Rebecca T. Kirkland

Comparison of adrenal cortical tumors in children and adults

Morphologic features (abnormal mitoses, necrosis, vascular and capsular invasion, broad fibrous bands, cellular pleomorphism, size) previously suggested to be predictors of malignant behavior in adrenal cortical tumors were assessed individually in 23 (17 benign, 6 malignant) pediatric and 42 (29 benign, 13 malignant) adult tumors. Of these features, size was the only predictor of malignancy in pediatric tumors. All pediatric tumors weighing more than 500 g were malignant and all but one weighing less than 500 g were benign. The remaining features were present in both benign and malignant pediatric tumors, and pediatric benign tumors were significantly more likely to have mitoses (P <0.01), necrosis (P <0.001), broad fibrous bands (P <0.005), and moderate to severe pleomorphism (P <0.01) than were adult benign tumors. The authors conclude that pediatric tumors are more likely to be benign than previously thought, and that size is the only morphologic predictor of their biologic behavior.

Familial Hypopituitarism with Large Sella Turcica

We studied endocrine function in three siblings with short stature and enlargement of the sella turcica. Sellar volumes were 5.9, 3.7 and 4.0 standard deviations above age-specific means. Computed tomography or pneumoencephalography showed full sellae without suprasellar extension. Basal thyrotropin levels were low despite hypothyroidism and increments were less than 3 micromicron per milliliter after thyrotropin-releasing hormone injection. Stimulated growth hormone levels were less than 5 ng per milliliter, declining to less than 2 ng per milliliter after thyroxine treatment. Both thyroxine and growth hormone treatments were required for rapid growth. Impaired thyrotropin responses to thyrotropin-releasing hormone distinguish these patients from most cases of idiopathic or familial deficiency of thyrotropin and growth hormone. Persistent deficiency of growth hormone during thyroxine treatment indicates that the defects is not limited to thyrotropin structure or release. The findings are compatible with either familial neoplasia of the anterior pituitary or a regulatory defect promoting anterior pituitary-cell hyperplasia and inhibiting thyrotropin and growth hormone release.

Assessing Parental Utilization of the Poison Center: An Emergency Center-Based Survey

The purpose of this study was to identify and characterize caretakers who fail to utilize the poison center for unintentional poisonings involving children. We interviewed 210 caretakers of children evaluated for unintentional poisoning in the emergency center of an urban, universitybased teaching hospital to determine (1) whether demographic differences exist between those caretakers who contacted a poison center prior to the emergency center visit and those who did not and (2) whether differences exist in prevalence of poison prevention knowledge and behaviors between the two groups. Ninety-six (46%) of caretakers did not contact the poison center prior to the emergency center visit. Significant differences were found between the two groups for the following caretaker variables: race/ethnicity, language preference, age, level of education, country in which schooling occurred, and type of insurance coverage for the child. When logistic regression was used to control for confounding, the two variables associated with failure to use the poison center were black race and schooled outside the United States (primarily in Mexico). Poison center callers reported a higher prevalence of poison prevention knowledge and behaviors than noncallers. Educational interventions should be targeted to the groups of caretakers identified who do not use the poison center.

Degenerative neurologic disease in patients formerly treated with human growth hormone

One or more lots of pituitary GH supplied by the NHPP may have been contaminated with CJD pathogen. If so, it is probable that the contaminated hormone was dispensed before 1978, and there is reason to believe that it was dispensed in the late 1960s. The contamination may have been limited to one lot of GH, but this is not known with certainty. Purification methods used by the NHPP since 1978 probably exclude the CJD pathogen, but this is not yet certain. The risk to patients treated since 1978, therefore, probably is low. There is no evidence to date that GH from either of the pharmaceutical suppliers has been or is contaminated. Purification procedures used by these sources also should exclude the pathogen. To exclude the possibility that they are contaminated with the CJD pathogen, 1 1/2 to 3 years will be required to test batches of the pituitary GH used previously. The experiment needed to show that the purification method used by NHPP excludes the scrapie agent will take up to 1 year. Planning for epidemiologic studies in patients treated with pituitary GH is under way. Biosynthetic GH prepared by recombinant DNA techniques has been in clinical trial in the United States for 3 1/2 years. It has been shown to be as effective as pituitary GH in promoting growth. However, it produces a higher incidence of GH antibodies than pituitary GH preparations do. Pediatric endocrinologists support the FDA in its effort to gather the information needed to approve biosynthetic GH for treatment of GH deficiency at an early date.

Functioning Adrenocortical Tumors in Childhood

Neoplasms of the adrenal cortex are rare during childhood [1]. Their presentation is often a dramatic example of the effects of steroid over-production. The diagnosis is usually suspected in a child who manifests signs of adrenocortical hyperfunction, such as virilization, sexual precocity or Cushing’s syndrome.

Serum gonadotropin levels in female adolescents with congenital adrenal hyperplasia

Summary Adolescent females with congenital adrenal hyperplasia frequently have menstrual disorders. An investigation of the hypothalamic-pituitary-gonadal axis in three patients under good control was performed by determining serum levels of LH and FSH. The lack of midcycle peaks in those with a history of poor control and cyclicity observed in one with good control suggest that postnatal exposure to adrenal androgens can disrupt the normal hypothalamic-pituitary-gonadal axis.

