Imaging

CHICAGO – Cardiac CT angiography in the emergency department safely redirects to home the many patients who would otherwise be admitted for acute chest pain, according to results of the prospective, randomized ACRIN PA 4005 trial.

Low- to intermediate-risk patients who receive cardiac computed tomographic angiography (CCTA) were more likely to be discharged directly from the emergency department (ED), to have shorter hospital stays, and to have more than double the coronary artery disease (CAD) diagnosed than were those receiving a traditional evaluation.

Moreover, none of the 640 patients who had a negative CCTA died or had a myocardial infarction within 30 days after presentation (95% confidence interval, 0-0.57), Dr. Harold Litt, principal investigator of ACRIN (American College of Radiology Imaging Network) PA 4005, said at the annual meeting of the American College of Cardiology.

The upper limit of the confidence interval met the study’s prespecified safety threshold of less than 1%, and may be robust enough to help sway ED physicians who have been unwilling to adopt a CT-based strategy because similar findings from other randomized trials were not sufficiently powered.

"This is a large public health problem," Dr. Litt said, noting that roughly 2%-3% of patients are discharged from the ED with an unrecognized MI.

Conversely, more than 6 million Americans visit the ED for chest pain each year. Only 10%-15% are ultimately diagnosed with acute coronary syndrome (ACS), with most admitted to hospitals at a staggering cost of more than $3 billion annually.

The ACRIN PA 4005 trial randomized 1,370 patients with symptoms consistent with possible ACS from five clinical sites to undergo at least 64-slice CCTA or traditional evaluation, comprising mostly – but not limited to – exercise treadmill test, stress test with imaging, and stress echocardiography. They had an average TIMI (Thrombolysis in Myocardial Infarction) risk score of 0-2 and an electrocardiogram without acute ischemia. Their average age was about 50 years, and 60% were black.

Half of the 908 CCTA patients were discharged directly from the ED, compared with 23% of the 642 traditional-care patients (95% CI, 21.4-32.2).

The overall length of stay was 18 hours and 25 hours, respectively, but decreased even further to 12 hours for the 602 CCTA patients who had a negative scan, said Dr. Litt, chief of cardiovascular imaging at the University of Pennsylvania Health System in Philadelphia.

The CCTA group was also less likely than was the traditional-care group to have negative findings on invasive angiography (29% vs. 53%; 95% CI, –48.8-3.3).

The finding of more incidental CAD diagnoses in the CCTA arm vs. the traditional-care arm (9% vs. 3.5%; 95% CI, 0-11.2) is more problematic to interpret.

"Will this result in better prevention for them as they go on?" he asked. "Will they be encouraged to have lifestyle modifications and be put on statins, etc., resulting in lower future event rates and not showing up in the emergency room? Or will it just result in more testing that won’t be a benefit to them? We don’t know the answer to that."

No significant differences were observed in a 30-day resource utilization that included catheterization, revascularization, repeat ED visit, rehospitalization, and cardiologist visit. A 1-year follow-up is being obtained, and cost modeling will be conducted, he said. The possibility for substantial health care savings exists, however, as low- to intermediate-risk patients account for 50%-70% of cases presenting with possible ACS.

Overall, MI was reported within 30 days after presentation in 10 CCTA patientsand 5 traditional-care patients (1% vs. 11%; CI, –5.6-5.7). One serious adverse event (bradyarrhythmia) occurred in each group. There were no cardiac deaths in the traditional-care group.

Dr. Litt acknowledged that CCTA does increase radiation exposure, but said that radiation dosage is very technology dependent and that current technology has reduced the average radiation dose to less than that from nuclear myocardial perfusion studies. He also cautioned that the ACRIN PA 4005 results should not be extrapolated to groups with a higher risk of clinically significant coronary disease.

Invited discussant Dr. Thomas Gerber, a professor of medicine and radiology at Mayo Clinic in Jacksonville, Fla., asked why the investigators chose to focus on coronary CT angiography instead of the "triple rule-out" CT angiography strategy to evaluate the coronary arteries, pulmonary arteries, and thoracic aorta, and whether there were any patients who had pulmonary embolism or aortic dissection on subsequent evaluation.

Dr. Litt said they did track PE and acute aortic syndromes, and will report these findings in the future. The investigators used CCTA because they wanted to focus on patients in whom exclusion of ACS was the primary diagnostic question. He acknowledged that not all dissections are visible on CT, but added that "we are getting to the point where the radiology dose from a triple rule-out isn’t all that much higher than from a coronary CT. So in light of that new technology, that question may need to be reevaluated."

In a separate interview, Dr. James G. Adams, professor and chair of emergency medicine at Northwestern University in Chicago, said that no test is perfect, that all the evidence shows that coronary CT is at least as good as other testing strategies used in the initial evaluation of patients with acute chest pain, and that there are fewer hospital admissions.

"This [study] will certainly be used to promote coronary CT for patients at low to moderate risk of coronary disease," he said. "I believe that emergency physicians will increase their use."

Adoption of the CCTA approach depends on much more than whether emergency physicians find the results convincing, emergency physician Dr. Robert Solomon of Allegheny General Hospital in Pittsburgh said in an interview.

"Cardiology and radiology must also buy into it, and the resources necessary to enable clinicians to use this approach must be made available," he said. "This includes cardiologists, radiologists, and trained technologists. The necessary resources will not be available 24-7, even at tertiary care centers, so timing will always be an issue."

