A case of hypothalamic hypopituitarism accompanied by recurrent severe hypoglycemia

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Abstract
Introduction 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. Case description 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. Discussion and Evaluation 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. Conclusions 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.

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