Endocrine Consult

A 42-year-old obese woman with type 2 diabetes, diabetic retinopathy, hyper­tension, and hirsutism presents to discuss an elevated prolactin level of 144.8 ng/mL (normal range, 4.8 to 23.3 ng/mL) found by her Ob-Gyn two months ago. She complained of galactorrhea and no menses for one year. A repeat prolactin level was also elevated, at 109 ng/mL.

A pituitary MRI with contrast showed a “subtle area of delayed enhancement in the right pituitary, consistent with a 5-mm microadenoma.” The patient was prescribed the dopamine agonist cabergoline (0.25 mg, to be taken twice a week), with a plan to follow up in two to three months.

Q: In obtaining a thorough history, what additional questions should be asked of this patient?

There are many causes of hyperprolactinemia. Factors that can increase prolactin secretion include pregnancy, nursing, physiologic stress, estrogen use, polycystic ovary syndrome, hypothyroidism, and chronic renal or hepatic failure. Head trauma, use of certain medications (verapamil, neuroleptics, antipsychotics, and antidepressants), and presence of nonsecretory sellar or suprasellar masses can also increase prolactin levels. 

In general, signs and symptoms are due to either the effect of excess hormone secretion (ie, galactorrhea and amenorrhea) or local compression (ie, new-onset or persistent headache, dizziness, visual changes, and vision loss). A review of medications, including estrogen therapy, and history of fertility or gonadal dysfunction should be documented. Elevated prolactin levels can result in secondary hypogonadism.¹

Note: While the case patient is female, it should be emphasized that prolactinomas do occur in men. The incidence is, overall, low. In addition to the symptoms listed above, men can present with decreased libido and infertility.¹

Q: What additional diagnostic tests should be ordered as part of the work-up of galactorrhea and amenorrhea in this patient?

Laboratory evaluation should include a repeat serum prolactin test, measurements of TSH and free T4, and a pregnancy test. (A serum testosterone level should be checked in men.) If the results come back normal and if other diagnoses are excluded, the most likely diagnosis is a prolactinoma. In this case, a pituitary MRI should be obtained. Visual field testing can be performed in individuals with specific visual complaints, especially loss or impairment of peripheral vision.

Q: What is the incidence of prolactinoma in the general population?

Prolactin-secreting adenomas, or prolactinomas, are the most common type of pituitary adenoma, accounting for approximately 60% overall.¹ They occur at a frequency of six to 10 cases per million each year.² Prolactinomas are almost always benign; malignant tumors are extremely rare.³

Tumors are classified as microadenomas or macroadenomas, depending on the size. A microadenoma is defined as an intrasellar mass less than 10 mm in diameter. A macroadenoma, defined as larger than 10 mm in diameter, can cause enlargement of the sella turcica.^1,4 The larger the size of the prolactinoma, the greater the prolactin level and higher the likelihood of mass-effect symptoms.⁴

Q: What are the options for treatment of a prolactinoma?

There are several options for treatment of prolactinomas. After discussing all of the available options with the patient, the choice of therapy should be determined by the patient’s desires and potential plans for pregnancy. It is acceptable to observe the tumor with serial MRIs and serum prolactin measurements, provided the tumor is very small and the patient is asymptomatic.⁴

Medication therapy involves treatment with a dopamine agonist, which directly inhibits prolactin secretion by the tumor and therefore suppresses tumor growth. The goal of medication therapy is to suppress the prolactin level to normal range and restore gonadal function. The two dopamine agonists used are bromocriptine and cabergoline. 

Bromocriptine was the first drug available in the United States to effectively treat pituitary adenomas. Its most common adverse effects include nausea, vomiting, dizziness, and postural hypotension. These effects can be minimized or avoided if the drug is started at a low dose, gradually increased, and taken at bedtime. The adverse effects usually subside with continued use; however, in some patients they persist and therefore the drug has to be discontinued.

Cabergoline is a non-ergot dopamine agonist that is more efficacious, overall better tolerated, and longer acting than bromocriptine. It is dosed twice weekly, whereas bromocriptine is dosed once daily.⁴ One factor to consider in a female patient is whether she is of child-bearing age and is interested in conception. Both bromocriptine and cabergoline are designated as category B; however, in animal studies cabergoline has been associated with maternal toxicity, increase in fetal death, and growth retardation and death due to decreased milk secretion by the mother. Therefore, it should only be used during pregnancy if the need has been clearly established.

Dopamine agonists are approximately 80% to 90% effective in decreasing prolactin levels and reducing tumor size in microadenomas and 60% to 70% in macroadenomas. The major drawback of using medication is that it does not always provide permanent results. Hyperprolactinemia and tumor growth can resume upon discontinuation of the drug, even if the patient has taken it for several years.¹ The rate of recurrence after discontinuing therapy can be anywhere from 26% to 69%, and the highest likelihood occurs within a year of withdrawal.⁴ Close clinical follow-up is thus important.

Surgery, typically a transphenoidal resection, is performed by a neurosurgeon. Success of surgery is based on tumor size and basal prolactin level prior to the procedure. It is more effective in restoring normal prolactin levels and resolution of symptoms in microadenomas than in macroadenomas. Progressive vision loss, pituitary apoplexy, and intolerance to dopamine agonists are indications for surgery.¹

Radiation therapy is reserved for those patients who have residual tumors postsurgery and have not responded to or are intolerant to dopamine agonists. Response to radiation is slow; it can sometimes take several years to achieve full effect. Gamma-knife radiation is sometimes used, but experience with this procedure is limited thus far in prolactinomas.

Overall, the vast majority of prolactinomas are benign and fairly straightforward to manage clinically.³           

REFERENCES
1. Greenspan F, Gardner D. Basic & Clinical Endocrinology, 7th ed. New York: McGraw-Hill; 2004.

2. Ciccarelli A, Daly A, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8(1):3-6.

3. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.

4. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline. J Clinical Endocrinol Metab. 2011;96(2):273-288.

A 42-year-old obese woman with type 2 diabetes, diabetic retinopathy, hyper­tension, and hirsutism presents to discuss an elevated prolactin level of 144.8 ng/mL (normal range, 4.8 to 23.3 ng/mL) found by her Ob-Gyn two months ago. She complained of galactorrhea and no menses for one year. A repeat prolactin level was also elevated, at 109 ng/mL.

A pituitary MRI with contrast showed a “subtle area of delayed enhancement in the right pituitary, consistent with a 5-mm microadenoma.” The patient was prescribed the dopamine agonist cabergoline (0.25 mg, to be taken twice a week), with a plan to follow up in two to three months.

Q: In obtaining a thorough history, what additional questions should be asked of this patient?

There are many causes of hyperprolactinemia. Factors that can increase prolactin secretion include pregnancy, nursing, physiologic stress, estrogen use, polycystic ovary syndrome, hypothyroidism, and chronic renal or hepatic failure. Head trauma, use of certain medications (verapamil, neuroleptics, antipsychotics, and antidepressants), and presence of nonsecretory sellar or suprasellar masses can also increase prolactin levels. 

In general, signs and symptoms are due to either the effect of excess hormone secretion (ie, galactorrhea and amenorrhea) or local compression (ie, new-onset or persistent headache, dizziness, visual changes, and vision loss). A review of medications, including estrogen therapy, and history of fertility or gonadal dysfunction should be documented. Elevated prolactin levels can result in secondary hypogonadism.¹

Note: While the case patient is female, it should be emphasized that prolactinomas do occur in men. The incidence is, overall, low. In addition to the symptoms listed above, men can present with decreased libido and infertility.¹

Q: What additional diagnostic tests should be ordered as part of the work-up of galactorrhea and amenorrhea in this patient?

Laboratory evaluation should include a repeat serum prolactin test, measurements of TSH and free T4, and a pregnancy test. (A serum testosterone level should be checked in men.) If the results come back normal and if other diagnoses are excluded, the most likely diagnosis is a prolactinoma. In this case, a pituitary MRI should be obtained. Visual field testing can be performed in individuals with specific visual complaints, especially loss or impairment of peripheral vision.

Q: What is the incidence of prolactinoma in the general population?

Prolactin-secreting adenomas, or prolactinomas, are the most common type of pituitary adenoma, accounting for approximately 60% overall.¹ They occur at a frequency of six to 10 cases per million each year.² Prolactinomas are almost always benign; malignant tumors are extremely rare.³

Tumors are classified as microadenomas or macroadenomas, depending on the size. A microadenoma is defined as an intrasellar mass less than 10 mm in diameter. A macroadenoma, defined as larger than 10 mm in diameter, can cause enlargement of the sella turcica.^1,4 The larger the size of the prolactinoma, the greater the prolactin level and higher the likelihood of mass-effect symptoms.⁴

Q: What are the options for treatment of a prolactinoma?

