Thyroid Hormone Secretion Research Articles

Efficacy of Vitamin-D Supplement on Thyroid Profile in Children with Graves’ Disease

BACKGROUND: Many studies have shown low Vitamin-D level as a risk factor for autoimmune diseases, especially multiple sclerosis and thyroid disease. Graves’ disease (GD) is an autoimmune disease caused by autoantibodies that stimulate thyroid-stimulating hormone (TSH) receptors by increasing thyroid hormone synthesis and secretion. Several studies report that many patients with autoimmune thyroid disease including GD have low Vitamin-D status.
 AIM: The objective of the study was to evaluate the effect of Vitamin-D supplement on GD patients on improvement in thyroid hormone levels.
 METHODS: Open random clinical trial was conducted in GD patients to determine changes in thyroid hormone to achieving normal levels between those receiving methimazole plus Vitamin-D supplementation compared with those who only received methimazole. Patients were checked for TSH receptor antibody, thyroid profile and Vitamin-D level before treatment and rechecked for thyroid profile and Vitamin-D level 3 months after treatment. t-test used to compare the drug efficacy (p < 0.05) in two groups.
 RESULTS: From 25 children with GD accompanied by Vitamin-D deficiency with an average value of Vitamin-D was 16 ng/mL. GD children who receive methimazole with Vitamin-D supplement had elevated TSH levels in the 3rd month of therapy that was significantly different compared to GD children who received methimazole only (p = 0.00), and the increase of TSH was also followed by an increase in Vitamin-D levels.
 CONCLUSION: All children with GD had Vitamin D deficiency, and the addition of Vitamin-D supplement to GD therapy would improve TSH faster than children who did not receive Vitamin-D supplement.

The concentration of triiodothyronine and thyroxine in colostrum, milk and plasma of cows

Milk contains key nutrients in optimal proportions, which makes it to be an important component of the human diet. Despite the fact that consumers receive with milk a significant amount of readily available nutrients, milk can be a source of dangerous factors of chemical and biological origin. The level of physiological hormones found in milk is not a limiting factor and is studied solely for scientific purposes. However, milk hormones can have a negative effect on the health of consumers. Based on this, the aim of this work was to study the concentration of triiodothyronine and thyroxine in colostrum, milk and blood plasma of cows at different stages of lactation. The secretion of the mammary gland and blood plasma of cows of Ukrainian black-and-white dairy breed, in their 2nd–5th lactations with milk yield 5100–5700 kg of milk per previous lactation was the object of the study. The concentration of triiodothyronine and thyroxine using enzyme-linked immunosorbent assay was investigated in withdrawn samples. The obtained data indicates that the highest level of secretion of iodine-containing thyroid hormones with milk is observed on 1st–4th days of lactation. Thereafter, the concentration of hormones in milk statistically significant decreases by 2.8–3-fold (P ˂ 0.001) till 30–40th day of lactation. The high concentration of iodine-containing hormones in colostrum allows to enhance metabolic processes in calves. Studies of the concentration of thyroid hormones in the blood plasma of cows showed a gradual increase from the beginning of lactation till 10th–14th and then till 30th–40th days of lactation. By 10th–14th days we observed 2.2-fold growth of triiodothyronine level (P ˂ 0.001), and till 30th–40th days this parameter has increased by another 12.5 %. The level of thyroxine on 10th–14th days of lactation was higher, compared to such in the beginning of lactation by 62.2 % (P ˂ 0.001), and by 30th–40th day increase was by 40.9 %. The main reasons for such changes are the formation of lactation dominant, the discharge of hormones secreted by the breast and the stimulation of metabolic processes during lactation. The prospects of further research lie in investigation of the dependence of triiodothyronine and thyroxine levels in the secretion of the mammary gland on productivity, breed, age and diet of animals.

