Hypopituitarism Following Tuberculous Meningitis (TBM)

The Journal of Clinical Endocrinology & Metabolism, 2007

Introduction: Overactivity of the hypothalamic-pituitary-adrenal axis through a program set by early growth patterns is hypothesized to lead to central obesity, insulin resistance, and hypertension. We therefore examined links between adrenal steroid production and birth weight, rapid early growth, and body mass index (BMI), blood pressure, waist circumference, and resistance to insulin in early childhood through the action of adrenal steroids. Methods: Timed overnight urine samples were collected in 461 children from a large representative birth cohort. In total 244 boys and 188 girls aged 8.2–8.4 yr completed the protocol. The excretion rates of individual steroids were measured to determine total androgen and cortisol metabolites. Indices of activity of 5α-androgen reduction of androgens and cortisol metabolites and 11β-hydroxy steroid dehydrogenase activity were calculated. Results: In both boys and girls, total urinary androgen and cortisol metabolites were positively related t...

Endocrinologist, 2004

We report a child with primary renal tubular alkalosis who had hypokalemia, profound hyperreninemia, and hypoaldosteronism. A 14-year-old girl presented with short stature and delayed puberty. Laboratory evaluation disclosed hypokalemia, hypochloremia, hypomagnesemia, alkalosis, hypocalciuria, and a markedly elevated rennin at 2859 ng/mL/h and a suppressed aldosterone at 2.5 ng/dL. Subsequently, as the serum potassium normalized, renin levels gradually declined (16.78 ng/mL/h) and, despite this renin reduction, aldosterone levels progressively increased (61.7 ng/dL). The patient's clinical course highlights the preeminent role of potassium, as a direct regulator of aldosterone synthesis, versus the indirect action of renin. This observation suggests potassium is by and large a major regulator of aldosterone synthesis in renal saltwasting disorders.

Medicina

Background and objectives: Intrauterine growth restriction is thought to be implicated in long-term programming of hypothalamic–pituitary–adrenal axis activity. We investigated adrenal function in adolescents born small for gestational age (SGA) in relation to their postnatal growth and cardiovascular parameters. Materials and Methods: Anthropometric parameters, blood pressure, heart rate, dehydroepiandrosterone sulfate (DHEAS), and cortisol levels were assessed in 102 adolescents aged 11–14 years followed from birth (47 SGA and 55 born appropriate for gestational age (AGA)). Results: Mean DHEAS levels were higher in SGA adolescents with catch-up growth (SGACU+), compared with AGA. Second-year height velocity and body mass index (BMI) gain during preschool years were positively related to DHEAS levels. Morning cortisol levels and systolic and diastolic blood pressure were higher in SGA adolescents without catch-up growth (SGACU−) compared with AGA. Second-year BMI gain was inversely...

Clinical Chemistry and Laboratory Medicine (CCLM), 2015

Treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be monitored by salivary androstenedione (A-dione) and 17α-hydroxyprogesterone (17OHP) levels. There are no objective criteria for setting relevant target values or data on changes of 17OHP and A-dione during monitoring.We evaluated A-dione and 17OHP levels in nearly 2000 salivary samples collected during long-term treatment of 84 paediatric patients with classic 21-hydroxylase deficiency.A-dione and 17OHP levels and its ratio 17OHP/A-dione remained constant from 4 to 11 years with no sex-related differences. During puberty, A-dione and 17OHP levels both increased, starting at earlier age in girls than in boys. The ratio 17OHP/A-dione declined. Normalised A-dione concomitant with elevated 17OHP [1.43 nmol/L (0.46–4.41) during prepuberty; 2.36 nmol/L (0.63–8.89) for boys and 1.99 nmol/L (0.32–6.98) for girls during puberty] could be obtained with overall median glucocorticoid doses of 11–15 mg/mNormalise...

