Góralska Magdalena, Pokrzywa Agata, Stańczyk Agnieszka, Libura Maria, Bednarczuk Tomasz
Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland.
Department of Internal Medicine and Endocrinology, University Clinical Center of the Medical University of Warsaw, Warsaw, Poland.
Front Endocrinol (Lausanne). 2025 Jun 4;16:1517334. doi: 10.3389/fendo.2025.1517334. eCollection 2025.
The prevalence of hypothalamic-pituitary-adrenal impairment (HPAI) in adults with Prader Willi Syndrome (PWS) remains unclear despite its clinical relevance. The aim of our study was to assess the prevalence of HPA axis impairment in adults with PWS based on the results of the high dose short synacthen test (HDSST), as well as to analyze the effects of hydrocortisone (HCT) therapy in this population.
Retrospective analysis.
Thirty adult patients (14 men, 16 women, aged 18-28 years) with genetically confirmed PWS. Twenty-two patients (73.3%) had been adequately treated with human recombinant growth hormone (rhGH). Due to hypogonadotropic hypogonadism, all patients received hormone replacement therapy.
Physical examination included measuring height, weight and body fat percentage (using the electrical bioimpedance method). Based on HDSST results, patients were divided into two groups: with HPA axis impairment (cortisol < 500 nmol/L at 30 minute), and AS (adrenal sufficiency; cortisol ≥ 500 nmol/L at the 30 minute). Clinical symptoms of adrenal insufficiency (AI), body weight and body fat percentage were evaluated at baseline, after 6 and 12 months of follow-up.
Fourteen of the 30 patients (46.7%) showed a 30-min cortisol peak <500 nmol/L, and were assigned to the HPAI group. Peak cortisol levels at 30' and 60' were significantly lower in the HPAI group compared to the Control one, respectively (<0.001) Correlation analysis revealed that basal cortisol was positively correlated with cortisol levels at both 30' and 60' of the HDSST (r = 0.872, < 0.001 and r = 0.829, < 0.001, respectively). Fatigue, myalgia and muscle weakness occurred more often in the HPAI group than in the Control group (90.9% vs. 20%, = 0.01, 90.9% vs. 0%, =0.001, respectively). All symptomatic patients with HPAI received HCT treatment (10 mg/day) in two divided doses. Fatigue, myalgiaand muscle weakness improved significantly after 12 months of HCT therapy (P<0.001). No adverse effects of HCT treatment were observed, such as weight gain, body fat percentage increase or metabolic abnormalities.
The results of our study suggest that the HPA axis should be routinely evaluated in adult patients with PWS. Short term, low-dose HCT treatment in symptomatic patients with HPAI is safe and can reduce symptoms of fatigue, myalgia and muscle weakness. However, the benefits and adverse effects of HCT treatment in this population require confirmation in prospective, placebo-controlled randomized clinical studies.
尽管下丘脑 - 垂体 - 肾上腺功能损害（HPAI）在普拉德 - 威利综合征（PWS）成人患者中具有临床相关性，但其患病率仍不清楚。我们研究的目的是基于高剂量短程促肾上腺皮质激素试验（HDSST）结果评估PWS成人患者中HPA轴功能损害的患病率，并分析氢化可的松（HCT）治疗对该人群的影响。
回顾性分析。
30例经基因确诊的PWS成年患者（14例男性，16例女性，年龄18 - 28岁）。22例患者（73.3%）接受了充分的重组人生长激素（rhGH）治疗。由于促性腺激素缺乏性性腺功能减退，所有患者均接受了激素替代治疗。
体格检查包括测量身高、体重和体脂百分比（采用生物电阻抗法）。根据HDSST结果，患者分为两组：HPA轴功能损害组（30分钟时皮质醇<500 nmol/L）和肾上腺功能正常组（AS，30分钟时皮质醇≥500 nmol/L）。在基线、随访6个月和12个月时评估肾上腺皮质功能减退（AI）的临床症状、体重和体脂百分比。
30例患者中有14例（46.7%）30分钟时皮质醇峰值<500 nmol/L，被归入HPAI组。HPAI组30分钟和60分钟时的皮质醇峰值分别显著低于对照组（<0.001）。相关性分析显示，基础皮质醇与HDSST 30分钟和60分钟时的皮质醇水平呈正相关（r分别为0.872，<0.001和r = 0.829，<0.001）。HPAI组疲劳、肌痛和肌肉无力的发生率高于对照组（分别为90.9%对20%，P = 0.01；90.9%对0%，P = 0.001）。所有有症状的HPAI患者均接受HCT治疗（10 mg/天，分两次给药）。HCT治疗12个月后，疲劳、肌痛和肌肉无力明显改善（P<0.001）。未观察到HCT治疗的不良反应，如体重增加、体脂百分比升高或代谢异常。
我们的研究结果表明，对于PWS成年患者应常规评估HPA轴。对有症状的HPAI患者进行短期、低剂量HCT治疗是安全的，可减轻疲劳、肌痛和肌肉无力症状。然而，HCT治疗对该人群的益处和不良反应需要在前瞻性、安慰剂对照的随机临床研究中得到证实。
