Hormone Reserve Research Articles

Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

Intercellular contacts affect secretion and biosynthesis of pancreatic islet cells.

Cell protein biosynthesis is regulated by different factors, but implication of intercellular contacts on alpha and beta cell protein biosyntheses activity has not been yet investigated. Islet cell biosynthetic activity is essential in regulating not only the hormonal reserve within cells but also in renewing all the proteins involved in the control of secretion. Here we aimed to assess whether intercellular interactions affected similarly secretion and protein biosynthesis of rat alpha and beta cells. Insulin and glucagon secretion were analyzed by ELISA or reverse hemolytic plaque assay, and protein biosynthesis evaluated at single cell level using bioorthogonal noncanonical amino acid tagging. Regarding beta cells, we showed a positive correlation between insulin secretion and protein biosynthesis. We also observed that homologous contacts increased both activities at low or moderate glucose concentrations. By contrast, at high glucose concentration, homologous contacts increased insulin secretion and not protein biosynthesis. In addition, heterogeneous contacts between beta and alpha cells had no impact on insulin secretion and protein biosynthesis. Regarding alpha cells, we showed that when they were in contact with beta cells, they increased their glucagon secretion in response to a drop of glucose concentration, but, on the other hand, they decreased their protein biosynthesis under any glucose concentrations. Altogether, these results emphasize the role of intercellular contacts on the function of islet cells, showing that intercellular contacts increased protein biosynthesis in beta cells, except at high glucose, and decreased protein biosynthesis in alpha cells even when glucagon secretion is stimulated.

Use of Triggers on in vitro Fertilization and Evaluation of Risk Factors for Sub-Optimal Maturation Rate.

To compare the oocyte maturation rate in the treatment of in vitro fertilization (IVF) in terms of the use of human chorionic gonadotropin (hCG), agonist gonadotropin-releasing hormone (GnRH) and dual trigger and to evaluate the associated risk factors for sub-optimal maturation rates. A retrospective cohort study with 856 women who underwent IVF. They performed oocyte retrieval and were classified into 3 groups (1 - hCG, 2 - GnRH agonist, 3 - dual trigger). The primary outcome was maturation rate per trigger, and the secondary outcomes were the pregnancy rate per oocyte retrieval and the correlations between low maturation rate as well as the clinical and treatment characteristics of women. The maturation rate was 77% in group 1; 76% in group 2, and 83% in group 3 (p = 0.003). Group 2 showed women with better ovarian reserve, greater number of oocytes collected, and more mature oocytes and embryos compared with the other groups (p < 0.001). The cumulative clinical pregnancy rate was no different between the groups (p = 0.755). Low ovarian reserve and low doses of follicle-stimulating hormone (FSH) administered during the stimulus were associated with a higher chance of null maturation rate. The oocyte maturation rates and IVF results were similar in all groups. Low ovarian reserve is associated with the worst treatment results.

Early postnatal cold imprinting influence on the adult rats’ adrenal medulla functional state

The article describes the cold imprinting modifying effect on the adrenomedullary cells functional state in adult animals. It has been shown that short-term cold exposure in early ontogenesis leads to an increase in norepinephrine reserves in the adult rats’ adrenal glands. With these animals test cooling, the phenylethanolamine-N-methyltransferase activity in the adrenal glands decreases, thereby preserving the hormone reserves, which is the thermogenesis dominant activator in the mammalian body.

Biochemical Markers of Ovarian Reserve in Females, Effect of Exercise on Such Reserves