This study was sponsored by the Commonwealth of Pennsylvania Department of Health and the American Radiology Imaging Network Foundation. Dr. Litt reported grant funding and travel reimbursement from Siemens Medical Solutions and consulting fees from Medrad-Bayer. The study was simultaneously published online in the New England Journal of Medicine (2012 March 26 [doi:10.1056/NEJMoa1201163]).

CHICAGO – Cardiac CT angiography in the emergency department safely redirects to home the many patients who would otherwise be admitted for acute chest pain, according to results of the prospective, randomized ACRIN PA 4005 trial.

Low- to intermediate-risk patients who receive cardiac computed tomographic angiography (CCTA) were more likely to be discharged directly from the emergency department (ED), to have shorter hospital stays, and to have more than double the coronary artery disease (CAD) diagnosed than were those receiving a traditional evaluation.

Moreover, none of the 640 patients who had a negative CCTA died or had a myocardial infarction within 30 days after presentation (95% confidence interval, 0-0.57), Dr. Harold Litt, principal investigator of ACRIN (American College of Radiology Imaging Network) PA 4005, said at the annual meeting of the American College of Cardiology.

The upper limit of the confidence interval met the study’s prespecified safety threshold of less than 1%, and may be robust enough to help sway ED physicians who have been unwilling to adopt a CT-based strategy because similar findings from other randomized trials were not sufficiently powered.

"This is a large public health problem," Dr. Litt said, noting that roughly 2%-3% of patients are discharged from the ED with an unrecognized MI.

Conversely, more than 6 million Americans visit the ED for chest pain each year. Only 10%-15% are ultimately diagnosed with acute coronary syndrome (ACS), with most admitted to hospitals at a staggering cost of more than $3 billion annually.

The ACRIN PA 4005 trial randomized 1,370 patients with symptoms consistent with possible ACS from five clinical sites to undergo at least 64-slice CCTA or traditional evaluation, comprising mostly – but not limited to – exercise treadmill test, stress test with imaging, and stress echocardiography. They had an average TIMI (Thrombolysis in Myocardial Infarction) risk score of 0-2 and an electrocardiogram without acute ischemia. Their average age was about 50 years, and 60% were black.

Half of the 908 CCTA patients were discharged directly from the ED, compared with 23% of the 642 traditional-care patients (95% CI, 21.4-32.2).

The overall length of stay was 18 hours and 25 hours, respectively, but decreased even further to 12 hours for the 602 CCTA patients who had a negative scan, said Dr. Litt, chief of cardiovascular imaging at the University of Pennsylvania Health System in Philadelphia.

The CCTA group was also less likely than was the traditional-care group to have negative findings on invasive angiography (29% vs. 53%; 95% CI, –48.8-3.3).

The finding of more incidental CAD diagnoses in the CCTA arm vs. the traditional-care arm (9% vs. 3.5%; 95% CI, 0-11.2) is more problematic to interpret.

"Will this result in better prevention for them as they go on?" he asked. "Will they be encouraged to have lifestyle modifications and be put on statins, etc., resulting in lower future event rates and not showing up in the emergency room? Or will it just result in more testing that won’t be a benefit to them? We don’t know the answer to that."

No significant differences were observed in a 30-day resource utilization that included catheterization, revascularization, repeat ED visit, rehospitalization, and cardiologist visit. A 1-year follow-up is being obtained, and cost modeling will be conducted, he said. The possibility for substantial health care savings exists, however, as low- to intermediate-risk patients account for 50%-70% of cases presenting with possible ACS.

Overall, MI was reported within 30 days after presentation in 10 CCTA patientsand 5 traditional-care patients (1% vs. 11%; CI, –5.6-5.7). One serious adverse event (bradyarrhythmia) occurred in each group. There were no cardiac deaths in the traditional-care group.

Dr. Litt acknowledged that CCTA does increase radiation exposure, but said that radiation dosage is very technology dependent and that current technology has reduced the average radiation dose to less than that from nuclear myocardial perfusion studies. He also cautioned that the ACRIN PA 4005 results should not be extrapolated to groups with a higher risk of clinically significant coronary disease.

Invited discussant Dr. Thomas Gerber, a professor of medicine and radiology at Mayo Clinic in Jacksonville, Fla., asked why the investigators chose to focus on coronary CT angiography instead of the "triple rule-out" CT angiography strategy to evaluate the coronary arteries, pulmonary arteries, and thoracic aorta, and whether there were any patients who had pulmonary embolism or aortic dissection on subsequent evaluation.

Dr. Litt said they did track PE and acute aortic syndromes, and will report these findings in the future. The investigators used CCTA because they wanted to focus on patients in whom exclusion of ACS was the primary diagnostic question. He acknowledged that not all dissections are visible on CT, but added that "we are getting to the point where the radiology dose from a triple rule-out isn’t all that much higher than from a coronary CT. So in light of that new technology, that question may need to be reevaluated."

In a separate interview, Dr. James G. Adams, professor and chair of emergency medicine at Northwestern University in Chicago, said that no test is perfect, that all the evidence shows that coronary CT is at least as good as other testing strategies used in the initial evaluation of patients with acute chest pain, and that there are fewer hospital admissions.

"This [study] will certainly be used to promote coronary CT for patients at low to moderate risk of coronary disease," he said. "I believe that emergency physicians will increase their use."