American Journal of Human Biology, 2017

Objectives: Humans-and several other apes-exhibit a unique pattern of post-natal adrenal maturation; however, the causes and consequences of variation in adrenal development are not well understood. In this study, we examine developmental and age-related maturation of the adrenal gland (measured via dehydroepiandrosteronesulfate [DHEA-S]) for potential life-history associations with growth and mucosal immunity in a rural population of immune-challenged Bolivian juveniles and adolescents. Methods: Salivary DHEA-S, anthropometrics, and salivary mucosal immunity (secretory IgA [sIgA]) were measured in 171 males and females, aged 8-23. Results: Males with greater energy (i.e. fat) stores showed higher DHEA-S levels. Controlling for age and energetic condition (to control for phenotypic correlation), higher DHEA-S was associated with higher mucosal immunity (sIgA) among both males and females. Higher DHEA-S levels were positively associated with growth (i.e. height and strength) in males. Conclusions: In accordance with predictions derived from life-history theory, males with higher energy stores secrete more adrenal androgens. This suggests that adrenal maturation is costly and subject to constraints; that is, only males with sufficient reserves will invest in accelerated adrenal maturation. Further, DHEA-S appears to have a measureable influence on immunocompetence in adolescent males and females; therefore, deficits in DHEA-S may have important consequences for health and maturation during this period. Adrenal maturation is an important, but understudied component of human growth and development.

Pediatric Research, 2014

Clinical Investigation nature publishing group Background: Clinical findings in children with premature adrenarche (PA) correlate only partly with circulating levels of adrenal androgens. It is not known whether the prepubertal low circulating concentrations of testosterone (T) and dihydrotestosterone, together with those of adrenal androgens, are capable of activating the androgen receptor. Methods: This cross-sectional study was performed at a university hospital. Circulating androgen bioactivity was measured in 67 prepubertal children with clinical signs of PA and 94 control children using a novel androgen bioassay. results: Circulating androgen bioactivity was low in the PA and control children. In the subgroup of children (n = 28) with serum T concentration over the assay sensitivity (0.35 nmol/l) and a signal in the androgen bioassay, we found a positive correlation between androgen bioactivity and serum T (r = 0.50; P < 0.01) and the free androgen index (r = 0.61; P < 0.01) and a negative correlation with serum sex hormone-binding globulin concentration (r = −0.41; P < 0.05). conclusion: Peripheral metabolism of adrenal androgen precursors may be required for any androgenic effects in PA. However, the limitations in the sensitivity of the bioassay developed herein may hide some differences between the PA and control children.

Hormone Research in Paediatrics, 2011

The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth weight &lt;10 percentile). In 52 adolescent boys (17.5 years) we assessed circulating androgen levels (T, Δ4-adione, DHEAS), overnight serum cortisol profiles (every 20 min), ACTH stimulation test (250 µg i.v.) and analysis of 24-hour urinary adrenal steroid excretion. Urinary excretion of adrenal androgen and cortisol metabolites were significantly lower in the SGA compared to the AGA group. Basal morning cortisol levels were lower in adolescents born SGA compared to those born AGA (365 mmol/l, interquartile range (IQR) 284–413 vs. 445 mmol/l, IQR 377–495, p = 0.04), but overnight cortisol profiles (AUC) did not differ. The ACTH test showed equally stimulated levels of cortisol for those born...

