ENDOCRINE TUMOURS: Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases.

BACKGROUND AND AIMS: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. METHODS: A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' RESULTS: Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20-7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. CONCLUSION: TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure.

Substernal goiter and laryngopharyngeal reflux

ABSTRACT Objective This study aims to compare the prevalence of laryngopharyngeal reflux signs between two groups of patients undergoing thyroidectomy for voluminous goiter: substernal goiters and voluminous cervical goiter without thoracic extension. Subjects and methods A retrospective case-control study was performed with data retrieved of the charts of the patients submitted to thyroidectomies occurred at a tertiary care center (Head and Neck Surgery Department, University of São Paulo Medical School) between 2010 and 2014. The selected thyroidectomies were allocated in two groups for study: patients with substernal goiters and patients with voluminous cervical goiter without thoracic extension. Cervical goiters were selected by ultrasonography mensuration. Clinical criterion was used to define substernal goiter. Results The average thyroid volume in patients with substernal goiter was significantly greater than the average volume in patients with only cervical goiter (p < 0.001). The prevalence of signs of reflux laryngitis at laryngoscopy was significantly greater in substernal goiter patients (p = 0.036). Moreover, substernal goiter was considered as the unique independent variable for high reflux laryngitis signs at laryngoscopy (OR = 2.75; CI95%: 1.05-7.20; p = 0.039) when compared to only cervical goiter patients. Conclusion This study shows a significant association between substernal goiters and signs of laryngopharyngeal reflux at preoperative laryngoscopy. Therefore, when compared with voluminous cervical goiters, the substernal goiters increase the chance of reflux laryngitis signs in patients.

Substernal goiter and laryngopharyngeal reflux.

OBJECTIVE: This study aims to compare the prevalence of laryngopharyngeal reflux signs between two groups of patients undergoing thyroidectomy for voluminous goiter: substernal goiters and voluminous cervical goiter without thoracic extension. SUBJECTS AND METHODS: A retrospective case-control study was performed with data retrieved of the charts of the patients submitted to thyroidectomies occurred at a tertiary care center (Head and Neck Surgery Department, University of São Paulo Medical School) between 2010 and 2014. The selected thyroidectomies were allocated in two groups for study: patients with substernal goiters and patients with voluminous cervical goiter without thoracic extension. Cervical goiters were selected by ultrasonography mensuration. Clinical criterion was used to define substernal goiter. RESULTS: The average thyroid volume in patients with substernal goiter was significantly greater than the average volume in patients with only cervical goiter (p < 0.001). The prevalence of signs of reflux laryngitis at laryngoscopy was significantly greater in substernal goiter patients (p = 0.036). Moreover, substernal goiter was considered as the unique independent variable for high reflux laryngitis signs at laryngoscopy (OR = 2.75; CI95%: 1.05-7.20; p = 0.039) when compared to only cervical goiter patients. CONCLUSION: This study shows a significant association between substernal goiters and signs of laryngopharyngeal reflux at preoperative laryngoscopy. Therefore, when compared with voluminous cervical goiters, the substernal goiters increase the chance of reflux laryngitis signs in patients.

Hypothyroidism associated with parathyroid disorders.

Hypothyroidism may occur in association with congenital parathyroid disorders determining parathyroid hormone insufficiency, which is characterized by hypocalcemia and concomitant inappropriately low secretion of parathormone (PTH). The association is often due to loss of function of genes common to thyroid and parathyroid glands embryonic development. Hypothyroidism associated with hypoparathyroidism is generally mild and not associated with goiter; moreover, it is usually part of a multisystemic involvement not restricted to endocrine function as occurs in patients with 22q11 microdeletion/DiGeorge syndrome, the most frequent disorders. Hypothyroidism and hypoparathyroidism may also follow endocrine glands' damages due to autoimmunity or chronic iron overload in thalassemic disorders, both genetically determined conditions. Finally, besides PTH deficiency, hypocalcemia can be due to PTH resistance in pseudohypoparathyroidism; when hormone resistance is generalized, patients can suffer from hypothyroidism due to TSH resistance. In evaluating patients with hypothyroidism and hypocalcemia, physical examination and clinical history are essential to drive the diagnostic process, while routine genetic screening is not recommended.

VEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular unit in normal state and during goitrogenesis.

