Pituitary-thyroid Axis Function Research Articles

Function of Pituitary-Thyroid Axis in Copper-Deficient Rats

Thirty male weanling Sprague-Dawley rats were fed either a copper-deficient diet (0.85 mg Cu/kg) or a copper-adequate diet (8 mg Cu/kg). After 7 weeks, the rats were fasted for 12 hours, and injected intravenously with thyrotropin-releasing hormone (TRH, 30 ng/100 g body weight). Six rats from each treatment were killed at 0, 0.5, 1, 2 and 4 hours after TRH injection. Sera obtained at 0, 0.5 and 1 hour, and at 0, 2 and 4 hours were used for the radioimmunoassay of thyroid-stimulating hormone (TSH) and thyroxine (T4), respectively. Reduction in liver copper content confirmed that the rats fed the test diet were copper-deficient. Serum TSH levels appeared to have peaked at 30 minutes but declined to a level higher than basal at 1 hour. No difference in TSH response was observed between the 2 treatments. Serum T4 response to TRH was reduced in the copper-deficient as compared to the adequate rats at all time intervals. After 2 hours a slight elevation was observed in the controls, but marked elevations in T4 were observed in both treatments at 4 hours. This reduction in T4 levels could be due to an impaired T4 synthesis or release in copper-deficient rats.copper deficiency thyroid-stimulating hormone thyroxine

Changes in quality of life after thyroidectomy in subjects with thyroid cancer in relation to the dose of levothyroxine.

Previous studies demonstrated decreased quality of life (QoL) in differentiated thyroid cancer (DTC) survivors and suggested QoL variability related to time from thyroidectomy and levothyroxine dosage. The aims of this study were to evaluate QoL in thyroidectomized subjects in different levothyroxine states and to evaluate the association between TSH and thyroid hormones and QoL. Prospective 5-year study enrolling 208 patients thyroidectomized for DTC, studied in one to four times according to levothyroxine dosage: withdrawal (WITHD), complete (C-SUPP) and mild TSH-suppression (M-SUPP), replacement (REPL). Each patient was allowed to participate into the study more than one time. A total of 300 evaluations were collected, consisting of detailed thyroid hormone profile and QoL assessment through the ThyPRO questionnaire. Comparing the four groups, significant differences were found for anxiety, impaired social and daily life and item 12 (overall impact of thyroid disease) domains (p < 0.05). Interestingly, C-SUPP subjects reported the best scores in almost all ThyPRO scales. Significant correlations were found between QoL and pituitary-thyroid axis function, as well as between QoL and gender, being females more affected. At multiple regression analyses fT3 demonstrated to be the best explanatory factor for overall impact of thyroid disease on the patient's life, followed by gender. TSH-suppressive doses of levothyroxine are more effective in improving QoL in DTC patients after thyroidectomy. These results confirm the urgent need of further studies aimed to define the best treatment of hypothyroidism, effective on well-being and harmless for patients.

An analysis of clinical characteristics and postoperative complications in children craniopharyngioma.

Children treated for craniopharyngioma (CP) experience significant morbidity. We aimed to investigate the clinical characteristics and postoperative complications of pediatric CP and to determine risk factors for complications to provide a theoretical basis for postoperative treatment. In this retrospective analysis, we screened clinical data concerning children with CP who had undergone surgery at our hospital from December 2011 to June 2015. We statistically analyzed the relationship between age, sex, disease course, tumor location, extent of tumor resection, and neuroendocrine axis dysfunction. Of 240 patients (males, n = 144; females, n = 96; mean age, 8.33 ± 4.64years), the main clinical presentations were headache (n = 151, 62.92%), vomiting (n = 84, 35%), vision changes (n = 101, 42.08%), polydipsia and polyuria (n = 47, 19.58%), and growth retardation (n = 42, 17.5%). Hypothalamic-pituitary dysfunction was the most common postoperative complication. There were 216 (90.00%) and 181 (75.42%) patients with pituitary-thyroid and pituitary-adrenal axis injuries, respectively. Being a prepubescent girl was a risk factor for impaired pituitary-thyroid and pituitary-adrenal axis function (P < 0.05). No correlation was found between sex (male), age, disease course, tumor location, extent of tumor resection, and impaired pituitary-thyroid and pituitary-adrenal axis function (P > 0.05). Pituitary-gonad axis injury was observed in 91 (37.92%) patients. Saddle and suprasellar region tumors were risk factors for impaired pituitary-gonad axis function (P < 0.05). No statistically significant correlation was found between sex, disease course, extent of resection, and impaired pituitary-gonad axis function (P > 0.05). Routine screening for complications during treatment is indicated for children with CP, to optimize the timing of interventions and reduce long-term morbidity.

Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L.

Circulating concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are partly heritable traits. Recent studies have advanced knowledge of their genetic architecture. Epigenetic modifications, such as DNA methylation (DNAm), may be important in pituitary-thyroid axis regulation and action, but data are limited. To identify novel associations between fT3, fT4, and TSH and differentially methylated positions (DMPs) in the genome in subjects from 2 Australian cohorts. We performed an epigenome-wide association study (EWAS) of thyroid function parameters and DNAm using participants from: Brisbane Systems Genetics Study (median age 14.2 years, n = 563) and the Raine Study (median age 17.0 years, n = 863). Plasma fT3, fT4, and TSH were measured by immunoassay. DNAm levels in blood were assessed using Illumina HumanMethylation450 BeadChip arrays. Analyses employed generalized linear mixed models to test association between DNAm and thyroid function parameters. Data from the 2 cohorts were meta-analyzed. We identified 2 DMPs with epigenome-wide significant (P < 2.4E-7) associations with TSH and 6 with fT3, including cg00049440 in KLF9 (P = 2.88E-10) and cg04173586 in DOT1L (P = 2.09E-16), both genes known to be induced by fT3. All DMPs had a positive association between DNAm and TSH and a negative association between DNAm and fT3. There were no DMPs significantly associated with fT4. We identified 23 differentially methylated regions associated with fT3, fT4, or TSH. This study has demonstrated associations between blood-based DNAm and both fT3 and TSH. This may provide insight into mechanisms underlying thyroid hormone action and/or pituitary-thyroid axis function.

MON-576 Ultrasound Changes of Healthy Thyroides over Six Years in Adults

Background. The need to re-test adults with negative thyroid ultrasound has not been elucidated yet. The aim of this study was to evaluate the incidence of thyroid disease in patients with previously negative thyroid US and to find any possible correlation with anamnestic or clinical features, and pituitary-thyroid axis function changes. Methods. Subjects who resulted without thyroid nodules in a screening study (1) were re-tested after at least 5 years. Anamnestic (familiarity, radiation therapy, previous pregnancies, smoking habit) and physical data (thyroid palpation, anthropometric measurements, blood pressure) were collected. Neck ultrasound evaluation was performed by an experienced endocrinologist who recorded detailed thyroid and nodules characteristics. When nodules were present, American Thyroid Association classification for prediction of thyroid cancer risk was applied. Serum samples were collected for measurement of TSH, free thyroid hormones, calcitonin and anti-thyroid antibodies. Clinical and anamnestic, physical, sonographic and serological characteristics were analyzed with logistic regression analysis for subjects with nodules versus those without nodules. Results. A total of 111 subjects were enrolled (43 M, 68 F). Half of them presented new thyroid nodules, mostly smaller than 1 cm and not suspicious. The 4% had high levels of anti-thyroid antibodies. Ninety-seven percent were euthyroid. Incidence of thyroid diseases was higher in women, especially in nulliparous. Comparing clinical characteristics of subjects with and without nodules, the only statistically significant difference concerned thyroid volume adjusted for body weight or surface (p<0.05). Finally, none of the anamnestic, physical, sonographic or serological values were predictive of the risk of developing thyroid nodules at logistic regression analysis. Conclusions. These results suggest that it is not indicated to repeat thyroid US after only 6 years in healthy subjects, even if they might develop small and clinically irrelevant thyroid nodules. (1) Gnarini VL, Brigante G, Della Valle E, Diazzi C, Madeo B, Carani C, Rochira V, Simoni M 2013 Very high prevalence of ultrasound thyroid scan abnormalities in healthy volunteers in Modena, Italy. J Endocrinol Invest 36:722-728.

Genome-wide meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone.

