The syndrome of apparent mineralocorticoid syndrome (AME) results from defective 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2). This enzyme is co-expressed with the mineralocorticoid receptor (MR) in the kidney and converts cortisol to its inactive metabolite cortisone. Its deficiency allows the unmetabolized cortisol to bind to the MR inducing sodium retention, suppression of PRA and hypertension. Thus, the syndrome is a disorder of the kidney. We present here the first patient affected by AME cured by kidney transplantation. Formerly, she was considered to have a mild form of the syndrome (Type II), but progressively she developed renal failure which required dialysis and subsequent kidney transplantation. To test the ability of the transplanted kidney to normalise the patient's cortisol metabolism, we gave, in two different experiments, 25 and 50 mg/day of cortisone acetate or 15 and 30 mg/day of cortisol after inhibition of the endogenous cortisol by synthetic glucocorticoid (methylprednisolone and dexamethasone). The AME diagnostic urinary steroid ratios tetrahydrocortisol+5alphatetrahydrocortisol/tetrahydrocortisone and cortisol/cortisone were measured by gas chromatography/mass spectrometry. Transplantation resulted in lowering blood pressure and in normalization of serum K and PRA. After administration of a physiological dose of cortisol (15 mg/day), the urinary free cortisol/cortisone ratio was corrected (in contrast to the A-ring reduced metabolites ratio), confirming that the new kidney had functional 11beta-HSD2. This ratio was abnormally high when the supra-physiological dose of cortisol 30 mg/day was given. After cortisone administration, the tetrahydrocortisol+5alphatetrahydrocortisol/tetrahydrocortisone ratio resulted normalised with both physiological and supra-physiological doses, confirming that the hepatic reductase activity is not affected. As expected, the urinary free cortisol/cortisone ratio was normal with physiological, but increased after supra-physiological doses of cortisone. The described case indicates a normalisation of cortisol metabolism after kidney transplantation in AME patient and confirms the supposed pathophysiology of the syndrome. Moreover, it suggests a new therapeutic strategy in particularly vulnerable cohorts of patients inadequately responsive to drug therapy or with kidney failure.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Etizolam in the treatment of generalized anxiety disorder: a controlled clinical trial.

A total of 45 patients with generalized anxiety disorder were treated twice daily for 2 weeks, on a double-blind basis, with 0.5 mg etizolam, 0.5 mg alprazolam or 3 mg bromazepam, and symptoms were assessed using Hamilton's rating scale for anxiety and Hamilton's rating scale for depression. Patients then received the same drug for a further 2 weeks, the drugs being given three times daily if a poor response was observed during the first 2 weeks. All drugs displayed equivalent anxiolytic activity after 2 weeks, but etizolam displayed a progressive increase in anxiolytic activity over 4 weeks of treatment. Etizolam also possessed a more marked antidepressant effect than did alprazolam or bromazepam. There were no differences in the tolerability of the three drugs.

Adult↗

PubMedDate not supplied

Calcium ion and pituitary hormones: effect of calcium channel blockers on stimulated secretion of pituitary hormones.

The effects of two calcium channel blockers nifedipine (20 mg sublingual), and verapamil (10 mg i.v.) on growth hormone (GH), thyrotropin (TSH), prolactin (PRL) and gonadotropin (LH and FSH) secretion induced by growth hormone releasing hormone (GHRH), hypoglycemia, thyrotropin releasing hormone (TRH), metoclopramide and gonadotropin releasing hormone (GnRH), were studied in a group of normal volunteers (27 men and 8 women). Neither nifedipine nor verapamil had any effect on PRL, TSH or gonadotropin release. Verapamil did not cause variations in GH secretion following GHRH and insulin-induced hypoglycemia, whereas nifedipine significantly reduced the elevation in GH induced by GHRH; however the GHRH-mediated GH rise still remained within the normal range in all subjects. Our results suggest that neither nifedipine nor verapamil have important effects on stimulated pituitary hormone secretion, at least under conditions of acute administration.

Adolescent↗

PubMedDate not supplied

A reevaluation of methodological aspects of a commercial RIA kit for plasma renin activity.

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Humans↗

PubMedDate not supplied

[The optic and trigemino-facial reflexes in the diagnosis of multiple sclerosis].

The optic facial reflex (ofr) has been studied in a group of subjects affected by multiple sclerosis (ms) and compared with the trigemino-facial reflex (tfr) as well as clinical data. From the literature it appears that the afferent pathway of the ofr, after the optic chiasma crosses the midbrain tegmentum and from there goes directly to the pons. The ofr was impaired in 14 subjects out of 20 (70%), the tfr only in 7 (35%). This difference is attributed to the fact that the visual pathways are frequently affected by demyelinating processes. The ofr in contrast with the tfr, because of anatomophysiological differences, does not supply the exact localization of the damage. In our series of patients affected by ms the data from ofr reflected exactly the signs of optic nerve lesions. When these were not found, ofr abnormality was attributed to lesions located behind the chiasma or in the midbrain. A close correspondence between data supplied from the ofr and the diagnosis of ms according to Mc Alpine is emphasized: this makes the ofr a very useful diagnostic test of ms. The combined use of ofr and tfr, in addition to fulfilling the criteria of detecting multiple sites of demyelination, can be useful to investigate the brain stem.

Adult↗