There are several options for treatment of prolactinomas. After discussing all of the available options with the patient, the choice of therapy should be determined by the patient’s desires and potential plans for pregnancy. It is acceptable to observe the tumor with serial MRIs and serum prolactin measurements, provided the tumor is very small and the patient is asymptomatic.⁴

Medication therapy involves treatment with a dopamine agonist, which directly inhibits prolactin secretion by the tumor and therefore suppresses tumor growth. The goal of medication therapy is to suppress the prolactin level to normal range and restore gonadal function. The two dopamine agonists used are bromocriptine and cabergoline. 

Bromocriptine was the first drug available in the United States to effectively treat pituitary adenomas. Its most common adverse effects include nausea, vomiting, dizziness, and postural hypotension. These effects can be minimized or avoided if the drug is started at a low dose, gradually increased, and taken at bedtime. The adverse effects usually subside with continued use; however, in some patients they persist and therefore the drug has to be discontinued.

Cabergoline is a non-ergot dopamine agonist that is more efficacious, overall better tolerated, and longer acting than bromocriptine. It is dosed twice weekly, whereas bromocriptine is dosed once daily.⁴ One factor to consider in a female patient is whether she is of child-bearing age and is interested in conception. Both bromocriptine and cabergoline are designated as category B; however, in animal studies cabergoline has been associated with maternal toxicity, increase in fetal death, and growth retardation and death due to decreased milk secretion by the mother. Therefore, it should only be used during pregnancy if the need has been clearly established.

Dopamine agonists are approximately 80% to 90% effective in decreasing prolactin levels and reducing tumor size in microadenomas and 60% to 70% in macroadenomas. The major drawback of using medication is that it does not always provide permanent results. Hyperprolactinemia and tumor growth can resume upon discontinuation of the drug, even if the patient has taken it for several years.¹ The rate of recurrence after discontinuing therapy can be anywhere from 26% to 69%, and the highest likelihood occurs within a year of withdrawal.⁴ Close clinical follow-up is thus important.

Surgery, typically a transphenoidal resection, is performed by a neurosurgeon. Success of surgery is based on tumor size and basal prolactin level prior to the procedure. It is more effective in restoring normal prolactin levels and resolution of symptoms in microadenomas than in macroadenomas. Progressive vision loss, pituitary apoplexy, and intolerance to dopamine agonists are indications for surgery.¹

Radiation therapy is reserved for those patients who have residual tumors postsurgery and have not responded to or are intolerant to dopamine agonists. Response to radiation is slow; it can sometimes take several years to achieve full effect. Gamma-knife radiation is sometimes used, but experience with this procedure is limited thus far in prolactinomas.

Overall, the vast majority of prolactinomas are benign and fairly straightforward to manage clinically.³           

REFERENCES
1. Greenspan F, Gardner D. Basic & Clinical Endocrinology, 7th ed. New York: McGraw-Hill; 2004.

2. Ciccarelli A, Daly A, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8(1):3-6.

3. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.

4. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline. J Clinical Endocrinol Metab. 2011;96(2):273-288.

A 42-year-old obese woman with type 2 diabetes, diabetic retinopathy, hyper­tension, and hirsutism presents to discuss an elevated prolactin level of 144.8 ng/mL (normal range, 4.8 to 23.3 ng/mL) found by her Ob-Gyn two months ago. She complained of galactorrhea and no menses for one year. A repeat prolactin level was also elevated, at 109 ng/mL.

A pituitary MRI with contrast showed a “subtle area of delayed enhancement in the right pituitary, consistent with a 5-mm microadenoma.” The patient was prescribed the dopamine agonist cabergoline (0.25 mg, to be taken twice a week), with a plan to follow up in two to three months.

Q: In obtaining a thorough history, what additional questions should be asked of this patient?

There are many causes of hyperprolactinemia. Factors that can increase prolactin secretion include pregnancy, nursing, physiologic stress, estrogen use, polycystic ovary syndrome, hypothyroidism, and chronic renal or hepatic failure. Head trauma, use of certain medications (verapamil, neuroleptics, antipsychotics, and antidepressants), and presence of nonsecretory sellar or suprasellar masses can also increase prolactin levels. 

In general, signs and symptoms are due to either the effect of excess hormone secretion (ie, galactorrhea and amenorrhea) or local compression (ie, new-onset or persistent headache, dizziness, visual changes, and vision loss). A review of medications, including estrogen therapy, and history of fertility or gonadal dysfunction should be documented. Elevated prolactin levels can result in secondary hypogonadism.¹

Note: While the case patient is female, it should be emphasized that prolactinomas do occur in men. The incidence is, overall, low. In addition to the symptoms listed above, men can present with decreased libido and infertility.¹

Q: What additional diagnostic tests should be ordered as part of the work-up of galactorrhea and amenorrhea in this patient?

Laboratory evaluation should include a repeat serum prolactin test, measurements of TSH and free T4, and a pregnancy test. (A serum testosterone level should be checked in men.) If the results come back normal and if other diagnoses are excluded, the most likely diagnosis is a prolactinoma. In this case, a pituitary MRI should be obtained. Visual field testing can be performed in individuals with specific visual complaints, especially loss or impairment of peripheral vision.

Q: What is the incidence of prolactinoma in the general population?

Prolactin-secreting adenomas, or prolactinomas, are the most common type of pituitary adenoma, accounting for approximately 60% overall.¹ They occur at a frequency of six to 10 cases per million each year.² Prolactinomas are almost always benign; malignant tumors are extremely rare.³

Tumors are classified as microadenomas or macroadenomas, depending on the size. A microadenoma is defined as an intrasellar mass less than 10 mm in diameter. A macroadenoma, defined as larger than 10 mm in diameter, can cause enlargement of the sella turcica.^1,4 The larger the size of the prolactinoma, the greater the prolactin level and higher the likelihood of mass-effect symptoms.⁴

Q: What are the options for treatment of a prolactinoma?

There are several options for treatment of prolactinomas. After discussing all of the available options with the patient, the choice of therapy should be determined by the patient’s desires and potential plans for pregnancy. It is acceptable to observe the tumor with serial MRIs and serum prolactin measurements, provided the tumor is very small and the patient is asymptomatic.⁴

Medication therapy involves treatment with a dopamine agonist, which directly inhibits prolactin secretion by the tumor and therefore suppresses tumor growth. The goal of medication therapy is to suppress the prolactin level to normal range and restore gonadal function. The two dopamine agonists used are bromocriptine and cabergoline. 

Bromocriptine was the first drug available in the United States to effectively treat pituitary adenomas. Its most common adverse effects include nausea, vomiting, dizziness, and postural hypotension. These effects can be minimized or avoided if the drug is started at a low dose, gradually increased, and taken at bedtime. The adverse effects usually subside with continued use; however, in some patients they persist and therefore the drug has to be discontinued.

Cabergoline is a non-ergot dopamine agonist that is more efficacious, overall better tolerated, and longer acting than bromocriptine. It is dosed twice weekly, whereas bromocriptine is dosed once daily.⁴ One factor to consider in a female patient is whether she is of child-bearing age and is interested in conception. Both bromocriptine and cabergoline are designated as category B; however, in animal studies cabergoline has been associated with maternal toxicity, increase in fetal death, and growth retardation and death due to decreased milk secretion by the mother. Therefore, it should only be used during pregnancy if the need has been clearly established.

Dopamine agonists are approximately 80% to 90% effective in decreasing prolactin levels and reducing tumor size in microadenomas and 60% to 70% in macroadenomas. The major drawback of using medication is that it does not always provide permanent results. Hyperprolactinemia and tumor growth can resume upon discontinuation of the drug, even if the patient has taken it for several years.¹ The rate of recurrence after discontinuing therapy can be anywhere from 26% to 69%, and the highest likelihood occurs within a year of withdrawal.⁴ Close clinical follow-up is thus important.

Surgery, typically a transphenoidal resection, is performed by a neurosurgeon. Success of surgery is based on tumor size and basal prolactin level prior to the procedure. It is more effective in restoring normal prolactin levels and resolution of symptoms in microadenomas than in macroadenomas. Progressive vision loss, pituitary apoplexy, and intolerance to dopamine agonists are indications for surgery.¹

Radiation therapy is reserved for those patients who have residual tumors postsurgery and have not responded to or are intolerant to dopamine agonists. Response to radiation is slow; it can sometimes take several years to achieve full effect. Gamma-knife radiation is sometimes used, but experience with this procedure is limited thus far in prolactinomas.

