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Objective: We aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter., Methods: We retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi., Results: The median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005)., Conclusion: Overall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment., Methods: Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly., Results: After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery., Conclusion: For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: Levothyroxine (L-T4) is the standard therapy of hypothyroidism. Our purpose was to compare the effectiveness of the L-T4 liquid formulation with respect to L-T4 tablet in hypothyroid patients without malabsorption or drug interference. Twenty-one subjects with high thyroid-stimulating hormone (TSH) values under therapy with L-T4 tablets were switched to liquid L-T4 at the same dosage given 30 minutes before breakfast., Results: TSH values significantly declined 2 months after from the switch to liquid L-T4, reaching the normal range in most cases. In 15 (of the 21 patients) who switched back to tablets, TSH increased again to the hypothyroid range. Since the liquid L-T4 formulation resulted in better TSH level control, all patients were finally treated with the liquid L-T4, and TSH, free tri-iodothyronine and free thyroxine were evaluated again after 6 and 12 months, resulting in normal ranges in all subjects., Conclusions: The change from tablets to liquid oral formulation normalized serum TSH levels, while switching back to tablets caused thyrotropin levels to worsen. These results suggest that the liquid L-T4 formulation is more effective than tablets in controlling TSH levels in hypothyroid patients in the absence of malabsorption, gastric disorders, or drug interference., Abbreviations: BMI = body mass index FT3 = free tri-iodothyronine FT4 = free thyroxine L-T4 = levothyroxine PPIs = proton-pump inhibitors TSH = thyroid-stimulating hormone.

Objectives: To review a stepwise approach to the evaluation and treatment of subclinical hyperthyroidism., Methods: English-language articles regarding clinical management of subclinical hyperthyroidism published between 2007 and 2012 were reviewed., Results: Subclinical 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., Conclusion: The 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.

Objective: To 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., Methods: The clinical and biochemical data from the study patient are presented and the pertinent literature is reviewed. A risk analysis for this complication is highlighted., Results: A 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., Conclusions: This 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.

Objective: To 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., Methods: In 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., Results: Patient 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., Conclusion: High 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.

Objective: To 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., Methods: We 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., Results: The 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

Objective: To report the effects of pretreatment with recombinant human thyrotropin (rhTSH) on radioiodine uptake (RAIU) and subsequent radioiodine therapy in 30 patients with symptomatic nontoxic or toxic multinodular goiter., Methods: Patients received a single injection of rhTSH (0.1 mg in 21 and 0.3 mg in 9 patients). Thyroid function tests were performed before and 72 hours after rhTSH administration. Both 4-hour and 24-hour RAIU studies were done after rhTSH administration and repeated at 48 to 52 hours and at 72 hours, respectively. Then all patients were treated with 30 mCi of 131 I., Results: All study patients experienced symptomatic relief by 1 to 2 months. In addition to the previously reported twofold increase over the baseline RAIU at 24 hours, we found that a second 24-hour RAIU showed a further twofold increase (quadrupling of the RAIU over baseline) at 72 hours after administration of 0.1 mg of rhTSH (from 22% to 43%; P<0.001) and 0.3 mg of rhTSH (from 16% to 37%; P = 0.002), with no significant difference between doses on the RAIU at 24 hours or at 72 hours. Additionally, the RAIU value at 4 hours and 52 hours after administration of 0.1 mg and 0.3 mg of rhTSH revealed a fourfold increase for each dose--from 7% to 28% (P<0.001) and from 5% to 21% (P = 0.002), respectively., Conclusion: In patients with symptomatic toxic or nontoxic multinodular goiter, 0.1 mg and 0.3 mg of rhTSH were equally efficacious at inducing a quadrupling of the low or low-normal baseline RAIU values at 72 hours after injection. Subsequent radioiodine therapy alleviated compressive and thyrotoxic symptoms in all 30 treated patients. Future studies should help determine doses of rhTSH and radioiodine therapy that are optimal in iodine-sufficient and insufficient regions of the world.

Objective: To report our results in treating 16 patients with low radioiodine uptake (RAIU) multinodular goiter who had obstructive symptoms or suppressed thyroid-stimulating hormone (TSH or thyrotropin), indicating mild hyperthyroidism., Methods: Six patients were treated with 0.3 mg of recombinant human thyrotropin (rhTSH) followed by 30 mCi of (131)I 72 hours later. Ten patients were treated with 0.9 mg of rhTSH followed by 30 mCi of (131)I 24 hours later., Results: Of the 16 treated patients, all 10 with compressive symptoms and both patients with weight loss had remission or improvement, as did 1 of 2 patients with atrial fibrillation. All patients with suppressed TSH had a return to normal levels or became hypothyroid. During the next 3 to 7 months, estimated gland size reduction was 30 to 40%. Three of the 6 patients who received 0.3 mg of rhTSH and 6 of the 10 patients who received 0.9 mg of rhTSH, in conjunction with (131)I therapy, ultimately had TSH levels indicative of hypothyroidism. Mild radiation thyroiditis developed in only one patient, and no other side effects occurred., Conclusion: The 0.3-mg dose of rhTSH seemed to be as efficacious as the 0.9-mg dose. The greater than fourfold increase in RAIU at 72 hours after administration of rhTSH in our study is more than twofold higher than the 24-hour RAIU results previously reported in normal subjects and in patients with multinodular goiter. These findings have implications for future expanded studies and alternative dosing regimens in treating patients with both multinodular goiter and subclinical hyperthyroidism.

