Obesity and Cortisol Status

Abstract

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 11beta-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.

Obesity and psychiatric disorders: Commonalities in dysregulated biological pathways and their implications for treatment

“…An altered mitochondrial energy production, particularly in skeletal muscles (Rogge, 2009), and dysregulation in the HPA axis are also observed in obese people (Duclos et al, 2001, Salehi et al, 2005. Support for neurotransmitter disturbances in obesity is obtained by findings of decreased availability of dopamine D2 receptors in the CNS of obese individuals (Wang et al, 2001, Wang et al, 2009.…”

Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism

“…1 A and B). Obesity is associated with numerous endocrine abnormalities affecting the somatotrophic, thyroid, and glucocorticoid axes (22)(23)(24). Thus, we asked whether obesity not only promotes JNK activation in the CNS, but also in the pituitary.…”

Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

“…There is support that age, gender, body mass index (BMI), and depression/anxiety can influence serum cortisol and were therefore used as covariates. 46,47 After logit analyses, BMI and age were found to be inappropriate for being used as continous variables within the logistic regression analyses and were therefore dichotomized (cutoffs 65 years and BMI 25). The HADS was treated as a continuous variable.…”