The hypothalamic-pituitary-adrenal axis in the neuroendocrine regulation of food intake and obesity: The role of corticotropin releasing hormone

The aim of this paper is to review the present knowledge on the role of the hypothalamic-pituitary-adrenal axis in the control of food intake and the pathogenesis of obesity and to discuss, on the basis of available literature, the interactions between other neurosystems and this hormonal axis. Food intake is influenced by a system of physiologic signals and behavioral controls consisting of positive and negative sensory feedback mechanisms. It is regulated by a complex neuroendocrine system consisting of peripheral signals (cortisol, leptin) in constant interplay with central neurosystems such as the cocaine-amfetamine-regulated transcript system. In these neurosystems, corticotropin-releasing hormone, pro-opiomelanocortin, melanin-concentrating hormone and neuropeptide Y are actively involved. The corticotropin-releasing hormone system is widely distributed throughout the brain, but it is particularly abundant in the medial parvocellular division of the paraventricular nucleus. Within the brain corticotropin-releasing hormone with its two receptor types, its binding protein and its closely related peptide urocortin forms a network of neuronal pathways capable of interacting with other circuitries controlling food intake and sympathetically-mediated thermogenesis. A defect in the synthesis and release of corticotropin-releasing hormone has been implicated in the development of obesity in laboratory animals. This condition is alleviated by exogenous corticotropin-releasing hormone treatment. The relationship between the neuropeptide Y system and the hypothalamic-pituitary-adrenal axis is complex and seems to include positive feedback between neuropeptide Y and corticosteroids and negative feedback between corticotropin-releasing hormone and neuropeptide Y. Leptin is involved in the regulation of energy balance by interacting with the hypothalamic-pituitary-adrenal axis. In the past, we have shown by cross-correlation analysis, that under physiological conditions cortisol and plasma leptin levels are related to each other in a time-related negative and positive fashion over 24 h. © 2004 Taylor & Francis Ltd

Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility

Luteal phase deficiency (LPD) is a consequence of the corpus luteum (CL) inability to produce and preserve adequate levels of progesterone. This is clinically manifested by short menstrual cycles and infertility. Abnormal follicular development, defects in neo-angiogenesis or inadequate steroidogenesis in the lutein cells of the CL have been implicated in CL dysfunction and LPD. LPD and polycystic ovary syndrome (PCOS) are independent disorders sharing common pathophysiological profiles. Factors such as hyperinsulinemia, AMH excess, and defects in angiogenesis of CL are at the origin of both LPD and PCOS. In PCOS ovulatory cycles, infertility could result from dysfunctional CL. The aim of this review was to investigate common mechanisms of infertility in CL dysfunction and PCOS. © 2012 Springer Science+Business Media, LLC

Oocyte maturation in assisted reproductive techniques

Human oocyte maturation is a long process during which nuclear maturation occurs resulting in germinal vesicle breakdown (transition from prophase I to metaphase II) and extrusion of the first polar body. During oocyte maturation, in parallel with nuclear maturation, a number of events take place in the oocyte cytoplasm that assist fertilization and early embryonic development. So far several attempts have been made to mature human oocytes in vitro. The main patient group to which in vitro maturation (IVM) has been applied is polycystic ovarian syndrome. In a concise review we present the techniques used for the IVM of oocytes and the role of hormones and growth factors in IVM and subsequent fertilization and early embryonic development. © 2006 New York Academy of Sciences

Different outcomes in sporadic versus familial medullary thyroid cancer

Background: Medullary thyroid carcinoma (MTC) has varying clinical course with familial cases (fMTC) diagnosed earlier than sporadic MTC (spMTC). Methods: A total of 273 MTCs (familial: n = 110 [40.3%], males: 38.5%) were followed for 1-35 years (median 5.0 years). Fifty one of the familial cases were operated because of positive findings at genetic screening. Disease extent at diagnosis and follow-up was recorded. Results: Mean age at diagnosis was: fMTC = 33.85 ± 16.5 years (range 4-74) and spMTC = 52.6 ± 14.0 years (range 16-81, P <.001). This difference remained when genetic screening cases were excluded. fMTCs had more frequently multifocality, smaller size, and more favorable stage at diagnosis (stages I and II: 60.9% vs 47.9%, stage III: 30.0% vs 23.9%, stage IV: 9.1% vs 28.9%, P =.01). fMTC had lower preoperative and postoperative calcitonin, more frequently remission (59.1% vs 47.2%) and less frequently progressive disease (8.2% vs 35.0%, P <.001). After excluding genetic screening cases, no difference in stage at diagnosis was observed. Outcome was more favorable in fMTC compared to sporadic (P =.002); the 10-year probability of lack of progression of disease differed significantly between fMTCs and spMTCs (86.4% vs 65.0%, P <.001). Conclusion: After excluding genetic screening cases, although stage at diagnosis is similar, disease outcome remains worse in sporadic compared to fMTCs. © 2018 Wiley Periodicals, Inc

Thyroglobulin antibodies as a potential predictive marker of papillary thyroid carcinoma in patients with indeterminate cytology