Thyroid gland vasculature has a distinguishable characteristic of endothelial fenestrae, a critical component for proper molecular transport. However, the signaling pathway that critically governs the maintenance of thyroid vascular integrity, including endothelial fenestrae, is poorly understood. Here, we found profound and distinct expression of follicular epithelial VEGF-A and vascular VEGFR2 that were precisely regulated by circulating thyrotropin, while there were no meaningful expression of angiopoietin-Tie2 system in the thyroid gland. Our genetic depletion experiments revealed that VEGFR2, but not VEGFR3, is indispensable for maintenance of thyroid vascular integrity. Notably, blockade of VEGF-A or VEGFR2 not only abrogated vascular remodeling but also inhibited follicular hypertrophy, which led to the reduction of thyroid weights during goitrogenesis. Importantly, VEGFR2 blockade alone was sufficient to cause a reduction of endothelial fenestrae with decreases in thyrotropin-responsive genes in goitrogen-fed thyroids. Collectively, these findings establish follicular VEGF-A-vascular VEGFR2 axis as a main regulator for thyrotropin-dependent thyroid angiofollicular remodeling and goitrogenesis.

MicroRNAs in thyroid development, function and tumorigenesis.

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that modulate the vast majority of cellular processes. During development, the correct timing and expression of miRNAs in the tissue differentiation is essential for organogenesis and functionality. In thyroid gland, DICER and miRNAs are necessary for accurately establishing thyroid follicles and hormone synthesis. Moreover, DICER1 mutations and miRNA deregulation observed in human goiter influence thyroid tumorigenesis. The thyroid malignant transformation by MAPK oncogenes is accompanied by global miRNA changes, with a marked reduction of "tumor-suppressor" miRNAs and activation of oncogenic miRNAs. Loss of thyroid cell differentiation/function, and consequently iodine trapping impairment, is an important clinical characteristic of radioiodine-refractory thyroid cancer. However, few studies have addressed the direct role of miRNAs in thyroid gland physiology. Here, we focus on what we have learned in the thyroid follicular cell differentiation and function as revealed by cell and animal models and miRNA modulation in thyroid tumorigenesis.

[A rare observation of intralaryngeal aberrant goiter]. / Redkoe nablyudenie interlaringeal'nogo aberrantnogo zoba.

This paper was designed to report a rare observation of intralaryngeal aberrant goiter associated with goiter of the main thyroid tissue and chronic suppurative otitis media complicated by the polyp that causes occlusion of the auditory passage. The histomorphological investigation of the material harvested intraoperatively following rehabilitation of the purulent focus in the middle ear and the removal of the tumour from the inside of the right vestibular fold confirmed the diagnosis of colloid goiter.

Respiratory Manifestations of Hypothyroidism: A Systematic Review.

BACKGROUND: Hypothyroidism has been associated with increased pulmonary morbidity and overall mortality. A systematic review was conducted to identify the prevalence and underlying mechanisms of respiratory problems among patients with thyroid insufficiency. METHODS: PubMed and EMBASE databases were searched for relevant literature from January 1950 through January 2015 with the following study eligibility criteria: English-language publications; adult subclinical or overt hypothyroid patients; intervention, observational, or retrospective studies; and respiratory manifestations. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement was followed, and Cochrane's risk of bias tool was used. RESULTS: A total of 1699 papers were screened by two independent authors for relevant titles. Of 109 relevant abstracts, 28 papers underwent full-text analyses, of which 22 were included in the review. Possible mechanisms explaining respiratory problems at multiple physiological levels were identified, such as the ventilator control system, diaphragmatic muscle function, pulmonary gas exchange, goiter caused upper airway obstruction, decreased capacity for energy transduction, and reduced glycolytic activity. Obstructive sleep apnea syndrome was found among 30% of newly diagnosed patients with overt hypothyroidism, and demonstrated reversibility following treatment. The evidence for or against a direct effect on pulmonary function was ambiguous. However, each of the above-mentioned areas was only dealt with in a limited number of studies. Therefore, it is not possible to draw any strong conclusions on any of these themes. Moreover, most studies were hampered by considerable risk of bias due for example to small numbers of patients, lack of control groups, randomization and blinding, and differences in body mass index, sex, and age between subjects and controls. CONCLUSION: Mechanistic data linking hypothyroidism and respiratory function are at best limited. This area of research is therefore open for retesting hypotheses, using appropriate study designs and methods.

[The choice of surgery in patients with diffuse toxic goiter]. / Vybor ob''ema operatsii u bol'nykh diffuznym toksicheskim zobom (s kommentariem).