Background: Female who are in fertile period of their life and prefer a sedentary life style rather than performing regular physical exercise, whether light or heavy exercise show different hormonal pattern which effect their physical health. Such hormonal changes are directly related to the level of ovarian reserve of hormones which are negatively affected by lack of exercise. The ovarian pool of hormones decline with age and also lack of physical exercise. Among the large pool of biochemical markers AMH (anti-mullerian hormone) appears to be the most important and helpful indicator of ovarian reserve. Inclusion criteria: Healthy females between 25 to 35 years of age were included in the study. Exclusion criteria: Females below 25 years and above 35 years of age were excluded from the study, in addition those females having some medical problem or using some medication were also excluded from the study. Material and Methods: 20 females consented to participate in the study who were divided in two groups. These females were living a sedentary life before they joined the gymnasium. One group was subjected to light aerobic exercise and other group to heavy physical exercise. Tests before the start of study were conducted and were repeated after 08 weeks of study to observe the effect of both exercises on the ovarian reserves of different hormones. Results: The comparison between both groups were observed, the values before and after exercise has a remarkable difference, a decrease in values were observed in body weight, BMI, waist and hip ratio after exercise. Slight reduction in E2 and FSH level after aerobic exercises was observed. Whereas in heavy exercise group significant difference i.e. increase in level of FSH was observed at the same time, significant decrease in AMH level was also observed. The difference between E2 and LH had no significance in heavy exercise group. Conclusion: Those females who were living sedentary life and performed light aerobic exercise, even for a longer time period did not showed significant change in the E2, LH, FSH and AMH level of hormones. However, heavy exercise reduces the level of AMH and increases the level of FSH. These finding suggest heavy exercise may affect fertility in a negative way especially in females with low ovarian reserves. Keywords: Exercise, spinning, ovarian reserve, AMHh anti-mullerian hormone

Associations between thyroid-stimulating hormone and hypertension according to thyroid cyst status in the general population: a cross-sectional study

BackgroundThe absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status.MethodsWe conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40–74 years who participated in an annual health checkup in 2014.ResultsIn the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = − 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = − 0.03, p = 0.525).ConclusionsTSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.

Accelerated Renal Atherosclerosis in Congenital Nephrotic Syndrome: A Silent Fatal Inevitable Event

Accelerated atherosclerosis and thrombosis can be common, rapid evolving as short as two years in consequence of severe proteinuria in infancy who had low reserve of thyroid hormone and hyperlipidemia. This case report recommends and insist on aggressive treatment of hypothyroidism and hyperlipidemia besides to albumin infusion and folic acid to prevent hyperhomocysteinemia due to hypothyroidism side effect. This case was an evidence that imbalance of serum albumin level as a porter of lipids and LDL level can be a predisposing factor for accelerated atherosclerosis in other organs needs to more investigation for approve.

Prevalence of Anterior Pituitary Dysfunction Twelve Months or More following Traumatic Brain Injury in Adults: A Systematic Review and Meta-Analysis.

The objective of this study is to systematically review clinical studies that have reported on the prevalence of chronic post-traumatic brain injury anterior pituitary dysfunction (PTPD) 12 months or more following traumatic brain injury (TBI). We searched Medline, Embase, and PubMed up to April 2017 and consulted bibliographies of narrative reviews. We included cohort, case-control, and cross-sectional studies enrolling at least five adults with primary TBI in whom at least one anterior pituitary axis was assessed at least 12 months following TBI. We excluded studies in which other brain injuries were indistinguishable from TBI. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) score. We also considered studies that determined growth hormone deficiency and adrenocorticotrophic hormone reserve using provocation test to be at low risk of bias. Data were extracted by four independent reviewers and assessed for risk of bias using a data extraction form. We performed meta-analyses using random effect models and assessed heterogeneity using the I2 index. We identified 58 publications, of which 29 (2756 participants) were selected for meta-analysis. Twelve of these were deemed to be at low risk of bias and therefore "high-quality," as they had NOS scores greater than 8 and had used provocation tests. The overall prevalence of at least one anterior pituitary hormone dysfunction for all 29 studies was 32% (95% confidence interval [CI] 25-38%). The overall prevalence in the 12 high-quality studies was 34% (95% CI 27-42%). We observed significant heterogeneity that was not solely explained by the risk of bias. Studies with a higher proportion of participants with mild TBI had a lower prevalence of PTPD. Our results show that approximately one-third of TBI sufferers have persistent anterior pituitary dysfunction 12 months or more following trauma. Future research on PTPD should differentiate between mild and moderate/severe TBI.

Models and Tools for Studying Enteroendocrine Cells.

Gut hormones produced by gastrointestinal enteroendocrine cells modulate key physiological processes including glucose homeostasis and food intake, making them potential therapeutic candidates to treat obesity and diabetes. Understanding the function of enteroendocrine cells and the molecular mechanisms driving hormone production is a key step toward mobilizing endogenous hormone reserves in the gut as a therapeutic strategy. In this review, we will discuss the variety of ex vivo and in vitro model systems driving this research and their contributions to our current understanding of nutrient-sensing mechanisms in enteroendocrine cells.

