A 5 10/12-year-old girl with clinical and laboratory signs of endogenous hypercortisolism had evidence of ACTH hypersecretion in a standardized dexamethasone suppression test but had surprisingly low plasma ACTH concentrations before and after ovine corticotropin releasing hormone (oCRH) stimulation. To establish the diagnosis of pituitary disease and to localize the suspected microadenoma, we performed bilateral simultaneous inferior sinus petrosus blood sampling under CRH stimulation (oCRH 1 microgram/kg as an i.v. bolus). No major side effects were noted. Inferior petrosal blood ACTH concentrations did not differ from peripheral blood under basal sampling conditions but were higher in the effluent of the left half of the pituitary 5 min after oCRH stimulation. During transsphenoidal exploration of the sella an ACTH-producing microadenoma was removed from the left portion of the anterior pituitary gland. Signs of hypercortisolism remitted after surgery. Simultaneous bilateral sinus petrosus blood sampling under oCRH stimulation is a useful lateralization procedure even with small ACTH-producing adenomas. This technique may help to avoid unsuccessful surgical exploration in children with Cushing disease.

An adrenal size index (ASI) was specifically designed to improve ultrasound evaluation of adrenal size in the 1st year of life. In 84 newborns and infants, ASI and plasma dehydroepiandrosterone sulphate (DHEA-S) concentrations were determined to study in vivo changes in adrenal size and cortical zonal composition. ASI was higher (P less than 0.0001) in the first 2 postnatal weeks (median 60.5 mm2) than in the rest of the first year (median 39.6 mm2) and showed a negative correlation with chronological age (r = -0.41). A positive correlation existed between DHEA-S concentrations and ASI (r = 0.29) as well as ASI relative to body weight (r = 0.57). These data and changes in gland echogenicity are consistent with histopathological observations that the early decrease in adrenal size is due to involution of the fetal zone. In four patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) deficiency, ASI and plasma concentrations of pre-defect steroid were determined. Two patients with severe salt loss had markedly elevated ASI, which returned to normal during treatment. Two patients without severe salt loss had pretreatment ASI in the upper normal range, which decreased with treatment. Our findings indicate that ASI is useful in assessing physiological changes in adrenal size and, in conjunction with DHEA-S determinations, in adrenal cortex composition. ASI may aid in the early diagnosis of the salt-losing variety of 21-OHase deficiency. ASI is an instantaneously available tool which, in addition to biochemical and clinical data, can be used to monitor treatment of 21-OHase deficiency.

The proportion of the short-term height velocity SDS that can be explained by the tested treatment and disease variables is low (< or = 9.8%). Conclusions drawn from observed changes in height velocity during single short follow-up intervals on treatment modalities must therefore be viewed with caution. In the long run, however, use of daily hydrocortisone doses > 25 mg/m2/day and of synthetic glucocorticoids started early in the course of the disease does not only lead to a transient deceleration of height velocity in growing children with 21-hydroxylase deficiency, but carries a definite risk for decreased final height.

Two brothers with familial isolated growth hormone deficiency type IA homozygous for the same 6.7 kb deletion on chromosome 17 including the growth hormone gene were intermittently treated with various forms of hGH for more than 7 years. While the elder brother (Patient 1) showed a good growth response to pituitary hGH, the younger one (Patient 2) developed high titre growth blocking hGH antibodies early in the course of treatment and grew only 2.2\p=n-\3.9 cm/year on a hGH dose of 12\p=n-\26IU/m2 per week. When the younger brother was changed to a higher dose (33 IU/m2 per week) of biosynthetic methionyl hGH he had striking catch-up growth and he has subsequently maintained a height velocity of 10.0 cm/year for the last 2 years. During this time his antibody titres have decreased over 1000\x=req-\ fold. These findings demonstrate that therapy with biosynthetic methionyl hGH may provide an effective form of treatment for subjects with isolated growth hormone deficiency type IA who do not grow in response to native hGH, and imply that biosynthetic methionyl hGH may be less antigenic than pituitary derived hGH.

Infection-triggered, life-threatening salt-loss and hyperkalaemia developed in two male infants with wasting, inappropriately low plasma aldosterone concentrations and elevated plasma renin activity. The presumptive diagnosis of a defective terminal step in aldosterone biosynthesis was made by the presence of large amounts of 11-dehydrotetrahydrocorticosterone and its 18-hydroxylated metabolite (18-OH-THA), free 18-hydroxycorticosterone (18-OH-B) and 18-hydroxytetrahydrocorticosterone in the urine of both patients. The diagnosis of corticosterone methyl oxidase type II (CMO II) deficiency was confirmed by an elevated urinary 18-OH-THA to tetrahydroaldosterone ratio in one boy and by an elevated plasma 18-OH-B to aldosterone ratio in the other boy. Unknown steroids responsible for the salt-loss were not identified. Sodium supplementation but not short-term high dose oral 9 alpha-fluorcortisol (FF) normalized the hyponatraemia in one patient, in whom sodium (Na+)/potassium (K+) co-transport was decreased. Both patients eventually received long-term FF treatment to prevent impairment of longitudinal growth caused by chronic salt-loss. The diagnosis of CMO II deficiency should always be confirmed by elevated precursor-product ratios in urine or plasma, using radioimmunoassays with prior chromatographic separation. Metabolic studies as the short-term response of serum Na+ to high dose FF may not be helpful in differentiating aldosterone biosynthetic defects from end-organ resistance to mineralocorticoids.