Guran Tulay, Guran Omer, Paketci Cem, Kipoglu Osman, Firat Irfan, Turan Serap, Atay Zeynep, Haliloglu Belma, Bereket Abdullah
Department of Pediatric Endocrinology, Faculty of Medicine, Marmara University Hospital, Fevzi Cakmak Mh.Mimar Sinan Cd.No 41., Ustkaynarca/Pendik, 34899, Istanbul, Turkey,
Pituitary. 2015 Aug;18(4):456-60. doi: 10.1007/s11102-014-0594-5.
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.
HPA function was investigated in three STWS patients to characterise consequences of impaired LIF/LIFR signalling on adrenal function.
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.
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.
STWS patients may develop central adrenal insufficiency due to impaired LIF/LIFR signalling. LIF/LIFR system plays a role in human HPA axis regulation.
施图韦-维德曼综合征（STWS）（MIM #601559）是一种罕见的常染色体隐性疾病，由白血病抑制因子受体（LIFR）基因突变引起。STWS具有涉及造血、骨骼、神经和免疫系统的多种临床特征。由于猝死风险增加，STWS的死亡率很高。LIFR的异二聚化通过细胞内Janus激酶（JAK）/STAT3信号级联介导白血病抑制因子（LIF）信号传导。LIF/LIFR系统在下丘脑-垂体-肾上腺（HPA）轴中高度表达并对其起调节作用。
对3例STWS患者的HPA功能进行研究，以明确LIF/LIFR信号受损对肾上腺功能的影响。
本研究纳入了来自4个不相关土耳其家庭的6例经基因证实的STWS患者。其中3例在2岁前发生猝死。至少在两个不同时间点通过测定清晨血清皮质醇和血浆促肾上腺皮质激素（ACTH）浓度进行基础肾上腺功能测试。对3例存活患者进行了低剂量促肾上腺皮质激素刺激试验和胰高血糖素刺激试验，以探究肾上腺功能。
所有患者均携带相同的LIFR（p.Arg692X）突变。我们年龄最大的患者在多次测量中清晨血清皮质醇和血浆ACTH水平降低。3例患者中有2例对胰高血糖素的皮质醇反应减弱（<18μg/dl），其中1例对低剂量（1μg）ACTH刺激的皮质醇反应临界值降低，符合中枢性肾上腺功能不全。
STWS患者可能由于LIF/LIFR信号受损而发生中枢性肾上腺功能不全。LIF/LIFR系统在人类HPA轴调节中起作用。