Serum Free Cortisol During Glucagon Stimulation Test In Healthy Short-Statured Children And Adolescents

The total cortisol (TC) response may be measured during the glucagon stimulation test (GST) for growth hormone (GH) reserve in order to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements of TC are unreliable in conditions of albumin and cortisol-binding globulin (CBG) alterations (e.g., hypoproteinemia or CBG deficiency). We aimed to measure the serum free cortisol (sFC) response to the GST in children and adolescents and determine whether it could predict the GH response to glucagon stimulation. Infants and children with either short stature or growth attenuation who were referred for evaluation of GH reserve underwent the GST. The study population consisted of 103 subjects (62 females), median age 3.9 years (range, 0.5-14). The mean basal and peak TC levels were 13.3 ± 6.7 μg/dL and 29.6 ± 8.8 μg/dL, respectively. The mean basal and peak sFC levels were 0.7 ± 0.8 μg/dL and 1.7 ± 1.1 μg/dL, respectively. There was a negative correlation between peak TC and age ( r = -0.3, P = .007) but not between peak sFC and age ( r = -0.09, P = .36). Ninety-five percent of the patients had peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL. Our results on a cohort of healthy short-statured children can serve as reference values for the sFC response during GST. Based on these results, we propose peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL for defining normalcy of the HPA axis during the GST in children and adolescents. ACTH = adrenocorticotrophic hormone BMI = body mass index CBG = cortisol-binding globulin GH = growth hormone GST = glucagon stimulation test HPA = hypothalamic-pituitary-adrenal SDS = standard deviation score sFC = serum free cortisol TC = total cortisol.

Impact of Ferritin Load on Gonadal Reserve among Regular Transfused β-Thalassemia

Background: Iron overload in association with persistent anemia is responsible for endocrine dysfunction in β-thalassemia patients, blood transfusion combined with iron-chelation can modify life quality in these children, but they tend to suffer from delayed maturity and endocrine dysfunction. Aim: This study aims to correlate degree of hypogonadism to ferritin load in regular transfused β-thalassemia patients. Methods: It was carried out on 30 β-thalassemia major (TM) patients aged 12 to 18 years, puberty was assessed clinically, blood picture on Cell-Dyne 2700, ferritin level and pattern of FSH, LH, testosterone and estradiol before and after gonadotropin (GnRH) analogue stimulation test, they were determined on ARCHITECT ABBOTT system. Results: Twenty patients had not yet achieved puberty, FSH level was 1.45 ± 1.88 mIU/ml before (GnRH) analogue and 3.78 ± 4.19 mIU/ml after 4 hours of injection. LH level was 1.91 ± 4.79 mIU/ml before (GnRH) test, while after 4 hours it was 6.52 ± 7.50 mIU/ml, 88.24% of males had low serum testosterone level, 84.6% of girls had low serum estradiol level, FSH, LH, estradiol, testosterone before and after GNRH analogue were statistically insignificant, mean ferritin level was 3344.32 ± 1142.142 ng/ml, with insignificant correlation to hormonal pattern before and after GnRH therapy. Conclusion: Iron overload and hypogonadism are the presenting data in this study, insignificant correlation between ferritin level and hormonal reserve pattern, there may be another etiology in pathophysiology of low gonadal reserve such as severe anemia, chronic disease and may be genetic predisposition underlying susceptibility to iron toxicity, which need further investigations.

GP3-3: The diagnostic accuracy of pegvisomant-primed glucagon stimulation test (PV-GST) compared to insulin tolerance (ITT) and glucagon stimulation (GST) tests in evaluating adult growth hormone (GH) reserve

GP3-3: The diagnostic accuracy of pegvisomant-primed glucagon stimulation test (PV-GST) compared to insulin tolerance (ITT) and glucagon stimulation (GST) tests in evaluating adult growth hormone (GH) reserve

Evaluation of ovarian reserve and function in female patients treated with oral isotretinoin for severe acne: an exploratory study

