Life-Threatening Hyponatremia Following a Low-Iodine Diet: A Case Report and Review of all Reported Cases Report and Review of all Reported Cases

ObjectiveTo report a case of life-threatening hyponatremia as a complication of a 4-week long low-iodine diet and highlight the risk factors for this complication by reviewing all previously reported cases.MethodsThe clinical and biochemical data from the study patient are presented and the pertinent literature is reviewed. A risk analysis for this complication is highlighted.ResultsA 66-year-old Vietnamese woman had a total thyroidectomy and bilateral neck lymph node dissection for papillary thyroid carcinoma. A whole body radioiodine scan demonstrated 2 foci of activity in the anterior neck. The patient received recombinant human thyrotropin (rhTSH) and was admitted for radioiodine therapy. She had strictly adhered to a low-iodine diet for 4 weeks in preparation for ablation. The patient was on a thiazide diuretic for her hypertension, which was discontinued on admission. On admission, the patient started feeling light-headed, dizzy, and nauseated. Blood tests revealed a critical serum sodium concentration of 107 mEq/L. Further investigations confirmed hypotonic hyponatremia, which had developed despite being euthyroid after receiving rhTSH. The patient was managed accordingly and made a full recovery.ConclusionsThis case, in addition to the reviewed cases, emphasizes the importance of preventing and managing this rare but relatively dangerous complication. Based on an analysis of the reviewed cases, the risk factors for developing this complication are a prolonged low-iodine diet, the elimination of salt from the diet, and the use of thiazide diuretics. All patients in the reported cases were older than 65 years of age. (Endocr Pract. 2011;17:e113-e117)     

Risk Factors for Developing Hyponatremia in Thyroid Cancer Patients Undergoing Radioactive Iodine Therapy

Background

Due to the alarming increase in the incidence of thyroid cancer worldwide, more patients are receiving postoperative radioactive iodine (RAI) therapy and these patients are given a low-iodine diet along with levothyroxine withdrawal to induce a hypothyroid state to maximize the uptake of RAI by thyroid tissues. Recently, the reported cases of patients suffering from life-threatening severe hyponatremia following postoperative RAI therapy have increased. This study aimed to systematically assess risk factors for developing hyponatremia following RAI therapy in post-thyroidectomy patients.

Methods

We reviewed the medical records of all thyroid cancer patients who underwent thyroidectomy and postoperative RAI therapy from July 2009 to February 2012. Demographic and biochemical parameters including serum sodium and thyroid function tests were assessed along with medication history.

Results

A total of 2229 patients (47.0±11.0 years, female 76.3%) were enrolled in the analysis. Three hundred seven patients (13.8%) of all patients developed hyponatremia; 44 patients (2.0%) developed moderate to severe hyponatremia (serum Na⁺≤130 mEq/L) and another 263 (11.8%) patients showed mild hyponatremia (130 mEq/L<serum Na⁺≤135 mEq/L). In univariate analysis, old age, female sex, presence of hypertension, presence of diabetes, use of thiazide diuretics, use of angiotensin receptor blocker or angiotensin-converting enzyme inhibitors, lung metastasis, and hyponatremia and lower estimated glomerular filtration rate at the start of RAI therapy were significantly associated with hyponatremia in patients undergoing RAI therapy after total thyroidectomy. Multivariate analysis showed that old age, female sex, use of thiazide diuretics, and hyponatremia at the initiation of RAI therapy were independent risk factors for the development of hyponatremia.

Conclusion

Our data suggest that age greater than 60 years, female sex, use of thiazide, and hyponatremia at the initiation of RAI therapy are important risk factors for developing hyponatremia following RAI therapy in post-thyroidectomy patients.     

