Arieh Kauschansky

Growth and pituitary-adrenal function in children with severe asthma treated with inhaled budesonide

BACKGROUND The increased use of inhaled corticosteroids in the management of asthma raises concern about the safety of these drugs in children. We sought to determine the safety of long-term administration of inhaled budesonide in young children with asthma. METHODS We studied 15 children 2 to 7 years old who had severe perennial asthma. They inhaled 100 micrograms of budesonide twice daily for three to five years. Efficacy was assessed by serial evaluation of respiratory symptoms and the need for other medications, and safety by serial evaluation of height, height velocity, weight, bone age, and pituitary-adrenal function. RESULTS The severity of asthma decreased within the first month after the initiation of therapy, as demonstrated by a 58 percent reduction in the number of days with symptoms of asthma and a 75 percent decrease in the use of bronchodilators. This improvement was maintained thereafter. The growth pattern of all patients, including their height, weight, and bone age, was normal (as compared with standard normal values) throughout the treatment period. Pituitary-adrenal function was not adversely affected by the treatment, as demonstrated by normal serum cortisol concentrations in the morning and 60 minutes after stimulation with corticotropin, normal 24-hour serum cortisol concentrations (mean [+/- SD] of samples collected at 30-minute intervals for 24 hours, 8.4 +/- 4.2 micrograms per deciliter [232 +/- 116 nmol per liter]), and normal urinary cortisol excretion (34 +/- 9 micrograms [95 +/- 25 nmol] per day). CONCLUSIONS Prolonged administration of 200 micrograms of inhaled budesonide daily to young children with severe asthma does not impair growth or pituitary-adrenal function.

Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys.

objectives The differentiation of constitutional delayed puberty (CDP) from gonadotrophin deficiency (GD) in boys at referral poses a difficult challenge. The effectiveness of the GnRH agonist (GnRH‐a) test in distinguishing between the two conditions was evaluated and compared with findings of the GnRH and hCG stimulation tests.

Normal diurnal variation in serum cortisol concentration in asthmatic children treated with inhaled budesonide

BACKGROUND Twenty-four-hour serum cortisol secretion is a sensitive parameter for the assessment of the pituitary-adrenal function of asthmatic children treated with inhaled corticosteroids. This study was undertaken to determine the effect of the long-term administration of inhaled budesonide on 24-hour cortisol production in young children with asthma. METHODS We studied 11 children, aged 7 to 12 years, with severe perennial asthma. All had been receiving 100 micrograms of inhaled budesonide twice daily, administered with a spacer device, for 3 to 5 years. Serum cortisol concentration was measured at 8:00 A.M., 60 minutes after intravenous administration of 0.25 mg of corticotropin, and every 30 minutes for 24 hours in an open-design study. Urinary cortisol secretion was measured by 24-hour urine collection. All determinations were made with a radioimmunoassay kit. RESULTS The individual morning serum cortisol concentration and the serum cortisol concentration at 60 minutes after corticotropin stimulation were within normal limits in all children. The 24-hour urinary cortisol excretion was also normal. The individual 24-hour serum cortisol concentration showed a normal pattern in all children, with no evidence of nocturnal suppression of serum cortisol concentration. CONCLUSION Prolonged (3 to 5 years) administration of 200 micrograms/day of inhaled budesonide in young children with severe asthma does not impair pituitary-adrenal function, even according to the sensitive test for 24-hour serum cortisol secretion.

Insulin-like growth factor-I and IGF binding protein-3 remain high after GnRH analogue therapy in girls with central precocious puberty

OBJECTIVE IGF‐I rises in normal adolescence and in central precocious puberty (CPP), secondary to a rise in sex steroids and GH. The aim of this study was to examine changes in serum IGF‐I and its major binding protein IGFBP‐3 after pharmacological arrest of puberty.

Prolonged vaginal bleeding during central precocious puberty therapy with a long‐acting gonadotropin‐releasing hormone agonist

OBJECTIVE To describe our experiment with the treatment of GnRH-a in premenarchal girls with idiopathic central precocious puberty (CPP). PATIENTS AND METHODS Twenty-eight girls, aged 6.5-11 years, with idiopathic central precocious puberty were treated every 28 days with an intramuscular depot gonadotropin releasing hormone agonist (GnRH-a) in an attempt to delay sexual maturation. RESULTS Eight of the 28 (28.5%) developed vaginal bleeding after GnRH-a administration. Of these, prolonged vaginal bleeding of 11-13 days occurred in four girls, three recurrent episodes occurred in one during the second injection, and in one other girl the 4th episode occurred after 6 months of treatment. CONCLUSION Uterine bleeding following GnRH-a treatment in premenarchal girls with CPP is common, and may be massive and recurrent, since most episodes resolved spontaneously and necessitated no further treatment, careful advice should be given to the girls and their families prior to treatment initiation, in an attempt to avoid unnecessary anxiety and achieve better compliance.

