Sandra L. Blethen

Effect of Pubertal Stage and Recent Blood Glucose Control on Plasma Somatomedin C in Children with Insulin-dependent Diabetes Mellitus

One hundred and fifty-five children with insulin-dependent diabetes mellitus were studied to determine the relationship of plasma somatomedin C concentrations to pubertal stage, recent blood glucose control, duration of diabetes, and daily insulin dosage. Plasma somatomedin C, as measured by radioimmunoassay, increased with age and the progression of puberty in both boys and girls, but was not different from those of normal children aged 5–18 yr. In diabetic children under 5 yr of age, plasma somatomedin was significantly lower than in normal children. These results are different from those reported previously in diabetic children, in which somatomedin activity was measured using a pig cartilage bioassay. In boys, puberty was accompanied by an increase in hemoglobin A1c from 11.6 to 14.1% despite a 36–44% increase in total daily insulin dosage adjusted for body weight. In girls, puberty was also associated with an increase in hemoglobin A1c (12.1–15.1%) without a change in weight-adjusted insulin dose. Although there was no apparent correlation between hemoglobin A1c and somatomedin C in the group as a whole (r = −0.078), multiple regression analyses demonstrated a significant negative correlation between these two variables (P < 0.001) when considered independently of age, sex, pubertal stage, duration of diabetes, and insulin dose. Pubertal status had a significant (P < 0.01) effect on plasma somatomedin C; plasma somatomedin C was also significantly positively correlated with the duration of diabetes (P < 0.01) but not with weight adjusted insulin dose. SMC concentration was not correlated with age when this variable was considered independently of puberty (P = 0.26). The data indicate that puberty and metabolic control both have significant yet independent effects on somatomedin C in children with insulin-dependent diabetes. In addition, the increased somatomedin C associated with puberty may contribute to the accelerated development of diabetic complications seen at this time, while the lowering of somatomedin C associated with worsening metabolic control may adversely affect linear growth.

Growth hormone treatment in Noonan syndrome: The National Cooperative Growth Study experience☆☆☆★★★♢

We evaluated the response to growth hormone (GH) therapy in 150 children (97 boys) with Noonan syndrome (NS) by analyzing growth data from children with NS who were enrolled in the National Cooperative Growth Study and compared those data with National Cooperative Growth Study growth data from children with idiopathic growth hormone deficiency (IGHD) and Turner syndrome (TS). Children with NS were significantly shorter than those with IGHD and TS. The annualized growth rates for years 1, 2, 3, and 4 of therapy in patients with NS who were naive to previous GH therapy were significantly greater than baseline. Their growth rates for years 1, 2, 3, and 4 were intermediate between those in children with IGHD and TS and were significantly different from both. A significant improvement occurred in height SD scores for those 42 children with NS who have been monitored for at least 4 years of GH therapy. Three of six boys with NS for whom adult height data were available exceeded their pretreatment predicted heights.

Slipped Capital Femoral Epiphysis in Children Treated with Growth Hormone

We examined the association between slipped capital femoral epiphysis (SCFE) and growth hormone (GH) treatment in 16,514 children who had not been treated with GH prior to their enrollment in the Nati

Possible abnormalities of steroid secretion in children with Smith-Lemli-Opitz syndrome and their parents

In early infancy, two unrelated children with Smith-Lemli-Opitz syndrome were found to have elevated levels of androgen sulfates. When the steroid conjugates in the serum of normal infants were hydrolyzed and chromatographed on Sephadex LH-20, 4 androgen containing peaks (I, II, III, IV) were found. In the serum from these two infants with Smith-Lemli-Opitz syndrome, Peaks I and III were increased, but Peaks II and IV were absent. The parents of the two children, and of three additional unrelated children with Smith-Lemli-Opitz syndrome, had exaggerated 17-hydroxyprogesterone responses to an intravenous bolus of ACTH. These findings suggest that a defect in steroid metabolism may be linked to the Smith-Lemli-Opitz syndrome.

A long-acting human growth hormone (Nutropin Depot): efficacy and safety following two years of treatment in children with growth hormone deficiency.

