Central hyperthyroidism due to an ectopic TSH-secreting pituitary tumor: a case report and literature review.

Ectopic thyroid-stimulating hormone (TSH)-secreting tumors are extremely rare, with only 15 reported cases in the literature. Herein, we described a 60-year-old female patient with thyrotoxicosis and elevated or unsuppressed levels of TSH. Family history and laboratory and genetic tests did not support a diagnosis of resistance to thyroid hormone (RTH). Given the unsuppressed TSH, TSH-secreting tumor was suspected, and magnetic resonance imaging (MRI) of the pituitary gland was performed. Surprisingly, the MRI scans revealed a nodule in the nasopharynx rather than a pituitary tumor in the sella region. Further evaluation using Gallium-68 DOTATATE positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT) demonstrated increased DOTATATE uptake in the nasopharyngeal nodule. Additionally, an octreotide suppression test (OST) revealed an obvious reduction in TSH levels, further supporting the suspicion of the nasopharyngeal mass as the cause of inappropriate TSH secretion. To prepare for surgery, the patient received preoperative administration of octreotide, resulting in the normalization of TSH and thyroid hormone levels. The patient subsequently underwent successful surgical removal of the nasopharyngeal mass. Following the procedure, the patient experienced complete resolution of hyperthyroidism symptoms, with TSH declined and thyroid hormone levels returned to normal. Histochemistry analysis of the tumor revealed positive staining for TSH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and somatostatin receptor 2 (SSTR2). We discussed differential diagnosis of hyperthyroidism due to inappropriate TSH secretion, with a particular emphasis on the importance of 68Ga-DOTATATE PET/CT in combination with OST for identifying ectopic pituitary tumors.

Retracting the thyroid matters: Who develops asymptomatic transient thyrotoxicosis after parathyroidectomy.

BACKGROUND: Hyperthyroidism after parathyroidectomy is not a well-understood complication. We sought to determine the incidence and risk factors of hyperthyroidism after parathyroidectomy. MATERIALS AND METHODS: This is a prospective study of 91 patients undergoing parathyroidectomy. Pre- and post-operative thyroid-stimulating hormone(TSH) and free thyroxine(T4) levels at two-week follow-ups were collected. Bivariate analyses were conducted to compare demographics, laboratory results, and intraoperative findings between patients with normal and suppressed post-parathyroidectomy TSH. RESULTS: Twenty-two(24.2 â€‹%) patients had suppressed TSH after parathyroidectomy and 2(2.2 â€‹%) reported symptoms of hyperthyroidism. All hyperthyroidism resolved within 6 weeks. No patients required medical treatment. Compared to the normal TSH group, the suppressed TSH group had significantly more bilateral explorations(91.0 â€‹% vs. 58.0 â€‹%, p â€‹= â€‹0.006), and superior parathyroid resections(95.5 â€‹% vs. 65.2 â€‹%, p â€‹= â€‹0.006). CONCLUSION: Transient hyperthyroidism is common following parathyroidectomy, which is likely associated with intraoperative thyroid manipulation. Gentle retraction of thyroid glands in parathyroidectomy is warranted, especially during superior parathyroid gland resection.

Hyperthyroidism: A Review.

Importance: Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. Observations: The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Conclusions and Relevance: Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

Preliminary Results of Utrasound-Guided Percutaneous Radiofrequency Ablation in the Treatment of Refractory Non-nodular Hyperthyroidism.