Adoption of the CCTA approach depends on much more than whether emergency physicians find the results convincing, emergency physician Dr. Robert Solomon of Allegheny General Hospital in Pittsburgh said in an interview.

"Cardiology and radiology must also buy into it, and the resources necessary to enable clinicians to use this approach must be made available," he said. "This includes cardiologists, radiologists, and trained technologists. The necessary resources will not be available 24-7, even at tertiary care centers, so timing will always be an issue."

This study was sponsored by the Commonwealth of Pennsylvania Department of Health and the American Radiology Imaging Network Foundation. Dr. Litt reported grant funding and travel reimbursement from Siemens Medical Solutions and consulting fees from Medrad-Bayer. The study was simultaneously published online in the New England Journal of Medicine (2012 March 26 [doi:10.1056/NEJMoa1201163]).

CHICAGO – Cardiac CT angiography in the emergency department safely redirects to home the many patients who would otherwise be admitted for acute chest pain, according to results of the prospective, randomized ACRIN PA 4005 trial.

Low- to intermediate-risk patients who receive cardiac computed tomographic angiography (CCTA) were more likely to be discharged directly from the emergency department (ED), to have shorter hospital stays, and to have more than double the coronary artery disease (CAD) diagnosed than were those receiving a traditional evaluation.

Moreover, none of the 640 patients who had a negative CCTA died or had a myocardial infarction within 30 days after presentation (95% confidence interval, 0-0.57), Dr. Harold Litt, principal investigator of ACRIN (American College of Radiology Imaging Network) PA 4005, said at the annual meeting of the American College of Cardiology.

The upper limit of the confidence interval met the study’s prespecified safety threshold of less than 1%, and may be robust enough to help sway ED physicians who have been unwilling to adopt a CT-based strategy because similar findings from other randomized trials were not sufficiently powered.

"This is a large public health problem," Dr. Litt said, noting that roughly 2%-3% of patients are discharged from the ED with an unrecognized MI.

Conversely, more than 6 million Americans visit the ED for chest pain each year. Only 10%-15% are ultimately diagnosed with acute coronary syndrome (ACS), with most admitted to hospitals at a staggering cost of more than $3 billion annually.

The ACRIN PA 4005 trial randomized 1,370 patients with symptoms consistent with possible ACS from five clinical sites to undergo at least 64-slice CCTA or traditional evaluation, comprising mostly – but not limited to – exercise treadmill test, stress test with imaging, and stress echocardiography. They had an average TIMI (Thrombolysis in Myocardial Infarction) risk score of 0-2 and an electrocardiogram without acute ischemia. Their average age was about 50 years, and 60% were black.

Half of the 908 CCTA patients were discharged directly from the ED, compared with 23% of the 642 traditional-care patients (95% CI, 21.4-32.2).

The overall length of stay was 18 hours and 25 hours, respectively, but decreased even further to 12 hours for the 602 CCTA patients who had a negative scan, said Dr. Litt, chief of cardiovascular imaging at the University of Pennsylvania Health System in Philadelphia.

The CCTA group was also less likely than was the traditional-care group to have negative findings on invasive angiography (29% vs. 53%; 95% CI, –48.8-3.3).

The finding of more incidental CAD diagnoses in the CCTA arm vs. the traditional-care arm (9% vs. 3.5%; 95% CI, 0-11.2) is more problematic to interpret.

"Will this result in better prevention for them as they go on?" he asked. "Will they be encouraged to have lifestyle modifications and be put on statins, etc., resulting in lower future event rates and not showing up in the emergency room? Or will it just result in more testing that won’t be a benefit to them? We don’t know the answer to that."

No significant differences were observed in a 30-day resource utilization that included catheterization, revascularization, repeat ED visit, rehospitalization, and cardiologist visit. A 1-year follow-up is being obtained, and cost modeling will be conducted, he said. The possibility for substantial health care savings exists, however, as low- to intermediate-risk patients account for 50%-70% of cases presenting with possible ACS.

Overall, MI was reported within 30 days after presentation in 10 CCTA patientsand 5 traditional-care patients (1% vs. 11%; CI, –5.6-5.7). One serious adverse event (bradyarrhythmia) occurred in each group. There were no cardiac deaths in the traditional-care group.

Dr. Litt acknowledged that CCTA does increase radiation exposure, but said that radiation dosage is very technology dependent and that current technology has reduced the average radiation dose to less than that from nuclear myocardial perfusion studies. He also cautioned that the ACRIN PA 4005 results should not be extrapolated to groups with a higher risk of clinically significant coronary disease.

Invited discussant Dr. Thomas Gerber, a professor of medicine and radiology at Mayo Clinic in Jacksonville, Fla., asked why the investigators chose to focus on coronary CT angiography instead of the "triple rule-out" CT angiography strategy to evaluate the coronary arteries, pulmonary arteries, and thoracic aorta, and whether there were any patients who had pulmonary embolism or aortic dissection on subsequent evaluation.

Dr. Litt said they did track PE and acute aortic syndromes, and will report these findings in the future. The investigators used CCTA because they wanted to focus on patients in whom exclusion of ACS was the primary diagnostic question. He acknowledged that not all dissections are visible on CT, but added that "we are getting to the point where the radiology dose from a triple rule-out isn’t all that much higher than from a coronary CT. So in light of that new technology, that question may need to be reevaluated."