Journal of Clinical …, 2009

Context: In some patients, PCOS may develop as a consequence of an exaggerated adrenarche during pubertal development. Objective: The aim of the study was to assess adrenal function during childhood and pubertal development in daughters of women with PCOS (PCOSd). Design: We included 98 PCOSd [64 during childhood (ages 4-8 yr) and 34 during the peripubertal period (ages 9-13 yr)] and 51 daughters of control women (Cd) [30 during childhood and 21 during the peripubertal period]. In both groups, an acute ACTH-(1-24) stimulation test (0.25 mg) and an oral glucose tolerance test were performed. Bone age and serum concentrations of cortisol, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), glucose, and insulin were determined. Results: PCOSd and Cd were similar in age and body mass index. During the peripubertal period, basal and poststimulated DHEAS concentrations were higher in PCOSd compared to Cd. Among PCOSd, 12.5% of girls in childhood and 32.4% in peripuberty presented biochemical evidence of exaggerated adrenarche. Stimulated insulin was higher in PCOSd compared to Cd during childhood (P ϭ 0.03) and peripuberty (P ϭ 0.03). An advancement of 8 months between bone and chronological age was observed in peripubertal PCOSd compared to Cd. Conclusions: In PCOSd, basal and stimulated DHEAS concentrations were higher during the onset of puberty. Around 30% of the PCOSd demonstrated an exacerbated adrenarche, which may reflect increased P450c17 activity. In addition, a modest advance in bone age was observed, probably secondary to the hyperinsulinemia and/or adrenal hyperandrogenism.

The Journal of Pediatrics, 1993

Hypothalamic-pltultary-gonadal function was evaluated In 24 prepubertal children with chronic renal failure (CRF). Among the 47 boys, 5 were receiving conservative treatment and four long-term dialysis. Another eight boys were studied 6 months to 3.3 years after renal transplantation; their ages ranged from 5 years 8 months to 45V2 years. Among the girls, two patients were receiving conservative treatment and five long-term dialysis; their ages ranged from 3V2 years to 44 years 2 months. In boys with CRF, but not in those after transplantation, mean serum follicle-stimulating hormone 60 minutes after administration of gonadotropin releasing hormone (GnRH) was lower than in 48 control prepubertal boys (mean _ SD" 2.53 ___ 4.34 vs 6.25 + 2.84 IU/L, respectively; p <0.04). Testosterone steroldogenlc capacity after 4 week of stimulation with human chorionic gonadofropin and androgen sensitivity (percentage of decrease of serum sex hormone-binding globulin 4 week after intramuscular administration of testosterone enanthate) were normal. In girls, no difference between those with CRF and a control group of 49 girls was found after intravenous administration of GnRH. However, after intramuscular administration of GnRH agonlst, serum follicle-stimulating hormone concentration was lower in girls with CRF than in control girls (p <0.02); six of seven control girls had an increase of serum estradiol to more than 55 pmol/L, whereas three of seven girls with CRF had no response, and serum follicle-stimulating hormone failed to Increase after GnRH agonist therapy in two of these patients. We conclude that hypothalamlc-pituitary function is not normal in some prepubertal boys and girls with CRF, particularly in those with low serum albumin concentrations. On the other hand, testlcular and ovarian steroidogenlc capacity Is not Impaired, and the biologic response to androgens in boys is preserved. (J PEDIArR 4993; Pubertal development is frequently delayed and often incomplete in pubertal children with chronic renal failure. Many factors are involved) -3 but the mechanism of the disturbances in hypothalamic-pituitary-gonadal function is Supported by grants from the Consejo Nacional de Investigaciones Cientificas y T6cnicas (CONICET) of Argentina, the World Health Organization, and Programa Latinoamericano de Capac-itaci6n e Investigaci6n en Reproducci6n Humana (PLACIRH).

Journal of clinical research in pediatric endocrinology, 2010

Most steroid disorders of the adrenal cortex come to clinical attention in childhood and in order to investigate these problems, there are many challenges to the laboratory which need to be appreciated to a certain extent by clinicians. The analysis of sex steroids in biological fluids from neonates, over adrenarche and puberty present challenges of specificities and concentrations often in small sample sizes. Different reference ranges are also needed for interpretations. For around 40 years, quantitative assays for the steroids and their regulatory peptide hormones have been possible using immunoassay techniques. Problems are recognised and this review aims to summarise the benefits and failings of immunoassays and introduce where tandem mass spectrometry is anticipated to meet the clinical needs for steroid analysis in paediatric endocrine investigations. It is important to keep a dialogue between clinicians and the laboratory, especially when any laboratory result does not make ...