Serum TSH Concentrations Research Articles

Voluntary Exercise-Induced Activation of Thyroid Axis and Reduction of White Fat Depots Is Attenuated by Chronic Stress in a Sex Dimorphic Pattern in Adult Rats.

The activity of the hypothalamus-pituitary-thyroid (HPT) axis is inhibited by energy deficit, by acute or chronic stress, but activated by cold exposure or exercise. Because stress curtails acute cold induced activation of HPT, we evaluated the effect of chronic stress on HPT axis response to voluntary exercise, a persistent energy-demanding situation. Adult male and female Wistar rats were exposed to restraint stress, 30 min/day for 2 weeks, or to isolation (Iso) [post-natal day [PND] 30–63]. Exercise was performed (7 p.m.−7 a.m.) in a running wheel, sedentary controls stayed in individual cages (Sed); at 7 a.m. they were housed with their cage mate or individually (Iso); food intake by the exercised group was measured day and night to pair-fed Sed. At sacrifice, hormones, mRNA levels and tissue weights were quantified. Control or restrained adult rats had access to running wheel daily for 2 weeks. Compared to C, exercise decreased white adipose tissue (WAT) mass in females and males, increased hypothalamic paraventricular nucleus (PVN)-Trh expression in males proportionally to exercise performed, and increased TSH and T4 serum concentration in females. These changes were not detected in restrained groups. Starting at PND 63 control (2/cage) and isolated (1/cage) rats either exercised on 10 alternated nights or were sedentary. In control male animals, compared to Sed rats, exercise did not decrease WAT mass, nor changed HPT axis activity, but increased Pomc and deiodinase 2 (Dio2) expression in mediobasal hypothalamus (MBH), adrenergic receptor β3 and uncoupling protein-1 in brown adipose tissue. In control female animals, exercise decreased WAT mass, increased Pomc, Dio2, and Trhde expression in MBH, and TSH serum concentration. Iso females had lower TSH and T4 serum concentration, Dio2 and Trhde expression in MBH than controls. The stress response was higher in isolated males than females, but in males it did not alter the effects of exercise, in contrast to isolated females that had a blunted response to exercise compared to controls. In conclusion, chronic stress interferes with metabolic effects produced by exercise, such as loss of WAT mass, coincident with dampening of HPT activity.

A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management

Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS.Methods: Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed.Results: During hormonal evaluation elevated serum concentration of FSH and LH and decreased serum concentration of estradiol were measured. The genetic testing revealed translocation 7;14 (t(7;14)) and inversion 7 in 22% of examined cells which confirmed the initial hypothesis of NBS. The diagnosis was finally verified by identifying a Slavic founder mutation, c.657_661del5, on both allels of the NBN gene. Furthermore, hormonal serum evaluation conducted after four weeks allowed the patient to be diagnosed with premature ovarian insufficiency (POI) suspected earlier on the grounds of preliminary examinations (ultrasound imaging and laboratory tests).Conclusions: Chromosomal instability resulting from a mutation present in Nijmegen breakage syndrome patients might be a causative factor of premature ovarian insufficiency. Therefore, females diagnosed with NBS should undergo additional diagnostic procedures in order to determine further management and treatment.

MON-601 Optimizing the Mean TSH Target Range for Thyroid Hormone (L-T4) Replacement in Primary Hypothyroidism

A commonly advocated TSH target range for guiding the dosage of thyroid hormone (L-T4) replacement in primary hypothyroidism is 0.3 to 3.0 mU/L. This is based on the physiological acceptability of individual TSH levels within this range. Individual serum TSH concentrations, however, vary about their mean TSH concentration even in patients who have been stable on the same dose of L-T4. Predictably, when the mean TSH level is near the upper (or lower limit) of the above stated target range, some individual TSH levels will be above (or below) the target range. This study was designed to assess the variability of individual TSH levels above and below their corresponding mean serum level, and to identify a range for mean TSH levels that would minimize the frequency of the associated individual TSH levels being outside of the 0.3 to 3.0 mU/L target range. Sixty patients (yielding 368 TSH determinations) with primary hypothyroidism were receiving L-T4 replacement in an appropriate and unchanged dosage that maintained their mean TSH levels between 0.3 to 3.0 mU/L for up to 3 years. Achievement of the stable L-T-4 dosage was declared after an initial titration stage before the beginning of the stable interval. Patients non-compliant with their prescribed L-T4 dosage were excluded. The number of TSH determinations and the percentages of the patients whose mean TSH levels were between the bracketed subsets of the 0.3 to 3.0 mU/L target range (below), are presented as having individual TSH levels >3.0 mU/L, 0.3-3.0 mU/L, and <0.3 mU/L respectively: [0.3 to <0.5] 13, 0.0%, 61.5%, 38.5%; [0.5 to <1.0] 39, 0.0%, 82.1%, 17.9%; [1.0 to <1.5] 90 3.3%, 92.2%, 4.4%; [1.5 to <2.0] 141, 5.7%, 93.6%, 0.7%; [2.0 to <2.5] 59, 15.3%, 84.7%, 0.0%; [2.5 to 3.0] 26, 34.6%, 65.4%, 0.0%. Based on this data, establishing a mean TSH level of 1.0 to 2.0 mU/L would minimize the frequency of individual TSH levels above or below the physiologic TSH target range of 0.3 to 3.0 mU/L and, in doing so, minimize the frequency of rechecking serum TSH levels or unnecessarily changing dosages of L-T4.

