Roberto Lanes

ACTH stimulation tests and plasma dehydroepiandrosterone sulfate levels in women with hirsutism

BACKGROUND: Hirsutism in women is a clinical manifestation of excessive production of androgens. The source of the excess androgen may be either the ovaries or the adrenal glands, and distinguishing between these sources may be difficult. METHODS: To determine whether measurements of plasma dehydroepiandrosterone (DHEA) sulfate and ACTH stimulation tests, both widely used in the evaluation of hirsutism in women, provide useful information, we performed both tests in 22 normal women and 31 female patients with hirsutism. The hormones measured in plasma during the ACTH stimulation tests were progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA, androstenedione, 11-deoxycortisol, and cortisol. RESULTS: The women with hirsutism were divided into four groups based on their individual responses to ACTH stimulation: patients with a possible 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency, those with a possible 21-hydroxylase deficiency, those with a possible 11 beta-hydroxylase deficiency, and those with no apparent defect in steroidogenesis. The results in 19 patients (61 percent) suggested subtle defects in adrenal steroidogenesis. There was no significant correlation between the basal plasma DHEA sulfate levels and the hormonal response to ACTH, nor were the basal levels of hormones predictive of the levels after ACTH stimulation. Eleven patients had significantly elevated basal levels of plasma DHEA sulfate; only 5 of these 11 had responses to ACTH suggestive of compromised steroidogenesis. Thirteen patients who had responses suggestive of defective steroidogenesis had DHEA sulfate levels within the normal range. CONCLUSIONS: A substantial proportion of women with hirsutism have mild defects in adrenal steroidogenesis, revealed by an ACTH stimulation test, that are indicative of late-onset (nonclassic) congenital adrenal hyperplasia. Measurements of basal steroid levels are not helpful in differentiating among the causes of increased androgen production in such patients and may be misleading.

The triglyceride/HDL-cholesterol ratio as a marker of cardiovascular risk in obese children; association with traditional and emergent risk factors

Objectives:  To determine the presence of traditional and emergent cardiovascular risk factors and to evaluate the triglyceride/high‐density lipoprotein cholesterol (Tg/HDL‐C) ratio as a marker for cardiovascular disease and metabolic syndrome (MS) in obese children.

Impaired Somatomedin Generation Test in Children with Insulin-dependent Diabetes Mellitus

Recent studies have suggested a partial block in somatomedin (SM) production or growth hormone (GH) action in IDDM. Twelve well-nourished diabetic children (9 males and 3 females with a mean age of 11.2 ± 3.3 yr), six with an HbA1c of 7.9–11.2% (group A) and six with an HbA1c of 12.5–15.6% (group B), were studied as follows: the GH response after 100 μg of oral clonidine and the SM generation capacity after i.m. administration of 0.2 U/kg/dose of human growth hormone (hGH) for 4 days. Group B diabetic subjects had a significantly higher mean ± SD GH increase after clonidine than did group A patients (Δ of 17.4 ± 4.9 versus 5.7 ± 6.0 ng/ml, P < 0.01); the basal GH of both groups were similar (1.6 ± 0.7 versus 2.3 ± 1.4 ng/ml). In contrast, the SM response to hGH was significantly decreased in group B children as compared with those in group A (Δ of 0.3 ± 0.3 versus 1.2 ± 0.4 U/ml, P ± 0.01). The basal SM levels of both groups were normal for age. GH and SM correlated with HbA1c levels (r = +O.80, P < 0.01; r = −0.79, P < 0.01, respectively); there was no correlation with plasma and urine glucose or serum cholesterol, cortisol, and transferrin. Our data indicate a blunted SM response to hGH in group B diabetic subjects; this defect in SM generation is apparently not present in group A subjects. A biologically inactive GH molecule and poor nutrition seem unlikely, but circulating inhibitory factors not picked up by our radioimmunoassay, the degree of diabetes control, or a still unclear metabolic derangement may be contributing to this defect.

Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in growth-hormone-treated and untreated patients.

Objective: To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents. Methods: Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal. Results: Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents. Conclusions: GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.

Cardiac mass and function, carotid artery intima-media thickness and lipoprotein (a) levels in children and adolescents with type 1 diabetes mellitus of short duration.