Hyperthyroidism in adolescents

The term 'hyperthyroidism' refers to a form of thyrotoxicosis due to inappropriate high synthesis and secretion of thyroid hormone(s) by the thyroid. The leading cause of hyperthyroidism in adolescents is Graves' disease (GD); however, one should also consider other potential causes, such as toxic nodular goitre (single or multinodular), and other rare disorders leading to excessive production and release of thyroid hormones. The term 'thyrotoxicosis' refers to a clinical state resulting from inappropriate high thyroid hormone action in tissues, generally due to inappropriate high tissue thyroid hormone levels. Thyrotoxicosis is a condition with multiple aetiologies, manifestations, and potential modes of therapy. By definition, the extrathyroidal sources of excessive amounts of thyroid hormones, such as iatrogenic thyrotoxicosis, factitious ingestion of thyroid hormone, or struma ovarii, do not include hyperthyroidism. The aetiology of hyperthyroidism/and thyrotoxicosis should be determined. Although the diagnosis is apparent based on the clinical presentation and initial biochemical evaluation, additional diagnostic testing is indicated. This testing should include: (1) measurement of thyroid-stimulating hormone receptor (TSHR) antibodies (TRAb); (2) analysis of thyroidal echogenicity and blood flow on ultrasonography; or (3) determination of radioactive iodine uptake (RAIU). A 123I or 99mTc pertechnetate scan is recommended when the clinical presentation suggests toxic nodular goitre. A question arises regarding whether diagnostic workup and treatment (antithyroid drugs, radioiodine, surgery, and others) should be the same in children and adolescents as in adults, as well as whether there are the same goals of treatment in adolescents as in adults, in female patients vs in male patients, and in reproductive or in postreproductive age. In this aspect, different treatment modalities might be preferred to achieve euthyroidism and to avoid potential risks from the treatment. The vast majority of patients with thyroid disorders require life-long treatment; therefore, the collaboration of different specialists is warranted to achieve these goals and improve patients' quality of life.

Thyrotropin-releasing hormone axonal varicosities appear to innervate dopaminergic neurons in the human hypothalamus.

Thyrotropin-releasing hormone (TRH) has a critical role in the central regulation of thyroid-stimulating hormone (TSH) from the anterior pituitary, and subsequently, thyroid hormone secretion from the thyroid gland. In addition to its role in the regulation of HPT axis, TRH is a potent regulator of prolactin (PRL) secretion by stimulating PRL secretion either directly from lactotrophs or indirectly via its action on the tuberoinfundibular dopamine (TIDA) neurons. In rodents, the TRH neurons which regulate TSH and thyroid hormone secretion, called hypophysiotropic TRH neurons, are in the medial subdivision of the parvicellular paraventricular nucleus (PVN). In humans, the PVN also contains a large population of TRH neurons, especially in its medial part, but the location of hypophysiotropic TRH neurons is not yet known. In addition to regulating TSH and PRL secretion, TRH also functions as a neurotransmitter/neuromodulator. In rodents and teleosts, TRH axons densely innervate TIDA neurons to inhibit tyrosine hydroxylase (TH) biosynthesis, neuronal firing, and dopamine turnover which may contribute to increasing PRL secretion. No such connections have been reported in humans, although dopaminergic neurons express TRH receptors and TRH also regulates PRL secretion. The objectives of this study were to map TRH-IR and TH-IR structures in the human hypothalamus with single-label light microscopic immunocytochemistry and study their interaction with double-label light microscopic immunocytochemistry. We show that TRH-IR nerve terminals densely surround TH-IR neurons (perikarya and dendrites) in the infundibulum of the human hypothalamus. The micrographs illustrating these juxtapositions were taken by Olympus BX45 microscope equipped with a digital camera and with 100X oil immersion objective. Composite images were created from the consecutive micrographs if the neurons were larger than the frame of the camera, using Adobe Photoshop software. As no gaps between TRH-IR and TH-IR elements were seen, these contacts may be functional synapses by which TRH regulates the activity of dopaminergic neurons and subsequently TSH and PRL secretion.

Derivation and 97% Purification of Human Thyroid Cells From Dermal Fibroblasts.

