Duarte Pignatelli

Mutational Characterization of Steroid 21-Hydroxylase Gene in Portuguese patients with Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common inherited disorder of adrenal hormone biosynthesis due to mutations in the 21-hydroxylase gene, CYP21A2. Genotyping for ten of the most frequent mutations was performed in 84 Portuguese CAH patients: 10 salt-wasters, 6 simple-virilizers and 68 non-classical patients. The patients were diagnosed by a level of 17-hydroxyprogesterone above 10 ng/ml either in basal conditions or after an ACTH 0,25 mg IV Test. A variety of genotyping techniques were used to detect these ten mutations. CYP21A2 mutations were detected in 91.7% (77/84) of the patients. The frequency of alleles carrying two or more CYP21A2 mutations (9.5% - 16/168) is higher than in other populations. The most frequent mutations identified in our population were V281L (41.7%) and deletions/conversions involving the promoter region of the CYP21A2 gene (28.3%). A decreased frequency of IVS2-12C/A>G mutation (5.6%) was the most characteristic feature of our population. This study allow the characterization of the mutational spectrum of CAH patients, mainly non-classical CAH, with 21-hydroxylase deficiency from Portugal showing specific genetic features of this population which reveals differences with worldwide countries.

Etomidate and Cushing's syndrome.

Schmidt er al. in their recent paper (Anaesthesia 1985; 40: 5 8 3 4 ) have presented data which provided very strong evidence for the synergistic effects of naloxone in combination with buprenorphine in pain relief. This finding had been previously reported by Dum and Herz, who showed that the agonist potency of higher doses of buprenorphine was increased by the concomitant administration of the opioid antagonist naltrexone. They explained this apparently paradoxical effect by suggesting that it might be due to cooperativity at the receptor.’ We have considered such an explanation in attempting to clarify our own findings. in which naloxone potentiated the effects of opioid agonists, i.e. analgesic nitrous oxide2 and morphine3 and which led us to postulate the use of pure opioid antagonists as analg e s i c ~ . ~ Furthermore, as a result of this work we have proposed the dual system hypothesis of pain perception, based on the presence of both an opioid and antiopioid system with differential sensitivities to nalo x ~ n e . ~ . ~ . ~ . ~ Using this hypothesis it is possible to explain these paradoxical effects of pure opioid antagonists. Experimental confirmation of the presence of such an hyperalgesic anti-opioid system has been presented by Wu el a / . , who have localised this system in the pontine-medullary region.’ References