SUN-465 Thyrotropin-Releasing Hormone-Degrading Ectoenzyme Controls Thyrotropin Secretion and Body Weight in Male Rodents

Thyrotropin-releasing hormone (TRH) is expressed in the brain, and a few peripheral tissues. Apart from controlling TSH secretion from the pituitary, it has an anorexic effect. TRH is a short-lived intercellular signaling molecule, hydrolyzed by the TRH-degrading ectoenzyme (TRH-DE), a narrow specificity peptidase which only known biological substrate is TRH. TRH-DE activity is mainly detected in brain, with an uneven distribution among regions; at the base of the third ventricle, Trhde is expressed by β2 tanycytes whose end-feet form synaptoid contacts with TRH terminals in the external layer of the median eminence (ME). Tanycyte TRH-DE activity is sensitive to thyroid hormone feedback and energy balance clues and may contribute to adjust the thyroid axis to changing energy needs. To test whether this enzyme is relevant for energy balance, we used mice generated in the B6/129S background in which Trhde exon 2 was deleted and backcrossed to C57BL/6NJ background for 11 generations. TRH-DE activity was reduced in heterozygote (HT) and eliminated in homozygote (KO) compared to wild type (WT) animals. Male mice (70-75 days old) were switched from a standard diet to a high fat high fructose diet (HFFD) for 9 weeks. On HHFD, KO animals ingested less kcal and gained less body weight (BW) than WT animals. Bio-impedance data indicated a lower fat mass in KO mice, compared to WT or HT mice. Glucose tolerance was higher in KO mice than in WT or HT mice. To clarify the specific relevance of tanycyte TRH-DE, we used adeno-associated virus (AAV) vectors in male rats to either knock down (with TRH-DE*, a dominant negative isoform) or overexpress TRH-DE in ME tanycytes. Serum TSH concentration increased when TRH-DE activity decreased, and the converse occurred when TRH-DE activity increased. Thus, TRH-DE activity from β2-tanycytes controls the concentration of TSH in the circulation, probably because it regulates the turnover of TRH before entry into the hypothalamus-pituitary portal vessels. However, 2- or 3-weeks treatment with AAV-TRH-DE or AAV-TRH-DE* did not affect BW. To further test the role of peripheral TRH-DE activity, a phosphinic analogue of TRH (P-TRH) was administered to adult male HFFD mice during 28 days through osmotic pumps connected to an intraperitoneal catheter. P-TRH treatment reduced TRH-DE activity in serum, but not inside the blood brain barrier, compared with mice treated with vehicle; however, treatment with P-TRH did not change food consumption and BW. In conclusion, ablation of TRH-DE impedes diet-induced obesity in male mice, possibly through enhanced thyroid axis activity and amplification of the anorectic effect of TRH. Supported in part by grants from DGAPA-UNAM (PAPIIT IN206712, IN206416, IN212719), and CONACYT (CB154931, CB254960 and PN562).

Age and Assay Related Changes of Laboratory Thyroid Function Tests in the Reference Female Population.