Overall, the vast majority of prolactinomas are benign and fairly straightforward to manage clinically.³           

REFERENCES
1. Greenspan F, Gardner D. Basic & Clinical Endocrinology, 7th ed. New York: McGraw-Hill; 2004.

2. Ciccarelli A, Daly A, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8(1):3-6.

3. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.

4. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline. J Clinical Endocrinol Metab. 2011;96(2):273-288.

Despite therapeutic advances in diabetes management, the majority of patients with diabetes are unable to achieve glycemic targets proven to reduce the burden of the disease. This burden not only involves the quality of life of patients with diabetes who experience the complications of this disease; it also includes the burden to society. One out of every five health care dollars is spent on caring for someone with diabetes—the majority on treating the complications.¹

Major barriers to patients’ ability to achieve glycemic goals include the need to make behavioral changes, lack of awareness of glycemic levels, and fear of hypoglycemia.²

Q: Is self-monitoring of blood glucose worthwhile in diabetes?

Studies have shown a benefit from self-monitoring of blood glucose (SMBG) in patients using insulin but not in those taking oral antidiabetic drugs. However, the American Diabetes Association recommends that patients with diabetes monitor their glucose once daily if they are being treated with noninsulin therapy and at least three times daily if they are taking insulin.³

Guidelines from the American Association of Clinical Endocrinologists (AACE) state that patients taking noninsulin or once-daily insulin therapy who have not achieved A1C targets should monitor at least twice daily, while those at target should monitor at least once daily. Those taking multiple daily injections should perform SMBG at least three times per day. If patients experience frequent hypoglycemia, AACE suggests monitoring glucose more often.⁴

The A1C test provides the “big picture,” the average daily glucose level during the previous 90 to 120 days, and correlates with end-organ impact. It does not identify glycemic variability, hypoglycemia, or hyperglycemia.

By contrast, SMBG patterns provide day-to-day data that can be used to select and manage glucose control programs and ultimately optimize a patient’s A1C. SMBG provides a measure of the specific pharmacologic impact of medications and, through feedback, allows design and implementation of physiologic insulin-replacement programs.

One example of SMBG is to have patients monitor glucose in pairs (ie, pick a meal each day and do a premeal and two-hour postmeal reading) and ask them to keep a log or download the data from their meter in the office. This type of monitoring can be enlightening and self-empowering for the patient in that it can provide valuable information regarding the glycemic response to the particular meal.

Intensive glycemic management has been shown to reduce the incidence and progression of diabetic complications. However, it is associated with an increase in severe hypoglycemia. This is worrisome for both patients and providers, as severe hypoglycemia has been associated with an increase in risk for mortality. SMBG can assist patients in understanding how their lifestyle affects their diabetes, as well as identifying hypoglycemia for those who may have hypoglycemia unawareness (ie, who lack the relevant symptoms).

Q: What is continuous glucose monitoring (CGM)?

CGM devices give real-time readouts of current glucose levels. They utilize a subcutaneous sensor that is inserted in the abdomen and worn for 3 to 7 days (depending on which device is used). The sensor sends an electronic signal to a receiver worn by the patient.

There are three major CGM devices that have been approved by the FDA and are available for both personal and professional use. Health care providers can purchase the units and have patients wear them for retrospective analysis; this is a reimbursable expense. All available CGM devices measure glucose values in the interstitial fluid. The sensor reads electrical current produced by the same glucose-oxidase reaction that is utilized by glucose meters that patients use to perform fingersticks for home monitoring.

Currently available CGM systems need to be calibrated at least twice daily. Sensor calibration entails the pairing of the fingerstick value with the sensor value from the interstitial space. Calibration confirms sensor accuracy during various points by “teaching” the sensor the glucose value that corresponds with the electrical current signal.

There is a known physiologic lag time that occurs between fingerstick and sensor values. This lag time is typically up to 15 minutes but is increased with rapidly changing glucose values.

Q: What are the benefits of CGM?

Recent studies have shown CGM can improve A1C without increasing the incidence of hypoglycemia.⁵

CGM systems have both low and high glucose threshold alarms that can be set to alert once the threshold is reached. The newest generation devices can also predict hypoglycemia or hyperglycemia by tracking rate of change, and users can be alerted to a potential event. This would then allow them to take appropriate action, such as consuming food or carbohydrates or taking insulin as necessary. (Before taking any action, the glucose should first be confirmed by SMBG.)

Software programs allow for review of glucose data, which can assist in identifying trends not appreciated by typical SMBG testing (such as nocturnal hypoglycemia and meal-time excursions). This allows for adjustment of insulin regimens to reduce the incidence of these events.

Q: Can CGM replace SMBG?

While CGM can provide much more detail regarding glucose trends and patterns, it is not a replacement for SMBG. CGM should not be used as a replacement for SMBG to dose insulin for meal- or activity-related adjustments. All dosing decisions should be based on the SMBG.

Currently, CGM is indicated for patients 18 or older, in conjunction with SMBG for the purpose of improving glycemic control:

• to identify and aid in management of glycemic patterns not recognized with typical SMBG

• to prevent glycemic excursions of hypoglycemia and hyperglycemia.

Its use is supported by ADA and AACE guidelines for glucose monitoring.

Q: Who would benefit from CGM?

Suitable candidates for CGM include those with a high degree of glycemic variability, those with hypoglycemic unawareness, shift workers, patients who use insulin pumps, athletes, and women who are planning to become or are pregnant. Patients should work closely with their health care team and perform regular SMBG.

It has been suggested that patients need comprehensive training and follow-up visits to fully understand the large amount of data that they can be confronted with, in order to fully benefit from these devices.⁶ While the accuracy is improving, there are a few limitations to this technology, including false alarms. Studies have also shown a positive correlation between sensor wear time (hours per week) and greater reductions in A1C.⁵

Conclusion
Glucose monitoring is a necessary tool—for patients as well as providers—that assists in identifying how patients’ lifestyles affect their diabetes.

Despite therapeutic advances in diabetes management, the majority of patients with diabetes are unable to achieve glycemic targets proven to reduce the burden of the disease. This burden not only involves the quality of life of patients with diabetes who experience the complications of this disease; it also includes the burden to society. One out of every five health care dollars is spent on caring for someone with diabetes—the majority on treating the complications.¹

Major barriers to patients’ ability to achieve glycemic goals include the need to make behavioral changes, lack of awareness of glycemic levels, and fear of hypoglycemia.²

Q: Is self-monitoring of blood glucose worthwhile in diabetes?

Studies have shown a benefit from self-monitoring of blood glucose (SMBG) in patients using insulin but not in those taking oral antidiabetic drugs. However, the American Diabetes Association recommends that patients with diabetes monitor their glucose once daily if they are being treated with noninsulin therapy and at least three times daily if they are taking insulin.³

Guidelines from the American Association of Clinical Endocrinologists (AACE) state that patients taking noninsulin or once-daily insulin therapy who have not achieved A1C targets should monitor at least twice daily, while those at target should monitor at least once daily. Those taking multiple daily injections should perform SMBG at least three times per day. If patients experience frequent hypoglycemia, AACE suggests monitoring glucose more often.⁴

The A1C test provides the “big picture,” the average daily glucose level during the previous 90 to 120 days, and correlates with end-organ impact. It does not identify glycemic variability, hypoglycemia, or hyperglycemia.

By contrast, SMBG patterns provide day-to-day data that can be used to select and manage glucose control programs and ultimately optimize a patient’s A1C. SMBG provides a measure of the specific pharmacologic impact of medications and, through feedback, allows design and implementation of physiologic insulin-replacement programs.

One example of SMBG is to have patients monitor glucose in pairs (ie, pick a meal each day and do a premeal and two-hour postmeal reading) and ask them to keep a log or download the data from their meter in the office. This type of monitoring can be enlightening and self-empowering for the patient in that it can provide valuable information regarding the glycemic response to the particular meal.

Intensive glycemic management has been shown to reduce the incidence and progression of diabetic complications. However, it is associated with an increase in severe hypoglycemia. This is worrisome for both patients and providers, as severe hypoglycemia has been associated with an increase in risk for mortality. SMBG can assist patients in understanding how their lifestyle affects their diabetes, as well as identifying hypoglycemia for those who may have hypoglycemia unawareness (ie, who lack the relevant symptoms).

Q: What is continuous glucose monitoring (CGM)?

CGM devices give real-time readouts of current glucose levels. They utilize a subcutaneous sensor that is inserted in the abdomen and worn for 3 to 7 days (depending on which device is used). The sensor sends an electronic signal to a receiver worn by the patient.