Oculo‐palato‐cerebral dwarfism: a new syndrome

Three of four offspring of consanguineous parents presented a unique association of microcephaly, mental retardation, spasticity, connective tissue abnormalities, cleft palate, persistent hypertrophic primary vitreous, and short stature. In one patient brain atrophy was documented. All the affected individuals had severe asthma and it is thought that the asthma is associated with the syndrome complex. Genetic transmission is most likely autosomal recessive. We believe this constellation of findings to be a new genetic syndrome and have termed it the oculo‐palato‐cerebral dwarfism syndrome.

Hyperprolactinemia after treatment of long-acting gonadotropin-releasing hormone analogue Decapeptyl * in girls with central precocious puberty

OBJECTIVE To clarify the effects of prolonged treatment with long-acting GnRH analogue on serum PRL levels. DESIGN Blood PRL levels were measured at 9 A.M. every 28 days for a period of 6 months. SETTING Pediatric Endocrine Clinic, Hasharon Hospital, Petah Tiqva, Israel. PATIENTS Thirteen girls with idiopathic central precocious puberty. RESULTS Hyperprolactinemia developed in 5 of 13 girls after treatment with long-acting GnRH-a; mean blood PRL in all 13 girls rose significantly from 11.9 +/- 5.6 to 21.5 +/- 12.5 micrograms/L (mean +/- SD). CONCLUSIONS The mechanism of hyperprolactinemia in our patients is unclear. It may have resulted from a decline in the release of the hypothalamic PRL inhibitory factor. Clinically, transient hyperprolactinemia during long-acting GnRH-a treatment for central precocious puberty also may reflect a constant depression of LH secretion.

Syndrome of alopecia totalis and 17b-hydroxysteroid dehydrogenase deficiency

A distinct and previously undescribed syndrome of alopecia totalis, ichthyosis, and male pseudohermaphroditism due to steroid 17b-hydroxysteroid dehydrogenase deficiency was observed in an Israeli-Arab newborn infant.

Insight: prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism and management plan.

We have previously described our data collected after administration of gonadotropin releasing hormone-agonist (GnRH-a) to delay sexual maturation, in premenarchal girls suffering from idiopathic central precocious puberty.(1) We have explained the recurrent episodes of bleeding due to discontinuation of the estrogen support of the proliferative and stable endometrium. The recognition in recent years of the extra-pituitary functions of GnRH-a, the ability of GnRH to stimulate prostaglandin production and the known role of prostaglandins in irregular vaginal bleeding prompted us to seek alternative explanations to our data. We suggest considering a potential clinical use of combination therapies of GnRH agonists and prostanoid receptor antagonists to treat central precocious puberty.

Familial Lipoid Adrenal Hyperplasia: Genetic Marker Data and an Approach to Prenatal Diagnosis

Some of the anatomic endocrine, and genetic aspects of lipoid adrenal hyperplasia were studied in an inbred Israeli-Arab family with two affected sibs. One sib, a genetic female, presented with acute Addisonian crisis. Endocrine studies documented elevated ACTH levels and no detectable steroids of gonadal or adrenal origin. The other patient, a male pseudo-hermaphrodite, was found at autopsy to have typical lipoid adrenal hyperplasia and ectopic adrenal tissue adjacent to an intra-abdominal testicle. Complete vagina, uterus, and fallopian tubes were present in addition to the Wolffian structures. This unique observation supports the view that steroids may be necessary for Müllerian inhibitory factor to induce regression of Müllerian structures. The segregation of 27 autosomal markers was studied in one affected and five unaffected sibs. Genetic linkage to HLA, MNS, and GPT is unlikely. In addition, the affected sib is heterozygote for a haplotype of chromosome 1 which includes the Rh, Fy, PGM-1 systems. Determination of fetal gender by the combined use of ultrasonography and amniocentesis is suggested for prenatal diagnosis and improved risk counselling.