Hormone and metabolic profiles in children and adolescents with type I diabetes mellitus.

Diurnal concentrations of glucose, the major regulatory hormones, and selected biochemistries were measured serially throughout a 25-h period in 38 healthy type I diabetic patients, 25 patients with acute ketoacidosis, and 20 normal subjects. Poor glucose control, meal intolerance, and hypercortisolemia were the dominant abnormalities in the healthy diabetic subjects. Ketonemia due to elevated plasma beta-hydroxybutyrate concentrations without ketonuria (nitroprusside reaction) was a frequent finding in a group of poorly controlled diabetic subjects. In the patients with acute ketoacidosis, the dominant abnormalities were overproduction of epinephrine and cortisol. High glucagon and growth hormone concentrations were documented in about one-half of these patients. We conclude that (1) the hyperglycemia, meal intolerance, and abnormal ketone body metabolism seen in these patients are caused by inadequacies in their insulin regimens; (2) ketone body underutilization contributes to diabetic ketosis; (3) epinephrine and cortisol overproduction are important components of acute ketoacidosis; and (4) the complex hormone-metabolic interactions in type I diabetes can best be explained by a multihormonal hypothesis with the primary defect being loss of beta-cell function.

Low plasma norepinephrine responses to acute hypoglycemia in children with isolated growth hormone deficiency.

Norepinephrine (NE) is a neurotransmitter of the sympathetic nervous system which is important in GH secretion. It also is a counterregulatory hormone which is released in response to insulin hypoglycemia. We measured the plasma NE, epinephrine, GH, and cortisol responses to insulin-induced hypoglycemia in 29 short healthy children. The 8 patients (5 males and 3 females) which had isolated GH deficiency had no plasma NE response to insulin hypoglycemia, whereas mean plasma NE increased 2-fold in the 21 GH-sufficient children. Plasma epinephrine concentrations increased in both groups, but were lower in the GH-deficient patients. While these findings do not permit us to determine whether the reduced plasma catecholamine responses to acute hypoglycemia are the cause, the consequence, or unrelated to the GH deficiency, we speculate that there is a relationship between the NE and GH deficiencies.

Elevated plasma beta-hydroxybutyrate concentrations without ketonuria in healthy insulin-dependent diabetic patients.

Plasma beta-hydroxybutyrate (beta-OHB) concentrations and simultaneous urine tests for ketonuria (nitroprusside reaction) were evaluated every 4 h throughout a 24-h study in 10 healthy insulin-dependent diabetics who had poor control based on home urine tests and elevated hemoglobin A1C. Concurrent measurements of the major carbohydrate regulatory hormones were made in the diabetic group and in a control population of 20 age-matched subjects. In the diabetics, 73% of the beta-OHB measurements were elevated. Only 43% of the abnormal beta-OHB values were associated with ketonuria. The diabetic subjects also showed exaggerated diurnal patterns for plasma beta-OHB and cortisol. There were no significant differences for the other regulatory hormones in the diabetic and normal groups. We conclude that 1) abnormal plasma beta-OHB levels without ketonuria are prevalent in poorly controlled diabetics; 2) negative nitroprusside tests for ketonuria underestimate the presence of ketonemia due to increased beta-OHB concentrations; 3) both insulin deficiency and glucocorticoid excess may influence ketone body metabolism in insulin-dependent diabetic patients.

Effect of clonidine on plasma cortisol concentrations.

There is a debate whether the fall in plasma cortisol concentrations after the early morning dosing of clonidine represents drug effect or normal diurnal variation. We compared the cortisol patterns of children after a 7:30 AM oral dose of clonidine (0.075 or 0.150 mg/m2) with the cortisol concentrations that resulted from diurnal variation. Some subjects had the diurnal study on day 1 and the clonidine study on day 2, whereas for others the testing sequence was reversed. Our results indicate that clonidine, in either dose, does not cause a fall in plasma cortisol levels greater than that with normal diurnal variation.

Psychosexual behavior in hypopituitary men: a controlled comparison of gonadotropin and testosterone replacement.

Nine gonadotropin-deficient hypopituitary men were cycled through periods of treatment with testosterone (T), gonadotropin (Gn), and placebo (Pl) using a blind cross-over design. Self-reports of sexual behavior, recordings of nocturnal penile tumescence (NPT), and sex steroid levels were obtained during each treatment period. Subjects had significantly higher plasma T during the T and Gn treatments than during the control periods. Similarly, self-reported frequency of ejaculation and ratings of libido as well as duration measures of NPT were significantly higher on T and Gn. Two thirds of the sample had no sociosexual experience. Behavioral differences between the T and Gn periods were minimal. These data support the hypothesis that Gn and T are equally effective in stimulating specific aspects of male psychosexual behavior.

