The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and <25 kg/m(2)), overweight (BMI, 25.1-30 kg/m(2)), and obese (BMI, >30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease

Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status

INTRODUCTION: The effects of endogenous cortisol (F) excess on bone mass and vertebral fractures have still not been thoroughly investigated. The aim of this cross-sectional case-control study was to investigate factors influencing bone demineralization and vertebral fractures in different conditions of F excess, i.e. Cushing's disease and adrenal and ectopic Cushing's syndrome. MATERIALS AND METHODS: Eighty consecutive patients and 80 controls were prospectively enrolled: 37 patients (21 females) with pituitary ACTH-secreting adenoma, 18 (14 females) with adrenocortical adenoma, 15 (11 females) with adrenal carcinoma of mixed secretion, and 10 (three females) with ectopic ACTH secretion. The groups had similar age. At diagnosis, bone mineral density (BMD) was determined by the dual-energy x-ray absorptiometry technique at the lumbar spine (L1-L4) and femoral neck; vertebral fractures were investigated by standard spinal radiographs. RESULTS: When comparing the groups with different etiology of F excess, the patients with ectopic ACTH secretion had higher F and lower BMD values than the other subgroups. Morning F (P = 0.03) and testosterone levels (P = 0.04) correlated with lumbar BMD. Vertebral fractures were found in 61 (76%) of the patients, were multiple in 52 (85%) of the cases, and clinically evident in 32 (52%). Only multiple fractures were more frequent in patients with ectopic ACTH hypersecretion (P < 0.05). Lumbar spine BMD was the best predictor of vertebral fractures (P < 0.01). Surprisingly, amenorrheic and eumenorrheic women had similar BMD values and fracture prevalence. CONCLUSION: A high prevalence (76%) of vertebral fracture was revealed, regardless of the etiology of the patients' hypercortisolism. The harmful effects of F excess at the spine were partly counterbalanced by the increased androgen production but were not affected by gonadal status in women

The role for growth hormone in linking arthritis, osteoporosis, and body composition

Adults with either GH deficiency (GHD) or GH excess have bone, metabolic, and somatic impairments. This review deals with available data on the relationship between GH status, bone mass, articular disorders, and body composition. GHD subjects have reduced bone mineralization and increased fracture rates. Acromegalic artropathy occurs in virtually all patients and in its late degenerative stages may resemble osteoarthritis. Abnormalities in GH/IGF-I were observed in patients with different forms of arthritis. When concerning body composition (BC), both severe and partial GHD are characterized by increased fat mass, especially truncal, and reduced lean mass. In acromegaly, an increase in body weight, lean mass, and extracellular water, and reduced fat mass were observed; these abnormalities did not always disappear after the normalization of GH/IGF-I levels. On the contrary, long-term GH replacement at physiological doses improved the abnormalities in BC and increased bone mineral density in men with adult-onset GHD, but discordant data were obtained for the bone effects in women. In conclusion, both GHD and GH excess are responsible for some well-defined alterations in metabolism, BC, bone mass, and joint physiology. Their normalization (by GH replacement or treatment of acromegaly) reverses most of these abnormalities, thus confirming their GH-related etiology

The role of growth hormone in glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. GC influence bone metabolism via a modulation of different components of the GH/IGF-I system. GH has multiple anabolic effects on bone, either direct or mediated by IGF-I. GH-deficient subjects have significant reduction in bone mineralization, bone turnover markers, and increased fracture risk when compared with healthy age-matched controls. The increase of bone remodeling achieved by recombinant human GH (rhGH) therapy may be helpful in both males and females with decreased bone turnover and impaired osteoblastic function such as subjects with GC excess. rhGH treatment may improve lean body mass and skeletal muscle mass that may further reduce fracture risk in GIO patients. Nevertheless, the real efficacy of rhGH and IGF-I treatment in GIO and during aging is still controversial and further well-designed prospective controlled studies are necessary in order to clarify this issue, thus identifying who could potentially benefit from GH treatment

Growth hormone excess with onset in adolescence: clinical appearance and long-term treatment outcome

BACKGROUND: Limited data are available on clinical presentation and treatment strategy in patients with GH-secreting adenomas with onset in adolescence. OBJECTIVE: To report results of diagnosis and treatment in adolescents with GH and IGF-I excess. DESIGN: Analytical, observational, retrospective. SUBJECTS: Thirteen patients (five females and eight males, age 15-20 years) all with macroadenoma (two extrasellar, 11 invasive). MAIN OUTCOME MEASURES: Height, body mass index (BMI), GH and IGF-I levels, tumour volume at diagnosis and after treatment. INTERVENTIONS: Transsphenoidal surgery, octreotide subcutaneous (OCT, 0.3-0.8 mg/day), octreotide-LAR i.m. (LAR, 20-30 mg/q28 days), lanreotide i.m. (LAN, 60-90 mg/q28 days), bromocriptine (BRC, 5 mg/day), cabergoline (CAB, 1-2 mg/week). RESULTS: Concomitant hyperprolactinaemia was found in eight patients (61.5%). All girls presented with amenorrhoea, which was associated with galactorrhoea in two patients; all boys presented with symptoms of tumour mass compression such as visual disturbance or headache; two girls also had these symptoms. Height at diagnosis was above the 97th centile in four of five girls and in six of eight boys. None of the patients had altered lipid profile while homeostasis model assessment of insulin resistance (HOMA-IR; 2.8 +/- 0.9) and beta-cell function (HOMA-beta, 207.6 +/- 98.1%) were higher than predicted (1% and 100%, respectively). First-line treatment was surgery in two patients and somatostatin analogues associated with dopaminergic drugs in 11 patients. None of the patients operated on were cured while six of 11 patients receiving pharmacotherapy (6-24 months) were controlled. In these six, tumour volume was reduced by 51.0 +/- 25.2% (median 51.5%). As second-line treatment, all the 11 patients treated with somatostatin analogues underwent surgical removal of their tumours. Surgery was successful in four patients and second-line pharmacotherapy in six patients. One patient was lost at follow-up and two patients maintained active acromegaly despite different treatment schedules; both patients were then treated with radiotherapy. At the last follow-up, there was a significant decrease in insulin levels, HOMA-IR and HOMA-beta without any change in lipid profile. CONCLUSIONS: The clinical presentation of GH-secreting adenomas in adolescent girls is associated with menstrual disturbances and in boys with symptoms of mass effects; tall stature is characteristic in both. First-line treatment with depot somatostatin analogues followed by surgery and then by a second course of somatostatin analogues was successful and safe in 11 of 13 patients