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The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study.
Krysiak, R, Szkrobka, W, Okopien, B
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2016;(2):71-6
Abstract
BACKGROUND One of the most frequent adverse effects of interferon-α therapy is thyroiditis. Metformin was found to improve insulin sensitivity in hepatitis C patients, as well as to reduce elevated thyrotropin levels in patients with hypothyroidism. The aim of this study was to investigate the effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with interferon-induced thyroiditis. METHODS The study included 2 matched groups of women with type 2 diabetes and untreated subclinical hypothyroidism: patients with interferon-induced thyroiditis (n=8) and patients with Hashimoto's thyroiditis (n=12). Fasting plasma glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, the estimated glomerular filtration rate, as well as serum levels of thyrotropin, thyroid hormones, prolactin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment. RESULTS Apart from reducing plasma glucose, HOMA1-IR and glycated hemoglobin, metformin decreased serum levels of thyrotropin. Circulating levels of thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. The effect of metformin on serum thyrotropin was stronger in patients with interferon-induced thyroiditis than in patients with Hashimoto's thyroiditis, as well as correlated with its impact on insulin sensitivity. CONCLUSIONS Our results indicate that metformin may be an effective agent in patients with interferon-induced hypothyroidism.
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2.
Levels of craving influence psychological challenge and physiological reactivity.
Frings, D, Eskisan, G, Spada, MM, Albery, IP
Appetite. 2015;:161-5
Abstract
Behavioural and cognitive pathways that lead to the activation and escalation of craving have been studied extensively. Conversely, limited efforts have been directed towards understanding how craving relates to motivational systems and neuroendocrine responses. These can be understood using the biopsychosocial model of challenge and threat. In the current study, forty participants with varying levels of chocolate craving undertook two word searches, with the prospect of winning a piece of chocolate. Amongst those with high levels of craving, participation in this task led to motivational states of challenge relative to those with lower levels. This was reflected by changes in cardiac reactivity driven by differences in sympathetic-adrenal-medullar and hypothalamic-pituitary-adrenal axis activation. This finding suggests that craving can be associated with states of motivational challenge and thus affect cardiac reactivity.
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3.
The effects of carbohydrate supplementation during the second of two prolonged cycling bouts on immunoendocrine responses.
Li, TL, Gleeson, M
European journal of applied physiology. 2005;(5-6):391-9
Abstract
The purpose of this study was to examine the effect of carbohydrate (CHO) feeding during the second of two 90-min cycling bouts (EX1 started at 09:00 and EX2 started at 13:30) at 60% VO2max on leucocyte redistribution, neutrophil degranulation and oxidative burst and plasma IL-6 and stress hormone responses. This study consisted of two trials, which were completed in a counterbalanced order and separated by at least 4 days. Subjects (n=9) consumed a lemon flavoured 10% w/v CHO (glucose) or placebo (PLA) beverage during EX2: 500 ml just before exercise and 250 ml every 20 min during exercise. Venous blood samples were taken 5 min before exercise, immediately post-exercise, and 18-h post-EX2 for both trials. The main findings of this study were that ingestion of CHO compared with PLA during EX2 better maintained plasma glucose concentration, blunted the responses of plasma adrenaline, ACTH, cortisol, GH and IL-6, and attenuated the leukocytosis and monocytosis, but had no effect on neutrophil degranulation and oxidative burst activity. Furthermore, the immunoendocrine disturbances induced by two bouts of prolonged exercise returned to resting values within 18 h. These findings suggest that ingestion of CHO compared with PLA during the second of two bouts of 90-min cycling at 60% VO2max better maintains plasma glucose, blunts hypothalamic-pituitary-adrenal activation, and attenuates leucocyte trafficking, but does not affect neutrophil function. Furthermore, the disturbances of immunoendocrine responses induced by two bouts of prolonged exercise on the same day recover within 18 h.
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4.
Effects of mometasone furoate dry powder inhaler and beclomethasone dipropionate hydrofluoroalkane and chlorofluorocarbon on the hypothalamic-pituitary-adrenal axis in asthmatic subjects.
