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)     

Updated Review of Nuclear Molecular Imaging of Thyroid Cancers

ObjectivesWe initiate this comprehensive review to update the advances in this field by objectively elucidating the efficacies of promising radiopharmaceuticals.MethodsWe performed a comprehensive PUBMED search using the combined terms of “thyroid cancer” and “radiopharmaceuticals” or “nuclear medicine”, yielding 3273 and 11026 articles prior to December 31, 2020, respectively.ResultsBased on the mechanism of molecular metabolism, the evaluation of differentiated thyroid cancer and dedifferentiated thyroid cancer is largely centered around radioiodine and fluorine 18 (¹⁸F)-fludeoxyglucose, respectively. Further, ¹⁸F-L-dihydroxyphenylalanine and gallium 68 DOTATATE are the preferred tracers for medullary thyroid cancer. In dedifferentiated medullary thyroid cancer and anaplastic thyroid cancer, ¹⁸F-fludeoxyglucose is superior.ConclusionsThe future lies in advances in molecular biology, novel radiopharmaceuticals and imaging devices, paving ways to the development of personalized medication for thyroid cancer patients.     

Two Cases of Statin-Induced Myopathy Caused By Induced Hypothyroidism

ObjectiveTo present information regarding the potential danger of performing levothyroxine withdrawal radioiodine scans and treatment in patients with thyroid cancer who are concurrently taking lipid-lowering agents.MethodsWe review the clinical history, serial laboratory data, and radiologic findings in 2 patients with multifocal papillary carcinoma of the thyroid.ResultsBoth study patients had substantial elevations of muscle enzymes or myopathies (or both) when they were withdrawn from levothyroxine therapy, during treatment with lipid-lowering agents, in preparation for radioiodine scanning and treatment.ConclusionExtreme caution should be exercised when levothyroxine therapy is withdrawn from patients taking lipid-lowering agents. Such patients should be monitored very closely or, when appropriate, recombinant human thyroid-stimulating hormone injections should be used rather than levothyroxine withdrawal in this setting. (Endocr Pract. 2008;14:726-731)     

Thyroid Disease in Chronic Hepatitis C Infection Treated With Combination Interferon-a and Ribavirin: Management Strategies and Future Perspective

ObjectiveHepatitis C virus (HCV) infection is one of the major epidemics afflicting young people in both developed and developing countries. The most common endocrine disorder associated with this infection, especially in conjunction with interferon-α (IFN-α)-based therapy, is thyroid disease (TD). This review examines the development of TD before, during, and after the completion of treatment with combination IFN-α and ribavirin (RBV) for chronic HCV infection. We also summarize the current understanding of the natural history of the condition and propose management and follow-up guidelines.MethodsPubMed was searched up to June 30, 2011 for English-language publications that contained the search terms “hepatitis C virus,” “chronic hepatitis C,” “HCV,” “thyroid disease,” “thyroiditis,” “autoimmunity,” “inter-feron-alpha,” and “ribavirin.” Additional publications were identified from the reference lists of identified papers. The included studies were original research publications and included combination IFN-α and RBV use in patients that developed TD.ResultsThe prevalence of TD before combination IFN-α and RBV therapy ranges from 4.6 to 21.3%; during therapy, 1.1 to 21.3%; and after therapy, 6.7 to 21.3%. The most common TD is thyroiditis. Thyroid function testing (TFT) frequency and diagnostic criteria for various thyroid conditions are not standardized, and many of the existing studies are retrospective.ConclusionPatients undergoing this therapy should be assessed with a standardized protocol to appropriately detect and manage developed TD. Based on the currently available literature, we recommend that patients receiving combination interferon-α and RBV therapy undergo monthly thyrotropin (TSH) level testing. (Endocr Pract. 2013;19:292-300)     

Immunoglobulin Preparations Can Mislead Clinical Decision-Making in Follow-Up of Differentiated Thyroid Cancer