SummaryBackgroundLaboratory thyroid function tests play a central role in the diagnosis of thyroid disorders. The aim of our cross-sectional study was to determine reference values for thyroid tests in a rigorously selected group of Montenegrin females, investigate the impact of possible age-related changes and the influence of the interassay bias between three frequently used immunoassays.MethodsFemale subjects were randomly selected, aged between 20 and 69 and 946 of them met the selection criteria. TSH, fT3, fT4, thyroid peroxidase and thyroglobulin antibodies were measured. Eighty samples were further analyzed on two other immunochemistry platforms.ResultsMedian TSH progressively increased with age, there was no difference in fT3, while fT4 was significantly higher in the two oldest groups compared to the others. When using the age-related 97.5 percentile of TSH the percentage of reclassification was highest in the 20–29 years of age group (5.2%, p<0.05). In the oldest band, 7.7% had TSH values above cohort-specific and below the age-related upper reference limit. Bland-Altman bias plots revealed the highest interassay absolute mean difference between compared TSH assays of 24.5% and for fT4 assays of 13.8%.ConclusionsThe correlation coefficients between fT3 assays from different manufacturers were low. Serum TSH and fT4 concentrations increased with age and the implementation of age-specific TSH reference intervals would be of interest. The bias between the three commercial immunoassays indicated that the standardization of thyroid function tests is a task of great importance.

Syndromes of Resistance to Thyroid Hormone Action.

Thyroid hormone (TH) action is crucial for the development of several tissues.A number of syndromes are associated with reduced responsiveness to thyroid hormones, expanding the original definition of thyroid hormone resistance, firstly described by Refetoff and collaborators in 1967, which is characterized by elevated circulating levels of T4 and T3 with measurable serum TSH concentrations, as a consequence of mutations of thyroid hormone receptor beta (TRβ), recently named as RTHβ. More recently, another form of insensitivity to TH has been identified due to mutations in the thyroid hormone receptor alpha (TRα), named RTHα. In this chapter we will focus the discussion on the phenotype of RTHβ and RTHα. These diseases share the same pathogenic mechanism caused by dominant negative mutations in TH receptor genes that reduce T3 binding or affect the recruitment of cofactors. As a consequence, thyroid hormone actions are impaired at the tissue level. The phenotypic manifestations of RTHβ and RTHα are to some extent correlated with the degree of disruption and the tissue distribution of the TRs being characterized by variable coexistence of hypothyroid or thyrotoxic manifestations in RTHβ or by a congenital hypothyroid features in RTHα despite normal TSH and borderline low free T4.

Is 3-4 Weeks Required for TSH to Rise Post Thyroidectomy? A prospective Study and Discussion of its Implications on Patient Care.

Context:In patients with differentiated thyroid cancer (DTC), for the purpose of radioiodine (131I) whole-body scan and treatment of remnant, or residual tumor, or metastatic disease, thyroid hormone withdrawal remains the standard approach for raising thyroid-stimulating hormone (TSH) levels to ensure adequate radioiodine uptake. Thyroid hormone is withdrawn 3–4 weeks prior radioiodine therapy (RAIT) to allow the serum-TSH concentration to rise to above 25–30 mU/L.Aims:We studied the time taken for TSH to rise in 40 patients after total thyroidectomy operated for DTC.Settings and Design:Prospective observational study.Methods and Materials:40 patients with proven differentiated thyroid cancer attending a tertiary care center were studied.Statistical Analysis Used:Data was analyzed by using SPPSS software for windows (version 15, SPSS Inc., Chicago, USA).Results:After performing preoperative TSH in all patients excluding preoperative TSH elevation, it was planned to collect weekly postoperative samples till TSH ≥30. The mean (standard deviation, SD) age of the cohort was 40 (13) years with 35 females (88%) and their mean (SD) preoperative TSH was 3.6 (1.35) mIU/L. At the end of the first week postoperatively, the mean TSH of the cohort was 24.25 (6) with 8 patients (20%) achieving the cut-off of TSH ≥30 mIU/L and 30 patients (75%) achieving TSH level ≥20 mIU/L. At the end of the second week, the mean TSH was 53 (17) with all patients (100%) achieving a TSH level >30 mIU/ml.Conclusions:An iodine whole-body scan can be performed in 10–14 days after total thyroidectomy instead of the usual wait time of 4 weeks. This could improve patient QOL and avoid complications related to prolonged hypothyroidism.

Onemocnění štítné žlázy v seniorském věku

The incidence of most thyroid diseases are prevalent in women in ratio 8 : 1 to men, and especially hypothyroidism arises with age. Unrecognized thyroid dysfunction leads to increased: cardiovascular risk, bone fractures, cognitive impairment, depression, and mortality. The symptoms of thyroid diseases can be nonspecific or common in seniors with ageing complaints. The interpretation of thyroid function tests, the physiological changes in secretion and metabolism of thyrotropin (TSH) and thyroid hormones must be considered, as well as the influence of comorbidities, certain drugs, and individual set point of pituitary gland. According to many observations the serum TSH, thyroxine (T4), concentrations depend on age, comorbidities, and medical treatment - these together sometimes make the diagnosis of thyroid dysfunction complicated in older population. The observational data may suggest a diminished pituitary sensitivity to T4 in the ageing population. According to several studies, serum TSH concentration is probably age-dependant and the upper limit of TSH could be 5.28-5.9 mIU/l in those who are > 70 years old. Therapy of thyroid dysfunction is different in elderly persons than in young people; hypothyroidism should be treated with caution, because high doses of thyroxine can lead to cardiac arrhythmias and increased bone turnover. Hyperthyroidism could be treated either with surgery or preferable with radioiodin. Especially the diagnosis of subclinical hypothyroidism should be made with caution after concerning different important circumstances. Nevertheless there are certain conditions, when subclinical hypothyroidism must be treated. Key words: ageing - hyperthyroidism - hypothyroidism - thyroid diseases.