Chrousos, GP, Ghaly, L, Shedden, A, Iezzoni, DG, Harris, AG
Chest. 2005;(1):70-7
Abstract
STUDY OBJECTIVES Mometasone furoate dry powder inhaler (MF-DPI) [400 mug] is an inhaled corticosteroid (ICS) that is effective in the treatment of asthma. MF-DPI has a low potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis at its clinical dose. The effect of MF-DPI, 400 microg qd, on the HPA axis was compared to that of beclomethasone dipropionate (BDP) using hydrofluoroalkane (HFA) and chlorofluorocarbon (CFC) propellants via metered-dose inhalers (MDIs) twice daily. DESIGN AND INTERVENTIONS This randomized, third-party blind, parallel-group study compared the effects of MF-DPI 400 mug one puff qd in the morning (n = 18), HFA-BDP 200 microg two puffs MDI bid (n = 18), and CFC-BDP 400 microg two puffs MDI bid (n = 17) for 14 days on the area under the 24-h serum cortisol concentrations curve (AUC(0-24)) and on total 24-h urinary free cortisol excretion in mild asthmatic subjects. Effects on morning/evening peak expiratory flow (PEF) and on inhaled albuterol use were also assessed. Adverse events that occurred during or > or = 30 days after the study were recorded. RESULTS The mean decrease from baseline in the serum cortisol concentrations AUC(0-24) in the MF-DPI group was significantly less than in either the HFA-BDP (p = 0.024) or the CFC-BDP (p = 0.011) groups. Decreases in serum cortisol concentrations AUC(0-24) in the two BDP groups did not differ from one another. The MF-DPI group trended toward higher morning and evening PEF than either BDP group. Treatment-associated adverse events were reported by seven subjects in the MF-DPI group, vs one subject in the HFA-BDP and three subjects in the CFC-BDP groups; these were mild, and no subject discontinued treatment due to an adverse event. CONCLUSIONS Fourteen days of treatment with MF-DPI 400 microg qd was associated with a significantly lesser decrease in the serum cortisol concentrations AUC(0-24) compared with HFA-BDP 200 microg MDI or CFC-BDP 400 microg MDI bid.
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5.
The mu-opioid receptor gene polymorphism (A118G) alters HPA axis activation induced by opioid receptor blockade.
Wand, GS, McCaul, M, Yang, X, Reynolds, J, Gotjen, D, Lee, S, Ali, A
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2002;(1):106-14
Abstract
An A118G nucleotide exchange in exon 1 of the mu-opioid receptor causes an Asn40Asp substitution polymorphism in the receptor's extracellular domain. In vitro studies show that the Asp40 variant of the mu-opioid receptor binds beta-endorphin three times more avidly than the more common Asn40 variant. Paraventricular corticotropin releasing hormone neurons, which activate the HPA axis, express mu-opioid receptors and are modulated by beta-endorphin neurons. This preliminary study was designed to test the hypothesis that the Asn40Asp substitution polymorphism in the mu-opioid receptor influences HPA axis activation induced by opioid receptor blockade. Thirty-nine healthy men were genotyped (A vs. G) and then underwent opioid receptor blockade with Naloxone. Subjects expressing the A118G receptor variant had greater cortisol responses to opioid receptor blockade. Also, a significant difference in the rate of increase of ACTH (slope) between A/A and A/G was observed between 30-90 minutes as well as a significant difference in the rate of decrease after 90 minutes. Moreover, subjects expressing the variant polymorphism had lower scores on the Conscientiousness Factor and associated subscales of NEO Personality Inventory compared to subjects expressing the common receptor. Because serotonin also modulates the CRF neuron, subjects were genotyped for a functional polymorphism within the serotonin transporter gene. We did not see differences in hormone responses resulting from expression of this functional polymorphism. It is plausible that persons expressing the mu-opioid receptor variant have altered HPA axis dynamics and altered responses to other physiological processes regulated through activation of the mu-opioid receptor.
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6.
The glutamate antagonist riluzole and its effects upon basal and stress-induced activity of the human hypothalamus-pituitary-adrenocortical system in elderly subjects.
Kniest, A, Wiesenberg, C, Weber, B, Colla, M, Heuser, I, Deuschle, M
Neuropsychobiology. 2001;(2):91-5
Abstract
There is preclinical evidence that CRH is released in response to a glutamatergic stimulation. However, it is not clear, whether glutamate plays a role in the physiological stress response. We tested whether the antiglutamatergic drug riluzole dampens the response of the hypothalamus-pituitary-adrenocortical (HPA) system to both a mental and a physical stressor. Nine male elderly healthy subjects received placebo and 150 mg riluzole for 2 days in a randomized balanced order. Blood was withdrawn every 15 min for estimation of cortisol and ACTH from 14.00 to 20.00 h. Between 16.00 and 16.45 h, the subjects were subjected to a cognitive challenge paradigm. Further, between 19.02 and 19.15 an individually adapted physical stress test was performed. After riluzole treatment, baseline ACTH and cortisol concentrations were unchanged when compared to placebo treatment. Also, after the mental stressor, there was no difference between both treatment conditions. In contrast, the cortisol (riluzole vs. placebo: 148 +/- 60 vs. 183 +/- 98 nmol/l) and ACTH response (20.2 +/- 11.9 vs. 40.7 +/- 61.9 pmol/l) to the physical stressor tended to be lower after riluzole pretreatment. In conclusion, the antiglutamatergic drug riluzole did not have any effects upon HPA system activity under baseline and cognitive-stress-induced conditions in elderly subjects. However, a trend for dampening the endocrine response to physical stress emerged.