Somatomedin activity and diabetic control in children with insulin-dependent diabetes.

To test the hypothesis that somatomedin activity is influenced by diabetes and its metabolic regulation, the relationship between somatomedin activity and diabetic control as assessed by hemoglobin A1C was investigated in 40 children with insulin-dependent diabetes. An inverse correlation between hemoglobin A1C and serum somatomedin activity was statistically significant. The data suggest that abnormalities of linear growth, which can occur in children with poorly controlled diabetes, may involve abnormalities in net somatomedin activity.

Long-term prospective evaluation of offspring of diabetic mothers.

We have suggested that altered maternal metabolism may affect the subsequent anthropometric and neuropsychological development of children who were in utero during disturbances in maternal fuel economy. This study reports the physical growth through 8 yr of age and the neuropsychological development through 4 yr of age in offspring of diabetic mothers (ODM). At birth, 50% of infants had weights greater than 90th percentile for gestational age. By 12 mo, length and weight were similar to the general population. Height remained normal until 7 yr of age, when it became slightly greater than average. After 5 yr of age, relative weight increased dramatically, and by 8 yr of age, half of the ODM had weights greater than 90th percentile. This childhood obesity in ODM is correlated with maternal prepregnant weight and independently with amniotic fluid insulin at 32-38 wk gestation. The Brazelton Neonatal Behavioral Assessment Scale (BNBAS) was administered to 185 newborn ODM. Significant correlations were found between poorer second- and third-trimester glycemic regulation and lower scores in three of four newborn BNBAS dimensions. The Stanford-Binet Intelligence Scale was measured in 102 ODM at 4 yr of age. We found an inverse correlation between childhood IQ and second- and third-trimester maternal lipid metabolism (serum free fatty acids and beta-hydroxybutyrate). This correlation is not explained by adverse perinatal events, socioeconomic status, maternal IQ, ethnicity, or diabetes type. These long-range associations between altered maternal metabolism and childhood growth and development continue to support Freinkel's hypothesis of fuel-mediated teratogenesis.

Glucosuria in children with diabetes: advantages of the 2-drop Clinitest method.

In order to assess the actual and theoretical limitations of using the traditional urinary glucose determinations as an indicator of plasma glucose concentration, we have measured plasma and urine glucose concentrations in 37 children with diabetes mellitus. A constant blood withdrawal system enabled an accurate estimate of the glucose concentration presented to the renal glomerulus over the 30-min period of blood collection and urine formation. The theoretical range of plasma glucose over which the 5-Drop and 2-Drop Clinitest methods are sensitive is 32 mg/dl and 81 mg/dl, respectively. This suggests that the 2-Drop method is the procedure of chioce for most insulin-dependent diabetic patients. Nevertheless, the extremely wide range of plasma glucose corresponding to a given urinary glucose measurement limits the precision with which any single urine test can be interpreted.

Standard parameters of diabetic control: are they reliable?

To evaluate the reliability of the tradional methods to assess short-term control of diabetes, 25 children with insulin-dependent diabetes were studied with a 24-h glucose profile in addition to the traditional assessment techniques. Patient compliance was elminated as much as possible from the experimental design. The correlation of the routine methods with the 24-h glucose profile was excellent, and a scoring system for control was empirically derived. The single method of assessment that correlated best with the overall control score was the traditional daily urine test. In 6 of the 25 subjects studied, relative hypoglycemia was observed, occurring asymptomatically at night, and was followed by a hyperglycemic rebound. Traditional assessment techniques did not detect this event. Five additional patients had symptomatic daytime hypoglycemia. We conclude that the traditional daily urine tests are adquate indicators of day-to-day control in most diabetic patients, given adquate compliance. Our data also suggest that asymptomatic nocturnal hypoglycemia occurs frequently in children with diabetes, although clinical proof is difficult in the absence of a 24-h glucose profile.

Schmidt's syndrome in a child with diabetes mellitus.

Schmidt's syndrome (thyroid and adrenal insufficiency) and concurrent diabetes mellitus represent an intriguing multiple endocrinopathy in children. This report describes an eleven-year-old girl with diabetes of eight years' duration presenting in adrenal crisis. Serum thyroxine was undetectable, and antibodies to both thyroglobulin and adrenal tissue were found in high titer. The child's condition stabilized with hormonal replacement therapy, except for persistent growth failure. Approximately two years later she succumbed during a rapidly fulminant episode of ketoacidosis. The natural history of her illness supports recent speculation based on serologic data that juvenile diabetes mellitus may be an immunologic disorder in some children.

Cyclosporine A inhibits calcemic hormone-induced bone resorption in vitro.

We have investigated the in vitro effects of cyclosporine (CsA), a potent immunosuppressive agent, on bone resorption induced by calcemic hormones. CsA inhibited parathyroid hormone (PTH), prostaglandin E2, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3), and osteoclast-activating factor induced resorption of fetal rat limb bones in a dose-dependent manner. Established ongoing resorptive activity in bone was also inhibited by CsA. The CsA inhibition of bone resorption could be partially surmounted by higher concentrations of PTH and 1,25(OH)2D3. The inhibitory effects of CsA on limb bone resorption were reversible. Neither protein nor DNA synthesis were inhibited by treatment of limb bones with CsA. Thus, the inhibitory effect of this agent on bone resorption is not a cytotoxic one. These data could suggest that the induction of bone resorption by the calcemic hormones involves an immune cell derived mediator such as a lymphokine.

Virilizing adrenocortical tumors in childhood: eight cases and a review of the literature.