PURPOSE: To assess the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of refractory non-nodular hyperthyroidism. METHODS: This was a single-center retrospective study in 9 patients with refractory non-nodular hyperthyroidism (2 males, 7 females; median age, range, 36 years, 14-55 years) who underwent RFA between August 2018 and September 2020. The incidence of post-procedural complications, changes in thyroid volume, thyroid function and the use and dosages of anti-thyroid drugs, were compared pre- and post-RFA. RESULTS: All patients completed the procedure successfully, and no serious complications occurred. Three months after ablation, thyroid volumes were significantly decreased with the mean volumes of the right and left lobes reduced to 45.6% (10.9 ± 2.2 ml/23.9 ± 7.2 ml, p < 0.001) and 50.2% (10.8 ± 7.4 ml/21.5 ± 11.4 ml, p = 0.001) of the volumes within 1 week after ablation. The thyroid function was gradually improved in all patients. At 3 months post-ablation, the levels of FT3 and FT4 were returned to the normal range (FT3, 4.9 ± 1.6 pmol/L vs. 8.7 ± 4.2 pmol/L, p = 0.009; FT4, 13.1 ± 7.2 pmol/L vs. 25.9 ± 12.6 pmol/L, p = 0.038), the TR-Ab level was significantly lower (4.8 ± 3.9 vs. 16.5 ± 16.4 IU/L, p = 0.027), and the TSH level was significantly higher (0.76 ± 0.88 vs. 0.03 ± 0.06, p = 0.031) than that before-ablation. Additionally, three months after RFA, the anti-thyroid medication dosages were reduced to 31.25% compared to baseline (p < 0.01). CONCLUSION: Ultrasound-guided RFA in the treatment of refractory non-nodular hyperthyroidism was safe and effective in this small group of patients with limited follow-up. Further studies with larger cohorts and longer follow-up are needed to validate this potential new application of thyroid thermal ablation.

Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis.

Hyperthyroidism is a common condition with a global prevalence of 0·2-1·3%. When clinical suspicion of hyperthyroidism arises, it should be confirmed by biochemical tests (eg, low TSH, high free thyroxine [FT4], or high free tri-iodothyonine [FT3]). If hyperthyroidism is confirmed by biochemical tests, a nosological diagnosis should be done to find out which disease is causing the hyperthyroidism. Helpful tools are TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy. Hyperthyroidism is mostly caused by Graves' hyperthyroidism (70%) or toxic nodular goitre (16%). Hyperthyroidism can also be caused by subacute granulomatous thyroiditis (3%) and drugs (9%) such as amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors. Disease-specific recommendations are given. Currently, Graves' hyperthyroidism is preferably treated with antithyroid drugs. However, recurrence of hyperthyroidism after a 12-18 month course of antithyroid drugs occurs in approximately 50% of patients. Being younger than 40 years, having FT4 concentrations that are 40 pmol/L or higher, having TSH-binding inhibitory immunoglobulins that are higher than 6 U/L, and having a goitre size that is equivalent to or larger than WHO grade 2 before the start of treatment with antithyroid drugs increase risk of recurrence. Long-term treatment with antithyroid drugs (ie, 5-10 years of treatment) is feasible and associated with fewer recurrences (15%) than short-term treatment (ie, 12-18 months of treatment). Toxic nodular goitre is mostly treated with radioiodine (131I) or thyroidectomy and is rarely treated with radiofrequency ablation. Destructive thyrotoxicosis is usually mild and transient, requiring steroids only in severe cases. Specific attention is given to patients with hyperthyroidism who are pregnant, have COVID-19, or have other complications (eg, atrial fibrillation, thyrotoxic periodic paralysis, and thyroid storm). Hyperthyroidism is associated with increased mortality. Prognosis might be improved by rapid and sustained control of hyperthyroidism. Innovative new treatments are expected for Graves' disease, by targeting B cells or TSH receptors.

Hyperthyroidism in McCune-Albright Syndrome - a case report.

OBJECTIVES: We intend to describe a case of McCune-Albright Syndrome (MAS), a rare disease characterized by fibrous dysplasia (FD), cutaneous hyperpigmentation and hyperfunctioning endocrinopathies (HFE). CASE PRESENTATION: We report the case of a 13-year-old male child who presented with a café-au-lait macule in the lumbosacral region and disabling polyostotic FD, requiring several surgical interventions and bisphosphonates from the age of 3 years (Y) + 9 months (M) due to persistent and severe pain. Hyperthyroidism (HT) became apparent at 5 Y + 1 M with a T3/T4 ratio greater than 20. Treatment with anti-thyroid drugs (ATD) was carried out for 7 Y and there was a progressive improvement in pain complaints 8 M after starting ATD, allowing treatment with pamidronate to be discontinued. Total thyroidectomy was performed at 12 Y + 5 M. CONCLUSIONS: This is a case of MAS-associated HT that reflects the deleterious effect of thyroid hormone excess on FD, reinforcing the need of having a low threshold for suspicion of HFE that may arise.