There are three major CGM devices that have been approved by the FDA and are available for both personal and professional use. Health care providers can purchase the units and have patients wear them for retrospective analysis; this is a reimbursable expense. All available CGM devices measure glucose values in the interstitial fluid. The sensor reads electrical current produced by the same glucose-oxidase reaction that is utilized by glucose meters that patients use to perform fingersticks for home monitoring.

Currently available CGM systems need to be calibrated at least twice daily. Sensor calibration entails the pairing of the fingerstick value with the sensor value from the interstitial space. Calibration confirms sensor accuracy during various points by “teaching” the sensor the glucose value that corresponds with the electrical current signal.

There is a known physiologic lag time that occurs between fingerstick and sensor values. This lag time is typically up to 15 minutes but is increased with rapidly changing glucose values.

Q: What are the benefits of CGM?

Recent studies have shown CGM can improve A1C without increasing the incidence of hypoglycemia.⁵

CGM systems have both low and high glucose threshold alarms that can be set to alert once the threshold is reached. The newest generation devices can also predict hypoglycemia or hyperglycemia by tracking rate of change, and users can be alerted to a potential event. This would then allow them to take appropriate action, such as consuming food or carbohydrates or taking insulin as necessary. (Before taking any action, the glucose should first be confirmed by SMBG.)

Software programs allow for review of glucose data, which can assist in identifying trends not appreciated by typical SMBG testing (such as nocturnal hypoglycemia and meal-time excursions). This allows for adjustment of insulin regimens to reduce the incidence of these events.

Q: Can CGM replace SMBG?

While CGM can provide much more detail regarding glucose trends and patterns, it is not a replacement for SMBG. CGM should not be used as a replacement for SMBG to dose insulin for meal- or activity-related adjustments. All dosing decisions should be based on the SMBG.

Currently, CGM is indicated for patients 18 or older, in conjunction with SMBG for the purpose of improving glycemic control:

• to identify and aid in management of glycemic patterns not recognized with typical SMBG

• to prevent glycemic excursions of hypoglycemia and hyperglycemia.

Its use is supported by ADA and AACE guidelines for glucose monitoring.

Q: Who would benefit from CGM?

Suitable candidates for CGM include those with a high degree of glycemic variability, those with hypoglycemic unawareness, shift workers, patients who use insulin pumps, athletes, and women who are planning to become or are pregnant. Patients should work closely with their health care team and perform regular SMBG.

It has been suggested that patients need comprehensive training and follow-up visits to fully understand the large amount of data that they can be confronted with, in order to fully benefit from these devices.⁶ While the accuracy is improving, there are a few limitations to this technology, including false alarms. Studies have also shown a positive correlation between sensor wear time (hours per week) and greater reductions in A1C.⁵

Conclusion
Glucose monitoring is a necessary tool—for patients as well as providers—that assists in identifying how patients’ lifestyles affect their diabetes.

Despite therapeutic advances in diabetes management, the majority of patients with diabetes are unable to achieve glycemic targets proven to reduce the burden of the disease. This burden not only involves the quality of life of patients with diabetes who experience the complications of this disease; it also includes the burden to society. One out of every five health care dollars is spent on caring for someone with diabetes—the majority on treating the complications.¹

Major barriers to patients’ ability to achieve glycemic goals include the need to make behavioral changes, lack of awareness of glycemic levels, and fear of hypoglycemia.²

Q: Is self-monitoring of blood glucose worthwhile in diabetes?

Studies have shown a benefit from self-monitoring of blood glucose (SMBG) in patients using insulin but not in those taking oral antidiabetic drugs. However, the American Diabetes Association recommends that patients with diabetes monitor their glucose once daily if they are being treated with noninsulin therapy and at least three times daily if they are taking insulin.³

Guidelines from the American Association of Clinical Endocrinologists (AACE) state that patients taking noninsulin or once-daily insulin therapy who have not achieved A1C targets should monitor at least twice daily, while those at target should monitor at least once daily. Those taking multiple daily injections should perform SMBG at least three times per day. If patients experience frequent hypoglycemia, AACE suggests monitoring glucose more often.⁴

The A1C test provides the “big picture,” the average daily glucose level during the previous 90 to 120 days, and correlates with end-organ impact. It does not identify glycemic variability, hypoglycemia, or hyperglycemia.

By contrast, SMBG patterns provide day-to-day data that can be used to select and manage glucose control programs and ultimately optimize a patient’s A1C. SMBG provides a measure of the specific pharmacologic impact of medications and, through feedback, allows design and implementation of physiologic insulin-replacement programs.

One example of SMBG is to have patients monitor glucose in pairs (ie, pick a meal each day and do a premeal and two-hour postmeal reading) and ask them to keep a log or download the data from their meter in the office. This type of monitoring can be enlightening and self-empowering for the patient in that it can provide valuable information regarding the glycemic response to the particular meal.

Intensive glycemic management has been shown to reduce the incidence and progression of diabetic complications. However, it is associated with an increase in severe hypoglycemia. This is worrisome for both patients and providers, as severe hypoglycemia has been associated with an increase in risk for mortality. SMBG can assist patients in understanding how their lifestyle affects their diabetes, as well as identifying hypoglycemia for those who may have hypoglycemia unawareness (ie, who lack the relevant symptoms).

Q: What is continuous glucose monitoring (CGM)?

CGM devices give real-time readouts of current glucose levels. They utilize a subcutaneous sensor that is inserted in the abdomen and worn for 3 to 7 days (depending on which device is used). The sensor sends an electronic signal to a receiver worn by the patient.

There are three major CGM devices that have been approved by the FDA and are available for both personal and professional use. Health care providers can purchase the units and have patients wear them for retrospective analysis; this is a reimbursable expense. All available CGM devices measure glucose values in the interstitial fluid. The sensor reads electrical current produced by the same glucose-oxidase reaction that is utilized by glucose meters that patients use to perform fingersticks for home monitoring.

Currently available CGM systems need to be calibrated at least twice daily. Sensor calibration entails the pairing of the fingerstick value with the sensor value from the interstitial space. Calibration confirms sensor accuracy during various points by “teaching” the sensor the glucose value that corresponds with the electrical current signal.

There is a known physiologic lag time that occurs between fingerstick and sensor values. This lag time is typically up to 15 minutes but is increased with rapidly changing glucose values.

Q: What are the benefits of CGM?

Recent studies have shown CGM can improve A1C without increasing the incidence of hypoglycemia.⁵

CGM systems have both low and high glucose threshold alarms that can be set to alert once the threshold is reached. The newest generation devices can also predict hypoglycemia or hyperglycemia by tracking rate of change, and users can be alerted to a potential event. This would then allow them to take appropriate action, such as consuming food or carbohydrates or taking insulin as necessary. (Before taking any action, the glucose should first be confirmed by SMBG.)

Software programs allow for review of glucose data, which can assist in identifying trends not appreciated by typical SMBG testing (such as nocturnal hypoglycemia and meal-time excursions). This allows for adjustment of insulin regimens to reduce the incidence of these events.

Q: Can CGM replace SMBG?

While CGM can provide much more detail regarding glucose trends and patterns, it is not a replacement for SMBG. CGM should not be used as a replacement for SMBG to dose insulin for meal- or activity-related adjustments. All dosing decisions should be based on the SMBG.

Currently, CGM is indicated for patients 18 or older, in conjunction with SMBG for the purpose of improving glycemic control:

• to identify and aid in management of glycemic patterns not recognized with typical SMBG

• to prevent glycemic excursions of hypoglycemia and hyperglycemia.

Its use is supported by ADA and AACE guidelines for glucose monitoring.

Q: Who would benefit from CGM?

Suitable candidates for CGM include those with a high degree of glycemic variability, those with hypoglycemic unawareness, shift workers, patients who use insulin pumps, athletes, and women who are planning to become or are pregnant. Patients should work closely with their health care team and perform regular SMBG.

It has been suggested that patients need comprehensive training and follow-up visits to fully understand the large amount of data that they can be confronted with, in order to fully benefit from these devices.⁶ While the accuracy is improving, there are a few limitations to this technology, including false alarms. Studies have also shown a positive correlation between sensor wear time (hours per week) and greater reductions in A1C.⁵

Conclusion
Glucose monitoring is a necessary tool—for patients as well as providers—that assists in identifying how patients’ lifestyles affect their diabetes.

Q: I often detect thyroid nodules in the course of a routine exam or as an incidental finding during diagnostic imaging. How commonly are these found in the general population? 

Thyroid nodules are found on routine physical examination in 3% to 7% of patients. It is important to note that 50% of patients with one palpable nodule on physical exam will have additional nodules on ultrasonography.

