Rhabdomyolysis and Peroneal Nerve Compression Associated With Thyroid Hormone Withdrawal in the Setting of Remnant Ablation: Review of the Literature

ObjectiveTo review the putative mechanisms whereby hypothyroidism is associated with severe myopathy, neural injury, and acute compartment syndrome and report a case of nontraumatic common peroneal nerve compression associated with hypothyroidism-induced rhabdomyolysis in a patient with diabetes prepared for remnant ablation after thyroidectomy for differentiated thyroid carcinoma.MethodsWe performed a review of the Englishlanguage literature on the PubMed database using the terms hypothyroidism, muscle disease, hypothyroid myopathy, rhabdomyolysis, compression neuropathy, and acute compartment syndrome.ResultsMyopathy occurs frequently among patients with overt hypothyroidism; however, severe myoneural injury seems to be precipitated or accompanied by comorbid conditions. Focal peroneal neuropathy may be related to hypothyroidism-induced extrinsic compression from severe myopathy and soft tissue swelling in a narrowed fascial compartment.ConclusionSevere short-term iatrogenic hypothyroidism may lead to severe myopathy and compression nerve injury in patients with underlying diabetic neuropathy. We recommend avoidance of withdrawal of thyroid hormone for purposes of remnant ablation among patients with preexisting diabetic neuropathy. (Endocr Pract. 2011;17:629-635)     

Hyperkalemia Develops in Some Thyroidectomized Patients Undergoing Thyroid Hormone Withdrawal in Preparation for Radioactive Iodine Ablation for Thyroid Carcinoma

Objective: Hyponatremia is observed in hypothyroidism, but it is not known if hypo- or hyperkalemia is associated with hypothyroidism. To study these questions, we determined serum potassium (K⁺) levels in thyroidectomized patients undergoing levothyroxine withdrawal before radioactive iodine (RAI) therapy for thyroid carcinoma.Methods: We retrospectively studied the records of 108 patients who had undergone total thyroidectomy for thyroid carcinoma followed by levothyroxine withdrawal and then ablation with RAI at Nagasaki University Hospital from 2009–2013. Blood samples were analyzed for serum K⁺ concentrations when patients were euthyroid just before levothyroxine withdrawal and hypothyroid 21 days after levothyroxine withdrawal. We determined the proportion of patients who developed hyperkalemia (K⁺ ≥5 mEq/L) and hypokalemia (K⁺ ≤3.5 mEq/L).Results: Five (4.6%) patients developed hyperkalemia and 2 (1.9%) patients developed hypokalemia after levothyroxine withdrawal. The mean serum K⁺ level after levothyroxine withdrawal was significantly higher than before levothyroxine withdrawal (4.23 ± 0.50 mEq/L vs. 4.09 ± 0.34 mEq/L; P<.001). After levothyroxine withdrawal, serum K⁺ values were significantly correlated with age, serum sodium and creatinine levels, and the estimated glomerular filtration rate but not with serum free thyroxine or thyroid-stimulating hormone concentrations. The finding of an elevated serum K⁺ of >0.5 mEq/L after levothyroxine withdrawal was more prevalent with age >60 years (odds ratio [OR], 4.66; P = .026) and with the use of angiotensin-II receptor blockers or angiotensin-converting enzyme inhibitors (OR, 3.53; P = .033) in a multivariate analysis.Conclusion: Hyperkalemia develops in a small percentage of hypothyroid patients after thyroid hormone withdrawal, especially in patients over 60 years of age who are using antihypertensive agents that inhibit the reninangiotensin- aldosterone system.Abbreviations: ACE-I = angiotensin-converting enzyme inhibitor ARB = angiotensin-II receptor blocker Cr = creatinine eGFR = estimated glomerular filtration rate Eu-K⁺ = serum level of K⁺ in the euthyroid state Hypo-K⁺ = serum level of K⁺ in the hypothyroid state K⁺ = potassium Na⁺ = sodium ?K⁺ = Hypo-K⁺ value minus Eu-K⁺ value RAI = radioactive iodine TSH = thyroid-stimulating hormone     