Thyroid hormones are essential for the normal function of almost all human tissues, and have critical roles in metabolism, differentiation and growth. Free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels are under strong genetic influence; however, most of the heritability is yet unexplained. In order to identify novel loci associated with fT3, fT4 and TSH serum levels we performed a genome-wide meta-analysis of 7411206 polymorphisms in up to 1731 euthyroid individuals from three Croatian cohorts from Dalmatia region: two genetically isolated island populations and one mainland population. Additionally, we also performed a bivariate analysis of fT3 and fT4 levels. The EPHB2 gene variant rs67142165 reached genome-wide significance for association with fT3 plasma levels (P = 9.27 × 10-9) and its significance was confirmed in bivariate analysis (P = 9.72 × 10-9). We also found a genome-wide significant association for variant rs13037502 upstream of the PTPN1 gene and TSH plasma levels (P = 1.67 × 10-8). We identified a first genome-wide significant variant associated with fT3 plasma levels, as well as a novel locus associated with TSH plasma levels. These findings are biologically relevant and enrich our knowledge about the genetic basis of pituitary-thyroid axis function.

Effect of repetitive potassium iodide on elderly rat’s thyroid

Background: Nuclear power plant emergencies had often been accompanied by radioactivity release into the environment, thyroid cancer is one of the major health consequences due to the effect of radioactive iodine (131I) that emits ϒ ray and β particles resulting in thyroid DNA damage and late onset thyroid cancer. Intake of a single dose of potassium iodide (KI) is recommended to reduce this risk. However in case of prolonged radioiodine release as noticed during Chernobyl and Fukushima accidents, more than one dose of KI may be basic to ensure adequate protection [1]. Whereas a single dose of KI is admitted to be safe, knowledge about the effects of repeated KI administration are scarce, few studies demonstrated the potential efficiency of repetitive KI intake in humans [2] and non-human primates [3] without hormonal variations. These studies are relevant in the field of radiation protection and give a base evidence of the possible use of repetitive KI. On the other hand, we have studies on rodents that showed an impact of chronic iodine excess on pituitary thyroid axis function [4]. Our previous work on adult male rats demonstrated the safety of repeated administration of KI over 8 days [5]. Indeed in the elderly persons KI administration in case of nuclear emergency remains a topic of debate, because of the possible impact in cardiovascular diseases. Thyroid hormones are well-known for their profound effects on cardiovascular function and metabolism; myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive even to subtle changes in the concentrations of circulating pituitary and/or thyroid hormones i.e. subclinical hypothyroidism and hyperthyroidism. It is well established that hyperthyroidism induces a hyper-dynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Atrial fibrillation is the most common cardiac arrhythmia in the elderly, the prevalence and incidence increase with advancing age [6]. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Objective: The aim of this study is to assess the effects of repeated KI intake on the thyroid function of aged male rats. Methods: A twelve months old male rats were subjected to either KI or saline solution over 8 days. Clinical biochemistry, pituitary and thyroid hormones level, and thyroid genes expression were analyzed 30 days after the treatment discontinuation. Findings: urinary assessment shows a subtle increase of some parameters (Creatinin, Uric Acid, Urea, Glucose, Potassium, Sodium and Chlorine), plasma biochemistry reveals a subtle variation of some parameters (an increase of Creatinin, Glucose and phosphorus; and a decrease of Chlorine level). Regarding pituitary-thyroid hormones we get a significant decrease of TSH level without thyroid hormones variation. At the molecular level, we observe a significant increase of TPO (+100%), AIT (+299%) and Tg (+38%) mRNA expression. On the other hand we get a significant decrease of TSHR (-51%) mRNA expression. Conclusion and perspectives: Our first results indicate that repeated KI intake affects the clinical biochemistry and the pituitary-thyroid axis function in elderly rats. To go further we are investigating the impact of these variations on the cardiovascular function and its parameters. Cardiac output data, cardiovascular gene expression, oxidative stress and inflammatory analysis are being processed. This study will contribute to the evolution of iodine policy and the harmonization of the current KI guidelines.