Therapeutic plasma exchange in hyperthyroidism prior to surgery.

PURPOSE: Therapeutic plasma exchange (TPE) is a treatment option to reduce thyroid hormones in the event of contraindication or unresponsiveness to antithyroid drugs (ATDs). METHODS: We analyzed 11 patients with hyperthyroidism who received TPE prior to surgery between January 2008 and December 2016 at our center. RESULTS: In total, 41 processes were applied to 11 patients with hyperthyroidism. The median age was 40 years, and 90.9% of the patients were female. Seven patients had Graves' disease, while four had a toxic multinodular goiter. The distribution of TPE indications comprised contraindication to ATDs (64%) and insufficient response to ATDs (36%). An adequate response was not obtained with TPE in two patients, and cholestyramine plus methimazole and Lugol solution were applied. The median number of TPE sessions was 3. During the TPE period, a ß-blocker was applied concurrently except in one patient who was contraindicated for the drug. The reduction in FT3 and FT4 hormones and the increase in TSH levels were statistically significant after TPE application (p values of 0.003, 0.033 and 0.008, respectively). Regarding adverse events of TPE application, an allergic reaction was seen in one patient, while prolongation of prothrombin time without any clinical findings was seen in another patient. Ten patients underwent total thyroidectomy, and one patient underwent a gynecological surgery procedure without any major complications. CONCLUSION: The American Society for Apheresis guideline, which is the most referenced guideline, mentions the utilization of TPE before thyroid surgery, only in patients with thyrotoxicosis despite the wider necessity of this treatment choice under the condition of uncontrolled hyperthyroidism prior to any kind of surgery. We concluded that TPE is a reliable and effective application in patients with hyperthyroidism before any surgical procedure, according to our study results.

Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter.

Background: Although hyperfunctioning thyroid disorders were thought to be protective against malignancy, some recent studies reported a high incidence of incidentally discovered cancer in patients with hyperfunctioning benign thyroid disorders. We performed this study to estimate the incidence and predictors of malignant thyroid disease in patients with toxic nodular goiter (TNG). Patients and Methods. The data of 98 patients diagnosed with TNG were reviewed (including toxic multinodular goiter SMNG and single toxic nodule STN). The collected data included patients age, gender, systemic comorbidities, family history of thyroid malignancy, previous neck radiation, type of disease (multinodular or single), size of the dominant nodule by the US, operative time, and detection of significant lymph nodes during operation. Based on the histopathological analysis, the cases were allocated into benign and malignant groups. Results: Malignancy was detected in 21 patients (21.43%). Although age distribution was comparable between the two groups, males showed a significant increase in association with malignancy. Medical comorbidities and family history of cancer did not differ between the two groups. However, TMNG showed a statistically higher prevalence in the malignant group. Operative data, including operative time and lymph node detection, were comparable between the two groups. On regression analysis, both male gender and TMNG were significant predictors of malignancy. Conclusion: The presence of thyroid hyperfunction is not a protective factor against malignancy, as malignancy was detected in about 1/5 of cases. Male gender and TMNG were significant risk factors of malignancy in such patients.

Severe thyrotoxicosis as initial presentation of gastric choriocarcinoma: a case report.

BACKGROUND: Extragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin. CASE PRESENTATION: A 62-year-old Hispanic female presented with a 3-week history of shortness of breath, palpitations, extreme weakness, new-onset hot flashes, and right flank pain. Her physical examination was remarkable for tachycardia, hepatomegaly, hyperreflexia, and tremor; goiter was absent. Laboratory studies revealed increased lactate dehydrogenase, alkaline phosphatase, suppressed thyroid stimulating hormone, very elevated T4, and absent thyroid stimulating immunoglobulin. 18F-fluorodeoxyglucose positron emission tomography-computed tomography exhibited hepatomegaly with multiple large fluorodeoxyglucose-avid liver masses and a focus of fluorodeoxyglucose avidity in the stomach with no structural correlate. A thyroid scan (99mTcO 4 - ) showed diffusely increased tracer uptake. She was started on propranolol and methimazole. Upon stabilization of severe thyrotoxicosis, upper endoscopy was performed, showing a ~ 5 cm bleeding lesion in the greater stomach curvature body; biopsy was consistent with choriocarcinoma; beta-human chorionic gonadotropin hormone was 2,408,171 mIU/mL. The patient received methotrexate followed by etoposide and cisplatin. Methimazole was titrated down, and upon liver failure the medication was stopped. The thyrotoxicosis was effectively controlled with antithyroid drug and concurrent chemotherapy. At ~ 1.5 months after initial diagnosis, the patient died due to bleeding/acute liver failure with coagulation defects followed by multiple organ failure. CONCLUSIONS: Severe thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options.

Use of Lithium in Hyperthyroidism Secondary to Graves' Disease: A Case Report.

BACKGROUND The therapeutic approach to Graves' disease (GD) comprises thionamides, radioiodine ablation, or surgery as first-line therapy, and cholestyramine and oral iodine as second-line therapies. The role of lithium (Li) in GD as a primary or adjunctive therapy remains contentious. We present a case of GD managed by Li therapy with oral iodine solution. CASE REPORT A 26-year-old man, admitted with acute blast crisis secondary to chronic myeloid leukemia (CML), reported palpitations, 40-lb weight loss, heat intolerance, and fatigue. An examination revealed sinus tachycardia, elevated body temperature, and thyromegaly. Laboratory evaluation confirmed hyperthyroidism (TSH <0.005 mcIU/l, FT4 5.57 ng/dl, TT3 629 ng/dl) secondary to GD (TRAb >40 IU/l, TSIg 178%). Thionamides and surgery were contraindicated due to pancytopenia from a blast crisis. Inability to maintain post-radiation precautions precluded use of RAI. Cholestyramine was attempted and discontinued due to nausea. We introduced oral Li carbonate with oral iodine, which the patient tolerated. Thyroid functions improved with therapy (TSH 0.007 mcIU/l, FT4 0.82 ng/dl, TT3 122 ng/dl) with stable Li level (0.5-0.8 mmol/l). CONCLUSIONS Li inhibits iodine uptake through interference with sodium-iodide symporter and tyrosine iodination, thyroglobulin structure changes, peripheral deiodinase blockage, and preventing TSH and TSIg stimulation. Our case shows that a low therapeutic level of Li, in combination with oral iodine, can suppress thyroid overactivity without adverse effects. We suggest that low-dose Li carbonate is a safe and effective adjunctive antithyroid medication to be considered if primary therapies for hyperthyroidism are unavailable.

Effect of thyroid function on pre-ß1 high-density lipoprotein levels in patients with Graves' disease undergoing radioiodine treatment.

CONTEXT: The metabolism of HDL is altered in thyroid dysfunctions. Preß-1 HDL is a very small discoidal precursor HDL and promotes cholesterol efflux via ABCA1. The effects of thyroid dysfunctions on pre-ß1 HDL are unknown. Thyroid hormone regulates ANGPTL3 expression, which may participate in HDL metabolism in thyroid dysfunctions. OBJECTIVE: To determine the variation of HDL subfractions, especially preß-1 HDL in thyroid dysfunctions, and whether ANGPTL3 mediates the effect of thyroid function on HDL metabolism. METHODS: We recruited 26 patients with Graves' disease undergoing radioiodine treatment. They were evaluated at three time points: at baseline, when they were hypothyroid after radioiodine treatment, and when they were on stable levothyroxine replacement and euthyroid. RESULTS: The concentrations of smaller HDL particles Preß-1 HDL and HDL3 were highest at the hyperthyroid state, and lowest at the hypothyroid state. While the larger HDL particles HDL2 and HDL1 changed just the opposite. Preß1-HDL and HDL3 were positively correlated to fT3 and fT4, while were negatively correlated to TSH. In contrast, HDL1 was negatively associated with fT3 and fT4, while was positively associated with TSH. The correlations between thyroid hormones and HDL subfractions remained significant after adjusting for ANGPTL3. CONCLUSIONS: There is a shift form smaller HDL particles pre-ß1 HDL and HDL3 to larger HDL particles HDL2 and HDL1 in hypothyroidism, while the change is just the opposite in hyperthyroidism. In future, cholesterol efflux capacity should be measured to determine if the function of HDL particles also changes with the shifting of HDL subfractions.