In a separate interview, Dr. James G. Adams, professor and chair of emergency medicine at Northwestern University in Chicago, said that no test is perfect, that all the evidence shows that coronary CT is at least as good as other testing strategies used in the initial evaluation of patients with acute chest pain, and that there are fewer hospital admissions.

"This [study] will certainly be used to promote coronary CT for patients at low to moderate risk of coronary disease," he said. "I believe that emergency physicians will increase their use."

Adoption of the CCTA approach depends on much more than whether emergency physicians find the results convincing, emergency physician Dr. Robert Solomon of Allegheny General Hospital in Pittsburgh said in an interview.

"Cardiology and radiology must also buy into it, and the resources necessary to enable clinicians to use this approach must be made available," he said. "This includes cardiologists, radiologists, and trained technologists. The necessary resources will not be available 24-7, even at tertiary care centers, so timing will always be an issue."

This study was sponsored by the Commonwealth of Pennsylvania Department of Health and the American Radiology Imaging Network Foundation. Dr. Litt reported grant funding and travel reimbursement from Siemens Medical Solutions and consulting fees from Medrad-Bayer. The study was simultaneously published online in the New England Journal of Medicine (2012 March 26 [doi:10.1056/NEJMoa1201163]).

MADISON, WIS. – Nearly one-fifth of all patients referred for parathyroidectomy were misdiagnosed with primary hyperparathyroidism in a retrospective study of 324 consecutive patients.

Notably, many of these patients had undergone comprehensive work-ups prior to surgical referral that clearly diagnosed secondary hyperparathyroidism.

Patrice Wendling/IMNG Medical Media

"This demonstrates that there’s a prevalent misunderstanding of parathyroid pathophysiology," Dr. James Iannuzzi said at the annual meeting of the Central Surgical Association. "In particular, vitamin D deficiency accounted for the majority of misdiagnosis."

Using ICD-9 codes for hyperparathyroidism, benign, or malignant parathyroid tumors or hypercalcemia, the authors identified 381 patients who were referred to the endocrine surgery division at the University of Rochester (N.Y.) Medical Center between 2008 and 2011 for parathyroidectomy. Primary hyperparathyroidism (HPT) was defined by a calcium level of at least 10 mg/dL plus a parathyroid hormone (PTH) level of more than 50 pg/mL. Thirty patients were excluded for renal failure and 27, for coding errors.

Among the remaining 324 patients, 264 were correctly diagnosed and 60 (18.5%) were misdiagnosed with primary HPT, said Dr. Iannuzzi, a general surgery resident at the university. Fifty-four (90%) of the misdiagnosed patients had secondary HPT at the time of the referral. For 43 patients, this was clear at the time of referral, and 11 had secondary HPT as their sole diagnosis after follow-up. Six patients had hypercalcemia but not HPT. Half of the hypercalcemic patients were referred after a single spuriously elevated calcium level, only to have their calcium drop to normal levels after follow-up, he said.

Most of the 54 patients with secondary HPT had vitamin D deficiency (37 patients). Other causes were gastric bypass (4 patients), celiac disease (2 patients), and unclear etiology (11 patients). Mean calcium and PTH levels among patients with secondary HPT were 9.3 mg/dL and 92 pg/mL, respectively.

In all, 42 (70%) of the 60 misdiagnosed patients underwent inappropriate localized imaging, of which 57% were falsely positive.

"These studies are not indicated; likely to be falsely positive, as we show; and cause patients and referring physicians to more aggressively push for unindicated and potentially harmful surgery because of a finding on a scan," Dr. Jacob Moalem said in an interview. Dr. Moalem, an endocrine surgeon at the University of Rochester, was the senior author of the paper.

Part of the problem is that ultrasound is highly user dependent, and sonographers can be easily misled by exophytic nodules, hypoechoic structures that were subcentimeters, or lymph nodes. Sestamibi scans in this clinical setting also are likely to be positive because of the activated mitochondria. Thus, it is very important that the pretest diagnosis be correct, Dr. Moalem and Dr. Iannuzzi stressed.

Many patients were found to have an elevated PTH during evaluation for symptoms that could have been consistent with primary HPT. Such symptoms were present in 46 of the 60 misdiagnosed patients, the majority of which were from nephrolithiasis (22 patients), he said. Also relevant were bone loss in 15 and vague symptoms such as fatigue or depression in 11.

Although surgery may seem like a simple solution for patients who have an elevated PTH level, symptoms, and positive imaging findings, the operation can be harmful for those with secondary HPT because they’re dependent on increased PTH levels to maintain calcium homeostasis, Dr. Iannuzzi said. Parathyroidectomy is associated with 95%-98% cure rates for primary HPT, but patients with secondary HPT are unlikely to have an intraoperative drop in PTH levels. As a result, they often undergo a bilateral neck exploration that predisposes them to nerve injury. More importantly, if the parathyroid tissue they’re dependent on is removed, it may create irreversible hypoparathyroidism.

"Vigilance is absolutely necessary to avoid unindicated and potentially harmful surgery," Dr. Iannuzzi cautioned.

Invited discussant Dr. Herbert Chen, chair of general surgery and leader of the endocrine oncology group at the University of Wisconsin in Madison, said that the results underscore the role of surgeons as diagnosticians.

"This finding really emphasizes that as surgeons we are not merely technicians operating at the whim of our referring physicians, but have a responsibility to lead in the diagnostic phase of patient care," he said.