Lack of Relationships Between Serum Prolactin Concentrations and Classical Cardiovascular Risk Factors in Eastern Croatian Older Adults.

BackgroundRelationships between serum prolactin concentrations and various CV risk factors in older adults have rarely been assessed. The aim of this study was to examine the relationships between serum prolactin concentrations and CV risk factors in older patients with multiple CV risk factors.Material/MethodsThis case-control study included 92 patients, 50–89 years old (median, 69 years), with multiple CV risk factors. We used data from general practice electronic health records and biochemical laboratory tests. Patients were divided according to categories of CV risk factors.ResultsSerum prolactin concentrations were significantly higher in elderly people (≤65 vs. >65) and in men (70.65±58.02 vs. 150.82±114.05 mIU/L), as well as in patients with lower renal function (156.70±127.23 vs. 72.53±37.25 mIU/L, the bottom vs. top quartile of creatinine clearance), higher serum homocysteine and TSH concentrations, and in those who used NSAID and statins. Parameters indicating chronic inflammation (CRP) and renal function decline (creatinine clearance) were significantly and independently correlated with increased serum prolactin concentrations in multiple regression analysis.ConclusionsWhen assessing the relationships between prolactin and CV risk factors in older people with multiple CV risk factors, the effect of renal function decline and chronic inflammation should receive attention.

Age-associated functional morphology of thyroid and its impact on the expression of vimentin, cytokeratins and VEGF. The role of nigella in refinement.

Aging causes morphological and functional changes in the thyroid gland. Free radicals play a key role in the pathology of normal aging. Vimentin and cytokeratin are cytoskeletal intermediate filaments that are often used as indirect indices of tissue injury. The aim of the study was to clarify the age-related alterations in the structure and function of the thyroid gland. The relationship between oxidative/antioxidative stress markers and cytoskeletal intermediate filaments (vimentin and cytokeratin) and oxidative/antioxidative stress markers as well as vascular endothelial growth factor (VEGF) during aging were elucidated. Finally, the role of Nigella sativa (NS) oil in ameliorating age-related alterations of the structure and function of the thyroid gland was studied. Thirty Sprague-Dawley albino rats were divided into five groups: young adult control, young adult NS-treated, late adult control, late adult NS-treated, and senile. The age of young adult, late adult, and senile rats was nearly 7, 18 and 22 months, respectively. NS oil was added to food pellets and was administered at a daily dose of 0.1 g/kg body weight for one month. The thyroid gland was dissected and fixed immediately in 10% formalin saline. The assessment of thyroid structure was based on hematoxylin and eosin, and Masson's trichrome stainings, and histomorphometric analysis of the deparaffinized sections. Localization and distribution of vimentin and cytokeratin filaments was assessed by immunohistochemistry. Measurements of VEGF gene expression by qPCR and oxidative/antioxidative markers (malondialdehyde and glutathione content, superoxide dismutase activity) in thyroid gland homogenates were performed. Serum concentration of thyroid hormones (T3, T4) and TSH were assessed by radioimmunoassay. Follicles in the late adult control group were dilated and disrupted. Follicular cells showed cytoplasmic vacuolation. Follicles in the thyroids of senile rats were of irregular shape, often with cellular exfoliations. Many follicles were dilated and lined with flattened cells. A notable amelioration of these morphological alterations was observed in late adult NS-treated rats. Decrease in serum T3 and T4 levels and increase in TSH levels were observed in the late adult control and senile groups. A clear shift of the oxidative/antioxidative markers (MDA/ /GSH, SOD) was observed in the late adult control and senile groups in favor of oxidants. Administration of NS to late adult rats resulted in normalization of these parameters. Increased area of collagen fibers, immunoreactivity of vimentin and cytokeratin filaments and VEGF gene expression were observed in the thyroids of late adult and senile rat groups as compared to young animals. The mean number of follicular cells decreased in the late adult control and senile groups. Administration of NS to the late adult rats returned these parameters to the level of the young adult rats. Aging-related alterations in both structure and function of the rat thyroid gland that are associated with increased indices of oxidative stress might be abrogated by administration of antioxidative agents present in Nigella sativa oil.