Background: The success in rescuing thyroid deficiency in mice using thyroid cells derived from embryonic stem (ES) cells, together with the discovery of human induced pluripotent stem cells (iPSCs) from somatic cells, has raised the possibility of patient-specific thyroid cell replacement. In this study we demonstrate that human thyroid follicular cells can be derived from human iPSCs and show the ability of highly purified and differentiated cells to secrete thyroid hormone.Research Design and Methods: Human iPSCs were derived from adult skin fibroblasts using RNA reprogramming and differentiated in vitro into thyroid follicular cells by exposure to activin A, ethacridine and TSH as we have previously described for human ES cells. The resulting thyroid cells were then highly purified using double antibody cell sorting.Results: The iPSCs derived from human dermal fibroblasts showed stem cell-like morphologic changes and expressed pluripotent stem cell markers as assessed using qPCR, immunofluorescence staining, and FACS analysis. These cells retained their pluripotential characteristics as shown by teratoma formation after murine transplantation. Definitive endoderm cells were induced with activin A and the transcription factor TAZ was significantly induced on ethacridine treatment and translocated to the nucleus. Thyroid transcription factors NKX2-1 and PAX8 were also highly expressed in activin A derived endoderm cells and further induced by ethacridine. Following terminal differentiation with TSH, there was enhanced thyroid follicle formation, high expression of the thyroid specific genes—TG, TPO, TSHR and NIS, and secretion of thyroid hormone (T4) in vitro. Furthermore, we were able to achieve a 97% purification of TSHR+/NIS+ expressing cells after differentiation using a single purification procedure.Conclusions: These findings demonstrate that mature adult dermal fibroblasts can be matured into human iPSCs which have the potential to form functional thyroid follicular cells. This lays the groundwork for future person–specific thyroid regenerative therapy.

Graves' disease.

Graves' disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism and occurs at all ages but especially in women of reproductive age. Graves' hyperthyroidism is caused by autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid hormone secretion, releasing the thyroid gland from pituitary control. TSHR autoantibodies also underlie Graves' orbitopathy (GO) and pretibial myxoedema. Additionally, the pathophysiology of GO (and likely pretibial myxoedema) involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expansion and inflammation. Although the aetiology of GD remains unknown, evidence indicates a strong genetic component combined with random potential environmental insults in an immunologically susceptible individual. The treatment of GD has not changed substantially for many years and remains a choice between antithyroid drugs, radioiodine or surgery. However, antithyroid drug use can cause drug-induced embryopathy in pregnancy, radioiodine therapy can exacerbate GO and surgery can result in hypoparathyroidism or laryngeal nerve damage. Therefore, future studies should focus on improved drug management, and a number of important advances are on the horizon.

Tirotoxicosis e hipertiroidismo

Thyrotoxicosis is a clinical disorder caused by an caused by the effect of excess of thyroid hormone in tissues, whereas hyperthyroidism refers to an increased thyroid hormone synthesis and secretion. Diagnosis is achieved by the measurement of the serum TSH and thyroid hormones (thyroxine and triiodothyronine). Etiology has to be identified in order to set up a proper treatment. Graves-Basedow disease (an autoimmune thyroid disorder) is the commonest cause of hyperthyroidism, followed by toxic nodular goiter or toxic thyroid adenoma (autonomous secreting thyroid nodules). In the thyroiditis, the thyroid gland is inflamed and the thyroid hormones are released. In the estruma ovarii the thyroid hormones have an extrathyroidal origen whereas in thyrotoxicosis facticia the origin of such an excess is exogenous. Etiological diagnosis of thyrotoxicosis and hyperthyroidism is based on clinical examination, laboratory and imaging (ultrasonography and scintigraphy) tests. The treatment of hyperthyroidism depends on the etiology and is focused in treating the symptoms as well as in reduce the synthesis and secretion of thyroid hormones (pharmacological treatment, radioiodine therapy and surgery).