The Effect of Hydroalcohlic Vac Extract on Pituitary-Thyroid Axis Function in Adult Male Rats

The Effect of Hydroalcohlic Vac Extract on Pituitary-Thyroid Axis Function in Adult Male Rats

A Locus on Chromosome 1p36 Is Associated with Thyrotropin and Thyroid Function as Identified by Genome-wide Association Study

Thyroid hormones are key regulators of cellular growth, development, and metabolism, and thyroid disorders are a common cause of ill health in the community. Circulating concentrations of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) have a strong heritable component and are thought to be under polygenic control, but the genes responsible are mostly unknown. In order to identify genetic loci associated with these metabolic phenotypes, we performed a genome-wide association study of 2,120,505 SNPs in 2014 female twins from the TwinsUK study and found a significant association between rs10917469 on chromosome 1p36.13 and serum TSH (p = 3.2 × 10(-8)). The association of rs10917469 with serum TSH was replicated (p = 2.0 × 10(-4)) in an independent community-based sample of 1154 participants in the Busselton Health Study. This SNP is located near CAPZB, which might be a regulator of TSH secretion and thus of pituitary-thyroid axis function. Twenty-nine percent of white individuals carry the variant, and the difference in mean TSH concentrations between wild-type individuals and those homozygous for the minor G allele was 0.5 mU/l, which is likely to be clinically relevant. We also provide evidence of suggestive association (p < 5.0 × 10(-6)) of other SNPs with serum TSH, free T4, and free T3 concentrations, and these SNPs might be good targets for further studies. These results advance understanding of the genetic basis of pituitary-thyroid axis function and metabolic regulation.

Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes

Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) therapies represent a novel approach to cancer treatment via disruption of immune tolerance to antigens located on tumor cells. Disruption of immune tolerance, however, may occur at a cost. A host of immune related adverse events (IRAEs) are associated with anti-CTLA-4 therapy. Autoimmune hypophysitis has been reported in up to 17% of patients with melanoma and renal cell carcinoma treated with this therapy. Familiarity with the spectrum of IRAEs connected to these therapies is paramount for endocrinologists, oncologists and those involved in the care of these subjects. We review here key aspects of diagnosis and treatment of anti-CTLA-4 antibody therapy resultant IRAEs. We describe the first two cases of hypopituitarism in prostate cancer subjects undergoing experimental therapy with ipilimumab. The clinical evidence strongly suggests that the prostate cancer subjects developed autoimmune hypophysitis as a consequence of anti-CTLA-4 treatment. High dose glucocorticoid treatment resulted in markedly improved symptoms, and resolution of focal symptoms and diabetes insipidus. One subject recovered pituitary-thyroid axis function after 9 months; however, both continue to require GC replacement. These cases highlight the importance of early screening and treatment for hypopituitarism in all subjects undergoing treatment with anti-CTLA-4 therapy to prevent a potentially fatal outcome from secondary adrenal insufficiency, a readily treatable disease. We recommend mandatory long term follow-up to monitor the development of other hormonal deficits.

CLINICAL STUDY: Alterations in pituitary‐thyroid axis function among opioid‐dependent subjects after acute and protracted abstinence

The aim of the present study was to investigate the changes in the pituitary-thyroid axis (PTA) and the time course of the hormonal alterations in subjects with opioid dependence after abstinence. Blood samples from in-patients with opioid dependence and age- and sex-matched healthy controls were collected. The severity of opioid abuse and of withdrawal symptoms was assessed. Results were compared between patients with opioid dependence (n = 30) and healthy controls (n = 30). We found that free triiodothyronine and free thyroxine levels were comparable with healthy controls while thyroid-stimulating hormone (TSH) was lower in patients in acute opioid abstinence period. Also, TSH levels in patients remained lower than controls after 30 days of abstinence. These results indicate that PTA function is altered in opioid-dependent subjects. These data highlight the importance of screening the thyroid function for individuals with chronic opioid dependence.

