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The circadian pattern of serum TSH in normal children, aged 5-18 yr, is characterized by a nocturnal surge and is presumably related in some way to a biological clock within the central nervous system. To look for patients deficient in the nocturnal TSH surge, we studied 52 children with hypothalamic-pituitary disorders. Thirteen of the children were hypothyroid, as judged by subnormal serum free T4 (FT4). The hypothyroid patients had a mean nocturnal TSH surge of 22% (range, -30% to +114%), significantly less than that of normal controls (mean, 124%; 95% confidence limits, 47-300%; n = 96; P less than 0.01). Only 1 of the hypothyroid children had a value for the nocturnal TSH surge (114%) that was within the normal range. Nineteen of the 52 patients with hypothalamic-pituitary disorders had subnormal nocturnal TSH surges; their mean iodothyronine values were significantly less than those of the 33 patients with normal surges [total T4, 73 +/- 4 (mean +/- SE) vs. 109 +/- 3 nmol/L (P less than 0.01); FT4, 13 +/- 1.0 vs. 19 +/- 0.5 pmol/L (P less than 0.01)]. These data demonstrate a clear association of a deficient nocturnal TSH surge and low iodothyronine concentration in children with hypothalamic-pituitary disorders. We performed both TRH tests and nocturnal TSH surge tests in 11 of the children with central hypothyroidism; TRH was abnormal in only 2, while the nocturnal surge test was abnormal in 10 of the 11. We suggest that the nocturnal surge of TSH is important for maintenance of thyroid function and conclude that the nocturnal TSH surge is a much more sensitive test than the TSH response to TRH for the diagnosis of central hypothyroidism.

A review of 339 treated acute iron ingestions was conducted to define treatment guidelines better. According to the poison center protocol, ingestions of 20-40 mg/kg of elemental iron required only home treatment, and ingestions of greater than or equal to 40 mg/kg required hospital referral. Gastrointestinal symptoms developed in 23% of patients. There were no seriously ill patients. No serious toxicity developed in patients ingesting 40-60 mg/kg. In 199 cases in which the dose ingested was known, the mean dose was 39.5 mg/kg. The peak measured serum iron levels ranged from 12 to 539 micrograms/dl. In 129 cases with serum iron levels reported, increasing serum iron levels were associated with vomiting (p = 0.006). Of 88 patients who received deferoxamine, 14 had urine color change. Urine color change was associated with symptoms (p = 0.005) but not with iron dose or peak serum iron level. The poison center protocol was changed to home management for ingestions of 20-60 mg/kg unless significant symptoms developed and hospital referral for ingestions greater than or equal to 60 mg/kg.

The dawn phenomenon consists of a rise in plasma glucose levels or insulin requirements in the early morning. This phenomenon has been observed in normal adults and in patients with diabetes mellitus. To determine whether this phenomenon also occurs in normal children and adolescents, we evaluated plasma glucose, insulin, C-peptide, and growth hormone levels during the early morning in 31 normal children between the ages of 8 and 18 yr. Blood samples were obtained through an indwelling catheter every 20 min for growth hormone and hourly for glucose, insulin, and C-peptide from 2100 to 0900 h. Glucose levels decreased slowly overnight from 2100 to 0900 h, despite increases in growth hormone levels. No significant rise in insulin or C-peptide levels was detected in the early morning in these normal subjects. There were no significant differences between prepubertal and pubertal children. We conclude that glucose, insulin, and C-peptide levels remain stable overnight, suggesting that the dawn phenomenon is not observed in normal children.

We studied the neurologic abnormalities in 41 men with isolated hypogonadotropic hypogonadism. Findings included anosmia, hyposmia, mirror movements, ocular motor abnormalities, cerebellar dysfunction, and pes cavus foot deformity. One-third of the subjects had a family history of delayed sexual maturation. Patients with a family history of delayed sexual maturation had a significantly higher incidence of olfactory dysfunction, mirror movements, and pes cavus foot deformity. Our data suggest that isolated hypogonadotropic hypogonadism and its accompanying neurologic abnormalities may arise from a genetically linked developmental abnormality of CNS structures.

