11ß-hydroxysteroid dehydrogenase type-II activity is affected by grapefruit juice and intense muscular work

ABSTRACT Objective The enzymatic activity of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) is key to protecting mineral corticoid receptors from cortisol and has been implicated in blood pressure regulation. Grapefruit juice (GFJ) and acidity are thought to inhibit this enzyme in vitro. This study examines the effect of GFJ and intense exercise on 11β-HSD2 enzyme activity in vivo. Subjects and methods Eighteen subjects ingested GFJ or apple juice (CON) on separate days prior to reporting to the laboratory in a randomized order. Saliva (Sal) samples were obtained at baseline, 15 and 45 minutes post-treadmill stress test; Sal cortisone (E) and cortisol (F) levels were determined, and the Sal cortisone:cortisol (E:F) ratio was used as an index of 11β-HSD2 enzyme activity at rest and after intense muscular work. Results GFJ treatment decreased baseline 11β-HSD2 enzyme activity (44%) and Sal-E (28%) compared to CON (both, p < 0.05). Sal-E (r = 0.61, p < 0.05) and Sal-F (r = 0.66, p < 0.05) were correlated with diastolic blood pressure (DBP) in GFJ-treated individuals. Treadmill stress significantly increased Sal-E and Sal-F but did not alter 11β-HSD2 enzyme activity regardless of treatment. When treatments were examined separately, CON 11β-HSD2 enzyme activity decreased by 36% (p < 0.05) from baseline to 15 post-treadmill exercise. Conclusion Our findings suggest that GFJ and intense muscular work decrease 11β-HSD-2 activity independently, and no additive effect was noted. The association between DBP and the levels of Sal-F and Sal-E during the GFJ trial should be interpreted cautiously and warrants further investigation.

Study on serum and urinary cortisol levels of asthmatic patients after treatment with high dose inhaled beclomethasone dipropionate or budesonide.

BACKGROUND: The potential for long-term adverse effects from inhaled corticosteroids relates to their systemic absorption. With increasing use of high dose inhaled corticosteroids, there is need to establish whether similar doses of beclomethasone dipropionate (BDP) and budesonide (BUD) produce clinically important differences in untoward side effects specially hypothalamo-pituitary-adrenal (HPA) axis suppression. METHODS: Fifteen asthmatic patients were started on BDP or BUD (2000 microg/day) through spacer for six weeks. Serum cortisol (9 AM and 4 PM), 24-hour urinary steroid and pulmonary function testing parameters were performed. RESULTS: The serum cortisol levels were not found to be suppressed with either BDP or BUD. Similarly no significant changes were found in 24 hours urinary excretion of steroids with either of the drugs. Significant improvement was found in values of forced expiratory volume in the first second (FEV1) with BDP. With BUD the changes in forced vital capacity (FVC) and FEV1 were found to be significant. CONCLUSION: BDP or BUD in high doses of 2000 microg/day given upto six weeks through spacer are equally effective for treatment of bronchial asthma and do not cause any significant change in serum and urinary cortisol levels, and adrenal function/HPA axis.

Síndrome de exceso aparente de mineralocorticoides por déficit de 11 ß hidroxiesteroide deshidrogenasa / A syndrome of apparent mineralocorticoid excess associated with a deficiency of 11 ß-hydroxysteroid dehydrogenase

An 11-year old girl was seen in 1981 with hypokalemia, low renin, low aldosterone, and severe hypertension. A medical adrenalectomy with dexamethasone and aminoglutethimide, and the blockade of mineralocorticoid receptors with spironolactone improved her condition, but the blockade of glucocorticoid receptors with RU-486 worsened it. An aldosterone infusion induced no changes. A sister was born in 1982 with similar findings. Both patients had an impaired ability to convert cortisol to cortisone after an oral load of 200 mg cortisol. In urine, an elevated ratio for metabolites of cortisol to metabolites of cortisone was found. These data suggested a defect in the activity of renal 11ß-hydroxysteroid dehydrogenase. Both parents were asymptomatic, phenotypically normal and non-consanguineous. Their urinary metabolites of cortisol and cortisone were normal before and after stimulation with ACTH. However, the mother reached a peak plasma cortisone concentration 3 SD below the mean reached by normal subjects after an oral 200-mg cortisol load, a fact that suggests that this test could be used to detect heterozygotes. The genetic studies revealed a homozygous mutation on exon 3 of the HSD11K gene, which by substituting TGC for CGC changes Arg 213 for Cys and induces a loss of 84 percent of the enzymatic activity in transfected cells. Both unrelated parents had the same heterozygous mutation. Both patients have been treated with dexamethasone but have also required spironolactone. The older sister has also required high doses of nifedipine to lower her blood pressure. After 19 years of follow-up, the older sister has become normotensive and normokalemic under therapy, and reached a final height of 140 cm at age 17. The younger sister has increased her mean blood pressure at a rate of 1 mm Hg per year, in spite of treatment. Her final height is 143.5 cm

Problemas en el tratamiento de la enfermedad de Cushing / Problems in the management of Cushing's disease

Los resultados del tratamiento de la enfermedad de Cushing siguen siendo muy variables, lo cual indica que aún no se conoce su fisiopatogenia. La revisión de 12 casos en los que el diagnóstico se estableció mediante pruebas hormonales y tomografia craneal computada y se sometieron a microcirugía hipofisaria, reveló que el índice de curación fue bajo (42 por ciento) después del primer tratamiento y que el resto falleció (tres pacientes) o requirió de otro tratamiento. Se puede concluir que aunque en la actualidad no hay dificultad para establecer el diagnóstico, su tratamiento debe individualizarse. En caso de microadenoma el tratamiento de elección es operación transesfenoidal y, cuando se presenta persistencia, el siguiente recurso puede ser radioterapia ordinaria auxiliada por fármacos en forma temporal para disminuir los efectos del cortisol elevado en la sangre. En caso de macradenoma, que es índice de mal pronóstico, se debe hacer hipofisectomía y seguirse de radiación ordinaria. La adrenolectomía debe reservarse para los casos en que haya contraindicación absoluta para la operación hipofisaria