AIM: to define clear individual indications for different operations for diffuse toxic goiter by research of immunological markers of thyrotoxicosis recurrence probability. MATERIAL AND METHODS: Long-term results of survey and treatment of 215 patients with diffuse toxic goiter are presented. Patients were divided into 2 groups. The 1st group consisted of 31 patienrs who underwent conventional partial thyroidectomy. Group 2 included 184 patients. They were divided into 2 subgroups depending on type of surgery. Subgroup A included 59 patients after partial thyroidectomy and subgroup B - 125 patients after total thyroidectomy. In group 2 surgery was defined based on only level of antibodies against TSH-receptors. RESULTS: Recurrence incidence was 16 and 0% in groups 1 and 2 respectively. CONCLUSION: In patients with diffuse toxic goiter partial thyroidectomy is possible if normal titer of antibodies against TSH-receptors is present (<1.5 U/l). Total thyroidectomy is advisable in titer ≥1.5 U/l.

Subclinical Hypothyroidism in PCOS: Impact on Presentation, Insulin Resistance, and Cardiovascular Risk.

Aim of Study. To assess status of thyroid function and thyroid disorders particularly subclinical hypothyroidism (SCH) in subjects with polycystic ovarian syndrome (PCOS) and impact of SCH on various clinical and biochemical parameters and cardiovascular risk in PCOS. Methods. Hundred females diagnosed with PCOS as per Rotterdam criteria and 100 normal controls were recruited and were subjected to elaborate anthropometric, clinical, and biochemical assessment. Results. Notable findings included significantly higher frequency of subjects with subclinical hypothyroidism (p = 0.0002), autoimmune thyroiditis (p < 0.001), and goitre (p = 0.02) in polycystic ovarian syndrome subjects compared to control subjects. Further SCH PCOS subjects were found to harbor significantly higher HOMA-IR (p < 0.05) and frequency of subjects with dyslipidemia (p < 0.05) compared to both euthyroid PCOS and euthyroid control subjects. Though frequency of subjects with cardiovascular risk factors was higher in SCH PCOS group than euthyroid PCOS group, it failed to reach statistical significance. Conclusion. We concluded that PCOS is associated with high incidence of SCH and AIT compared to normal population and SCH poses increased risk of cardiovascular disorder in PCOS.

[The mother-placenta-fetus system in diffuse toxic goiter: Morphopathological aspects].

OBJECTIVE: to compare the clinical and morphological parallels of the mother-placenta-fetus system in diffuse toxic goiter (DTG) through current morphological examinations. SUBJECTS AND METHODS: Sixty-five women whose pregnancy occurred with DTG were examined using both clinical and morphological studies (light, scanning electron, and atomic-force microscopies and macro- and microelement analysis); the placenta and uterus were investigated. RESULTS: Destructive changes and microrelief impairment, resulting from circulatory disorders (ischemia) and hemic hypoxia, were observed in the presence of DTG during pregnancy. Abnormal placental immaturity developed; the number of terminal villi decreased; sclerosis occurred. The magnitude of changes showed up to a greater extent in the myometrium, umbilical cord, and placenta of women, whose pregnancy occurred with DTG, and in patients with disease recurrence. In preeclampsia, plethora, stasis, and thrombosis were added to circulatory disorders. CONCLUSION: Not only the diagnosis itself of DTG, but also the type of its course and the pattern of obstetric disease, primarily preeclampsia, affect the state of structural components of the uteroplacental unit.

The impact of goitre and its treatment on the trachea, airflow, oesophagus and swallowing function. A systematic review.

In this systematic review, we investigated the effects of goitre and its treatment on the trachea and the oesophagus. A total of 6355 papers were screened in scientific databases, which disclosed 40 original studies (nine descriptive and 31 interventional). Although most studies are hampered by a number of methodological shortcomings, it is uncontested that goitre affects the trachea as well as the oesophagus in a large proportion of people. This leads to upper airway obstruction, swallowing dysfunction, or both, which may remain undisclosed unless specifically investigated for. Assessment of the tracheal dimensions should be done by magnetic resonance imaging or computed tomography, and detection of upper airway obstruction by flow volume loops, with focus on the inspiratory component. A clinical evaluation of the oesophageal function is difficult to implement and could be replaced by available and validated questionnaires on swallowing. Although radioiodine therapy and thyroidectomy relieve the negative effect of goitre on the trachea and the oesophagus, many issues remain unexplored.