Objective: Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid-specific thyroglobulin (Tg) antibodies present in the donor plasma may interfere with the interpretation of measurements of Tg autoantibodies (Tg-Abs) in the recipient’s plasma and potentially trigger an immune response in the recipient’s immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient outcomes are not known. Tg is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer (DTC) following total thyroidectomy and radioactive iodine ablation. However, the presence of Tg-Abs in the circulation interferes with Tg measurements. Assessment of levels of Tg-Abs is thus recommended as a part of standard follow-up of DTC together with Tg testing.Methods: To understand the potential mechanisms and pathophysiologic significance of possible interferences associated with administration immunoglobulin preparations and Tg measurement, we overview the current knowledge on interactions between Tg autoimmunity and immunoglobulin preparations and illustrate diagnostic challenges and perspectives for follow-up of patients with DTC treated with exogenous immunoglobulins.Results: In patients with DTC treated with immunoglobulin preparations, monitoring of thyroid cancer using Tg and Tg-Abs is challenging due to possible analytical interferences through passive transfer of exogenous antibodies from immunoglobulin preparations.Conclusion: Analytical interferences must be suspected when a discrepancy exists between clinical examination and diagnostic tests. Collaboration between endocrinologists, biologists, and pharmacologists is fundamental to avoid misdiagnosis and unnecessary medical or radiologic procedures.Abbreviations: CT = computed tomography; DTC = differentiated thyroid cancer; FNAB = fine-needle aspiration biopsy; HAb = heterophile antibody; IMA = immunometric assay; IVIg = intravenous immunoglobulin; RAI = radioactive iodine; RIA = radioimmunoassay; SCIg = subcutaneous immunoglobulin; Tg = thyroglobulin; Tg-Ab = thyroglobulin autoantibody; Tg-MS = thyroglobulin mass spectrometry; TPO-Ab = thyroid peroxidase autoantibody; TSHR-Ab = thyrotropin receptor autoantibody     

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)     

Long-Term Follow-Up of a Patient With Papillary Thyroid Carcinoma,Elevated Thyroglobulin Levels,and Negative Imaging Studies

ObjectiveTo describe a patient with papillary thyroid carcinoma who had measurable thyroglobulin (Tg) levels for 20 years without clinical or imaging evidence of a malignant lesion.MethodsWe reviewed the clinical course, pathologic findings, Tg measurements, and results of various imaging studies in our patient and reviewed the literature regarding Tg-positive, diagnostic total-body radioiodine scan-negative patients with thyroid cancer.ResultsFour months after a 3.5- by 3.5-cm follicular thyroid cancer was removed from the anterior neck area of a 5-year-old girl, a bilateral subtotal thyroidectomy was performed. At age 12 years, she presented with a 2-cm mass on the right side of the neck. After a completion thyroidectomy, recurrent mixed papillary-follicular thyroid cancer was found scattered throughout the remaining thyroid parenchyma. Although a postoperative diagnostic total-body radioiodine scan did not reveal uptake of ¹³¹I, the Tg level was 58 ng/mL. Despite Tg levels as high as 2,528 ng/mL, the patient had no clinical evidence of thyroid cancer during a 20-year period of follow-up. Moreover, numerous imaging studies, including total-body scanning after the administration of 150 mCi of ¹³¹I and [¹⁸F]fluorodeoxyglucose positron emission tomography, were negative. Review of pathologic specimens from both operations with use of updated diagnostic criteria indicated that the tumor was a papillary thyroid carcinoma.ConclusionOur observations and the observations of other investigators indicate that some thyroid cancers produce Tg so efficiently that high levels of Tg may be associated with tumors that remain too small to be detected by imaging studies. The Tg levels may remain stable, decline, or even disappear over time without treatment. (Endocr Pract. 2005;11:43-48)     

A Stepwise Approach to the Evaluation and Treatment of Subclinicalhyperthyroidism

