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Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the safety and efficacy of thyroid artery embolization (TAE) in the treatment of nodular goiter (NG)., Methods: During a 5.5-year period, 56 consecutive patients with a NG underwent TAE. In Group A, there were 20 patients with a solitary/dominant 5-11-cm nodule, and in Group B, there were 36 patients with numerous nodules. Of the 56 patients, 47 (84%) had a retrosternal goiter and 25 had hyperthyroidism. In all patients, clinical and radiological evaluations were made at baseline and 6 months after TAE, and these parameters were statistically compared., Results: In 56 patients, 145 of the 146 thyroid arteries were successfully embolized. The 30-day mortality rate was 1.8%. Minor and major complications occurred in 25 and 2 patients, respectively. Six months after the TAE, the mean nodule volume was reduced from 80.2 mL to 25.0 mL, the mean thyroid volume was reduced from 147.0 mL to 62.6 mL, and the mean intrathoracic extension was reduced from 31.7 mm to 15.9 mm (P < .001). Of the 22 patients with non-Graves hyperthyroidism, 19 (86%) became euthyroid. The mean thyroid-related patient-reported outcome scores improved from 155.4 to 70.4 (P < .001). Of the 51 patients, 50 (98%) declared that they would recommend TAE to other patients with NG., Conclusions: TAE is safe and effective for the treatment of NG, with a significant volume reduction of the nodule(s) and thyroid gland., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

Part 2 of this series of Continuing Education articles on benign thyroid disorders deals with nodular goiter, hypothyroidism, and subacute thyroiditis. Together with Part 1 (which dealt with various forms of hyperthyroidism), this article is intended to provide relevant information for specialists in nuclear medicine dealing with the clinical management of patients with benign thyroid disorders, the primary audience for this series. Goiter, an enlargement of the thyroid gland, is a common endocrine abnormality. Constitutional factors, genetic abnormalities, or dietary and environmental factors may contribute to the development of nodular goiter. Most patients with nontoxic nodular goiter are asymptomatic or have only mild mechanical symptoms (globus pharyngis). Work-up of these patients includes measurement of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, thyroid autoantibodies, ultrasound imaging, thyroid scintigraphy, and fine-needle aspiration biopsy of nodules with certain ultrasound and scintigraphic features. Treatment for multinodular goiter includes dietary iodine supplementation, surgery, radioiodine therapy (to decrease thyroid size), and minimally invasive ablation techniques. Hypothyroidism ranges from rare cases of myxedema to more common mild forms (subclinical hypothyroidism). Primary hypothyroidism often has an autoimmune etiology. Clinical presentations differ in neonates, children, adults, and elderly patients. Work-up includes thyroid function tests and ultrasound imaging. Nuclear medicine is primarily used to locate ectopic thyroid tissue in congenital hypothyroidism or to detect defects in iodine organification with the perchlorate discharge test. Treatment consists of thyroid replacement therapy with l-thyroxine, adjusting the daily dose to the individual patient's metabolic and hormonal requirements. Subacute thyroiditis is a self-limited inflammatory disorder of the thyroid gland, often associated with painless or painful swelling of the gland and somatic signs or symptoms. Inflammation disrupts thyroid follicles resulting in a rapid release of stored thyroxine and triiodothyronine causing an initial thyrotoxic phase, often followed by transient or permanent hypothyroidism. Although subacute thyroiditis is often related to a viral infection, no infective agent has been identified. Subacute thyroiditis may be caused by a viral infection in genetically predisposed individuals. Work-up includes lab tests, ultrasound imaging, and radionuclide imaging. Thyroid scintigraphy demonstrates different findings depending on the phase of the illness, ranging from very low or absent tracer uptake in the thyroid gland in the hyperthyroid phase to a normal appearance in the late recovery phase. Since subacute thyroiditis is self-limited, treatment is directed toward relief of pain. High-dose nonsteroidal antiinflammatory drugs are usually the first-line treatment. If severe pain persists, a course of corticosteroids may be necessary. Permanent hypothyroidism develops in up to 15% of patients with subacute thyroiditis, even more than 1 y after presentation., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Thyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its cardiac complications like dilated cardiomyopathy is limited. Therefore, this study aimed to explore the thyrotoxicosis presentation and management and identify factors associated with dilated cardiomyopathy in a tertiary hospital in Northern Ethiopia., Methods: An institution-based cross-sectional study was conducted in Ayder Comprehensive Specialized Hospital from 2017 to 2018. Data from 200 thyrotoxicosis cases were collected using a structured questionnaire. After describing variables, logistic regression was conducted to identify independent predictors of dilated cardiomyopathy. Statistical significance was declared at p < 0.05., Results: Mean age at presentation of thyrotoxicosis was 45 years and females accounted for 89 % of the cases. The most frequent etiology was multinodular toxic goiter (51.5 %). As well, the most common symptoms and signs were palpitation and goiter respectively. Thyroid storm occurred in 6 % of the cases. Out of 89 patients subjected to echocardiography, 35 (39.3 %) of them had dilated cardiomyopathy. And, the odds of dilated cardiomyopathy were higher in patients who had atrial fibrillation (AOR = 15.95, 95 % CI:5.89-38.16, p = 0.001) and tachycardia (AOR = 2.73, 95 % CI:1.04-7.15, p = 0.040). All patients took propylthiouracil and 13.0 % of them experienced its side effects. Concerning β-blockers, propranolol was the most commonly (78.5 % of the cases) used drug followed by atenolol (15.0 %). Six patients underwent surgery., Conclusions: In developing countries like Ethiopia, patients with thyrotoxicosis have no access to methimazole which is the first-line anti-thyroid drug. Besides, they greatly suffer from dilated cardiomyopathy (due to late presentation) and side effects of propylthiouracil. Therefore, we recommend that patients should get adequate health information about thyrotoxicosis and anti-thyroid drugs including their side effects. Additionally, hospitals and other concerned bodies should also avail of TSH tests and methimazole at an affordable cost. Furthermore, community awareness about iodized salt and iodine-rich foods should be enhanced.