Background: Isotretinoin affects the levels of female hormones and ovaries in patients with severe acne.Objective: This study evaluated the effects of isotretinoin on the ovarian reserve and levels of female hormones in patients with severe acne.Methods: Thirty-two female patients with severe acne were enrolled. All the patients were treated with oral isotretinoin 0.5–2 mg/kg/d. The total cumulative dose for a full course was 120–135 mg/kg. The treatment duration ranged from 5 to 8 months. The serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and antral follicle count (AFC) and ovarian volume (OV) were evaluated before and after treatment.Results: After treatment, the mean FSH, LH, and E2 levels were significantly lower than before treatment. In addition, the mean AFC and OV decreased after treatment, although the difference was not significant.Conclusion: The results of this exploratory study do not demonstrate that oral isotretinoin has an impact in ovarian function. In contrast, isotretinoin affects levels of female hormones in patients with severe acne.

Embryonic exposure to excess thyroid hormone causes thyrotrope cell death

Central congenital hypothyroidism (CCH) is more prevalent in children born to women with hyperthyroidism during pregnancy, suggesting a role for thyroid hormone (TH) in the development of central thyroid regulation. Using the zebrafish embryo as a model for thyroid axis development, we have characterized the ontogeny of negative feedback regulation of thyrotrope function and examined the effect of excess TH on thyrotrope development. We found that thyroid-stimulating hormone β subunit (tshb) and type 2 deiodinase (dio2) are coexpressed in zebrafish thyrotropes by 48 hours after fertilization and that TH-driven negative feedback regulation of tshb transcription appears in the thyroid axis by 96 hours after fertilization. Negative feedback regulation correlated with increased systemic TH levels from the developing thyroid follicles. We used a transgenic zebrafish that expresses GFP under the control of the tshb promoter to follow thyrotrope fates in vivo. Time-lapse imaging revealed that early exposure to elevated TH leads to thyrotrope cell death. Thyrotrope numbers slowly recovered following the removal of excess TH. These data demonstrate that transient TH exposure profoundly impacts the thyrotrope population during a critical period of pituitary development and may have long-term implications for the functional reserve of thyroid-stimulating hormone (TSH) production and the TSH set point later in life.

Insulin Administration Acutely Decreases Vaspin Serum Concentrations in Humans

It has been hypothesized that insulin might mediate meal-related diurnal variation in vaspin serum concentrations. We therefore investigated whether insulin affects serum vaspin levels in humans. Vaspin serum concentrations were determined by ELISA in 10 healthy individuals, who underwent an insulin tolerance test (ITT) for the evaluation of pituitary ACTH and growth hormone reserve. The ITTs were started 08:00 am after an overnight fast with a bolus i.v. insulin dose of 0.15 IU/kg body weight (Actrapid™). Blood samples were taken at -15, 0, 15, 30, 60, 90, and 120 min after insulin administration. 15 min after insulin administration, vaspin serum concentrations decreased by 19 ± 6%, continued to decrease by 42 ± 12% at 60 min and returned to 88 ± 7% of initial values 120 min after insulin administration. Our data suggest that meal-related changes in serum vaspin concentrations might be mediated by insulin.

A Case of Central Diabetes Insipidus: Evaluation in Pregnancy

A 20 years old woman, admitted in our Centre at the 6th week of pregnancy, was affected by Central Diabetes Insipidus and since the age of 10 years old she assumed desmopressin at a dose of 30mg/nostril/day. She was primigravida, with normal past medical history. Fasting blood levels were normal; specific gravity of the urine: 1006; no glucosuria or proteinuria was present. Urinary and plasma osmolality were 245 and 287 mOsm/l; water intake about 2700mL/day; diuresis 2000mL/day. On the basis of the value of urine output and osmolality the dose of desmopressin was Increased at 40 mg/nostril/day. Patient was evaluated every month with fluid balance, urine volume, osmolality, and serum electrolytes. Daily dosage of desmopressin was 40mg/nostril for all the duration of pregnancy according to a trend of an adequate fluid and electrolytes balance and in absence of symptoms. Mean blood Pressure was 100/60 mmHg; coagulation, liver, renal function were normal. Fetal monitoring with periodic ultrasound detected a normal intrauterine growth. Patient had an uncomplicated labor of a healthy male baby at the 39th week. Because of an insufficient dilatation of the cervical canal caesarian section was chosen. Despite a previous Central Diabetes Insipidus may worsen in a pregnant with impaired reserve of Antidiuretic Hormone because of the changes in osmoregulatory system and increased levels of vasopressinasis in middle and late pregnancy, our patient required a slightly higher dose of desmopressin in the first trimester. Contrary to expectations the need of desmopressin did not increase during the weeks.

