Prevalence of elevated thyroid-stimulating hormone levels in obese children and adolescents.

OBJECTIVE: To determine the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents referred to pediatric endocrinology clinics. METHODS: We undertook a retrospective review of medical records of 191 obese and 125 nonobese children (younger than 18 years old). Data about age, sex, body mass index, TSH, thyroid functions, thyroid antibodies, thyroid size, and medications were collected. RESULTS: Six obese patients had Hashimoto disease and TSH values from 0.73 to 12.73 mIU/L; they were excluded from the study analyses. Of the remaining 185 obese subjects, 20 (10.8%) had TSH levels >4 mIU/L, but no control subject measurement exceeded this TSH value. The highest TSH concentration in an obese study subject was 7.51 mIU/L. When obese children with TSH levels >4 mIU/L were classified in a third group, the mean TSH in the rest of the obese children was comparable with that in the control group (1.98 +/- 0.84 [SD] and 1.95 +/- 0.80 mIU/L, respectively; post hoc analysis of variance, P = .945). Obese subjects with increased TSH values had a mean body mass index similar to that for obese subjects with normal TSH levels (34.98 +/- 6.12 [SD] and 34.29 +/- 7.84 kg/m2, respectively). CONCLUSION: Mild elevation of TSH values in the absence of autoimmune thyroid disease is not uncommon in some obese children and adolescents. This is the second study in the United States to report this observation. Our study did not identify any special characteristics of obese subjects with TSH elevation in comparison with obese children with normal TSH levels and the control group. Current medical knowledge does not support routine screening for thyroid dysfunction in obese children.

Pseudohypoparathyroidism type 1A and morbid obesity in infancy.

OBJECTIVE: To describe an infant with early excessive weight gain as the principle manifestation of pseudohypoparathyroidism (PHP) type 1a and Albright hereditary osteodystrophy (AHO). METHODS: We describe the clinical and laboratory findings in an infant with early excessive weight gain without evidence of hyperphagia and review relevant literature. RESULTS: The proband's birth weight was 4047 g (1.4 SD). She was breastfed from birth. Excessive weight gain was noted by 1 month of age. At 3 months of age, hard subcutaneous nodules were observed, and histologic analysis of a biopsied lesion suggested a possible diagnosis of ossified pilomatricoma. At 6 months of age, she was documented to have mild hypothyroidism. Abnormal weight gain continued despite a caloric intake of about 65 kcal/kg per day. At 11 months of age, 2 new subcutaneous hard nodules were identified, which in the context of excessive weight gain and evolving mild primary hypothyroidism, suggested a unifying diagnosis of PHP type 1a and AHO. GNAS sequence analysis was performed, which revealed a 4-base deletion (Nt565delGACT) in exon 8. CONCLUSIONS: As more monogenic causes of severe early obesity are described, it is important to consider PHP type 1a in the differential diagnosis. Lack of short stature, skeletal abnormalities, or absence of PTH resistance should not exclude this diagnosis in a young child.

TNF-alpha and glucocorticoid receptor interaction in L6 muscle cells: a cooperative downregulation of myosin heavy chain.

Sepsis is associated with increased expression of TNF-alpha with subsequent activation of nuclear factor-kappa B (NF-kappaB). The glucocorticoid receptor (GR) and NF-kappaB function as mutual antagonists and induction of the latter is believed to play a major role in the acquired glucocorticoid resistance that occurs in some septic patients. GR expression and function has been reported to be elevated in septic muscle suggesting a limited effect of the activated NF-kappaB on GR function in this context. In this study, the L6 myocyte cell line was used as an in vitro model for a sepsis-like condition in skeletal muscle. While short or long term treatment with TNF-alpha had no effect on GR expression, glucocorticoid-dependent downregulation of GR occurred with a kinetic profile that is accelerated relative to that observed in most cells. This downregulation was not affected by co-treatment or prior priming of L6 cells with TNF-alpha. The synthetic glucocorticoid, dexamethasone (DEX) blunted TNF-alpha-stimulated NF-kappaB activation in L6 cells. However, although effective at activating an NF-kappaB transcriptional response, TNF-alpha treatment exerted a minimal effect in myoblasts and no effect in myotubes on GR transcriptional activity. This limited impact of TNF-alpha on GR activity was not universal as TNF-alpha and DEX exerted an additive effect on the reduction in myosin heavy chain (MHC) protein expression caused by either agent alone. Thus, the selective perseverance of GR function in the presence of increased levels of glucocorticoids and TNF-alpha during sepsis or other inflammatory states may exacerbate muscle protein breakdown.

Recent advances in hyperinsulinemic hypoglycemia of infancy.

UNLABELLED: Hyperinsulinemia-induced hypoglycemia is the most common cause of persistent hypoglycemia in adults, children, and infants. Our understanding of the disorders responsible for this type of hypoglycemia has been increasing due to the recent discoveries in the molecular and biochemical regulation of insulin secretion. In this article, we review the current knowledge of the pathophysiology, clinical presentation, and diagnosis of disorders that cause hyperinsulinemic hypoglycemia of infancy. We highlight the distinction between the diffuse and focal forms of the disease, especially the promising results with (18)F-L-dopa positive emission tomography (PET) scanning for preoperative localization and distinction to guide the extent of surgical removal of pancreatic tissue that may result in cure rather than persistence of disturbed carbohydrate metabolism. CONCLUSION: Despite all these discoveries, much remains to be learned, as currently about one third of infants with hyperinsulinemic hypoglycemia have no identifiable cause.

Hyperinsulinemic hypoglycemia of infancy: the challenge continues.

Hypoglycemia due to hyperinsulinemia is the most common cause of persistent hypoglycemia in infants and children. Recent discoveries in the molecular and biochemical regulation of insulin secretion have dramatically increased our understanding of the disorders responsible for syndromes of hyperinsulinemic hypoglycemia. Here, we briefly review the current knowledge of disorders of the K(ATP) channel, activating mutations of glucokinase and glutamate dehydrogenase (GDH) and other disorders that may be associated with specific phenotypes and permit appropriate targeted therapies. Despite these advances, much remains to be learned. We do not understand the mechanisms or defects in many instances, including defective carbohydrate glycosylation syndromes and perinatal hypoxia, both of which may be associated with hyperinsulinemia. Most importantly, preoperative distinction between diffuse and focal lesions cannot be always reliably made even after selective arterial infusion with calcium, glucose or a sulfonylurea with concurrent hepatic venous sampling for insulin. The ability to distinguish diffuse from localized lesions has profound implications for therapeutic approaches, prognosis and genetic counseling. To date, about 50% of individuals with hyperinsulinemic hypoglycemia of infancy can be correctly categorized. Thus, the challenge continues.