Assessment of hypothalamic-pituitary-adrenal axis impairment and effects of hydrocortisone treatment in adults with Prader-Willi syndrome.

Nearly half of adults with Prader-Willi syndrome showed HPA axis impairment based on high dose short synacthen test results.

• 14 of 30 patients (46.7%) showed a 30-min cortisol peak <500 nmol/L and were assigned to the HPAI group.
• The study included 30 adult patients (14 men, 16 women, aged 18-28 years) with genetically confirmed PWS.
• 22 patients (73.3%) had been adequately treated with human recombinant growth hormone (rhGH).
• All patients received hormone replacement therapy due to hypogonadotropic hypogonadism.

Peak cortisol levels at both 30 and 60 minutes during HDSST were significantly lower in the HPAI group compared to the adrenal sufficiency control group.

• Peak cortisol levels at 30' and 60' were significantly lower in the HPAI group compared to the Control group (P<0.001).
• The threshold for HPA axis impairment was defined as cortisol <500 nmol/L at the 30th minute of HDSST.
• Adrenal sufficiency was defined as cortisol ≥500 nmol/L at the 30th minute.

Basal cortisol level was positively correlated with cortisol levels at both 30 and 60 minutes of the HDSST.

• Basal cortisol was positively correlated with cortisol at 30' (r = 0.872, P < 0.001).
• Basal cortisol was positively correlated with cortisol at 60' (r = 0.829, P < 0.001).

Fatigue, myalgia, and muscle weakness occurred significantly more often in patients with HPA axis impairment than in those with adrenal sufficiency.

• Fatigue occurred in 90.9% of the HPAI group vs. 20% of the Control group (P=0.01).
• Myalgia and muscle weakness occurred in 90.9% of the HPAI group vs. 0% of the Control group (P=0.001).
• Symptoms were assessed at baseline prior to any hydrocortisone treatment.

Low-dose hydrocortisone treatment significantly improved fatigue, myalgia, and muscle weakness in symptomatic patients with HPA axis impairment after 12 months.

• All symptomatic patients with HPAI received hydrocortisone treatment at 10 mg/day in two divided doses.
• Fatigue, myalgia, and muscle weakness improved significantly after 12 months of HCT therapy (P<0.001).
• Clinical symptoms were evaluated at baseline, after 6 months, and after 12 months of follow-up.

No adverse effects of hydrocortisone treatment were observed in terms of weight, body fat percentage, or metabolic parameters.

• No weight gain, body fat percentage increase, or metabolic abnormalities were observed with HCT treatment.
• Body fat percentage was measured using the electrical bioimpedance method.
• Body weight and body fat percentage were evaluated at baseline, after 6 and 12 months of follow-up.