A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131 I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To evaluate the results of treatment of recurrent nodular goiter using sclerotherapy with polidocanol., Material and Methods: A comparative analysis of sclerotherapy (30 patients) and conventional surgical treatment (17 patients) of recurrent goiter was performed., Results: Sclerotherapy ensures reduction of nodes (linear dimensions of nodes decreased by 14.2±1.1 mm after 3 courses), correction of endocrine imbalance in patients with functional autonomy and relief of initial signs of cervical organ compression in all patients with recurrent goiter. Sclerotherapy is associated with less pain syndrome and no need for inpatient treatment. However, the most significant advantage is reduced risk of complications. Hypoparathyroidism and laryngeal paresis developed in 53 and 24% of patients after conventional surgery while these events were not observed after sclerotherapy., Conclusion: Sclerotherapy with polidocanol is a perspective alternative to conventional surgery for recurrent nodular goiter.

Background: Children with Pendred syndrome (PS) and non-syndromic enlarged vestibular aqueduct (NSEVA) represent a group of pre-lingual hearing-impaired individuals with rehabilitation challenges. Objective: To evaluate receptive language capabilities in a pediatric cohort with PS and NSEVA. Materials and methods: Twenty-four (24) children diagnosed with either PS or NSEVA, were examined using the Peabody Picture Vocabulary Test (PPVT) and compared to a cohort of 55 Danish children with normal hearing, as well as to a mixed group of 29 children with hearing impairment of congenital and hereditary non-syndromal type. In addition, test results were compared to normative data (PPVT-4 US standard scores). Results: PS/NSEVA children's PPVT-4 test scores fall within the normative data for the PPVT-4 (US) but proved to be significantly lower statistically, when compared to Danish children with normal hearing ( p <.0001) or to children with mixed non-syndromic hereditary hearing impairment ( p =.006). Implantation age was significantly later for the PS/NSEVA group (median = 43 months), compared to the mixed non-syndromic hereditary congenial hearing impairment group (median = 11 months). Conclusions and significance: Children with PS/NSEVA perform below age equivalent for receptive vocabulary outcome when compared to both children with normal hearing, and children with non-syndromic mixed hereditary congenital hearing impairment who receive cochlear implants earlier.

Subclinical hyperthyroidism is a common clinical entity, defined by serum TSH below the reference range, with normal FT4 and FT3 levels in an asymptomatic patient. Whether or not subclinical hyperthyroidism should be treated remains a matter of debate. Cross-sectional and longitudinal population-based studies demonstrate association of subclinical hyperthyroidism with risk of atrial fibrillation and osteoporosis, and with cardiovascular and all-cause mortality. However, there are no randomized clinical trials addressing whether long-term health outcomes are improved by treating subclinical hyperthyroidism; in the absence of evidence one way or the other, it seems appropriate to use decision trees taking account of TSH concentration and presence of risk factors (age>65 years or post-menopause, osteoporosis and cardiac disease)., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: This study aimed to compare the effectiveness and safety of long-term methimazole (MMI) and radioiodine (RAI) in the treatment of toxic multinodular goiter (TMNG). Methods: In this randomized, parallel-group trial, 130 consecutive and untreated patients with TMNG, aged <60 years, were enrolled and randomized to either long-term MMI or RAI treatment. Both groups of patients were followed for 60-100 months, with median durations of 72 and 84 months in the MMI and RAI groups, respectively. Results: In the MMI and RAI groups, 12 and 11 patients, respectively, were excluded because of side effects, choosing other modes of treatment and not returning for follow-up; 53 and 54 patients, respectively, completed the study for 60-100 months. In the MMI group, two patients (3.8%) experienced subclinical hypothyroidism, and 51 (96.2%) remained euthyroid until the end of study. The dosage of MMI to maintain euthyroidism was 6.3 ± 2.0, 4.5 ± 0.9, and 4.1 ± 1.0 mg daily during the first, third, and fifth years of continuous MMI treatment. One patient had elevated liver enzymes, and three developed skin reactions during the first three months, but no adverse effects from MMI occurred from 4 to 100 months of therapy. In the RAI group, 22 (41%) became hypothyroid, 12 (22%) had persistence or recurrence of hyperthyroidism, and 20 (37%) became euthyroid after 16.7 ± 2.7 mCi 131 I. Conclusion: Long-term, low-dose MMI treatment for 60-100 months is a safe and effective method for treatment of TMNG, and is not inferior to RAI treatment.

