Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-04T21:55:27.290Z Has data issue: false hasContentIssue false

Depression and Endocrine Disorders: Focus on the Thyroid and Adrenal System

Published online by Cambridge University Press:  06 August 2018

Dominique L. Musselman
Affiliation:
Emory University School of Medicine, Atlanta, Georgia, US
Charles B. Nemeroff*
Affiliation:
Emory University School of Medicine, Atlanta, Georgia, US
*
Charles B. Nemeroff, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, PO Drawer AF, 1529 Pierce Drive, Suite 4000, Atlanta, GA 30322, US

Abstract

Of the various hypothalamic–pituitary–end organ axes, the thyroid and adrenal systems have been implicated most often in affective disorders. Patients with primary thyroid disease have high rates of depression, and patients with Addison's disease or Cushing's syndrome have relatively high rates of affective and anxiety symptoms. However, the major support for these endocrine axes in the pathophysiology of mood disorders comes from studies in which alterations in components of the hypothalamic–pituitary–thyroid (HPT) and the hypothalamic–pituitary–adrenal (HPA) axes have been documented in patients with primary depression. Concerning the HPT axis, depressed patients have been reported to have: (a) alterations in thyroid-stimulating hormone response to thyrotropin-releasing hormone (TRH); (b) an abnormally high rate of antithyroid antibodies; and (c) elevated cerebrospinal fluid (CSF) TRH concentrations. Moreover, tri-iodothyronine has been shown conclusively to augment the efficacy of various antidepressants. Concerning the HPA axis, depressed patients have been reported to exhibit: (a) adrenocorticoid hypersecretion; (b) enlarged pituitary and adrenal gland size; and (c) elevated CSF corticotropin-releasing factor concentrations. All of the HPA axis alterations in depression studied thus far are state-dependent, whereas the HPT axis alterations may be partially trait and partially state markers.

Type
Research Article
Copyright
Copyright © 1996 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adinoff, B., Nemeroff, C.B., Bissette, G., et al (1991) Inverse relationship between CSF TRH concentrations and the TSH response to TRH in abstinent alcohol-dependent patients. American Journal of Psychiatry, 148, 15861588.Google ScholarPubMed
Amsterdam, J. D., Winokur, A., Abelman, E., et al (1983) Cosyntropin (ACTH) stimulation test in depressed patients and healthy subjects. American Journal of Psychiatry, 140, 907.Google Scholar
Amsterdam, J. D., Marinelli, D. L., Arger, P., et al (1987) Assessment of adrenal gland volume by computed tomography in depressed patients and healthy volunteers: a pilot study. Psychiatry Research, 21, 189197.Google Scholar
Arana, G. W., Baldesarrini, R. J. & Ornsteen, M. (1985) The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Archives of General Psychiatry, 42, 11931204.CrossRefGoogle ScholarPubMed
Arato, M., Banki, C. M., Nemeroff, C. B., et al (1986) Hypothalamic–pituitary–adrenal axis and suicide. Annals of New York Academy of Science, 487, 263270.CrossRefGoogle ScholarPubMed
Axelson, D. A., Doraiswamy, P. M, Boyko, O. B., et al (1992) In vivo assessment of pituitary volume using MRI and systematic sterology: relationship to dexamethasone suppression test results in patients with affective disorder. Psychiatry Research, 46, 6370.Google Scholar
Banki, C. M., Bissette, G., Arato, M., et al (1987) Cerebrospinal fluid corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. American Journal of Psychiatry, 144, 873877.Google Scholar
Banki, C. M., Bissette, G., Arato, M., et al (1988) Elevation of immunoreactive CSF TRH in depressed patients. American Journal of Psychiatry, 145, 15261531.Google Scholar
Banki, C. M., Karmacsi, L., Bissette, G., et al (1992) CSF corticotropin-releasing hormone and somatostatin in major depression: response to antidepressant treatment and relapse. European Neuropsychopharmacology, 2, 107113.CrossRefGoogle ScholarPubMed
Bartalena, L., Placidi, G. F., Martino, E., et al (1990) Nocturnal serum thyrotropin (TSH) surge and the TSH response to TSH-releasing hormone: dissociated behavior in untreated depressive. Journal of Clinical Endocrinology and Metabolism, 71, 650655.Google Scholar
