Subgrouping Of The Hpa Axis Perturbations

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Throughout recently performed studies (67-70), we have been able to single out subgroups of the functional status of the HPA axis within a general population of non-cushingoid middle-aged men. The first group was characterized by a high morning cortisol peak, a normal circadian rhythm (variability) and feedback regulation (dexamethasone) along

Table 23.2 Stages of the hypothalamic-pituitary-adrenal axis status and feedback regulation with peripheral consequences


Endocrine Status

Feedback regulation

Peripheral consequences

I. Steady-state

II. Acute stress

III. Repeated stress

IV. Chronic stress

Normal High cortisol

High — Low cortisol Normal — Low GH and sex steroids Low cortisol

Low GH and sex steroids

Normal Normal

Normal — Blunted



I Accumulation of visceral fat I Glucose, fatty acids and triglycerides Visceral obesity Metabolic syndrome Elevated BP Visceral obesity Metabolic syndrome Elevated BP and HR

GH, growth hormone; BP, blood pressure; HR, heart rate.

with a brisk cortisol response to lunch. Such men are in general lean, measured as BMI and WHR, with higher values of IGF-I than average, and low total and low density lipoprotein (LDL) cholesterol as well as blood pressure.

The other group identified was characterized by the absence of a morning cortisol peak and cir-cadian rhythm, a blunted suppression of cortisol by overnight low dose dexamethasone and a poor lunch-induced cortisol response. Such men suffer from obesity with a predominance of centrally located body fat, low testosterone and IGF-I concentrations, high glucose, insulin, triglycerides, total and LDL cholesterol, blood pressures and heart rate, while high density lipoprotein cholesterol is low. These relationships are all highly statistically significant (P values < 0.001), and consistent with the current opinion about the health consequences of an abnormally functioning HPA axis (17). Such men thus have visceral obesity with metabolic syndrome, including hypercholesterolaemia and hypertension. This is in contrast to men with a normal HPA axis function, and further emphasizes the importance of the HPA axis for human health (17,67—70).

In an attempt to highlight the importance of the HPA axis in human health, we performed multidimensional scaling analyses of the anthropometric, metabolic and circulatory risk factors for CVD, type 2 diabetes and stroke (70). Under the influence of an abnormal HPA axis, as described above, all these risk factors congregate into one distinct, strongly intercorrelated cluster (70). This indicates an overriding direct control of the conventional risk factors by such HPA axis perturbations.

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