Fatigue after traumatic brain injury: Association with neuroendocrine, sleep, depression and other factors

Objective: Define associations between post-traumatic brain injury (TBI) fatigue and abnormalities in neuroendocrine axes, sleep, mood, cognition and physical functioning.Design: Survey.Setting: Large community hospital-based rehabilitation centre.Participants: Convenience sample of 119 individuals at least 1 year post-TBI.Outcome measures: Multidimensional Assessment of Fatigue (MAF); Fatigue Severity Scale (FSS); neuroendocrine assessments–growth hormone (GH) reserve, thyroid, cortisol and testosterone levels; visual analogue pain rating; Pittsburgh Sleep Quality Index; Beck Depression Inventory–II; Disability Rating Scale; Craig Handicap Assessment and Reporting Technique; Neurobehavioural Functioning Inventory.Results: Fifty-three per cent reported fatigue on the MAF and one-third on the FSS; 65% were found to have moderate/severe GH deficiency; 64% had adrenal insufficiency (low fasting cortisol); 12% had central hypothyroidism; and 15% of men had testosterone deficiency. Pituitary dysfunction did not correlate with fatigue or other symptoms. Predictors of MAF total scores were female gender, depression, pain and self-assessed memory deficits. Predictors of FSS scores were depression, self-assessed motor deficits and anti-depressant usage.Conclusions: Robust correlates of fatigue were gender, depression, pain and memory and motor dysfunction. Investigation of post-TBI fatigue should include screening for depression, pain and sleep disturbance. There was no correlation between pituitary dysfunction and fatigue; however, the relatively high prevalence of hypothyroidism and adrenal dysfunction suggests screening for these hormone deficiencies.

De l'importance de l'activité physique dans la prévention du cancer du sein

The positive role of physical activity on the risk of breast cancer is a reality, supported by many epidemiologic case-control and cohort studies as well as biological mechanisms. Analysis of literature tends to show a benefit on breast cancer, in primary prevention as well as in tertiary prevention, with a moderate physical activity of three hours, or more, per week. This benefit is real for all women (even with overweight, family history or nulliparity), whatever the type of physical activity, but it has to be regular during all the life. The benefit is linked to the degree of total energy expense per week. Physical activity has a direct action mainly on three levels, the metabolism of sexual steroids, the sensitivity to insulin, and the immunizing pathways and an indirect action through the fatty mass, which is an hormonal reserve. Promoting a regular physical activity among women, with guidelines and explanations remains a necessity in public health care.

Pseudohypogonadism: defective masculinization in a subject with normal FSH, ICSH and testosterone secretion.

A 19-year old male is presented with clinical signs of hypoandrogenism but normal excretion of FSH, ICSH and testosterone. In addition, the Clomiphene stimulation test had revealed a normal hormonal reserve. Cariotypes taken from blood and skin ruled out mosaicism as a possible cause. These findings and the absence of response to exogenous testosterone suggested peripheral resistance to androgen. The name "pseudo-hypogonadism" is again suggested for this rare condition in which defective masculinization is at variance with the hormonal studies which are normal.

Analysis of the hypothalamus in a case of X-linked lissencephaly with abnormal genitalia (XLAG)

X-linked lissencephaly with abnormal genitalia (XLAG) is characterized by lissencephaly, absent corpus callosum and ambiguous genitalia. We examined hypothalamic dysfunctions in a XLAG case with a novel mutation of the ARX gene, and performed immunohistochemical evaluation of the diencephalons in autopsy brain. A 1-year-old boy showed intractable epilepsy, persistent diarrhea and disturbed temperature regulation. This case had abnormalities in circadian rhythms and pituitary hormone reserve test. He died of pneumonia. The globus pallidus and subthalamic nucleus was not identified, and the putamen and thalamus were dysplasic. The suprachiasmatic nucleus was absent. A few neurons immunoreactive for vasopressin seemed to form the ectopic supraoptic-like nucleus. The diencephalons were disturbed differently in each sub-region, and the changes may be related to various hypothalamic dysfunctions.