Those thoughts were echoed by fellow discussant Dr. Allan Siperstein, chair of endocrine surgery at the Cleveland Clinic, who also asked what lab panels are used to assess patients with mild hyperparathyroidism. Dr. Iannuzzi said that they use an extensive panel including ionized calcium, magnesium, phosphorus, vitamin D, and urinary calcium. Dr. Moalem emphasized that the diagnosis of primary HPT must be made based on simultaneously high or high-normal calcium and PTH measurements. Imaging studies have no role in making or refuting the diagnosis and should be used to guide the operative approach only when the diagnosis of primary HPT has been definitively established.

Dr. Iannuzzi and his coauthors reported no relevant financial disclosures.

MADISON, WIS. – Nearly one-fifth of all patients referred for parathyroidectomy were misdiagnosed with primary hyperparathyroidism in a retrospective study of 324 consecutive patients.

Notably, many of these patients had undergone comprehensive work-ups prior to surgical referral that clearly diagnosed secondary hyperparathyroidism.

Patrice Wendling/IMNG Medical Media

"This demonstrates that there’s a prevalent misunderstanding of parathyroid pathophysiology," Dr. James Iannuzzi said at the annual meeting of the Central Surgical Association. "In particular, vitamin D deficiency accounted for the majority of misdiagnosis."

Using ICD-9 codes for hyperparathyroidism, benign, or malignant parathyroid tumors or hypercalcemia, the authors identified 381 patients who were referred to the endocrine surgery division at the University of Rochester (N.Y.) Medical Center between 2008 and 2011 for parathyroidectomy. Primary hyperparathyroidism (HPT) was defined by a calcium level of at least 10 mg/dL plus a parathyroid hormone (PTH) level of more than 50 pg/mL. Thirty patients were excluded for renal failure and 27, for coding errors.

Among the remaining 324 patients, 264 were correctly diagnosed and 60 (18.5%) were misdiagnosed with primary HPT, said Dr. Iannuzzi, a general surgery resident at the university. Fifty-four (90%) of the misdiagnosed patients had secondary HPT at the time of the referral. For 43 patients, this was clear at the time of referral, and 11 had secondary HPT as their sole diagnosis after follow-up. Six patients had hypercalcemia but not HPT. Half of the hypercalcemic patients were referred after a single spuriously elevated calcium level, only to have their calcium drop to normal levels after follow-up, he said.

Most of the 54 patients with secondary HPT had vitamin D deficiency (37 patients). Other causes were gastric bypass (4 patients), celiac disease (2 patients), and unclear etiology (11 patients). Mean calcium and PTH levels among patients with secondary HPT were 9.3 mg/dL and 92 pg/mL, respectively.

In all, 42 (70%) of the 60 misdiagnosed patients underwent inappropriate localized imaging, of which 57% were falsely positive.

"These studies are not indicated; likely to be falsely positive, as we show; and cause patients and referring physicians to more aggressively push for unindicated and potentially harmful surgery because of a finding on a scan," Dr. Jacob Moalem said in an interview. Dr. Moalem, an endocrine surgeon at the University of Rochester, was the senior author of the paper.

Part of the problem is that ultrasound is highly user dependent, and sonographers can be easily misled by exophytic nodules, hypoechoic structures that were subcentimeters, or lymph nodes. Sestamibi scans in this clinical setting also are likely to be positive because of the activated mitochondria. Thus, it is very important that the pretest diagnosis be correct, Dr. Moalem and Dr. Iannuzzi stressed.

Many patients were found to have an elevated PTH during evaluation for symptoms that could have been consistent with primary HPT. Such symptoms were present in 46 of the 60 misdiagnosed patients, the majority of which were from nephrolithiasis (22 patients), he said. Also relevant were bone loss in 15 and vague symptoms such as fatigue or depression in 11.

Although surgery may seem like a simple solution for patients who have an elevated PTH level, symptoms, and positive imaging findings, the operation can be harmful for those with secondary HPT because they’re dependent on increased PTH levels to maintain calcium homeostasis, Dr. Iannuzzi said. Parathyroidectomy is associated with 95%-98% cure rates for primary HPT, but patients with secondary HPT are unlikely to have an intraoperative drop in PTH levels. As a result, they often undergo a bilateral neck exploration that predisposes them to nerve injury. More importantly, if the parathyroid tissue they’re dependent on is removed, it may create irreversible hypoparathyroidism.

"Vigilance is absolutely necessary to avoid unindicated and potentially harmful surgery," Dr. Iannuzzi cautioned.

Invited discussant Dr. Herbert Chen, chair of general surgery and leader of the endocrine oncology group at the University of Wisconsin in Madison, said that the results underscore the role of surgeons as diagnosticians.

"This finding really emphasizes that as surgeons we are not merely technicians operating at the whim of our referring physicians, but have a responsibility to lead in the diagnostic phase of patient care," he said.

Those thoughts were echoed by fellow discussant Dr. Allan Siperstein, chair of endocrine surgery at the Cleveland Clinic, who also asked what lab panels are used to assess patients with mild hyperparathyroidism. Dr. Iannuzzi said that they use an extensive panel including ionized calcium, magnesium, phosphorus, vitamin D, and urinary calcium. Dr. Moalem emphasized that the diagnosis of primary HPT must be made based on simultaneously high or high-normal calcium and PTH measurements. Imaging studies have no role in making or refuting the diagnosis and should be used to guide the operative approach only when the diagnosis of primary HPT has been definitively established.

