Paula M. Hale

Nocturnal Serum Growth Hormone Concentration is not Augmented by Short-Term Testosterone Infusion in Pubertal Boys

ABSTRACT: Chronic exposure to testosterone (T) increases growth hormone (GH) secretion. To determine whether acute exposure to T would also enhance GH secretion, we infused saline, followed 1 wk later by T, for 18-24 h at one-third the adult male production rate in 12 pubertal boys and at the adult male production rate in eight additional pubertal boys. Blood was obtained every 20 min for GH and every 30 min for T from 2000-0800 h. Though infusion significantly increased serum T concentrations in all 20 boys, mean GH concentration, GH pulse frequency, and GH pulse amplitude did not increase compared to the saline infusion night. The secretory dynamics of GH as a function of 3-h time blocks from 2000-0800 h were also determined in the eight boys who received the higher dose of T. The profile for mean GH concentration, pulse frequency, pulse amplitude, and peak area were not affected by acute infusion of T at concentrations sufficient to alter LH secretion. This suggests that, at least in pubertal boys, one must be exposed to T for a period longer than 12-18 h to induce increased GH secretion.

31 GROWTH HORMONE SECRETORY PATTERNS - AID TO DIAGNOSIS OF GROWTH PROBLEMS

Since GH responses to provocative (PGH) stimuli are often not reflective of physiological GH secretion, PGH was compared with integrated physiological GH secretion (ICGH) in 133 children and adolescents ages 4-18, with abnormal growth (<5th or >95th % for height and/or abnormal growth velocity). ICGH was determined by continuous ambulatory blood withdrawal pump (collected in one hr aliquots) over 12 h (1800-0600) or 24 h (1800-1800) in 87, or by 12 h intermittent q 20 min sampling (1800-0600) in 46 patients. The following morning all children had either arginine-insulin (AI) induced hypoglycemia (118) or oral clonidine (C) (15) tests. Serum somatomedin C, T/E2, bone age and T4 were also correlated with growth velocity and GH responses. In 33, 24 h ICGH correlated highly with, but was not more informative than 12 h ICGH (1800-0600) performed in all patients. Discordant GH levels (PGH vs ICGH, × and peaks) were present in 47 of 120 (40-50% of children with constitutional delay (CD) of growth), depending on the criteria for normality used. Low ICGH (<2 ng/ml) was seen in 42, and borderline ICGH (2-3 ng/ml) in 21. Low (<7 ng/ml) or borderline (7-10 mg/ml) GH responses to AI or C were seen in 48 and 19 children respectively. ICGH was useful in excluding a Dx of GH deficiency (GHD) in 14 patients with low PGH, while the Dx GHD was further substantiated in 26 patients. ICGH proved most valuable in patients with CD-delayed adolescence and/or emotional stress where “transient” GHD and discordant GH values are often obtained on pharmacologic testing.

State of the Art: Islet Cell Antibody Tests

The discovery of anti-islet cell antibodies (ICAbs) in the sera of individuals with insulin- dependent diabetes (IDDM) was a significant milestone in the history of diabetes research. ICAbs have been found in the sera of 60%-85% of new-onset diabetic patients. It has been suggested that ICAbs play a role in the destruction of beta cells possibly by complement- mediated beta cell lysis, or by acting as mediators in antibody- dependent cell-mediated cytotoxicity. ICAbs have been shown to be markers of ongoing beta cell destruction. The presence of ICAbs has preceded the appearance of clinical evidence of IDDM by as long as eight years. The detection of ICAbs in first-degree relatives of individuals with IDDM identifies a population at risk for developing IDDM. Means of intervention need to be established to prevent progressive beta cell destruction in these individuals.

30 ACUTE AND CHRONIC EFFECTS OF CLONIDINE ON GROWTH HORMONE AND GONADOTROPIN SECRETION IN ADOLESCENT BOYS

Clonidine, a presumed α2 agonist, is a potent stimulus for GH in man and gonadotropins in rodents. To assess the acute and chronic effects of this drug on GH and gonadotropins in adolescents, we studied 4 boys in early to mid-puberty, sampling blood every 15-20 min for LH and FSH (x ± SE mIU/ml) and hourly for GH, before and after one or two oral 0.15mg/m2 doses of clonidine. (*=p < .05 vs control):Clonidine had no effect on LH pulse frequency or the circadian pattern of LH, FSH or GH secretion. It was consistently followed within 2h by a GH peak comparable to the spontaneous pulses. This effect on GH was maintained in pt. #4 after chronic therapy. We conclude: 1) clonidine has a modest effect, if any, on gonadotropins at this stage of human puberty; 2) growth should be followed closely in adolescents on clonidine therapy.