ObjectivesTo review a stepwise approach to the evaluation and treatment of subclinical hyperthyroidism.MethodsEnglish-language articles regarding clinical management of subclinical hyperthyroidism published between 2007 and 2012 were reviewed.ResultsSubclinical hyperthyroidism is encountered on a daily basis in clinical practice. When evaluating patients with a suppressed serum thyrotropin value, it is important to exclude other potential etiologies such as overt triiodothyronine toxicosis, drug effect, nonthyroidal illness, and central hypothyroidism. In younger patients with mild thyrotropin suppression, it is acceptable to perform testing again in 3 to 6 months to assess for persistence before performing further diagnostic testing. In older patients or patients with thyrotropin values less than 0.1 mIU/L, diagnostic testing should proceed without delay. Persistence of thyrotropin suppression is more typical of nodular thyroid autonomy, whereas thyroiditis and mild Graves disease frequently resolve spontaneously. The clinical consequences of subclinical hyperthyroidism, such as atrial dysrhythmia, accelerated bone loss, increased fracture rate, and higher rates of cardiovascular mortality, are dependent on age and severity. The decision to treat subclinical hyperthyroidism is directly tied to an assessment of the potential for clinical consequences in untreated disease. Definitive therapy is generally selected for patients with nodular autonomous function, whereas antithyroid drug therapy is more appropriate for mild, persistent Graves disease.ConclusionThe presented stepwise approach to the care of patients presenting with an isolated suppression of serum thyrotropin focuses on the differential diagnosis, a prediction of the likelihood of persistence, an assessment of potential risks posed to the patient, and, finally, a personalized choice of therapy. (Endocr Pract. 2012;18: 772-780)     

Hürthle cell Thyroid Carcinoma Presenting as A “Hot” Nodule

ObjectiveTo report an unusual clinical scenario and a rare histopathologic finding of Hürthle cell thyroid carcinoma in a patient with an autonomous thyroid nodule.MethodsWe describe the presentation and clinical course leading to the surprising histopathologic diagnosis of Hürthle cell carcinoma in a pediatric patient who was diagnosed with hyperthyroidism presenting as a solitary toxic nodule.ResultsA 13-year-old white girl presented with a recent history of a palpable thyroid nodule during a routine primary care clinic visit. She was asymptomatic, and thyroid function tests revealed a suppressed thyrotropin concentration, high-normal free thyroxine concentration, and elevated triiodothyronine concentration. The patient underwent dedicated thyroid ultrasonography revealing a 3.5-cm complex mass in the left lobe with increased central vascularity. Iodine 123 imaging of the thyroid demonstrated homogenous, hyperintense activity in the left lobe. The right lobe was not visualized. A solitary toxic nodule was diagnosed, and, considering her age, she was referred for surgical management. The patient underwent a left lobectomy with isthmusectomy. Pathologic examination revealed a 5-cm, encapsulated, well-differentiated Hürthle cell carcinoma with negative margins and no lymphovascular invasion. The patient underwent subsequent completion thyroidectomy with no evidence of residual carcinoma in the right thyroid lobe.ConclusionsMalignancy in autonomously functioning thyroid nodules is rare. Most of the thyroid nodules presenting as “hot” on radioiodine scintigraphy are benign follicular adenomas. However, this case represents a rare clinical entity, and it highlights the need for clinicians to be vigilant and aware that occasionally carcinomas can masquerade as scintigraphic “hot” nodules. (Endocr Pract. 2011;17:e68-e72)     

Evaluation Of Various Doses Of Recombinant Human Thyrotropin In Patients With Multinodular Goiters

ObjectiveTo assess the safety, adverse effects, and radioactive iodine uptake (RAIU) of recombinant human thyrotropin (rhTSH) using a range of doses in patients with multinodular goiters.MethodsIn this open-label study conducted between June 2002 and December 2004, euthyroid patients with small nontoxic multinodular goiters and normal thyrotropin concentrations were recruited from 4 sites in the United States. Baseline assessments included thyroid function tests, electrocardiogram, Holter monitoring, hyperthyroid symptom scale, flow-volume loop, and measurement of thyroglobulin and thyroperoxidase antibodies. Patients had a baseline 24-hour scan and thyroid iodine I 123 (¹²³I) uptake evaluated at 6, 24, and 48 hours after rhTSH administration. Each patient received a single intramuscular injection of 0.03-mg, 0.1-mg, or 0.3-mg rhTSH followed 24 hours later by 400 μCi ¹²³I orally. Iodine 123 uptakes were again measured 6, 24, and 48 hours later, and a scintigram scan was performed at 24 hours. Thyroid function tests, flow-volume loop, Holter monitoring and/or electrocardiograms, and thyroid ultrasonography to assess thyroid size were performed serially.ResultsTwenty-eight patients participated. Median goiter size was 20 mL (range, 7-79 mL). After each rhTSH dose, the radioiodine uptake approximately doubled at each time point compared with baseline uptake. Small rises in serum thyroxine and triiodothyronine were seen in some patients, especially after 0.3-mg rhTSH, and mild symptoms of hyperthyroidism developed in several patients. Flow-volume loop showed transient, mild asymptomatic worsening in 1 patient with a 35.2 mL goiter, although thyroid volume measurements were unchanged. Minor electrocardiogram and/or Holter changes were seen in several patients.ConclusionsA flat dose-response curve exists over the range of rhTSH doses tested, with an approximate doubling of thyroid RAIU. All patients tolerated rhTSH well, but the rise in thyroid hormone levels and adverse effects after rhTSH doses of 0.1 mg or higher theoretically might not be well tolerated in older or sicker patients and appear unjustified given the lack of a greater rise in RAIU compared with the 0.03-mg dose. Future studies evaluating rhTSH doses less than 0.1 mg in patients with multinodular goiter are justified. (Endocr Pract. 2008;14:832-839)     

Delayed 131-I First Treatment After Surgery has No Impact on the Median Term Outcome of Patients with Intermediate Risk Differentiated Thyroid Cancer

Objective: In intermediate risk (IR) differentiated thyroid cancer (DTC) patients, selective use of radioiodine (131-I) for remnant ablation and/or as adjuvant therapy (RRA) is advocated. The recently suggested postoperative evaluation could delay the use of RRA. The aim of this study was to evaluate if a delayed RRA can worsen the clinical outcome of IR-DTC patients.Methods: Four hundred and fourteen consecutive IR-DTC patients were divided according to the time elapsed from surgery to RRA, <6 months (group A, 186/414 &lsqb;44.9%]), or ≥6 months (group B, 228/414 &lsqb;55.1%]). Clinical and biochemical data were collected, and clinical outcome was analyzed at the first evaluation (EV) after RRA (first-EV) and after a median of 6 years of follow-up (last-EV).Results: No difference in the clinical outcome of group A and B was found. Since a different activity of 131-I could have an impact on the outcome, we separately analyzed the groups according to the 131-I activity (low-activity group: 1,110 MBq/30 mCi &lsqb;n = 320], and high-activity group: 3,700 MBq/100 mCi &lsqb;n = 94]), further subdivided according to the time elapsed from surgery to RRA. No major differences were found in both the low- and high-activity groups when comparing the features of their subgroups A and B, as far as in their clinical outcome.Conclusion: The time elapsed between surgery and the first 131-I treatment does not influence the clinical outcome of IR-DTC patients. This finding allows a more relaxed attitude in the decision making process whether to perform the RRA in IR-DTC cases in which a selective use of 131-I is recommended.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; EV = evaluation; HR = high risk; 131-I = radioiodine; IR = intermediate risk; LR = low risk; rhTSH = recombinant human thyroid-stimulating hormone; RRA = radioiodine for remnant ablation; Tg = thyroglobulin; TgAb = thyroglobulin autoantibody; US = ultrasound     

Radioiodine Remnant Ablation: Current Indications and Dosing Regimens

ObjectiveTo review and comment on current indica tions for radioiodine remnant ablation (RRA) in patients with differentiated thyroid cancer.MethodsThe stratification of patients as potential candidates for RRA, the benefits and risks of RRA, and the optimal preparation and administered doses of iodine 131 for RRA are discussed.ResultsWhen RRA for patients with low and inter mediate-risk differentiated thyroid cancer is being consid ered, the benefits—including survival, influence on mor bidity and recurrence, and ease of monitoring—should be weighed against the potential risks. RRA should have limited use in many low-risk patients, particularly those with stage I disease who are young and have small pri mary tumors, no lymph node involvement, and no extrano dal invasion. Measurement of serum thyroglobulin 6 to 8 weeks after thyroidectomy during levothyroxine suppres sion can be used for further stratification of risk in these patients. RRA should be used only selectively in low to intermediate-risk patients and reserved primarily for older patients with large tumors, extensive lymph node involve ment, and high-risk (tall cell, insular) subtypes of differ entiated thyroid cancer. Most low-risk to intermediate-risk patients who do warrant RRA can be prepared with recom binant human thyroid-stimulating hormone and given the smallest dose possible (30 to 50 mCi of iodine 131) for successful remnant ablation. Single-photon emission com puted tomography-computed tomographic imaging and dosimetry are new tools that can help in the management of many patients with thyroid cancer.ConclusionAlthough a large database study has shown a trend of increased use of RRA after thyroidectomy between 1990 and 2008 in the United States, recent studies and guidelines suggest a more limited use in patients with low-risk disease, which may change this trend. (Endocr Pract. 2012;18:604-610)     

Evolving Approaches in Managing Radioactive Iodine-Refractory Differentiated Thyroid Cancer

ObjectiveTo discuss the approach to care of patients with advanced differentiated thyroid cancer (DTC), in particular those with radioactive iodine (RAI)-refractory disease, and the transition to systemic treatment.MethodsA PubMed search was conducted using the search terms “radioactive iodine-refractory, differentiated thyroid cancer and treatment” restricted to a 2000-2012 timeframe, English language, and humans. Relevant articles were identified from the bibliographies of selected references. Four patient cases are presented to illustrate the clinical course of RAI-refractory DTC.ResultsThe current standard of care for early stage DTC could include surgery, RAI in some cases, and thyroid hormone suppression. For advanced RAI-refractory DTC, clinical practice guidelines established by the National Comprehensive Cancer Network and the American Thyroid Association recommend, as one option, the use of systemic therapy, including kinase inhibitors. Numerous trials are underway to evaluate the clinical benefit of these targeted therapies.ConclusionPreliminary results are encouraging with respect to the clinical benefit of targeted systemic therapies. However, at present there is no consensus on the criteria that define RAI-refractory disease and the optimal timing for transition to systemic therapy. There remains a need to establish common criteria to enhance patient care and enable better comparison across clinical studies. (Endocr Pract. 2014;20:263-275)     

Early and Late Toxicity of Radioiodine Therapy: Detection and Management

ObjectiveTo review the early and late toxicity associated with radioiodine (¹³¹I) therapy, highlighting the need for early detection and, where possible, preventive measures.MethodsWe performed a literature search on MEDLINE using the terms radioiodine, ¹³¹I toxicity, complications, Graves disease, and thyroid cancer and chose the most relevant studies for this review. Where appropriate, we refer to our own published series of patients as well.ResultsUptake of ¹³¹I into the salivary glands, lacrimal glands, fetal thyroid, and adult thyroid accounts for the early toxic effects of radioiodine therapy. Delayed radiation effects to the gonads, bone marrow, and cell nuclei give rise to late complications. Toxicity may also arise from uptake into metastatic tumors located at vulnerable sites, including the spinal cord, brain, and lungs.ConclusionAlthough radioiodine therapy for benign and malignant thyroid disorders is usually well tolerated, clinicians involved in the management of thyroid disorders need to be aware of the potential toxicity of radioiodine and take all measures to reduce these effects to a minimum. (Endocr Pract. 2010;16:1064-1070)     