The inheritance of isolated hypogonadotrophic hypogonadism (IHH) is not fully determined. Although men with this diagnosis can be treated to induce fertility, it is not known whether their offspring will inherit the hormonal deficiency. We evaluated the hypothalamic-pituitary-gonadal axis in nine children (born to men with IHH) during the first few months of life. This axis normally shows activation in infancy similar to that which occurs at puberty. Luteinizing hormone (LH) releasing hormone stimulated a peak LH response in excess of prepubertal levels (39.0 +/- 11 mIU/ml [mean +/- SD]). Testosterone in males (6.2 +/- 2.8 nmol/l and oestradiol in two of the females (320 and 100 pmol/l) were also in excess of prepubertal levels. These infants of men with IHH showed no evidence of inheriting hypogonadotrophic hypogonadism. While further studies will be conducted at the usual age of puberty to confirm spontaneous activation of the hypothalamic-pituitary-gonadal axis, our studies suggest that it may be possible to assess the integrity of this axis at a much younger age.

A 65-year-old female presented with only gastrointestinal symptoms eight to ten hours after an acute ingestion of an unknown amount of lithium carbonate. The serum lithium concentration was 8.5 mEq/L. Forty-eight hours postingestion she developed acute renal failure, deteriorating mental status, and cardiovascular collapse. Despite both hemodialysis and peritoneal dialysis the patient died approximately four and one-half days after ingestion. A direct nephrotoxic effect of lithium is proposed.

We evaluated the circadian variation of serum TSH in 96 normal children, aged 5-18 yr. Blood samples were obtained hourly for 24 h, and serum TSH was measured using an immunoradiometric assay with a sensitivity of 0.2 mU/L and an intraassay coefficient of variation of 4.9%. The nadir serum TSH value, defined by the three consecutive hourly TSH concentrations having the lowest mean, occurred between 1000 and 1900 h, while the peak TSH value, defined by the three consecutive hourly TSH concentrations having the greatest mean, occurred between 2100 and 0600 h. The mean nadir serum TSH was 1.6 +/- 0.1 mU/L, and the mean peak TSH was 3.7 +/- 0.2 mU/L. The mean nocturnal TSH surge (percent increase in TSH from nadir to peak) was 144% (95% confidence limits, 50-300%) and did not correlate with serum T4, free T4, or T3 concentrations. Seventy-six children were given TRH (7 micrograms/kg). The mean peak serum TSH after TRH was 16.0 +/- 1.1 mU/L (95% confidence limits, 9.0-42.0 mU/L), and it occurred by 30 min after TRH administration in 92% of the children. The absolute peak nocturnal serum TSH and peak post-TRH serum TSH values correlated significantly (r = 0.62; P less than 0.001), while age, gender, and pubertal status did not correlate with either the nocturnal TSH surge or the TSH response to TRH. We conclude that normal children have a circadian variation of serum TSH characterized by a nocturnal TSH surge, and that the peak of serum TSH, which occurs at night, correlates with the peak serum TSH level after TRH administration.

A 1-month-old infant suffered cardiac arrest shortly after presentation to the emergency department. The child had a history of heart disease treated with digoxin. The infant died despite intensive resuscitative efforts, including the use of digoxin-specific Fab antibodies. A brief discussion of this case and the use of digoxin-specific antibodies is presented.

Advances in the neurochemistry of learning suggest that many endogenous substances modulate learning processes. Endorphins promote or interfere with learning depending on dose (physiologic versus pharmacologic), task (negative versus positive consequences), and learning stage during which the substance is administered. Endorphins cause amnesia for extraneous details of a task (allowing focusing on main events) and prevent extinction of a learned task (even when forgetting might be adaptive). We have summarized endorphin physiology and review studies of endorphins in animal learning. Implications for the study of human attention and learning disorders are presented.

