Vesna Plavšić

Absent spermatogenesis despite early bilateral orchidopexy in 17-ketoreductase deficiency

We describe a 26-year-old patient with 17-ketoreductase deficiency who was raised as a male from 8 months and whose left testis was brought down at the age of 2.5 years and the right testis at the age of 4. Despite the early orchidopexy and not significantly decreased serum testosterone, he was sterile, and biopsy of the testes at the age of 26 revealed absence of spermatogenesis. This case indicates that the absence of spermatogonia in previously reported patients whose testes remained undescended until a later age could not be attributed solely to cryptorchidism. We suggest that decreased intratesticular testosterone due to steroidogenic defect in the developing testis mainly contributes to the arrest of spermatogenesis.

Effects of ritanserin, a novel serotonin-s2 receptor antagonist, on the secretion of pituitary hormones in normal humans

The availability of a new potent and selective serotonin-S2 antagonist, ritanserin (RIT), encouraged us to further investigate the effect of serotonin on the basal secretion of anterior pituitary hormones in normal humans. Administered in a single 30-mg dose to group 1 consisting of 10 normal women, RIT failed to affect the baseline LH, FSH, GH or TSH levels. In group 2 consisting of 20 normal subjects (ten males and ten females), the same dose of RIT decreased in parallel both ACTH and Cortisol levels but only at 180 min. Group 3 consisting of 8 normal men was studied on three separate occasions seven days apart: each subject received graded doses of 10 mg, 20 mg and 30 mg RIT. The mean baseline PRL concentration at 180 min as well as the net integrated area under the hormone curve (nAUC) decreased only after the highest dose, while the baseline Cortisol concentrations at 180 min as well as the corresponding nAUC values displayed a clear dose-dependent response. The findings indicated the serotonin-S2 receptors to be only partially involved in the basal secretion of ACTH in normal humans.

Xerostomia in patients with triple A syndrome – a newly recognised finding

Abstract Triple A syndrome is characterised by achalasia, alacrima, adrenal insufficiency and progressive neurological abnormalities including impaired autonomic nervous function. We present five patients with triple A syndrome in whom we describe xerostomia for the first time, a symptom which was presumed to be practically exclusive to Sjøgren syndrome and familial dysautonomia. Conclusion We recommend the investigation of salivation in all patients with triple A syndrome and treatment of xerostomia in order to ease swallowing. Further, our results corroborate earlier doubts that some patients with Sjøgren syndrome, especially those with the so-called “achalasia sicca” syndrome and adrenocortical insufficiency, actually had triple A syndrome. Therefore, adrenocortical function should be assessed in all patients with Sjøgren syndrome, particularly in those with difficulties in swallowing, because even latent adrenocortical insufficiency could be life-threatening for these patients in stressful situations.

Effects of ritanserin, a specific serotonin-S2 receptor antagonist, on the release of anterior pituitary hormones during insulin-induced hypoglycemia in normal humans

The role of serotonin in the insulin hypoglycemia (IH) stimulated secretion of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) and Cortisol (F) was studied in a group of 12 normal subjects during the control period after placebo and a consecutive six-day treatment with 20 mg ritanserin (RIT) per day. RIT failed to affect the baseline levels of all the four hormones as well as the PRL response to IH (p>0.5). The serum GH response to IH was moderately diminished after RIT, the reduction of integrated trapezoidal area under hormone curves (nAUC) being 50.7% ± 6.9% (p<0.005). Furthermore, RIT was found to slightly decrease the plasma ACTH response to IH, the reduction of nAUC being 36.3% ± 2.6% (p<0.005). Decrease in the corresponding plasma F response to IH was accompanied by 29.1% ± 2.4% reduction of nAUC (p<0.005). According to our results, serotonin-S2 receptors appeared to be moderately involved in IH-induced release of GH, but slightly in that of ACTH, leaving unaffected that of PRL.

Extraovarian steroid cell tumor 'not otherwise specified' as a rare cause of virilization in twelve-year-old girl.