Incidental finding of thyroid nodules has increased dramatically with the more frequent use of imaging in medicine (eg, carotid Doppler studies and chest/neck CT). The estimated prevalence of clinically undetected nodules in the general population, as detected by ultrasonography, is 20% to 76%. This wide variation results from technical and definitional ­issues.

Q: What tests should I order if I feel a thyroid nodule on examination or find one or more on a nonrelated imaging study? 

All patients with a palpable or incidental thyroid nodule should undergo thyroid ultrasonography. A serum thyroid-stimulating hormone (TSH) is the best initial screening test for thyroid function. If the TSH is low, it raises suspicion for a hyperfunctioning nodule or gland; a free T4 (thyroxine) and total T3 (triiodothyronine) should follow. If hyperthyroidism is confirmed, a “hot nodule” should be considered. (See section on thyroid scintigraphy below.)

If the TSH is high, measurement of antithyroid peroxidase antibodies (TPOAb) is appropriate. Measurement of serum thyroglobulin is not usually required in the evaluation of thyroid nodules.

Factors that increase the risk for malignancy are: growing and/or fixed nodule; firm or hard consistency; cervical adenopathy; history of head and neck irradiation; family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC); age < 14 or > 70 years; male sex; and persistent dysphonia, dysphagia, or dyspnea.

Q: When should I order a thyroid uptake and scan (thyroid scintigraphy)?

Thyroid scintigraphy may be helpful primarily in patients with a low serum TSH to detect hot nodules. Based on the pattern of radionuclide uptake, nodules are classified as hyperfunctioning (“hot”), hypofunctioning (“cold”), or indeterminate (neither hot nor cold). Hot nodules are almost never malignancies. Cold and indeterminate nodules may be malignant in 3% to 15% of cases. If the TSH is high or normal, the nodules will likely be cold or indeterminate, which has little predictive value.

Q: When should I consider ordering a thyroid fine-needle aspiration (FNA)?

It was once commonly assumed that a finding of multiple nodules on ultrasonography represented a decreased risk for thyroid malignancy. However, it is now known that the risk for malignancy is similar for solitary nodules, nodules in multinodular glands, or nodules embedded in large goiters. Additionally, the risk for cancer in nodules that are palpable on exam and in clinically undetectable nodules found incidentally is very similar (5.0% to 6.4% vs 5.4% to 7.7%, respectively).

Ultrasonographic characteristics can help identify suspicious nodules. This can be helpful in a multinodular gland, from which the nodule(s) chosen for FNA should be the one(s) with the most suspicious characteristics—not necessarily the largest. FNA is typically done by ultrasonographic guidance for more accurate sampling.

Ultrasound findings that may indicate malignancy include: hypoechogenicity in a solid or complex nodule; microcalcifications; irregular margins; intranodular vascularity; rounded appearance; and shape of the nodule more tall (anteroposterior) than wide (transverse).

When two or more of the characteristics above are present, the risk for malignancy increases. Often, ultrasound reports do not include sufficient information on these characteristics. When unsure about a nodule, the clinician should consult the radiologist, who can review the films with him/her for the presence or absence of the above characteristics.

In general, FNA is recommended for:

• Nodules > 1.0 cm that are solid and hypoechoic

•  Nodules of any size with ultrasound findings suggestive of extracapsular growth or metastatic cervical lymph nodes

•  Nodules of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; increased calcitonin levels in the absence of interfering factors

•  Nodules of diameter < 1.0 cm that have ultrasound findings associated with malignancy; the coexistence of two or more suspicious ultrasound criteria greatly increases the risk of thyroid cancer

•  Nodules previously found benign by FNA cytology that have grown significantly or have new suspicious characteristics.

Conclusion
Thyroid ultrasonography is extremely helpful for classification of thyroid nodules based on characteristics that increase the likelihood of malignancy. TSH, thyroid antibody tests, and thyroid scintigraphy assess thyroid function. Serial ultrasonography can follow nodules found to be low-risk and suspicious nodules with benign FNA results. If significant changes occur, reaspiration or surgery should be considered. 

Referral to an endocrinologist is strongly recommended when there is not a clear course of clinical action (eg, cells are atypical or follicular neoplasm cannot be excluded) or a diagnosis of thyroid cancer is suspected. Excellent guidelines for the management of thyroid nodules can be found on the American Association of Clinical Endocrinologists Web site (https://www.aace.com/files/thyroid-guidelines.pdf).

Q: I often detect thyroid nodules in the course of a routine exam or as an incidental finding during diagnostic imaging. How commonly are these found in the general population? 

Thyroid nodules are found on routine physical examination in 3% to 7% of patients. It is important to note that 50% of patients with one palpable nodule on physical exam will have additional nodules on ultrasonography.

Incidental finding of thyroid nodules has increased dramatically with the more frequent use of imaging in medicine (eg, carotid Doppler studies and chest/neck CT). The estimated prevalence of clinically undetected nodules in the general population, as detected by ultrasonography, is 20% to 76%. This wide variation results from technical and definitional ­issues.

Q: What tests should I order if I feel a thyroid nodule on examination or find one or more on a nonrelated imaging study? 

All patients with a palpable or incidental thyroid nodule should undergo thyroid ultrasonography. A serum thyroid-stimulating hormone (TSH) is the best initial screening test for thyroid function. If the TSH is low, it raises suspicion for a hyperfunctioning nodule or gland; a free T4 (thyroxine) and total T3 (triiodothyronine) should follow. If hyperthyroidism is confirmed, a “hot nodule” should be considered. (See section on thyroid scintigraphy below.)

If the TSH is high, measurement of antithyroid peroxidase antibodies (TPOAb) is appropriate. Measurement of serum thyroglobulin is not usually required in the evaluation of thyroid nodules.

Factors that increase the risk for malignancy are: growing and/or fixed nodule; firm or hard consistency; cervical adenopathy; history of head and neck irradiation; family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC); age < 14 or > 70 years; male sex; and persistent dysphonia, dysphagia, or dyspnea.

Q: When should I order a thyroid uptake and scan (thyroid scintigraphy)?

Thyroid scintigraphy may be helpful primarily in patients with a low serum TSH to detect hot nodules. Based on the pattern of radionuclide uptake, nodules are classified as hyperfunctioning (“hot”), hypofunctioning (“cold”), or indeterminate (neither hot nor cold). Hot nodules are almost never malignancies. Cold and indeterminate nodules may be malignant in 3% to 15% of cases. If the TSH is high or normal, the nodules will likely be cold or indeterminate, which has little predictive value.

Q: When should I consider ordering a thyroid fine-needle aspiration (FNA)?

It was once commonly assumed that a finding of multiple nodules on ultrasonography represented a decreased risk for thyroid malignancy. However, it is now known that the risk for malignancy is similar for solitary nodules, nodules in multinodular glands, or nodules embedded in large goiters. Additionally, the risk for cancer in nodules that are palpable on exam and in clinically undetectable nodules found incidentally is very similar (5.0% to 6.4% vs 5.4% to 7.7%, respectively).

Ultrasonographic characteristics can help identify suspicious nodules. This can be helpful in a multinodular gland, from which the nodule(s) chosen for FNA should be the one(s) with the most suspicious characteristics—not necessarily the largest. FNA is typically done by ultrasonographic guidance for more accurate sampling.

Ultrasound findings that may indicate malignancy include: hypoechogenicity in a solid or complex nodule; microcalcifications; irregular margins; intranodular vascularity; rounded appearance; and shape of the nodule more tall (anteroposterior) than wide (transverse).

When two or more of the characteristics above are present, the risk for malignancy increases. Often, ultrasound reports do not include sufficient information on these characteristics. When unsure about a nodule, the clinician should consult the radiologist, who can review the films with him/her for the presence or absence of the above characteristics.

In general, FNA is recommended for:

• Nodules > 1.0 cm that are solid and hypoechoic

•  Nodules of any size with ultrasound findings suggestive of extracapsular growth or metastatic cervical lymph nodes

•  Nodules of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; increased calcitonin levels in the absence of interfering factors

•  Nodules of diameter < 1.0 cm that have ultrasound findings associated with malignancy; the coexistence of two or more suspicious ultrasound criteria greatly increases the risk of thyroid cancer

•  Nodules previously found benign by FNA cytology that have grown significantly or have new suspicious characteristics.

Conclusion
Thyroid ultrasonography is extremely helpful for classification of thyroid nodules based on characteristics that increase the likelihood of malignancy. TSH, thyroid antibody tests, and thyroid scintigraphy assess thyroid function. Serial ultrasonography can follow nodules found to be low-risk and suspicious nodules with benign FNA results. If significant changes occur, reaspiration or surgery should be considered. 