Dr. Iannuzzi and his coauthors reported no relevant financial disclosures.

MADISON, WIS. – Nearly one-fifth of all patients referred for parathyroidectomy were misdiagnosed with primary hyperparathyroidism in a retrospective study of 324 consecutive patients.

Notably, many of these patients had undergone comprehensive work-ups prior to surgical referral that clearly diagnosed secondary hyperparathyroidism.

Patrice Wendling/IMNG Medical Media

"This demonstrates that there’s a prevalent misunderstanding of parathyroid pathophysiology," Dr. James Iannuzzi said at the annual meeting of the Central Surgical Association. "In particular, vitamin D deficiency accounted for the majority of misdiagnosis."

Using ICD-9 codes for hyperparathyroidism, benign, or malignant parathyroid tumors or hypercalcemia, the authors identified 381 patients who were referred to the endocrine surgery division at the University of Rochester (N.Y.) Medical Center between 2008 and 2011 for parathyroidectomy. Primary hyperparathyroidism (HPT) was defined by a calcium level of at least 10 mg/dL plus a parathyroid hormone (PTH) level of more than 50 pg/mL. Thirty patients were excluded for renal failure and 27, for coding errors.

Among the remaining 324 patients, 264 were correctly diagnosed and 60 (18.5%) were misdiagnosed with primary HPT, said Dr. Iannuzzi, a general surgery resident at the university. Fifty-four (90%) of the misdiagnosed patients had secondary HPT at the time of the referral. For 43 patients, this was clear at the time of referral, and 11 had secondary HPT as their sole diagnosis after follow-up. Six patients had hypercalcemia but not HPT. Half of the hypercalcemic patients were referred after a single spuriously elevated calcium level, only to have their calcium drop to normal levels after follow-up, he said.

Most of the 54 patients with secondary HPT had vitamin D deficiency (37 patients). Other causes were gastric bypass (4 patients), celiac disease (2 patients), and unclear etiology (11 patients). Mean calcium and PTH levels among patients with secondary HPT were 9.3 mg/dL and 92 pg/mL, respectively.

In all, 42 (70%) of the 60 misdiagnosed patients underwent inappropriate localized imaging, of which 57% were falsely positive.

"These studies are not indicated; likely to be falsely positive, as we show; and cause patients and referring physicians to more aggressively push for unindicated and potentially harmful surgery because of a finding on a scan," Dr. Jacob Moalem said in an interview. Dr. Moalem, an endocrine surgeon at the University of Rochester, was the senior author of the paper.

Part of the problem is that ultrasound is highly user dependent, and sonographers can be easily misled by exophytic nodules, hypoechoic structures that were subcentimeters, or lymph nodes. Sestamibi scans in this clinical setting also are likely to be positive because of the activated mitochondria. Thus, it is very important that the pretest diagnosis be correct, Dr. Moalem and Dr. Iannuzzi stressed.

Many patients were found to have an elevated PTH during evaluation for symptoms that could have been consistent with primary HPT. Such symptoms were present in 46 of the 60 misdiagnosed patients, the majority of which were from nephrolithiasis (22 patients), he said. Also relevant were bone loss in 15 and vague symptoms such as fatigue or depression in 11.

Although surgery may seem like a simple solution for patients who have an elevated PTH level, symptoms, and positive imaging findings, the operation can be harmful for those with secondary HPT because they’re dependent on increased PTH levels to maintain calcium homeostasis, Dr. Iannuzzi said. Parathyroidectomy is associated with 95%-98% cure rates for primary HPT, but patients with secondary HPT are unlikely to have an intraoperative drop in PTH levels. As a result, they often undergo a bilateral neck exploration that predisposes them to nerve injury. More importantly, if the parathyroid tissue they’re dependent on is removed, it may create irreversible hypoparathyroidism.

"Vigilance is absolutely necessary to avoid unindicated and potentially harmful surgery," Dr. Iannuzzi cautioned.

Invited discussant Dr. Herbert Chen, chair of general surgery and leader of the endocrine oncology group at the University of Wisconsin in Madison, said that the results underscore the role of surgeons as diagnosticians.

"This finding really emphasizes that as surgeons we are not merely technicians operating at the whim of our referring physicians, but have a responsibility to lead in the diagnostic phase of patient care," he said.

Those thoughts were echoed by fellow discussant Dr. Allan Siperstein, chair of endocrine surgery at the Cleveland Clinic, who also asked what lab panels are used to assess patients with mild hyperparathyroidism. Dr. Iannuzzi said that they use an extensive panel including ionized calcium, magnesium, phosphorus, vitamin D, and urinary calcium. Dr. Moalem emphasized that the diagnosis of primary HPT must be made based on simultaneously high or high-normal calcium and PTH measurements. Imaging studies have no role in making or refuting the diagnosis and should be used to guide the operative approach only when the diagnosis of primary HPT has been definitively established.

Dr. Iannuzzi and his coauthors reported no relevant financial disclosures.

Evidence of inflammation on spinal MRIs was "marginally predictive" of new syndesmophyte formation 2 years later at the vertebral sites where inflammation was observed, in a study of over 100 patients with ankylosing spondylitis.

