Cortisol receptor resistance: the variability of its clinical presentation and response to treatment.

Abstract

Primary (partial) cortisol receptor resistance was previously reported in a total of 7 patients and 14 asymptomatic family members. Its occurrence is considered to be extremely rare. In the present study we report on 6 patients (2 males and 4 females) with the syndrome. The first male patient presented with mild hypertension. Hydrochlorothiazide therapy resulted in life-threatening hypokalemia. The second male patient had slight hypertension without hypokalemia. All four female patients presented between the age of 20-30 yr with acne, hirsutism, and irregular menstruations. Low dose dexamethasone therapy (1-1.5 mg/day) was of clinical benefit in these patients. All patients showed insufficient suppression of serum cortisol concentrations in the overnight 1-mg dexamethasone test. The diurnal rhythm of ACTH and cortisol was intact, albeit at an elevated level. There was a normal increase in ACTH, cortisol, and GH (except in one obese patient) in response to insulin-induced hypoglycemia, while cortisol production was elevated in three patients. Circulating adrenal androgen levels were increased in all patients. Glucocorticoid receptors were investigated in a whole cell dexamethasone binding assay in mononuclear leukocytes. In the first male patient, the number of receptors was very low, while the affinity was lower than that in controls. A lowered affinity to dexamethasone was found in one female patient, while a lowered number of receptors was found in three patients. In the second male patient, no abnormalities were found. As a bioassay for glucocorticoid action we also measured dexamethasone suppressibility of mitogen-stimulated incorporation of [3H]thymidine in mononuclear leukocytes. In the male patient with normal receptor status, dexamethasone suppressibility of [3H]thymidine incorporation was significantly lower than that in healthy controls with respect to both maximal suppression and IC50. Partial cortisol receptor resistance might be less rare than previously thought. In the six patients presented, at least three different forms can be recognized. Therapy with dexamethasone was successful in female patients with acne and hirsutism, as the secondary increase in the production of adrenal androgens was effectively controlled.

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

“…This discrepancy can be attributed to differences in patient selection criteria. Although MEF 50 and MEF 25 are less accurate parameters of expiratory flow, the significance and consistency of this finding indicate that the effect of FP on lung function is most probably caused by an effect on the small airways rather than by an effect on the larger airways.…”

“…34 From our analysis of the MEFV curves, we hypothesise that the anatomical location of the anti-inflammatory effect of inhaled steroids is in the smaller airways. Significant changes were observed in MEF 50 and MEF 25 . In contrast to other studies, 31 we found no effect on FVC and PEF.…”

“…The FEV 1 /FVC ratio (prebronchodilator) showed a similar pattern of change (mean difference 0.065, p=0.024, rmANOVA). There were significant changes in MEF 50 from the second month of treatment (0.29 (0.07) l; p=0.002) and in MEF 25 from the third month of treatment (0.32 (0.09) l; p=0.008, fig 5A, B). Neither FVC nor PEF were affected and remained unchanged in both groups.…”

“…The concentration of cortisol was determined using kits supplied by Diagnostics Products Corporation (Los Angeles, California, USA). 25 …”

Causas raras de pseudo-hermafroditismo feminino: quando suspeitar?

“…Clinicamente, os pacientes apresentam-se sem os sinais da síndrome de Cushing, a despeito da presença de hipercortisolismo bioquímico. A apresentação clínica varia desde a ausência de sintomas ou queixas sutis de fadiga crônica até quadros clínicos mais exuberantes com hipertensão arterial e alcalose hipocalêmica e, caso predomine a hipersecreção de andró-genos, o quadro clínico pode apresentar-se, na mulher, com sinais de virilização (acne, hirsutismo, oligomenorréia, oligoanovulação e infertilidade), na criança com pubarca precoce e no homem podem ocorrer alterações da espermatogênese e infertilidade (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51).…”