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)     

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)     

Parathyroidectomy-Induced Thyroiditis

ObjectiveTo highlight the possibility of development of thyroiditis after parathyroidectomy.MethodsClinical and laboratory findings in 2 cases are presented, and the relevant literature is reviewed.ResultsIn 2 women (84 years old and 55 years old) with no history of thyroid disease in one of them and a remote history of excision of a follicular adenoma in the other, thyrotoxicosis developed a few days to a week after parathyroidectomy for primary hyperparathyroidism. The first patient underwent bilateral cervical exploration with removal of a right inferior parathyroid adenoma, whereas the second patient had excision of 3¹/₂ parathyroid glands for 4-gland hyperplasia and 2 benign nodules from the left thyroid lobe. Both surgical procedures were uncomplicated. Neither patient had received any iodinated contrast agents or medications such as lithium or amiodarone before presentation. Laboratory results showed elevated levels of free thyroxine, suppressed thyroid-stimulating hormone levels, very low radioiodine uptake (in the second patient), and an elevated thyroglobulin level (in the first patient). Both patients were treated symptomatically with β-adrenergic antagonists. Thyroid function normalized and symptoms diminished after 1 to 2 months.ConclusionParathyroidectomy-induced thyroiditis is underrecognized. The majority of patients are asymptomatic, although clinically significant thyrotoxicosis can also occur. Candidates for parathyroidectomy should be informed of this potential complication, and thyroid function should be assessed if clinically indicated. (Endocr Pract. 2010;16:656-659)     

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)     

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)     

Metastatic Struma Ovarii Treated With Total Thyroidectomy and Radioiodine Ablation

ObjectiveTo present a rare case of metastatic struma ovarii, review the related literature, and discuss the management.MethodsA case report of a patient with metastatic struma ovarii is presented. The treatment plan, postoperative care, and follow-up are discussed. We conducted a MEDLINE search of the English-language literature seeking additional cases of metastatic struma ovarii. In addition to the current case, the previous 40 cases of metastatic struma ovarii were reviewed and analyzed.ResultsThe mean age of the patients at presentation was 43 years. All patients underwent resection of the primary tumor. The most common sites of involvement for struma ovarii metastatic disease have been the peritoneum, mesentery, and omentum. After primary tumor resection, a wide range of additional treatments have been used, including chemotherapy, resection of metastatic disease, external beam radiation therapy, and radioiodine ablation.ConclusionIn cases of metastatic struma ovarii, we recommend total thyroidectomy in conjunction with radioiodine scanning and radioiodine ablation. Thyroglobulin levels should be followed as a tumor marker, and diagnostic radioiodine scans should be performed to screen for residual or recurrent disease. Although this treatment strategy is well established for thyroid cancer, long-term outcomes of this treatment for struma ovarii are still unknown. (Endocr Pract. 2009;15:167-173)     

Initial Adoption of Recombinant Human Thyroid-Stimulating Hormone Following Thyroidectomy in the Medicare Thyroid Cancer Patient Population

