The acute effect of resistance exercise on serum growth hormone and blood glucose in healthy non-obese adolescent subject

Background: The growth hormone (GH) response to resistance training is altered by many factors including sex steroid concentrations, fitness, intensity of exercise, age, gender, duration of exercise and glycemic state but the exact understanding of the interplay of different exercises to GH levels and its induced physiological adaptations is still obscure. This study aimed to see how resistance exercise affects GH levels and its correlation to plasma glucose levels in healthy non-obese adolescent subjects.Methods: 48 healthy non-obese adolescent subjects, 24 males and 24 females were included in the study. High volume exercise training regimen was used which involved major muscle group of arms, legs and trunk. Pre and post exercise levels of serum GH and random blood sugar were estimated in male and female groups.Results: The mean body mass index (BMI) of male and female groups was 23.22±3.12 kg/m2 and 20.40±4.49 kg/m2, respectively. The post-exercise serum GH levels in male and females increased significantly by 0.54±1.041 ng/ml (p<0.05) and 0.85±1.023 ng/ml (p<0.001) respectively. The random blood sugar levels in males after exercise significantly increased (p<0.05) by 7.16±12.61 mg/dl and in females by 6.20±12.09 mg/dl (p<0.05). There was significant correlation (p<0.05) between increase in serum GH levels and increase in random blood sugar levels in both male and female group.Conclusions: Exercise induced increase in GH and its interplay with serum glucose can be better gained access into via metanalytical/elaborate studies of the major hormones and fuels involved.

The Biochemical Diagnosis of Acromegaly

Background: The diagnosis of acromegaly still poses a clinical challenge, and prolonged diagnostic delay is common. The most important assays for the biochemical diagnosis and management of acromegaly are growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Objective: Discuss the role of IGF-1, basal serum GH, and nadir GH after oral glucose tolerance test (OGTT) for the diagnosis, management, and treatment of patients with acromegaly. Methods: We performed a narrative review of the published data on the biochemical diagnosis and monitoring of acromegaly. An English-language search for relevant studies was conducted on PubMed from inception to 1 January 2021. The reference lists of relevant studies were also reviewed. Results: Serum IGF-1 levels, basal GH values, and nadir GH after OGTT play a major role in the diagnosis, management, and treatment of patients with acromegaly. Measurement of IGF-1 levels is the key factor in the diagnosis and monitoring of acromegaly, but basal and nadir GH following OGTT are also important. However, several factors may significantly influence the concentrations of these hormones, including assay methods, physiologic and pathologic factors. In some cases, discordant GH and IGF-1 levels may be challenging and usually requires additional data and monitoring. Conclusion: New GH and IGF-1 standards are much more precise and provide more accurate tools to diagnose and monitor patients with acromegaly. However, all these biochemical tools have their limitations, and these should be taken under consideration, along with the history, clinical features and imaging studies, when assessing patients for acromegaly.

Sex differences in somatotrope response to fasting: biphasic responses in male mice

Anterior pituitary somatotropes are important metabolic sensors responding to leptin by secreting growth hormone (GH). However, reduced leptin signals caused by fasting have not always correlated with reduced serum GH. Reports show that fasting may stimulate or reduce GH secretion, depending on the species. Mechanisms underlying these distinct somatotrope responses to fasting remain unknown. To define the somatotrope response to decreased leptin signaling we examined markers of somatotrope function over different time periods of fasting. Male mice were fasted for 24 and 48 h, with female mice fasted for 24 h compared to fed controls ad libitum. Body weight and serum glucose were reduced in both males and females, but, unexpectedly, serum leptin was reduced only in males. Furthermore, in males, serum GH levels showed a biphasic response with significant reductions at 24 h followed by a significant rise at 48 h, which coincided with the rise in serum ghrelin levels. In contrast, females showed an increase in serum GH at 24 h. We then explored mechanisms underlying the differential somatotrope responses seen in males and observed that pituitary levels of Gh mRNA increased, with no distinction between acute and prolonged fasting. By contrast, the Ghrhr mRNA (encoding GH releasing hormone receptor) and the Ghsr mRNA (encoding the ghrelin receptor) were both greatly increased at prolonged fasting times coincident with increased serum GH. These findings show sex differences in the somatotrope and adipocyte responses to fasting and support an adaptive role for somatotropes in males in response to multiple metabolic signals.