Multicystic ovaries in primary hypothyroidism.

Nine of 12 girls diagnosed consecutively as having severe and longstanding primary hypothyroidism were found to have multicystic ovaries when evaluated by pelvic ultrasound examination. The cysts resolved rapidly with thyroid replacement therapy. The patients had either elevated or high normal plasma luteinizing hormone levels which decreased markedly after thyroid therapy. Five of seven patients tested with luteinizing hormone-releasing hormone had attenuated gonadotropin responses; the other two reacted normally. The pathogenesis of the cysts remains uncertain. Use of pelvic ultrasound scan has documented a high frequency of multicystic ovaries in girls with primary hypothyroidism.

Data on virilization and erotosexual behavior in male hypogonadotropic hypopituitarism during gonadotropin and androgen treatment.

The goal of this investigation was to assess whether or not gonadotropin therapy enhanced the degree of virilization and psychosexual behavior of men with hypogonadotropic hypopituitarism. Pre- and post-gonadotropin assessments of virilization in four men indicated that gonadotropin therapy was associated with dramatic improvements in the degree of virilization that each man previously obtained on androgen only. Retrospective interview data on erotosexual behavior indicated improved erotosexual function on gonadotropin as compared to the prior androgen treatment. These data suggest that complete virilization in these men was partially gonadotropin dependent. Whether or not the behavioral benefits reported by these men represented a direct or synergistic effect of gonadotropin in the expression of erotosexual behavior or an indirect effect of improved virilization can not be answered by these data.

Triad of hypopituitarism, granulomatous hypophysitis, and ruptured Rathke's cleft cyst.

A 19-year-old girl with pituitary insufficiency and a large sella turcica was found to have granulomatous hypophysitis in association with a Rathke's cleft cyst. We think that the inflammatory process represents a foreign body reaction to leakage of cyst contents, with destruction of pituitary tissue.

Vasoactive intestinal peptide producing neuroblastoma.

The Verner-Morrison syndrome has been described in 19 previous patients with ganglioneuroma and ganglioneuroblastoma but never neuroblastoma. Its occurrence following treatment of a neuroblastoma with chemotherapy with maturation of the tumor has only been reported on one previous occasion. Our case suggests that vasoactive intestinal polypeptide may be used not only as a diagnostic indicator for the presence of a neural crest tumor but also as a marker to monitor maturation of the tumor and indicate an improving prognosis.

Outcome of lower L-thyroxine dose for treatment of congenital hypothyroidism.

The appropriateness of the recommended L-thyroxine dose (10-15 micrograms/kg/day) for the treatment of congenital hypothyroidism has been questioned because of the risk of iatrogenic hyperthyroidism. We report the outcome of 23 newborns with congenital primary hypothyroidism treated with 25 micrograms L-thyroxine per day (5.3-9.2 micrograms/kg/day) and followed for an average of 59 months. Serum thyroxine (T4) values increased (X = 11.4 +/- 2.7 micrograms/dL) within 4 weeks posttherapy; eight infants had T4 levels > or = 13 micrograms/dL on only half the currently recommended dose. Thyroid-stimulating hormone (TSH) values remained elevated in 18 of 21 patients for 2-21 months despite a high-normal T4. Psychometric tests were performed in 19 of the 23 patients. The mean Full Scale IQ for the congenital hypothyroid group (n = 16) was 101.4 +/- 13.2 with comparable Verbal and Performance IQ scores. Patients with a bone age (BA) of < or = 32 weeks or T4 < 2 micrograms/dL at initial evaluation had significantly Lower Verbal IQ scores. A standardized parent-report assessment of behavioral and emotional functioning revealed subgroup scale scores that were indistinguishable from nonclinical norms. We conclude that (1) average range IQ scores and positive behavioral adaptation are observed in congenitally hypothyroid children treated with L-thyroxine doses lower than currently recommended; (2) the L-thyroxine dose should be individualized to prevent iatrogenic hyperthyroidism; (3) TSH normalization should not be a primary objective of treatment, and (4) a prospective study comparing the advantages and risks of different doses of L-thyroxine is needed.