Objective: To demonstrate the clinical course in a young female with gonadotroph adenoma causing ovarian stimulation. Patient and methods: Our patient was a 23-year-old woman with a history of oligomenorrhea who had previously undergone bilateral ovarian wedge resection owing to the clinical appearance of polycystic ovaries. Two years later, she sought treatment for headache, galactorrhea, history of spotting and lower abdominal distension. FSH, LH, b-LH, inhibin A and B, estradiol, prolactin (PRL), and bchorionic gonadotrophin (b-CG) were measured, and the responses of FSH, LH and b-LH to thyrotrophin-releasing hormone (TRH) were documented. Immunohistochemical analysis of the tumor tissue was performed after surgery. Five years after the trans-sphenoidal surgery, the patient again became oligomenorrheic. A large recurrent adenoma was diagnosed on CT one year later. Transvaginal ultrasound showed ovaries of normal size with multiple small cystic formations simulating a polycystic pattern, While the patient was awaiting surgery, a pituitary apoplexy occurred. Emergency decompressive surgery was performed and the patient fully recovered. Results: Enlarged ovaries were found on ultrasound examination simulating a hyperstimulationlike pattern. At that time, elevated levels of FSH (13.4 IU/l) and marginally elevated levels of b-LH (1.43 ng/ml) were found, whereas the level of LH (0.5 IU/l) was subnormal. Plasma estradiol was markedly supranormal (6150 pmol/l). Levels of inhibin A and B were elevated (326 pg/ml and 588 pg/ml respectively). The prolactin level (70 ng/ml) was increased, whereas b-chorionic gonadotrophin (b-CG) was normal. Signi®cantly increased FSH, LH, and b-LH responses to TRH stimulation were documented. Pituitary macroadenoma was found on MRI scan and removed by trans-sphenoidal surgery. Immunohistochemical examination showed high positivity for b-CG and LH, and slight positivity for FSH. Five years after the surgery, estradiol was elevated (1160 pmol/l), whereas basal levels of LH (4.65 IU/l) and FSH (3.98 IU/l) were not suppressed. After the second operation, immunostaining of the adenoma tissue con®rmed the previous ®ndings. Conclusions: Measurement of gonadotrophins in our case did not prove to be a method for identifying a large recurrent gonadotroph pituitary adenoma. The sonographic ovarian imaging varied from a polycystic-to an ovarian hyperstimulation-like pattern during the evolution of the tumour.

Five children with adrenocorticotropic hormone (ACTH) insensitivity associated with autonomic nervous system disorders are described. At the time of diagnosis, four of them had osteoporosis. The fifth patient died and skeletal roentgenograms were not done. Osteoporosis was subsequently discovered in one of our previously reported patients with ACTH insensitivity. We assume that osteoporosis is, at least partly, the result of decreased adrenal androgen production. Human leucocyte antigen typing failed to establish any linkage.

Nonclassic steroid 21-hydroxylase deficiency is an attenuated adrenal enzyme defect that is commonly the basis of hyperandrogenic syndromes. Inherited as an autosomal recessive trait, it is known to occur with high frequency in the general population and with increased frequency in a number of ethnic groups, including the Yugoslav population. Following expansion of the original data on 21 families in Croatia to a total of 49 Croatian and Serbian families, we establish that this enzymatic disorder is increased in this Slavic population and provide an updated estimate for the gene frequency of 0.092 (0.035\x=req-\ 0.149). Also in keeping with earlier reports, we continue to note the absence of association between nonclassic 21\ x=r eq-\ hydroxylase deficiency occurring among Yugoslavs and HLA-B14;DR1.Nonclassic steroid 21-hydroxylase deficiency is an autosomal recessive disorder that is known to occur with very high frequency generally, and which in addition shows increased prevalence in certain ethnic populations (1). This partial adrenal enzyme defect may or may not be clinically manifest in af¬ fected individuals, but can be identified by hor¬ mone criteria. Mild to moderate elevations of serum androgens result from increased secretion by the adrenal of androgens and of androgenic precursors which undergo peripheral conversion to active hormones. Biochemical indices of reduced adrenal 21-hydroxylation are serum elevations of the steroid intermediates 17a-hydroxyprogesterone (17-OHP), the principal substrate of 21-hy-droxylase, which fails to be converted to 11-deoxycortisol (compound S), the direct precursor of Cor¬ tisol, and also of A4-androstenedione (A4-A), im¬ mediately distal to 17-OHP in the androgenic pathway. Clinical effects arising from 21-hydroxy¬ lase deficiency vary between individuals and the different ages within the same individual.The first population genetic study on nonclassic 21-hydroxylase deficiency (1) identified an in¬ creased incidence among Yugoslavs, estimating the gene frequency among this population to be 0.125 (0.042-0.268 (95% confidence limits)) based on data from 21 families in Zagreb, SR Croatia, Yu¬ goslavia (1). This study observed that positive link¬ age disequilibrium between nonclassic 21-hydroxy¬ lase deficiency and HLA-B14;DR1 existing in other ethnic groups at increased risk, Ashkenazic Jews, Hispanics, and Italians, was absent in the Yu¬ goslav patient group.The population genetic analysis of the original study in 167 families was based on inference of genotype and gene counting as follows: Obligate hétérozygotes (the parents of affected offspring) in each pedigree were genotyped by HLA association and ACTH stimulation hormone testing. Occur¬ rence of the nonclassic deficiency trait in a tested parent identified the presence of a nonclassic de¬ ficiency alíele also on the second haplotype. Con¬ sidering that the second (nontransmitted) haplotypes of known hétérozygotes still represent a Klinika za djecje bolesti REBRO1 and Centar za tipizaciju tkiva REBRO2,

