Hyperthyroidism.

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.

Thyroid Embolization for Nonsurgical Treatment of Nodular Goiter: A Single-Center Experience in 56 Consecutive Patients.

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.

Thyrotoxicosis and dilated cardiomyopathy in developing countries.

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 ß-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.

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.

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 131I 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.

Effective Preoperative Plasmapheresis Treatment of Severe Hyperthyroidism in a Patient with Giant Toxic Nodular Goiter and Methimazole-Induced Agranulocytosis.

Agranulocytosis is a rare but very serious complication of thyrostatic therapy. In severe hyperthyroidism, the removal of circulating thyroid hormones by plasmapheresis may be an effective therapeutic option. This report describes the therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis, which occurred after 2 weeks of taking methimazole. During hospitalization, methimazole treatment was discontinued and therapy with steroids, a beta blocker, propylthiouracil, Lugol's solution, lithium carbonate, and antibiotics were initiated. Granulocyte colony growth stimulating factor was also used to resolve agranulocytosis. Due to the failure to achieve euthyreosis using this approach, we decided to conduct thyroid surgery, as a life-saving action, after preparation of the patient by plasmapheresis. Two plasmapheresis procedures were performed, resulting in a decrease in the concentration of free thyroid hormones. Total thyroidectomy was performed and there were no complications during surgery. We conclude that plasmapheresis may be considered as an effective alternative treatment option for the preparation of patients with hyperthyroidism for surgery, when the clinical situations prevent the use of conventional treatments for hyperthyroidism and when immediate life-saving surgery is necessary.

[Sclerotherapy as an alternative to surgery for recurrent nodular goiter]. / Skleroterapiya kak al'ternativa operatsii pri lechenii bol'nykh s retsidivnym uzlovym zobom.

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.

Receptive language acquisition in a pediatric population with Pendred syndrome and non-syndromic enlarged vestibular aqueduct.

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.

Graves' disease, multinodular goiter and subclinical hyperthyroidism.

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).

Treatment of Toxic Multinodular Goiter: Comparison of Radioiodine and Long-Term Methimazole Treatment.

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 131I. 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.

Intra-capsular total thyroid enucleation versus total thyroidectomy in treatment of benign multinodular goiter. A prospective randomized controlled clinical trial.

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.

Cochlear Cell Modeling Using Disease-Specific iPSCs Unveils a Degenerative Phenotype and Suggests Treatments for Congenital Progressive Hearing Loss.

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.

Recombinant human thyrotropin stimulated 131I treatment for multinodular goiter.

The aim of the study was to investigate the effects of rhTSH stimulation before 131I 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 131I treatment compared to placebo or 131I 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 131I therapy, and 126 to either placebo and 131I or 131I alone. rhTSH-stimulated 131I vs placebo and 131I or 131I 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 131I treatment for MNG showed significant benefits in thyroid volume reduction. 131I 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 131I therapy resulted in a greater TVR than 131I 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 131I therapy may be more potent than 131I alone in treating patients with non-toxic MNG who either had a contraindication for or declined surgery.

Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters.

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.

Effectiveness and Mechanism of Preoperative Lugol Solution for Reducing Thyroid Blood Flow in Patients with Euthyroid Graves' Disease.

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.

Combination of Ultrasound-Guided Percutaneous Microwave Ablation and Radioiodine Therapy in Benign Thyroid Disease: A 3-Month Follow-Up Study.

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 ±â€Š7.9 ml (30.5 % ±â€Š4.6 % (p < 0.05)). By utilizing the combined therapy, administered activity could be reduced by 26.6 % ±â€Š4.8 % (p < 0.05) and hospitalization time by 30.9 % ±â€Š19.9 % (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.

Multiple thyroid nodules in the lung: metastasis or ectopia?

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 .

[Multinodular goitre: not always harmless]. / Multinodulair struma: niet altijd onschuldig.

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.