Relationship among thyroid stimulating hormone level and sex hormones, blood lipids and insulin resistance in patients with polycystic ovary syndrome

Objective To explore the relationship among thyroid stimulating hormone level and sex hormone level, blood lipid level and insulin resistance in patients with polycystic ovary syndrome. Methods From February 2014 to February 2017, eighty cases with polycystic ovary treated in the People's Hospital of Longhua, Shenzhen were selected as the research object.The clinical data of all patients were collected to check the indexes of thyroid function, lipid metabolism, glucose metabolism, and sex hormone related indexes, and the insulin resistance index (HOMA-IR) was calculated according to the related indexes of glucose metabolism.The patients were divided into group according to the level of thyrotropin, group A (thyrotropin 4.0mIU / L). According to the patient's insulin resistance index, the patients were divided into IR group and non IR group.According to the blood lipid metabolism index, the patients were divided into abnormal blood lipid group and non lipid abnormality group.The levels of thyrotropin and sex hormone related indexes were compared in different groups, and the correlation between thyrotropin level and various indexes was analyzed. Results The differences in body mass index ((23.3±4.2) kg/m2 vs.(23.8±3.5) kg/m2 vs.(25.6±5.2) kg/m2), luteinizing hormone((11.9±1.1)U/L vs.(11.7±1.2)U/L vs.(9.5±1.0)U/L), low density lipoprotein cholesterol ((2.4±0.9) mmol/L vs.(2.7±0.7) mmol/L vs.(2.9±0.8) mmol/L), high-density lipoprotein cholesterol ((1.5±0.4) mmol/L vs.(1.5±0.5) mmol/L vs.(1.3±0.2) mmol/L), triglyceride ((1.1±0.8) mmol/L vs.(1.5±0.9) mmol/L vs.(1.8±0.7) mmol/L), and apolipoprotein A ((1.8±0.5) mg/L vs.(1.7±0.4) mg/L vs.(1.5±0.3) mg/L) among group A, B and C were statistically significant (F=8.456, 9.587, 11.245, 10.784, 10.847, 10.214, P<0.05). The serum TSH concentration in group IR was significantly higher than that in non IR group ((3.1±1.1) mU/L vs.(2.3±0.8) mU/L) (t=3.551, P<0.05). The serum LH concentration in group IR was significantly lower than that in non IR group((9.4±1.1)U/L vs.(11.2±2.1)U/L) (t=3.739, P<0.05). The level of TSH in dyslipidemia group was significantly higher than that of non dyslipidemia group((3.2±1.3) mU/L vs.(2.4±1.1) mU/L) (t=3.551, P<0.05), and the level of LH in dyslipidemia group was significantly lower than that of non dyslipidemia group((9.3±1.6)U/L vs.(11.6±2.4)U/L) (t=4.709, P<0.05). The TSH level in patients with polycystic ovary syndrome was positively correlated with body mass index, three acylglycerol, low density lipoprotein cholesterol and insulin resistance index(r=0.272, 0.317, 0.364, 0.227)( P=0.015, 0.004, 0.003, 0.043), and there was a negative correlation with luteinizing hormone and high-density lipoprotein cholesterol(r=-0.616, -0.254) (P=0.000, 0.034). Conclusion Hyperthyroidism in patients with polycystic ovary syndrome is associated with abnormal blood lipid, abnormal sex hormone levels, and insulin resistance. Key words: Polycystic ovary syndrome; thyroid stimulating hormone; sex hormones; blood lipids; insulin resistance