Strabismus and congenital hypothyroidsm

Summary A survey of 63 children with congenital hypothyroidism revealed that 43 per cent had strabismus which persisted after thyroid replacement therapy. An additional 10 per cent had nystagmus. The persistence of ocular findings depsite thyroid replacement therapy constitutes a significant physical sign of congenital hypothyroidism

Adult Height in Girls with Turner Syndrome Treated with Low-Dose Estrogens and Androgens

OBJECTIVE: To determine if low dosages of estrogens and androgens administered to girls with Turner syndrome adversely affected their adult height. DESIGN: A nonrandomized control trial of nine girls. SETTING: The endocrine clinic at Texas Childrens Hospital in Houston, Texas, an academic referral center. PARTICIPANTS: Participants had chromosomal defects consistent with Turner syndrome. Informed consent was obtained in accordance with institutional review board procedures. Eligibility criteria included an absence of previous hormone treatment. No one withdrew from this study because of adverse effects. INTERVENTIONS: Hormonal replacement therapy was initiated with conjugated estrogen 0.15 mg and tluoxymesterone 1 mg administered daily. MAIN OUTCOME MEASURES: Outcome measurements were a comparison of the final heights following treatment versus the predicted adult heights prior 10 treatment. RESULTS: The predicted adult height in these children prior to treatment was 140.0 ± 4.4 cm (mean ± SD); the actual adult height was 139.63 ± 4.1 cm. The difference was 0.37 ± 3.54 cm, which was not statistically significant by Wilcoxon signed-rank test (p=0.23). The 95% confidence interval on this difference ranged from −3.1 to 2.3 cm, which indicates a true mean height loss of no more than 3.1 cm or a true mean gain of no more than 2.3 cm. CONCLUSIONS: Our results indicate that hormone replacement therapy with low dosages of conjugated estrogens and androgens starting at 10–11 years of age in children with Turner syndrome does not adversely affect actual adult height.

Plasma Renin Activity and the Response to Sodium Depletion in Salt-Losing Congenital Adrenal Hyperplasia

Summary: Mineralocorticoid therapy was discontinued in 14 subjects, ages 7–17 years, with salt-losing congenital adrenal hyperplasia. The level of plasma renin activity (PRA) was determined in relation to the cumulative loss of sodium (intake-urinary output) over 4–12 days. Although the magnitude and rate of response varied, PRA increased in all subjects. There was a significant positive correlation between cumulative sodium loss and PRA (r = 0.585, P < 0.001, n = 76), and a significant negative correlation between serum sodium concentration and PRA (r = - 0.736, P < 0.001, n = 76). Significant sodium loss and elevation of PRA were seen prior to the development of hyponatremia. Thus, elevated PRA appeared to be a more sensitive indicator of sodium loss than serum sodium concentration.Fifteen infants, ages 1–33 months with salt-losing congenital adrenal hyperplasia, who were treated with subcutaneous pellets of 11-deoxycorticosterone acetate (DOCA), were also studied. PRA decreased following implantation of the DOCA pellets over 1–6 months. In most instances there was a subsequent increase in PRA, beginning at 1–8 months post implantation. There was a significant negative correlation between serum sodium and PRA (r = −0.669, P < 0.001, n = 78) in these infants. However, there were four instances in which elevated PRA was associated with normal serum sodium.Sodium balance studies were also performed on 14 of these infants during 29 admissions. All balance studies were performed at approximately 3 or 6 months after DOCA pellet implantation. On a diet containing 2 mEq Na/kg body weight per day, sodium balance was positive and there was no significant change in sodium excretion over the 3 days of observation. When a 1 mEq Na/kg/day diet was given, sodium balance was neutral on day 3 of the study, and fractional urinary sodium excretion (FeNa) decreased from 0.49 ± 0.33, S.D. on day 1 to 0.23 ± .09% on day 3 (P < 0.001, n = 19). This change was statistically significant. Net sodium balance on either diet was independent of PRA. Elevated PRA was not necessarily associated with adverse symptomatology.Thus in infants treated with DOCA pellets, elevated PRA was associated with indices of sodium depletion and decreased availability of DOCA. The dietary sodium requirement for infants treated with DOCA appeared to be 1–2 mEq/kg body weight/day.Speculation: Although increased PRA indicated the subjects response to sodium depletion, it did not predict the ability to maintain sodium balance. There must be factors other than mineralocorticoid therapy, some possibly renin-dependent, contributing to the ability to compensate for sodium depletion. Nevertheless, increased PRA may be taken as an indication to either increase mineralocorticoid dosage or sodium intake.

Clinical Features and Management of Overdosage with Thyroid Drugs

SummaryAccidental ingestion and overdose of medications used in thyroidal illnesses may occur because of the frequency of these diagnoses. This review discusses acute overdosage of 4 groups of medicines.Acute ingestion of thyroid replacement medications occurs very frequently. Overdosage in children is usually asymptomatic and a benign condition; after evacuation of the stomach, propranolol may be used to treat symptomatic children. Other therapeutic regimens are rarely indicated in this age group.Ingestions of large amounts of antithyroid medications occur very rarely and limited information regarding treatment is available in the medical literature.Acute ingestion of iodine often results in corrosive injury of the gastrointestinal tract and renal damage. Cardiopulmonary collapse secondary to circulatory failure, oedema of the epiglottis and aspiration pneumonias may cause death. Administration of starch and sodium thiosulphate, maintenance of airway and stabilisation of circulation are the major components of therapy.Acute overdosage of β-blockers is uncommon but can be lethal. Patients may appear well initially but they can suddenly develop convulsions and profound cardiovascular collapse requiring instant aggressive therapy. Potassium and glucose concentrations should be monitored. The usage of atropine, isoprenaline (isoproterenol), glucagon and prenalteral is discussed.