Background: Due to high recurrence rate after subtotal thyroidectomy, most of centers have shifted to total thyroidectomy as a surgical treatment for benign multinodular goiter (BMNG), but serious complications, as laryngeal nerve affection & hypocalcaemia, are still present. This study aimed to evaluate treatment of BMNG using intra-capsular total thyroid enucleation in comparison to standard total thyroidectomy., Patients &methods: This is a prospective randomized controlled clinical trial conducted in a hospital in the period from December 2009 to December 2015. Of total 224 patients with clinically BMNG. 112 patients operated by intracapsular total thyroid enucleation (ITTE group) and the other 112 patients operated by standard total thyroidectomy (STT group). The minimal follow up period was 36 months., Results: The mean operative time in ITTE group was (93.7 ± 9.6 min) compared to (86.9 ± 8.3 min) in STT group. Transient recurrent laryngeal nerve (RLN) palsy was 0% in ITTE group VS 7.1% in STT group. No cases (0%) developed permanent RLN palsy in ITTE group VS 0.9% in STT group. Symptomatic transient hypocalcaemia occurred in 1.8% in ITTE group VS 11.6% in STT group. No cases (0%) developed permanent hypocalcaemia in ITTE group VS 0.9% in STT group. No recurrence (0%) in both groups after minimal 3 years of follow up., Conclusion: Intracapsular Total thyroid enucleation technique is safe with the least serious complications, especially RLN injury and hypoparathyroidism, with no recurrence, but this technique still not radical so couldn't be used in suspicious cases for malignancy., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Hearing impairments are the most common symptom of congenital defects, and they generally remain intractable to treatment. Pendred syndrome, the most frequent syndromic form of hereditary hearing loss, is associated with mutations in the anion exchanger pendrin. Loss of pendrin function as an anion exchanger is thought to be causative, but rodent models do not exhibit progressive deafness. Here, we report a degenerative phenotype exhibiting mutant pendrin aggregates and increased susceptibility to cellular stresses in cochlear epithelial cells induced from patient-derived induced pluripotent stem cells (iPSCs). These degenerative phenotypes were rescued by site-specific gene corrections. Moreover, low-dose rapamycin and metformin reduced aggregation and cell death. Our results provide an unexpected, comprehensive understanding of deafness due to "degenerative cochlear disease" and may contribute to rational therapeutic development. This iPSC-based disease model provides an approach to the study of pathogenesis and therapeutic development for hereditary hearing loss., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of the study was to investigate the effects of rhTSH stimulation before 131 I treatment in patients with MNG., Methods: Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS database (all until January 2016). Randomized controlled trials (RCTs) that assessed the efficacy of rhTSH-stimulated 131 I treatment compared to placebo or 131 I treatment alone were collected. Two authors performed the data extraction independently., Results: Six RCTs involving 294 patients with MNG were included in this review. Altogether 168 patients were randomized to rhTSH-stimulated 131 I therapy, and 126 to either placebo and 131 I or 131 I alone. rhTSH-stimulated 131 I vs placebo and 131 I or 131 I alone for MNG showed no statistically significant difference in quality of life and all-cause mortality. rhTSH- (at a dose of 0.03 mg and above) stimulated 131 I treatment for MNG showed significant benefits in thyroid volume reduction. 131 I treatment with rhTSH stimulation at high doses (0.03 mg, 0.1 mg, 0.3 mg and 0.45 mg) for MNG caused significantly higher adverse effects and hypothyroidism., Conclusions: The overall results indicated that using rhTSH at high doses of 0.03-0.45 mg before 131 I therapy resulted in a greater TVR than 131 I therapy alone for patients with non-toxic MNG. However, an increased incidence of adverse effects and hypothyroidism was observed in patients receiving high-dose of rhTSH pretreatment than in patients who received low-dose rhTSH pretreatment. Therefore, a dose of 0.03 mg rhTSH pretreatment before 131 I therapy may be more potent than 131 I alone in treating patients with non-toxic MNG who either had a contraindication for or declined surgery.

