Carol A. Huseman

Sexual precocity in association with septo-optic dysplasia and hypothalamic hypopituitarism.

Sexual precocity in association with abnormalities of the central nervous system is well known, but its occurrence with hypothalamic hypopituitarism is most unusual. We report five females with septo-optic dysplasia, blindness, and multiple pituitary tropic hormone deficiencies: all were growth hormone and adrenocorticotropic hormone deficient; two had diabetes insipidus; one had sexual precocity, and one had early pubertal maturation, whereas three were prepubertal and responded to administration of synthetic gonadotropin-releasing hormone. These children retained ability to secrete gonadotropins despite the presence of anterior hypothalamic disease. Experimental data from primates plus our observations on these patients raise questions about the role of the anterior hypothalamus in gonadotropin secretion in man.

Anabolic effect of biosynthetic growth hormone in cystic fibrosis patients

The purpose of this study was to determine whether GH treatment of cystic fibrosis (CF) patients can result in an anabolic effect, i.e., increased weight gain, improved growth rate, nitrogen retention, and improved pulmonary function. Nine prepubertal endocrinologically normal CF patients (3 girls, 6 boys; chronological age (CA) 5.5–9.8 years, and bone age (BA) 4.5–9.0 years), received recombinant human growth hormone (rhGH) 0.3 mg/kg/week subcutaneously for a period of 12 months (N = 8) or 9 months (N = 1). Normal glucose tolerance was determined before treatment. Pulmonary function studies and anthropometric measurements were done every 3 months. Thyroid status, somatomedin C (SmC), BA, and routine chemistries were evaluated every 6 months. The pretreatment growth velocity averaged 5.7 ± 0.3 (SE) cm/year and significantly increased to 7.8 ± 0.4 (SE) cm/year during therapy, (P < 0.01). Standard deviation scores (SDS) for height significantly increased during rhGH therapy as compared with pretreatment, (P < 0.05). Weight of the patients during rhGH therapy did not significantly change during or after rhGH therapy. After therapy, all patients showed a significant increase in arm muscle area (AMA) and a significant decrement in arm fat area (AFA) (P < 0.01). Net nitrogen anabolism was negative in all subjects before therapy but became more positive in five patients during rhGH therapy. Three patients achieved positive nitrogen retention. SmC values significantly increased from a mean value of 0.62 ± 0.1 (SE) U/ml to 1.6 ± 0.6 (SE) U/ml after therapy. BA advanced 1.0 ± 0.1 SE per year after treatment. Of the seven patients able to perform adequate pulmonary function testing, improvement occurred in FVC, FEV10, and PEFR in 5, 5, and 4 patients, respectively, but these changes did not reach statistical significance. We conclude that biosynthetic rhGH therapy had a significant anabolic effect in CF patients as shown by increased growth velocity, SmC values, increased protein and decreased fat stores, and a positive or less negative net nitrogen retention in five of the patients. Pediatr Pulmonol. 1996;22:90–95.

Pitfalls in Using Human Chorionic Gonadotropin Stimulation Test to Diagnose Anorchia

Previous studies have concluded that surgical exploration is unnecessary in genetic male subjects with nonpalpable tests who fail to respond to human chorionic gonadotropin. Lack of response suggested absent testicular tissue. We report on 2 patients thought to have anorchia because of lack of response to human chorionic gonadotropin stimulation. Testes were found in both patients. Genetic and phenotypic male subjects with nonpalpable testes who fail to have increased testosterone after human chorionic gonadotropin stimulation should undergo laparoscopy. If testicular structures are present at laparoscopy surgical exploration is indicated. Unresponsiveness to human chorionic gonadotropin may be evidence of nonexistent or dysfunctional Leydig cells rather than evidence of complete absence of testicular tissue.

Congenital lipodystrophy: An endocrine study in three siblings

Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal...

Congenital lipodystrophy. II. Association with polycysticovarian disease

cultures were obtained from air-conditioning systems, patient rooms, or other rooms to confirm environmental contamination. As a result, no definite conclusions can be drawn as to the route of transmission of infection in our five patients. Previous reports have attempted to correlate the presence of airborne spore contamination and simultaneous occurrences of aspergillosis in compromised patients. 7-~ Elimination of sources of contamination resulted in the disappearance of cases of aspergillosis. Other reports suggest endogenous routes of transmission, such as the gastrointestinal tract and nasopharynx7 There is no information suggesting the incubation period for infection. In view of the limited ep idemiologic information concerning Aspergillus infections, outbreaks of disease in susceptible populations may warrant Careful environmental investigation, including culture confirmation. Specific recommendations for management of contaminated areas can only follow from a better understanding of the transmission o f disease,

Treatment of congenital virilizing adrenal hyperplasia patients with single and multiple daily doses of prednisone