Recombinant Human Thyroid-Stimulating Hormone To Stimulate 131-1 Uptake For Remnant Ablation And Adjuvant Therapy

ObjectiveTo review the current literature with regard to the use of recombinant human thyroid stimulating hormone (rhTSH) as an adjunct to radioactive iodine (RAI) remnant ablation and adjuvant therapy.MethodsLiterature review of clinical studies examining rhTSH and/or thyroid hormone withdrawal preparations for RAI remnant ablation. The primary endpoints evaluated were (1) effectiveness at ablating the thyroid bed as demonstrated by the lack of significant uptake in the thyroid bed on follow-up diagnostic imaging and (2) effectiveness in facilitating the adjuvant therapy function of RAI ablation as manifested by follow-up thyroid stimulating hormone (TSH)-stimulated serum thyroglobulin levels and clinical outcomes (recurrence rates, likelihood of having no evidence of disease at final follow-up).ResultsRAI remnant ablation can be successfully achieved using either traditional thyroid hormone withdrawal or recombinant human TSH preparation. While initial studies included primarily thyroid cancer patients at low risk of recurrence, more recent studies suggest that rhTSH can also be effectively used as preparation for RAI ablation in patients with an intermediate or high risk of recurrence. Furthermore, while early studies focused primarily on the endpoint of thyroid bed remnant ablation, more recent retrospective studies suggest that final clinical outcomes (recurrence rates, likelihood of achieving no evidence of disease status at final follow-up) over 5-10 years of follow-up are very similar with either method of preparation.ConclusionrhTSH is an effective alternative to thyroid hormone withdrawal in preparation for RAI remnant ablation in patients without evidence of distant metastases who are at low, intermediate, or high risk of recurrence.     

Renal Function and Plasma Renin activity as Potential Factors Causing Hyperkalemia in Patients with Thyroid Carcinoma Undergoing Thyroid Hormone Withdrawal For Radioactive Iodine Therapy

Objective: Hypothyroidism is not commonly considered a cause of hyperkalemia. We previously reported that hyperkalemia was observed mainly in elderly patients treated with renin-angiotensin-aldosterone system (RAS) inhibitors when levothyroxine treatment was withdrawn for the thyroidectomized patients with thyroid carcinoma to undergo radioactive iodine treatment. Here, we investigated whether acute hypothyroidism causes hyperkalemia in patients who were not treated with RAS inhibitors. We also investigated factors influencing potassium metabolism in hypothyroid patients.Methods: We conducted a single-center, prospective cohort study of 46 Japanese patients with thyroid carcinoma undergoing levothyroxine withdrawal prior to radioiodine therapy. All patients were normokalemic before levothyroxine withdrawal. Blood samples were analyzed 3 times: before, and at 3 and 4 weeks after levothyroxine withdrawal. We investigated factors that may be associated with the elevation of serum potassium levels from a euthyroid state to a hypothyroid state.Results: None of the patients developed symptomatic hyperkalemia. The mean serum potassium level was significantly higher at 4 weeks after levothyroxine withdrawal compared to baseline. The serum sodium levels, the estimated glomerular filtration rate (eGFR), and the plasma renin activity (PRA) decreased significantly as hypothyroidism advanced. In contrast, the plasma levels of adrenocorticotropic hormone, cortisol, aldosterone, and antidiuretic hormone were not changed, while serum thyroid hormone decreased. At 4 weeks after their levothyroxine withdrawal, the patients' serum potassium values were significantly correlated with the eGFR and the PRA.Conclusion: Acute hypothyroidism can cause a significant increase in the serum potassium level, which may be associated with a decreased eGFR and decreased circulating RAS.Abbreviations: ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ATPase = adenosine triphosphatase; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; K⁺ = potassium; Na⁺ = sodium; PRA = plasma renin activity; RAS = renin-angiotensin-aldosterone system; T4 = thyroxine; TSH = thyroid-stimulating hormone     

The Role of Recombinant Human Thyrotropin for Diagnostic Monitoring of Patients with Differentiated Thyroid Cancer

