Serum ghrelin concentrations are increased in children with growth hormone insensitivity and decrease during long-term insulinlike growth factor-I treatment.

BACKGROUND: Ghrelin increases food intake, body weight, and growth hormone (GH) secretion. Serum concentrations of ghrelin are low in obese hyperinsulinemic persons, are reduced by infusion of insulin into normal-weight subjects, and are increased in underweight hypoinsulinemic patients with anorexia nervosa. Laron syndrome is an autosomal recessive disorder of GH insensitivity that results in decreased insulinlike growth factor-I (IGF-I) synthesis and growth failure. These patients have elevated GH levels, excess adipose tissue, and are insulin resistant. Because IGF-I has insulinlike actions and patients with GH insensitivity syndrome (GHIS) exhibit excess adiposity, we sought to determine whether ghrelin levels were elevated in these patients and potentially regulated by IGF-I replacement. METHODS: Thirteen children with GHIS and 20 normal control children matched for age, sex, and body mass index underwent complete physical examination and a fasting blood draw at baseline. The GHIS subjects then underwent follow-up fasting blood draws during therapy with human recombinant IGF-I (80-120 mug/kg, given subcutaneously twice daily). Fasting glucose, insulin, and IGF-I concentrations were measured at the time of collection. Fasting total ghrelin levels were measured on stored serum samples. RESULTS: The GHIS subjects had 2-fold higher fasting ghrelin levels (2926 +/- 1869 pg/mL) compared with the normal control children (1492 +/- 493 pg/mL; P = 0.009), and mean ghrelin values were reduced 56% during 6.4 +/- 0.2 years of IGF-I replacement (P < 0.05). CONCLUSIONS: Growth hormone resistance and low IGF-I levels are associated with elevated ghrelin levels, which may potentiate GH secretion and adiposity in these children. Suppression of ghrelin during IGF-I treatment suggests a novel mechanism potentially regulating ghrelin levels.

Obesity and type 2 diabetes mellitus: a population-based study of adolescents.

A cross-sectional, population-based study was conducted on 1,647 Turkish adolescents to determine the prevalence of obesity, impaired fasting glucose (IFG) and type 2 diabetes mellitus (DM2), and to determine whether the recent increase in DM2 prevalence in some countries is applicable to this population. Information was gathered through a questionnaire. All children were screened with physical examination and fasting plasma glucose. 10.7% of adolescents were overweight (BMI 85-95th percentile) and 3.6% were obese (BMI > or =95th percentile). Mean BMI was 20.25 +/- 3.31 kg/m2 with maximum BMI 35.88 kg/m2. No child was diagnosed with DM2; 1.96% had IFG (110-126 mg/dl). No significant relationship was found between IFG and obesity, socio-economic status (SES) or family history of DM. The risk of obesity was increased among children with family history of DM or obesity, and among those who had low physical activity and were of high SES level. This analysis represents the population-based data upon which future studies will be based.

Neonatal hyperthyroidism associated with isolated submandibular sialadenitis: is it just a coincidence?

Isolated submandibular sialadenitis is extremely rare in the neonatal period. All reported cases had predisposing factors such as prematurity, dehydration, anatomic deformities, calculi, and long-term oro-gastric tube feeding. Here, we present a case of neonatal isolated submandibular sialadenitis without any known risk factors and who was diagnosed later with hyperthyroidism secondary to maternal Graves' disease. Both sialadenitis and hyperthyroidism resolved with appropriate treatment. While both conditions are rare and important in neonatal emergency care, the possibility of neonatal hyperthyroidism should be explored in cases with isolated sialadenitis if there is no other risk factor. Possible mechanisms for this uncommon association are discussed.

A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia.

Autosomal dominant hypocalcemia resulting from gain-of-function mutations of the calcium sensing receptor (CASR) is a rare familial disorder that can become evident at any age. We report a novel mutation (E767K) of the CASR in a family with autosomal dominant hypocalcemia. Ten members of the family had a history of hypocalcemia. The index case exhibited marked hypocalcemia and seizures in the newborn period, while her father who also has hypocalcemia, was largely asymptomatic except for a myocardial infarction-like event at 21 years of age, a new presentation of the disorder. The E767K mutation, which resides in the second extracellular loop adjacent to the fifth transmembrane domain, co-segregated with hypocalcemia in these two individuals. Both subjects are heterozygous for the mutation. The proband is also heterozygous for the previously reported CASR polymorphism of G990R in the intracellular domain, while her father is homozygous. The co-segregation of this naturally occurring mutation with autosomal dominant hypocalcemia supports the previously reported experimental model in which it was proposed that the three acidic residues (767, 758, and 759) in exo-loop 2 in CASR help maintain an inactive conformation of the receptor.