SUN-LB129 Thyroglobulin Stimulates the Secretion of Thyroxine From Thyroid Epithelial Cells in Suspension Culture via Nuclear Factor-κB Signaling Pathway

The nuclear factor (NF)-κB signaling pathway controls a variety of biological functions such as cell growth and differentiation as well as immune and inflammatory responses. Two distinct pathways of NF-κB activation are known. NF-κB signaling via non-canonical pathway plays an important role in maintaining normal thyroid function, namely, thyroid cells survival and expression of thyroid-specific proteins, such as NIS, TPO and thyroglobulin (Tg). The primary function of thyroid cells is the production of thyroid hormones, which are cleaved out by various processing enzymes from the modified tyrosine residues of the Tg molecule. Although Tg is currently recognized as no more than a scaffold protein for thyroid hormone synthesis, our group has shown that Tg stimulates the proliferation of rat thyroid follicular FRTL-5 cells via PI3K pathway. The signaling pathways underlying various functions of thyroid cells have been extensively investigated but some discrepancies still exist, depending on the experimental model systems and the types of cells used. Recently, our group discovered that Tg may directly regulate the synthesis of thyroid hormones in thyroid cells. In this study, we performed suspension culture of porcine thyroid cells and aimed to elucidate the mechanism of the effect of Tg on thyroid cells. Porcine thyroid epithelial cells were prepared from thyroid gland by enzymatic digestion and cultured in monolayer or in suspension culture. Various concentrations of Tg were added to the medium and cultured for several days. Then, the conditioned medium was collected and the amount of thyroid hormone was measured by reversed phase chromatography; the cells were harvested and mRNA levels of hormone-processing enzymes, cathepsin B, K, L and dipeptidyl peptidase I, II (DPP I, II), were measured by quantitative PCR. The amount and activation of cell signaling molecules were also evaluated by western blotting. Tg stimulated the secretion of thyroid hormone, thyroxine, from porcine thyroid cells in suspension culture, however, no stimulation by Tg was observed in monolayer culture. The expression of mRNAs of cathepsin B, K and L were reduced and that of DPP II was increased by the treatment of Tg in suspension culture. Tg increased the amount of NF-κB p52 and Rel B dose dependently. On the other hand, TSH had little effects on the amount of these proteins. Tg and TSH both activated PDK1 and MAPK p44/42 but not Akt. These results suggest that Tg regulates thyroid hormone synthesis in totally different way from TSH by altering the expression levels of hormone-processing enzymes in thyroid cells. This stimulatory effect might be mediated by NF-κB signaling pathway, whereas the proliferative effect of Tg under these conditions might be exerted via MAPK signaling pathway. The detailed mechanisms of these effects of Tg on thyroid cells are under investigation.

SAT-449 Factors Associated with Reduced Thyroid Hormones in Cushing Syndrome Patients Before and After Surgical Cure