Prognostic Value of Serum Thyroglobulin Measured at 48 Hours Versus 72 Hours after Second Dose of Recombinant Human Thyrotropin in Surveillance of Well-Differentiated Thyroid Cancer

ObjectiveThe sensitivity of thyroglobulin (Tg) to detect differentiated thyroid cancer recurrence increases with the rise of the thyrotropin level. Since 1998, recombinant human thyrotropin (rhTSH) has been commercially available for this purpose. The traditional protocol for using rhTSH calls for 2 daily injections of rhTSH, followed by the measurement of Tg 72 hours after the second dose. In this study, we compared the performance of rhTSH-stimulated Tg (rhTSH-Tg) obtained at 48 versus 72 hours after the second rhTSH.MethodsA retrospective chart review of 1088 patients with thyroid cancer was conducted. Two hundred forty-nine rhTSH-Tg, without measurable Tg antibody, were identified, 134 of which were obtained at 48 hours (4-day test) and 115 at 72 hours after the second rhTSH (5-day test). The ability of rhTSH-Tg to identify recurrence or persistence of differentiated thyroid cancer and to predict response to therapy at the end of the study period was compared between the 2 groups.ResultsThe median duration of follow-up was 8 years. When recurrent/persistent cancer was present based on a combination of unstimulated Tg, imaging and procedures, the ratio of rhTSH-Tg ≥ 1 ng/mL was similar in both groups (P value: .153). The negative predictive value of rhTSH-Tg to predict response to therapy over the long term was 95% or higher in 4-day and 5-day tests.ConclusionTg measured 48 and 72 hours after the second dose of rhTSH may provide a comparable prognostic value. These results encourage further studies to identify new protocols to obtain rhTSH-Tg.     

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)     

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)     

Graves Ophthalmopathy After Radiation Treatment of Thyroid Cancer

ObjectiveTo describe a patient with metastatic thyroid cancer who developed Graves ophthalmopathy after treatment with radioiodine (I 131) and external beam radiation.MethodsWe present a case report that includes clinical, laboratory, and radiologic findings and a brief review of the literature.ResultsA 49-year-old woman who had had a total thyroidectomy and neck dissection followed by I 131 treatment 5 years earlier for papillary thyroid cancer presented for follow-up management after recent neck dissection for recurrent disease. Because she had thyroglobulin antibodies, she was again treated with I 131 after preparation with recombinant human thyroid-stimulating hormone. A post-treatment scan revealed uptake in the right iliac crest. A fludeoxyglucose F 18 positron emission tomography/computed tomography fusion scan revealed osseous metastases in the right pelvis, and external beam radiotherapy was delivered to this area. Approximately 5 months later, she developed periocular swelling and excessive tearing. Magnetic resonance imaging of the orbits revealed enlargement of the extraocular muscles. Serum thyroid-stimulating immunoglobulins were greatly elevated.ConclusionThis case corroborates an earlier report to suggest that radiation-associated thyroid injury in a patient with thyroid cancer may be followed by Graves ophthalmopathy and appearance of thyroid-stimulating immune-globulins in the serum. (Endocr Pract. 2008;14:419-421)     

Potential Use of Recombinant Human Thyrotropin in the Treatment of Distant Metastases in Patients with Differentiated Thyroid Cancer

ObjectiveIn order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC.MethodsWe have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines.ResultsExogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-determined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW.ConclusionThe rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC. (Endocr Pract. 2013;19:139-148)     

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)