Journal of Endocrinological Investigation

Thyroid hormone has a direct resorptive effect on bone. Thyroid hormone therapy in doses that suppress pituitary TSH production result in a reduction in bone density. Osteocalcin is a bone matrix protein. Serum levels are a sensitive marker for bone turnover and are increased in hyperthyroid patients. In order to establish an animal model to study the effects of thyroid hormone on bone turnover, we measured rat femur osteocalcin mRNA following in vivo administration of thyroid hormone. Young CD rats weighing 60–90 g were given daily ip injections of T3, T4, or saline (control) for 12 days. Blood was obtained for radioimmunoassays, and RNA was extracted from femurs and analyzed by Northern blot using a 60-mer synthetic oligonucleotide probe corresponding to bases 360–420 of rat osteocalcin mRNA, labeled with [32P] ATP by 5′-endlabeling. Serum TSH concentrations were suppressed to subnormal levels by the lowest doses of T3 and T4, and to undetectable levels by the higher doses. Increases in serum T3 and T4 concentrations were proportional to the dose of each administered hormone. T3, 5 and 10 µg/100 g body weight, resulted in a 43% and 62% increase in osteocalcin mRNA, respectively. T4, 5, 10, and 20 µg/100 g body weight, resulted in a 35%, 47%, and 135% increase in osteocalcin mRNA, respectively. These data demonstrate that in vivo administration of either T4 or T3 to young rats results in a significant dose-dependent increase in femur osteocalcin mRNA concentrations.

Irisin is a newly identified myokine secreted by skeletal muscle and has significant effects on body metabolism. Thyroidal functional state has a profound influence on the metabolism of human body. Therefore, the aim of this study was to investigate the possible changes in serum irisin concentrations before and after treatment in hypothyroid subjects. The study included 26 patients with overt hypothyroidism due to Hashimoto thyroiditis and 19 healthy subjects. Baseline serum thyroid function tests and presence of thyroid autoantibodies and levels of creatine kinase (CK) and irisin were measured in both groups. All measurements in the hypothyroid group were repeated after euthyroidism was achieved. Serum irisin levels were significantly lower in the hypothyroid groups than the control group (p < 0.001). Negative correlation between irisin and thyroid stimulating hormone and CK levels (r = − 0.623, p < 0.001 and r = − 0.389, p = 0.008, respectively) and a positive correlation between irisin and free thyroxine (fT4) levels (r = 0.570, p < 0.001) was found. Serum CK levels decreased significantly after treatment (p < 0.001). Serum irisin levels significantly increased (from 57.4 to 99.8 U/L, p < 0.001) when the hypothyroid patients were treated to achieve euthyroidism. To the best of our knowledge, this is the first study providing insight that low serum irisin levels significantly increased following treatment to euthyroid state in overt hypothyroid patients with Hashimoto thyroiditis. Larger scale studies are needed to confirm these results and to ensure irisin as a possible biomarker of Hashimoto’s thyroiditis.

Association of subclinical hypothyroidism with type 2 diabetes and its complications has been previously documented. These reports were, however, inconclusive and mainly gathered from Chinese and East Asian populations. In this study, we aimed to determine the prevalence of subclinical hypothyroidism and its relationship with diabetic nephropathy in Iranian individuals with type 2 diabetes, drawn from a white Middle Eastern population with an increasing prevalence of diabetes. In this cross-sectional study, 255 Iranian participants with type 2 diabetes and without history of thyroid disorders were included. Patients with TSH > 4.2 mIU/L and normal T4 were classified as having subclinical hypothyroidism. Diabetic nephropathy was diagnosed based on abnormal 24-h urinary albumin or protein measurements (24-h urinary albumin ≥30 mg/day or 24-h urinary protein ≥150 mg/day). Multivariate logistic regression was employed to obtain the OR for the relationship between subclinical hypothyroidism and diabetic nephropathy. We found that subclinical hypothyroidism and diabetic nephropathy were as prevalent as 18.1 and 41.2 %, respectively, among the participants. We also found that subclinical hypothyroidism was independently associated with higher rates of diabetic nephropathy, after multivariable adjustment (OR [95 % CI] 3.23 [1.42–7.37], p = 0.005). We found that the prevalence of subclinical hypothyroidism in Iranian diabetic population was among the highest rates reported to date. Our data supported the independent association of subclinical hypothyroidism with diabetic nephropathy, calling for further investigations to evaluate their longitudinal associations.

