What Is Hyperthyroidism?

This JAMA Patient Page describes hyperthyroidism causes, symptoms, diagnosis, and treatment options.

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.

Management of foetal hyperthyroidism in a mother with autoimmune hypothyroidism: A case report.

Foetal hyperthyroidism is mediated by transplacental passage of thyroid stimulating antibodies (TSAbs) and affects mothers with autoimmune (AI) thyroid disease. We report a case of a 33-year-old woman with a history of AI hypothyroidism and raised TSI after 2 stillbirths with suspect foetal hyperthyroidism. At 20.5 gestational weeks (GW) of her third pregnancy, foetal tachycardia and goitre were detected. TSI levels were 30.9mUI/mL. Methimazole (MMI) was started and adjusted based on ultrasound signs (foetal heart rate and thyroid gland vascularisation). The neonate was born at 35GW and cord blood revealed decreased TSH and normal free T4. MMI was started in the neonate at 2 days of life due to the appearance of asymptomatic hyperthyroidism. This case illustrates a rare recurrence of foetal hyperthyroidism in a mother with AI hypothyroidism. Pregestational thyroidectomy, TSAbs determination, early ultrasound diagnosis and foetal therapy helped us to improve obstetric outcomes.

Safety and efficacy of prophylactic treatment for hyperthyroidism induced by iodinated contrast media in a high-risk population.

Introduction: The use of iodinated contrast media (ICM) can lead to thyrotoxicosis, especially in patients with risk factors, such as Graves' disease, multinodular goiter, older age, and iodine deficiency. Although hyperthyroidism may have clinically relevant effects, whether high-risk patients should receive prophylactic treatment before they are administered ICM is still debated. Aim of the study: We aimed to demonstrate the safety and efficacy of prophylactic treatment with sodium perchlorate and/or methimazole to prevent ICM-induced hyperthyroidism (ICMIH) in a population of high-risk cardiac patients. We ran a cost analysis to ascertain the most cost-effective prophylactic treatment protocol. We also aimed to identify possible risk factors for the onset of ICMIH. Materials and methods: We performed a longitudinal retrospective study on 61 patients admitted to a tertiary-level cardiology unit for diagnostic and/or therapeutic ICM-procedures. We included patients with available records of thyroid function tests performed before and after ICM were administered, who were at high risk of developing ICMIH. Patients were given one of two different prophylactic treatments (methimazole alone or both methimazole and sodium perchlorate) or no prophylactic treatment. The difference between their thyroid function at the baseline and 11-30 days after the ICM-related procedure was considered the principal endpoint. Results: Twenty-three (38%) of the 61 patients were given a prophylactic treatment. Thyroid function deteriorated after the administration of ICM in 9/61 patients (15%). These cases were associated with higher plasma creatinine levels at admission, higher baseline TSH levels, lower baseline FT4 levels, and no use of prophylactic treatment. The type of prophylaxis provided did not influence any onset of ICMIH. A cost-benefit analysis showed that prophylactic treatment with methimazole alone was less costly per person than the combination protocol. On multivariate analysis, only the use of a prophylactic treatment was independently associated with a reduction in the risk of ICMIH. Patients not given any prophylactic treatment had a nearly five-fold higher relative risk of developing ICMIH. Conclusion: Prophylactic treatment can prevent the onset of ICMIH in high-risk populations administered ICM. Prophylaxis is safe and effective in this setting, especially in cardiopathic patients. Prophylaxis with methimazole alone seems to be the most cost-effective option.

The Role of Nuclear Medicine in Benign Thyroid Disease.

Since the mid-twentieth century, the radionuclide thyroid scan has been utilized in the management of benign thyroid disorders. In current medical practice, patients with hyperthyroidism are referred for thyroid scintigraphy, while patients with goiters and thyroid nodules are most often evaluated by ultrasound or computed tomography. Since thyroid scintigraphy reflects the functional state of the gland, it provides information that anatomical imaging lacks. Therefore, radionuclide imaging of the thyroid is the imaging modality of choice in the evaluation of the hyperthyroid patient. In addition, patients with so-called subclinical hyperthyroidism often present a diagnostic dilemma to the clinician since the causative factor must be determined for proper patient management. The aim of this manuscript is to illustrate the imaging characteristics of thyroid disorders commonly seen in clinical practice resulting in thyrotoxicosis or pending thyrotoxicosis, so that correlation with clinical presentation and pertinent laboratory data will lead to the correct diagnosis.

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.

Iatrogenic hyperthyroidism in primary congenital hypothyroidism: prevalence and predictive factors.

OBJECTIVES: Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4 dosage. Currently, information regarding iatrogenic hyperthyroidism and predictive factors for permanent hypothyroidism (P-CH) among Thai patients is lacking. The aim of this study is to determine the prevalence and factors for predicting iatrogenic hyperthyroidism at one month after LT4 initiation and for predicting P-CH in primary CH infants. METHODS: This retrospective cohort study involved 87 infants with primary CH. Patients were classified by thyroid status at one month after LT4 initiation. At 3 years, patients were reevaluated after LT4 cessation and assigned as P-CH or transient CH (T-CH). Differences between groups were analyzed. RESULTS: One month after LT4 initiation, 35.6% of patients were classified as having iatrogenic hyperthyroidism. An initial LT4 dose of 10.2 µg/kg/day (sensitivity 64.5%, specificity 71.4%) was a suitable cutoff value for predicting iatrogenic hyperthyroidism, wherein 55.6 and 21.6% of patients were treated with initial doses of ≥10.2 and <10.2 µg/kg/day, respectively (p=0.004). Initial LT4 dose was the only predictive factor for thyroid status after initial treatment. At reevaluation, 47.4% of patients were diagnosed with P-CH. LT4 dosage at 3 years of age was significantly higher in patients with P-CH (3.3 vs. 2.85 µg/kg/day, p=0.02) and the only relevant factor for predicting P-CH. CONCLUSIONS: Iatrogenic hyperthyroidism is common among infants with primary CH when treated with the recommended LT4 dosage. LT4 dose was the only factor for predicting iatrogenic hyperthyroidism after LT4 initiation and the diagnosis of P-CH.

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.

Estimating short and longer-term exposure of domestic cats to dietary iodine fluctuation.

Hyperthyroidism is a common endocrinopathy of domestic felines. In humans, toxic nodular goitre is pathophysiologically similar to feline hyperthyroidism and can be caused by chronically low or fluctuating dietary iodine intake. The aetiopathogenesis of feline hyperthyroidism is not known, but chronically low or fluctuating dietary iodine intake is likely common. This study assessed habitual iodine intake in domestic cats by: (1) conducting a dietary survey involving 361 owners of 549 cats, (2) analysing iodine content of 119 cat feeds, 38 urine and 64 hair samples and (3) assessing variation in iodine content of eight cat feeds over 4-6 different batches. Owners varied their cats feed regularly, usually on a day-to-day basis and often between wet and dry feeds with differing flavours. The majority (78%; 93 of 119) feeds for cats were within the guideline range for iodine. Of the 22% (n = 26 feeds) that were not compliant, the majority (n = 23) were below the nutritional minimum value with most (n = 16) being dry kibble. Iodine content of feeds did not vary considerably between types of feed or feed packaging, but variation between different batches of the same feed was 14-31%. Hence, urine iodine in cats also varied markedly. Cats being treated for hyperthyroidism had lower hair iodine. In conclusion, a survey assessing how domestic cats are fed, together with an analysis of commercial cat feeds suggests that domestic cats are likely to experience chronically low or fluctuating dietary iodine intake. The latter is supported by wide variation in urine iodine content.

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.