Objective: Recombinant human thyroid-stimulating hormone (rhTSH) has been approved for diagnostic (1998) and therapeutic (2008) indications in conjunction with radioactive iodine (RAI) administration post-thyroidectomy. Potential benefits of rhTSH, including avoidance of hypothyroidism side effects and shorter, less costly hospital stays, have not been assessed at the population level within the United States. In this study we quantify utilization, outcomes, and associated costs of rhTSH within the nationally representative Surveillance, Epidemiology, and End Results (SEER)-Medicare patient population.Methods: We conducted a retrospective analysis of beneficiaries aged >65 years diagnosed within the SEER-Medicare data with differentiated thyroid cancer. Endpoints examined included (1) rhTSH utilization in the 2 years post-thyroidectomy (patients diagnosed 1996–2011 &lsqb;utilization cohort]) and (2) comparison of resource utilization and costs as a function of rhTSH receipt in the 30 days prior to and 1 year following therapeutic RAI administration (patients diagnosed 2008–2011 &lsqb;resource use cohort]). All costs were adjusted to reflect 2013 dollars.Results: A total of 6,482 patients met inclusion criteria, of which, 1,363 (21.0%) received rhTSH. Receipt varied by region and was higher in the South (18%), Northeast (28%), and West (44%) compared to the Midwest (10%), and lower in census tracts in the bottom quartile of high school education rates (odds ratio 0.68, 95% confidence interval &lsqb;CI] 0.55–0.83). rhTSH receipt was not associated with patient sex, age, comorbidities, or stage. Post-therapeutic RAI, 1,444 patients were assessed for resource utilization (2008–2011). The average cost of rhTSH was $905 per patient, with $2,483 being spent on average among patients who received rhTSH in association with therapeutic RAI. rhTSH receipt was not significantly associated with total inpatient days or number of outpatient and emergency department visits. Multivariable analyses showed similar overall costs among patients who did versus did not receive rhTSH (cost ratio &lsqb;CR] 0.96, 95% CI 0.86–1.09), partially due to increased mean outpatient costs ($5,213 vs. $4,190) being offset by lower inpatient costs ($3,493 vs. $6,143). Overall costs were significantly higher in multivariable analyses among patients with distant metastatic disease (CR 1.92, 95% CI 1.58–2.32) and multiple comorbidities (CR 2.15, 95% CI 1.83–2.53).Conclusion: rhTSH recipients had higher outpatient, lower inpatient, and similar total Medicare payments as those not receiving rhTSH in conjunction with RAI, lending support to the use of rhTSH as a cost-neutral treatment option from the payer perspective.Abbreviations: CI = confidence interval; CMS = Centers for Medicare & Medicaid Services; CR = cost ratio; HCPCS = Healthcare Common Procedure Coding System; IQR = interquartile range; mCi = millicurie; OR = odds ratio; PET = positron emission tomography; RAI = radioactive iodine; rhTSH = recombinant human thyroid-stimulating hormone; RR = risk ratio; SEER = Surveillance, Epidemiology, and End Results     

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)     

Assessing The Risk of False-Negative Fine-Needle Aspiration Cytology and of Incidental Cancer in Nodular Goiter

ObjectiveIn cases of multinodular goiter with negative cytologic result, reasonable management options include surgical treatment, simple follow-up, or more recently introduced conservative therapies such as laser or radiofrequency ablation, and recombinant human thyroid-stimulating hormone-augmented radioiodine. For patients who are eligible for follow-up or nonsurgical treatments, the possibility that they may have an undiagnosed malignancy (false-negative [FN]-fine-needle aspiration cytology [FNAC] result or incidental thyroid cancer [ITC]) should be considered. The aim of our study was to assess the risk of malignancy in patients known to have presumably benign thyroid disease.MethodsSurgical series of patients who underwent total thyroidectomy for benign disease between 2000 and 2010 at two Italian centers were reviewed. Patients with any preoperative suspicion of malignancy were excluded.ResultsHistologic examination revealed that 84 of 970 (8.6%) thyroidectomized patients had malignancy (5% ITC and 3.6% FN-FNAC), with 89.8% of ITCs having a diameter <10 mm, and 65.7% of FN-FNAC cancers having a diameter >30 mm. Sixty-seven thyroid malignancy patients (79.8%) had stage I disease (American Joint Committee on Cancer criteria). The risk of FN-FNAC increases with increasing size of the nodule, while the risk of ITC increases as nodule size decreases.ResultsThe risk of malignancy in presumably benign thyroid disease cannot be overlooked, but can be minimized through skillfully performed ultrasonography (US) examination and FNAC. Once a patient with multinodular goiter is referred for follow-up or nonsurgical therapy, careful US surveillance is mandatory. (Endocr Pract. 2013;19:444-450)     

Determinants of Long-Term Outcome after Radioiodine Therapy for Solitary Autonomous Thyroid Nodules

