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Thyroid and adrenal axis in major depression: a controlled study in outpatients

Departments of Endocrinology and Metabolism, ¹ Psychiatry, ² Clinical Chemistry and ³ Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands and ⁴ Department of Psychiatry, Free University, Amsterdam, The Netherlands

(Correspondence should be addressed to J P Brouwer, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Email: j.p.brouwer{at}amc.uva.nl)

Objective: Major depressive disorder has been associated with changes in the hypothalamus–pituitary–thyroid (HPT) axis and with hypercortisolism. However, the changes reported have been at variance, probably related to in- or outpatient status, the use of antidepressant medication and the heterogeneity of depression. We therefore conducted a controlled study in unipolar depressed outpatients who had been free of antidepressants for at least 3 months.

Design: We assessed endocrine parameters in 113 depressed outpatients and in 113 sex- and age-matched controls.

Methods: Patients were included if they had a major depression according to a Structural Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM), fourth edition (SCID-IV) and if they had a 17-item Hamilton rating scale for depression (HRSD) score of 16. Endocrine parameters contained serum concentrations of TSH, (free) thyroxine, tri-iodothyronine, cortisol, thyroid peroxidase (TPO) antibody titre and 24-h urinary excretion of cortisol.

Results: The serum concentration of TSH was slightly higher in depressed patients as compared with controls (P < 0.001), independent of the presence of subclinical hypothyroidism and/or TPO antibodies (n = 28). All other HPT axis parameters were similar in both groups. The 24-h urinary cortisol excretion was similar in patients and controls. In atypical depression, serum cortisol was lower than in non-atypical depression (P = 0.01). Patients with neither melancholic depression nor severe depression (HRSD 23) had altered endocrine parameters. Finally, serum TSH values could not be related to cortisol values.

Conclusion: When compared with matched control subjects, outpatients with major depression had slightly higher serum TSH, while urinary cortisol levels were similar. Furthermore, we observed lower serum cortisol in atypical depression than in non-atypical depression.

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