ObjectiveTo describe the evolving role of recombinant human thyrotropin in the diagnostic evaluation of patients treated for differentiated thyroid carcinoma.MethodsA systematic review was performed of published English language articles appearing in PubMed using terms “recombinant thyrotropin” and “thyroid cancer”. The author selected articles for inclusion based upon potential for clinical impact of the reported findings.ResultsThe addition of recombinant human thyrotropin to diagnostic testing replaced the requirement for thyroid hormone withdrawal and symptomatic hypothyroidism that had been necessary to generate sufficient endogenous thyrotropin for radioiodine scanning and thyroglobulin testing. The high negative predictive value of stimulated thyroglobulin testing removed the need for serial radioiodine scanning for many patients, but repeated stimulated testing rarely appeared to add significantly. The development of highly sensitive second generation thyroglobulin assays may replace the need for stimulated testing in a subset of patients.ConclusionRecombinant human thyrotropin-stimulated testing continues to be a valuable component of follow-up testing in the first year after initial treatment of differentiated thyroid cancer. (Endocr Pract. 2013;19: 157-161)     

Optimum Recombinant Human Thyrotropin Dose in Patients With Differentiated Thyroid Carcinoma and End-Stage Renal Disease

ObjectiveTo evaluate serum thyrotropin (TSH) concentrations after conventional (0.9 mg) or half-dose (0.45 mg) administration of recombinant human TSH (rhTSH) injections intramuscularly in patients with end-stage renal disease and differentiated thyroid cancer.MethodsIn this case series, we administered 2 doses of 0.9-mg rhTSH or 2 doses of 0.45-mg rhTSH to 3 patients with renal failure and differentiated thyroid cancer who were receiving hemodialysis. Basal serum TSH concentrations were assessed while the patients were taking thyroid hormone therapy. Serum TSH was measured on days 2, 3, 5, 8, 10, 14, and 17 of the study. Thyroglobulin and thyroglobulin antibodies were also measured on days 5 and 7. Patients were asked to report any adverse effects.ResultsPatient 1, who received 2 injections of 0.9- mg rhTSH administered on days 1 and 3, had persistently elevated serum TSH levels for approximately 11 days. Peak serum TSH measured on day 5 was 644 mIU/L. Self-limited diarrhea was the only reported adverse effect. Patients 2 and 3 received 0.45 mg of rhTSH on 2 consecutive days (days 1 and 2), and both exhibited persistently elevated serum TSH levels for 12 days. The peak serum TSH values on day 3 were 402 mIU/L in Patient 2 and 386 mIU/L in Patient 3. No adverse events were observed in these 2 patients. Patient 2 received thyrotropin alfa for injection to confirm disease status. Patient 3 also received a radioiodine dose because of presumed persistent disease.ConclusionHigh serum TSH levels achieved after conventional and half-dose administration of rhTSH suggest that a dose adjustment might be considered in patients with end-stage renal disease. (Endocr Pract. 2008;14: 961-966)     

Silent Thyroiditis,Isolated Corticotropin Deficiency,and Alopecia Universalis in a Patient With Ulcerative Colitis and Elevated Levels of Plasma Factor VIII: An Unusual Case of Autoimmune Polyglandular Syndrome Type 3

ObjectiveTo describe an unusual case of autoimmune polyglandular syndrome (APS) type 3 and provide a brief review of the literature.MethodsWe present the clinical course and laboratory data of a patient with silent thyroiditis, isolated corticotropin (adrenocorticotropic hormone or ACTH) deficiency, alopecia universalis, and ulcerative colitis with an associated hypercoagulable state. The related literature is also reviewed briefly.ResultsA 43-year-old man who had a history of ulcerative colitis with an associated hypercoagulable state and alopecia universalis was referred to the endocrinology department for evaluation of fatigue and a mildly elevated level of thyrotropin (thyroid-stimulating hormone or TSH). He previously had mildly increased TSH levels, for which low-dose levothyroxine therapy had been prescribed. During use of this therapy, a suppressed TSH level developed, necessitating discontinuation of thyroid hormone therapy; a subsequent increase in TSH value was followed by a spontaneous return to euthyroidism. An ACTH stimulation test revealed adrenal insufficiency. His ACTH level was low, 21-hydroxylase antibodies were not present, and further testing demonstrated otherwise intact pituitary function. Magnetic resonance imaging of his pituitary gland showed normal findings. Treatment with hydrocortisone promptly decreased his fatigue. He was found to have an elevated factor VIII level as the cause of his hypercoagulable state. The patient continues to feel well with use of hydrocortisone therapy and has normal thyroid function.ConclusionThis patient’s components of APS type 3 have not been previously reported; thus, the complex nature of the APS variants is supported. (Endocr Pract. 2009;15:138-142)     