ObjectiveTo determine the incidence and clinical predictors of hypothyroidism in one institution after radioiodine treatment of solitary toxic nodules.MethodsWe retrospectively analyzed the outcome of radioiodine therapy in 105 patients with solitary autonomous thyroid nodules treated at our institution during a 10-year period (January 1996 to December 2005; mean duration of follow-up, 53 ± 34 months). Patients were monitored until the development of hypothyroidism, death, or the end of the study period. The cumulative incidence of hypothyroidism was determined by Kaplan-Meier life-table analysis, and predictors of hypothyroidism were determined by using a Cox regression model.ResultsThe cumulative incidence of hypothyroidism was 11% at 1 year, 33% at 5 years, and 49% at 10 years. The development of hypothyroidism was not associated with age, sex, radioiodine dose, radioiodine uptake, or degree of suppression of extranodal tissue on scintiscans. The predictors of occurrence of hypothyroidism were pretreatment with antithyroid medications (P = .004; relative risk = 1.94) and positive thyroid antibody status (P = .008; relative risk = 1.84). Antibody-positive patients showed an earlier progression toward hypothyroidism than did antibody-negative patients.ConclusionHypothyroidism is a common outcome of radioiodine treatment for autonomous thyroid nodules. In this study, coexistent thyroid autoimmunity and pretreatment with antithyroid medications were significant risk factors for the development of hypothyroidism. (Endocr Pract. 2008;14:543-549)     

Bisphosphonates and Osteonecrosis of the Jaw: A Retrospective Study

ObjectiveTo assess the prevalence of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonate therapy and in those who were bisphosphonate naïve.MethodsWe undertook a retrospective review of medical records of patients at the New York Harbor Health Care System from 1999 through 2004. Charts were selected for review if patients had a Current Procedural Terminology (CPT) code suggestive of ONJ or if they had ever received bisphosphonate therapy.ResultsAmong 1,951 medical records reviewed, we identified 2 patients with ONJ who had received bisphos-phonates and 2 patients with ONJ who were bisphospho-nate naïve. Both patients treated with bisphosphonates had multiple myeloma and were receiving monthly infusions. They had initially received pamidronate before treatment was changed to zoledronic acid. In each case, ONJ was precipitated by a routine dental extraction. The prevalence of ONJ in our patient population receiving intravenously administered bisphosphonates was 1 in 71.5. Of the 2 cases of ONJ in bisphosphonate-naïve patients, osteora-dionecrosis was clearly incriminated in 1 patient and potentially the causative factor in the other patient as well. No patients receiving orally administered bisphosphonates had ONJ, nor did this complication occur in any patients receiving parenteral bisphosphonate therapy for disorders such as osteoporosis or Paget’s disease of bone.ConclusionBisphosphonates remain an important option for management of metabolic bone disease and complications of malignant disease. The overall prevalence of ONJ in patients receiving bisphosphonates seems to be very low; however, patients receiving intense parenteral therapy for an underlying malignant condition appear to have a uniquely elevated risk for the development of this complication. A causal relationship between bisphosphonates and ONJ remains to be proved and merits further investigation. (Endocr Pract. 2007;13:232-238)     

Hyponatremia: Mechanisms and Newer Treatments

ObjectiveTo review the neural and renal mechanisms of osmotic homeostasis, provide a rationale for the sensitivity of the central nervous system to hyponatremia, and outline modern approaches to therapy of acute and chronic hyponatremia.MethodsReview of relevant literature with focus on physiologic mechanisms.ResultsWith careful monitoring, acute hyponatremia can be managed, while minimizing risks both of continued hyponatremia and the osmotic demyelination that can occur with overly rapid correction of severe hyponatremia. Chronic hyponatremia due to disorders of volume regulation (congestive heart failure or cirrhosis) or to syndrome of inappropriate antidiuretic hormone release can be managed effectively with vasopressin V2 receptor antagonists, but there is no evidence that controlling the hyponatremia enhances survival associated with the underlying diseases.ConclusionsTherapy in the acute setting balances the risk of the osmotic disturbance with the risk of overly rapid correction. The V2 receptor antagonist tolvaptan has enhanced our ability to improve chronic hyponatremia in conditions such as congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormone hypersecretion. (Endocr Pract. 2010;16:882-887)     

Severe Hyponatre mia Due to Rosiglita zone Use in an Elderly Woman With Diabetes Mellitus: A Rare Cause of Syndrome of Inappropriate Antidiuretic Hormone Secretion

