Biomedical subjects

Stephen H LaFranchi

Publications and source records attributed to Stephen H LaFranchi.

7 recordsLinked to original sources

PubMed2005

Is thyroid inadequacy during gestation a risk factor for adverse pregnancy and developmental outcomes?

A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. This paper reports on the individual session that examined thyroid inadequacy during gestation as a risk factor for adverse pregnancy and developmental outcomes. For this session the following papers were presented: "Adverse Pregnancy Outcomes"; "Thyroid Physiology in the Fetus"; "New England Data: Cretinism Revisited-Preventing Fetal Brain Damage when Mothers Have Subclinical Hypothyroidism"; "Dutch Data: Pregnancy, Maternal Thyroid (Dys)function and Outcome of the Offspring"; and "Report on the Wales Controlled Antenatal Thyroid Screening Study (CATS); A Prospective RCT." These presentations were formally discussed by invited respondents well as others in attendance. Salient points from this session about which there was agreement include the following. Maternal hypothyroidism is associated with complications of pregnancy and adverse effects on the fetus. These risks are greater in women with overt hypothyroidism compared to subclinical hypothyroidism, and also appear to be increased in women with euthyroid autoimmune thyroid disease. If maternal hypothyroidism is treated adequately, this appears to reduce the risk for adverse outcomes. The demonstration of a pattern of ontogeny of fetal cerebral cortex deiodinases and thyroid hormone receptors, beginning by 7-8 weeks' gestation, is circumstantial evidence that thyroid hormone plays an important role in fetal neurodevelopment. Significant fetal thyroid hormone production and secretion does not begin until approximately 20 weeks' gestation. If there is a significant role for thyroid hormone in fetal neurodevelopment before 20 weeks' gestation, it likely is of maternal origin. Studies demonstrate low levels of thyroxine in the fetal coelomic fluid and blood prior to 12-14 weeks' gestation. Published data consistently document a relationship between maternal thyroid deficiency during pregnancy and problems with neuropsychological development of the offspring.

Animals↗

PubMed2005

Androgen replacement in adolescents and young women with hypopituitarism.

The aim of this study was to test the hypothesis that young women with androgen deficiency due to hypopituitarism would benefit from androgen replacement in the form of dehydroepiandrosterone (DHEA). Five young women, age 15.2-23.1 years, with panhypopituitarism were studied in a 12-month double blind placebo-controlled crossover trial of DHEA replacement in a dose 50 mg/day (Belmar Pharmacy, Lakewood, CO). All had growth hormone (GH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and antidiuretic hormone deficiencies. Gonadotropin deficiency was complete in three and partial in two. The patients were evaluated at baseline, 6 months and 12 months. Serum hormone levels, body composition, lumbar bone mineral density (BMD), exercise capacity and tests of psychological function were performed. DHEA replacement restored serum DHEA levels to normal, 359.8+/-337 ng/dl (12.5+/-11.7 nmol/l). The Life Situation Survey showed significantly better life satisfaction on DHEA than placebo (110 vs 102, p = 0.05). Trends for improved maximal oxygen uptake (VO2), and decreased percent body fat did not reach statistical significance. In conclusion, androgen replacement with DHEA should be considered in young women with panhypopituitarism. Further studies over longer periods in larger groups of patients are necessary to better evaluate the effects of DHEA replacement on BMD, muscle strength and body composition.

Adipose Tissue↗

PubMed2004

A novel presentation of familial glucocorticoid deficiency (FGD) and current literature review.

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder, which manifests as isolated glucocorticoid deficiency with normal mineralocorticoid function. The disease is secondary to ACTH unresponsiveness, with low serum cortisol concentrations in the presence of markedly elevated ACTH levels. Approximately 40% of patients with FGD have an identifiable mutation in the ACTH receptor gene. The typical presentation of FGD includes recurrent hypoglycemia, failure to thrive, and hyperpigmentation prior to 5 years of age. Patients with point mutations in the ACTH receptor gene are noted to be of tall stature. We report a patient with an atypical initial presentation of this condition. Our patient differed from the typical presentation by having late age of onset, short stature, and few symptoms of FGD. Sequence analysis of the ACTH receptor gene showed compound heterozygosity, with two previously reported mutations: S74I and T159K. Her unique presentation further illustrates the phenotypic heterogeneity of this disorder in light of reported mutations.

Adolescent↗

PubMed2003

Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome.