Estrogen effects on thyroid iodide uptake and thyroperoxidase activity in normal and ovariectomized rats

Sex steroids interfere with the pituitary–thyroid axis function, although the reports have been controversial and no conclusive data is available. Some previous reports indicate that estradiol might also regulate thyroid function through a direct action on the thyrocytes. In this report, we examined the effects of low and high doses of estradiol administered to control and ovariectomized adult female rats and to pre-pubertal females. We demonstrate that estradiol administration to both intact adult and pre-pubertal females causes a significant increase in the relative thyroid weight. Serum T3 is significantly decreased in ovariectomized rats, and is normalized by estrogen replacement. Neither doses of estrogen produced a significant change in serum TSH and total T4 in ovariectomized, adult intact and pre-pubertal rats. The highest, supraphysiological, estradiol dose produced a significant increase in thyroid iodide uptake in ovariectomized and in pre-pubertal rats, but not in control adult females. Thyroperoxidase activity was significantly higher in intact adult rats treated with both estradiol doses and in ovariectomized rats treated with the highest estradiol dose. Since serum TSH levels were not significantly changed, we suggest a direct action of estradiol on the thyroid gland, which depends on the age and on the previous gonad status of the animal.

Somatostatin treatment of congenital chylothorax may induce transient hypothyroidism in newborns

Aim: To describe a group of neonates with congenital, non-traumatic chylothorax, one of whom developed transient hypothyroidism following treatment with somatostatin. Methods: The charts of seven infants with congenital chylothorax were reviewed in terms of their clinical presentation, the severity of their disease, the complications they presented and the duration of their hospitalization. Their pituitary–thyroid axis function was monitored in particular. Results: The seven infants, all preterm (32–34 wk), suffered from congenital chylothorax and hydrops fetalis diagnosed during the prenatal period. Four were treated by intrauterine drainage, and four had congenital malformations. Hospitalization lasted from 32 to 120 d. Three of the infants suffered from thrombocytopenia, three had chronic lung disease, and one suffered from Gram-negative sepsis. The infant treated with somatostatin initially had normal thyroid function, but later developed primary transient hypothyroidism and was treated with L-thyroxine. The thyroid screening tests for the infants who were not treated with somatostatin were all normal. Conclusions: Repeated doses of somatostatin were effective in reducing chylus production. Administering this treatment earlier should be considered in order to minimize known complications. The only potential side effect observed was primary transient hypothyroidism. Therefore, careful monitoring of the pituitary–thyroid axis is advised.

Somatostatin treatment of congenital chylothorax may induce transient hypothyroidism in newborns

To describe a group of neonates with congenital, non-traumatic chylothorax, one of whom developed transient hypothyroidism following treatment with somatostatin. The charts of seven infants with congenital chylothorax were reviewed in terms of their clinical presentation, the severity of their disease, the complications they presented and the duration of their hospitalization. Their pituitary-thyroid axis function was monitored in particular. The seven infants, all preterm (32-34 wk), suffered from congenital chylothorax and hydrops fetalis diagnosed during the prenatal period. Four were treated by intrauterine drainage, and four had congenital malformations. Hospitalization lasted from 32 to 120 d. Three of the infants suffered from thrombocytopenia, three had chronic lung disease, and one suffered from Gram-negative sepsis. The infant treated with somatostatin initially had normal thyroid function, but later developed primary transient hypothyroidism and was treated with L-thyroxine. The thyroid screening tests for the infants who were not treated with somatostatin were all normal. Repeated doses of somatostatin were effective in reducing chylus production. Administering this treatment earlier should be considered in order to minimize known complications. The only potential side effect observed was primary transient hypothyroidism. Therefore, careful monitoring of the pituitary-thyroid axis is advised.

The long-term effect of replacement therapy in a short girl with autoimmune atrophic thyroiditis of prepubertal onset.

A 9 yr 11 mo old girl was admitted to our hospital because of short stature. Her growth rate gradually decreased and her height was 120 cm (–2.5 SD) on admission. The mother’s and father’s heights were 157 cm (–0.2 SD) and 163 cm (–1.3 SD), respectively. Her bone age was retarded (6 yr 10 mo). An MRI indicated pituitary enlargement, which mimicked adenoma. Evaluation of the pituitary-thyroid axis and thyroid function proved she had primary hypothyroidism (T3 0.5 ng/ml, T4 1.0 μg/dl, TSH 1,030 μU/ml). These findings, thyroid autoantibody (anti-microsome antibody 400 xs) and histopathology (moderate fibrosis and mild lymphocytic infiltration) suggested acquired hypothyroidism due to autoimmune atrophic thyroiditis of prepubertal onset. Since the evaluation, she has been treated with levothyroxine. The pituitary enlargement disappeared within 3 mo after levothyroxine replacement. The growth rate increased and her height reached 153.2 cm (–1.0 SD) during 10 yr replacement (at 19 yr 11 mo of age). An improvement in her final height was obtained by long-term thyroid hormone replacement therapy. Enough endocrinological study and repeated MRI evaluation are necessary in cases of pituitary enlargement which mimics adenoma before considering surgery.

