Obesity: the hormonal milieu.

PURPOSE OF REVIEW: Obesity has reached epidemic proportions throughout the world and poses significant health and economic burdens to both developed and developing societies. Most recent data from the NHANES study (2003-2004) report that 17.1% of US children are overweight and 32.2% of adults are obese, a significant increase compared with data obtained only 6 years earlier. RECENT FINDINGS: The neurohormonal control of appetite, body composition, and glucose homeostasis is mediated by hormones secreted from adipose tissue, endocrine glands, and enteroendocrine cells, which converge at the vagus nerve, brainstem and hypothalamus to modulate complex interactions of neurotransmitters and central appetite-regulating peptides. These hormonal signals are tightly regulated to maintain body weight/adiposity within a narrow, individually defined range that may be further impacted by variables such as ingested calories, meal composition, and lifestyle. SUMMARY: Clinical manifestations of obesity, the metabolic syndrome and impaired glucose tolerance reflect biochemical alterations in a complex hormonal milieu. Elucidation of these hormonal perturbations in obese patients has already provided novel pharmacologic treatments to improve weight management and address the metabolic sequelae of obesity. The remarkable redundancy of these hormones, however, and their interactions make a monopharmaceutical approach unlikely to be successful.

Shedding light on hypovitaminosis D and rickets.

The recent resurgence of the ancient disease of vitamin D deficiency rickets and the widespread presence of hypovitaminosis D across the age spectrum pose significant challenges for today's clinicians. Furthermore, new research into previously unsuspected actions of vitamin D in multiple cell systems offer the possibility that vitamin D will play an increasingly important role in our understanding of a wide variety of disease states.

Pituitary adenomas in childhood: development and diagnosis.

Pituitary adenomas account for approximately 2.7% of all supratentorial tumors in the pediatric age range, and children are more likely than adults to develop a functioning adenoma. X chromosome inactivation studies indicate that pituitary adenomas arise from the clonal expression of a single mutated cell, and various intracellular mechanisms contribute to tumoral transformation. Functional pituitary tumors in childhood result in physical and biochemical effects of excess production of the oversecreted hormone, such as ACTH, prolactin, human growth hormone, TSH, LH, or FSH. In the clinical approach to pituitary adenomas, it is important to establish the presence of hormonal excess prior to undertaking imaging studies.

Correlates of adiponectin and the leptin/adiponectin ratio in obese and non-obese children.

Adiponectin is an adipocyte secreted protein that has been reported to increase fatty acid oxidation and improve insulin sensitivity. Our aim was to study the relationship between adiponectin and leptin, body fat, insulin and lipoproteins in obese compared to non-obese children matched for age and gender. Adiponectin serum concentrations were significantly lower in the obese compared to the non-obese children (9.1+/-3.7 vs 17.1+/-12.3 microg/ml, p <0.05), in contrast to serum leptin concentrations which were greater in the obese compared to the non-obese subjects (31.8+/-11.1 vs 8.2+/-5.7 ng/ml, p <0.001). When considered as a single group to assess adiponectin concentrations over a spectrum of body size, adiponectin values correlated inversely with body weight (r = -0.33, p <0.05) and BMI (r = -0.35, p <0.05). Adiponectin values correlated directly with HDL-C (r = 0.47, p <0.005), but not with total cholesterol, IGF-I, or leptin binding activity. Since leptin and adiponectin change inversely in relation to BMI, the leptin/adiponectin (L/A) ratio was determined as a potential index relating adiposity to the development of complications of obesity. The L/A ratio was eight-fold greater in the obese compared to the non-obese children, and correlated more strongly with BMI (r = 0.779, p <0.0001) and with HDL-C (r = -0.53, p <0.001), than did adiponectin alone. The L/A ratio also correlated significantly with triceps skinfold thickness (TSF) (r = 0.77, p <0.001) and percent body fat (r = 0.79, p <0.0001) in non-obese children. These data suggest that adiponectin concentrations are already differentially regulated in childhood obesity. The index of increased leptin concentration corrected by reduced adiponectin values (L/A ratio) merits investigation as a marker for morbidities associated with childhood obesity.

Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial.

Pubertal gynecomastia is thought to result from transient imbalances between estrogen and androgen concentrations. Anastrozole (ARIMIDEX), a potent and selective aromatase inhibitor, decreases estrogen and increases testosterone concentrations in pubertal boys. The safety and efficacy of anastrozole for the treatment of pubertal gynecomastia were evaluated. In a randomized, double-blind, placebo-controlled study of 80 boys, aged 11-18 yr, with pubertal gynecomastia that had not reduced over a 3-month interval, subjects received either anastrozole (1 mg) or placebo once daily for 6 months. A response was defined as a 50% or greater reduction in the calculated volume of both breasts combined using ultrasonography measurements. A comparison of response rates was performed using logistic regression analysis. Secondary end points included changes in serum hormone concentrations. The percentage of patients with a response was 38.5% for the anastrozole group and 31.4% for the placebo group (odds ratio, 1.513; 95% confidence interval, 0.496-4.844; P = 0.47). At 6 months, the median percent change in the testosterone/estradiol ratio was 166% for the anastrozole group and 39% for the placebo group. Anastrozole treatment was well tolerated. In patients with pubertal gynecomastia, no significant difference in the percentage of patients with a 50% or greater reduction in total breast volume, as calculated from ultrasonography measurements, was demonstrated between the anastrozole and placebo groups.

Effects of one year of recombinant human growth hormone (GH) therapy on cardiac mass and function in children with classical GH deficiency.

Cardiac mass and function were evaluated in 10 children with classical GH deficiency. Echocardiograms were performed at baseline, 3, 6, and 12 months after initiation of recombinant human (rh) GH therapy (0.3 mg/kg.wk). Before treatment, left ventricular (LV) mass indexed to body surface area (BSA) was low or low normal (<50 g/m(2)) in five children compared with reference control data. Height SD score (-3.2 +/- 0.9 vs. -1.8 +/- 1.3 yr; P < 0.01), growth velocity SD score (-2.7 +/- 1.6 vs. 5.8 +/- 3.1; P < 0.01), LV mass (36 +/- 9 vs. 60 +/- 30 g; P < 0.02), LV mass/BSA (51 +/- 12 vs. 72 +/- 11 g/m(2); P < 0.01), LV mass/height (36 +/- 9 vs. 54 +/- 15 g/m; P < 0.02), and LV mass/m(2.7) (36 +/- 12 vs. 45 +/- 8; P < 0.05) increased significantly with rhGH therapy. Pretreatment LV mass/BSA correlated inversely with fold increase in LV mass/BSA over the year (r = -0.83; P < 0.01). Load-dependent indices of diastolic performance were normal at baseline and did not change with rhGH therapy. Percentage increase of mean velocity of circumferential shortening, an index of systolic function, correlated with fold increase in LV mass/BSA (r = 0.88; P < 0.02) over the year of rhGH administration. LV mass can be lower than predicted for body size in some children with severe GH deficiency but is responsive to rhGH replacement. LV mass/BSA increases into the normal range during the first year of rhGH therapy. The rate of increase of LV mass is greater than the increase in BSA during rhGH treatment, suggesting that GH could also be a trophic factor for the heart.

Leptin and the adipocyte endocrine system.

Although adipose tissue has long been considered to be metabolically passive and primarily responsible for energy storage, recent scientific advances have dramatically altered our understanding of the function of this ubiquitous tissue. The fat cell is a transducer of energy supply for the changing metabolic needs of the body, modulating glucose homeostasis, hypothalamic function, sympathetic output, vascular tone, immune response, and reproduction. Through endocrine/autocrine and paracrine actions, adipocyte-derived molecules defend the body during periods of energy deficit and stress. With the development of obesity, maladaptive responses to adipose excess result in pathologic states of inflammation, coagulopathy, and altered insulin sensitivity.