Goiter, an enlargement of the thyroid gland, is a common problem in clinical practice associated with iodine deficiency, increase in serum thyroid-stimulating hormone (TSH) level, natural goitrogens, smoking, and lack of selenium and iron. Evidence suggests that heredity also has an important role in the etiology of goiter. The current classification divides goiter into diffuse and nodular, which may be further subdivided into toxic (associated with symptoms of hyperthyroidism, suppressed TSH or both), or nontoxic (associated with a normal TSH level). Nodular thyroid disease with the presence of single or multiple nodules requires evaluation due to the risk of malignancy, toxicity, and local compressive symptoms. Measurement of TSH, accurate imaging with high-resolution ultrasonography or computed tomography, and fine-needle aspiration biopsy are the appropriate methods for evaluation and management of goiter. This review discusses the clinical presentation, diagnostic evaluation, and treatment considerations of nontoxic diffuse and nodular goiters.

Background: To reduce intraoperative and postoperative complications, using Lugol solution to preoperatively prepare patients with Graves' disease has (1) rapidly reduced the severity of thyrotoxicosis and (2) reduced the vascularity of the thyroid gland. The vascularity reduction normally accompanies reducing the severity of thyrotoxicosis. However, the effects and mechanism of Lugol solution for reducing blood flow have not been well investigated in the patients with euthyroid (normally functioning thyroid) Graves' disease., Methods: Twenty-five patients with euthyroid Graves' disease being preoperatively treated with Lugol solution for 10 days were measured, at baseline and on the operative day, for (1) superior thyroid artery blood flow; (2) systemic angiogenic factor (VEGF); and (3) systemic inflammatory factor [interleukin (IL)-16]., Results: All three parameters were significantly (p < 0.0001) lower after 10 days of Lugol solution treatment. The average reductions were blood flow: 60% (0.294 vs. 0.117 L/min), serum VEGF: 55% (169.8 vs. 76.7 pg/mL), and serum IL-16: 50% (427.2 vs. 214.2; pg/mL)., Conclusion: Lugol solution significantly reduced thyroid arterial blood flow, VEGF, and IL-16, even in patients with euthyroid Graves' disease. We recommend routine preoperative Lugol solution treatment for all patients with Graves' disease.

Purpose: Pilot studies of combined therapies treating benign nodular goiters reported promising results. The aim of this study was to investigate the effectiveness of combined microwave ablation (MWA) and radioiodine therapy (RIT) with a special focus on thyroid function at the 3-month follow-up., Materials and Methods: 15 patients (median age: 55 years) with a large goiter and benign thyroid nodules or Graves' disease were treated with the combined therapy. Serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroglobuline (Tg) and, additionally, antibody levels against thyroglobulin (TgAb), thyrotropin receptors (TRAb) and thyroid peroxidase (TPOAb) were measured at enrollment, post MWA and at the 3-month follow-up (3MFU). Furthermore, the goiter volume, I-131 dose and hospitalization time were analyzed to evaluate effectiveness. MWA was operated under local anesthesia with a system working in a wavelength field of 902 to 928 MHz., Results: TSH, T4, T3 and Tg did not change at 3MFU, except for in two patients in whom the initial TSH levels improved to normal thyroid functioning levels at follow-up. One of the patients developed a high TRAb-level that receded back into the normal range. At 3MFU, the combined therapy showed a mean thyroid volume reduction of 26.4 ml ± 7.9 ml (30.5 % ± 4.6 % (p < 0.05)). By utilizing the combined therapy, administered activity could be reduced by 26.6 % ± 4.8 % (p < 0.05) and hospitalization time by 30.9 % ± 19.9 % (p < 0.05)., Conclusion: The data confirmed the effectiveness of the combination of MWA with RIT. The combined therapy is an innovative and conservative approach and could become a safe alternative to surgery for the treatment of very large benign nodular goiters. Due to the short follow-up and the limited number of patients, further studies will be necessary., Key Points: • The combined therapy shows a significant volume reduction in benign nodular goiters. • Initial MWA improves the RIT results by reducing the required therapy activity. • Thyroid function is preserved after combined therapy., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Intrapulmonary thyroid tissue with no malignant history of the thyroid gland is extremely rare. Usually, it is interpreted as ectopic thyroid tissue. Here we describe a case of bilateral pulmonary thyroid nodules with a history of multinodular thyroid goiter., History: A 37-year-old female had recurrent multinodular thyroid goiter and showed bilateral pulmonary nodules on CT scan. Video-assisted thoracic surgery (VATS) was performed for the largest nodule biopsy. Pathological and molecular examinations were done after biopsy, and both were shown the characters of benign thyroid tissues. To eliminate the possibility of thyroid carcinoma metastases, total thyroidectomy with modified radical neck dissection was performed, and there were no malignant pathological findings. After surgery, this patient accepted adjuvant radiometabolic treatment for ablation of the remaining intrapulmonary nodules. Her thyroglobulin level decreased to an undetectable level, and she has currently survived for 24 months after surgery., Clinical Significance: In this case, pulmonary ectopic thyroid and metastasizing thyroid carcinoma should both be considered, but the metastatic pattern and benign pathological characters were inconsistent with any of the corresponding diagnosis. Ultimately, this patient accepted postoperative treatment of thyroid carcinoma metastasis., Conclusions: This is a rare thyroid disease with malignant behavior but no pathological evidence. Careful diagnosis and postoprative follow-up should be carried out whenever such nodules are encountered in clinical practice., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1255194331453728 .

