Clinic of Endocrinology, Clinical Center Serbia, Belgrade, Serbia.
Endocrine. 2011 Dec;40(3):325-31. doi: 10.1007/s12020-011-9516-8. Epub 2011 Aug 24.
In familial cases of combined pituitary hormone deficiency the most common mutations are that of Prophet of Pit 1 (PROP1) gene. PROP1 mutations are associated with deficiencies of growth hormone, thyrotropin, prolactin, and gonadotropins (follicle-stimulating hormone and luteinizing hormone), with evolving adrenocorticotropin (ACTH) deficiency in some cases. On imaging in most patients the pituitary gland is hypoplastic, but occasionally transient pituitary enlargement is found. We report a 22-year-old female initially diagnosed at age 12 with familial hypopituitarism due to PROP1 mutation, who presented with coma and respiratory arrest (acute hyponatremia). She was urgently treated in Intensive Care Unit of Emergency Center with hypertonic saline and stress doses of hydrocortisone, which resulted in the fast increase of plasma osmolality resulting in the osmotic demyelination syndrome. Simultaneously and incidentally on computed tomography scan a large sellar and suprasellar mass were reported as possible Rathke's cleft cyst or craniopharyngioma. Once the patient was stable, ACTH deficiency was documented. She remained replaced with hydrocortisone and subsequently underwent transphenoidal surgery. The removed sellar content revealed no pituitary adenoma or pituitary cells, but only an eosinophilic, colloid-like mass, and necrotic acellular debris. Her sister with hypopituitarism had an empty sella. Genetic testing in both sisters revealed the same homozygous c.150delA mutation in PROP1 gene. Here we report two sisters with the same PROP1 mutation who presented in adulthood with different pituitary morphology, one of them with a large sellar and suprasellar mass, in which transphenoidal surgery provided an extremely rare opportunity for a histopathological analysis of the sellar content. Due to the lack of endocrine care during the transition period hypocortisolism which evolved, a consequence of PROP1 mutation, was not recognized. Empirical use of hydrocortisone in the Intensive Care in our patient with life-threatening acute hyponatremia was appropriate but because glucocorticoid therapy on its own corrects hyponatremia even after stopping hypertonic saline infusion, the risk for over-correction of hyponatremia in ACTH deficiency is high.
在家族性垂体激素缺乏症病例中，最常见的突变是 Prophet of Pit 1（PROP1）基因的突变。PROP1 突变与生长激素、促甲状腺素、催乳素和促性腺激素（卵泡刺激素和黄体生成素）缺乏有关，在某些情况下会出现促肾上腺皮质激素（ACTH）缺乏的情况。在大多数患者的影像学检查中，垂体呈发育不良，但偶尔会发现短暂的垂体增大。我们报告了一位 22 岁女性，她在 12 岁时被诊断为家族性垂体功能减退症，是由于 PROP1 基因突变引起的，她因急性低钠血症导致昏迷和呼吸停止而被紧急送入急诊中心的重症监护病房。她接受了高渗盐水和氢化可的松应激剂量的紧急治疗，导致血浆渗透压迅速升高，从而导致渗透性脱髓鞘综合征。同时，在计算机断层扫描上报告了一个大的鞍上和鞍上肿块，可能是 Rathke 裂隙囊肿或颅咽管瘤。一旦患者稳定下来，就记录到了 ACTH 缺乏症。她继续接受氢化可的松替代治疗，随后接受了经蝶窦手术。切除的鞍内容物未发现垂体腺瘤或垂体细胞，只有嗜酸性、胶样物质和坏死的无细胞碎片。患有垂体功能减退症的姐姐有一个空蝶鞍。对两姐妹进行基因检测显示，PROP1 基因均存在相同的纯合 c.150delA 突变。在这里，我们报告了两位患有相同 PROP1 突变的姐妹，她们在成年期表现出不同的垂体形态，其中一位患有大的鞍上和鞍上肿块，经蝶窦手术为鞍内容物的组织病理学分析提供了一个极其罕见的机会。由于在过渡期间缺乏内分泌护理，皮质醇缺乏症（由于 PROP1 突变而发展）没有得到识别。在我们的患者中，由于危及生命的急性低钠血症，经验性使用氢化可的松在重症监护室是合适的，但由于糖皮质激素治疗本身可以纠正低钠血症，即使在停止高渗盐水输注后也是如此，因此在 ACTH 缺乏症中，低钠血症过度纠正的风险很高。