We describe two sisters (40 and 42 years old) heterozygous for adrenoleukodystrophy who have multiple endocrine disorders. In addition to the characteristic neurological symptoms, the younger patient has Addison disease and primary hypothyroidism attributable to autoimmune thyroiditis, and the older one has Graves disease. Both patients have loss of body hair and sparse scalp hair, which have not been reported previously in women heterozygous for adrenoleukodystrophy. After the institution of glucocorticoid replacement therapy, the younger sister, who has adrenal insufficiency, has shown unexpected neurological improvement.

Growth hormone (GH) responses to sleep, insulin hypoglycaemia and arginine infusion. A few children with no apparent cause for their short stature, continue to grow poorly despite normal GH responses (>15mU/L) to pharmacological stimuli. It has been suggested that their GH secretion during sleep may more accurately reflect their true GH reserve. We have compared sleep related GH secretion (GH-Sleep) with GH responses to insulin hypoglycaemia (GH-I) and arginine infusion (GH-Arg.) in 19 children referred to our Growth Clinic. Blood was withdrawn continuously through an indwelling thromboresistant catheter (Cormed SL-65 Continuous Blood Withdrawal Pump) and divided into 15 minute aliquots, throughout approximately 5 hours of EEG monitored sleep. The following morning an, insulin hypoglycaemia/arginine infusion test was performed. GH was measured by radioiuununoassay. 2 patients had normal GH-Arg. responses but GH-Sleep peaks less than 15mU/~. Correlation coefficients, r, for peak serum GH levels were :for GH-I & GH-Sleep 0.55 (p<0.02), GH-Arg. & GH-Sleep 0.52 (p<0.02) and GH-I & GH-Arg. 0.56 (p <0.02). We conclude that sleep studies of GH reserve are indicated only when the results of stimulation tests are inconsistent with clinical findings.

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.

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.

Five individuals with the asymptomatic, 'nonclassical', 'cryptic' form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OH) deficiency from 5 unrelated families were discovered during hormonal studies and HLA-typing performed in a series of 24 families with CAH due to 21-OH deficiency. Four of the 5 individuals with the 'cryptic' form of CAH belong to families where the index case was a patient with the classical form of CAH due to 21-OH deficiency. The fifth one originated from a family where the index case was a girl with the 'non-classical', 'late-onset' form of the disease. All the 5 individuals had no clinical symptoms in spite of clearcut biochemical signs of 21-OH deficiency: increased 17-OH-progesterone (17-OHP), dehydroepiandrosterone and androstenedione levels, particularly after ACTH-stimulation. The 17-OHP response upon ACTH stimulation of heterozygotes for this 'non-classical' form of 21-OH deficiency did not differ from the response of heterozygous individuals for the classical form of the disease. The results of this study confirm the hypothesis that individuals with the 'cryptic' form of CAH due to 21-OH deficiency are genetic compounds bearing one allele for the severe, classical form, and on the homologous locus, another one for the mild 'nonclassical' form of CAH due to 21-OH deficiency. Their genotype was 21-OHsevere/21-OHmild, The gene for 'cryptic' 21-OH deficiency, as well as the gene for the classical form of the disease is linked to the HLA system, but in our population apparently it is not in genetic disequilibrium with the antigens B 14 DR 1, as it was shown for other populations studied up to now.