Ghrelin, an endogenous ligand of the GH secretagogue receptor, stimulates appetite and causes obesity in animal models and in humans when given in pharmacologic doses. Prader-Willi Syndrome (PWS) is a genetic obesity syndrome characterized by GH deficiency and the onset of a voracious appetite and obesity in childhood. We, therefore, hypothesized that ghrelin levels may play a role in the expression of obesity in this syndrome. We measured fasting serum ghrelin levels in 13 PWS children with an average age of 9.5 yr (range, 5-15) and body mass index (BMI) of 31.3 kg/m2 (range, 22-46). The PWS group was compared with 4 control groups: 20 normal weight controls matched for age and sex, 17 obese children (OC), and 14 children with melanocortin-4 receptor mutations (MC4) matched for age, sex, and BMI, and a group of 3 children with leptin deficiency (OB). In non-PWS subjects, ghrelin levels were inversely correlated with age (r = 0.36, P = 0.007), insulin (r = 0.55, P < 0.001), and BMI (r = 0.62, P < 0.001), but not leptin. In children with PWS, fasting ghrelin concentrations were not significantly different compared with normal weight controls (mean +/- SD; 429 +/- 374 vs. 270 +/- 102 pmol/liter; P = 0.14). However, children with PWS did demonstrate higher fasting ghrelin concentrations (3- to 4-fold elevation) compared with all obese groups (OC, MC4, OB) (mean +/- SD; 429 +/- 374 vs. 139 +/- 70 pmol/liter; P < 0.001). In conclusion, ghrelin levels in children with PWS are significantly elevated (3- to 4-fold) compared with BMI-matched obese controls (OC, MC4, OB). Elevation of serum ghrelin levels to the degree documented in this study may play a role as an orexigenic factor driving the insatiable appetite and obesity found in PWS.

Adolescent↗

PubMed2003

Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome.

The objective of this study was to investigate the effects of GH administration on pulmonary function, sleep, behavior, cognition, linear growth velocity, body composition, and resting energy expenditure (REE) in children with Prader-Willi syndrome. The study used a 12-month, balanced, randomized, double-blind, placebo-controlled, cross-over experimental design. Twelve subjects were randomized to GH (0.043 mg/kg x d) or placebo intervention for 6 months and then crossed over to the alternate intervention for 6 months. Differences in outcome variables were determined by paired t tests. Peak flow rate, percentage vital capacity, and forced expiratory flow rate improved and number of hypopnea and apnea events and duration of apnea events trended toward improvement after GH intervention. The only difference in cognition or behavior was an increase in hyperactivity scale on the Behavior Assessment System for Children after GH intervention. Linear growth velocity, REE, and lean mass were higher (67%, 19%, and 7.6%, respectively), and fat mass and percentage body fat were lower (10.3% and 8.1%, respectively) after GH intervention. GH administration did not change mean fasting ghrelin concentration. GH intervention improved body composition and REE and may contribute to better sleep quality and pulmonary function. GH administration did not impact fasting ghrelin concentration.

Adolescent↗

PubMed2003

Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is characterized by severe obesity, hyperphagia, hypogonadism, and GH deficiency. Unlike individuals with common obesity, who have low fasting-plasma ghrelin concentrations, those with PWS have high fasting-ghrelin concentrations that might contribute to their hyperphagia. Treatment with octreotide, a somatostatin agonist, decreases ghrelin concentrations in healthy and acromegalic adults and induces weight loss in children with hypothalamic obesity. This pilot study was performed to determine whether octreotide administration (5 microg/kg.d) for 5-7 d lowers ghrelin concentrations and affects body composition, resting energy expenditure, and GH markers in children with PWS. Octreotide treatment decreased mean fasting plasma ghrelin concentration by 67% (P < 0.05). Meal-related ghrelin suppression (-35%; P < 0.001) was still present after intervention but was blunted (-11%; P = 0.19). Body weight, body composition, leptin, insulin, resting energy expenditure, and GH parameters did not change. However, one subject's parent noted fewer tantrums over denial of food during octreotide intervention. In conclusion, short-term octreotide treatment markedly decreased fasting ghrelin concentrations in children with PWS but did not fully ablate the normal meal-related suppression of ghrelin. Further investigation is warranted to determine whether long-term octreotide treatment causes sustained ghrelin suppression, changes eating behavior, and induces weight loss in this population.

Behavior↗

PubMed2002

Adolescent thyroid disorders.

Thyroid disorders are common in adolescence. Thyroid nodules can present in this age group, and although most are benign, malignancy is not unheard of. Chronic lymphocytic thyroiditis can present as hypothyroidism, while the adolescent with a goiter due to autoimmune thyroid disease is frequently euthyroid. Graves disease is a common etiology of hyperthyroid presentation in this age group. While there are known genetic and iatrogenic conditions that may predispose thyroid problems, they may also happen randomly in the general population. Thyroid problems may present as a goiter, a nodule, or a general cluster of abnormal symptoms and physical findings. The unique challenge to the provider of adolescent health care is that thyroid problems can adversely affect growth and development during puberty, a crucial period of hormonal interaction. This chapter addresses the diagnosis, treatment alternatives, and prognosis for a variety of common and uncommon thyroid abnormalities in adolescents. Many are readily treatable if recognized promptly, and even thyroid cancer often can be effectively treated and managed. Physicians treating the adolescent population have to be aware of the various thyroid problems that their patients can face.

Adolescent↗