Elizabeth Stoner

Proscar: five-year experience

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.

IS SALT‐WASTING IN CONGENITAL ADRENAL HYPERPLASIA DUE TO THE SAME GENE AS THE FASCICULATA DEFECT?

Clinical studies in patients with 21‐hydroxylase deficiency congenital adrenal hyperplasia (CAH) were designed to ascertain the genetics of the salt‐wasting component of the disorder. The gene controlling aldosterone biosynthesis may not be the same gene that controls 21‐hydroxylase in the adrenal zona fasciculata. This we infer from the following clinical observations: (1) concordance for salt‐wasting is not observed in all HLA‐identical sibs with CAH; (2) the defect in aldosterone biosynthesis does not persist throughout life as does the fasciculate defect; (3) there is a significantly increased gene frequency of B40 and Bw47 in salt‐wasting CAH; (4) obligate heterozygote parents of patients with salt‐wasting CAH do not express a partial defect in aldosterone biosynthesis, as they do in the fasciculata. These observations cast doubt on the accepted concept of the autosomal recessive transmission of the glomerulosa 21‐hydroxylase deficiency.

Biochemical studies of a patient with hereditary hepatorenal tyrosinemia: evidence of glutathione deficiency.

ABSTRACT: Metabolic and enzymatic studies in a patient with hereditary tyrosinemia demonstrated for the first time a deficiency of erythrocyte and hepatic glutathione. Markedly decreased hepatic fumarylacetoacetate hydrolase activity was demonstrated in this patient. The activities of hepatic enzymes not involved in tyrosine metabolism were also determined. Assay of mixed function oxidase activity demonstrated low levels of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase, suggesting decreased hepatic detoxification capacity. 5-Aminolevulinic acid dehydratase activity was undetectable. Succinylacetone (4,6- dioxoheptanoic acid), an abnormal metabolic product secondary to fumarylacetoacetate hydrolase deficiency was found in serum and urine. Succinylacetone was demonstrated to inhibit 5-aminolevulinic acid dehydratase in vitro, as did the urine, plasma, and red cell Iysates of the patient.

Resolution of the clinical features of tyrosinemia following orthotopic liver transplantation for hepatoma

The clinical history before transplantation and subsequent clinical and biochemical course of 3 children and one adult with hereditary tyrosinemia treated by orthotopic hepatic transplantation is described. All four patients are now free of their previous dietary restrictions and appear to be cured of both their metabolic disease and their hepatic neoplasm.

Apparent Mineralocorticoid Excess Causing Hypertension and Hypokalemia in Children

Cortisol 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) deficiency was observed in four patients with apparent mineralocorticoid excess. The 11 beta-HSD deficiency was demonstrated by a markedly decreased urinary tetrahydrocortisone/tetrahydrocortisol (THE/THF) ratio (less than 1 in normal children) during infusion of ACTH and administration of hydrocortisone. We propose that in these patients the 11 beta-HSD deficiency impairs the metabolism of cortisol to cortisone, resulting in a prolonged cortisol half-life, suppression of ACTH, and normal serum cortisol. The 11 beta-HSD deficiency protects the patient from adrenal insufficiency despite the low cortisol secretion; the prolonged half-life of cortisol may contribute to the hypertension and hyporeninemia observed in this disorder. Continuous intravenous hydrocortisone administration resulted in increased blood pressure and decreased serum potassium. Addition of spironolactone during continued administration of 20 mg per day of hydrocortisone resulted in a decrease in blood pressure and a rise in serum potassium. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid. These findings may account for this syndrome of apparent mineralocorticoid excess.

THE EFFECT OF TREATMENT ON FINAL HEIGHT IN CLASSICAL CONGENITAL ADRENAL HYPERPLASIA (CAH)

One of the goals of glucocorticoid therapy in classical CAH is to suppress excess androgen production to prevent premature epiphyseal closure and resultant short stature. This retrospective study was conducted to determine if the final height (FH) of 45 adult patients (pts) with CAH was influenced by the clinical variant (salt-wasting (SW) vs simple virilizing (SV)), age diagnosis was made and treatment initiated, and the degree of hormonal control. Good or poor hormonal control were determined from levels of 24 hr urinary 17-KS, serum Δ4-androstenedione (Δ4-A) and 17-OHP. The patient was assigned to the category of good control if more than 50% of daily urinary 17-KS or serum Δ4-A were normal for age (mean±2SD) or if 50% of the serum 17-OHP levels were < 1000 ng/dl. All others were assigned to the poor control category; 3 pts had insufficient data for assignment. Final height was compared to the mid-parental height (MPH), to the normal population, and to 5 never treated pts with SVCAH. The mean final Ht for all male patients was 163.2 cm and for all female patients was 153.3 cm. Conclusion: The adult height of 3 never treated females was not different from any treated females, whether in good or poor control, SW or SV, or treated early or late. Among the treated males, height was not different whether they were in good or poor control, SW or SV, or treated early or late. Although the 2 never treated males are shorter than treated males, the small number of pts precludes statistical analysis. The mean final heights of all pts were significantly less than the mean heights of males and females in the normal population.