We report our experience on venous sampling of the inferior petrosal sinuses for basal and CRH-stimulated ACTH and PRL gradients in 8 patients with surgically proven Cushing’s disease who had normal preoperative neuroradiological studies. In 7 patients basal plasma ACTH concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral sinus; the gradients were enhanced by oCRH administration. In one out of two patients who had previously undergone unsuccessful pituitary microsurgery, neither basal nor oCRH-induced ACTH increases led to correct localization of the microadenoma within the pituitary. In 4 out of 7 patients basal serum PRL concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral; only two out of 4 showed an increase in PRL levels after oCRH injection. Our study confirms that simultaneous and bilateral venous sampling of inferior petrosal sinuses is a valuable means to identify the site of microadenomas in patients with Cushing’s disease without neuroradiological evidence of the tumor. This procedure may give misleading results in patients previously operated on. Unilateral or predominant increases of PRL concentration during catheterization of the inferior petrosal sinuses, when present, always lateralize to the side of the corticotroph adenoma, providing a possible additional signal of the presence of the tumor.

Prolactin, growth hormone and thyroid stimulating hormone responses to thyrotropin releasing hormone (TRH) and metoclopramide were determined in 12 alcoholic men with biopsy proven liver disease and were compared to those of 8 age matched normal controls. All subjects were challenged with TRH (400 μg) and metoclopramide (10 mg) given as an intravenous bolus each on a separate day. Alcoholics had increased basal prolactin and growth hormone levels compared to controls. Alcoholics had a brisk and statistically significant (p < 0.01) response for each of the 3 hormones studied in response to TRH. In contrast to the alcoholics, the controls did not demonstrate a growth hormone response to TRH. Moreover, the TSH response to TRH of the alcoholics was exaggerated (p<0.05) compared to that of the controls. In response to metoclopramide, alcoholics had a brisk prolactin response, failed to demonstrate a TSH response, and had a decline in growth hormone when compared to controls. These results for alcoholics with liver disease differ from those reported for individuals with renal failure while those for the controls are similar to previously reported normal responses. These data suggest that liver disease and renal disease must differ in terms of their patterns of hypothalamic-pituitary neuroregulation as documented by their differing pituitary hormone responses to TRH and metoclopramide.

Background: Mechanical overload and poor quality of contractile elements related to metabolic abnormalities concur to motor disability of obesity. The independent contribution of these factors to motor dysfunction in obese individuals is scarcely defined. Aim: Aim of the study is to test the hypothesis that metabolic factors may independently affect motor function in obesity. Methods: Leg maximum power output per unit body mass (Ẇmb), per unit fat-free mas (Ẇffm) and fatigue in daily functioning were assessed in 635 obese [body mass index (BMI)≥35 kg/m2] individuals (286 men, 349 women) aged 19–78 yr. The independent effects of age, BMI, insulin resistance and the five components of the metabolic syndrome on Ẇmb, Ẇffm and fatigue were evaluated by multivariate analysis. Results: A multiple regression analysis revealed that in both genders Ẇmb (denoting the individual’s performance capability during anaerobic tasks) was independently reduced by age (p<0.001), BMI (p<0.05–0.001) and abnormalities of glucose metabolism (p<0.06–0.01), while Ẇffm (representing the muscle intrinsic anaerobic capability) was affected only by age (p<0.001) and glucose metabolism impairment (p<0.06–0.01). In both genders fatigue was increased by age (p<0.001) and BMI (p<0.05–0.01), but augmented by low levels of HDL-cholesterol in men only (p<0.05). Conclusions: Besides depending on mechanical overload and age, low muscle power output in obese individuals was independently associated also with metabolic abnormalities related to impaired glucose homeostasis. Fatigue and performance, although similarly influenced by age and body mass excess, are affected by different metabolic factors.