Time course of recovery of adrenal function in children treated for leukemia.

OBJECTIVE: Many protocols for treating children with early B-cell lineage acute lymphoblastic leukemia use 28 consecutive days of high-dose glucocorticoids during induction therapy. We prospectively studied the effects of this therapy on adrenal function. STUDY DESIGN: Ten children with early B-cell lineage acute lymphoblastic leukemia were evaluated by cosyntropin (corticotropin (1-24)) stimulation testing before initiation of dexamethasone therapy and every 4 weeks thereafter until adrenal function returned to normal. RESULTS: All 10 patients had normal adrenal function before dexamethasone treatment and insufficient adrenal responses 24 hours after completing therapy. Each child felt ill for 2 to 4 weeks after completing therapy. Although 7 patients recovered normal adrenal function after 4 weeks, 3 patients did not have normal adrenal function until 8 weeks after discontinuing therapy. Statistically significant differences in both basal and corticotropin-stimulated cortisol levels were noted when comparing tests performed at baseline, 24 hours after completing therapy, and 4 weeks after completing therapy. CONCLUSION: High-dose dexamethasone therapy, a standard treatment for early B-cell acute lymphoblastic leukemia, can cause adrenal insufficiency lasting more than 4 weeks after cessation of treatment. This problem might be avoided by tapering doses of glucocorticoids and providing supplemental glucocorticoids during periods of increased stress.

Parathyroid carcinoma in a child.

Parathyroid carcinoma is a rare cause of hypercalcemia in children but should be considered in a child presenting with an extremely elevated serum calcium level. The authors report the fifth case of parathyroid carcinoma in a child less than 16 years of age.

Epidermal growth factor stimulates insulin-like growth factor-binding protein-1 expression in the neonatal rat.

Insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) appear to be important in the regulation of perinatal growth. We have shown previously that administration of epidermal growth factor (EGF) to newborn rat pups inhibits growth and decreases serum IGF-I concentrations. The experiments described here were designed to investigate the effect of EGF on the IGFBPs using ligand blots of serum and Northern analysis of hepatic RNA. EGF administration caused a rapid (within 2 h) 2-fold increase in the serum IGFBP-1 concentration. Hepatic IGFBP-1 mRNA increased even more rapidly, was increased at least 2-fold at 2 h, and remained elevated 4 h after EGF. The response to EGF was specific to IGFBP-1; IGFBP-2 hepatic mRNA content was not increased over the control value, and serum IGFBP-3 and -4 concentrations were not changed by ligand blot analysis. The IGFBP-1 response to EGF was most dramatic in the first few days of life. Although EGF lowered circulating insulin levels, EGF stimulated IGFBP-1 secretion in the presence of exogenously administered insulin. Thus, the increase in IGFBP-1 did not appear to be mediated by changes in serum insulin. These results demonstrate that EGF increases serum IGFBP-1 concentrations, probably by stimulating synthesis. The association of decreased growth and increased IGFBP-1 concentrations after EGF treatment suggests that elevated IGFBP-1 concentrations may restrict IGF bioactivity in the neonatal rat.

Suppression of insulin-like growth factor I during epidermal growth factor-induced growth retardation.

Epidermal growth factor (EGF) attenuates growth when administered to rats less than 2 wk of age but lacks growth-retarding properties when given to older animals. Because the insulin-like growth factors (IGF) are postulated to be important regulators of somatic growth during the perinatal period, we examined the effect of exogenous EGF on serum and tissue concentrations of IGF-I and hepatic expression of mRNA for IGF-I and IGF-II. A single injection of EGF (500 ng/g body wt) produced a significant (P less than 0.01) decline in serum IGF-I concentration within 4 h in newborn rat pups [controls, 46.2 +/- 9.1 (SD) ng/ml; EGF treated, 29.4 +/- 4.0 ng/ml] but was ineffective in 2-wk-old animals (control IGF-I, 72.8 +/- 15.1 vs. 64.0 +/- 13.7 ng/ml). When the EGF was given on days 0-3 of life, circulating IGF-I concentrations were suppressed further (control, 61.4 +/- 8.6; EGF treated, 32.5 +/- 8.6 ng/ml). Despite the change in circulating IGF-I levels in the newborn rats, the amount of IGF-I extractable from liver and kidney of growth-retarded animals was not significantly different from control. Likewise, IGF-I and IGF-II mRNA expression in liver, as assessed by blot hybridization, was unchanged by the EGF treatment. The rapid decline in IGF-I concentration after EGF administration, coupled with the restriction of this phenomenon the first 2 wk of extrauterine life, implies that changes in IGF-I are involved in the pathogenesis of EGF-induced growth retardation.