Graves' disease presenting as bi-ventricular heart failure with severe pulmonary hypertension and pre-eclampsia in pregnancy--a case report and review of the literature.

BACKGROUND: Graves' disease, a well-known cause of hyperthyroidism, is an autoimmune disease with multi-system involvement. More prevalent among young women, it appears as an uncommon cardiovascular complication during pregnancy, posing a diagnostic challenge, largely owing to difficulty in detecting the complication, as a result of a low index of suspicion of Graves' disease presenting during pregnancy. Globally, cardiovascular disease is an important factor for pregnancy-related morbidity and mortality. Here, we report a case of Graves' disease detected for the first time in pregnancy, in a patient presenting with bi- ventricular heart failure, severe pulmonary hypertension and pre- eclampsia. Emphasis is placed on the spectrum of clinical presentations of Graves' disease, and the importance of considering this thyroid disorder as a possible aetiological factor for such a presentation in pregnancy. CASE PRESENTATION: A 30-year-old Bangladeshi-Bengali woman, in her 28th week of pregnancy presented with severe systemic hypertension, bi-ventricular heart failure and severe pulmonary hypertension with a moderately enlarged thyroid gland. She improved following the administration of high dose intravenous diuretics, and delivered a premature female baby of low birth weight per vaginally, twenty four hours later. Pre-eclampsia was diagnosed on the basis of hypertension first detected in the third trimester, 3+ oedema and mild proteinuria. Electrocardiography revealed sinus tachycardia with incomplete right bundle branch block and echocardiography showed severe pulmonary hypertension with an estimated pulmonary arterial systolic pressure of 73 mm Hg, septal and anterior wall hypokinesia with an ejection fraction of 51%, grade I mitral and tricuspid regurgitation. Thyroid function tests revealed a biochemically hyperthyroid state and positive anti- thyroid peroxidase antibodies was found. (99m)Technetium pertechnetate thyroid scans demonstrated diffuse toxic goiter as evidenced by an enlarged thyroid gland with intense radiotracer concentration all over the gland. The clinical and biochemical findings confirmed the diagnosis of Graves' disease. CONCLUSIONS: Graves' disease is an uncommon cause of bi-ventricular heart failure and severe pulmonary hypertension in pregnancy, and a high index of clinical suspicion is paramount to its effective diagnosis and treatment.

[The use of phytotherapy for treatment of thyroid diseases].

The main tasks during treatment of hyperplastic thyroid diseases--to stop the growth of thyroid nodules; compensation of hypothyrosis; normalization of thyroid size. One of the perspective methods in combine therapy of diffuse and mix goiter is a phytotherapy. The most often for thyroid diseases we have used the plant drug Polentilla alba, which on Ukrainian market was registered as "Alba". Investigation has shown, that phytodrug of Polentilla alba could be recommended for monotherapy and for combine conservative therapy of diffuse and mix benign euthyroid goiter, and also for complex treatment of toxic and hypothyroid goiters.

A pattern of cerebral perfusion anomalies between major depressive disorder and Hashimoto thyroiditis.

BACKGROUND: This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion. DESIGN: Analysis of data derived from two separate data banks. SAMPLE: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25). ASSESSMENT: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by (99 m)Tc-ECD SPECT. Statistical analysis was done through logistic regression. RESULTS: MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group. CONCLUSION: In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD.

The role of iodine in human growth and development.

Iodine is an essential component of the hormones produced by the thyroid gland. Thyroid hormones, and therefore iodine, are essential for mammalian life. Iodine deficiency is a major public health problem; globally, it is estimated that two billion individuals have an insufficient iodine intake. Although goiter is the most visible sequelae of iodine deficiency, the major impact of hypothyroidism due to iodine deficiency is impaired neurodevelopment, particularly early in life. In the fetal brain, inadequate thyroid hormone impairs myelination, cell migration, differentiation and maturation. Moderate-to-severe iodine deficiency during pregnancy increases rates of spontaneous abortion, reduces birth weight, and increases infant mortality. Offspring of deficient mothers are at high risk for cognitive disability, with cretinism being the most severe manifestation. It remains unclear if development of the offspring is affected by mild maternal iodine deficiency. Moderate-to-severe iodine deficiency during childhood reduces somatic growth. Correction of mild-to-moderate iodine deficiency in primary school aged children improves cognitive and motor function. Iodine prophylaxis of deficient populations with periodic monitoring is an extremely cost effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle.