Siri Barbara, D'Alessandro Annamaria, Maiorana Arianna, Porzio Ottavia, Ravà Lucilla, Dionisi-Vici Carlo, Cappa Marco, Martinelli Diego
Division of Metabolic Diseases and Hepatology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Department of Paediatrics, Città della Salute e della Scienza, OIRM, University of Turin, 10126 Turin, Italy.
Eur J Endocrinol. 2023 Nov 8;189(5):485-494. doi: 10.1093/ejendo/lvad137.
Single Large Scale Mitochondrial DNA Deletions (SLSMDs), Pearson Syndrome (PS) and Kearns-Sayre Syndrome (KSS), are systemic diseases with multiple endocrine abnormalities. The adrenocortical function has not been systematically investigated with a few anecdotal reports of overt adrenal insufficiency (AI). The study aimed to assess the adrenocortical function in a large cohort of SLSMDs.
A retrospective monocentric longitudinal study involved a cohort of 18 SLSMDs patients. Adrenocortical function was evaluated by baseline adrenocorticotrophic hormone (ACTH) and cortisol measurements and by high- (HDT) and low-dose (LDT) ACTH stimulation tests and compared with 92 healthy controls (HC).
Baseline adrenocortical function was impaired in 39% of patients and by the end of the study, 66% of PS and 25% of KSS showed an insufficient increase after ACTH stimulation, with cortisol deficiency due to primary AI in most PS and subclinical AI in KSS. Symptomatic AI was recorded in 44% of patients. Peak cortisol levels after ACTH stimulation tests were significantly lower in patients than in HC (P < .0001), with a more reduced response to LDT vs HDT (P < .05).
Our study highlights that cortisol deficiency due to primary AI represents a relevant part of the clinical spectrum in SLSMDs, with more severe impairment in PS than in KSS. Basal and after-stimulus assessment of adrenocortical axis should be early and regularly investigated to identify any degree of adrenocortical dysfunction. The study allowed the elaboration of a diagnostic process designed for the diagnosis, treatment, and follow-up of adrenocortical abnormalities in SLSMDs.
单一大规模线粒体DNA缺失（SLSMDs）、皮尔逊综合征（PS）和卡恩斯-塞尔综合征（KSS）是伴有多种内分泌异常的全身性疾病。肾上腺皮质功能尚未得到系统研究，仅有少数关于明显肾上腺功能不全（AI）的轶事报道。本研究旨在评估一大群SLSMDs患者的肾上腺皮质功能。
一项回顾性单中心纵向研究纳入了18例SLSMDs患者。通过基础促肾上腺皮质激素（ACTH）和皮质醇测量以及高剂量（HDT）和低剂量（LDT）ACTH刺激试验评估肾上腺皮质功能，并与92名健康对照者（HC）进行比较。
39%的患者基础肾上腺皮质功能受损，到研究结束时，66%的PS患者和25%的KSS患者在ACTH刺激后升高不足，大多数PS患者因原发性AI导致皮质醇缺乏，而KSS患者为亚临床AI。44%的患者记录到有症状的AI。ACTH刺激试验后患者的皮质醇峰值水平显著低于HC（P <.0001），对LDT的反应比对HDT的反应降低更明显（P <.05）。
我们的研究强调，原发性AI导致的皮质醇缺乏是SLSMDs临床谱的一个重要组成部分，PS中的损害比KSS更严重。应尽早并定期对肾上腺皮质轴进行基础和刺激后评估，以识别任何程度的肾上腺皮质功能障碍。该研究有助于制定一个针对SLSMDs肾上腺皮质异常的诊断、治疗和随访的诊断流程。
