Diminished Glucocorticoid Negative Feedback in Polydipsic Hyponatremic Schizophrenic Patients

• Published in: The journal of clinical endocrinology and metabolism 2007-02, Vol.92 (2), p.698-704
• Main Authors: Goldman, Morris B., Wood, Gordon, Goldman, Megan B., Gavin, Michelle, Paul, Stacey, Zaheer, Suhaila, Fayyaz, Ghazala, Pilla, Ramani S.
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - blood; Adult; Anti-Inflammatory Agents - administration & dosage; Antipsychotic Agents - administration & dosage; Biological and medical sciences; Butyrophenones - administration & dosage; Drinking - physiology; Endocrinopathies; Feedback, Physiological - drug effects; Feedback, Physiological - physiology; Female; Fundamental and applied biological sciences. Psychology; Glucocorticoids - blood; Hippocampus - physiology; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - blood; Hyponatremia - metabolism; Hyponatremia - physiopathology; Male; Medical sciences; Middle Aged; Schizophrenia - drug therapy; Schizophrenia - metabolism; Schizophrenia - physiopathology; Vertebrates: endocrinology; Water-Electrolyte Imbalance - metabolism; Water-Electrolyte Imbalance - physiopathology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-1131

Context: The mechanism and significance of diminished glucocorticoid negative feedback in schizophrenia is unknown but is more commonly observed in schizophrenic patients with primary polydipsia. Polydipsic patients, especially those who are also hyponatremic, exhibit other neuroendocrine abnormalities that have been linked to hippocampal pathology. Objective: The objective of the study was to determine the effect of cortisol on plasma ACTH under conditions thought to be most sensitive to hippocampal influences. Design: The design was repeated measures. Setting: The study was conducted at an inpatient clinical research center. Participants: Participants included eight polydipsic hyponatremic and eight polydipsic normonatremic as well as six schizophrenic patients without water imbalance. Eight healthy community volunteers matched for age and gender were also studied. Intervention: Metyrapone (750 mg) was administered orally at 1430 and 1900 h. Beginning at 1930 h, hydrocortisone was infused over 150 min at 0.03 mg/kg·h. Blood samples and other measures were obtained at 20-min intervals from 1850 to 2320 h. Main Outcome Measures: Plasma ACTH and cortisol were measured. Results: ACTH levels did not decline significantly during the cortisol infusion in the polydipsic hyponatremic group. For any given level of cortisol, ACTH levels were higher in the hyponatremic group. Although levels declined after cortisol in the other three groups, the decline was greatest in patients without water imbalance. Conclusions: The marked impairment in glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients is consistent with hippocampal mineralocorticoid dysfunction.