Microfilter Paper Method for Antipyrine Determination in Whole Blood by High Pressure Liquid Chromatography

A method for measuring antipyrine in whole blood collected on filter paper is described. A 6.2-mm diameter disc (1/4 in) is punched out, eluted with distilled water, and then extracted with 5 ml of dichloromethane/pentane (50:50, vol/vol). After reconstitution of the dried residue, reverse-phase high pressure liquid chromatography is used to quantitate antipyrine using an internal standard. A mixture of 15% acetonitrile in 0.006 M phosphate buffer pH 7.2 was used as the mobile phase. Chromatography was carried out under isocratic conditions for 15 min. The retention time of antipyrine was 3.6 min. Intra- and interassay coefficients of variation were 3.1% and 7.2%, respectively. The limit of sensitivity was 6 ng/injection. The amount of blood in a 6.2-mm filter paper disc was calculated to be 8.4 +/- 0.8 (SD) microliter. Antipyrine half-lives, apparent volumes of distribution, and metabolic clearance rates measured from the filter paper concentrations or directly from plasma were virtually identical. Antipyrine was stable on filter paper for less than or equal to 6 weeks at room temperature. The method reported is convenient; requires a small amount of blood, which can be easily obtained by fingerstick; and readily permits the measurement of antipyrine clearance in the pediatric as well as adult populations.

Empty sella syndrome in childhood

The empty sella syndrome is common in middle-aged women, usually presenting with headache, and only occasionally associated with endocrine or visual abnormalities. It is rare in childhood. Childhood cases tend to present either with endocrine disturbances, visual symptoms, or with craniofacial syndromes. We present three cases of complete empty sella with childhood onset, each discovered unexpectedly during evaluation of endocrine or visual dysfunction.

Neuronal Ceroid Lipofuscinosis With Hypergonadotropic Hypogonadism

A case of adolescent-onset neuronal ceroid lipofuscinosis presenting with chorea and evidencing pyramidal and cerebellar dysfunction as well as hypergonadotropic hypogonadism is reported. In this patient, primary ovarian failure may be due to accumulation of ceroid in the ovaries. ( J Child Neurol 1986; 1:142-144)

Effect of Acute Dietary Sodium Alterations in Normotensive and Hypertensive Children

INTRODUCTION We studied the effect of dietary sodium changes on sodium conservation, body weight, blood pressure and the renin-aldosterone axis in thirteen normotensive children, seven children with essential hypertension, four hypertensive children with renal disease, and four patients with dexamethasone-suppressible hyperaldo-steronism (DSH). The changes in aldosterone excretion, renin activity (PRA), and weight, with dietary alterations were similar in normotensive children in those with essential hypertension. There were no leant changes in blood pressure or serum potassium either group. The hypertensive children with renal : showed more uniform changes in blood pressure, at PRA was variable. In addition, we observed hyperdosteronism both in the baseline and low salt periods, i there was a failure on the high salt diet to suppress dosterone below baseline values. The children with demonstrated a low and fixed PRA, fixed aldorone excretion and statistically significant changes in Jood pressure. On the low salt diet, the children with were able to conserve sodium without increasing aldosterone excretion, suggesting that a factor than aldosterone was involved in sodium conseron. These studies provide infoimation on the metaz response of normotensive and hypertensive children |acute alterations in sodium intake. The data suggest there are differences in the response of the ngiotensin-aldosterone axis depending on the fogy of the hypertension. «Print Address: eth Stoner, M.D., Department of Pediatrics on of Pediatric Endocrinology, ^New York Hospital-Cornell Medical Center, 58th Street, New York, NY 10021 phone No. (212) 472-5658 Although many studies have been carried out on the relationship between dietary sodium, blood pressure, and the renin-angiotensin-aldosterone axis in adult subjects, few studies have been performed in children /1-3/. This study was undertaken to provide information on the effects of varying dietary salt intake in normotensive children and in children with hypertension of various etiologies. In particular, we sought to assess the regulatory mechanisms mediating the hypertension and salt balance in patients with DSH. PATIENTS AND METHODS All aspects of this investigation were conducted in the Pediatric Clinical Research Center of The New York Hospital-Cornell Medical Center under institutionallyapproved protocols. Informed consent was obtained as required from the patients or their parents/guardians. We evaluated the therapeutic advisability of discontinuing medications in each case. After discontinuation of any anti-hypertensive agents, we began the study in each patient once the patient was in metabolic balance, with no changes in weight, sodium balance, renin and aldosterone on a regular salt diet.