Background: Hypercortisolemia adversely affects thyroid hormone secretion. We previously described the temporal pattern of thyroid function recovery in 23 patients (1). However, the factors leading to suppression and recovery of the hypothalamic-pituitary-thyroid (HPT) axis in Cushing’s syndrome (CS) are not fully understood. We performed two separate studies to investigate these factors. Methods: In study 1, we examined patients (pts, n=62) with CS who underwent curative surgery and recorded their serum morning and evening cortisol, ACTH, tumor volume and duration of symptoms and 24-hour urine free cortisol (UFC) at baseline and the morning serum free T4, TSH and T3 at six-month intervals after cure. Data were log-transformed and Pearson correlations were performed. Linear mixed models were used to study factors that predict recovery of thyroid function. In study 2, we examined the diurnal variation of TSH by performing hourly TSH measurement between 3—7 PM and 12—4 AM on a cohort of pts (n=45) before surgery. Wilcoxon Signed-Rank method was used for comparisons of mean TSH across time and Pearson correlations were performed on log-transformed data. P values <.05 were considered significant. Results: Study 1: In this larger cohort, we confirmed previous findings of suppressed or low normal fT4 and TSH values with active hypercortisolism, with normalization after cure that reflected changes in the T3:TSH, fT4:TSH and T3:fT4 ratios. There were inverse linear correlations between log10 UFC, serum AM and PM cortisol; and log10 TT3, fT4 and TSH before surgery. Independent negative prognosticators of circulating fT4 recovery included UFC greater than 1000mcg/day (nl: 3.5—45mcg/day), duration of symptoms of less than one year, and ACTH levels greater than 60pg/mL(nl: 5—45pg/mL) Study 2: The nocturnal (12 - 4AM) TSH surge was reduced, so that the difference in day and night TSH values was not statistically significant; this contrasts with the 30—50% nocturnal TSH increase above daytime values seen in healthy subjects. There was an inverse relationship between UFC and nocturnal TSH, daytime TSH and TBG values, but there was no direct relationship between UFC and percent changes in nocturnal TSH values. Conclusions: Our findings suggest that a deficit in TSH stimulation of the thyroid gland may explain the reduction in T3 and T4 levels. There is a dose-response relationship between various measures of hypercortisolemia and both thyroid hormones and the pattern of TSH secretion. Finally, the severity of hypercortisolism correlates with a longer time to recovery of the HPT axis in pts with CS after curative surgery. 1. Shekhar S et al. HPG and HPT Axes in Cushing Syndrome. J Endocr Soc, 3 S1, April May 2019

Thyroid stimulating hormone β-subunit splice variant is expressed in all fractional subsets of bone marrow hematopoietic cells and peripheral blood leukocytes and is modulated during bacterial infection

Thyroid stimulating hormone (TSH), a hormone produced in the anterior pituitary, is used to regulate thyroid hormone secretion. It has been known for over three decades that TSH is made by the cells of the immune system; however, the functional role of immune system TSH is unclear. We previously demonstrated that an alternatively-spliced isoform of TSHβ, referred to as the TSHβ splice variant (TSHβv), is the primary form of TSHβ made by hematopoietic cells in mice and humans. Most studies have linked TSHβv expression to myeloid cells of the immune system; however, it has recently been demonstrated that plasma cells in patients with Hashimoto’s thyroiditis may be a source of immune system TSHβv. Here, we demonstrate that TSHβv is expressed in bone marrow precursors of lymphoid cells, monocytes, and granulocytes, as well as in mesenteric lymph node (MLN) cells. Plasma cells generated by in vitro culture with bacterial lipopolysaccharide (LPS), and MLN cells from mice infected with L. monocytogenes expressed TSHβv. There was an increase in the intensity of intracellular TSHβv expression in MLN cells following exposure to LPS, and in the proportion of TSHβv+ CD138+ MLN cells following L. monocytogenes infection. The number of TSHβv+ cells increased in MLN cells, particularly among CD138+ cells, following bacterial infection. This was confirmed by an increase in gene expression of BLIMP-1, the transcription factor for CD138, following infection. Levels of circulating thyroxine dropped significantly in mice 24 hrs post-infection. These findings suggest that immune system TSHβv may contribute to the host immune response during bacterial infection.

Monitoring of Thyroid Malfunction and Therapies in Pregnancy and the Postpartum Period: A Systematic Updated Critical Review of the Literature.

From the very beginning of pregnancy, the maternal thyroid has to adapt to increased thyroid hormone secretion of up to 50%. This is paralleled by changes in thyroid-stimulating hormone secretion and by the thyroid-topic action of human chorionic gonadotropin. Thus, hypothyroidism and hyperthyroidism may occur. Many women exhibit preexisting thyroid diseases. This review tries to add the most recently published approaches to diagnosing thyroid malfunction in pregnancy to existing guidelines. Different literature-based approaches to diagnosing thyroid malfunction during pregnancy and the postpartum period were applied. To diagnose thyroid malfunction in pregnancy, trimester-specific reference ranges for thyroid-stimulating hormone and T4 are used. Definitions of thyroid malfunction are given. Treatment schedules for various thyroid diseases were reviewed and, on the basis of recent findings, were revised where necessary. For a daily clinical workup, this outline not only suggests diagnostic and therapeutic steps but also refers to frequent pitfalls and misinterpretations of laboratory data. Although the body of knowledge is increasing rapidly, the authors believe that this review is able to present new ideas concerning diagnostic and therapeutic tools for thyroid malfunction in pregnancy and the postpartum period. Nevertheless, there seems to remain room for individual approaches based on the personal experience of physicians who deal with these issues regularly.