Objective: To describe a complicated case of metastatic papillary thyroid carcinoma and the use of recombinant human thyrotropin (thyroid-stimulating hormone) (rhTSH) in conjunction with treatment with radioactive iodine (131I)., Methods: We present a detailed case report and discuss the use of rhTSH in this setting., Results: A 62-year-old Filipino man with a history of incompletely treated papillary thyroid cancer sought medical assistance in the emergency department because of weakness of the right upper extremity. Imaging studies showed a large mediastinal mass in association with C7 vertebral body erosion and spinal cord impingement. A cervical lymph node biopsy revealed papillary thyroid carcinoma, follicular variant. Further imaging studies disclosed widely metastatic disease. The patient subsequently had a complicated treatment course and received rhTSH in conjunction with 131I treatment., Conclusion: This unusual case demonstrates possible complications of metastatic papillary thyroid carcinoma along with innovations in treatment options, including the use of rhTSH to stimulate the uptake of radioiodine by thyroid cancer cells.

Objective: To describe the use of recombinant human thyrotropin (thyroid-stimulating hormone) (rhTSH) to assist in radioiodine therapy in a patient with thyroid carcinoma who was unable to produce sufficient endogenous thyrotropin when hypothyroid and to review the related literature., Methods: The study patient underwent formal dosimetric analysis and received radioiodine in conjunction with rhTSH. Follow-up scanning studies were performed., Results: We found good localization of radioiodine on the posttherapy scans after administration of (131)I while the patient continued to receive thyroxine replacement after two intramuscularly administered injections of rhTSH. Some of his metastatic lesions disappeared and his serum thyroglobulin level decreased after the first rhTSH-assisted dose of (131)I was administered. His blood radioiodine clearance rate was unexpectedly more rapid in the hypothyroid state than when he was euthyroid (taking thyroxine) after administration of rhTSH. His whole-body clearance rate was more delayed when he was hypothyroid. Swelling of some of the metastatic thyroid cancer lesions developed when the patient was hypothyroid and after rhTSH was administered, the latter being much more rapid in onset., Conclusion: Therapeutic doses of radioiodine can be delivered with the assistance of rhTSH administration while patients continue to take suppressive doses of thyroxine. Metastatic thyroid carcinoma lesions can swell rapidly after administration of rhTSH. The commercially available form of rhTSH is approved only for diagnostic use. Its safety and efficacy in assisting radioiodine therapy have not been fully determined.

Objective: To review two phase III clinical trials with recombinant human thyrotropin (rhTSH) in patients with treated thyroid cancer, which led to its approval by the Food and Drug Administration., Methods: The trial designs, the results of radioiodine scanning, and the findings with use of both scanning and thyroglobulin (Tg) response are described. In the overall study design, the findings on whole-body radioiodine scanning were compared after use of two techniques--administration of rhTSH and withdrawal of thyroid hormone therapy., Results: In the first phase III trial, two independent reviewers assessed 127 scan pairs and found 21 scan pairs to be discordant. In 18 of these cases, the scan after thyroid hormone withdrawal was judged as better than the scan after rhTSH administration. Subsequent analysis, however, revealed some problems with the protocol, and adjustments and standardizations were implemented for the second phase III trial, for which multiple blood samples were also obtained for serum Tg determinations. In this second study, 195 of 220 scan pairs were concordant, and only 25 pairs were discordant--17 were better after thyroid hormone withdrawal and 8 were better after rhTSH administration (P<0.1). The Tg response to rhTSH was not sufficiently reliable independently but was useful in combination with whole-body scanning (detection rate of 85 to 90%)., Conclusion: The data indicate that rhTSH will be useful for investigation and long-term follow-up of patients with treated thyroid cancer.

Objective: To determine the frequency of liver dysfunction in patients with hyperthyroidism., Methods: We analyzed the clinical records of 30 consecutive patients with Graves' disease to identify the spectrum of abnormal results of liver function tests. The values for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma -glutamyltransferase (GGT), and total bilirubin were examined., Results: The frequencies of increased levels of AP, AST, ALT, GGT, and bilirubin in the current study group were similar to but somewhat lower than those reported in previous studies. Of the 30 study patients, 11 (37%) had at least one abnormal result of a liver function test. All 30 patients in the study had determinations of AP (not fractionated), of which 10 values (33%) were above normal (range, 124 to 283 U/L). Of the 30 patients who had determinations of AST, 5 (17%) had increased values that ranged from 36 to 71 U/L. Six of the 23 patients (26%) with determinations of ALT had increased values that ranged from 45 to 157 U/L. Of the 25 patients who had measurements of GGT, 6 had above normal results (range, 69 to 331 U/L). In addition, 2 of the 24 patients (8%) with determinations of total bilirubin had increased levels., Conclusion: These findings indicate that abnormal results of liver function tests are common in patients with hyperthyroidism and make the diagnosis of concomitant, unrelated liver disease difficult until the euthyroid state has been established.