Horm Metab Res 2005; 37(4): 193-197
DOI: 10.1055/s-2005-861374
© Georg Thieme Verlag KG Stuttgart · New York

Obesity and Cortisol Status

M.  Salehi1 , A.  Ferenczi1 , B.  Zumoff1
  • 1Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, USA
Further Information

Publication History

Received 10 August 2004

Accepted after revision 18 October 2004

Publication Date:
13 June 2005 (online)


The fact, that obesity is a prominent feature of hypercortisolism (Cushing’s syndrome) has stimulated investigation on the possible existence of the reverse relationship, namely that hypercortisolism is a feature of obesity. We have reviewed half a century of literature on this question, and have found out the following: (1) Hypercortisolism can exist in two forms: systemic hypercortisolism, in which there is an overall bodily excess of cortisol, and tissue, or intracellular, hypercortisolism, in which there is increased intracellular concentration of cortisol without an overall bodily excess. (2) There are two parameters of systemic hypercortisolism: CPR and plasma cortisol concentration. Proper evaluation of the first parameter requires correction for the active metabolic mass, which is best performed by expressing CPR per gram of urinary creatinine. The second parameter can be confounded by the marked moment-to-moment fluctuations in plasma cortisol concentrations due to cortisol’s episodic secretion. Proper evaluation requires measuring the 24-hour mean concentration. Of these two parameters of systemic cortisol status, the plasma concentration is the more critical and accurate. (3) Corrected CPR is normal in obese individuals, and 24-hour mean plasma cortisol concentrations are slightly but definitely subnormal. This combination of findings indicates diminished stimulability of the hypothalamic-pituitary-adrenal (HPA) axis, which normally regulates bodily cortisol status. This deduction is supported by empirical studies on HPA reactivity. (4) Tissue hypercortisolism, due to increased intracellular activity of 11β-HSD-1, which catalyzes reduction of cortisone to cortisol, has been reported in obese mice and humans. The findings of various studies are not consistent, and whether the enzymatic overactivity is a cause or a result of obesity is still unclear.


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1 There may be some degree of adrenal insufficiency under stress in either dysthyroidism type. In hyperthyroidism, the patient may be unable to increase the already increased cortisol production any further, while in hypothyroidism, the cortisol production system is chronically suppressed and possibly unable to respond promptly to stress.

Barnett Zumoff, M.D.

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