Takai Maiko, Kaneto Hideaki, Kamei Shinji, Mune Tomoatsu, Kaku Kohei
Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192 Japan.
Springerplus. 2015 Apr 10;4:173. doi: 10.1186/s40064-015-0934-6. eCollection 2015.
Hypothalamic hypopituitarism is relatively rare cause of secondary adrenal deficiency which is often accompanied by severe hypoglycemia. Hydrocortisone replacement therapy is essential for this condition, but gastrointestinal symptom such as nausea and vomiting is not well-recognized adverse effect of hydrocortisone.
A 64-year-old-woman was referred to our hospital because of frequent severe hypoglycemia. She was diagnosed as type 2 diabetes when she was 58 years old but had not been treated since she was 60. We ruled out the possibility of exogenous administration of insulin or other anti-diabetic drugs, insulinoma and insulin autoimmune syndrome. After glucose injection, she once became conscious, but severe hypoglycemia was often observed even after that. In addition, counter-regulatory hormone levels were not increased even at the time of hypoglycemia. We conducted several hormone load tests. In corticotropin-releasing hormone (CRH) load test, excess and delayed reaction of ACTH was observed. In thyrotropin-releasing hormone (TRH) load test, TSH and prolactin were normally secreted in response to TRH. In luteinizing hormone-releasing hormone (LHRH) load test, delayed reaction of LH and FSH was observed. Based on such hormone loading tests, we diagnosed this patient as idiopathic hypothalamic hypopituitarism and consequent adrenal deficiency. We immediately intravenously injected hydrocortisone and started oral hydrocortisone therapy. However, just after taking hydrocortisone, vomiting was often observed which disturbed sufficient steroid hormone replacement, leading to recurrent hypoglycemia. Therefore, we stopped hydrocortisone and instead started an alternative treatment with prednisolone. After that, vomiting and hypoglycemia were not observed at all.
We diagnosed this subject as hypothalamic hypopituitarism mainly by the following two findings: (1) excess and delayed reaction of ACTH in CRH load test, (2) delayed reaction of LH and FSH in LHRH load test.
We should be aware of the possibility of hypothalamic hypopituitarism as a cause of recurrent severe hypoglycemia. Also, we should be aware that hydrocortisone could induce gastrointestinal symptom and that in such a case we should stop hydrocortisone and start prednisolone to sufficiently replace steroid hormone and avoid recurrent hypoglycemia.
下丘脑性垂体功能减退是继发性肾上腺皮质功能减退相对少见的病因，常伴有严重低血糖。氢化可的松替代治疗对该病症至关重要，但恶心和呕吐等胃肠道症状是氢化可的松未被充分认识的不良反应。
一名64岁女性因频繁严重低血糖被转诊至我院。她58岁时被诊断为2型糖尿病，但60岁后未再接受治疗。我们排除了外源性使用胰岛素或其他降糖药物、胰岛素瘤及胰岛素自身免疫综合征的可能性。静脉注射葡萄糖后，她曾一度清醒，但此后仍常出现严重低血糖。此外，即使在低血糖时，反向调节激素水平也未升高。我们进行了多项激素激发试验。在促肾上腺皮质激素释放激素（CRH）激发试验中，观察到促肾上腺皮质激素（ACTH）反应过度和延迟。在促甲状腺激素释放激素（TRH）激发试验中，促甲状腺激素（TSH）和催乳素对TRH反应正常分泌。在促黄体生成素释放激素（LHRH）激发试验中，观察到促黄体生成素（LH）和促卵泡生成素（FSH）反应延迟。基于这些激素激发试验，我们将该患者诊断为特发性下丘脑性垂体功能减退及随之而来的肾上腺皮质功能减退。我们立即静脉注射氢化可的松并开始口服氢化可的松治疗。然而，服用氢化可的松后不久，常出现呕吐，这干扰了足够的类固醇激素替代，导致低血糖反复发生。因此，我们停用氢化可的松，转而开始用泼尼松龙进行替代治疗。此后，未再观察到呕吐和低血糖。
我们将该患者诊断为下丘脑性垂体功能减退主要基于以下两项发现：（1）CRH激发试验中ACTH反应过度和延迟；（2）LHRH激发试验中LH和FSH反应延迟。
我们应意识到下丘脑性垂体功能减退作为反复严重低血糖病因的可能性。此外，我们应意识到氢化可的松可诱发胃肠道症状，在这种情况下，我们应停用氢化可的松并开始使用泼尼松龙，以充分替代类固醇激素并避免低血糖反复发生。