Six patients with congenital virilizing adrenal hyperplasia were evaluated on single- and multiple-dose prednisone schedules. Each of the treatment periods was for one month. Patients were evaluated by 24-hour urinary excretion of 17-ketosteroids and pregnanetriol, as well as 0900 plasma concentrations of 17-hydroxyprogesterone, progesterone, and testosterone. By the criteria of urinary excretion of KS and PNT appropriate for chronologic age, three of the six patients were adequately controlled on prednisone given once a day. Prednisone administered twice daily at 12-hourly intervals either in equally divided doses or with a larger dose in the evening, however, resulted in adequate suppression in all patients. Because of the marked diurnal variation of plasma 17-OHP, the time of day that the sample is drawn is critical. Afternoon samples are often misleadingly low. Plasma 17-OHP concentration may reflect escape from therapeutic control sooner than urinary KS and PNT excretion. There was no correlation between 17-OHP and P values. Plasma concentration of T was not a reliable indicator of good control, since T values were often at prepubertal levels when urinary KS and PNT were elevated.

PRIMARY HYPOTHYROIDISM OF CHILDHOOD: EVALUATION OF THE HYPOTHALAMIC‐PITUITARY GONADAL AXIS BEFORE AND DURING L‐THYROXINE REPLACEMENT

Hypothyroidism is frequently associated with abnormal sexual development. To determine the longitudinal influence of thyroxine replacement on the hypothalamic pituitary gonadal axis, we studied five prepubertal hypothyroid girls and two boys before, and all the girls six weeks and one year after, thyroxine replacement. All girls showed significantly elevated basal gonadotrophin concentrations before treatment. Following one year of therapy, despite all girls having begun puberty, basal gonadotrophin concentrations were significantly decreased in the four euthyroid girls as compared with our normal pubertal girls. The fifth girl studied at one year was hypothyroid at the time of testing and her gonadotrophin values were increased even above previous basal values. Pretreatment serum TSH values inversely correlated with maximum pretreatment incremental LH (r= ‐0.54) and FSH (r= ‐0.52) responses to LHRH. Serum TSH values directly correlated with PRL concentrations (r =+0.82). Of the two hypothyroid boys evaluated, Patient 1 was mildly hypothyroid and showed normal prepubertal basal LH, FSH, testosterone and low normal LHRH responsiveness. Patient 2, who was more severely hypothyroid, had elevated basal gonadotrophin secretion and responsiveness to LHRH but prepubertal testosterone concentrations.

Hypothalamic Hamartoma: A Report of 2 Cases

Two patients with hypothalamic hamartoma presented with isosexual precocious puberty. LHRH challenge showed a pubertal LH response in both cases. Serum FSH responses to LHRH were pubertal in case 1, but prepubertal for case 2. Computed tomography revealed isodense noncontrast-enhancing retrosellar mass lesions in both cases. The tumors were composed of mature neurons and neuroglial tissue. Electron microscopy of the lesions failed to demonstrate dense core (neurosecretory) granules in either case. Subtotal removal of the harmartomas resulted in decreased LH responsiveness to LHRH in both cases. Serum FSH responsiveness to LHRH was not significantly suppressed postoperatively in case 1, and FSH responsiveness to LHRH in case 2 showed exaggerated levels, more typical of very young prepubertal girls. Postoperative magnetic resonance imaging (MRI) scans of both patients are also presented.

Theophylline treatment in the neonate with apnea: effect on growth hormone, thyroid hormone and TRH induced TSH secretion.

Caffeine has been shown to markedly alter growth hormone (GH), thyroid stimulating hormone (TSH), and thyroid hormones in animal studies. Similar studies in the human are lacking. To determine the effect of theophylline treatment on endocrine function in neonates with apnea, 10 infants were studied prospectively pretreatment, immediately following therapeutic blood levels of theophylline, at 2, 4, and 6 weeks thereafter and finally 2 weeks after discontinuation of theophylline. T4, free T4, T3, GH, and basal and stimulated TSH were measured at each study period. Results show no significant difference consequent to theophylline therapy on basal thyroid or GH secretion and thyrotropin-releasing hormone (TRH) induced TSH response at any study interval. We conclude there is no evidence to suspect abnormality occurring in growth, thyroid function and GH secretion in neonates receiving theophylline for breathing disorders.

SUPPRESSION OF GROWTH HORMONE AND THYROID HORMONE ASSOCIATED WITH VALPROIC ACID THERAPY

Valproic acid (VA) is a commonly used anticonvulsant. One proposed mechanism of action for VA is enhancement of central GABAergic tone by inhibition of GABA transaminase. We report suppression of somatic growth, hGH, and thyroid function in 5 girls, ages 2-14 years, maintained o therapeutic VA serum levels (60-120 ug/ml) for 15-84 months.All children showed suppressed hGH values to L-Dopa(A) or insulin(B) testing during VA therapy. hGH responses, Free T4 and SMC values normalized with concomitant increases in growth velocity after VA was stopped. Summary: Chronic VA therapy can suppress hGH, T4, SMC, and inhibit growth. This effect may be due to exhaustion of the stimulatory effect of GABA on the somatotrope or thyrotrope during chronic VA therapy. Growth must be carefully monitored in all patients on VA therapy.