Bissette, G., Widerlov, E., Walleus, H., et al (1986) Alterations in cerebrospinal fluid concentrations of somatostatin-like immunoreactivity in neuropsychiatric disorders. Archives of General Psychiatry, 43, 11481151.Google Scholar
Carpenter, W. & Bunney, W. (1971) Adrenal cortical activity in depressive illness. American Journal of Psychiatry, 128, 3140.CrossRefGoogle ScholarPubMed
Carroll, B. J., Martin, F. I. & Davis, B. (1968) Pituitary–adrenal function in depression. Lancet, 556, 13731374.CrossRefGoogle Scholar
DeBellis, M. D., Gold, P. W., Geracioti, T. D., et al (1993) Fluoxetine significantly reduces CSF CRH and AVP concentrations in patients with major depression. American Journal of Psychiatry, 150, 656657.Google Scholar
Duval, F., Macher, J. P. & Mokrani, M. C. (1990) Difference between evening and morning thyrotropin responses to protirelin in major depressive episode. Archives of General Psychiatry, 47, 443448.Google Scholar
Evans, D. L. & Nemeroff, C. B. (1983) Use of dexamethasone suppression test using DSM–III criteria on an inpatient psychiatric unit. Biological Psychiatry, 18, 505511.Google Scholar
Extein, I., Pottash, A. L. C. & Gold, M. S. (1981) The thyrotropin-releasing hormone test in the diagnosis of unipolar depression. Psychiatry Research, 5, 311316.CrossRefGoogle ScholarPubMed
Fava, G. A., Sonino, N. & Morphy, M. A. (1987) Major depression associated with endocrine disease. Psychiatric Developments, 5, 321348.Google Scholar
Fossey, M. D., Lydiard, R. B., Larara, M. T., et al (1990) CSF thyrotropin-releasing hormone in patients with anxiety disorders. Biological Psychiatry, 27(suppl), 167A.Google Scholar
France, R. D., Urban, B., Krishnan, K. R. R., et al (1988) CSF Corticotropin-releasing factor-like immunoreactivity in chronic pain patients with and without major depression. Biological Psychiatry, 23, 8688.CrossRefGoogle Scholar
Gibbons, J. L. & McHugh, P. R. (1962) Plasma Cortisol in depressive illness. Journal of Psychiatry Research, 1, 162171.CrossRefGoogle ScholarPubMed
Gold, M. S., Pottash, A. C. & Extein, I. (1982) Symptomless autoimmune thyroiditis in depression. Psychiatry Research, 6, 261269.CrossRefGoogle ScholarPubMed
Gold, P. W., Chrousos, G. P., Kellner, C., et al (1984) Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. American Journal of Psychiatry, 141, 619627.Google Scholar
Gold, P. W., Loriaux, D. L., Roy, A., et al (1986) Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. New England Journal of Medicine, 314, 13291334.Google Scholar
Goldstein, J., van Cauter, E., Linkowski, P., et al (1980) Thyrotropin nyctohemeral pattern in primary depression. Difference between unipolar and bipolar women. Life Science, 27, 16951703.CrossRefGoogle Scholar
Haggerty, J. J., Simon, J. S., Evans, D. L., et al (1987) Relationship of serum TSH concentration and antithyroid antibodies to diagnosis and DST response in psychiatric inpatients. American Journal of Psychiatry, 144, 14911493.Google Scholar
Haggerty, J. J., Evans, D. L., Golden, R. N., et al (1990a) The presence of anti-thyroid antibodies in patients with affective and non-affective psychiatric disorders. Biological Psychiatry, 27, 5160.Google Scholar
Haggerty, J. J., Garbutt, J. C., Simon, J. S., et al (1990b) Subclinical hypothyroidism: a review of neuropsychiatric aspects. International Journal of Psychiatric Medicine, 20, 193208.CrossRefGoogle ScholarPubMed
Holsboer, F., Haack, D., Gerken, A., et al (1984) Plasma dexamethasone concentrations and different suppression response of Cortisol and corticosterone in depressives and controls. Biological Psychiatry, 19, 281291.Google Scholar
Jaeckle, R. S., Kathol, R. G., Lopez, J. F., et al (1987) Enhanced adrenal sensitivity to exogenous ACTH stimulation in major depression. Archives of General Psychiatry, 44, 233240.Google Scholar
Joffe, R. T., Singer, W., Levitt, A. J., et al (1993) A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Archives of General Psychiatry, 50, 387394.Google Scholar
Kalin, N. H., Risch, S. C., Janowsky, D. S., et al (1982) Plasma ACTH and Cortisol concentrations before and after dexamethasone. Psychiatry Research, 7, 8792.Google Scholar
