Paul B. Kaplowitz

Delayed puberty in obese boys: Comparison with constitutional delayed puberty and response to testosterone therapy

OBJECTIVE To evaluate the results of a brief course of testosterone therapy in boys with delayed puberty and to compare the responses seen in boys with constitutional delayed puberty (CDP), boys with obesity, and boys with possible gonadotropin deficiency. DESIGN AND SETTING A retrospective chart review was done for 36 boys aged 14 years or older, seen between 1983 and 1996 because of delayed puberty, who were given 4 monthly injections of testosterone, 100 mg/mo, and had adequate follow-up. RESULTS There were 23 boys whose findings before and after treatment were consistent with a diagnosis of CDP. Testosterone treatment increased the growth rate from 4.3 cm/y to 11.2 cm/y (P <.00001), and mean testis length increased 0.6 to 0.8 cm in all (from a mean of 2.9 to 3.6 cm, P <.00001) in the 4 months after testosterone treatment. Serum testosterone 4 months after therapy was higher than that before therapy (P =.00003). Of 5 boys with growth hormone deficiency but unknown gonadotropin status, 2 had lack of progression after testosterone therapy and were believed to have permanent gonadotropin deficiency. Seven of the 36 boys were obese (body mass index, >25), and 6 had a response to testosterone similar to boys with CDP with clear pubertal progression. One obese boy and one nonobese boy were diagnosed as having isolated gonadotropin deficiency. CONCLUSIONS Monitoring the growth and genital responses to a 4-month course of testosterone injections helps to differentiate CDP from gonadotropin deficiency in boys with delayed puberty. Obese boys constitute a distinct category of boys with pubertal delay in terms of their growth, but their response to testosterone is similar to that observed in boys with classic CDP.

Radioimmunoassay of vasopressin in familial central diabetes insipidus

We examined plasma arginine-vasopressin concentrations by radioimmunoassay in two brothers, aged 6 and 7.5 years, with familial central diabetes insipidus inherited as an autosomal dominant trait. Plasma AVP was measured in relation to increasing plasma osmolality induced by water deprivation and hypertonic saline infusion. The brother with the more severe urinary concentrating defect had no detectable AVP when his plasma osmolality was as high as 306 mOsm/kg; the other brother had detectable but clearly subnormal AVP concentrations. The one brother tested had an apparently normal end-organ response to exogenous vasopressin. Chlorpropamide had a significant antidiuretic effect in the brother with detectable AVP levels, and a lesser effect in the other brother . Our findings suggest that intrafamilial variation in the severity of congenital DI is related to the degree of vasopressin deficiency.

Effect of growth hormone therapy on final versus predicted height in short twelve- to sixteen-year-old boys without growth hormone deficiency

The effect of growth hormone therapy on final height in 28 short boys without growth hormone deficiency was evaluated retrospectively. The boys had received growth hormone for at least 2 years and were close to final height when therapy was stopped. The mean estimated final height was very close to that predicted from the pretherapy bone age. The fact that bone age advanced a mean of 4.9 years during a mean of 3.5 years of therapy may account for the lack of effect on final height.

Marasmic-Kwashiorkor in an 8-Week-Old Infant Treated with Prolonged Clear Liquids for Diarrhea

From the Department of Pediatrics, University of North Carolina School of Medicine at Chapel Hill and the Research Triangle Insutute, Research Triangle Park, North Carolina. Correspondence to: Raymond B. Isely, M.D., Research Triangle Institute, P.O. Box 12194, Research Triangle Park, NC 27709. Received for publication August, 1978; revised February, 1979 and accepted May 8, 1979. Editorial Comment: This brief case report is published as

418 PERIPHERAL RESISTANCE TO THYROID HORMONE IN AN INFANT

Peripheral resistance to thyroid hormone is a rare syndrome characterized by elevated serum total and free T4 and T3 concentrations, an absence of clinical manifestations of hyperthyroidism and abnormal TSH suppression. We studied a clinically euthyroid 6 month old infant, the youngest patient with this syndrome yet described, to determine the mechanism of thyroid hormone resistance. The degree of pituitary insensitivity to T3 was investigated by measuring serum T4 and TSH, and the TSH response to TRH infusion (100 μg) in response to increasing doses of T3.Four times the replacement dose of T3 (40 μg/day) was required to normalize the serum T4 and the response to TRH. With 80 μg/day T3 the TSH response to TRH was virtually abolished, as occurs in hyperthyroidism, but there were no clinical signs of thyroid hormone excess. Specific nuclear T3 binding was compared in cultured skin fibroblasts from the patient and a normal infant. Binding was normal at low concentrations of unlabelled T3, but at high concentrations there was evidence for a second low-affinity T3 receptor. While resistance to thyroid hormone has been demonstrated in this infant, the cellular mechanisms are unclear.

Fibroblasts from a patient with Leprechaunism are resistant to Epidermal Growth Factor (EGF) as well as Insulin

Leprechaunism is characterized by severe intrauterine growth retardation and insulin resistance. We have reported (JCEM 48:495, 1979) that Leprechaun fibroblasts have diminished DNA synthesis in response to insulin or serum, despite apparently normal binding of 125I-insulin and 125I-somatomedin-C. The doubling time of Leprechaun fibroblasts is prolonged (96 vs 48 hrs.), suggesting an aberrant growth mechanism(s). To further characterize the defect in this syndrome, we compared the metabolic responses of Leprechaun and normal skin fibroblasts in culture. Stimulation of 3H-glucose uptake was minimal with low insulin (1-10 ng/ml) relative to control cells, but was comparable at higher insulin concentrations (1-10 μg/ml). Insulin-stimulated 3H-aminoisobutyric acid (3H-AIB) uptake by Leprechaun cells was less than normal at all concentrations tested. Defective responses of Leprechaun cells were not limited to insulin, since EGF also had diminished effects on 3H-AIB uptake and DNA synthesis. 125I-EGF binding, however, was normal. Conclusions: 1) In addition to defective responses to insulin, fibroblasts from our patient are resistant to the effects of EGF. 2) Since receptors for these peptides are apparently normal, it is likely that these cells have a post-receptor defect. 3) We speculate that Leprechaun cells have an alteration in a metabolic pathway which is involved in the action of multiple growth factors.