Impact of concurrent diabetes on periodontal health in patients with acromegaly

Previous studies have suggested excess GH/IGF1 secretion in patients with acromegaly is protective for periodontal health. Diabetes is prevalent comorbidity in patients of acromegaly and is associated with worsening of periodontal disease. The present study evaluates the periodontal health and cytokines status in treatment-naive active acromegaly patients with and without diabetes. Eleven patients, each of acromegaly with and without diabetes and 20 healthy controls were enrolled. Periodontal parameters were assessed. GCF and blood samples for IL-6, TGF-β1, and PDGF were obtained. Serum GH, IGF1, HbA1c, pituitary hormones and MRI sella were performed in patients with acromegaly. There was no significant difference in periodontal status of patients with acromegaly and healthy controls. However, a significant increase in serum IL-6 (p = 0.019) and TGF-β1 (p = 0.025) levels in patients with acromegaly was observed and all patients had concurrent hypogonadism. Nevertheless, the patients with acromegaly having diabetes had modestly higher CAL and PD and serum IL-6 levels (p = 0.051), but it could not exert adverse effects on periodontal health in presence of GH/IGF1 excess. GH/IGF1 excess did not exert a protective effect on periodontal status in acromegaly, possibly due to concurrent hypogonadism and opposing cytokines; however, it could mask the ill-effects of diabetes on periodontal health.

Digital analysis of hormonal immunostaining in pituitary adenomas classified according to WHO 2017 criteria and correlation with preoperative laboratory findings

OBJECTIVEThe authors sought to evaluate clinical and laboratory data from pituitary adenoma (PA) patients with functioning PA (associated with acromegaly [n = 10] or Cushing disease [n = 10]) or nonfunctioning PA (NFPA; n = 10) that were classified according to 2017 WHO criteria (based on the expression of the transcription factors pituitary-specific positive transcription factor 1 [Pit-1], a transcription factor member of the T-box family [Tpit], and steroidogenic factor 1 [SF-1]) and to assess the immunostaining results for growth hormone (GH) and adrenocorticotropic hormone (ACTH) in the corresponding tumors.METHODSClinical and laboratory data were collected retrospectively. The percentage of tumoral cells positive for Pit-1, Tpit, or SF-1 was assessed and ImageJ software was used to evaluate immunopositivity in PAs with 2 different antibodies against GH (primary antibody 1 [AbGH-1] and primary antibody 2 [AbGH-2]) and 2 different antibodies against ACTH (primary antibody 1 [AbACTH-1] and primary antibody 2 [AbACTH-2]).RESULTSCells with positive Pit-1 staining were more frequently observed in lesions from patients with acromegaly (acromegaly group) than in lesions from patients with Cushing disease (Cushing group; p < 0.001) and those from patients with NFPA (NFPA group; p < 0.001). The percentage of Tpit-positive cells was higher in the Cushing group than in the acromegaly (p < 0.001) and NFPA (p < 0.001) groups. No difference was detected regarding SF-1 frequency among all groups (p = 0.855). In acromegalic individuals, GH immunostaining levels varied depending on the antibody employed, and only one of the antibodies (AbGH-2) yielded higher values in comparison with the values for NFPA patients (p < 0.001). For all of the antibodies employed, no significant correlations were detected between GH tissue expression and the laboratory data (serum GH vs AbGH-1, p = 0.933; serum GH vs AbGH-2, p = 0.853; serum insulin-like growth factor–1 [IGF-1] vs AbGH-1, p = 0.407; serum IGF-1 vs AbGH-2, p = 0.881). In the Cushing group data, both antibodies showed similar ACTH tissue expression, which was higher than that obtained in the NFPA group (p < 0.001). There were no significant associations between ACTH immunohistochemical findings and ACTH serum levels (serum ACTH vs AbACTH-1, p = 0.651; serum ACTH vs AbACTH-2, p = 0.987). However, ACTH immunostaining evaluated with AbACTH-1 showed a significant correlation with 24-hour urinary cortisol (24-hour cortisol vs AbACTH-1, p = 0.047; 24-hour cortisol vs AbACTH-2, p = 0.071).CONCLUSIONSImmunostaining for Pit-1 and Tpit accurately identified lesions associated with acromegaly and Cushing disease, respectively. Conversely, SF-1 did not differentiate NFPA from lesions of the other two groups. Regarding hormonal tissue detection, results of the current investigation indicate that different antibodies may lead not only to divergent immunohistochemical results but also to lack of correlation with laboratory findings. Finally, PA classification based on transcription factor expression (Pit-1, Tpit, and SF-1), as proposed by the 2017 WHO classification of pituitary tumors, may avoid the limitations of PA classification based solely on digital immunohistochemical detection of hormones.