Kastin, A. J., Schalch, D. S., Ehrensing, R. H., et al (1972) Improvement in mental depression with decreased thyrotropin response after administration of thyrotropin-releasing hormone. Lancet, 2, 740742.Google Scholar
Kathol, R. G., Jaeckle, R. S., Lopez, J. R., et al (1989) Consistent reduction of ACTH responses to stimulation with CRH, vasopressin and hypoglycaemia in patients with depression. British Journal of Psychiatry, 155, 468478.Google Scholar
Kirkegaard, C. H., Faber, J., Hummer, L., et al (1979) Increased levels of TRH in cerebrospinal fluid from patients with endogenous depression. Psychoneuroendocrinology, 4, 227235.CrossRefGoogle ScholarPubMed
Kling, M. A., Rubinow, D. R., Doran, A. R., et al (1993) Cerebrospinal fluid immunoreactive somatostatin concentrations in patients with Cushing's disease and major depression: relationship to indices of corticotropin-releasing hormone and Cortisol secretion. Neuroendocrinology, 57, 7988.CrossRefGoogle ScholarPubMed
Krishnan, K. R. R., France, R. D., Pelton, S., et al (1985) What does the dexamethasone suppression test identify? Biological Psychiatry, 20, 957964.Google Scholar
Krishnan, K. R. R., Ritchie, J. C., Manepalli, A. N., et al (1988) What is the relationship between plasma ACTH and Cortisol in normal human and depressed patients. In HPA Axis: Physiology, Pathophysiology and Psychiatric Implications (eds Schatzberg, A. F. & Nemeroff, C. B.), pp. 115132. New York: Raven Press.Google Scholar
Krishnan, K. R. R., Ritchie, J. C., Saunders, W. B., et al (1990) Adrenocortical sensitivity to low dose ACTH administration in depressed patients. Biological Psychiatry, 27, 930933.CrossRefGoogle ScholarPubMed
Krishnan, K. R. R., Doraiswamy, P. M., Lurie, S. N., et al (1991) Pituitary size in depression. Journal of Clinical Endocrinology and Metabolism, 72, 256259.CrossRefGoogle ScholarPubMed
Lesem, M. D., Kaye, W. H., Bissette, G., et al (1994) Cerebrospinal fluid TRH immunoreactivity in anorexia nervosa. Biological Psychiatry, 35, 4853.Google Scholar
Linkowski, P., Mendlewicz, J., Leclerq, R., et al (1985) The 24 hour profile of ACTH and Cortisol in major depressive illness. Journal of Clinical Endocrinology and Metabolism, 61, 429438.CrossRefGoogle ScholarPubMed
Lobo, A., Perez-Echeverria, M. J., Jiminez-Aznarez, A., et al (1988) Emotional disturbances in endocrine patients. Validity of the scaled version of the General Health Questionnaire. British Journal of Psychiatry, 152, 807812.Google Scholar
Loosen, P. T., Chambliss, B., Debold, C. R., et al (1992) Psychiatric phenomenology in Cushing's disease. Pharmacopsychiatry, 25, 192198.Google Scholar
Maeda, K., Yoshimoto, Y. & Yamadori, A. (1993) Blunted TSH and unaltered PRL responses to TRH following repeated administration of TRH in neurologic patients: a replication of neuroendocrine features of major depression. Biological Psychiatry, 33, 277283.CrossRefGoogle ScholarPubMed
Nemeroff, C. B., Bissette, G., Martin, J. B., et al (1980) Effect of chronic treatment with thyrotropin-releasing hormone (TRH) or an analog of TRH (linear-β-alanine TRH) on the hypothalamic–pituitary–thyroid axis. Neuroendocrinology, 30, 193199.CrossRefGoogle ScholarPubMed
Nemeroff, C. B. & Evans, D. L. (1984) Correlation between the dexamethasone suppression test in depressed patients and clinical response. American Journal of Psychiatry, 141, 247249.Google ScholarPubMed
Nemeroff, C. B., Kalivas, P. W., Golden, R. N., et al (1984a) Behavioral effects of hypothalamic hypophysiotropic hormones, neurotensin, substance P and other neuropeptides. Pharmacological Therapies, 24, 156.Google Scholar
Nemeroff, C. B., Widerlov, E., Bissette, G., et al (1984b) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science, 226, 13421344.CrossRefGoogle ScholarPubMed
Nemeroff, C. B., Simon, J. S., Haggerty, J. J., et al (1985) Antithyroid antibodies in depressed patients. American Journal of Psychiatry, 142, 840843.Google Scholar
Nemeroff, C. B. & Evans, D. L. (1989) Thyrotropin-releasing hormone (TRH), the thyroid axis and affective disorder. Annals of the New York Academy of Sciences, 553, 304310.Google Scholar
Nemeroff, C. B., Bissette, G., Akil, H., et al (1991) Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy: corticotropin-releasing factor, beta-endorphin and somatostatin. British Journal of Psychiatry, 158, 5963.CrossRefGoogle ScholarPubMed
