Reference values for serum dehydroepiandrosterone-sulphate in healthy children and adolescents with emphasis on the age of adrenarche and pubarche.

OBJECTIVE: Adrenarche is a component of normal pubertal development. Recent decades have witnessed changes in the timing and tempo of puberty in different populations. We aimed to obtain normative data on dehydroepiandrosterone-sulphate (DHEA-S) secretion in healthy children and to evaluate the age of adrenarche, pubarche and the DHEA-S levels at which pubarche starts in both sexes. METHODS: Serum DHEA-S concentrations were measured in 531 healthy (291 female) Turkish children aged 1 month-18 years by an automated chemiluminescence method. Pubic hair development was evaluated. DHEA-S concentrations >108·4 nmol/l (40 µg/dl) were regarded as adrenarche. Age-related normative data were constructed. Age at adrenarche and pubarche and the DHEA-S levels at pubarche were estimated using ROC analyses. RESULTS: Serum DHEA-S levels were high in the first 6 months of life then declined below 108·4 nmol/l (40 µg/dl) with a cut-off age of 0·46 years for girls and 0·61 years for boys with 98% and 96% statistical sensitivity. Stable minimum levels were observed for the following 5 years. The cut-off age for DHEA-S levels rising above 108·4 nmol/l (40 µg/dl) was 8·0 and 7·0 years for girls for boys, respectively. DHEA-S levels at transition from Tanner stage P1 to P2 was 90·5 nmol/l (33·4 µg/dl) in girls and 118 nmol/l (43·6 µg/dl) in boys. Median (CI) DHEA-S levels were 170·7(94·8-336) and 244(119·2-357·7) nmo/l [63(35-124) and 90(44-132) µg/dl] in girls and boys, respectively, with Tanner stage P2 pubic hair. CONCLUSIONS: We established reference data of serum DHEA-S levels in a large group of children. Currently, adrenarche (DHEA-S>108·4 nmol/l) starts 1 year earlier in boys but higher DHEA-S levels are needed for transition from P1 to P2 in boys.

Effects of leukemia inhibitory receptor gene mutations on human hypothalamo-pituitary-adrenal function.

BACKGROUND: Stuve-Wiedemann syndrome (STWS) (MIM #601559) is a rare autosomal recessive disorder caused by mutations in the leukemia inhibitory factor receptor (LIFR) gene. STWS has a diverse range of clinical features involving hematopoietic, skeletal, neuronal and immune systems. STWS manifests a high mortality due to increased risk of sudden death. Heterodimerization of the LIFR mediates leukemia inhibitory factor (LIF) signalling through the intracellular Janus kinase (JAK)/STAT3 signalling cascade. The LIF/LIFR system is highly expressed in and regulates the hypothalamo-pituitary-adrenal (HPA) axis. OBJECTIVES: HPA function was investigated in three STWS patients to characterise consequences of impaired LIF/LIFR signalling on adrenal function. DESIGN: Six genetically proven STWS patients from four unrelated Turkish families were included in the study. Sudden death occurred in three before 2 years of age. Basal adrenal function tests were performed by measurement of early morning serum cortisol and plasma ACTH concentrations on at least two different occasions. Low dose synacthen stimulation test and glucagon stimulation tests were performed to explore adrenal function in three patients who survived. RESULTS: All patients carried the same LIFR (p.Arg692X) mutation. Our oldest patient had attenuated morning serum cortisol and plasma ACTH levels at repeated measurements. Two of three patients had attenuated cortisol response (<18 µg/dl) to glucagon, one of whom also had borderline cortisol response to low dose (1 µg) ACTH stimulation consistent with central adrenal insufficiency. CONCLUSIONS: STWS patients may develop central adrenal insufficiency due to impaired LIF/LIFR signalling. LIF/LIFR system plays a role in human HPA axis regulation.