ObjectiveTo describe the first case of syndrome of inappropriate antidiuretic hormone secretion with lifethreatening hyponatremia due to rosiglitazone therapy.MethodsWe describe the clinical, laboratory, and imaging findings of the study patient.ResultsAn 89-year-old woman with a 5-year history of type 2 diabetes mellitus was admitted to the emergency department because of unconsciousness. She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L). She had normal renal, cardiac, and adrenal function, and she did not have edema or volume depletion. The cause of hyponatremia was syndrome of inappropriate antidiuretic hormone secretion. We did not find any cause for her condition other than rosiglitazone, an antihyperglycemic drug that is increasingly being used in patients with type 2 diabetes mellitus. According to her medical history, rosiglitazone was prescribed 1 month previously after withdrawal of gliclazide. We stopped the rosiglitazone and administered hypertonic saline infusion to treat the hyponatremia. Saline infusion was stopped and blood sodium levels were stabilized in the normal range after 2 days. The patient’s plasma sodium concentration has remained in the reference range at follow-up visits.ConclusionsThis is the first reported case of syndrome of inappropriate antidiuretic hormone secretion as an adverse effect of rosiglitazone, and this drug should possibly be considered for addition to the list of drugs that cause this condition. (Endocr Pract. 2008;14:1017-1019)     

Successful management of differentiated thyroid cancer in a community-based endocrine practice

ObjectiveTo describe the range of differentiated thyroid cancer (DTC) cases, disease complexity, and treatment outcomes seen in our 3-physician community-based general endocrine practice during an 8-year period in order to make comparisons with published cohorts from university settings.MethodsMedical records of patients with DTC treated between 2002 and 2009 at Mountain Diabetes and Endocrine Center (Asheville, North Carolina) were reviewed. Pathologic features, staging, and disease status at last contact were determined. Multivariate analyses of adverse prognostic risk factors at diagnosis, recombinant human thyroid-stimulating hormone use, and radioiodine use were compared with the ultimate outcome of patients.ResultsWe treated a total of 167 patients with DTC during the study period (mean age at diagnosis, 44.4 years; mean duration of follow-up, 6.2 years). In our study cohort, 88.6% had papillary thyroid cancer, 74% had stage I disease, and 32.4% of those with papillary thyroid cancer had microscopic tumors (≤ 1 cm). Remission occurred in 67.1%, 17.1% had persistent disease, and 11.8% were indeterminate for remission; non-thyroid cancer death occurred in 2.6% and disease-specific death in 1.3%. The mean number of adverse prognostic risk factors per patient was 2.0 in those with remission and 4.7 in those with persistent disease.ConclusionCommunity-based endocrinologists evaluate the full spectrum of thyroid cancer disease complexity and can achieve excellent outcomes. In our current study group, disease persistence and diseasespecific death occurred in 17.1% and 1.3%, respectively. Individualization of care based on prognostic variables guided our diagnostic and therapeutic decisions. (Endocr Pract. 2012;18:170-178)     

Sellar Masses That Present With Severe Hyponatremia

ObjectiveHyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia.MethodsOver 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented.ResultsOf 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke’s cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P < .01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia.ConclusionSevere hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes. (Endocr Pract. 2014;20:1178-1186)     

Papillary Carcinoma of a Thyroglossal Duct Cyst in a Patient with Thyroid Hemiagenesis: Effectiveness of Conservative Surgical Treatment

ObjectiveTo describe a case of thyroglossal duct cyst carcinoma that arose in a patient with right thyroid lobe hemiagenesis.MethodsWe present the imaging, physical examination findings, treatment, and clinical course of the study patient.ResultsA 35-year-old woman was evaluated for a neck mass that had been present for 6 months and was slowly growing. She reported a previous diagnosis of right hemithyroid agenesis. The patient’s preoperative workup included ultrasonography of the neck and head and neck T1- and T2-weighted magnetic resonance imaging, which showed right hemithyroid agenesis and a cystic lesion in the median region of the neck below the hyoid bone. Findings from chest x-rays and thyroid function tests were normal. The patient underwent a modified Sistrunk procedure that included removal of the median portion of the hyoid bone. Histologic findings showed a 2.5-cm thyroglossal duct cyst with a 0.6-cm focus of follicular variant of papillary carcinoma with invasion of the cyst wall. Total thyroidectomy was not performed because of the absence of tumoral invasion of the parenchyma around the thyroglossal duct cyst and because the patient was at low risk for aggressive disease. Cervical ultrasonography examinations were performed 6, 12, and 24 months after treatment, and all findings were normal. Presently, the patient is symptom-free after 4 years of follow-up and has no evidence of disease.ConclusionIncidentally discovered, well-differentiated thyroid cancer that is confined to a thyroglossal duct cyst in a patient at low risk for aggressive disease can be adequately treated by a modified Sistrunk procedure that includes the median portion of the hyoid bone. (Endocr Pract. 2008;14:465-469)     