Context: It is normally recognized that the preferred treatment in large toxic thyroid nodules should be thyroidectomy., Objective: The aim of the study was to assess the efficacy of combined laser ablation treatment (LAT) and radioiodine 131 (131I) treatment of large thyroid toxic nodules with respect to rapidity of control of local symptoms, of hyperthyroidism, and of reduction of administered 131I activity in patients at refusal or with contraindications to surgery., Design and Setting: We conducted a pilot study at a single center specializing in thyroid care., Patients: Fifteen patients were treated with LAT, followed by 131I (group A), and a series of matched consecutive patients were treated by 131I only (group B)., Intervention(s): Laser energy was delivered with an output power of 3 W (1800 J per fiber per treatment) through two 75-mm, 21-gauge spinal needles. Radioiodine activity was calculated to deliver 200 Gy to the hyperfunctioning nodule., Main Outcome Measure(s): Thyroid function, thyroid peroxidase antibody, thyroglobulin antibody, ultrasound, and local symptoms were measured at baseline and up to 24 months., Results: Nodule volume reduction at 24 months was: 71.3 ± 13.4 vs 47.4 ± 5.5%, group A (LAT+131I) vs group B (131I), respectively; P < .001). In group A (LAT+131I), a reduction in radioiodine-administered activity was obtained (-21.1 ± 8.1%). Local symptom score demonstrated a more rapid reduction in group A (LAT+131I). In three cases, no 131I treatment was needed after LAT., Conclusions: In this pilot study, combined LAT/131I treatment induced faster and greater improvement of local and systemic symptoms compared to 131I only. This approach seems a possible alternative to thyroidectomy in patients at refusal of surgery.

We report a case of chronic idiopathic urticaria associated with nodular goiter and Graves disease. The urticaria resolved with normalization of the thyroid function.

Multinodular goitre has a slow and progressive growth. The clinical presentation of patients with multinodular goitre is variable and dependent on size, location and the functional state of the thyroid tissue. The most frequent clinical symptoms are caused by compression and deviation of the trachea and range from dyspnoea to acute asphyxia. Imaging is important to confirm the size of the multinodular goitre. Timing of the treatment can be critical. However, a good treatment guideline is lacking. There are two treatment options: radioactive iodine and surgical resection. The best treatment option and timing of treatment for patients with multinodular goitre should be assessed and decided on an individual basis. In this clinical report we present two patients who had a multinodular goitre with progressive symptoms for years. Patient A, 66 years of age, was successfully treated with radioactive iodine. Patient B, 77 years of age, underwent a total thyroidectomy.

Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss, goiter, and a partial defect in iodide organification, and is the most common syndromic hearing loss. Hearing loss is congenital in most cases and is accompanied by an enlarged vestibular aqueduct and a Mondini cochlea. Pendred syndrome and autosomal recessive deafness-4 (DFNB4) with enlarged vestibular aqueduct comprise a phenotypic spectrum caused by mutations in SLC26A4. Recently, mutations in FOXI1 and KCNJ10 have also been identified in DFNB4. Molecular mechanism of hearing loss and goiter remains to be elucidated, and therapies which can reverse or prevent the progression of the symptoms are not available. Here, we describe advances in the basic, clinical, and translational studies on Pendred syndrome.

We report a case of multinodular thyroid goiter in an 80-year-old man who successfully underwent tracheal stent placement for respiratory distress caused by the thyroid goiter and following two radiofrequency (RF) ablation sessions performed for thyroid volume reduction. This sequential treatment allowed elective stent removals four weeks after the second RF ablation session because the thyroid volume had been progressively reduced. Combination therapy of temporary airway stenting and RF ablation for the treatment of thyroid goiter has two advantages, i.e., immediate reliefs of dyspnea with airway stenting and reductions of the thyroid volume with RF ablation, and thus, allowing symptom reliefs even after the stent removals.