Interpretación de las pruebas de función tiroidea

&#x0D; &#x0D; &#x0D; &#x0D; Los desórdenes de la glándula tiroides son comunes y pueden afectar hasta el 10% de la población en general. En muchas ocasiones los síntomas pueden ser inespecíficos, por lo que el médico en busca de un trastorno tiroideo debe llegar a un diagnóstico funcional y anatómico. Las mediciones séricas de las hormonas tiroideas confirman si hay un exceso, un déficit o si las concentraciones son normales. Para ello, se requiere un rango de referencia de la población local, y específicamente por grupos de edad, para una correcta interpretación de las pruebas de función tiroidea. Las hormonas tiroideas juegan un papel fundamental en el sistema endocrino, controlan el metabolismo general del cuerpo, el desarrollo neural, el crecimiento normal y la maduración de los huesos, así como funciones cardiovasculares y renales, entre otras. En esta revisión se pretende dar una aproximación a las pruebas tiroideas más relevantes, partiendo de la biosíntesis y secreción de las hormonas tiroideas, hasta llegar al abordaje para un diagnóstico inicial del paciente con trastorno tiroideo, mencionando los aspectos más importantes de los diferentes patrones tiroideos. El tratamiento detallado de cada uno de ellos, supera las expectativas de esta revisión.&#x0D; &#x0D; &#x0D; &#x0D;

Thyroid disease in peri‑ and postmenopause period (literature review)

The interpretation of thyroid function tests should be cautiously made during the perimenopause and postmenopause period bearing in mind that physiologic changes do exist in this group of women in terms of secretion and metabolism of thyrotropin and thyroid hormones. Moreover the incidence of thyroid disorders increases in postmenopausal and elderly women. There is no consensus for screening postmenopausal women even though there is well‑known evidence about the effect of thyroid status on cognitive function, cardiovascular risk, bone turnover, and longevity. The diagnosis of any thyroid disorder is challenging in these patients because the symptoms are more subtle and attributed to menopausal symptoms. Management requires more attention in this population than that of younger groups, because high doses of L‑thyroxine can lead to cardiac complications and increased bone turnover. Furthermore radio‑iodine is preferred in treatment of hyperthyroidism in older patients. The risk of nodular thyroid disease and thyroid cancers increases in this group. Although the diagnostic approach is the same as for young patients, the risk of surgery is high and disease prognosis is worse. Decision for menopausal hormonal therapy should be individualized regardless of the concomitant presence of thyroid disorders.

Advances in research on anti-thyroid drugs for recurrence risk factors and predictive models of Graves′ disease

Graves′ disease, also known as diffuse toxic goiter, is an autoimmune disease with increased secretion of thyroid hormone. There are three effective treatments for Graves′ disease, which including anti-thyroid drugs (ATD), radioactive iodine and thyroidectomy. In general, ATD is the first choice of Graves′ disease treatment for domestic physicians, but the high recurrence rate has always been the deficiency of ATD treatment. Recurrence is mainly related to gender, age, smoking, course of disease, goiter and other factors. Among them, the reliability and applicability of single risk factor in evaluating the recurrence rate of Graves′ disease after ATD treatment are poor. The prediction model of multi-factor comprehensive score is helpful for the naive patients to choose the best treatment plan, to achieve the goal of precise treatment and to improve the remission rate of Graves′ disease drug treatment. In this paper, the reliability of risk factors for Graves′ disease recurrence after ATD treatment is evaluated, and the development and application of prediction models such as Graves′ recurrent events after therapy (GREAT) score, GREAT + score, and clinical severity score (CSS) are reviewed. Key words: Anti-thyroid drugs; Recurrence of Graves′ disease; Risk factor; Predictive model

