Diminished glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients

Morris B. Goldman, Gordon Wood, Megan B. Goldman, Michelle Gavin, Stacey Paul, Suhaila Zaheer, Ghazala Fayyaz, Ramani S. Pilla

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)698-704
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number2
DOIs
StatePublished - Jan 1 2007

Fingerprint

Glucocorticoids
Hydrocortisone
Feedback
Adrenocorticotropic Hormone
Psychogenic Polydipsia
Plasmas
Metyrapone
Mineralocorticoids
Water
Pathology
Inpatients
Schizophrenia
Healthy Volunteers
Blood
Outcome Assessment (Health Care)
Research

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Goldman, Morris B. ; Wood, Gordon ; Goldman, Megan B. ; Gavin, Michelle ; Paul, Stacey ; Zaheer, Suhaila ; Fayyaz, Ghazala ; Pilla, Ramani S. / Diminished glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 2. pp. 698-704.
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Diminished glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients. / Goldman, Morris B.; Wood, Gordon; Goldman, Megan B.; Gavin, Michelle; Paul, Stacey; Zaheer, Suhaila; Fayyaz, Ghazala; Pilla, Ramani S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 2, 01.01.2007, p. 698-704.

Research output: Contribution to journalArticle

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AU - Goldman, Morris B.

AU - Wood, Gordon

AU - Goldman, Megan B.

AU - Gavin, Michelle

AU - Paul, Stacey

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AU - Pilla, Ramani S.

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N2 - 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.

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