Somatostatin analogues are commercially available and used for the management of acromegaly and neuroendocrine tumours, but the expression of the receptors as a target in thyroid disease has not been explored. To assess somatostatin (SST) and somatostatin receptor (SSTR1-5) expression in both normal and thyroid disorders, as a potential target for somatostatin analogue therapy, 67 thyroid tissue specimens were reviewed: 12 differentiated thyroid carcinomas, 14 follicular adenomas, 17 multinodular goitres, 14 Graves disease, 10 Hashimotos thyroiditis specimens and five normal thyroids. Tissue was immunostained for SST and SSTR1-5. Positivity and the degree of positivity were recorded by double-blinded observers. Somatostatin receptor expression was highly expressed in normal tissue for SSTR1, 3, 4 and 5 (5 of 5, 4 of 5, 4 of 5 and 5 of 5 respectively) whilst SST and SSTR 2a and b were not expressed at all. The commonest receptor expressed for all pathological subtypes grouped together was SSTR2b (63 specimens). The commonest receptors expressed in differentiated thyroid cancer were SSTR5 (11 of 12 specimens) and SSTR2b (10 of 12 specimens). The commonest receptor expressed in benign disease was SSTR2b (53 of 55 specimens). SSTR5 was significantly under-expressed in Graves disease (P < 0.05). This study illustrates that SSTR 1, 3, 4 and 5 are highly expressed in normal, benign and malignant thyroid tissue. SSTR 2a and 2b appear absent in normal tissue and present in benign and malignant thyroid tissue (P < 0.02). This suggests that focussed SSTR2 treatment may be a potential therapeutic target., (© 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.)

Purpose of Review: To highlight recent advances in our understanding of the incidence of multinodular goitre (MNG) risk of malignancy, evaluation of patients with MNG, rates and factors predictive of malignancy in MNG, and the choice of surgical procedure for patients with neoplastic MNG., Recent Findings: The incidence of MNG when screened by ultrasound scanning (USS) is between 10 and 20% and when using high resolution USS can be up to 70%. The incidence of occult malignancy within MNG lies between 10 and 35% in surgical series. Younger patients and men have higher rates of malignancy, as do patients with a family history, prior irradiation and those with signs of compressive or invasive disease. Subtotal thyroidectomy has been rejected in favour of either total lobectomy or total thyroidectomy for most patients with MNG., Summary: An increasing number of patients with MNG will be encountered in surgical practice. Most patients can be cured with total lobectomy or total thyroidectomy, which minimizes recurrence rates and ensures an oncological approach to patients with incidentally discovered malignancy within MNG.

The results of treatment 272 patients with a nodular colloid goiter with the use of lazerinducted termotherapy (LITT) are analysed. I is established that in the developed modes of LITT application does not cause destructive changes in paranodular tissue and disorders of thyroid gland hormonal function. Duration of reverse development and substituting of nodular for a connecting tissue is determined by echogene and volume. With it increase the intensity of nodulus substituting for a connecting tissue goes down, extended the terms of nodulus regress. The indication to the repeated application of termotherapy is remaining tissue in the projections of nodulus scope from 42% and more an initial volume through 6 ms treatment. Absolute indications to repeated LITT is a presence of thyroid epithelium in remaining tissue of nodulus.

Background: Thyroid enlargement and thyroid nodules are common in the general population. This review concerns their proper diagnostic assessment and treatment., Methods: We selectively reviewed the literature from 1990 to 2012 and evaluated original articles and reviews retrieved from the PubMed database, as well as the recommendations of the following specialty societies: the German Societies of Endocrinology and Nuclear Medicine (Deutsche Gesellschaft für Endokrinologie, Deutsche Gesellschaft für Nuklearmedizin), the German Working Group for Endocrine Surgery (Chirurgische Arbeitsgemeinschaft Endokrinologie, CAEK), the European Thyroid Association, and the American Thyroid Association., Results: There have been very few randomized trials concerning the diagnosis and treatment of goiter. Nodular goiter can be managed by watchful waiting, drug treatment (initially with levothyroxine and iodide), radioactive iodine therapy, or surgery., Conclusion: Many patients with nodules need no treatment at all. Treatment is indicated, however, if the patient is symptomatic and/or has an autonomously functioning ("hot") nodule, or if cancer is suspected. Potentially cancerous nodules must be operated on. If euthyroid nodular goiter is to be treated with the main goal of size reduction, either surgery or radioactive iodine therapy can be used. Drug treatment is an option for small nodules or goiters, but iatrogenic hyperthyroidism must be avoided at all costs. The type of follow-up that is required depends on the chosen treatment.

The paper deals with the peculiarities of formation, clinical presentations and therapy of diffuse nontoxic goiter of children. The paper highlights the connection of the disease with the genetic predisposition, the impact of natural and anthropogenic strumagenes, immune processes. The clinical presentations of the diffuse nontoxic goiter are diffuse enlargement of thyroid gland, normal or high level of thyrotropichypophysis hormone when the content of thyroxin and triiodothyronine is normal, which is treated as the subclinic hypothyroidism syndrome. The variety of the disease pathogenesis theories leads to testing of different therapeutic methods, the principal ones among them are the use of iodine preparation and replacement therapy.