Unraveling the toxic effects of neonicotinoid insecticides on the thyroid endocrine system of lizards

The widespread use of neonicotinoids has resulted in large residues in the soil, which has a major impact on the lizards that inhabit the soil. Thyroid hormones play an important role in the growth and development of lizards. In this report, we assessed the disrupting effects of thyroid system on lizards after 28 days of continuous exposure to dinotefuran, thiamethoxam, and imidacloprid, respectively. Neonicotinoid insecticides could seriously affect the concentration of T4 in lizard plasma and the conversion of T4 to T3 in the thyroid gland. Specifically, exposure to dinotefuran affected the intake and utilization of iodine in the thyroid gland, resulting in insufficient thyroid function, which in turn lead to thyroid epithelial hyperplasia and follicular volume enlargement by negative feedback. Exposure to thiamethoxam could activate thyroid function, significantly increasing plasma T3 and T4 concentrations and promoting the binding of T3 and thyroid hormone receptors. Imidacloprid exposure could inhibit the secretion of thyroid hormones, leading to down-regulation of thyroid hormone receptors and related phase II metabolic enzyme genes. This study verified that the continuous exposure of neonicotinoids could affect the lizard thyroid endocrine system. The harm of neonicotinoids to reptiles deserved more attention.

Role of the Thyroid Gland in Expression of the Thyroid Phenotype of Sbp2-Deficient Mice.

Selenocysteine insertion sequence-binding protein 2, SBP2 (SECISBP2), is required for selenoprotein synthesis. Partial SBP2 deficiency syndrome manifests characteristic thyroid function tests. The Sbp2 deficiency mouse model, Sbp2 inducible conditional knockout (iCKO), replicates this thyroid phenotype and was used for pathophysiologic investigations. As selenoproteins have an antioxidative role in thyroid gland function, their deficiencies have potential to affect thyroid hormone (TH) synthesis. Sbp2 iCKO mice had larger thyroids relative to body weight and increased thyroidal thyroxine (T4) and triiodothyronine (T3) content while 5' deiodinases enzymatic activities were decreased. Possible mechanisms for the discrepancy between the increased thyroidal T3 and normal circulating T3 were investigated in dynamic experiments. Treatment with bovine thyroid-stimulating hormone (TSH) resulted in increased delta T4 in Sbp2 iCKO mice, indicating increased availability of preformed thyroidal TH. Next, the recovery of TH levels was evaluated after withdrawal of chemical suppression. At one day, Sbp2 iCKO mice had higher serum and thyroidal T3 concomitant with lower TSH, confirming increased capacity of TH synthesis in Sbp2 deficiency. Decreased TH secretion was ruled out as serum and thyroidal TH were high in Sbp2 iCKO mice. Treatment with a low-iodine diet also ruled out thyroidal secretion defect as both serum levels and thyroidal TH content similarly declined over time in Sbp2-deficient mice compared to wild-type (Wt) mice. This study provides evidence for unsuspected changes in the thyroid gland that contribute to the thyroid phenotype of Sbp2 deficiency, with increased thyroidal T4 and T3 content in the setting of increased TH synthesis capacity contributing to the circulating TH levels while thyroidal secretion is preserved.