Gene expression profile in functioning and non-functioning nodules of autonomous multinodular goiter from an area of iodine deficiency: unexpected common characteristics between the two entities.

PURPOSE: Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and non-functioning nodules, characterized by increased proliferation but opposite functional activity, may coexist in the same gland. To understand the distinct molecular pathology of each entity present in the same gland, the gene expression profile was evaluated by using the Affymetrix technology. METHODS: Total RNA was extracted from nodular and healthy tissues of two patients and double-strand cDNA was synthesized. Biotinylated cRNA was obtained and, after chemical fragmentation, was hybridized on U133A and B arrays. Each array was stained and the acquired images were analyzed to obtain the expression levels of the transcripts. Both functioning and non-functioning nodules were compared versus healthy tissue of the corresponding patient. RESULTS: About 16% of genes were modulated in functioning nodules, while in non-functioning nodules only 9% of genes were modulated with respect to the healthy tissue. In functioning nodules of both patients and up-regulation of cyclin D1 and cyclin-dependent kinase inhibitor 1 was observed, suggesting the presence of a possible feedback control of proliferation. Complement components C1s, C7 and C3 were down-regulated in both types of nodules, suggesting a silencing of the innate immune response. Cellular fibronectin precursor was up-regulated in both functioning nodules suggesting a possible increase of endothelial cells. Finally, Frizzled-1 was down-regulated only in functioning nodules, suggesting a role of Wnt signaling pathway in the proliferation and differentiation of these tumors. None of the thyroid-specific gene was deregulated in microarray analysis. CONCLUSION: In conclusion, the main finding from our data is a similar modulation for both kinds of nodules in genes possibly implicated in thyroid growth.

[Hyperthyroidism and an unexpected molar pregnancy]. / Hyperthyreoïdie en een onverwachte molazwangerschap.

BACKGROUND: A molar pregnancy is a rare complication of (non-viable) pregnancy and produces high levels of hCG-hormone. hCG has characteristics similar to TSH, and therefore (severe) hyperthyroidism can occur. The incidence of molar pregnancy is approximately 1 in 1000-1500 pregnancies. CASE DESCRIPTION: A 23-year-old woman had complaints of discomfort, nausea and vomiting. A urine pregnancy test was negative and laboratory tests showed a severe hyperthyroidism. After referral a molar pregnancy was diagnosed (hCG 1.7 million IU/L). She was treated by curettage. hCG levels insufficiently decreased in the following weeks, and gestational trophoblastic neoplasia was diagnosed. She needed several courses of methotrexate after which she completely recovered. CONCLUSION: Severe hyperthyreoidism can be caused by a molar pregnancy. A urine pregnancy test can be negative because of too high hCG-levels, also known as the hook effect. Early recognition and treatment are very important because of the risk of severe complications.

Syndrome of inappropriate secretion of thyroid-stimulating hormone in a subject with galactorrhea and menstrual disorder and undergoing infertility treatment: Case report.

RATIONALE: Syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) is a rare cause of hyperthyroidism. Thyroid-stimulating hormone (TSH) levels are usually normal or high, and triiodothyronine (FT3) and free thyroxine (FT4) levels are usually high in subjects with SITSH. PATIENT CONCERN: A 37-year-old woman had experienced galactorrhea and menstrual disorder for a couple of years before. She had undergone infertility treatment in 1 year before, hyperthyroidism was detected and she was referred to our institution. DIAGNOSIS: She was suspected of having SITSH and was hospitalized at our institution for further examination. The data on admission were as follows: FT3, 4.62 pg/mL; FT4, 1.86 ng/dL; TSH, 2.55 µIU/mL. Although both FT3 and FT4 levels were high, TSH levels were not suppressed, which is compatible with SITSH. In addition, in brain contrast-enhanced magnetic resonance imaging, nodular lesions were observed in the pituitary gland with a diameter of approximately 10 mm. In the thyrotropin-releasing hormone load test, TSH did not increase at all, which was also compatible with TSH-secreting pituitary adenoma. In the octreotide load test, the TSH levels were suppressed. Based on these findings, we diagnosed this subject as SITSH. INTERVENTIONS: Hardy surgery was performed after the final diagnosis. In TSH staining of the resected pituitary adenoma, many TSH-producing cells were observed. These findings further confirmed the diagnosis of pituitary adenoma producing TSH. OUTCOMES: Approximately 2 months after the operation, TSH, FT3, and FT4 levels were normalized. Approximately 3 months after the operation, she became pregnant without any difficulty. LESSONS: We should consider the possibility of SITSH in subjects with galactorrhea, menstrual disorders, or infertility. In addition, we should recognize that it is very important to repeatedly examine thyroid function in subjects with galactorrhea, menstrual disorder, or infertility.

Can Pretreatment Serum Beta-hCG be Used for Predicting Thyrotoxicosis in Gestational Trophoblastic Disease?

BACKGROUND: Gestational trophoblastic disease (GTD) comprises a diverse spectrum of entities of abnormal cellular proliferations originating in placental trophoblasts. The specific marker of GTD is beta-hCG which has a similar structure to the TSH molecule, interfering level of thyroid hormones. How and when to check for thyroid function test during this period remain challenging. OBJECTIVE: To assess values of pretreatment beta-hCG and its benefit for predicting thyrotoxicosis among patients with diagnoses of GTD. METHODS: Retrospective analytical study included all women diagnosed with GTD at Lampang Hospital from January 2010 to May 2020. The patients' pretreatment beta-hCG and thyroid function were collected. Sensitivity and specificity for detecting laboratory hyperthyroidism were reported and classified by pretreatment beta-hCG levels. RESULTS: Forty-four women with diagnoses of GTD were recruited. The range of pretreatment beta-hCG levels were classified  into 4 groups: beta-hCG > 50,000 IU/ml (group 1), beta-hCG > 100,000 IU/ml (group 2), beta-hCG > 150,000 IU/ml (group 3), beta-hCG > 200,000 IU/ml (group 4). The sensitivity for prediction of high fT4 were 100%, 94.1%, 94.1% and 88.2% in group 1,2,3 and 4, respectively, while the specificity were 12%, 20%, 32% and 44% in group 1,2,3 and 4, respectively. CONCLUSION: Pretreatment beta-hCG > 100,000 uIU/ml has the high sensitivity and acceptable specificity for predicting hyperthyroidism. So we don't need to check or wait for thyroid function test in patients who had beta-hCG < 100,000 IU/ml.

Thyroid storm as an early presentation of hCG-producing metastatic choriocarcinoma: a case report and review of the literature.

Human chorionic gonadotropin (hCG)-induced hyperthyroidism has been previously reported as a rare paraneoplastic syndrome in non-seminomatous germ cell tumours and usually presents with mild symptoms or subclinical thyrotoxicosis. We present a case of a young adult man who consulted with abdominal pain, nausea and emesis. On admission, he was found to be tachycardic, febrile, anxious and with icteric sclera and tenderness to palpation in the right upper abdomen. A right scrotal mass was also noted. Initial studies revealed transaminitis, hyperbilirubinaemia, suppressed thyroid-stimulating hormone and elevated free T4. Scrotal biopsy confirmed diagnosis of testicular choriocarcinoma with an elevated hCG level of 6074 mIU/mL, which was corrected to 6 760 713 mIU/mL when reassessed with dilution. The clinical scenario reflected hCG-induced thyrotoxicosis concerning for thyroid storm. Euthyroid state was restored after initiation of chemotherapy and a short course of methimazole. Unfortunately, the patient passed away due to progression of his malignant disease. This case suggests that when choriocarcinoma is suspected, the use of iodinated contrast agents should be limited to avoid precipitation of thyroid storm or worsening of hCG-induced hyperthyroidism. Moreover, if the clinical picture does not support a primary aetiology of hyperthyroidism and hCG is not concordantly elevated, reassessment of hCG by dilution should be considered as hCG assays are subject to prozone effect.

Bone Mineral Density in Adult Survivors of Pediatric Differentiated Thyroid Carcinoma: A Longitudinal Follow-Up Study.

Background: Survivors of pediatric differentiated thyroid carcinoma (DTC) receive thyrotropin-suppressive therapy to minimize disease recurrence. However, knowledge about long-term effects of subclinical hyperthyroidism on bone mineral density (BMD) in pediatric DTC survivors is scarce, as is the information regarding long-term consequences of permanent hypoparathyroidism on BMD. We evaluated BMD in pediatric DTC survivors and investigated if BMD was affected by subclinical hyperthyroidism and/or permanent hypoparathyroidism during long-term follow-up. Methods: In this nationwide longitudinal study, we determined BMD in the lumbar spine and femur by dual energy X-ray absorptiometry in 65 pediatric DTC survivors. Measurements were repeated after minimal 5 years of follow-up in 46 pediatric DTC survivors. BMD results were evaluated according to the recommendations of the International Society for Clinical Densitometry (ISCD) and WHO. At both visits, we determined biochemical parameters and markers of bone resorption (C-terminal telopeptide of type I collagen [ß-CTX]) and formation (N-propeptide of type I collagen [PINP] and osteocalcin). Results: First and second BMD measurements were done after a median follow-up of 17.0 (interquartile range [IQR] 8.0-25.0) and 23.5 (IQR 14.0-30.0) years after diagnosis, respectively. Median age at diagnosis was 15 years (IQR 13.0-17.0). Twenty-nine percent of the survivors had subclinical hyperthyroidism. In most survivors, BMD T- and Z-scores were within the reference range during both BMD evaluations. However, after 23.5 years of follow-up, a low BMD was found in 13.0%. In the 13 survivors with permanent hypoparathyroidism, BMD values did not differ after 5 years of follow-up compared with baseline values or in comparison with the 33 survivors without permanent hypoparathyroidism. During follow-up, turnover markers ß-CTX and PINP remained stable. Conclusions: This longitudinal study of pediatric DTC survivors demonstrated normal and stable median lumbar spine and femur BMD values after a median time of 17 and 23.5 years after diagnosis. However, compared with controls, a lower BMD was still found in 13.0% after prolonged follow-up despite intensive follow-up. Based on the studied follow-up period, these data do not provide convincing evidence in support of standard monitoring of bone mass among DTC survivors, but may be restricted to individual cases at low frequency. Trial Registration: This follow-up study was registered in The Netherlands Trial Register under no. NL3280 (www.trialregister.nl/trial/3280).

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

The aim of the study was to assess the occurrence and nature of immune-related endocrine adverse events (irAEs) among patients with non-small-cell lung cancer (NSCLC) treated with nivolumab. METHODS: The study group included 35 patients (15 women, 20 men, 65.8 ± 7.1 years) with NSCLC in stage IIIB (n = 16, 45.7%) and IV (n = 19,54.3%) who were treated with nivolumab. RESULTS: Of the studied patients, 34.3% (n = 12) developed endocrine irAEs (irAE group): 22.9% (n = 8) hyperthyroidism and 8.6% (n = 3) hypothyroidism, and in one case, hypophysitis was observed. The median irAEs onset time was 2 months. In the group of patients with thyroid disorders, permanent hypothyroidism eventually developed in 58.3%. The severity of the analyzed irAEs ranged from mild to moderate (Grade 1-2); the case of hypophysitis was estimated as Grade 3. The comparison of progression-free survival time (PFS) between the two groups showed longer PFS in patients in the irAE group (p = 0.021). Patients with irAE were treated significantly longer with nivolumab and they received more doses of nivolumab, however in Cox analysis we did not find patients with irAE to experience progression later than patients without them. CONCLUSIONS: Nivolumab therapy is associated with an increased risk of endocrine adverse effects, particularly thyroid dysfunction. Endocrine adverse effects can be successfully treated pharmacologically and usually do not require discontinuation of immunotherapy. The relationship between a better cancer prognosis in patients who developed endocrine irAE has not been found.