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One component of normal or pathophysiological neuroregulation of food intake involves histaminergic activity in the central nervous system, as influenced by concentrations and bioperiodicities of histamine and/or histamine receptors. This review examines possible relationships between anorexia, dietary intake and central nervous system histaminergic activity.

Low protein quality or quantity diets elevate both central histamine and histamine receptors (H1) in rats while significantly decreasing their food intake. When injected with histaminergic antagonists, rats fed low protein diets increase food intake and have improved efficiency of weight gain.

This review supports a dual hypotheses: central histaminergic activity is involved in the regulation of food intake, but food intake patterns (including dietary composition or energy content) can modify central histaminergic activity. This review also suggests that modified histamine and/or H1 receptor concentrations are potential mechanisms for elevated central histaminergic activity in food intake-related pathophysiological states.

Thus, dietary interventions (clinically- or self-imposed) which modify food intake or diet composition have the potential of affecting the histaminergic system. Also, drugs with antihistaminergic properties have the potential of affecting food intake/weight gain patterns by interfering with normal neurochemical signals.

Mercer LP et al., Dietary induced anorexia: a review of involvement of the histaminergic system. J Am Coll Nutr, 1996 Jun, 15:3, 223-30.

Early Life

Early Life

Close relationships exist between patterns of intra-uterine growth and the risk of ischaemic heart disease, hypertension, diabetes, insulin-resistance syndrome, obesity and some cancers later in life. Earlier studies placed emphasis on low birth weight and reduced growth, but it is now clear that disproportions in early growth are of great importance. Disproportion may be identified as disproportions of fetal and placental growth (and the risk of high blood pressure), or in head circumference, length and weight.

It is hypothesized that the availability of nutrients at different times during gestation, by interacting with the maternal and fetal hormonal profile, predisposes to different patterns of growth. The same interaction programmes critical metabolic functions and determines the metabolic capacity at all later ages. People who were exposed to severe undernutrition during the Dutch hunger winter showed increased adiposity if the exposure was during early pregnancy, but decreased adiposity if the exposure was during late pregnancy.

In men born in the UK, those with evidence of retarded fetal growth had significantly greater waist/hip circumference ratios for any given body mass index (the ratio fell with increasing weight at one year of age). In Mexican-Americans and non-Hispanic Caucasian Americans, people in the lowest third of birth weight had more truncal fat than those in the highest third.

Studies in rats suggest that programming of the hypothalamus, especially the hypothalamic-pituitary-adrenal axis might be the mechanism through which these changes are brought about.

Jackson AA et al., Nutritional influences in early life upon obesity and body proportions. Ciba Found Symp, 1996, 201:, 118-29; discussion 129-37, 188-93.

Hypertension (Adrenal Disorders)


Abnormalities of "adrenal" cortical and medullary function are important causes of "hypertension" in adults. Mineralocorticoid hypertension, characterized by spontaneous "hypokalemia" with excessive kaliuresis and low plasma renin activity, is most commonly caused by "aldosterone"-producing "adenoma" or, less frequently, by nonadenomatous adrenal "hyperplasia".

Pheochromocytomas are most commonly located in the adrenal medulla, where they may overproduce "norepinephrine" or "epinephrine".

Blumenfeld-JD: Hypertension and adrenal disorders. Curr. Opin. Nephrol. Hypertens. 1993 Mar; 2(2): 274-82.

Menopause & Adrenal Disorders


The impact of the menopause on androgen production is poorly understood. We have investigated the impact of the menopause, as well as other factors such as age, body mass index (BMI) and cigarette smoking, on ovarian and adrenal androgen levels in women aged 40-60 years.

The following variables were assessed; menopausal status (based on menstrual history and pattern and plasma progesterone), age, BMI, smoking, oestradiol (E2), oestrone (E1), LH, FSH, total testosterone (TT), androstenedione (A), SHBG, free androgen index (FAI), dihydroepiandrosterone (DHEA), dihydroepiandrosterone sulphate (DHEAS) and cortisol.

TT was positively related to A, BMI and LH. A was negatively related to age and FSH, and positively to DHEA, DHEAS and premenopausal status. SHBG was negatively related to BMI and positively to E1 and non-smoking. DHEA and DHEAS were negatively related to age and were higher in smokers. Both E1 and E2 were related to menopausal status and to FSH. Surprisingly, E2 was negatively related to BMI.

A variety of factors influence androgen production in this age group. Whereas it is difficult to predict the effect of menopause on androgen levels, LH stimulation of post-menopausal interstitial cells, modulated by a variety of factors including nutrition, and smoking, are likely to be relevant.

Bancroft J & Cawood EH: Androgens and the menopause; a study of 40-60-year-old women. Clin Endocrinol (Oxf), 1996 Nov, 45:5, 577-87.

Pregnancy (Adrenal Disorders)


In normal "pregnancy", the maternal "adrenal gland" adapts to the physiologic changes necessary to sustain gestation. These changes protect the "fetus" and the mother, allowing for increased shunting of "nutrients" to the fetus and protection of immunologic rejection. Adrenal disorders of pregnancy include overactive and underactive secretion of adrenocortical "hormones" and "tumors" that secrete too much catecholamine.

Hadden-DR: Adrenal disorders of pregnancy. Endocrinol-Metab-Clin-North-Am. 1995 Mar; 24(1): 139-51.



To investigate the possible role of impaired sympathetic nervous system and/or adrenal medullary function in the etiology of human obesity, we studied 64 Pima Indian men in whom sympathoadrenal function was estimated at baseline by measurements of 24-hour urinary norepinephrine (NE) and epinephrine (Epi) excretion rates under weight-maintenance conditions.

Body weight, body composition (hydrodensitometry), and body fat distribution (waist-to-thigh circumference ratio, W/T) were measured at baseline and follow-up.

Follow-up data were available on 44 subjects who gained on average 8.4 +/- 9.5 kg over 3.3 +/- 2.1 years. In these subjects, baseline NE excretion rate, adjusted for its determinants (i.e., fat free mass, fat mass, and W/T), correlated negatively with bodyweight gain. Baseline epinephrine excretion rate correlated negatively with changes in W/T.

A flow sympathetic nervous system activity is associated with body weight gain in humans. Also, a low activity of the adrenal medulla is associated with the development of central adiposity.

Tataranni PA et al., A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men. Obes Res, 1997 Jul, 5:4, 341-7.

Tests For Older Patients

Tests For Older Patients

Adrenal diseases are uncommon in older patients but can present insidiously. Adrenal masses are often discovered incidentally on abdominal CT scans and are usually benign, but they should be assessed for "hormone" production.

"Cushing's syndrome", or cortisol excess, is usually due to exogenous corticosteroids or a hormonally active "tumor". The overnight dexamethasone suppression test is an excellent screening test.

Adrenal insufficiency can be caused by "hemorrhage", tuberculosis, or "metastatic" "cancer". Maintaining a high index of suspicion of hidden adrenal disease, the primary care physician should apply an efficient approach to the diagnosis and initial management of adrenal diseases in older patients.

Ackermann-RJ: Adrenal disorders: know when to act and what tests to give. Geriatrics. 1994 Jul; 49(7): 32-7.

Adrenal Exhaustion


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