One-year treatment with DiaPep277 at a dosage of 1 mg is safe for use and well tolerated in children with recent-onset T1DM. However, it appears to have no beneficial effect in preserving beta-cell function or improving metabolic control.
Insulin-induced hypoglycemia (IIH) is the gold standard test for assessment of the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, but it may be hazardous. We sought to determine whether the standard (250 micrograms) or low-dose (1 microgram/1.73 m2) short ACTH test can replace IIH in patients with idiopathic multiple pituitary hormone deficiencies (MPHD). Three groups of subjects were studied: 1) control group, children with early or accelerated puberty and no other evidence of adrenal or pituitary pathology (n = 13, age 10.1 +/- 2.2 yr, 3 males); 2) patients with idiopathic hypothalamic pituitary insufficiency and either isolated GH deficiency or MPHD and preserved HPA function (n = 20, age 13.7 +/- 4.4 yr, 13 males); and 3) MPHD patients with impaired HPA axis function (n = 10, age 16.8 +/- 4.8 yr, 9 males). IIH and the 250 micrograms and 1 microgram/1.73 m2 ACTH tests were performed in groups 2 and 3; group 1 underwent only the ACTH tests. Pass peak cortisol level was defined as 520 nmol/L. No significant difference was noted between the standard and low-dose tests in the 30-min cortisol response to ACTH. Basal and peak cortisol levels attained on both ACTH tests were similar in groups 1 and 2 and significantly lower in group 3 (P < 0.0001). Both the 250 and 1 microgram ACTH tests were highly correlated with IIH (r = 0.71, P < 0.0001 for the 250 micrograms, r = 0.7, P < 0.0001 for the 1 microgram, n = 30), and both demonstrated high sensitivity (90% each) and specificity (100% and 90%, respectively) compared with IIH. We conclude that in idiopathic MPHD patients, both the standard and low-dose ACTH tests are equivalent to IIH in detecting HPA insufficiency. We suggest that they can replace IIH as a screening test for the integrity of the HPA axis in children with suspected MPHD.
The course of Graves' thyrotoxicosis in 7 prepubertal children (6.4 Ϯ 2.4 yr) was compared with that in 21 pubertal (12.5 Ϯ 1.1 yr) and 12 postpubertal (16.2 Ϯ 0.84 yr) patients. In the prepubertal group the main complaints were weight loss and frequent bowel movements (86%), whereas typical symptoms (irritability, palpitations, heat intolerance, and neck lump) occurred significantly less often (P Ͻ 0.01). The most prominent manifestation at diagnosis was accelerated growth and bone maturation: their height SD score was significantly greater than that of the pubertal and postpubertal patients (2.6 Ϯ 0.7 vs. 0.15 Ϯ 0.65 and 0.15 Ϯ 0.9, respectively, P Ͻ 0.001), and their bone age to chronological age ratio was 1.39 Ϯ 0.35 compared with 0.98 Ϯ 0.06 in the pubertal children (P ϭ 0.02). T 3 levels were also significantly higher than in the other two groups (9.9 Ϯ 2.9 nmol/L vs. 6.32 Ϯ 1.9 nmol/L and 6.02 Ϯ 2.0 nmol/L, P ϭ 0.01).All patients were initially prescribed antithyroid drugs (ATDs). Overall, adverse reactions to ATDs occurred in 35%, with a higher rate among the prepubertal children (71%) than the pubertal (28%) and postpubertal (25%) patients (P ϭ 0.08). Major adverse reactions were noted in two children, both prepubertal. Remission was achieved in 10 patients (28%). Although the rate of remission did not differ among the three groups, time to remission tended to be longer in the prepubertal children (P ϭ 0.09).In conclusion, thyrotoxicosis has an atypical presentation and more severe course in prepubertal children. Considering their adverse reactions to ATD, overall low remission rate, and long period to remission, definitive treatment should be considered earlier in this age group. (J Clin Endocrinol Metab 85: 3678 -3682, 2000)
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