Graves’ disease in children

R1 The diagnosis of Graves’ disease in children is based on detecting a suppression of serum TSH concentrations and the presence of anti-TSH receptor antibodies. 1/+++. R2 Thyroid ultrasound is unnecessary for diagnosis, but can be useful for assessing the size and homogeneity of the goiter. 2/+. R3. Thyroid scintigraphy is not required for the diagnosis of Graves’ disease. 1/+++. R4. The measurement of T4L and T3L levels is not necessary for the diagnosis of Graves’ disease in children but can be useful for the management and assessment of prognosis. 1/++. R5. In the absence of TSH receptor autoantibodies, the possibility of genetically inherited hyperthyroidism must be considered. 1/++. R6. Drug therapy is the primary line of treatment for children and consists of imidazole, carbimazole or thiamazole, with an initial dosage of 0.4 to 0.8mg/kg/day (0.3 to 0.6mg/kg/day for thiamazole) depending on the initial severity, up to maximum of 30mg. 1/++. R7. Propylthiouracil is contraindicated for children with Grave's disease. 1/+++. R8. Before starting treatment, it may be useful to perform a CBC in order to assess the degree of neutropenia caused by hyperthyroidism. It is not necessary to perform systematic CBCs during follow-up. 2/+. R9. An emergency CBC should be performed if symptoms include fever or angina. If neutrophil counts are <1000/mm3, synthetic antithyroid therapy should be discontinued or decreased and may be permanently contraindicated in severe (<500) and persistent neutropenia. Otherwise treatment may be resumed. 1/++. R10. Transaminases levels should be measured before initiating treatment. Systematic monitoring of liver function is not consensually validated. 2/+. R11. In cases of jaundice, digestive disorders or pruritus, measuring liver enzymes (AST, ALT), total and conjugated bilirubin and alkaline phosphatases is indicated. 1/++. R12. Patients and parents should be informed of the possible side effects of antithyroid agents. 1/+. R13. Therapeutic education of parents and children is important in ensuring the best possible treatment compliance. 2/++. R14. Given the specificities involved in the treatment of Graves’ disease in children, medical care should be provided by a specialist accustomed to treating endocrinopathies in pediatric patients. 2/+. R15. Depending on patient age, the severity of the disease at diagnosis and the persistence of anti-TSH receptor antibodies, the initial course of treatment must take place over an extended period of 3 to 6 years. R16.The anticipated success rates of medical treatment (50% of patients in remission following several years of treatment) should be explained to the family and the child. The possibility that radical treatment may be required in case of failure or intolerance of medical treatment should also be discussed. 1/++. R17.In females with Graves’ disease, it is important to explain that they must undergo an assessment by an endocrinologist before planning future pregnancies, from the start of pregnancy and during the course of pregnancy. This is true in all female patients, even those in remission after medical treatment, or those who have undergone radical treatment. R18.Indications for a radical treatment can arise in cases of: 1/+: contraindication to antithyroid agents; poorly controlled hyperthyroidism due to lack of compliance; relapse despite prolonged medical treatment; a request made by the family and child for personal reasons. R19.Surgery is the radical method of treatment used in children under 5 years of age, or in cases of very large, nodular, or compressive goiters. 2/++. R20. The surgeon's experience in dealing with thyroidectomies in children is likely to be the most significant determining factor in limiting the morbidity of the procedure (alongside any collaboration between a pediatric surgeon and an adult surgeon). 1/++. R21 When radical treatment is indicated, I-131 treatment may be discussed after 5 years (but more often after puberty), if the goiter is not too large. Experience from monitoring Graves’ disease in North American children is reassuring. 1/++.

Current Thyrotropin Immunoassays Recognize Macro-Thyrotropin Leading to Hyperthyrotropinemia in Females of Reproductive Age.

Macro-thyrotropin (macro-TSH) is a high molecular weight form of TSH that leads to hyperthyrotropinemia. This study was undertaken to examine the prevalence and nature of macro-TSH in females of reproductive age. Blood samples were taken from 1794 female patients who visited the Hamada Obstetrics and Gynecology Hospital in Tokyo, Japan, complaining of infertility. The serum of 305 patients with TSH concentrations >2.5 mIU/L was screened for macro-TSH by the polyethylene glycol method. Samples with TSH precipitation ratios by polyethylene glycol >70% were further analyzed using gel filtration chromatography (GFC), protein G columns, and 125I-TSH binding experiments. Screening of the 305 patients revealed that 63 had serum TSH precipitation ratios >70%. GFC revealed that immunoreactive TSH, with a molecular weight of approximately 150 kDa, eluted at higher ratios (79.6 ± 24.4%) in 27 of the 63 patients compared to 0.4 ± 2.0% in the control group. Serum TSH concentrations in 24 of the 27 patients were spuriously elevated due to human anti-mouse antibodies. Macro-TSH was found in the other three patients, and one of them had detectable anti-TSH autoantibodies. Eight of the remaining 36 patients who did not have high-molecular-weight TSH assessed by GFC had immunoglobulin G-associated TSH. Three commercially available TSH immunoassays (Elecsys®, Centaur®, and Architect®) all recognized macro-TSH leading to the elevated serum TSH concentrations. Macro-TSH was present in 0.17% of infertile women. Commercial TSH immunoassays recognized macro-TSH, resulting in the diagnosis of hyperthyrotropinemia.