Development of Thyroid Storm After Surgical Resection of A Thyrotropin-Secreting Pituitary Adenoma

ObjectiveTo describe a patient with a thyrotropinsecreting pituitary adenoma in whom postoperative thyroid storm developed.MethodsWe present a case report with details of the initial presentation, laboratory evaluation, surgical and pathologic findings, and subsequent course in a patient with a thyrotropin (thyroid-stimulating hormone or TSH)- secreting adenoma and postoperative thyroid storm.ResultsAn 18-year-old male patient presented with severe headaches and was found to have a large suprasellar tumor and a mildly elevated level of TSH. Thyroid storm developed immediately after surgical resection of the pituitary mass. Results of laboratory evaluation undertaken preoperatively became available after the patient had undergone the surgical procedure and revealed thyroid hormone levels 2 to 3 times the upper limit of normal. Propylthiouracil and β-adrenergic blocking agents controlled the postoperative thyrotoxicosis and were subsequently discontinued as his TSH and thyroid hormone levels normalized.ConclusionThis case demonstrates the rare case of a TSH-secreting adenoma in a young patient, which was complicated by the development of postoperative thyroid storm. In addition, this case emphasizes the importance of preoperative pituitary hormonal evaluation and treatment of hormonal abnormalities in all patients presenting with sellar or suprasellar tumors. (Endocr Pract. 2008;14:732- 737)     

Optimal Free Thyroxine Levels for Thyroid Hormone Replacement in Hypothyroidism

ObjectiveTo determine whether a difference exists in the free thyroxine level required to achieve a normal thyrotropin (thyroid-stimulating hormone or TSH) level between patients with primary hypothyroidism and euthyroid control subjects and compare the free thyroxine levels in patients with primary and secondary hypothyroidism receiving thyroid hormone replacement.MethodsWe retrospectively assessed TSH and free thyroxine values in 58 patients with primary hypothyroidism and 78 euthyroid control subjects for whom screening thyroid function tests had been performed. From the medical records, we also obtained free thyroxine values for 23 patients with central hypothyroidism receiving stable levothyroxine replacement therapy.ResultsThe mean free thyroxine level was significantly higher in patients with primary hypothyroidism than in euthyroid control subjects (1.36 ± 0.201 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), whereas the corresponding mean TSH concentrations did not differ significantly (1.60 ± 1.183 mlU/L versus 1.73 ± 0.792 mlU/L, P = .46). The mean free thyroxine value was also significantly higher in the patients with central hypothyroidism in comparison with that in the euthyroid control subjects (1.31 ± 0.278 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), and no significant difference was noted between the patients with primary and central hypothyroidism (1.36 ng/dL versus 1.31 ng/dL, P = .60).ConclusionPatients with hypothyroidism require a higher level of serum free thyroxine to achieve a normal TSH value in comparison with euthyroid control subjects. This finding suggests that patients with central hypothy-roidism should be treated to achieve free thyroxine levels in the upper part of the reference range. (Endocr Pract. 2008;14:550-555)     