OBJECTIVE To evaluate cardiac mass and function, carotid intima-media thickness, and serum lipid and lipoprotein (a) (Lpa) levels in children and adolescents with type 1 diabetes mellitus (DM) of short duration. BACKGROUND Diabetes mellitus has been found to be an important risk factor for macrovascular disease in adults. Increased serum lipids and Lpa levels have been reported in adolescents with type 1 DM; atherosclerotic vascular lesions involving a combination of fatty degeneration and vessel stiffening of the arterial wall and myocardial involvement impairing diastolic function may be present in adolescents and young adults with type 1 DM. DESIGN/METHODS Twenty children and adolescents (10 males, 10 females) diagnosed with type 1 DM before 3.4 +/- 3.3 years with a mean age of 11.9 +/- 3.6 years were studied; their HbA1c levels were 8.0 +/- 1.9%. Twenty healthy non-diabetic controls, 10 males and 10 females, aged 12.1 +/- 3.4 years, matched for height and weight, participated in the study. Fasting blood samples were obtained for lipid and Lpa analysis. Patients underwent transthoracic M-mode and two-dimensional echocardiographic evaluation for measurement of left atrial and ventricular dimensions and left ventricular (LV) wall thickness and mass. Stroke volume and cardiac output were measured using pulsed Doppler echocardiography; carotid intima-media thickness was measured using high-resolution mode B ultrasound. RESULTS Interventricular septal thickness (7.1 +/- 1.8 vs 7.0 +/- 1.5 mm), LV posterior wall thickness (7.1 +/- 1.4 vs 7.5 +/- 2.0 mm) and LV mass after correction for body surface area (70.6 +/- 27.4 vs 70.7 +/- 18.0 g/m2) were similar in patients and controls. Similarly, the LV ejection fraction at rest was similar in patients and controls (69.9 +/- 2.3 vs 70.0 +/- 0.6%), as were pulmonary venous flow velocities (0.56 +/- 0.09 vs 0.55 +/- 0.10 m/s for diastolic peak velocity, 0.54 +/- 0.08 vs 0.50 +/- 0.09 m/s for systolic peak velocity and 0.17 +/- 0.07 vs 0.19 +/- 0.05 m/s for atrial reversal filling). Carotid intima-media thickness (0.60 +/- 0.02 and 0.59 +/- 0.02 mm for the right and left carotid artery) was similar to that of controls (0.60 +/- 0.03 and 0.61 +/- 0.02 mm for the right and left carotid artery). Low density lipoprotein cholesterol and Lpa levels were increased in patients compared to controls (113.2 +/- 26.0 mg/dl and 20.1 +/- 11.7 mg/dl in patients vs 90.4 +/- 14.3 mg/dl and 9.8 +/- 2.9 mg/dl in controls; p <0.01), while total cholesterol, HDL cholesterol and serum triglyceride concentrations were similar to those in controls. CONCLUSIONS Although children and adolescents with type 1 DM seem not to show alterations in cardiac mass and function or early atherosclerotic changes in the first few years after diagnosis, their cardiovascular risk is increased as they present with dyslipidemia at an early stage of the disease.

Decreased secretion of cortisol and ACTH after oral clonidine administration in normal adults

Clonidine, a selective noradrenergic receptor agonist, has been shown to affect various hormones acutely. It increases growth hormone levels in animals and in human adults and children. The effect of clonidine upon ACTH and cortisol levels is not as clear, and both stimulatory and inhibitory effects have been reported. We found a significant decrease in plasma cortisol decreased. No changes in FSH, LH, or prolactin were seen after oral clonidine. Our data are compatible with an inhibitory noradrenergic mechanism modulating ACTH and cortisol secretion in normal adults.

Final height after combined growth hormone and gonadotrophin-releasing hormone analogue therapy in short healthy children entering into normally timed puberty

Combined gonadotrophin‐releasing hormone analogue and recombinant human growth hormone therapy has been used in an attempt to improve the final height of short non‐GH deficient adolescents with normally timed puberty; its use, however, is still controversial as only short‐term studies in a very limited number of patients have been undertaken, with either improvement in height prognosis or no beneficial effect on predicted growth. We have treated a group of extremely short healthy children with very low predicted adult heights entering into normally timed puberty with combined therapy, in order to determine whether we could improve their final height above their pretreatment predicted adult height.

