Anne Lenz

Obesity: the hormonal milieu.

Purpose of reviewObesity 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 findingsThe 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. SummaryClinical 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.

Bicalutamide and Third-Generation Aromatase Inhibitors in Testotoxicosis

Testotoxicosis, a form of gonadotropin-independent precocious puberty, results from an activating mutation of the luteinizing hormone receptor expressed in testicular Leydig cells. Affected males experience early testosterone secretion, virilization, advancing bone age, and resultant short stature. Recently, the use of combination therapy with a potent antiandrogen agent (bicalutamide) and a third-generation aromatase inhibitor (anastrozole or letrozole) was reported to yield encouraging short-term results. We present here the results of longer-term treatment (4.5 and 5 years) with this combination therapy in 2 boys who demonstrated that it is well tolerated, slows bone-age advancement in the face of continued linear growth, and prevents progression of virilization.

Epidermal growth factor’s activation of Ras is inhibited by four cardiac hormones

Eur J Clin Invest 2010; 40 (5): 408–413

Cardiac hormones inhibit proliferation of pancreatic cancer but not normal cells

Eur J Clin Invest 2010; 40 (8): 706–712

Cardiac hormones eliminate some human squamous lung carcinomas in athymic mice.

Eur J Clin Invest 2010; 40 (3): 242–249

Gender related differences in glucocorticoid therapy and growth outcomes among pubertal children with 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH).

Abstract Twenty-one-hydroxylase deficient congenital adrenal hyperplasia (CAH) causes glucocorticoid and mineralocorticoid deficiency, hyperandrogenism and short stature. Management of the pubertal CAH patient is particularly challenging. The purpose of this retrospective chart review study was to determine if pubertal males and females with simple virilizing CAH (SVCAH) required different glucocorticoid dosages at progressive Tanner stages. The relationship between hydrocortisone dose and height was also assessed. Twenty females and seventeen males with SVCAH were identified and followed throughout all stages of pubertal development. Males received an average hydrocortisone dose of 16.4±4.8 mg/m2/day and for females, 13.7±4.6 mg/m2/day. The glucocorticoid dosage in males was significantly higher than in females at Tanner stages 3 through 5. Higher doses were associated with a shorter (9.6 cm) achieved than anticipated adult height.

The Importance of the Adiponectin and Leptin Relationship in In Utero and Infant Growth

Adiponectin is an adipocyte-derived, insulin-sensitizing, and anti-inflammatory cytokine that circulates in concentrations a thousand-fold greater than those of leptin or insulin. Leptin is a fat cell derived, 16 kDa protein that acts centrally to signal long-term energy stores to the brain and induces satiety by stimulating anorexigenic and inhibiting orexigenic neuropeptides. Adiponectin is measurable in cord serum by the 24th week of gestation, and concentrations rise 20-fold to term. Cord blood adiponectin values are significantly higher than those found in children and adults, in whom concentrations are inversely related to fat mass and body mass index, and, in contrast, correlate positively to birth weight, body mass index, and weight to length ratio. Umbilical cord leptin correlates positively with birth weight across the spectrum of fetal growth patterns. While placenta can secrete adiponectin, most of the adipokine appears to originate from fetal brown adipose tissue that forms by 14 weeks gestation. High molecular weight adiponectin, the presumed active isoform, correlates with leptin concentrations in cord blood. Lower leptin values in cord blood from small for gestational age babies may play a role in programming catch-up growth during infancy, while low levels of adiponectin in small for gestational age infants may contribute to childhood obesity and insulin resistance. The ratio of total adiponectin to leptin has been shown to correlate positively with weight gain from birth to mid-infancy.