Influence of Levothyroxine With Recombinant Human Thyroid-Stimulating Hormone on Urinary Iodine Excretion Before Radioactive Iodine Administration

ObjectiveStimulation with recombinant human thyroid-stimulating hormone (rhTSH) before radioactive iodine administration for patients with thyroid cancer may increase the body iodine pool in the presence of continued levothyroxine; however, the precise significance of its influence remains unclear.MethodsThis was a prospective observational study conducted between March 2017 and August 2020. We measured the 24-hour urinary iodine excretion and urinary iodine-to-creatinine ratio in patients with thyroid cancer stimulated by rhTSH or thyroid hormone withdrawal (THW) before radioactive iodine administration. Oral iodine intake was controlled by a 7-day self-managed low iodine diet, followed by a strict 3-day low iodine diet while in the hospital.ResultsOverall, 343 subjects were included (rhTSH: n = 181; THW: n = 162). The mean levothyroxine dose in the rhTSH group was 115.2 μg daily. The median 24-hour urinary iodine and urinary iodine-to-creatinine ratio in the rhTSH group (71.0 [interquartile range, 57.5-88.0] μg/day and 80.0 [59.0-97.5] μg/gCr, respectively) were significantly higher than those in the THW group (42.0 [30.0-59.0] μg/day and 39.0 [28.0-61.3] μg/gCr, respectively; both P < .001). After propensity score matching by age, sex, body weight, and renal function (rhTSH: n = 106; THW: n = 106), consistent results for both values were observed for both methods. The increase in urinary iodine with the rhTSH method was smaller than the expected value calculated from the amount of levothyroxine.ConclusionUrinary iodine excretion was significantly higher among patients with rhTSH stimulation than those with THW, indicating that the rhTSH method slightly increases the body iodine pool.     

Diagnostic Predicament of Secondary Adrenal Insufficiency

ObjectiveTo propose an approach for the diagnosis of secondary adrenal insufficiency(AI) by presentation of 2 clinical cases and review of the literature.MethodsWe describe 2 patients who were considered to have a normal hypothalamic-pituitary-adrenal axis on the basis of an appropriate response to the high-dose (250 μg) cosyntropin stimulation test (HST), with use of a cutoff value of 20 μg/dL. Our first patient had undergone resection of a 4-cm pituitary tumor a few months previously, and the second patient had hyponatremia with empty sella syndrome. Both patients, however, had strong clinical evidence suggestive of secondary AI. On testing by the insulin tolerance test (ITT) in the first patient and the overnight metyrapone test (OMT) in the second patient, secondary AI was diagnosed. We reviewed the literature to compare the utility of the different tests for the diagnosis of secondary AI.ResultsAn 8 am serum cortisol value less than 5 μg/ dL or above 13 μg/dL and a stimulated cortisol level less than 16 μg/dL on both the low-dose cosyntropin stimulation test (LST) and the HST as well as above 22 μg/dL on the LST and above 30 μg/dL on the HST can reliably predict the functional status of the hypothalamic-pituitaryadrenal axis in chronic secondary AI. Values between these utoff points may necessitate further assessment with the OMT or ITT based on clinical suspicion.ConclusionWe recommend a 3-step diagnostic approach, with the first 2 steps performed together—starting with the 8 am basal cortisol determination in conjunction with either the LST (preferably) or the HST. In cases of an indeterminate response coupled with a strong clinical suspicion, the final step should be definitive testing with the OMT or ITT. (Endocr Pract. 2010;16:686-691)