Insular Variant of Poorly Differentiated Thyroid Carcinoma

ObjectiveTo present a case of an insular variant of poorly differentiated thyroid carcinoma (PDTC) and to review the literature related to diagnosis, natural history, and treatment of this unusual form of thyroid cancer.MethodsWe present the clinical, laboratory, and pathologic findings of the study patient and review Englishlanguage literature related to PDTC published between 1970 and the present.ResultsPDTC is a controversial and rare epithelial thyroid cancer, intermediate between differentiated thyroid carcinoma and anaplastic thyroid carcinoma that exhibits increased aggressiveness, propensity to local recurrence, distant metastases, and increased mortality. PDTC warrants aggressive management with total thyroidectomy followed by radioactive iodine ablation and potentially additional therapy for residual or recurrent disease. Some carcinomas do not take up radioactive iodine, and dedifferentiated clones of distant metastases may evolve. It is unclear whether chemotherapy is beneficial. Use of additional imaging modalities, including positron emission tomography, 18-fludeoxyglucose positron emission tomography/computed tomography, 18-fludeoxyglucose positron emission tomography/computed tomography/magnetic resonance imaging, ¹²⁴I positron emission tomography/computed tomography, positron emission tomography/magnetic resonance imaging fusion studies, and recombinant human thyrotropin-stimulated radioactive iodine uptake for cancer surveillance are discussed.ConclusionsPDTC is an unusual and aggressive form of thyroid cancer. Fine-needle aspiration cytology may not yield sufficient information to specifically diagnose PDTC. Aggressive management with total thyroidectomy and neck dissection followed by high-dose radioactive iodine remnant ablation is standard. Iodine I 131 whole body scanning is often the initial test for tumor surveillance, with other imaging modalities applied as needed. (Endocr Pract. 2011;17:115-121)     

Metastatic Renal Cell Carcinoma to the Thyroid Gland

ObjectiveTo examine the presentation, diagnosis, and appropriate management of renal clear cell carcinoma metastasis to the thyroid gland.MethodsWe describe a clinical case of solitary thyroid metastasis from renal clear cell carcinoma and present a comprehensive review of the related English-language literature. Common patterns of presentation and generalized overall management recommendations are evaluated and summarized.ResultsEight years after nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid mass. Cytology and histopathologic surgical findings were consistent with a solitary metastasis most compatible with metastatic clear cell carcinoma from his previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the patient remains disease-free 5 years later. Although uncommon, nearly 150 cases of clinically recognized metastatic renal cell carcinoma to the thyroid have been reported in the English-language literature. Metastatic disease from the kidney to the thyroid gland can occur more than 20 years after nephrectomy with the average time interval being 7.5 years. Obtaining a full clinical history in any patient who presents with a thyroid nodule is essential to allow consideration of possible metastatic disease from previous primary tumor. Metastatic disease to the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal cancer is limited to the thyroid gland only, prompt, appropriate surgical intervention can be curative.ConclusionMetastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of renal cell carcinoma. (Endocr Pract. 2008;14:1040-1046)     

Excess Thyroid Hormone and Carbohydrate Metabolism

ObjectiveTo review the pertinent basic and clinical research describing the complex effects of excess thyroid hormone on carbohydrate metabolism.MethodsWe performed a MEDLINE search of the English-language literature using a combination of words (ie, “thyrotoxicosis and diabetes,” “diabetic ketoacidosis and thyroid storm,” “carbohydrate metabolism and hyperthyroid,” “glucose homeostasis and thyrotoxicosis”) to identify key articles addressing various aspects of the thyroid’s influence on carbohydrate metabolism.ResultsThyroid hormone affects glucose homeostasis via its actions on a variety of organs including increased hepatic glucose output, increased futile cycling of glucose degradation products between the skeletal muscle and the liver, decreased glycogen stores in the liver and skeletal muscle, altered oxidative and nonoxidative glucose metabolism, decreased active insulin output from the pancreas, and increased renal insulin clearance. Thyroid hormone also affects adipokines and adipose tissue, further predisposing the patient to ketosis.ConclusionsThyrotoxicosis can alter carbohydrate metabolism in a type 2 diabetic patient to such an extent that diabetic ketoacidosis develops if untreated. Based on the current understanding of this relationship, all diabetic patients should be screened for thyroid dysfunction because correcting hyperthyroidism can profoundly affect glucose homeostasis. Similarly, patients presenting in diabetic ketoacidosis should undergo a thyroid function assessment. (Endocr Pract. 2009;15:254-262)     