Nemeroff, C. B., Krishnan, K. K. R., Reed, D., et al (1992) Adrenal gland enlargement in major depression: a computed tomographic study. Archives of General Psychiatry, 49, 384387.Google Scholar
Pitts, A. F., Kathol, R. G., Gehris, T. L., et al (1990) Elevated cerebrospinal fluid corticotropin-releasing hormone and arginine vasopressin in depressed patients with dexamethasone nonsuppression. Society of Neuroscience Abstracts, 16, 454.Google Scholar
Post, R. M., Gold, P., Rubinow, D. R., et al (1982) Peptides in cerebrospinal fluid of neuropsychiatric patients: an approach to central nervous system peptide function. Life Science, 31, 115.Google Scholar
Prange, A. J., Wilson, I. C., Rabon, A. M., et al (1969) Enhancement of imipramine antidepressant activity by thyroid hormone. American Journal of Psychiatry, 126, 457469.CrossRefGoogle ScholarPubMed
Prange, A. J., Wilson, I. C., Lara, P. P., et al (1972) Effects of thyrotropin-releasing hormone in depression. Lancet, ii, 9991002.Google Scholar
Prange, A. J., Loosen, P. T., Wilson, I., et al (1980) The therapeutic use of hormones of the thyroid axis in depression. In Neurobiology of Mood Disorders (eds Post, C. R. & Ballenger, J.), pp. 311322. Baltimore: Williams & Wilkins.Google Scholar
Reus, V. I., Berlkant, J., Galante, M., et al (1986) Proceedings of the 41st Annual Meeting of the Society of Biological Psychiatry. Washington, DC.Google Scholar
Risch, S. C., Lewine, R. J., Kalin, N. H., et al (1992) Limbic–hypothalamic–pituitary–adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia. Neuropsychopharmacology, 6, 95100.Google Scholar
Roy, A., Pickar, D., Paul, S., et al (1987) CSF corticotropin-releasing hormone in depressed patients and normal control subjects. American Journal of Psychiatry, 144, 641645.Google Scholar
Roy, A., Bissette, G., Nemeroff, C. B., et al (1990) Cerebrospinal fluid thyrotropin-releasing hormone concentrations in alcoholics and normal controls. Biological Psychiatry, 28, 767772.Google Scholar
Roy, A., Wolkowitz, O. M., Bissette, G., et al (1996) Cerebrospinal fluid thyrotropin-releasing hormone concentrations in depressed patients and normal controls: a negative report. American Journal of Psychiatry, 151, 600602.Google Scholar
Rubin, R. T., Phillips, J. J., Sadow, T. F., et al (1992) Adrenal gland volume in major depression: increase during the depressive episode and decrease with successful treatment. Proceedings of the American College of Neuropsychopharmacology Annual Meeting, 90.Google Scholar
Rubinow, D. R., Gold, P. W., Post, R. M., et al (1983) CSF somatostatin in affective illness. Archives of General Psychiatry, 40, 409412.Google Scholar
Sachar, E., Hellman, L., Fukushima, D., et al (1970) Cortisol production in depressive illness. Archives of General Psychiatry, 23, 289298.CrossRefGoogle ScholarPubMed
Schatzberg, A. F., Rothschild, A. J., Bond, T. C., et al (1984) The DST in psychotic depression: diagnostic and pathophysiologic implications. Psychopharmacology Bulletin, 20, 362364.Google Scholar
Swanson, L. W., Sawchenko, P. E., Rivier, J., et al (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology, 36, 165186.Google Scholar
Vale, W., Spiess, J., Rivier, C., et al (1981) Characterization of a 41 residue ovine hypothalamic peptide that stimulates secretion of corticotropin of β-endorphin. Science, 213, 13941397.Google Scholar
Veith, R. C., Lewis, N., Langohr, J. I., et al (1992) Effect of desipramine on cerebrospinal fluid concentrations of corticotropin-releasing factor in human subjects. Psychiatry Research, 46, 18.CrossRefGoogle Scholar
Weeke, A. & Weeke, J. (1980) The 24-hour pattern of serum TSH in patients with endogenous depression. Acta Psychiatria Scandinavica, 62, 6974.Google Scholar
Young, E. A., Watson, S. J., Kotun, J., et al (1990). Betalipotropin-beta-endorphin response to low-dose ovine corticotropin releasing factor in endogenous depression. Archives of General Psychiatry, 47, 449457.CrossRefGoogle Scholar
Zis, K. D. & Zis, A. (1987) Increased adrenal weight in victims of violent suicide. American Journal of Psychiatry, 144, 12141215.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.