Referral to an endocrinologist is strongly recommended when there is not a clear course of clinical action (eg, cells are atypical or follicular neoplasm cannot be excluded) or a diagnosis of thyroid cancer is suspected. Excellent guidelines for the management of thyroid nodules can be found on the American Association of Clinical Endocrinologists Web site (https://www.aace.com/files/thyroid-guidelines.pdf).

Q: I often detect thyroid nodules in the course of a routine exam or as an incidental finding during diagnostic imaging. How commonly are these found in the general population? 

Thyroid nodules are found on routine physical examination in 3% to 7% of patients. It is important to note that 50% of patients with one palpable nodule on physical exam will have additional nodules on ultrasonography.

Incidental finding of thyroid nodules has increased dramatically with the more frequent use of imaging in medicine (eg, carotid Doppler studies and chest/neck CT). The estimated prevalence of clinically undetected nodules in the general population, as detected by ultrasonography, is 20% to 76%. This wide variation results from technical and definitional ­issues.

Q: What tests should I order if I feel a thyroid nodule on examination or find one or more on a nonrelated imaging study? 

All patients with a palpable or incidental thyroid nodule should undergo thyroid ultrasonography. A serum thyroid-stimulating hormone (TSH) is the best initial screening test for thyroid function. If the TSH is low, it raises suspicion for a hyperfunctioning nodule or gland; a free T4 (thyroxine) and total T3 (triiodothyronine) should follow. If hyperthyroidism is confirmed, a “hot nodule” should be considered. (See section on thyroid scintigraphy below.)

If the TSH is high, measurement of antithyroid peroxidase antibodies (TPOAb) is appropriate. Measurement of serum thyroglobulin is not usually required in the evaluation of thyroid nodules.

Factors that increase the risk for malignancy are: growing and/or fixed nodule; firm or hard consistency; cervical adenopathy; history of head and neck irradiation; family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC); age < 14 or > 70 years; male sex; and persistent dysphonia, dysphagia, or dyspnea.

Q: When should I order a thyroid uptake and scan (thyroid scintigraphy)?

Thyroid scintigraphy may be helpful primarily in patients with a low serum TSH to detect hot nodules. Based on the pattern of radionuclide uptake, nodules are classified as hyperfunctioning (“hot”), hypofunctioning (“cold”), or indeterminate (neither hot nor cold). Hot nodules are almost never malignancies. Cold and indeterminate nodules may be malignant in 3% to 15% of cases. If the TSH is high or normal, the nodules will likely be cold or indeterminate, which has little predictive value.

Q: When should I consider ordering a thyroid fine-needle aspiration (FNA)?

It was once commonly assumed that a finding of multiple nodules on ultrasonography represented a decreased risk for thyroid malignancy. However, it is now known that the risk for malignancy is similar for solitary nodules, nodules in multinodular glands, or nodules embedded in large goiters. Additionally, the risk for cancer in nodules that are palpable on exam and in clinically undetectable nodules found incidentally is very similar (5.0% to 6.4% vs 5.4% to 7.7%, respectively).

Ultrasonographic characteristics can help identify suspicious nodules. This can be helpful in a multinodular gland, from which the nodule(s) chosen for FNA should be the one(s) with the most suspicious characteristics—not necessarily the largest. FNA is typically done by ultrasonographic guidance for more accurate sampling.

Ultrasound findings that may indicate malignancy include: hypoechogenicity in a solid or complex nodule; microcalcifications; irregular margins; intranodular vascularity; rounded appearance; and shape of the nodule more tall (anteroposterior) than wide (transverse).

When two or more of the characteristics above are present, the risk for malignancy increases. Often, ultrasound reports do not include sufficient information on these characteristics. When unsure about a nodule, the clinician should consult the radiologist, who can review the films with him/her for the presence or absence of the above characteristics.

In general, FNA is recommended for:

• Nodules > 1.0 cm that are solid and hypoechoic

•  Nodules of any size with ultrasound findings suggestive of extracapsular growth or metastatic cervical lymph nodes

•  Nodules of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; increased calcitonin levels in the absence of interfering factors

•  Nodules of diameter < 1.0 cm that have ultrasound findings associated with malignancy; the coexistence of two or more suspicious ultrasound criteria greatly increases the risk of thyroid cancer

•  Nodules previously found benign by FNA cytology that have grown significantly or have new suspicious characteristics.

Conclusion
Thyroid ultrasonography is extremely helpful for classification of thyroid nodules based on characteristics that increase the likelihood of malignancy. TSH, thyroid antibody tests, and thyroid scintigraphy assess thyroid function. Serial ultrasonography can follow nodules found to be low-risk and suspicious nodules with benign FNA results. If significant changes occur, reaspiration or surgery should be considered. 

Referral to an endocrinologist is strongly recommended when there is not a clear course of clinical action (eg, cells are atypical or follicular neoplasm cannot be excluded) or a diagnosis of thyroid cancer is suspected. Excellent guidelines for the management of thyroid nodules can be found on the American Association of Clinical Endocrinologists Web site (https://www.aace.com/files/thyroid-guidelines.pdf).

Q: I frequently counsel patients on family planning, pregnancy expectations, and postpartum concerns. Would you please discuss the specifics of postpartum thyroiditis?

Postpartum thyroiditis (PPT) affects about 5% to 10% of postpartum patients, as evidenced by biochemical thyroid dysfunction. It usually presents during the first three to nine months postpartum.

The condition may present as transient hyperthyroidism, transient hypothyroidism, or hyperthyroidism resolving to transient or permanent hypothyroidism. Only one-quarter to one-third of women experience both the hyperthyroid and hypothyroid phases; one-third of patients will have only a thyrotoxic or hypothyroid phase.

Those who are at risk for or develop PPT have underlying autoimmune thyroid disease (eg, Hashimoto’s thyroiditis). During pregnancy, the maternal immune system is partially suppressed; it rebounds dramatically after delivery, leading to increased risk for autoimmune thyroid disease in patients with thyroid peroxidase antibodies (TPOAb).

Q: How do I know if my patients are at risk for thyroid disease during or following pregnancy?

We need to ascertain who is at risk for PPT so we can appropriately evaluate and screen for the condition. It is important to educate your patients prior to or during pregnancy about the risk, timeline of occurrence, and signs/symptoms of PPT.

If possible, I recommend discussing this with patients in the family-planning stages. It would be helpful to ask the prospective mother about a family history of hyperthyroid or hypothyroid disease (eg, Grave’s disease or Hashimoto’s thyroiditis). It’s also important to inquire about other autoimmune diseases in the patient or in her family.

Other autoimmune conditions that increase the risk for thyroid disease are: systemic lupus erythematosus, rheumatoid arthritis, pernicious anemia, vitiligo, type 1 diabetes, and Addison’s disease. Of note, patients with type 1 diabetes are three times more likely than those without that condition to develop PPT.

Q: Which tests will provide the best information about risk for or presence of PPT? When should I order such tests? 

The thyroid-stimulating hormone (TSH) assay is the most sensitive laboratory test for thyroid function in a patient with a normal pituitary-thyroid axis. Testing for TPOAb is the best available screening tool for postpartum thyroiditis, being widely available, economical, and reproducible. Studies evaluating the utility of TPOAb have demonstrated a sensitivity of 46% to 89%, with a specificity of 91% to 98%. Depending on the timeline of the postpartum presentation, an elevated or low TSH level in conjunction with positive TPOAb is pathognomonic for PPT.

If the prospective or expectant mother has a personal or family history of an autoimmune disease, it would be a good idea to obtain a baseline TSH level and TPOAb. If unobtainable beforehand, a baseline TSH during pregnancy is prudent, since many of the signs and symptoms of hyper/hypothyroidism can be similar to those seen in “normal” pregnancy. A normal TSH in the face of elevated TPOAb increases the patient’s likelihood of developing Hashimoto’s thyroiditis or PPT. The best time to check TPOAb is before pregnancy or after delivery, since these antibodies can decrease or even normalize during pregnancy.

Q: Since PPT can be elusive, how might one clinically evaluate the postpartum patient?

The reasons for missed diagnosis of PPT are twofold. First, it results from women reporting few to no symptoms or simply “writing off” the signs and symptoms, thinking they’re related to the significant emotional/physical demands of caring for the new baby. Second, there is a lack of clinician recognition regarding the risk factors, clinical presentation, and frequency of PPT. Since one-third of the hyperthyroidism of PPT is asymptomatic or unreported by patients, it’s easy to see how clinicians can be uncertain whether postpartum anxiety, insomnia, palpitations, increased heart rate, and fatigue reflect thyrotoxicosis or “new mother demands.” Similarly, fatigue, constipation, impaired concentration/memory, weight gain, and depression can be interpreted as hypothyroidism or the emotional and physical challenges of infant care. Since either hyperthyroid or hypothyroid symptoms can be subtle, PPT goes undiagnosed—and therefore, untreated.