Serum Thyroid Hormone and Thyrotropin Concentrations in Adult Horses as They Age

With more horses remaining active longer in life, it is important to characterize changes that occur normally with aging, so that these can be differentiated from development of disease. The objective of the study was to test the hypotheses that geriatric horses have lower circulating concentrations of thyroid hormones and/or higher serum thyrotropin (TSH) concentrations compared to younger horses. Serum thyroid hormone and TSH concentrations from 71 normal, healthy horses that had participated in prior research projects were analyzed for effects of age, sex, and season when samples were obtained. All samples had been assayed in the same previously validated radioimmunoassays. There were no differences in serum concentrations of thyroid hormones or TSH by sex or season. Serum total thyroxine (T4) was greater in 3- to 6-year-old horses compared to all other age groups and was negatively correlated with age. There were no differences among age groups for free T4 and total and free tri-iodothyronine (T3). Serum TSH concentration was significantly greater in old horses (≥15 or ≥20 years) compared to young (3–10 years) and intermediate (11–14 years) age groups. Serum TSH was positively correlated with age. There were no significant differences in thyroid hormone responses to thyrotropin releasing hormone (TRH) among young, intermediate, or old horses. However, the TSH response to TRH was significantly different in both groups of older horses compared to intermediate and young horses. Serum total thyroxine concentrations decrease and serum TSH concentrations increase in horses as they age, with no changes in free T4 or T3.

Seasonal Changes in Serum Thyrotropin Concentrations Observed from Big Data Obtained During Six Consecutive Years from 2010 to 2015 at a Single Hospital in Japan.

This study analyzed big data for serum thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations in patients who had attended the outpatient clinic of Ito Hospital (Tokyo, Japan) during a recent six-year period (between January 1, 2010, and December 31, 2015) in order to investigate for seasonal changes. The serum TSH concentrations were reviewed for all 135,417 patients aged >20 years. Patients with any thyroid diseases were included, irrespective of whether they were receiving drug therapy. In total 1,637,721 serum samples were analyzed for TSH, 1,626,269 for fT3, and 1,669,381 for fT4. It was observed that the TSH concentrations showed annual changes during the six-year period. They decreased during the summer, while they increased during the winter. The TSH concentrations were negatively correlated with the daily temperatures (Spearman rank correlation coefficient -0.4486; p < 0.0001). The same applied for the correlation between fT3 concentrations and daily temperatures. The fact that the TSH concentrations show annual changes in areas where the temperature ranges during the year are rather wide should be borne in mind for interpretation of results.

Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats.

Cell therapy with mesenchymal stem cells (MSC) has been proposed for the treatment of diabetes mellitus (DM). It is known that the prevalence of thyroid disease is higher among diabetic patients than in general population. Therefore, our aim was to investigate the effect of the treatment with MSC on thyroid function and ROS generation in an experimental model of type 1 DM. Adult male Wistar rats were divided into the following groups: control, DM (80 mg/kg BW streptozotocin, iv.) and DM+MSC. MSC treatment occurred 4 weeks after DM induction and the animals were euthanized 4 weeks after MSC administration. We also evaluated the effect of co-culture with MSC or extracellular vesicles (EV) obtained from these cells on the rat thyroid cell line PCCL3 exposed to high glucose. Thyroid H2O2 generation was increased in DM, which was reversed by MSC treatment. These changes paralled a significant DuOx1 mRNA increase. The incubation of PCCL3 with high glucose increased extracellular H2O2 generation, which was reversed by both the co-culture with MSC and EV. Even though MSC treatment normalized thyroid ROS generation, serum thyroid hormone (TH) concentration remained low, along with increased serum TSH concentrations. Thyroperoxidase (TPO) activity, was reduced in DM, and MSC treatment did not normalize TPO. Therefore, we conclude that the treatment with MSC was able to reverse the increased thyroid H2O2 generation in diabetic animals and in PCCL3 cells exposed to high glucose, an effect probably mediated by EV produced by these cells, acting in a paracrine fashion.

Computed Tomography Density Change in the Thyroid Gland Before and After Radiation Therapy.