The main causes of simple diffuse goiter (SDG) and multinodular goiter (MNG) are iodine deficiency, increase in serum thyroid-stimulating hormone (TSH) level, natural goitrogens, smoking, chronic malnutrition, and lack of selenium, iron, and zinc. Increasing evidence suggests that heredity is equally important. Treatment of SDG and MNG still focuses on L-thyroxine-suppressive therapy surgery. Radioiodine alone or preceded by recombinant human TSH stimulation is widely used in Europe and other countries. Each of these therapeutic options has advantages and disadvantages, with acute and long-term side effects., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate short- and long-term effects of structured exercise program in euthyroid patients with Graves' disease., Methods: The study employed a retrospective case-control design. The exercise group (n = 62) underwent 3 weeks of structured exercise program consisting of daily walking, strengthening, and stretching exercises while the control group (n = 62) participated in leisure activities. Thyroid profile, aerobic capacity, and perceived fatigue were evaluated on in-patient admission and discharge. Time to discontinuation of anti-thyroid medication after discharge and time to relapse of symptoms were determined., Results: The exercise group increased estimated peak oxygen consumption (significant group-by-time ANOVA interaction, P < 0.001), decreased serum thyroxin (P = 0.038), increased serum thyrotropin (P = 0.071), and reported less fatigue (Fisher's exact test, p < 0.001) from admission to discharge. The anti-thyroid medication was withdrawn within 6 months of discharge in significantly greater proportion of subjects in the exercise than control group (84% vs. 18%). Conversely, the rate of relapse within 12 months of medication withdrawal was smaller in the exercise (29%) than control group (72%)., Conclusions: The results suggest that structured exercise program may normalize thyroid profile, improve aerobic capacity, and reduce fatigue on the short-term basis as well as reduce the need for anti-thyroid medication on the long-term basis.

Background: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG)., Objective, Design, and Setting: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study., Patients and Intervention: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I., Main Outcome Measures: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale., Results: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns., Conclusion: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

Thyroid nodules are very common, and although the majority are benign, approximately 5% may harbor malignancy. The evaluation of the patient with solitary thyroid nodule is generally straightforward and will typically include measurement of serum TSH to assess thyroid function and fine-needle aspiration biopsy of the nodule, with or without ultrasound (US) guidance. The approach to the patient with nontoxic multinodular goiter represents a more difficult problem for the clinician. All patients should have serum TSH measured to assess functional thyroid status and US examination to evaluate the number, size, and sonographic features of the nodules and assist in the selection of nodules that may need fine-needle aspiration biopsy. Patients with nodules yielding malignant cytology should be referred for surgery. Given the lack of reliable markers to predict biological behavior of nodules with suspicious (indeterminate) cytology, patients with such nodules are generally advised to have surgery, unless autonomous function of these nodules can be confirmed by scintigraphy. Most of these patients, however, will ultimately prove to have benign follicular tumors. Many patients with benign but large goiters may experience clinical symptoms of pressure, such as dysphagia, choking sensation, or airway obstruction. Such patients will often require surgery for alleviation of symptoms. In the absence of malignancy, asymptomatic patients may be observed. Radioactive iodine, commonly used in many parts of Europe, is safe and effective and may be a reasonable option for many patients. Periodic follow-up with neck palpation and US exam is recommended for all patients.

In recent years our knowledge on thyroid diseases in childhood has been increased. Several forms of congenital hypothyroidism (dysgenesis, dyshormongenesis, thyrotropin resistance and some central forms) are consequences of gene mutations. Maternal hypothyroxinemia due to severe iodine deficiency leads to early neurological damage and congenital hypothyroidism. Neonatal screening of congenital hypothyroidism and early treatment with l-thyroxin ensure good prognosis. Differential diagnosis of the various forms of congenital hypothyroidism in newborns is not an easy task. The need for treatment of transient hypothyroxinemia is still controversial. Diagnosis of juvenile lymphocytic thyroiditis can be ascertained by the clinical status, ultrasound examination, detection of anti-peroxydase antibodies, evaluation of thyroid function, and fine needle aspiration cytology. L-thyroxin therapy is recommended in cases of subclinical and manifest hypothyroidism. The transient form of the rare newborn hyperthyroidism is the consequence of maternal Graves-Basedow disease. It can be a sever condition and its permanent form is caused by TSH-receptor gene mutation. In the pathogenesis of autonomic thyroid adenoma mutations of the TSH-receptor and the alpha subunit of the stimulatory G-protein are involved. Treatment of Graves-Basedow disease in childhood is a debated question. The first choice is medical treatment with antithyroid and beta-blocking drugs. However, remission rate is low under this therapy, and the disease is characterised by frequent relapses. For this reason, the necessity of definitive therapy frequently arises. In Europe subtotal thyroidectomy is used as second choice of therapy, but clinical experience in the United States showed that radioiodine treatment is a safe and effective therapy for children and adolescents. Iodine deficient goitre in childhood is a form of iodine deficiency disorder. It is the consequence of adaptation to iodine deficiency. It can be treated by iodine or/and l-thyroxin, and its development can be prevented by iodinated salt. In childhood, thyroid nodule needs for a detailed investigation because of the possibility of thyroid cancer. Medullar thyroid carcinoma indicates genetic screening in the patients and their family, and the presence of disease-causing RET-proto-oncogene mutation confirms the need for total thyroidectomy already in childhood.