Here is an example to provide a clearer understanding:

PPT can go from hyperthyroid to hypothyroid over a four- to six-month period. I like to refer to this evolving process in its three phases to foster understanding of what is going on not only symptomatically but biochemically as well. The first phase starts with a bout of hyperthyroidism from an increased release of thyroid hormone (T4 and/or T3) as a result of nonpainful/nontender thyroid inflammation.

During this first phase, it’s unfortunate that many new mothers’ symptoms are “written off” as the anxieties associated with being a new mother. If a TSH is not ordered, the woman may feel that the clinician is correct in the assessment and that this is all a natural part of the postpartum period. If her hyperthyroid symptoms worsen, she is unlikely to seek follow-up care for fear of being deemed an “anxious mother,” and as a result, the correct diagnosis is missed. 

After approximately two months, the new mother feels better, as the excess thyroid hormones normalize. This is the second (euthryoid) phase. She may now be convinced that her symptoms of anxiety, agitation, palpitations, and insomnia were from the new experience of motherhood or from the new addition to her existing family. 

After two to three months of feeling well, she begins to experience symptoms of hypothyroidism, which is the third phase of PPT. Her symptoms may include depression, constipation, fatigue, and difficulty concentrating. This is another critical time in which the patient or her clinician may attribute her symptoms to all of the emotional changes and demands of caring for her infant. The clinician may question how the mother has felt over the previous couple of months, and since she has felt well, no thyroid studies are ordered. Again, not questioning the assessment, the mother moves on, only to experience worsening symptoms.

The problem here is that if her hypothyroidism is of a permanent nature, as in the case of autoimmune thyroid disease from Hashimoto’s, she will eventually become more symptomatic but may not return for screening or treatment, thinking this is part of the “normal” postpartum period.

Nearly 20% of PPT patients will remain hypothyroid and require lifelong thyroid hormone replacement. The remaining 80% may develop temporary hypothyroidism, requiring thyroid hormone replacement for up to one year, or the thyroiditis will be mild and resolve without the need for such treatment.

Things to Keep in Mind

Understanding who is at increased risk for PPT should prompt the clinician to check the TSH level and TPOAb before pregnancy, if possible. If the patient is pregnant and has the above stated risk factors for autoimmune thyroiditis, obtaining a baseline TSH level is prudent. In order to obtain a more accurate laboratory evaluation, it would be advisable to wait until after pregnancy to check TPOAb, since the maternal immune system is partially suppressed.

If TPOAb can’t be checked until after delivery, it would make clinical sense to test TSH at the same time (around month 3). In women with positive TPOAb before pregnancy and normal thyroid function throughout pregnancy, TSH should be checked at three and six months postpartum. Clinicians should remain astute and order a TSH any time in the interim if they suspect thyroid dysfunction based on patients’ symptoms. Literature supports annual TSH assays in patients in whom PPT resolved, as they have a markedly increased risk for permanent hypothyroidism.

Suggested Reading

Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007;92(8 suppl):S1-S47.

American Thyroid Association Web site. www.thyroid.org.

Stagno-Green A. Postpartum thyroiditis. J Clin Endocrinol Metab. 2002;87(9):4042-4047.

Q: I frequently counsel patients on family planning, pregnancy expectations, and postpartum concerns. Would you please discuss the specifics of postpartum thyroiditis?

Postpartum thyroiditis (PPT) affects about 5% to 10% of postpartum patients, as evidenced by biochemical thyroid dysfunction. It usually presents during the first three to nine months postpartum.

The condition may present as transient hyperthyroidism, transient hypothyroidism, or hyperthyroidism resolving to transient or permanent hypothyroidism. Only one-quarter to one-third of women experience both the hyperthyroid and hypothyroid phases; one-third of patients will have only a thyrotoxic or hypothyroid phase.

Those who are at risk for or develop PPT have underlying autoimmune thyroid disease (eg, Hashimoto’s thyroiditis). During pregnancy, the maternal immune system is partially suppressed; it rebounds dramatically after delivery, leading to increased risk for autoimmune thyroid disease in patients with thyroid peroxidase antibodies (TPOAb).

Q: How do I know if my patients are at risk for thyroid disease during or following pregnancy?

We need to ascertain who is at risk for PPT so we can appropriately evaluate and screen for the condition. It is important to educate your patients prior to or during pregnancy about the risk, timeline of occurrence, and signs/symptoms of PPT.

If possible, I recommend discussing this with patients in the family-planning stages. It would be helpful to ask the prospective mother about a family history of hyperthyroid or hypothyroid disease (eg, Grave’s disease or Hashimoto’s thyroiditis). It’s also important to inquire about other autoimmune diseases in the patient or in her family.

Other autoimmune conditions that increase the risk for thyroid disease are: systemic lupus erythematosus, rheumatoid arthritis, pernicious anemia, vitiligo, type 1 diabetes, and Addison’s disease. Of note, patients with type 1 diabetes are three times more likely than those without that condition to develop PPT.

Q: Which tests will provide the best information about risk for or presence of PPT? When should I order such tests? 

The thyroid-stimulating hormone (TSH) assay is the most sensitive laboratory test for thyroid function in a patient with a normal pituitary-thyroid axis. Testing for TPOAb is the best available screening tool for postpartum thyroiditis, being widely available, economical, and reproducible. Studies evaluating the utility of TPOAb have demonstrated a sensitivity of 46% to 89%, with a specificity of 91% to 98%. Depending on the timeline of the postpartum presentation, an elevated or low TSH level in conjunction with positive TPOAb is pathognomonic for PPT.

If the prospective or expectant mother has a personal or family history of an autoimmune disease, it would be a good idea to obtain a baseline TSH level and TPOAb. If unobtainable beforehand, a baseline TSH during pregnancy is prudent, since many of the signs and symptoms of hyper/hypothyroidism can be similar to those seen in “normal” pregnancy. A normal TSH in the face of elevated TPOAb increases the patient’s likelihood of developing Hashimoto’s thyroiditis or PPT. The best time to check TPOAb is before pregnancy or after delivery, since these antibodies can decrease or even normalize during pregnancy.

Q: Since PPT can be elusive, how might one clinically evaluate the postpartum patient?

The reasons for missed diagnosis of PPT are twofold. First, it results from women reporting few to no symptoms or simply “writing off” the signs and symptoms, thinking they’re related to the significant emotional/physical demands of caring for the new baby. Second, there is a lack of clinician recognition regarding the risk factors, clinical presentation, and frequency of PPT. Since one-third of the hyperthyroidism of PPT is asymptomatic or unreported by patients, it’s easy to see how clinicians can be uncertain whether postpartum anxiety, insomnia, palpitations, increased heart rate, and fatigue reflect thyrotoxicosis or “new mother demands.” Similarly, fatigue, constipation, impaired concentration/memory, weight gain, and depression can be interpreted as hypothyroidism or the emotional and physical challenges of infant care. Since either hyperthyroid or hypothyroid symptoms can be subtle, PPT goes undiagnosed—and therefore, untreated.

Here is an example to provide a clearer understanding:

PPT can go from hyperthyroid to hypothyroid over a four- to six-month period. I like to refer to this evolving process in its three phases to foster understanding of what is going on not only symptomatically but biochemically as well. The first phase starts with a bout of hyperthyroidism from an increased release of thyroid hormone (T4 and/or T3) as a result of nonpainful/nontender thyroid inflammation.

During this first phase, it’s unfortunate that many new mothers’ symptoms are “written off” as the anxieties associated with being a new mother. If a TSH is not ordered, the woman may feel that the clinician is correct in the assessment and that this is all a natural part of the postpartum period. If her hyperthyroid symptoms worsen, she is unlikely to seek follow-up care for fear of being deemed an “anxious mother,” and as a result, the correct diagnosis is missed. 

After approximately two months, the new mother feels better, as the excess thyroid hormones normalize. This is the second (euthryoid) phase. She may now be convinced that her symptoms of anxiety, agitation, palpitations, and insomnia were from the new experience of motherhood or from the new addition to her existing family. 

After two to three months of feeling well, she begins to experience symptoms of hypothyroidism, which is the third phase of PPT. Her symptoms may include depression, constipation, fatigue, and difficulty concentrating. This is another critical time in which the patient or her clinician may attribute her symptoms to all of the emotional changes and demands of caring for her infant. The clinician may question how the mother has felt over the previous couple of months, and since she has felt well, no thyroid studies are ordered. Again, not questioning the assessment, the mother moves on, only to experience worsening symptoms.