Heat Intolerance and Hyperhidrosis as the only Presenting Manifestations of Acromegaly: A Case Report

Acromegaly is a state of Growth Hormone (GH) excess characterised by coarse facial features, acral enlargement, hyperhidrosis, headache, visual disturbances and visceromegaly. The most common cause of acromegaly is pituitary adenoma. The average delay between onset of symptoms and diagnosis is about six years in acromegaly owing to its subtle clinical features at the disease onset.Early diagnosis is important to reduce the morbidities and mortality associated with acromegaly. Familiarisation of physicians with the signs and symptoms of the disease is an effective strategy for the early diagnosis of acromegaly. Here, the authors report a case of 38year-old female patient. After proper clinical examination, history and series of relevant investigations, the serum GH level was estimated and was found to be elevated (40 ng/mL). GH secreting pituitary macroadenoma presenting with heat intolerance and hyperhidrosis without the classical manifestations of acromegaly.

The GH Axis in Relation to Accepting an Early Macronutrient Deficit and Outcome of Critically Ill Patients

Context Changes in the GH axis during critical illness resemble fasting in healthy adults and contribute to hypercatabolism, which potentially affects outcome. Accepting macronutrient deficits by withholding parenteral nutrition (PN) during the first week in the intensive care unit (ICU; late PN) reduced complications and accelerated recovery as compared with early use of PN (early PN). Objective To investigate how late PN affects the GH axis in relation to its clinical outcome benefits. Design Preplanned subanalysis of the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients randomized controlled trial. Participants A total of 1128 patients for time-course study, 20 patients investigated for nocturnal GH pulsatility, and 600 patients investigated for muscle weakness, with early PN and late PN patients having comparable baseline characteristics. Intervention Withholding PN during the first ICU week (late PN) vs early PN. Main Outcome Measures Changes in serum GH, IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP1 concentrations from ICU admission to day 4 or last ICU day for patients with a shorter ICU stay (d4/LD) and association in multivariable analyses with likelihood of earlier live ICU discharge, risk of new infection, and muscle weakness. Results Late PN attenuated a rise in serum GH and IGF-I (P < 0.0001), did not affect IGFBP3, and attenuated a decrease in IGFBP1 concentrations from admission to d4/LD (P < 0.0001) as compared with early PN. Late PN decreased nonpulsatile (P = 0.005), but not pulsatile, GH secretion. Adjusting the multivariable models for the observed GH axis alterations increased the independent benefit of late PN for all outcomes. GH axis alterations induced by late PN were independently associated with adverse outcomes (P ≤ 0.03). Conclusion Accepting macronutrient deficits early during critical illness further suppressed the GH axis, which statistically attenuated its clinical outcome benefits.

Phenotypic spectrum and responses to recombinant human IGF1 (rhIGF1) therapy in patients with homozygous intronic pseudoexon growth hormone receptor mutation

Background Patients with homozygous intronic pseudoexon GH receptor (GHR) mutations (6Ψ) have growth hormone insensitivity (GHI) (growth failure, IGF1 deficiency and normal/elevated serum GH). We report 9 patients in addition to previously described 11 GHR 6Ψ patients and their responses to rhIGF1 therapy. Methods 20 patients (12 males, 11 families, mean age 4.0 ± 2.2 years) were diagnosed genetically in our centre. Phenotypic data and responses to rhIGF1 treatment were provided by referring clinicians. Continuous parametric variables were compared using Student t-test or ANOVA. Results 10/20 (50%) had typical facial features of GHI, 19/20 (95%) from consanguineous families and 18/20 (90%) of Pakistani origin. At diagnosis, mean height SDS: −4.1 ± 0.95, IGF1 SDS: −2.8 ± 1.4; IGFBP3 SDS: −3.0 ± 2.1 and mean basal and peak GH levels: 11.9 µg/L and 32.9 µg/L, respectively. 1/12 who had IGF1 generation test, responded (IGF1: 132–255 ng/mL). 15/20 (75%; 11M) received rhIGF1 (mean dose: 114 µg/kg twice daily, mean duration: 5.3 ± 2.5 years). Mean baseline height velocity of 4.7 ± 1.1 cm/year increased to 7.4 ± 1.8 cm/year (P = 0.001) during year 1 of therapy. Year 3 mean height SDS (−3.2 ± 1.0) was higher than pre-treatment height SDS (−4.3 ± 0.8) (P = 0.03). Mean cumulative increase in height SDS after year 5 was 1.4 ± 0.9. Difference between target height (TH) SDS and adult or latest height SDS was less than that of TH SDS and pre-treatment height SDS (2.1 ± 1.2 vs 3.0 ± 0.8; P = 0.02). Conclusion In addition to phenotypic heterogeneity in the cohort, there was mismatch between clinical and biochemical features in individual patients with 6Ψ GHR mutations. rhIGF1 treatment improved height outcomes.