The Endocrine System: Thyroid and Parathyroid

In the adult, the thyroid gland is located in the central compartment of the neck on the anterolateral aspect of the cervical trachea between the carotid sheaths. Patients with thyroid disorders require attentive care, and safe, successful surgery of the thyroid is dependent on an intimate knowledge of the anatomy and physiology of the gland. This review discusses nerve branches and function; arterial and venous blood supply; lymphatic drainage; histology; physiology; and thyroid hormone synthesis, secretion, and regulation. Nerve injuries and postoperative complications are summarized, as are functions of thyroid hormones. A thorough understanding of these relationships is imperative for proper medical recommendations, surgical procedure selection, and meticulous surgical technique to avoid complications. To provide safe care of patients with thyroid disorders, treating physicians must embrace the intricate details of the anatomy and physiology of this unique gland to avoid potentially devastating complications. This review contains 5 figures, 3 tables, and 29 references. Key Words: brachial cleft, lymphatic zones, recurrent laryngeal nerve, superior laryngeal nerve, nerve injury, thyroglossal duct cysts, thyroid, thyroidectomy

The Endocrine System: Thyroid and Parathyroid

In the adult, the thyroid gland is located in the central compartment of the neck on the anterolateral aspect of the cervical trachea between the carotid sheaths. Patients with thyroid disorders require attentive care, and safe, successful surgery of the thyroid is dependent on an intimate knowledge of the anatomy and physiology of the gland. This review discusses nerve branches and function; arterial and venous blood supply; lymphatic drainage; histology; physiology; and thyroid hormone synthesis, secretion, and regulation. Nerve injuries and postoperative complications are summarized, as are functions of thyroid hormones. A thorough understanding of these relationships is imperative for proper medical recommendations, surgical procedure selection, and meticulous surgical technique to avoid complications. To provide safe care of patients with thyroid disorders, treating physicians must embrace the intricate details of the anatomy and physiology of this unique gland to avoid potentially devastating complications. This review contains 5 figures, 3 tables, and 29 references. Key Words: brachial cleft, lymphatic zones, recurrent laryngeal nerve, superior laryngeal nerve, nerve injury, thyroglossal duct cysts, thyroid, thyroidectomy

Effects of Ciplukan Fruit Extract (Physallis peruvenia) on T4 levels in White Rats

Hyperthyroidism is a condition where there is an increase in thyroid hormone synthesis and secretion so that the level of thyroid hormone in the blood increases. In 2013, data showed 0.4% of Indonesia's population experienced hyperthyroidism. Ciplukan fruit (Physalis peruviana) is an Indonesian herb that is thought to have an effect on thyroid hormone. This research is an in vivo experimental study. The research subjects were 30 Wistar strain white rats divided into 5 groups: negative control (distilled water), positive control (PTU 100 mg / kgBW), groups 3, 4, and 5 Ciplukan fruit extracts at a dose of 250 mg/kgBW, 500 mg/kgBW, and 1000 mg/kgBW. The results of the examination showed a decrease in T4 levels in the treatment with positive control and administration of ciplukan fruit extracts. There was a difference in the reduction in T4 levels for the group giving ciplukan extract doses of 1, 2, and 3 (p &lt;0.05). It can be concluded that Ciplukan fruit extract with a dose of 250 mg/kgBW, 500 mg/kgBW, and 1000 mg/kgBW has potential as an anti-hyperthyroidism.

Differential Diagnosis of Thyrotoxicosis

Hyperthyroidism is characterized by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. Thyrotoxicosis is characterized by low serum thyroid-stimulating hormone (TSH) level and elevated serum levels of free thyroxine or free triiodothyronine, or both. Therefore, thyrotoxicosis is divided into two subtypes: thyrotoxicosis with hyperthyroidism such as Graves’ disease and Plummer’s disease, and thyrotoxicosis without hyperthyroidism such as painless and subacute thyroiditis. Here, I describe the differential diagnosis of hyperthyroidism; differentiation between Graves’ disease and Plummer’s disease; differentiation between Graves’ disease with and without thyroid storm. Further, I show the differentiation among Graves’ disease, painless thyroiditis and subacute thyroiditis. I believe that the proper diagnosis leads to appropriate treatment and management of thyrotoxicosis. J Endocrinol Metab. 2019;9(5):127-132 doi: https://doi.org/10.14740/jem600