Risk-Adapted Management of Thyroid Cancer

ObjectiveTo describe a risk-adapted management paradigm for patients with differentiated thyroid cancer.MethodsA risk-stratification approach is described that combines the standard clinical factors available during the initial evaluation with response-to-therapy variables to predict risk of death from thyroid cancer, risk of recurrence, and risk of failing initial therapy. This classic oncologic approach views risk stratification as an active, ongoing process in which risks are adjusted on the basis of accumulated clinical data, rather than considered as a static initial assessment that does not change.ResultsFrom a clinical standpoint, accurate realtime assessment of risk can be used to guide both the initial treatment recommendations (extent of thyroid surgical resection, role of radioiodine ablation, and degree of thyrotropin suppression) and the follow-up management paradigm (intensity of testing and modalities used to detect recurrent disease).ConclusionBy thinking like oncologists and individualizing therapy on the basis of initial and ongoing risk assessments, we can maximize the beneficial effects of aggressive therapy in patients with thyroid cancer who are likely to benefit from it, while minimizing potential complications and side effects in low-risk patients destined to have a full healthy productive life after minimal therapeutic intervention. (Endocr Pract. 2008;14:764-774)     

Diagnostic Confusion Attributable to Spurious Elevation of Both Total Thyroid Hormone and Thyroid Hormone Uptake Measurements in the Setting of Autoantibodies: Case Report and Review of Related Literature

ObjectiveTo review the effect of thyroid autoantibodies on thyroid function assays and to present a case in which thyroid autoantibodies resulted in spurious assay readings for both total thyroid hormone levels and thyroid hormone uptake measurements.MethodsWe present a detailed case, including serial laboratory data, and review the relevant literature.ResultsA 61-year-old man with a history of autoimmune disease presented for evaluation of abnormal results of thyroid function tests. The patient had been treated for hypothyroidism with levothyroxine and was noted to have an elevated total thyroxine (T₄) level in the setting of a low total triiodothyronine (T₃) value and a mildly elevated thyrotropin concentration. He had been referred for evaluation of a presumed deiodinase deficiency that impaired conversion of T₄ to T₃. During treatment with levothyroxine, these test results were confirmed, and the patient was also found to have an elevated T₄ uptake. These findings were initially thought to be due to an excess of transthyretin; however, more extensive testing revealed that the patient had an autoantibody to T₄ that interfered with the assays for both T₄ and T₄ uptake.ConclusionAutoantibodies to both T₃ and T₄ have been described. Such antibodies are not uncommon in patients with thyroid disease. On rare occasions, these antibodies may cause spurious assay readings and obscure the diagnosis. To our knowledge, this is the first report in which both the total T₄ level and the T₄ uptake were elevated because of the presence of autoantibodies. Thyroid hormone autoantibodies must be considered when clinicians encounter patients with unexplained abnormal results of thyroid function tests. (Endocr Pract. 2008; 14:738-742)     

Management of Low-Risk Differentiated Thyroid Cancer

ObjectiveTo summarize the definitions of and management recommendations for low-risk thyroid cancer made by the American and European Thyroid Associations and synthesize this information with the recent literature, including systematic evaluations of tumor staging systems guiding therapy.MethodsThe American Thyroid Association and European Thyroid Association guidelines were compared and pertinent literature since 2005 was reviewed.ResultsOf papillary thyroid microcarcinomas (PTMC), up to 50% breach the thyroid capsule, 64% have lymph node metastases, up to 43% are multifocal, and as many as 2.8% have distant metastases. Locoregional and distant recurrences are, respectively, as high as 5.9% and 1.5%. As many as 1 in 4 patients with a papillary thyroid carcinoma 1.5 cm or smaller develop persistent disease. Cancer-related mortality rates are usually less than 1%, but are as high as 2% in some reports. Tumor staging systems are too inaccurate to guide therapy.ConclusionIt is unlikely that many patients will forgo treatment after understanding their risk, especially when total thyroidectomy and radioiodine (¹³¹I) therapy can reduce the PTMC recurrence or persistence disease rate to zero. Preoperatively diagnosed PTMC should be treated with total or near-total thyroidectomy, regardless of tumor size. For very low-risk patients with unifocal PTMC smaller than 1 cm that is removed by chance during surgery to treat benign thyroid disease, lobectomy alone without ¹³¹I therapy may be sufficient therapy if there are no concerning histologic features and no tumor extension beyond the thyroid, metastases, history of head and neck irradiation, or positive family history—any of which requires total or near-total thyroidectomy and remnant ablation with 30 mCi. (Endocr Pract. 2007;13:498-512)     

Unusual Case of Amiodarone-Induced Thyrotoxicosis “Illicit” use of a Technetium Scan to Diagnose a Transiently Toxic Thyroid Nodule

ObjectiveTo present an unusual case of amiodarone-induced thyrotoxicosis (AIT) associated with an autonomously functioning thyroid nodule, which was detected by means of a technetium scan; review the existing literature regarding the association of AIT with autonomous thyroid nodules; and explore the use of radioisotope imaging studies in patients with AIT.MethodsWe describe a 62-year-old man with paroxysmal atrial fibrillation, receiving long-term amiodarone therapy, who was referred by his cardiologist for evaluation of abnormal thyroid function tests. He was found to have an unusual case of AIT, associated with an autonomously functioning thyroid nodule.ResultsThyroid function studies obtained by the patient’s cardiologist had shown a completely suppressed thyrotropin level and a free thyroxine level of 3.5 ng/dL. A 24-hour thyroid iodine 123 uptake and technetium Tc 99m pertechnetate scan revealed a “single, strong focus in the right thyroid lobe, with the rest of the thyroid gland...not well visualized.” Thyroid ultrasonography disclosed a single, well-defined 1.5-cm solid nodule. Repeated thyroid function studies revealed a normal thyrotropin level of 2.87 μIU/mL and a normal free thyroxine level of 2.4 ng/dL. The patient was managed conservatively with follow-up surveillance.ConclusionProspective studies should be performed to better ascertain the value of Tc 99m thyroid scanning in determining the cause of AIT. Until such studies have been completed, we suggest that nuclear studies are unlikely to be cost-effective for assessing all patients with AIT. One logical strategy would be to gain experience with scans in only those patients with known thyroid nodules, which have been detected during physical examination or by ultrasonography. The potential clinical utility of such an approach would be of considerable interest. (Endocr Pract. 2007;13:413-416)     

Overview of Molecular Biomarkers for Enhancing the Management of Cytologically Indeterminate Thyroid Nodules and Thyroid Cancer

ObjectiveTo provide information on molecular bio markers that can help assess cytologically indeterminate thyroid nodules.MethodsPublished studies on immunohistologic, somatic mutation, gene expression classifier, microRNA, and thyrotropin receptor messenger RNA biomarkers are reviewed, and commercially available molecular test pan els are described.ResultsThyroid nodules are common, and clinical guidelines delineate an algorithmic approach including serum thyroid-stimulating hormone measurement, diagnostic ultrasound examination, and, when appropriate, fine-needle aspiration (FNA) biopsy for determination of a benign versus malignant status. In clinical practice, approximately 20% of FNA-derived cytology reports are classified as “indeterminate” or follicular nodules that do not fulfill either benign or malignant criteria. In this set ting, the actual risk for malignancy of a cytologically indeterminate nodule ranges from approximately 15% to 34%. Research describing molecular biomarkers from thyroid cancer tissue has been applied to FNA-derived thyroid nodule material. There is also a serum molecular marker that has been reported with goals similar to those for the FNA-derived molecular markers: to enhance the preoperative diagnosis of thyroid cancer and reduce the large number of patients who have a diagnostic surgical procedure for benign thyroid nodules.ConclusionProgress toward the foregoing goals has been made and continues to evolve with the recent appearance of molecular biomarker tests that can be selectively applied for further assessment of cytologically indeterminate thyroid nodules. (Endocr Pract. 2012;18:611-615)     