To clarify the relative usefulness of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency, we studied 54 short prepubertal children--23 with growth hormone deficiency identified by stimulation tests and 31 with idiopathic short stature who had normal responses to growth hormone stimulation. Growth hormone levels were measured in plasma samples obtained every 20 minutes for either 12 or 24 hours. The results were compared with those in 46 normal prepubertal children. Children with growth hormone deficiency had significantly lower mean 24-hour growth hormone levels (1.0 microgram per liter; range, 0.5 to 1.8) than normal children (2.8 micrograms per liter; range, 0.8 to 5.8; P less than 0.001). However, the diagnostic usefulness of the spontaneous growth hormone test was inferior to that of the stimulation tests, since it identified only 57 percent of the children with growth hormone deficiency identified by the stimulation tests. In the remaining children with growth hormone deficiency, spontaneous growth hormone levels were within the normal range. Children with idiopathic short stature had a normal mean 24-hour level of growth hormone (3.0 micrograms per liter; range, 1.1 to 6.7). No child in this group had low levels of spontaneous growth hormone secretion. We conclude that the measurement of the spontaneous secretion of growth hormone in prepubertal short children had lower sensitivity and offered no diagnostic advantage over stimulation tests. Our data do not support the routine measurement of spontaneous growth hormone secretion in the diagnosis of growth hormone deficiency.

In normal individuals, serum TSH concentrations have a circadian pattern characterized by a nocturnal surge which begins in the late afternoon and reaches its peak after midnight. We assessed the nocturnal surge of TSH in 16 patients with pituitary and/or hypothalamic diseases, 6 of whom were judged to be hypothyroid. To assess the magnitude of the nocturnal surge in individual patients, TSH was measured in 5 serum samples obtained during the normal time of the TSH nadir in the late afternoon and in 5 samples obtained during the normal time of the peak of serum TSH after midnight. A significant nocturnal surge of TSH was defined as a significantly greater mean nighttime TSH level than the mean daytime TSH concentration. The nocturnal TSH surge was absent in the 6 patients with central hypothyroidism, while it was present in the 10 euthyroid patients with central lesions. In 6 hypothyroid patients who did not have pituitary or hypothalamic lesions, the nocturnal TSH surge was intact, indicating that hypothyroidism per se does not account for the deficient nocturnal TSH surge in central hypothyroidism. We conclude that central hypothyroidism is characterized by a deficient nocturnal surge of TSH, and accordingly, we suggest that evaluation of the circadian pattern of TSH may be a useful adjunct in making the diagnosis of hypothyroidism in patients with diseases involving the pituitary or hypothalamus.

The purpose of this study was to determine whether lithium carbonate (Li2CO3) is effectively adsorbed by activated charcoal (AC). Either 0 (control), 1.5, 3.0 or 9.0 grams of AC were added to Li2CO3 (300 mg) in distilled deionized water or simulated gastric fluid USP, filtered and and the filtrate analyzed for lithium by flame photometry. Adsorption of lithium was dependent on AC concentration and pH. In water, lithium was 14.7%, 26.5% and 40.4% adsorbed at AC:Li2CO3 ratios of 5:1, 10:1 and 30:1, respectively (p less than 0.05). In simulated gastric fluid, there was no significant adsorption at any of the AC concentrations studied. Since simulated gastric fluid more closely resembles in vivo conditions, the efficacy of AC in lithium carbonate overdoses is questionable but in vivo studies are needed to confirm these findings.

Kochan, Ivan (Baylor University, Dallas, Texas) and Sandra R. Rose. Fate of tubercle bacilli in lipopolysaccharide- and BCG-treated mice. J. Bacteriol. 84:291-294. 1962-The fate of intravenously injected tubercle bacilli in lipopolysaccharide (LPS)- and BCG-treated mice was compared in this study to that in BCG-vaccinated and untreated mice. The potentiality of the treatments in development of "nonspecific immunity" was evaluated by determining numbers of tubercle bacilli in tissue homogenized suspensions rather than by the usually employed survival time of infected animals. The results indicate that during the experimental period the fate of tubercle bacilli of the challenge infection was the same in LPS-treated and heat-killed BCG-treated mice as in the untreated animals. Shortly after infection, the bacillary number increased during a 4-day period; after this time their number declined, reaching about half of the original number by 10 days. The vaccination of animals with live BCG induced good immunity. The same numbers of tubercle bacilli in LPS-and BCG-treated as in normal mice raise doubts as to the efficacy of "nonspecific immunity" in the suppression of bacteria in treated animals.