Longitudinal Assessment of Pituitary-Thyroid Axis and Adrenal Function in Preterm Infants Raised by ‘Kangaroo Mother Care’

Objective: To assess whether complete kangaroo mother care (KMC), a skin-to-skin contact intervention, would affect longitudinal/developmental patterns of hormonal change. Method: An open randomized controlled trial was conducted in a large tertiary care hospital, comparing KMC and traditional care for newborn infants weighing less than 2,001 g. Eighty-seven healthy preterm (<37 weeks gestational age) infants from this study provided three blood-spot samples on filter paper: at randomization (postnatal age 1–5 days), 2 weeks later, and at calculated term (41 weeks gestational age). They met a number of additional inclusion criteria including discharge from the hospital within the first postnatal week. The levels of 17α-hydroxy-progesterone (17-OHP), thyroxine-stimulating hormone (TSH) and thyroxine (T₄) were assessed by radioimmunoassay. Birth weight (<1,800 or ≧1,800 g) and prenatal maternal corticosteroid treatment were taken into account in the analysis. Interventions: Complete KMC includes early discharge, positioning the infant on the parent’s chest in an upright position, 24 h/day in skin-to-skin contact, and breast-feeding. In the traditional care group, infants were discharged according to routine hospital practice. Results: Levels of 17-OHP and TSH decreased significantly from eligibility to calculated term while T₄ levels did not change significantly over time. Most importantly, overall, treatment (KMC) did not interact with the pattern of physiological change. Conclusions: Maturation of the pituitary-thyroid axis and adrenal function is apparently not compromised by KMC, at least in healthy preterm infants.

Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus.

Short-term experimental diabetes mellitus (DM) produces a significant decrease in serum thyroid hormones, a decreased or normal serum thyroid-stimulating hormone (TSH) and a reduction in hepatic and renal T4-5'-deiodination. However, little is known about the effects of chronic diabetes mellitus on the pituitary-thyroid axis function. We evaluated the changes induced by very short-term (6 days), short-term (15 days) and chronic (6 months) streptozotocin-induced diabetes mellitus in 3-month old female Dutch-Miranda rat serum T4, serum TSH and T4-5'-deiodinase activity in the thyroid and pituitary glands. Serum hormones were determined by specific radioimmunoassays. Iodothyronine-5'-deiodinase activities were assayed in the thyroid and pituitary microsomal fractions using 2 microM T4 as substrate. Mean serum T4 was significantly decreased from 3.3 to 2.0 micrograms/dl 6 days after diabetes mellitus induction, and from 2.2 to 1.5 micrograms/dl after 15 days of DM, with no significant changes in serum TSH, indicating a decreased pituitary TSH responsiveness to the diminished suppression by T4, even though pituitary T4-5'-deiodinase activity was unchanged. Thyroid T4-5'-deiodinase was unchanged after 6 days of diabetes mellitus, but was significantly increased from 20.6 to 37.0 pmol T3/mg protein after 15 days. Six months after diabetes mellitus induction, both serum T4 and thyroid T4-5'-deiodinase returned to normal ranges and serum TSH was unchanged, although pituitary T4-5'-deiodinase was now significantly decreased from 2.7 to 1.7 pmol T3/mg protein. These findings indicate that some kind of adaptation to chronic insulinopenia may occur at the thyroid level, but this does not seem to be true for the pituitary.

Alterations in Thyroid Hormones and Thyrotropin (TSH) in Morbidly Obese Patients before and after Vertical Gastroplasty.