Backround We investigated the efficacy of thyroglobulin antibodies (TgAb) in detecting malignancy in indeterminate thyroid nodules and evaluated the possible association between TgAb and autoimmunity in papillary thyroid carcinoma (PTC). Methods This retrospective, nonrandomized study included 1,646 patients who had undergone preoperative fine-needle aspiration biopsy to evaluate their thyroid nodules, and then standard total thyroidectomy. Of 194 patients (11.8%) with indeterminate nodules, 61 (31.4%) had PTC and 133 (68.6%) had benign nodules at the final histologic examination. Results Univariate analysis showed that multifocality (P =.002), bilaterality (P =.003), lymph-node metastasis (P =.030), and capsule penetration (P =.003) were significantly associated with positive TgAb in patients with indeterminate cytology and histopathologic diagnosis of PTC. The multivariate analysis showed that TgAb positivity (P <.001) and preoperative thyroid-stimulating hormone levels (P =.022) were independent predictive factor for PTC diagnosis in patients with indeterminate cytology. Conclusions Preoperative TgAb could be a marker for PTC in patients with indeterminate thyroid nodules, increasing diagnostic accuracy. TgAb positivity could also influence the clinical assessment and subsequent selection of total thyroidectomy. © 2016 Elsevier Inc

HbA1c presents low sensitivity as a post-pregnancy screening test for both diabetes and prediabetes in Greek women with history of gestational diabetes mellitus

Background and aim: Women with a history of gestational diabetes mellitus (GDM) are at increased risk for type 2 diabetes (T2D). It is thus recommended that an oral glucose tolerance test (OGTT) be performed after delivery. Recently, the use of glycated haemoglobin A1c (HbA1c) has been proposed as a simpler and faster method to diagnose glucose disorders. The aim of this study was to investigate whether HbA1c measurement can replace OGTT in the detection of prediabetes and T2D in women with a history of GDM. Patients and methods: We studied 1336 women (35.3 ± 5.8 years old) with a history of GDM 16.6 ± 28.2 months after delivery. All women were evaluated through an OGTT and a simultaneous HbA1c measurement. American Diabetes Association (ADA) criteria were used for the assessment of glucose disorders. Sensitivity and specificity of HbA1c were measured for the prediction of T2D and prediabetes, while Cohen’s coefficient of agreement (k) was calculated. ROC analysis was performed to evaluate the sensitivity and specificity of HbA1c. Results: Based on OGTT, 725 women (54.3%) were normal, 406 (30.4%) presented impaired fasting glucose (IFG), 48 (3.6%) impaired glucose tolerance (IGT), 74 (5.5%) combined IFG+IGT, and 83 presented with T2D (6.2%). By contrast, using HbA1c as a screening test, 1150 women (94.1%) were normal, while 49 (4.0%) had prediabetes and 23 (1.9%) T2D. Sensitivity of HbA1c for the diagnosis of prediabetes was 5.3% in comparison to OGTT, specificity was 99.2%, while for the diagnosis of T2D, the percentages were 29.6 and 100%, respectively. The consistency in classifying impaired glucose tolerance between HbA1c and OGTT was 59.7%. Cohen’s coefficient of agreement was k = 0.116, indicating slight agreement. Performing a ROC curve, the optimal value of distinctive ability of HbA1c was 4.6% in the case of prediabetes, while for diabetes, it was 5.5%. Conclusion: This study provided evidence that HbA1c can identify fewer women with prediabetes and T2D than OGTT, indicating that HbA1c cannot be recommended as an alternative post-pregnancy screening method. © 2018, Hellenic Endocrine Society

Corticotropin-releasing hormone inhibits in vitro oocyte maturation in mice

The expression of corticotropin-releasing hormone (CRH) receptor 1 messenger RNA in stages of follicle growth was examined by reverse transcriptase-polymerase chain reaction in long-term cultures of early preantral mouse follicles with and without CRH addition. Corticotropin-releasing hormone receptor 1 is present in stages of mouse follicle growth, whereas 10 -9, 10-7, and 10-6 mol/L CRH inhibits oocyte maturation in vitro, an effect reversed by antalarmin addition. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc

Links between HPA axis and adipokines: clinical implications in paradigms of stress-related disorders

Introduction: In the human organism, a constant interplay exists between the stress system [which includes the activity of the hypothalamic-pituitary-adrenal (HPA) axis] and the adipose tissue. This interplay is mediated by hormones of the HPA axis such as corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and glucocorticoids (GCs) and adipokines secreted by the adipose tissue. Areas covered: In this critical review, the bi-directional interactions between HPA axis and the most studied adipokines such as leptin and adiponectin, as well as the pro-inflammatory adipocytokines tumor necrosis factor (TNF) and interleukin (IL) 6 are presented. Furthermore, these interactions are described in normalcy as well as in specific clinical paradigms of stress-related disorders such as eating disorders, hypothalamic amenorrhea, and stress-related endogenous hypercortisolism states. Wherever new therapeutic strategies emerge, they are presented accordingly. Expert commentary: Additional research is needed to clarify the mechanisms involved in the interplay between the HPA axis and the adipose tissue. Research should be focused, in particular, on the development of new therapeutic means targeting dysfunctional adipose tissue in stress-related situations. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group