Latin American Consensus: Children Born Small for Gestational Age

BackgroundChildren born small for gestational age (SGA) experience higher rates of morbidity and mortality than those born appropriate for gestational age. In Latin America, identification and optimal management of children born SGA is a critical issue. Leading experts in pediatric endocrinology throughout Latin America established working groups in order to discuss key challenges regarding the evaluation and management of children born SGA and ultimately develop a consensus statement.DiscussionSGA is defined as a birth weight and/or birth length greater than 2 standard deviations (SD) below the population reference mean for gestational age. SGA refers to body size and implies length-weight reference data in a geographical population whose ethnicity is known and specific to this group. Ideally, each country/region within Latin America should establish its own standards and make relevant updates. SGA children should be evaluated with standardized measures by trained personnel every 3 months during year 1 and every 6 months during year 2. Those without catch-up growth within the first 6 months of life need further evaluation, as do children whose weight is ≤ -2 SD at age 2 years. Growth hormone treatment can begin in SGA children > 2 years with short stature (< -2.0 SD) and a growth velocity < 25th percentile for their age, and should continue until final height (a growth velocity below 2 cm/year or a bone age of > 14 years for girls and > 16 years for boys) is reached. Blood glucose, thyroid function, HbA1c, and insulin-like growth factor-1 (IGF-1) should be monitored once a year. Monitoring insulin changes from baseline and surrogates of insulin sensitivity is essential. Reduced fetal growth followed by excessive postnatal catch-up in height, and particularly in weight, should be closely monitored. In both sexes, gonadal function should be monitored especially during puberty.SummaryChildren born SGA should be carefully followed by a multidisciplinary group that includes perinatologists, pediatricians, nutritionists, and pediatric endocrinologists since 10% to 15% will continue to have weight and height deficiency through development and may benefit from growth hormone treatment. Standards/guidelines should be developed on a country/region basis throughout Latin America.

Decreased bone mass despite long-term estrogen replacement therapy in young women with Turner’s syndrome and previously normal bone density

OBJECTIVE To determine whether young women with Turners syndrome who had normal bone mineral density (BMD) before the induction of puberty maintain normal BMD in young adulthood. DESIGN Controlled clinical study. SETTING A private hospital clinical research setting. PATIENTS Young women with Turners syndrome in Tanner stage V of puberty with previously normal BMD. INTERVENTIONS Oral conjugated estrogens and progesterone acetate were administered continuously for a mean (+/-SD) of 4.1+/-1.0 years. Bone mineral densities and blood samples were evaluated. MAIN OUTCOME MEASURE(S) The BMD of the lumbar spine and the femoral neck was determined during young adulthood. The change in BMD over the previous 6 years also was evaluated. Serum concentrations of the carboxy-terminal propeptide of type 1 collagen and of the carboxy-terminal cross-linked telopeptide of type 1 collagen were measured. RESULT(S) The BMD of the lumbar spine was reduced significantly in our patients. There was no change in the BMD of the femoral neck or lumbar spine over a period of 6.1 years. Concentrations of the carboxy-terminal propeptide of type 1 collagen were decreased, whereas concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen were increased. CONCLUSION(S) Young women with Turners syndrome do not attain normal peak bone mass even when estrogen replacement therapy is begun in adolescence. Their low BMD seems to be due to decreased bone formation and increased bone resorption.

Growth hormone secretion in patients with constitutional delay of growth and pubertal development

Growth hormone levels were measured every 30 minutes during sleep over 9 hours in 20 prepubertal patients with constitutional delay of growth and puberty (CGD) and in 10 age-matched controls, all of whom had had normal GH responses to an orally administered dose of clonidine. We found no significant difference in the mean 9-hour overnight GH concentration between groups (4.5 +/- 1.8 ng/ml (mean +/- SD) in the CGD group, 4.4 +/- 2.8 ng/ml in the control group). Total GH output (258 +/- 99 U vs 222 +/- 135 U), total number of nocturnal GH pulses (3.6 +/- 0.8 vs 3.3 +/- 1.3), mean peak GH response during nocturnal sampling (13 +/- 1.2 ng/ml vs 13.2 +/- 1.3 ng/ml), and basal somatomedin C concentrations were not different in the children with growth delay and controls. We conclude that prepubertal patients with constitutional delay of growth and puberty secrete GH normally and do not seem to have any abnormality in GH regulation.