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Evaluation of the hypothalamic hypophyseal adrenal axis in patients receiving long-term hemodialysis
Insights
Patients with chronic renal failure exhibit impaired gastrointestinal absorption of dexamethasone, leading to abnormal suppression test results. This absorption issue, not a hypothalamic-pituitary-adrenal axis defect, affects hormone regulation.
Area of Science:
- Endocrinology
- Nephrology
- Pharmacology
Background:
- Chronic renal failure (CRF) can alter hypothalamic-pituitary regulation of various hormones.
- The hypothalamic-pituitary-adrenal (HPA) axis function in CRF patients requires further elucidation, particularly regarding exogenous steroid absorption and metabolism.
Purpose of the Study:
- To investigate the hypothalamic-pituitary-adrenal axis function in patients with chronic renal failure.
- To determine the cause of abnormal dexamethasone suppression test results in CRF patients.
Main Methods:
- Assessed HPA axis function using dexamethasone suppression tests (1 mg and 3 mg oral doses), metyrapone tests, and corticotropin stimulation tests.
- Measured plasma cortisol and adrenocorticotropic hormone (ACTH) levels following insulin-induced hypoglycemia.
- Evaluated dexamethasone pharmacokinetics, including blood levels, metabolic clearance, and oral absorption in CRF patients compared to controls.
Main Results:
- CRF patients showed normal plasma cortisol levels and normal responses to metyrapone and corticotropin stimulation tests.
- Abnormal dexamethasone suppression occurred with a 1 mg dose, but normalized with a 3 mg dose.
- Dexamethasone blood levels were lower in CRF patients, despite normal metabolic clearance and half-life, indicating poor oral absorption.
Conclusions:
- The abnormal dexamethasone suppression test in CRF patients is primarily due to impaired gastrointestinal absorption of the drug.
- The hypothalamic-pituitary-adrenal axis itself appears functionally intact in these patients.
- CRF necessitates careful consideration of drug absorption when interpreting endocrine test results.
Abstract:
Several alterations are present in the hypothalamic hypophyseal regulation of many hormones in patients with chronic renal failure. Evaluation of the hypothalamic hypophyseal adrenal axis in these groups of patients demonstrated normal levels of plasma cortisol. Dexamethasone suppression is abnormal after administration of 1 mg of oral dexamethasone, but normal after 3 mg. Dexamethasone blood levels were lower than the control after administration of 1 mg of oral dexamethasone. A dexamethasone metabolic clearance showed a similar half-life between the patients and controls. Oral absorption study showed poor absorption of the drug. Therefore, there is a problem of gastrointestinal absorption producing the abnormal dexamethasone suppression test in patients with renal failure. Results of metyrapone tests were normal. Corticotropin stimulation tests elicited a normal response. Insulin-induced hypoglycemia does not produce an increment in plasma cortisol or adrenocorticotropic hormone levels.