Thyroid nodules are common in the adult population. Widespread use of sensitive imaging studies often leads to their incidental discovery. Recent guidelines recommend thyroid-stimulating hormone determination and ultrasonography during initial nodule evaluation. Fine-needle aspiration is often performed to detect malignancy. However, the management of thyroid nodules in cardiac transplantation patients has not been directly addressed by recent guidelines. Confounding medications such as amiodarone and anti-coagulants present a management dilemma. The timing of fine-needle aspiration is crucial because (1) malignancy diagnosed pre-operatively usually precludes organ transplantation, and (2) patients undergoing solid-organ transplantation are at increased risk of developing de novo malignancies, including thyroid. With the rising incidence of thyroid cancer, donor-related malignancy will likely become a more prominent issue. This review addresses thyroid nodule management in the cardiac transplant population and provides recommendations for organ donation and transplantation in donors and recipients with thyroid cancer., (Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 +/- 62.0 mL, 20 females, 2 males, 64 +/- 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 +/- 17.6%) and II (21.6 +/- 17.8%), but not in group III (2.7 +/- 15.3%). After 12 months, TV decreased significantly in groups I (36.7 +/- 18.1%) and II (37.4 +/- 27.1%), but not in group III (19.0 +/- 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.

The treatment of benign multinodular goitre (MNG) is controversial, but surgery is recommended in large compressive goitres. While some patients decline surgery others may have contraindications due to comorbidity, since MNG is prevalent in the elderly. Therefore, non-surgical treatment alternatives are needed. Until recently, levothyroxine therapy was the preferred non-surgical alternative, but due to low efficacy and potential side-effects, it is not recommended for routine use in recent international guidelines. Conventional radioiodine ((131)I) therapy has been used for two decades as an effective and safe alternative to surgery in the treatment of symptomatic non-toxic MNG. Since much higher activities of (131)I are employed when treating non-toxic rather than toxic MNG, there has been reluctance in many countries to use this treatment modality. Frequently, the (131)I -uptake in a non-toxic MNG is low, which makes (131)I therapy less feasible. Another challenge is the negative correlation between the initial goitre size and goitre volume reduction (GVR). With its ability to more than double the thyroid (131)I-uptake, recombinant human TSH (rhTSH) increases the absorbed radiation dose and thus enhances the GVR by 35-56% at the expense of up to fivefold higher rate of permanent hypothyroidism. An alternative strategy is to reduce the administered (131)I-activity with a factor corresponding to the rhTSH induced increase in (131)I-uptake. Hereby, the extrathyroidal irradiation can be reduced without compromising efficacy. Thus, although in its infancy, and still experimental, rhTSH-augmented (131)I therapy may profoundly alter the non-surgical treatment of benign non-toxic MNG.

Context: High doses of (131)I are usually needed in the treatment of multinodular goitre (MNG) for effective thyroid volume (TV) reduction. Recombinant human thyroid-stimulating hormone (rhTSH) is an adjuvant to enhance (131)I uptake, allowing a decrease in radiation activity and enhancing (131)I efficacy., Objective: To evaluate whether rhTSH increases the efficacy of a fixed activity of (131)I for the treatment of MNG., Design: Two-year, observational, placebo-controlled study., Setting: Patients received 0.1 mg rhTSH (A), 0.005 mg rhTSH (B) or placebo (C). A fixed activity of 1.11 GBq of (131)I was administered 24 h after rhTSH or placebo., Patients: A total of 28 outpatients (26 females and two males) with MNG., Measurements: TSH, free T4, T3, thyroglobulin (Tg) and TV., Results: Basal radioactive iodine uptake and TV values were comparable among all groups. After rhTSH or placebo, peak levels of TSH, free T4, T3 and Tg were higher in A than in B or in C (p < 0.05). Hyperthyroidism was observed in A (n = 2), B (n = 6) and C (n = 4). Thyroid enlargement was reported in A (n = 3) and B (n = 6). After 24 months, 10 patients developed hypothyroidism (four in A, three in B and three in C). TV reduction was similar between A and B (37.2 +/- 25.5% vs. 39.3 +/- 27.9%, p = 0.88), but different from the non-significant reduction in C (15.3 +/- 28.3%, p = 0.08)., Conclusions: Followed by 1.11 GBq, a very low dose of 0.005 mg rhTSH was equally safe and effective as 0.1 mg rhTSH. Both doses increased the efficacy of radioiodine. Adverse events were mild, transient and readily treatable.