The problem here is that if her hypothyroidism is of a permanent nature, as in the case of autoimmune thyroid disease from Hashimoto’s, she will eventually become more symptomatic but may not return for screening or treatment, thinking this is part of the “normal” postpartum period.

Nearly 20% of PPT patients will remain hypothyroid and require lifelong thyroid hormone replacement. The remaining 80% may develop temporary hypothyroidism, requiring thyroid hormone replacement for up to one year, or the thyroiditis will be mild and resolve without the need for such treatment.

Things to Keep in Mind

Understanding who is at increased risk for PPT should prompt the clinician to check the TSH level and TPOAb before pregnancy, if possible. If the patient is pregnant and has the above stated risk factors for autoimmune thyroiditis, obtaining a baseline TSH level is prudent. In order to obtain a more accurate laboratory evaluation, it would be advisable to wait until after pregnancy to check TPOAb, since the maternal immune system is partially suppressed.

If TPOAb can’t be checked until after delivery, it would make clinical sense to test TSH at the same time (around month 3). In women with positive TPOAb before pregnancy and normal thyroid function throughout pregnancy, TSH should be checked at three and six months postpartum. Clinicians should remain astute and order a TSH any time in the interim if they suspect thyroid dysfunction based on patients’ symptoms. Literature supports annual TSH assays in patients in whom PPT resolved, as they have a markedly increased risk for permanent hypothyroidism.

Suggested Reading

Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007;92(8 suppl):S1-S47.

American Thyroid Association Web site. www.thyroid.org.

Stagno-Green A. Postpartum thyroiditis. J Clin Endocrinol Metab. 2002;87(9):4042-4047.

Q: I frequently counsel patients on family planning, pregnancy expectations, and postpartum concerns. Would you please discuss the specifics of postpartum thyroiditis?

Postpartum thyroiditis (PPT) affects about 5% to 10% of postpartum patients, as evidenced by biochemical thyroid dysfunction. It usually presents during the first three to nine months postpartum.

The condition may present as transient hyperthyroidism, transient hypothyroidism, or hyperthyroidism resolving to transient or permanent hypothyroidism. Only one-quarter to one-third of women experience both the hyperthyroid and hypothyroid phases; one-third of patients will have only a thyrotoxic or hypothyroid phase.

Those who are at risk for or develop PPT have underlying autoimmune thyroid disease (eg, Hashimoto’s thyroiditis). During pregnancy, the maternal immune system is partially suppressed; it rebounds dramatically after delivery, leading to increased risk for autoimmune thyroid disease in patients with thyroid peroxidase antibodies (TPOAb).

Q: How do I know if my patients are at risk for thyroid disease during or following pregnancy?

We need to ascertain who is at risk for PPT so we can appropriately evaluate and screen for the condition. It is important to educate your patients prior to or during pregnancy about the risk, timeline of occurrence, and signs/symptoms of PPT.

If possible, I recommend discussing this with patients in the family-planning stages. It would be helpful to ask the prospective mother about a family history of hyperthyroid or hypothyroid disease (eg, Grave’s disease or Hashimoto’s thyroiditis). It’s also important to inquire about other autoimmune diseases in the patient or in her family.

Other autoimmune conditions that increase the risk for thyroid disease are: systemic lupus erythematosus, rheumatoid arthritis, pernicious anemia, vitiligo, type 1 diabetes, and Addison’s disease. Of note, patients with type 1 diabetes are three times more likely than those without that condition to develop PPT.

Q: Which tests will provide the best information about risk for or presence of PPT? When should I order such tests? 

The thyroid-stimulating hormone (TSH) assay is the most sensitive laboratory test for thyroid function in a patient with a normal pituitary-thyroid axis. Testing for TPOAb is the best available screening tool for postpartum thyroiditis, being widely available, economical, and reproducible. Studies evaluating the utility of TPOAb have demonstrated a sensitivity of 46% to 89%, with a specificity of 91% to 98%. Depending on the timeline of the postpartum presentation, an elevated or low TSH level in conjunction with positive TPOAb is pathognomonic for PPT.

If the prospective or expectant mother has a personal or family history of an autoimmune disease, it would be a good idea to obtain a baseline TSH level and TPOAb. If unobtainable beforehand, a baseline TSH during pregnancy is prudent, since many of the signs and symptoms of hyper/hypothyroidism can be similar to those seen in “normal” pregnancy. A normal TSH in the face of elevated TPOAb increases the patient’s likelihood of developing Hashimoto’s thyroiditis or PPT. The best time to check TPOAb is before pregnancy or after delivery, since these antibodies can decrease or even normalize during pregnancy.

Q: Since PPT can be elusive, how might one clinically evaluate the postpartum patient?

The reasons for missed diagnosis of PPT are twofold. First, it results from women reporting few to no symptoms or simply “writing off” the signs and symptoms, thinking they’re related to the significant emotional/physical demands of caring for the new baby. Second, there is a lack of clinician recognition regarding the risk factors, clinical presentation, and frequency of PPT. Since one-third of the hyperthyroidism of PPT is asymptomatic or unreported by patients, it’s easy to see how clinicians can be uncertain whether postpartum anxiety, insomnia, palpitations, increased heart rate, and fatigue reflect thyrotoxicosis or “new mother demands.” Similarly, fatigue, constipation, impaired concentration/memory, weight gain, and depression can be interpreted as hypothyroidism or the emotional and physical challenges of infant care. Since either hyperthyroid or hypothyroid symptoms can be subtle, PPT goes undiagnosed—and therefore, untreated.

Here is an example to provide a clearer understanding:

PPT can go from hyperthyroid to hypothyroid over a four- to six-month period. I like to refer to this evolving process in its three phases to foster understanding of what is going on not only symptomatically but biochemically as well. The first phase starts with a bout of hyperthyroidism from an increased release of thyroid hormone (T4 and/or T3) as a result of nonpainful/nontender thyroid inflammation.

During this first phase, it’s unfortunate that many new mothers’ symptoms are “written off” as the anxieties associated with being a new mother. If a TSH is not ordered, the woman may feel that the clinician is correct in the assessment and that this is all a natural part of the postpartum period. If her hyperthyroid symptoms worsen, she is unlikely to seek follow-up care for fear of being deemed an “anxious mother,” and as a result, the correct diagnosis is missed. 

After approximately two months, the new mother feels better, as the excess thyroid hormones normalize. This is the second (euthryoid) phase. She may now be convinced that her symptoms of anxiety, agitation, palpitations, and insomnia were from the new experience of motherhood or from the new addition to her existing family. 

After two to three months of feeling well, she begins to experience symptoms of hypothyroidism, which is the third phase of PPT. Her symptoms may include depression, constipation, fatigue, and difficulty concentrating. This is another critical time in which the patient or her clinician may attribute her symptoms to all of the emotional changes and demands of caring for her infant. The clinician may question how the mother has felt over the previous couple of months, and since she has felt well, no thyroid studies are ordered. Again, not questioning the assessment, the mother moves on, only to experience worsening symptoms.

The problem here is that if her hypothyroidism is of a permanent nature, as in the case of autoimmune thyroid disease from Hashimoto’s, she will eventually become more symptomatic but may not return for screening or treatment, thinking this is part of the “normal” postpartum period.

Nearly 20% of PPT patients will remain hypothyroid and require lifelong thyroid hormone replacement. The remaining 80% may develop temporary hypothyroidism, requiring thyroid hormone replacement for up to one year, or the thyroiditis will be mild and resolve without the need for such treatment.

Things to Keep in Mind

Understanding who is at increased risk for PPT should prompt the clinician to check the TSH level and TPOAb before pregnancy, if possible. If the patient is pregnant and has the above stated risk factors for autoimmune thyroiditis, obtaining a baseline TSH level is prudent. In order to obtain a more accurate laboratory evaluation, it would be advisable to wait until after pregnancy to check TPOAb, since the maternal immune system is partially suppressed.

If TPOAb can’t be checked until after delivery, it would make clinical sense to test TSH at the same time (around month 3). In women with positive TPOAb before pregnancy and normal thyroid function throughout pregnancy, TSH should be checked at three and six months postpartum. Clinicians should remain astute and order a TSH any time in the interim if they suspect thyroid dysfunction based on patients’ symptoms. Literature supports annual TSH assays in patients in whom PPT resolved, as they have a markedly increased risk for permanent hypothyroidism.

Suggested Reading

Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007;92(8 suppl):S1-S47.

American Thyroid Association Web site. www.thyroid.org.

Stagno-Green A. Postpartum thyroiditis. J Clin Endocrinol Metab. 2002;87(9):4042-4047.