Insulin-like growth factor binding protein-3 secretion from cultured rat sertoli cells: dual regulation by follicle stimulating hormone and insulin-like growth factor-I.

The insulin-like growth factors (IGFs) are found in extracellular fluids bound to carrier proteins which influence the biological activity of the IGFs. Three structurally different binding proteins (BPs) have been isolated and cloned; each has distinct tissue specific expression and unique properties. We report here that testicular cells synthesize a specific subset of these binding proteins. Ligand blot analysis and RNA blot hybridization indicates that cultured peritubular cells synthesize primarily IGFBP-2. In contrast, as determined by ligand blot, RNA blot hybridization and N-linked deglycosylated studies, IGFBP-3 is predominantly synthesized by the Sertoli cell. In a dose dependent fashion, FSH markedly reduces the levels of IGFBP-3 in Sertoli cell conditioned medium. Similarly, isoproterenol, (Bu)2cAMP and cholera toxin also markedly reduce the abundance of IGFBP-3 in conditioned media. In contrast, IGF-I increases the concentrations of IGFBP-3 with the concentration required for half-maximal stimulation, approximately 20 ng/ml. Consistent with a peritubular cell origin, IGFBP-2 may be the predominant species found in interstitial fluid. In summary, our data reveal that the IGFBPs are expressed in a cell type specific manner in the testis. The opposing effects of FSH and IGF-I on Sertoli cell IGFBP-3 expression suggests a mechanism by which the IGF-I biological activity on Sertoli cell might be influenced.

CT demonstration of calcification in carcinoma of the lung.

Radiologic visualization of calcification within lung cancer is uncommon and may cause confusion and misdiagnosis. For this reason, we reviewed CT records of 353 patients undergoing initial evaluation of lung cancer for the presence of calcification within the tumor, both to document this finding and to estimate its prevalence. Twenty patients (6%) whose records indicated that CT showed calcification were identified, and their chest radiographs and CT scans were analyzed. Patients were included in the study if calcium was seen within the tumor on noncontrast pretreatment CT scans and if pathologic data were available. There were 15 lung and five mediastinal tumors. Fourteen were 5 cm or greater in diameter; three were between 3 and 5 cm, and three were 2 cm or smaller. Cell types of the tumors included small-cell carcinoma (eight patients), squamous cell carcinoma (seven patients), adenocarcinoma (four patients), and undifferentiated carcinoma (one patient). Patterns of calcification were amorphous (eight patients), punctate (10 patients), and reticular (two patients). Extent of tumor calcification and distribution (central, peripheral, or diffuse) did not correlate with cell type or size of the lesion. The visualization of calcium on chest radiographs and CT scans does not alone exclude the diagnosis of bronchogenic carcinoma.

Aldosterone-producing adenoma presenting with hypokalemic myopathy. Case report and review.

A 9-year-old boy who complained of fatigue, myalgias, and progressive weakness was found to have a markedly elevated serum creatine phosphokinase (CPK). He developed polyuria with polydipsia and was noted to be hypertensive and severely hypokalemic. Treatment with potassium and spironolactone alleviated his signs and symptoms and normalized the blood pressure and CPK. Initial studies revealed low plasma renin activity that did not increase with change from supine to upright position. Plasma aldosterone was consistently elevated in the supine position, decreased with upright posture, and was not suppressed by administration of dexamethasone. Plasma 18-hydroxycorticosterone also was elevated. Enhanced computerized tomography (CT) revealed a mass in the left adrenal that had not been seen on the initial unenhanced scan. Adrenal vein catheterization confirmed elevated plasma aldosterone on that side. Adrenalectomy was performed, and a well-encapsulated adenoma was found at examination of the surgical specimen. Postoperatively, suppression of plasma renin activity continued for many months without signs of aldosterone deficiency.