Background: We present a 12-year-old girl with a 5-year history of progressive virilization. Results: Regarding elevated plasma levels of 17-hydroxyprogesterone (17-OHP) and androgens, normal ultrasound and CT scan of ovaries and adrenal glands, the nonclassic form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency was presumed the cause of virilization. As the glucocorticoid therapy did not normalize high levels of 17-OHP and androgens, and the DNA analysis did not demonstrate a mutation causing CAH, a laparotomy was performed. Near the right ovary a tumor was found and extirpated. Pathohistological studies determined it to be a rare steroid cell tumor, ‘not otherwise specified’. Within the next months the signs of virilization resolved and menarche occurred. Conclusions: Steroid cell tumor should be considered in differential diagnosis of virilization in childhood. Regarding the age of our patient and pathohistological findings of the tumor, her prognosis is favorable.

Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) in Croatia

We report on the prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase in 20 at-risk pregnancies (16 salt-wasting and 4 simple virilizing families). We have diagnosed 3 affected fetuses (2 males and 1 female), 3 healthy homozygotes (2 males and 1 female), and 14 healthy heterozygotes (7 females and 7 males). These data were collected over 4 years. In 16 fetuses, the diagnosis was made with measurements of 17-hydroxyprogesterone (17-OHP) and Δ-4-androstenedione (Δ) in amniotic fluid (AF), human leukocyte antigen (HLA) typing of amniotic cells, as well as karyotypes between the 16th and 18th weeks of gestation. In 4 fetuses, DNA analysis of amniotic cells was also performed. In 3 pregnancies in which affected fetuses were suspected (on the basis of HLA typing and measurements of 17-OHP and Δ concentrations in AF), the fetuses were electively aborted between the 17th to 19th weeks of gestation by parental decision. In all aborted fetuses, diagnosis was confirmed with HLA typing, autopsy findings of hyperplastic adrenal glands, and ambiguous genitalia in female fetuses. Postnatal diagnosis was confirmed in healthy fetuses with HLA typing and serum measurements of 17-OHP concentrations, and in 4 of them with DNA analysis. In 3 of the 4 families, DNA analyses revealed the following mutations: in Family 1, the index case mutation was Intron 2, Exon 3/Exon 6, and the fetus was Normal/Exon 6; in Family 2, the index case mutation was Ex1 Int2 Ex3/Int2, and the fetus was Ex1 Int2 Ex3/Normal; and in Family 3, the index case mutation was Ex8356/Ex8356, and the fetus was Ex8356/Normal. We also report one case of prenatal diagnosis and treatment. Dexamethasone 0.5 mg BID (20 μg/kg/d) was given starting at 6th week of gestation. Prenatal diagnosis suggested, but did not prove, that the female fetus was a heterozygote as the fetus lacked the paternal mutation Ex8318. No mutation was found in the mother. The fetus, the mother, and the affected sib shared a haplotype, further suggesting heterozygosity. The unaffected status was confirmed postnatally. Am J. Med. Genet. 72:302–306, 1997.

ESP Bulletin Board

The ESPE Research Fellowship Grant is a highly prestigious research grant supported by Novo Nordisk A/S which is given to young investigators within the area of paediatric endocrinology enabling a 2-year research stay abroad in research centers of excellence. The two recipients in 2001 were: Dr. Mäkitie Outi from Helsinki in Finland who trained by Professor Perheentupa. She will go to the Hospital of Sick Children in Toronto, Canada, to work with Dr. W.G. Cole and Professor Daneman on a project named ‘Clinical and genetic aspects of infantile cortical hyperostosis’. Dr. Birgit Köhler from Marburg in Germany who was trained by Professor Grüters. She will go to INSERM Institution in Montpellier, France, to work in the laboratory of Professor Sultan on a project named ‘Interaction of the Wilms tumor suppressor (WT1) protein and the androgen receptor gene?’ Deadline for applications for the 2002 ESPE Research Fellowship Grants is March 1, 2002. Applications should be sent to: