a patient with stage IV metastatic gastric carcinoma. He was wrong, and the jury concluded that these alternatives injured the patient and hastened his death.

Certainly, Western medicine has been rightly and fairly criticized for failing to promote wellness through a healthy lifestyle, including diet, exercise, safety, emotional well-being, and stress management. However, when venturing from generally accepted health promotion strategies to a specific recommendation that an alternative agent “is good for” a specific problem, be careful. You may believe lavender oil is an effective antibiotic—but can you prove it?

If you choose lavender oil over a demonstrably effective antibiotic to treat pneumonia, and the patient deteriorates, you will be held accountable. The plaintiff will demand answers, and the jury will await your explanation. Reliance on vague concepts, not generally accepted in the literature (eg, “energy management,” detoxifying, unblocking “clogged” nervous systems), will be ridiculed by the plaintiff’s experts, and you will be skewered on cross-examination. It is not enough to personally “believe” in the alternative; you must be able to support your treatment decisions through the best evidence possible.

To be fair, this cuts both ways: Some Western medical practices are based on anecdotal evidence with minimal scientific support.  There was a time when a corneal abrasion was patched, a fractured clavicle was stabilized with a figure-of-eight dressing, and narcotics were withheld from a suffering patient with acute abdomen because it would “mask signs.” Our “Western” system is not immune from the impact of poor research, group-think, dogmas leading to inappropriate practice, and other sources of logical fallacy.

As NPs and PAs, we will be held to a scientific evidentiary standard. The standard of care will be based upon the care a reasonably prudent clinician would deliver in a similar situation. At trial, you will be confronted with a PA or NP on the stand testifying against you regarding what is reasonably prudent, acceptable care. Make sure your actions are scientifically defensible.

Interestingly, the standard for admitting a scientific opinion as expert testimony has changed. In 1923, Frye v United States¹ established that, for an expert opinion to be admissible, the testimony had to be based on what is “generally accepted in the scientific community.” In 1993, the Supreme Court case Daubert v Merrell Dow Pharmaceuticals² determined that the opinion need not be “generally accepted” but must be based on scientific method and must be relevant to the case; the judge serves as a “gatekeeper” to be sure the opinions flow from “scientific knowledge.”

Medical malpractice cases are based on state law. Some follow Frye, some Daubert. The latter is a more relaxed standard, but even in states following Daubert, an expert witness who purports to testify on an alternative treatment must follow the scientific method. For example, the webpage of the defendant chiropractor’s institute (still in business) currently claims that “Heart/Brain Entrainment Therapy balances frequencies of organs/glands/tissues. Everything in the universe resonates at a particular frequency—light, sound, and every cell, organ, gland, and tissue in you.”³

So, whatever Heart/Brain Entrainment Therapy is, for that theory to be admissible in a Frye jurisdiction it would likely have to be “generally accepted” in the medical community. To be admissible in a Daubert jurisdiction, proponents of the testimony would have to show evidence of a scientific methodology supporting the theory before the jury could hear any testimony about it. In either case, strategically, the defense attorney would likely file a motion to block either certain parts of the testimony or the testimony entirely.

IN SUM
Jurors expect sound scientific methodology supporting medical decisions; use care when selecting treatment for patients. Robustly adopt health promotion and general wellness strategies. However, if you use alternatives directed toward a specific therapy solving a specific problem, use them cautiously and with an awareness that the indication for the therapy should be scientifically defensible. —DML 

REFERENCES
1. Frye v United States, 293 F. 1013 (D.C. Cir. 1923).
2. Daubert v Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993).
3. Total Health Institute. Bioelectrical Energy, Quantum Frequency Resonance. www.totalhealthinstitute.com/about. Accessed July 14, 2015.

In March 2009, a 63-year-old man was diagnosed with stage IV gastric carcinoma with metastasis to the liver. His treating oncologist gave him a prognosis of about 10 months’ life expectancy with chemotherapy. The patient’s family searched for alternative treatment options and found a natural alternative treatment center claiming the ability to cure the patient.

The patient and his family decided to defer chemotherapy, and he was admitted to the alternative treatment center for three to four weeks of inpatient care. The treatment consisted of “colonic hydrotherapy,” supplements designed to cleanse the body, and a diet restricted to seed milk, vegetable juice, and spinach soup. 

After six days, the patient developed severe diarrhea, confusion, and profound weakness. He was taken to a local hospital and admitted with a diagnosis of acute renal failure. Dialysis attempts were unsuccessful, and the man died of respiratory distress secondary to acute renal failure a week later.

The plaintiff claimed that the treatment provided by the defendants was contraindicated and caused acute renal failure, noting that the patient’s kidney function had been relatively normal when he entered the treatment facility. The plaintiff claimed that defendant Dr N., a chiropractor, never reviewed any of the decedent’s medical records, did not discuss the proposed treatment plan with his treating physicians, and failed to properly monitor the patient’s condition, notice his deterioration, and provide timely transfer to a hospital.

The defendant claimed that the treatment given had no adverse effects on the decedent and that the acute renal failure was due to hepatorenal syndrome due to his advanced metastatic liver cancer.

What was the outcome? >>

OUTCOME 
A $2.5 million verdict was returned. An appeal was pending.

COMMENT 
This is a case against a chiropractor, so why discuss it in a journal dedicated to NP and PA practice? Because it involves scope of practice, alternative medicine, the safety of “natural” treatments, and the ethical and legal problems of making unsupportable promises to patients.

Know your scope of practice, and don’t overextend. Clinicians trained as specialists (eg, in pediatrics, midwifery, or anesthesia) should use caution departing from that area. Those trained as “generalists” need to be careful as well; even if you were trained in a family practice program, if you are a PA who  has worked in dermatology for the past 10 years, think twice about giving treatment or advice to your friend with a neurologic complaint. In the event of a lawsuit, the plaintiff will spend a great deal of time building your resume as an expert in your discipline, only to attack you as inexperienced and unqualified in the case in which you extended yourself.

Here a chiropractor, without ever examining the patient, directed the treatment of a very sick man in an area in which he was not qualified. While chiropractors may claim the ability to treat outside their traditional scope, the jury’s verdict in this case proves that they were not persuaded he was right to do so. The chiropractor, Dr N., eventually lost his license, based in part on the false promises he made about his ability to cure patients of “any and all diseases, including cancer, by restoring the body to its natural state ….” This opportunistic preying upon the most ill and vulnerable in our society likely irked the jurors, who returned a substantial award, considering that the patient’s short life expectancy was uncontested.

Handle alternative medicine with particular care, because an alternative treatment may not qualify as “medicine” at all. If we define medicine as the application of scientific principles to health care, an alternative that is unproven, unstudied, and unknown does not qualify. Rather, it is guesswork—with potentially devastating consequences.

In this case, through his company, the chiropractor based his treatment plan on guesswork that colonic hydrotherapy and severe dietary restrictions would help a patient with stage IV metastatic gastric carcinoma. He was wrong, and the jury concluded that these alternatives injured the patient and hastened his death.

Certainly, Western medicine has been rightly and fairly criticized for failing to promote wellness through a healthy lifestyle, including diet, exercise, safety, emotional well-being, and stress management. However, when venturing from generally accepted health promotion strategies to a specific recommendation that an alternative agent “is good for” a specific problem, be careful. You may believe lavender oil is an effective antibiotic—but can you prove it?

If you choose lavender oil over a demonstrably effective antibiotic to treat pneumonia, and the patient deteriorates, you will be held accountable. The plaintiff will demand answers, and the jury will await your explanation. Reliance on vague concepts, not generally accepted in the literature (eg, “energy management,” detoxifying, unblocking “clogged” nervous systems), will be ridiculed by the plaintiff’s experts, and you will be skewered on cross-examination. It is not enough to personally “believe” in the alternative; you must be able to support your treatment decisions through the best evidence possible.

To be fair, this cuts both ways: Some Western medical practices are based on anecdotal evidence with minimal scientific support.  There was a time when a corneal abrasion was patched, a fractured clavicle was stabilized with a figure-of-eight dressing, and narcotics were withheld from a suffering patient with acute abdomen because it would “mask signs.” Our “Western” system is not immune from the impact of poor research, group-think, dogmas leading to inappropriate practice, and other sources of logical fallacy.

As NPs and PAs, we will be held to a scientific evidentiary standard. The standard of care will be based upon the care a reasonably prudent clinician would deliver in a similar situation. At trial, you will be confronted with a PA or NP on the stand testifying against you regarding what is reasonably prudent, acceptable care. Make sure your actions are scientifically defensible.

Interestingly, the standard for admitting a scientific opinion as expert testimony has changed. In 1923, Frye v United States¹ established that, for an expert opinion to be admissible, the testimony had to be based on what is “generally accepted in the scientific community.” In 1993, the Supreme Court case Daubert v Merrell Dow Pharmaceuticals² determined that the opinion need not be “generally accepted” but must be based on scientific method and must be relevant to the case; the judge serves as a “gatekeeper” to be sure the opinions flow from “scientific knowledge.”

Medical malpractice cases are based on state law. Some follow Frye, some Daubert. The latter is a more relaxed standard, but even in states following Daubert, an expert witness who purports to testify on an alternative treatment must follow the scientific method. For example, the webpage of the defendant chiropractor’s institute (still in business) currently claims that “Heart/Brain Entrainment Therapy balances frequencies of organs/glands/tissues. Everything in the universe resonates at a particular frequency—light, sound, and every cell, organ, gland, and tissue in you.”³

So, whatever Heart/Brain Entrainment Therapy is, for that theory to be admissible in a Frye jurisdiction it would likely have to be “generally accepted” in the medical community. To be admissible in a Daubert jurisdiction, proponents of the testimony would have to show evidence of a scientific methodology supporting the theory before the jury could hear any testimony about it. In either case, strategically, the defense attorney would likely file a motion to block either certain parts of the testimony or the testimony entirely.

IN SUM
Jurors expect sound scientific methodology supporting medical decisions; use care when selecting treatment for patients. Robustly adopt health promotion and general wellness strategies. However, if you use alternatives directed toward a specific therapy solving a specific problem, use them cautiously and with an awareness that the indication for the therapy should be scientifically defensible. —DML 

REFERENCES
1. Frye v United States, 293 F. 1013 (D.C. Cir. 1923).
2. Daubert v Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993).
3. Total Health Institute. Bioelectrical Energy, Quantum Frequency Resonance. www.totalhealthinstitute.com/about. Accessed July 14, 2015.

In March 2009, a 63-year-old man was diagnosed with stage IV gastric carcinoma with metastasis to the liver. His treating oncologist gave him a prognosis of about 10 months’ life expectancy with chemotherapy. The patient’s family searched for alternative treatment options and found a natural alternative treatment center claiming the ability to cure the patient.

The patient and his family decided to defer chemotherapy, and he was admitted to the alternative treatment center for three to four weeks of inpatient care. The treatment consisted of “colonic hydrotherapy,” supplements designed to cleanse the body, and a diet restricted to seed milk, vegetable juice, and spinach soup. 

After six days, the patient developed severe diarrhea, confusion, and profound weakness. He was taken to a local hospital and admitted with a diagnosis of acute renal failure. Dialysis attempts were unsuccessful, and the man died of respiratory distress secondary to acute renal failure a week later.

The plaintiff claimed that the treatment provided by the defendants was contraindicated and caused acute renal failure, noting that the patient’s kidney function had been relatively normal when he entered the treatment facility. The plaintiff claimed that defendant Dr N., a chiropractor, never reviewed any of the decedent’s medical records, did not discuss the proposed treatment plan with his treating physicians, and failed to properly monitor the patient’s condition, notice his deterioration, and provide timely transfer to a hospital.

The defendant claimed that the treatment given had no adverse effects on the decedent and that the acute renal failure was due to hepatorenal syndrome due to his advanced metastatic liver cancer.

What was the outcome? >>

OUTCOME 
A $2.5 million verdict was returned. An appeal was pending.

COMMENT 
This is a case against a chiropractor, so why discuss it in a journal dedicated to NP and PA practice? Because it involves scope of practice, alternative medicine, the safety of “natural” treatments, and the ethical and legal problems of making unsupportable promises to patients.

Know your scope of practice, and don’t overextend. Clinicians trained as specialists (eg, in pediatrics, midwifery, or anesthesia) should use caution departing from that area. Those trained as “generalists” need to be careful as well; even if you were trained in a family practice program, if you are a PA who  has worked in dermatology for the past 10 years, think twice about giving treatment or advice to your friend with a neurologic complaint. In the event of a lawsuit, the plaintiff will spend a great deal of time building your resume as an expert in your discipline, only to attack you as inexperienced and unqualified in the case in which you extended yourself.

Here a chiropractor, without ever examining the patient, directed the treatment of a very sick man in an area in which he was not qualified. While chiropractors may claim the ability to treat outside their traditional scope, the jury’s verdict in this case proves that they were not persuaded he was right to do so. The chiropractor, Dr N., eventually lost his license, based in part on the false promises he made about his ability to cure patients of “any and all diseases, including cancer, by restoring the body to its natural state ….” This opportunistic preying upon the most ill and vulnerable in our society likely irked the jurors, who returned a substantial award, considering that the patient’s short life expectancy was uncontested.

Handle alternative medicine with particular care, because an alternative treatment may not qualify as “medicine” at all. If we define medicine as the application of scientific principles to health care, an alternative that is unproven, unstudied, and unknown does not qualify. Rather, it is guesswork—with potentially devastating consequences.

In this case, through his company, the chiropractor based his treatment plan on guesswork that colonic hydrotherapy and severe dietary restrictions would help a patient with stage IV metastatic gastric carcinoma. He was wrong, and the jury concluded that these alternatives injured the patient and hastened his death.

Certainly, Western medicine has been rightly and fairly criticized for failing to promote wellness through a healthy lifestyle, including diet, exercise, safety, emotional well-being, and stress management. However, when venturing from generally accepted health promotion strategies to a specific recommendation that an alternative agent “is good for” a specific problem, be careful. You may believe lavender oil is an effective antibiotic—but can you prove it?

If you choose lavender oil over a demonstrably effective antibiotic to treat pneumonia, and the patient deteriorates, you will be held accountable. The plaintiff will demand answers, and the jury will await your explanation. Reliance on vague concepts, not generally accepted in the literature (eg, “energy management,” detoxifying, unblocking “clogged” nervous systems), will be ridiculed by the plaintiff’s experts, and you will be skewered on cross-examination. It is not enough to personally “believe” in the alternative; you must be able to support your treatment decisions through the best evidence possible.

To be fair, this cuts both ways: Some Western medical practices are based on anecdotal evidence with minimal scientific support.  There was a time when a corneal abrasion was patched, a fractured clavicle was stabilized with a figure-of-eight dressing, and narcotics were withheld from a suffering patient with acute abdomen because it would “mask signs.” Our “Western” system is not immune from the impact of poor research, group-think, dogmas leading to inappropriate practice, and other sources of logical fallacy.

As NPs and PAs, we will be held to a scientific evidentiary standard. The standard of care will be based upon the care a reasonably prudent clinician would deliver in a similar situation. At trial, you will be confronted with a PA or NP on the stand testifying against you regarding what is reasonably prudent, acceptable care. Make sure your actions are scientifically defensible.

Interestingly, the standard for admitting a scientific opinion as expert testimony has changed. In 1923, Frye v United States¹ established that, for an expert opinion to be admissible, the testimony had to be based on what is “generally accepted in the scientific community.” In 1993, the Supreme Court case Daubert v Merrell Dow Pharmaceuticals² determined that the opinion need not be “generally accepted” but must be based on scientific method and must be relevant to the case; the judge serves as a “gatekeeper” to be sure the opinions flow from “scientific knowledge.”

Medical malpractice cases are based on state law. Some follow Frye, some Daubert. The latter is a more relaxed standard, but even in states following Daubert, an expert witness who purports to testify on an alternative treatment must follow the scientific method. For example, the webpage of the defendant chiropractor’s institute (still in business) currently claims that “Heart/Brain Entrainment Therapy balances frequencies of organs/glands/tissues. Everything in the universe resonates at a particular frequency—light, sound, and every cell, organ, gland, and tissue in you.”³

So, whatever Heart/Brain Entrainment Therapy is, for that theory to be admissible in a Frye jurisdiction it would likely have to be “generally accepted” in the medical community. To be admissible in a Daubert jurisdiction, proponents of the testimony would have to show evidence of a scientific methodology supporting the theory before the jury could hear any testimony about it. In either case, strategically, the defense attorney would likely file a motion to block either certain parts of the testimony or the testimony entirely.

IN SUM
Jurors expect sound scientific methodology supporting medical decisions; use care when selecting treatment for patients. Robustly adopt health promotion and general wellness strategies. However, if you use alternatives directed toward a specific therapy solving a specific problem, use them cautiously and with an awareness that the indication for the therapy should be scientifically defensible. —DML 

REFERENCES
1. Frye v United States, 293 F. 1013 (D.C. Cir. 1923).
2. Daubert v Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993).
3. Total Health Institute. Bioelectrical Energy, Quantum Frequency Resonance. www.totalhealthinstitute.com/about. Accessed July 14, 2015.

ANSWER
The radiographs demonstrate a left inferior pubic ramus fracture. The patient was referred to orthopedics for follow-up. She was given a walker and a series of home exercises for hip stretching and strengthening, as well as anti-inflammatories as needed for discomfort. She was scheduled for a four-week follow-up visit and repeat radiographs of the pelvis.

ANSWER
The radiographs demonstrate a left inferior pubic ramus fracture. The patient was referred to orthopedics for follow-up. She was given a walker and a series of home exercises for hip stretching and strengthening, as well as anti-inflammatories as needed for discomfort. She was scheduled for a four-week follow-up visit and repeat radiographs of the pelvis.

ANSWER
The radiographs demonstrate a left inferior pubic ramus fracture. The patient was referred to orthopedics for follow-up. She was given a walker and a series of home exercises for hip stretching and strengthening, as well as anti-inflammatories as needed for discomfort. She was scheduled for a four-week follow-up visit and repeat radiographs of the pelvis.

Team-based care lowers BP in hypertensive patients

A systematic review evaluated 80 trials (total N not defined), which included randomized controlled trials (RCTs) and quasi-experimental trials, to compare blood pressure control in hypertensive patients who received team-based care with that of patients who received usual care.¹

Team-based care was defined as adding new staff or changing the roles of existing staff to provide process support and share responsibility for hypertension care with a primary care provider. Examples included using staff to help with medication management, active patient follow-up, adherence, and self-management support. The mean duration of the interventions was 12 months.

The intervention group showed greater reductions in SBP (44 trials; 5.4 mm Hg; interquartile interval [IQI]=2.0-7.2) and DBP (38 trials; 1.8 mm Hg; IQI=0.7-3.2) compared with usual care.

Free medication, care involving nurses, pharmacists lead to lower BP

Another meta-analysis examined 37 RCTs (total N not provided) comparing blood pressure control in hypertensive patients who received team-based care with patients who received usual care.² The meta-analysis divided the studies by specific types of team-based interventions and analyzed the effect of each type on blood pressure control. It also analyzed studies based on what kind of health care professionals were involved in the intervention.

Team-based care appears to lower systolic blood pressure by 5 to 11 mm Hg and diastolic blood pressure by 2 to 6 mm Hg in patients with hypertension.

The largest absolute changes in both SBP and DBP were observed with the following interventions, compared with the control group: free medication (3 trials; SBP reduction (SBPR)=−11 mm Hg; interquartile range [IQR]=−15 to −9.1; DBP reduction [DBPR]=−6.4 mm Hg; IQR=−8.7 to −3.9); pharmacist recommending medication to physician (15 trials; SBPR=−9.3 mm Hg; IQR=−15 to −5.0; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); education about BP medications (23 trials; SBPR=−8.8 mm Hg; IQR=−12 to −4.3; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); and pharmacist-performed intervention (22 trials; SBPR=−8.4 mm Hg; IQR=−12 to −4; DBPR=−3.3 mm Hg; IQR=−6.9 to −0.90).

Patients who underwent team-based care interventions had greater SBP control (defined as <140, or <130 in patients with diabetes mellitus or chronic kidney disease) than the control group in trials involving nurses (8 trials; odds ratio [OR]=1.7; 95% confidence interval [CI], 1.5-1.9), trials conducted in community pharmacies (5 trials; OR=2.9; 95% CI, 1.8-4.6), and trials incorporating pharmacists into primary care clinics (9 trials; OR=2.2; 95% CI, 1.8-2.7).

Team-based care improves lipid control

An RCT of 6963 patients with type 2 diabetes mellitus in 9 clinics examined the proportion of patients receiving team-based care that achieved a target low-density lipoprotein (LDL) of ≤100 mg/dL compared with patients receiving usual care.³

Clinics were randomized to participate in team-based care (defined as a physician-pharmacist team in which the pharmacist reviewed the medical charts of patients with elevated LDL and then developed individualized, evidence-based treatment recommendations) or usual care, which involved access to a disease management program providing automated quality reporting, benchmarking, and care opportunity decision support.

Over 2 years, the team-based care model had significantly more patients with a lower LDL, more patients at LDL goal, and more patients on lipid-lowering medication (TABLE³).

Team-based care lowers BP in hypertensive patients

A systematic review evaluated 80 trials (total N not defined), which included randomized controlled trials (RCTs) and quasi-experimental trials, to compare blood pressure control in hypertensive patients who received team-based care with that of patients who received usual care.¹

Team-based care was defined as adding new staff or changing the roles of existing staff to provide process support and share responsibility for hypertension care with a primary care provider. Examples included using staff to help with medication management, active patient follow-up, adherence, and self-management support. The mean duration of the interventions was 12 months.

The intervention group showed greater reductions in SBP (44 trials; 5.4 mm Hg; interquartile interval [IQI]=2.0-7.2) and DBP (38 trials; 1.8 mm Hg; IQI=0.7-3.2) compared with usual care.

Free medication, care involving nurses, pharmacists lead to lower BP

Another meta-analysis examined 37 RCTs (total N not provided) comparing blood pressure control in hypertensive patients who received team-based care with patients who received usual care.² The meta-analysis divided the studies by specific types of team-based interventions and analyzed the effect of each type on blood pressure control. It also analyzed studies based on what kind of health care professionals were involved in the intervention.

Team-based care appears to lower systolic blood pressure by 5 to 11 mm Hg and diastolic blood pressure by 2 to 6 mm Hg in patients with hypertension.

The largest absolute changes in both SBP and DBP were observed with the following interventions, compared with the control group: free medication (3 trials; SBP reduction (SBPR)=−11 mm Hg; interquartile range [IQR]=−15 to −9.1; DBP reduction [DBPR]=−6.4 mm Hg; IQR=−8.7 to −3.9); pharmacist recommending medication to physician (15 trials; SBPR=−9.3 mm Hg; IQR=−15 to −5.0; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); education about BP medications (23 trials; SBPR=−8.8 mm Hg; IQR=−12 to −4.3; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); and pharmacist-performed intervention (22 trials; SBPR=−8.4 mm Hg; IQR=−12 to −4; DBPR=−3.3 mm Hg; IQR=−6.9 to −0.90).

Patients who underwent team-based care interventions had greater SBP control (defined as <140, or <130 in patients with diabetes mellitus or chronic kidney disease) than the control group in trials involving nurses (8 trials; odds ratio [OR]=1.7; 95% confidence interval [CI], 1.5-1.9), trials conducted in community pharmacies (5 trials; OR=2.9; 95% CI, 1.8-4.6), and trials incorporating pharmacists into primary care clinics (9 trials; OR=2.2; 95% CI, 1.8-2.7).

Team-based care improves lipid control

An RCT of 6963 patients with type 2 diabetes mellitus in 9 clinics examined the proportion of patients receiving team-based care that achieved a target low-density lipoprotein (LDL) of ≤100 mg/dL compared with patients receiving usual care.³

Clinics were randomized to participate in team-based care (defined as a physician-pharmacist team in which the pharmacist reviewed the medical charts of patients with elevated LDL and then developed individualized, evidence-based treatment recommendations) or usual care, which involved access to a disease management program providing automated quality reporting, benchmarking, and care opportunity decision support.

Over 2 years, the team-based care model had significantly more patients with a lower LDL, more patients at LDL goal, and more patients on lipid-lowering medication (TABLE³).

Team-based care lowers BP in hypertensive patients

A systematic review evaluated 80 trials (total N not defined), which included randomized controlled trials (RCTs) and quasi-experimental trials, to compare blood pressure control in hypertensive patients who received team-based care with that of patients who received usual care.¹

Team-based care was defined as adding new staff or changing the roles of existing staff to provide process support and share responsibility for hypertension care with a primary care provider. Examples included using staff to help with medication management, active patient follow-up, adherence, and self-management support. The mean duration of the interventions was 12 months.

The intervention group showed greater reductions in SBP (44 trials; 5.4 mm Hg; interquartile interval [IQI]=2.0-7.2) and DBP (38 trials; 1.8 mm Hg; IQI=0.7-3.2) compared with usual care.

Free medication, care involving nurses, pharmacists lead to lower BP

Another meta-analysis examined 37 RCTs (total N not provided) comparing blood pressure control in hypertensive patients who received team-based care with patients who received usual care.² The meta-analysis divided the studies by specific types of team-based interventions and analyzed the effect of each type on blood pressure control. It also analyzed studies based on what kind of health care professionals were involved in the intervention.

Team-based care appears to lower systolic blood pressure by 5 to 11 mm Hg and diastolic blood pressure by 2 to 6 mm Hg in patients with hypertension.

The largest absolute changes in both SBP and DBP were observed with the following interventions, compared with the control group: free medication (3 trials; SBP reduction (SBPR)=−11 mm Hg; interquartile range [IQR]=−15 to −9.1; DBP reduction [DBPR]=−6.4 mm Hg; IQR=−8.7 to −3.9); pharmacist recommending medication to physician (15 trials; SBPR=−9.3 mm Hg; IQR=−15 to −5.0; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); education about BP medications (23 trials; SBPR=−8.8 mm Hg; IQR=−12 to −4.3; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); and pharmacist-performed intervention (22 trials; SBPR=−8.4 mm Hg; IQR=−12 to −4; DBPR=−3.3 mm Hg; IQR=−6.9 to −0.90).

Patients who underwent team-based care interventions had greater SBP control (defined as <140, or <130 in patients with diabetes mellitus or chronic kidney disease) than the control group in trials involving nurses (8 trials; odds ratio [OR]=1.7; 95% confidence interval [CI], 1.5-1.9), trials conducted in community pharmacies (5 trials; OR=2.9; 95% CI, 1.8-4.6), and trials incorporating pharmacists into primary care clinics (9 trials; OR=2.2; 95% CI, 1.8-2.7).

Team-based care improves lipid control

An RCT of 6963 patients with type 2 diabetes mellitus in 9 clinics examined the proportion of patients receiving team-based care that achieved a target low-density lipoprotein (LDL) of ≤100 mg/dL compared with patients receiving usual care.³

Clinics were randomized to participate in team-based care (defined as a physician-pharmacist team in which the pharmacist reviewed the medical charts of patients with elevated LDL and then developed individualized, evidence-based treatment recommendations) or usual care, which involved access to a disease management program providing automated quality reporting, benchmarking, and care opportunity decision support.

Over 2 years, the team-based care model had significantly more patients with a lower LDL, more patients at LDL goal, and more patients on lipid-lowering medication (TABLE³).