Late diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Congenital adrenal hyperplasia results from 21-hydroxylase deficiency in more than ninety percent of cases. The classical form of 21-hydroxylase deficiency presents in the neonatal period with virilization or adrenal insufficiency, with or without concurrent salt wasting. We report on a rare case of classic 21-hydroxylase deficiency diagnosed in late adulthood. A 39-year-old male patient presented for workup of infertility. Urologic investigation revealed small testes, bilateral testicular masses, and asthenozoospermia. The patient's steroid metabolism showed markedly increased levels of adrenal androgens, in particular of 17-hydroxyprogesterone amd 21-deoxycortisol. The gas chromatographic-mass spectrometric (GC-MS) urinary steroid profile was dominated by metabolites of 17-hydroxyprogesterone, while the endogenous glucocorticoid production was subnormally low. ACTH levels in plasma were elevated. These hormonal findings were consistent with 21-hydroxylase deficiency. Therapy with dexamethasone was initiated. The CTP21A2 gene analysis revealed the mutation I172N (ATC --> AAC) in exon 4 of allele 1 and a large gene deletion in allele 2. Cases of 21-hydroxylase deficiency diagnosed in late adulthood are rare; however, clinicians should be alert of this possibility.     

Synthesis and evaluation of a new series of mechanism-based aromatase inhibitors.

A series of new 4-(alkylthio)-substituted androstenedione analogues was designed as potential suicide inhibitors of aromatase on the basis of mechanistic considerations on the mode of action of the enzyme. Their synthesis and biological evaluation are described. Among the most interesting are the 4-[(difluoromethyl)thio]-, 4-[(fluoromethyl)thio]-, and 4-[(chloromethyl)thio]androstenediones 12, 13, and 14 with respective IC50's of 2.7, 0.8, and 0.94 microM. Compound 12 was a reversible inhibitor of aromatase while compounds 13 and 14 displayed time-dependent kinetics of inhibition with respective KI's and half-times of inactivation of 30 nM and 3.75 min for 13 and 30 nM and 3 min for 14. The inhibition of aromatase by 14 was NADPH-dependent, and was protected by the presence of substrate (0.5-1 microM), while beta-mercaptoethanol (0.5 mM) failed to protect the enzyme from inactivation. Dialysis failed to reactivate aromatase previously inactivated by 14. The mechanistic implications of these findings are discussed.     

Determination of correction based on natural visual acuity in myopes]

The authors demonstrate the possibility to assess the correction in ametropes according to the value of their natural vision. To this end they use normalized optotype tables with Landolt rings which have a constant diminution coefficient between individual consecutive lines. By means of this elaborated method the authors were able to assess in twenty myopic subjects that a correction of -1.0 corresponds to an improvement by four lines, one line thus corresponds to a correction of -0.25 dioptres.     

Differential effect of catechol-O-methyltransferase Val158Met genotype on emotional recognition abilities in healthy men and women.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism modulates executive functions and working memory and recent neuroimaging studies implicate an association with emotional processing. We examined the relationship between the COMT Val158Met polymorphism and facial emotion recognition and differentiation in 100 healthy individuals. Compared to Met homozygosity, Val homozygosity was associated with better and faster recognition of negative facial expressions such as anger and sad. Our study provides evidence for a possible influence of the COMT polymorphism on emotion recognition abilities in healthy subjects. Additional research is needed to further define the neurocognitive phenotypes associated with COMT polymorphisms.     

Post-radiotherapy hyperthyroidism: a rare complication of cancer treatment in the child]

Abnormalities of thyroid function, specially hypothyroidism, are common complications of head and neck irradiation for childhood cancer. Hyperthyroidism is rare and can be misdiagnosed. We report two observations of this condition. OBSERVATIONS: The first patient received conventional craniospinal irradiation for a localized medulloblastoma. Three years later, he presented with profuse sweating, irritability and paroxysmal tachycardia. Biologic evaluation revealed a peripheral hyperthyroidism. The patient was treated with antithyroidian hormonal treatment. The second patient received an irradiation for an undifferentiated nasopharyngeal carcinoma. Three years later, she developed a progressive thyrotoxicosis which was attributed to hyperthyroidism after six months of evolution. Hormonal treatment improved the clinical state after several weeks. CONCLUSION: Hyperthyroidism is a rare complication of head and neck irradiation. This condition justifies a periodic and prolonged evaluation of thyroid function.     

Correlation between blood pressure and the level of monoamines in the cerebrospinal fluid of patients with cerebral haemorrhage. Case reports

The correlation between the noradrenalin (NA), dopamine (DA) and serotonin (5-HT) contents of cerebrospinal fluid (CSF) samples obtained from the cerebro-ventricular space and the systolic and diastolic blood pressure (BP) of two patients with cerebral haemorrhage were investigated. Significant correlation was found between CSF NA, CSF DA level and systolic BP in case I. There was no correlation between CSF catecholamine levels and diastolic BP and between serotonin level and BP. Significant correlation was observed in case II between CSF DA level and diastolic BP. There was no correlation between CSF serotonin level and BP. These results suggest that CSF catecholamines might play some role in the regulation of BP.     

Genetic alterations of Carney complex are not present in sporadic cardiac myxomas.

Cardiac myxomas are the most frequent cardiac tumors and cause for significant morbidity and mortality. Recent evidence indicates that cardiac myxomas are, in fact, neoplasms rather than organized thrombi. Cardiac myxomas may present as solitary lesions or in association with the Carney complex. Carney complex has been linked to chromosome 2p16 and the PRKAR1A gene at 17q22-24. In this study, we analyzed sporadic cardiac myxomas to evaluate whether the genetic alterations seen in Carney complex are present in non Carney complex associated cardiac myxomas as well. We analyzed microdissected material from 13 patients with cardiac myxomas for the markers PRKAR1 9CA, D2S2153, D2S2251 and D2S123. None of the cases demonstrated loss of heterozygosity or definite band changes suggestive of microsatellite instability for any of the markers used. We conclude that sporadic cardiac myxomas are genetically not related to Carney complex and most likely do not represent an incomplete form of Carney complex.