BACKGROUND: Published results of studies of thyroid function in obesity and after weight loss have differed. METHODS: The circulating concentrations of thyroid hormones and TSH were studied in 30 consecutive, euthyroid morbidly obese patients before and after weight loss from vertical gastroplasty, with the aim to determine the relation between body weight loss and pituitary-thyroid axis function. Serum TSH, free T3 (FT3) and free T4 (FT4) were measured before operation and repeated 6 and 18 months postoperatively. RESULTS: A significant increase, but within normal levels, in FT3 value at 6 and, mainly, at 18 months after gastroplasty was observed (p = 0.002). The FT4 value was slightly increased, at the same time and serum TSH was found to, be significantly decreased (p = 0.03 and p = 0.01 respectively). The relative increase in FT4 was negatively correlated with excess body weight and Body Mass Index reduction. This correlation was only moderate with values ranging from r = 0.34 to r = 0.47. CONCLUSIONS: Although there were statistically significant differences in thyroid function tests before and after loss of weight, these were not biologically significant. The hypophyseal/thyroid axis remains always active and contributes to body weight homeostasis and its regulation.

Blunted TSH and unaltered PRL responses to TRH following repeated administration of TRH in neurologic patients: A replication of neuroendocrine features of major depression

A blunted thyrotropin (TSH) and an unaltered prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) are widely recognized in neuroendocrinology of depression. We studied effects of repeated TRH administration of 1 mg/day for 10 days on the pituitary-thyroid axis function and PRL secretion in 16 euthyroid patients with neurological disorders. Although levels of serum thyroid hormones and of nonstimulated PRL were not affected by the treatment, baseline TSH levels were markedly inhibited. A blunted response of TSH to TRH was found without a significant effect on a PRL response to TRH after long-term treatment with TRH in four patients in whom a TRH test was performed. These changes are similar to those in depressed patients. TRH administration in this manner replicates a lowered sensitivity of thyrotrophs of the pituitary with a normal responsibility of lactotrophs in depression.

Cross-sectional and longitudinal study of the pituitary-thyroid axis in patients with thalassaemia major.

Thyroid dysfunction is known to occur frequently in thalassaemia major, but its prevalence and severity varies in different cohorts, and the long-term natural history is poorly described. We evaluated the pituitary/thyroid axis in thalassaemia major patients in a cross-sectional study and correlated abnormalities with indices of iron overload. Furthermore, the course of thyroid disease in thalassaemia major patients was assessed in a 15-year longitudinal study. Cross-sectional study: pituitary-thyroid axis function was examined in 37 patients (22 F, 15 M; aged 10-39 years, mean +/- SE = 21 +/- 1.4) out of a total of 43 who attended the Haematology and Endocrinology Clinics of Hadassah Hospital on a regular basis. The mean pretransfusion Hb level was 85 +/- 20 g/l, and all patients except one were treated with desferrioxamine (DF, mean +/- SE dose 20.2 +/- 2.6 mg/kg/day). Twenty-two had hypogonadotrophic hypogonadism (HH). Longitudinal study: 21 thalassaemia major patients were evaluated with TRH tests in 1976 and again in 1985. Fourteen of these and another eight were evaluated in both 1985 and 1991. Cross-sectional study: no patient had any clinical signs or symptoms of hypothyroidism; however, one had abnormally low T4, borderline low FT4 and normal T3 levels associated with an exaggerated TSH response to TRH consistent with mild hypothyroidism. This patient did not have a previous TRH test, but serial basal determinations over 7 years revealed a progressive decrease in thyroid function. Thirty-six patients had thyroid hormone levels within the normal range. Nine of these (24.3%) had only an exaggerated TSH response to TRH whereas seven others (19%) also had borderline elevated basal TSH levels. TSH response to TRH was not correlated with age, serum ferritin or liver function tests (ALT or GGT). Longitudinal study: mean TSH response to TRH decreased (P < 0.002), and mean T3 levels increased (P < 0.001) between 1975 and 1985. These findings are probably related to the initiation of DF treatment in 1981. During the last 6 years, four patients with previously normal TSH responses to TRH developed elevated peak TSH levels. Mean T3 concentrations decreased and TSH response to TRH increased significantly (P < 0.001 for both). (1) In this patient group the thyroid pituitary axis is less sensitive than the gonadal axis to iron-induced damage; only one out of 37 patients developed mild uncompensated hypothyroidism. (2) As opposed to the gonadal axis, the thyroid gland appears to fail before the central components of the axis. (3) Abnormal thyroid function may be reversible in the early stages. (4) Progression is variable, and it may take years to progress from normal to uncompensated hypothyroidism.