GROWTH HORMONE TREATMENT IN A CHILD WITH LATEX ALLERGY AND MYELOMENINGOCELE.50

Latex allergy is recognized with increasing frequency in children with myelomeningocele. A 5 year old female child with a documented history of latex allergy and myelomeningocele was evaluated for poor growth. The patient had a history of rashes/urticaria and one episode of wheezing upon exposure to products made of natural rubber latex. Following an endocrinologic evaluation growth hormone (GH) therapy was planned. GH is routinely dispensed in powdered form in a glass vial with rubber stopper and administered by insulin syringe. The stopper is entered by syringe multiple times (once when the diluent is added and then daily to withdraw the GH for injection), potentially releasing latex particles into the solution, which could be injected into the patient along with the GH. Prior to initiating GH therapy the patient had a positive latex-specific IgE antibody test =7.1 ng/ml (> than 2.0 ng/ml indicates a high propensity for developing an allergic reaction). Because of concern of anaphylaxis, the patient was admitted to the hospital for prick and intradermal skin testing with the prepared GH solution. In order to more closely mimic home administration of GH, the diluent was added 7 days prior to use. The vial was stored inverted (to maximize contact with the rubber stopper) and the rubber stopper entered several times with a needle. The patients response to this solution of GH (0.74 mg= daily dose) was equal to that of the negative control (saline) while demonstrating an adequate response to the positive control (histamine). The patient has been treated with GH (0.3 mg/kg/week) for a total of 9 months without any adverse reactions. Despite an increase in the latex-specific IgE antibody test to 11.1 ng/ml one month after the initiation of GH therapy, she has never experienced any local nor systemic reactions to the GH and continues on this current therapy. The development of latex allergy in children with myelomeningocele is of increasing concern. Latex allergy should not preclude treatment with GH. With appropriate measures, children with latex sensitivity may be treated with GH without adverse reaction.

TSH Receptor Antibodies in Neonatal Hyperthyroidism

The hyperthyroidism in Graves’ disease is caused by circulating autoantibodies which stimulate the thyroid gland (Burman and Baker, 1985). If these antibodies are present in a pregnant woman, they may cross the placenta and cause transient neonatal hyperthyroidism (Munro et al. , 1978). Delays in treatment or failure to detect neonatal hyperthyroidism may lead to chronic complications such as mental impairment or craniosynostosis (Daneman and Howard, 1980). A method to predict and diagnose neonatal hyperthyroidism would be valuable. Historically, methods to detect Graves1 autoantibodies involved laborious and difficult bioassay (Hensen et al. , 1984). We report here the use of a simple, commercially available radioimmunoassay to detect Graves1 autoantibodies in four cases of neonatal hyperthyroidism.

112 ACQUIRED PARTIAL 21-HYDROXYLASE DEFICIENCY IN A GIRL WITH PEUTZ-JEGHERS SYNDROME (PJS)

A 12 yo gypsy girl with PJS s/p resection of adenocarcinoma of the colon at age 4 presented with hirsutism and menorrhagia of 9 months duration. Menarche occurred at age 10 initially with regular periods. Previous reports of an increased incidence of gonadal as well as GI neoplasms in PJS prompted a thorough investigation. Thyroid function was normal. A small left ovarian cyst was present by pelvic ultrasound. No ovarian/adrenal masses were present on abdominal CT scan. ACTH stimulation test (0.25 mg IM) and dexamethasone suppression test (0.5 mg po q 12h × 5d) showed:The basal Δ5-17-OHP, 17-OHP, Δ4A and DHEA-S were elevated. Low ratios of Δ5 17-OHP/17-OHP (0.5) and DHEA/Δ4A (2.8) as well as high response of 17-OHP and Δ4A to ACTH were diagnostic of partial 21 hydroxylase deficiency. Suppression of adrenal steroids by dexamethasone further supported this diagnosis.