However, growth of syndesmophytes that were present at vertebral sites at baseline was not associated with evidence of inflammation on MRIs, reported Dr. Désirée van der Heijde, of Leiden University Medical Center, Leiden, the Netherlands, and her associates, in the March issue of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012;71:369-73).

Courtesy of Dr. Pedro Machado

"MRI inflammation in a vertebral unit slightly increases the likelihood of finding a new syndesmophyte in the same vertebral unit 2 years later, but does not predict the growth of already existing syndesmophytes," they wrote. The finding that most of the syndesmophytes grew in the vertebral units with no MRI evidence of inflammation suggests that "the relationship between MRI inflammation and syndesmophyte formation is not straightforward," they added.

The goal of the study was to address the association between inflammation of a vertebral unit (defined as "the region between two virtual lines through the middle of each vertebra") on MRI and the subsequent formation and growth of syndesmophytes, the excessive bone formation that represents the structural damage seen in ankylosing spondylitis (AS). The processes behind the formation of syndesmophytes in AS are not well understood and are not inhibited by treatment with tumor necrosis factor (TNF) blockers, despite the dramatic effects these agents have on inflammation, they noted.

They used data that included spinal MRI activity scores, from a random sample of people enrolled in ASSERT (AS Study for the Evaluation of Recombinant Infliximab Therapy), a 24-week study published in 2005 that compared infliximab to placebo in patients with active AS and followed patients in a open extension period up to 102 weeks, during which time everyone was treated with infliximab (Arthritis Rheum. 2005;52:582-91).

They analyzed information from 1,827 to 2,070 vertebral units from 177 to 183 patients, (the numbers varied, depending on the case definition and the reader of the MRI). MRI images of all 23 vertebral units of the spine – C2 to S1 – were scored on a scale of 0 to 3 (the presence of inflammation in a vertebral unit was defined as a score greater than 0), and a score from 4 to 6 if erosions were also evident.

After adjusting for possible confounders, the risk of developing a syndesmophyte in a vertebral unit with MRI evidence of inflammation was increased 1.5- to 2-fold, a statistically significant increase, they said.

Depending on the syndesmophyte definition used, the reader of the MRI, and the MRI case definition, 6%-32% of new syndesmophytes developed at the vertebral sites with evidence of active inflammation and 68%-94% of new syndesmophytes developed at the vertebral sites that had no evidence of active inflammation. Similar findings were observed for the syndesmophytes that were present at baseline: 0%-30% of the syndesmophytes that were present at baseline and grew were at sites of active inflammation, and 70%-100% of the syndesmophytes that grew "did so in vertebral units without inflammation," they reported.

"The subtle association between MRI activity and new syndesmophytes is in conflict with the absence of an effect of TNF blockers on structural damage," the authors wrote. One explanation they proposed was that the formation of syndesmophytes is "a post-inflammatory repair reaction that may only be inhibited if a TNF blocker is started early before inflammation gives way to repair."

Based on the finding that evidence of inflammation at the vertebral unit "only marginally predicts" the formation of new syndesmophytes at that site, "if inflammation is indeed the principle trigger of repair responses, a strong case can be made for early and aggressive anti-inflammatory treatment," they speculated. However, they added, "if inflammation and repair are independent pathways triggered by common factors, new therapies targeting the pathologically enhanced repair responses need to be developed."

One of the eight authors was supported by a grant from the Fundação para a Ciência e a Tecnologia (FCT); otherwise, the authors had no disclosures to report.

Evidence of inflammation on spinal MRIs was "marginally predictive" of new syndesmophyte formation 2 years later at the vertebral sites where inflammation was observed, in a study of over 100 patients with ankylosing spondylitis.

However, growth of syndesmophytes that were present at vertebral sites at baseline was not associated with evidence of inflammation on MRIs, reported Dr. Désirée van der Heijde, of Leiden University Medical Center, Leiden, the Netherlands, and her associates, in the March issue of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012;71:369-73).

Courtesy of Dr. Pedro Machado

"MRI inflammation in a vertebral unit slightly increases the likelihood of finding a new syndesmophyte in the same vertebral unit 2 years later, but does not predict the growth of already existing syndesmophytes," they wrote. The finding that most of the syndesmophytes grew in the vertebral units with no MRI evidence of inflammation suggests that "the relationship between MRI inflammation and syndesmophyte formation is not straightforward," they added.

The goal of the study was to address the association between inflammation of a vertebral unit (defined as "the region between two virtual lines through the middle of each vertebra") on MRI and the subsequent formation and growth of syndesmophytes, the excessive bone formation that represents the structural damage seen in ankylosing spondylitis (AS). The processes behind the formation of syndesmophytes in AS are not well understood and are not inhibited by treatment with tumor necrosis factor (TNF) blockers, despite the dramatic effects these agents have on inflammation, they noted.

They used data that included spinal MRI activity scores, from a random sample of people enrolled in ASSERT (AS Study for the Evaluation of Recombinant Infliximab Therapy), a 24-week study published in 2005 that compared infliximab to placebo in patients with active AS and followed patients in a open extension period up to 102 weeks, during which time everyone was treated with infliximab (Arthritis Rheum. 2005;52:582-91).

They analyzed information from 1,827 to 2,070 vertebral units from 177 to 183 patients, (the numbers varied, depending on the case definition and the reader of the MRI). MRI images of all 23 vertebral units of the spine – C2 to S1 – were scored on a scale of 0 to 3 (the presence of inflammation in a vertebral unit was defined as a score greater than 0), and a score from 4 to 6 if erosions were also evident.

After adjusting for possible confounders, the risk of developing a syndesmophyte in a vertebral unit with MRI evidence of inflammation was increased 1.5- to 2-fold, a statistically significant increase, they said.

Depending on the syndesmophyte definition used, the reader of the MRI, and the MRI case definition, 6%-32% of new syndesmophytes developed at the vertebral sites with evidence of active inflammation and 68%-94% of new syndesmophytes developed at the vertebral sites that had no evidence of active inflammation. Similar findings were observed for the syndesmophytes that were present at baseline: 0%-30% of the syndesmophytes that were present at baseline and grew were at sites of active inflammation, and 70%-100% of the syndesmophytes that grew "did so in vertebral units without inflammation," they reported.

"The subtle association between MRI activity and new syndesmophytes is in conflict with the absence of an effect of TNF blockers on structural damage," the authors wrote. One explanation they proposed was that the formation of syndesmophytes is "a post-inflammatory repair reaction that may only be inhibited if a TNF blocker is started early before inflammation gives way to repair."

Based on the finding that evidence of inflammation at the vertebral unit "only marginally predicts" the formation of new syndesmophytes at that site, "if inflammation is indeed the principle trigger of repair responses, a strong case can be made for early and aggressive anti-inflammatory treatment," they speculated. However, they added, "if inflammation and repair are independent pathways triggered by common factors, new therapies targeting the pathologically enhanced repair responses need to be developed."

One of the eight authors was supported by a grant from the Fundação para a Ciência e a Tecnologia (FCT); otherwise, the authors had no disclosures to report.

Evidence of inflammation on spinal MRIs was "marginally predictive" of new syndesmophyte formation 2 years later at the vertebral sites where inflammation was observed, in a study of over 100 patients with ankylosing spondylitis.

However, growth of syndesmophytes that were present at vertebral sites at baseline was not associated with evidence of inflammation on MRIs, reported Dr. Désirée van der Heijde, of Leiden University Medical Center, Leiden, the Netherlands, and her associates, in the March issue of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012;71:369-73).

Courtesy of Dr. Pedro Machado

"MRI inflammation in a vertebral unit slightly increases the likelihood of finding a new syndesmophyte in the same vertebral unit 2 years later, but does not predict the growth of already existing syndesmophytes," they wrote. The finding that most of the syndesmophytes grew in the vertebral units with no MRI evidence of inflammation suggests that "the relationship between MRI inflammation and syndesmophyte formation is not straightforward," they added.

The goal of the study was to address the association between inflammation of a vertebral unit (defined as "the region between two virtual lines through the middle of each vertebra") on MRI and the subsequent formation and growth of syndesmophytes, the excessive bone formation that represents the structural damage seen in ankylosing spondylitis (AS). The processes behind the formation of syndesmophytes in AS are not well understood and are not inhibited by treatment with tumor necrosis factor (TNF) blockers, despite the dramatic effects these agents have on inflammation, they noted.

They used data that included spinal MRI activity scores, from a random sample of people enrolled in ASSERT (AS Study for the Evaluation of Recombinant Infliximab Therapy), a 24-week study published in 2005 that compared infliximab to placebo in patients with active AS and followed patients in a open extension period up to 102 weeks, during which time everyone was treated with infliximab (Arthritis Rheum. 2005;52:582-91).

They analyzed information from 1,827 to 2,070 vertebral units from 177 to 183 patients, (the numbers varied, depending on the case definition and the reader of the MRI). MRI images of all 23 vertebral units of the spine – C2 to S1 – were scored on a scale of 0 to 3 (the presence of inflammation in a vertebral unit was defined as a score greater than 0), and a score from 4 to 6 if erosions were also evident.

After adjusting for possible confounders, the risk of developing a syndesmophyte in a vertebral unit with MRI evidence of inflammation was increased 1.5- to 2-fold, a statistically significant increase, they said.

Depending on the syndesmophyte definition used, the reader of the MRI, and the MRI case definition, 6%-32% of new syndesmophytes developed at the vertebral sites with evidence of active inflammation and 68%-94% of new syndesmophytes developed at the vertebral sites that had no evidence of active inflammation. Similar findings were observed for the syndesmophytes that were present at baseline: 0%-30% of the syndesmophytes that were present at baseline and grew were at sites of active inflammation, and 70%-100% of the syndesmophytes that grew "did so in vertebral units without inflammation," they reported.

"The subtle association between MRI activity and new syndesmophytes is in conflict with the absence of an effect of TNF blockers on structural damage," the authors wrote. One explanation they proposed was that the formation of syndesmophytes is "a post-inflammatory repair reaction that may only be inhibited if a TNF blocker is started early before inflammation gives way to repair."

Based on the finding that evidence of inflammation at the vertebral unit "only marginally predicts" the formation of new syndesmophytes at that site, "if inflammation is indeed the principle trigger of repair responses, a strong case can be made for early and aggressive anti-inflammatory treatment," they speculated. However, they added, "if inflammation and repair are independent pathways triggered by common factors, new therapies targeting the pathologically enhanced repair responses need to be developed."

One of the eight authors was supported by a grant from the Fundação para a Ciência e a Tecnologia (FCT); otherwise, the authors had no disclosures to report.