Nine patients with athyrotic or ectopic cretinism ages 6 mo.-17 yrs-were studied to examine the relation between age and the quantities of oral L-thyroxine (T4) adequate to restore TSH hypersecretion to normal levels by feedback control. All but one patient had very low levels of endogenous T4 (below 1.0 mug/100 ml) before treatment. However, based on clinical signs and serum T4-1 values, all were judged to be euthyroid or sub-clinically hyperthyroid by L-T4 replacement during the observation period. L-T4 dosage was increased or decreased by 25 or 50 mug/day at 2-12 mo. intervals, and the TSH response to exogenous thyrotropin-releasing hormone (TRH) was tested sequentially at each dose of L-T4 until a normal or slightly suppressed TSH response was obtained The L-T4 dosage which was associated with normal TSH responsiveness to TRH (the adequate L-T4 dose) was high in infancy (10 mug/kg/day), decreasing with age to a level of 3-4 mug/kg/day in pubertal children (correlation coefficient r=-0.820, P less than 0.01). The adequate L-T4 dose observed between 4 and 12 yrs of age was lower than the usually recommended dose (4-6 vs. 7-8 mug/kg/day). On these L-T4 doses, serum T4I concentrations were significantly higher in patients under 5 yrs of age than in older patients (8.3+/-1.5 vs. 6.5+/-0.7 mug/100 ml, P less than 0.02). Serum triiodothyronine (T3) values were also elevated in young children, decreasing with age to the normal range. TSH responses to TRH were completely suppressed at the serum T4-I levels of 9 mug/100 ml and T3 of 250 ng/100 ml or less in 7 patients over 4 yrs of age, but not in 2 younger patients. Although the number of patients examined was limited, these results suggest that the pituitary threshold for feedback regulation of TSH secretion by T4 decreases with age in children with cretinism and the usually recommended replacement doses of L-T4 between 4 and 12 yrs of age are probably overestimated.

An 8-yr-old girl is presented who had periodic attacks of vomiting, psychotic depression, drowsiness, and hypertension (160/110 mm Hg) for a period of 16 months after head injury. At the initiation of the attack, serum ACTH and vasopressin levels were prominently increased (610 pg/ml and 41 microunits/ml, respectively), followed by hypercortisolemia, hyponatremia, and hypoosmolality in plasma. Serum PRL also was elevated (91 ng/ml). Responses of GH and cortisol to insulin-induced hypoglycemia and those of TSH to TRH were reduced. Urinary excretion of epinephrine and norepinephrine were increased, while dopamine (DA) excretion was reciprocally decreased, resulting in a marked elevation of the epinephrine plus norepinephrine to DA ratio during the episodes (0.4-4.5); this was normalized on attack-free days (0.08-0.25). During the attack, the concentration of homovanillic acid, a major metabolite of DA in the brain, also was reduced in cerebrospinal fluids from 70 to 23 ng/ml. The administration of methyl-dopa and reserpine effectively suppressed the recurrence of the episode. Although the exact cause of this syndrome is unknown, a periodic metabolic dysfunction of catecholamine in the central nervous system might be postulated.

Human thyroid stimulating activity in 37 patients with juvenile hyperthyroidism was studied during the course of antithyroid drug treatment. Observation periods varied from 6 months to 6 years (average 3 years). The existence of human thyroid stimulator (HTS) in their sera was determined by triiodothyronine (T3) release from resected thyroid adenomas. A measurement of T3 above the control value of 140% was judged to be positive. Before treatment, 25 of the 28 patients with Graves' disease had HTS in their sera, one of the 7 patients with Hashimoto's thyroiditis had HTS, and none of the 19 normal children had HTS in their sera. During the therapy, 7 of 18 Graves' patients had HTS. After cessation of the therapy, 9 of 22 patients remained HTS-positive, and 8 of the 9 patients with positive HTS relapsed within 6 months, whereas in 13 HTS-negative patients, 3 escaped and 10 remained in remission. There was no significant correlation between human thyroid stimulating activity (HTSA) and the following: serum T3 concentration, 131I-thyroidal uptake, TSH responsiveness to TRH and antithyroid antibody titre. These results indicate that (1) almost all patients with Graves' disease have HTS when they are ina state of hyperthyroidism, (2) HTS tends to disappear with the clinicial remission, but its persistence seems to predict relapse in the future, and (3) routine laboratory tests cannot serve as alternative to HTS.