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Published on: September 15, 2017
Clinical characteristics of patients with unexplainable hypothalamic disorder diagnosed by the
Yuji Hataya1, Marie Okubo2, Takuro Hakata2,3
1Department of Diabetes and Endocrinology, Kobe City Medical Center General Hospital, 2-1-1, Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. yhataya@kcho.jp.
Insights
The corticotropin-releasing hormone (CRH) challenge test identified unexplained hypothalamic disorder (HD) with HPA axis dysfunction. Some patients experienced mild central adrenal insufficiency, with hydrocortisone offering limited fatigue relief.
Area of Science:
- Endocrinology
- Neuroendocrinology
- HPA Axis Research
Background:
- The corticotropin-releasing hormone (CRH) challenge test differentiates hypothalamic from pituitary disorders.
- The pathophysiology of unexplained hypothalamic disorder (HD) remains poorly understood.
- This study investigates the clinical features of patients with unexplainable HD.
Purpose of the Study:
- To elucidate the clinical characteristics of patients diagnosed with unexplainable hypothalamic disorder (HD) using the CRH challenge test.
- To understand the hypothalamic-pituitary-adrenal (HPA) axis function in these patients.
- To explore potential therapeutic responses to hydrocortisone supplementation.
Main Methods:
- Retrospective review of patients undergoing the CRH challenge test.
- Categorization into Normal Response (NR), Unexplainable-HD, Explainable-HD, and Pituitary Disorder (PD) groups based on cortisol and ACTH levels.
- Inter-group comparison of clinical characteristics.
Main Results:
- Unexplainable-HD patients showed lower peak ACTH than NR, despite a >2-fold increase.
- Serum cortisol increases were higher in unexplainable-HD compared to explainable-HD and PD groups.
- Patients exhibited attenuated diurnal cortisol variation, low urinary free cortisol, and chronic fatigue, with partial response to hydrocortisone.
Conclusions:
- Unexplainable HD patients exhibit hypothalamic-pituitary-adrenal (HPA) axis dysfunction, with some having mild central adrenal insufficiency.
- HPA axis dysfunction may represent a physiological adaptation, as hydrocortisone only partially alleviated fatigue.
- Further research into these patients could illuminate the pathophysiology of myalgic encephalitis/chronic fatigue syndrome.
Background:
The corticotropin-releasing hormone (CRH) challenge test can distinguish the disorders of the hypothalamus from those of the pituitary. However, the pathophysiology of hypothalamic disorder (HD) has not been fully understood. This study aimed to elucidate the clinical characteristics of patients with unexplainable HD, diagnosed by the CRH challenge test.
Methods:
We retrospectively reviewed patients who underwent the CRH challenge test. Patients were categorized into four groups as follows: patients with peak serum cortisol ≥18 μg/dL were assigned to the normal response (NR) group (n = 18), among patients with peak serum cortisol < 18 μg/dL and peak adrenocorticotropic hormone (ACTH) increase ≥two-fold, patients without obvious background pathology were assigned to the unexplainable-HD group (n = 18), whereas patients with obvious background pathology were assigned to the explainable-HD group (n = 38), and patients with peak serum cortisol < 18 μg/dL and peak ACTH increase
Results:
In the CRH challenge test, the peak plasma ACTH levels were significantly lower in the unexplainable-HD group than in the NR group, despite more than two-fold increase compared to basal levels. The increase in serum cortisol was significantly higher in the unexplainable-HD group than in the explainable-HD and PD groups. Although patients in the unexplainable-HD group showed a clear ACTH response in the insulin tolerance test, some patients had peak serum cortisol levels of < 18 μg/dL. Furthermore, attenuated diurnal variations and low normal levels of urinary free cortisol were observed. Most patients in the unexplainable-HD group were young women with chronic fatigue. However, supplementation with oral hydrocortisone at physiological doses reduced fatigue only in some patients.
Conclusions:
Patients with unexplainable HD diagnosed by the CRH challenge test had hypothalamic-pituitary-adrenal (HPA) axis dysfunction and some patients had mild central adrenal insufficiency. Hydrocortisone supplementation reduced fatigue only in some patients, suggesting that HPA axis dysfunction may be a physiological adaptation. Further investigation of these patients may help elucidate the pathophysiology of myalgic encephalitis/chronic fatigue syndrome.
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