BACKGROUND Nutropin Depots [somatropin (rDNA origin) for injectable suspension] is a long-acting form of human growth hormone (GH) to be administered by subcutaneous (s.c.) injection. The availability of this formulation offers the opportunity for greater convenience and compliance by decreasing the number of injections and frequency of administration required. OBJECTIVE To determine the efficacy and safety of a long-acting formulation of GH administered in children with GH deficiency (GHD) once or twice monthly for 2 years. PATIENTS Fifty-six previously untreated, prepubertal children with GHD received Nutropin Depot 1.5 mg/kg once monthly (1x/mo), or 0.75 mg/kg twice monthly (2x/mo) for 24 months. The mean pretreatment growth rate was 5.0 +/- 2.4 cm/yr. RESULTS The 0-12 mo growth rate (mean +/- SD) was 8.3 +/- 1.5 cm/yr in the 1x/mo group and 8.2 +/- 2.0 cm/yr in the 2x/mo group. The 12-24 month growth rate was 7.2 +/- 1.5 cm/yr in the 1x/mo group and 6.9 +/- 1.5 cm/yr in the 2x/mo group. During the 24 months of treatment, height standard deviation score (SDS) increased by 1.0 +/- 0.5 SD in the two groups combined (p <0.0001). The corresponding advancement in bone age was 2.2 +/- 0.7 yr, resulting in a gain in Bayley-Pinneau predicted adult height (PAH) SDS of 0.6 +/- 0.9 SD in the 1x/mo group and 0.6 +/- 1.0 SD in the 2x/mo group. No serious adverse events attributable to the study drug were reported. Injection site reactions were common, but resolved without intervention. Pre-dose fasting and postprandial glucose and insulin levels, as well as hemoglobin A1c levels, were unchanged from baseline values. CONCLUSIONS Treatment with Nutropin Depot is associated with catch-up growth and normal skeletal maturation and is a viable alternative to daily injections of GH in children with GHD.

Insulin treatment normalizes reduced free insulin-like growth factor-I concentrations in diabetic children.

OBJECTIVE We have recently demonstrated multiple aberrations in the GH–IGF axis in the sera of children with untreated insulin‐dependent diabetes mellitus (IDDM) which were restored after insulin replacement. However, the net result of these alterations in the IGF system on the concentrations of free/biologically available IGF‐I in the serum have not been examined directly in diabetic children. In the present study, the effect of diabetes and subsequent insulin replacement on the circulating free IGF‐I concentrations are assessed.

Comparison of Predicted and Adult Heights in Short Boys: Effect of Androgen Therapy

Summary: We evaluated the accuracy of height predictions based on the tables of Bayley and Pinneau (2) in 43 boys with short stature. Sixteen boys were treated with androgens and 27 received no treatment. In 17 boys whose bone ages were within normal limits, and who received no treatment, the mean ± SE predicted height of 164.9 ± 1.5 cm was not significantly different from the mean adult height (166.5 ± 1. 5 cm). The predicted height exceeded the actual adult height by more than 5.1 cm in only one instance [5.1 cm is the degree of accuracy reported by Bayley and Pinneau (2)]. In 10 boys, whose bone ages were severely delayed (more than 2 SD below their chronologic age) and also were not treated, predicted height overestimated adult height by more than 5.1 cm in five of them. This difference was statistically significant (P < 0.05).In five boys with normal bone ages, androgen therapy had no significant effect on either predicted height (168.1 ± 4.1 before, 166.8 ± 4.4 cm after) or actual adult height (166.5 ± 4.1 cm). The 11 boys with severely delayed bone ages had a significant increase in predicted height during androgen therapy (165.4 ± 1.5 to 169.8 ± 1.7 cm, P < 0.01), but actual adult height (162.4 ± 2. 4 cm) was not significantly greater than pretreatment predicted height. Further, the number of boys whose predicted height exceeded their adult height by 5.1 cm was not significantly different in treated (4/11) or untreated (5/10) boys.The Bayley-Pinneau method of predicting adult height markedly overestimates adult height in about one-half of boys who have a bone age delay of more than 2 SD. Short-term therapy with androgens does not alter this outcome.

Overnight dexamethasone suppression test: normal responses and the diagnosis of cushing's syndrome

Serum cortisol levels were measured the morning after the administration of 1 mg of dexamethasone. Only 5 of 190 subjects had serum cortisol levels greater than 2 micrograms/dL. Thus, the normal value after dexamethasone suppression is less than 2 micrograms/dL rather than less than 5 micrograms/dL as has generally been accepted. The distinction is important because some individuals with Cushings syndrome partially suppress their cortisol levels to less than 5 but more than 2 micrograms/dL during the test procedure. Thus, the use of 5 micrograms/dL as the normal value may lead to an unnecessary delay in diagnosis.

Do growth hormone (GH) serial sampling, insulin-like growth factor-I (IGF-I) or auxological measurements have an advantage over GH stimulation testing in predicting the linear growth response to GH therapy?

objective To compare the relative utility of GH secretion via pharmacological stimulation, overnight serial sampling, IGF‐I levels and auxological variables as predictors of change in height standard deviation score (ΔHt SDS) during GH treatment.

Regulation of the acid‐labile subunit of the insulin‐like growth factor ternary complex in patients with insulin‐dependent diabetes mellitus and severe burns

OBJECTIVE Little information is available regarding the regulation of serum acid‐labile subunit (ALS) in human disease. We have studied alterations in serum ALS of the insulin‐like growth factor (IGF) ternary complex in children with untreated insulin‐dependent diabetes mellitus (IDDM) and subjects with severe burns before and after insulin therapy. In addition, we have investigated the effect of insulin plus GH on serum ALS in burn patients.