Hypothyroidism is an established adverse effect of radiation therapy for head and neck cancer, and computed tomography (CT) density of the thyroid gland is lower in hypothyroid than euthyroid individuals. No previous studies have evaluated changes in CT densities of the thyroid gland caused by radiation therapy. The aim was to investigate the relationship between the change in CT density of the thyroid gland before and after radiation therapy for head and neck cancer and hypothyroidism. This retrospective study analyzed data of 24 patients treated by radiation therapy for head and neck cancers. After dosimetric analysis of received radiation therapy, a Picture Archiving and Communication System was used to manually contour the thyroid on pre-treatment CT images to enable determination of mean thyroid gland CT densities and received radiation doses. Pre- and post-treatment thyroid function was assessed on the basis of serum TSH concentrations. Multivariate and univariate analyses were used to determine what clinical factors are associated with post-radiation therapy decrease in CT density of the thyroid and Pearson's χ2 test was used to assess correlations between these densities and TSH concentrations. Mean CT densities of the thyroid gland decreased from before to after radiation therapy in 73.9% of our patients (median decrease 16.8 HU). Serum TSH concentrations were significantly higher in patients with greater then median decreases in CT density than in those with lesser or no decreases. Post-radiation therapy hypothyroidism may be predicted by significant decreases in CT density of the thyroid gland.

The association between subclinical hypothyroidism and erectile dysfunction.

Objectives:Erectile dysfunction (ED) is highly prevalent among males, and hypothyroidism is previously reported to be related with ED. However there have been rare studies to investigate the association between subclinical hypothyroidism (SCH) and ED, hence our objective was to fill this gap.Methods:ED patients who visited the Urology Outpatients Clinic owere recruited consecutively, and males from the Health Manage Center were included as the controls. Serum thyroid and sexual hormones were estimated, and the International Index of Erectile Function (IIEF-5) questionnaires were evaluated as well. Subjects with normal sexual hormones were included for statistical analysis.Results:One hundred nine ED patients and 32 healthy controls were included in this study. The ratio of SCH and euthyroidism in ED males was 29.36% and 66.06% respectively. The IIEF-5 scores in ED patients with SCH were significantly lower than the controls with euthyroidism (P<0.05). The serum concentrations of TSH and prolactin were significantly higher and free thyroxine lower in ED patients with SCH when compared with the controls with euthyroidism (all p<0.05), and no significant differences of estradiol and total testosterone were found between those two groups. However the IIEF-5 scores were not significantly different between males with SCH and euthyroidism among ED patients (P>0.05).Conclusions:SCH is common in ED patients and may be associated with ED, whereas the severity of ED is not related to SCH. Screening for thyroid dysfunction in men presenting with ED is recommended.

Sperm abnormalities: Adverse effects of thyroid dysfunction

Introduction: Despite the importance of thyroid hormones in reproduction, there are only a few studies that focus on male infertility. The objective of this study was to evaluate semen parameters in patients with hypothyroidism or hyperthyroidism. Materials and methods: Totally, 28 patients with thyroid disorders were evaluated for the semen parameters. Serum TSH and T4 concentrations were measured by ELISA. Complete semen analyses were performed based on WHO. Results: Pathozoospermia was seen in 32.14% of our patients. Two hyperthyroid patients and seven hypothyroid patients suffered sperm defects. None of pathozoospermia patients showed an alone sperm defects. Sperm multiple anomalies were our main findings. Conclusion: It seems that sperm characterizes strongly were affected. Although, we have a limited sample size, but sperm multiple abnormalities made our interest findings.

Evaluation of growth hormone-releasing peptide-2 for diagnosis of thyrotropin-producing pituitary adenomas.

Thyrotropin (TSH)-producing adenomas are a rare cause of hyperthyroidism and are a type of functional pituitary adenoma. The diagnosis of TSH-producing adenoma is a challenging problem in clinical endocrinology. Since growth hormone-releasing peptide-2 (GHRP-2) fails to induce TSH secretion in normal subjects, the effect of GHRP-2 on TSH levels was therefore examined in patients with TSH-producing adenomas. A total of 5 patients (4 women and 1 man) referred to our departments for further evaluation of pituitary hormones were followed-up using the GHRP-2, TSH-releasing hormone (TRH), octreotide, and bromocriptine tests to examine and evaluate TSH secretory dynamics in TSH-producing adenomas. Of 5 patients, 2 (40%) showed such a significant response, defined as a >50% increase in serum TSH level above baseline in the GHRP-2 test. Additionally, 1 patient showed a 48% increase in serum TSH level. In 1 patient whose adenoma was completely removed, basal serum concentrations of TSH were sufficiently suppressed after the operation, and serum TSH levels failed to increase in response to GHRP-2 administration. In 4 patients (80%), a poor response of serum TSH levels was observed in the TRH test. In 2 out of 5 patients (40%), serum TSH levels were significantly decreased following octreotide administration. No patient demonstrated a significant response to the bromocriptine test. In addition to TRH test, the GHRP-2 test as a potential diagnostic tool for TSH-producing pituitary adenomas.