Synchronous Parathyroid Carcinoma,Parathyroid Adenoma,and Papillary Thyroid Carcinoma in a Patient with Severe and Long-Standing Hyperparathyroidism

ObjectiveTo describe a patient presenting with the rare constellation of synchronous parathyroid carcinoma, parathyroid adenoma, and papillary thyroid carcinoma.MethodsWe summarize the clinical presentation, diagnostic work-up, surgical management, and pathologic features of our patient and review the pertinent literature.ResultsThe patient was a 59-year-old man who presented with severe clinical manifestations of long-standing primary hyperparathyroidism, a serum calcium concentration of 14.4 mg/dL, and a parathyroid hormone level of 2,023 pg/mL. He was found to have a 3.4-cm parathyroid carcinoma on the left side and a 3.2-cm papillary carcinoma in the right thyroid lobe. In addition, a 917-mg parathyroid adenoma was found on the right side.ConclusionSynchronous parathyroid and thyroid carcinomas are extremely rare. To our knowledge, our patient is the first documented case with a parathyroid adenoma in addition to synchronous parathyroid and thyroid carcinomas. The presence of concurrent parathyroid carcinoma and parathyroid adenoma can cause diagnostic confusion and should be considered in patients presenting with severe hyperparathyroidism. Any concomitant thyroid nodules must be investigated to rule out thyroid carcinoma. (Endocr Pract. 2009;15:463-468)     

Thyroid And Aging

Objective: Review physiologic thyroid function changes with aging and emphasize careful interpretation of tests in the aging population.Methods: Literature review.Results: Using age-specific thyroid-stimulating hormone (TSH) reference ranges should minimize or avoid the unnecessary diagnosis of thyroid disease in elderly patients. Subclinical thyroid dysfunction and abnormal TSH with normal thyroid levels may improve with time, so careful monitoring of thyroid function is recommended. Overt thyroid disease should always be treated.Conclusion: Clinical judgement is always warranted to decide how and when to treat subclinical thyroid disease in the elderly.Abbreviations: FT4 = free thyroxine; rT3 = reverse triiodothyronine; T3 = triiodothyronine; T4 = thyroxine; TFT = thyroid function test; TSH = thyroid-stimulating hormone     

Sentinel Lymph Node Biopsy Status Correlates With Postoperative Stimulated Thyroglobulin Levels in Low-Risk Papillary Thyroid Cancer Patients

ObjectiveRadioactive iodine (RAI) remnant ablation in low-risk papillary thyroid cancer (PTC) is controversial. Current patient selection guidelines recommend the use of postoperative stimulated thyroglobulin (stim-Tg), neck dissections, and sonography but fail to include sentinel lymph node biopsy (SLNB). The objective of this study was to evaluate the correlation between SLNB status and postoperative stimulated thyroglobulin as a surrogate marker of clinical outcome.MethodsRetrospective chart review of low-risk PTC patients who underwent a total thyroidectomy with SLNB at the McGill Thyroid Cancer Center. SLNBs were obtained using methylene blue dye. Biochemical measurements were acquired between 4 and 12 weeks postoperatively. Statistical analyses were performed using logistic regression models and receiver operating characterisitc (ROC) curves. A P-value < .05 was considered significant.ResultsNinety-six patients were included in this study. The positive SLNB rate was 14.6%. The mean postoperative Tg level was 1.41 μg/L. There were no significant correlations between the SLNB and the covariates analyzed (age, gender, histology, tumor size, and thyrotropin levels). Patients with negative SLNB were significantly more likely to have a lower stim-Tg (P < .0001). When postoperative Tg was analyzed as a categorical variable, a threshold of < 1 μg/L was significantly associated with a negative SLNB, with a sensitivity and specificity (determined by ROC curves) of 0.86 and 0.88, respectively.ConclusionThere exists a correlation between SLNB and postoperative Tg. This creates the possibility of a new approach to RAI administration among low-risk PTC patients incorporating SLNB to the current guidelines. (Endocr Pract. 2014;20:399-404)