Eight cases of adrenocortical tumor are presented with a review of the literature. Although such tumors are rare, they are important causes of inappropriate virilization and Cushing's syndrome in childhood. Clinical virilization with or without hypercortisolism was found in all eight children, who were 5 years old or younger. Excessive linear growth was noted, despite evidence of hypercortisolism. Serum levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and cortisol were elevated in all cases tested and appear to be useful diagnostic alternatives to the more traditional determinations of urine 17-ketosteroids and 17-hydroxycorticosteroids. Abdominal sonography and computed tomography have proven to be reliable tools for tumor localization. Surgical resection was the definitive therapy in all patients, and perioperative steroid replacement was essential. Histologic diagnosis appeared to have little bearing on prognosis, and the majority of pediatric patients have had clinically benign disease. At a mean follow-up of 3 years, seven of the eight children were alive and had no evidence of tumor recurrence.

Effect of thyroxine and growth hormone on the hypercholesterolemia of growth hormone deficiency.

To study the selective effect of thyroid hormone and growth hormone, alone and in combination on plasma cholesterol, 12 children were monitored monthly during three 4-month treatment periods. Plasma cholesterol was unaltered by growth hormone therapy alone (mean +/- SD, basal cholesterol level: 202 +/- 26 mg/dL; cholesterol level after growth hormone 200 +/- 24 mg/dL). With thyroxine (T4) replacement alone, or combined with growth hormone, a significant (P less than 0.01) decrement in plasma cholesterol occurred. (Thyroxine alone: 172 +/- 11 mg/dL; thyroxine and growth hormone: 172 +/- 10 mg/dL). Basal thyroid function tests, including TRH stimulation, were normal. Serum thyroxine levels decreased and serum triiodothyronine (T3) levels increased in response to growth hormone therapy. Linear growth increased significantly in response to growth hormone alone and both therapies combined. Serum values of T4 and T3 were significantly (P less than 0.001) correlated with basal cholesterol, r = 0.84 and r = 0.83, respectively. Our experience with euthyroid growth hormone deficiency confirms that modest hypercholesterolemia is characteristic of that disorder, and that growth hormone therapy has no statistically significant effect on plasma cholesterol. The modest hypercholesterolemia that does respond to thyroid replacement is further evidence of a subtle abnormality of thyroid function in such individuals. The mechanism whereby thyroid hormone has its cholesterol lowering effect in these apparently euthyroid subjects is unclear.

Serum cholesterol and triglycerides in children with growth hormone deficiency.

To test the hypothesis that hyperlipidemia is characteristic of growth hormone deficiency in childhood, we have measured serum cholesterol and triglyceride concentrations in 24 euthyroid children with growth hormone deficiency. Although modest elevations of cholesterol and/or triglyceride above the 95th percentile for age, race, and sex were present in 46% of the children studied, the mean (+/- 1 SD) cholesterol of 173 +/- 36 mg/dl and the mean triglyceride of 80 +/- 42 mg/dl were not significantly different from published normal mean values. Administration of human growth hormone for 4 mo to 15 of these subjects did not alter these mean cholesterol and triglyceride values, but did result in a marked improvement in the growth rate. Some individuals (n = 6) with a subnormal growth response to therapy and/or a low serum thyroxine and high serum cholesterol were treated for an additional 4 mo with growth hormone and thyroid hormone together. There was a statistically significant decrement in serum cholesterol in this group. We conclude that modest hyperlipidemia does exist in some children with growth hormone deficiency. Subclinical hypothyroidism may play a role in the hypercholesterolemia of some children, as may growth hormone deficiency itself. Any association of growth hormone and lipid metabolism remains to be clarified.

Vitiligo and juvenile diabetes mellitus.

Five juvenile diabetics had vitiligo. In two children, the vitiligo preceded the onset of diabetes. Four of the five patients had thyroid, adrenal, or gastric antibodies or a combination of these. In three children HLA-B8 antigens were detected, and one additional patient had HLA-Bw15. Of eight nondiabetic children with vitiligo, one had abnormal glucose tolerance. To the evidence supporting an autoimmune form of diabetes mellitus we add another observation: the association of insulin-dependent diabetes and childhood vitiligo.

Fluorinated corticosteroid toxicity in infants.

An 11-month-old girl died from complications of Cushing's syndrome. The latter was the result of routine topical and periocular dosages of fluorinated corticosteroids following corneal homografts for sclerocornea.

Conversion of progesterone-1,2-3-H to 5beta-pregnane-3,20-dione by brain tissue.

The presence of a 5beta-reductase acting to convert progesterone to 5beta-pregnane-3,20-dione is described in the soluble 105,000 x g fraction of a preparation of dog cerebral cortex. The function of this enzymatic activity is obscure but may be important in regulation of sensorium. 5beta-pregnane compounds are potent depressors of the central nervous system.

Plasma progesterone concentrations and infant temperament.

Progesterone and its metabolites are potent depressors of the central nervous system. Plasma progesterone concentrations significantly correlated with temperament ratings for approach/withdrawal (r = -0.35, p = 0.01) and intensity (r = -0.28, p = 0.04) among 42 normal infants. The median age at the time of the progesterone sample was 36 days. Easier infants tended to have higher plasma progesterone concentrations compared with more difficult infants (mean +/- SEM: 25 +/- 4 ng/dl versus 17 +/- 3 ng/dl, p = 0.15). Results are consistent with the hypothesis that progesterone or its metabolites may exert a behavioral depressor effect in infancy.