Spontaneous Hypercortisolism without Cushing's Syndrome

Vingerhoeds, A. C. M.; Thijssen, J. H. H.; Schwarz, Franz

doi:10.1210/jcem-43-5-1128

Cited by 155 publications

(76 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The syndrome of familiar glucocorticoid resistance, first described in 1976, is a disorder characterized by hypercorticosolism without Cushingoid features (Vingerhoeds et al 1976, Chrousos et al 1982. Since then, over ten kindreds and sporadic cases have been reported (Iida et al 1985, Lamberts et al 1986, 1992, Nawata et al 1987, Vecsei et al 1989, Hurley et al 1991, Karl et al 1993, 1996, Malchoff et al 1993.…”

Section: Gr Mutationsmentioning

confidence: 99%

Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes

Kino

Chrousos²

2001

Journal of Endocrinology

102

View full text Add to dashboard Cite

show abstract

Section: Gr Mutationsmentioning

confidence: 99%

Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes

Kino

Chrousos²

2001

Journal of Endocrinology

102

View full text Add to dashboard Cite

show abstract

“…Primary cortisol resistance, first described by Vingerhoeds et al (1), is a rare inherited disorder characterized by hypercortisolism without Cushingoid features. Clinical manifestations, if any, are secondary to excess circulating nonglucocorticoid adrenal steroids (1)(2)(3)(4)(5)(6)(7)(8)(9)(10), which cause hypertension with hypokalemia (2) and/or signs of androgen excess (7,9,10).…”

Section: Introductionmentioning

confidence: 99%

A mutation of the glucocorticoid receptor in primary cortisol resistance.

Malchoff

Brufsky²,

Reardon³

et al. 1993

J. Clin. Invest.

198

124

View full text Add to dashboard Cite

The precise molecular abnormalities that cause primary cortisol resistance have not been completely described. In a subject with primary cortisol resistance we have observed glucocorticoid receptors (hGR) with a decreased affinity for dexamethasone. We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance. Total RNA isolated from the index subject's mononuclear leukocytes was used to produce first strand hGR cDNAs, and the entire hGR cDNA was amplified in segments and sequenced. At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GT1) substitution at amino acid 729. When the wild-type hGR and hGR-Ile 729 were expressed in COS-1 cells and assayed for 13H1-Dexamathasone binding, the dissociation constants were 0.799±0.068 and 1.54±0.06 nM (mean±SEM) (P < 0.01), respectively. When the wild-type hGR and hGR-Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase (CAT) gene, the hGR-Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity. The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject. (J. Clin. Invest. 1993.91:1918-1925

show abstract

“…They show a wide spectrum of clinical symptoms, such as hypertension, hypokalemic alkalosis (2), fatigue, and hyperandrogenism (3). Vingerhoeds et al (2) reported a father and a son with GC resistance, and from then until now 20 additional patients and family members with this syndrome have been described (4).…”

mentioning

confidence: 99%

A Polymorphism in the Glucocorticoid Receptor Gene, Which Decreases Sensitivity to Glucocorticoids In Vivo, Is Associated With Low Insulin and Cholesterol Levels

et al. 2002

View full text Add to dashboard Cite

We investigated whether a polymorphism in codons 22 and 23 of the glucocorticoid (GC) receptor gene [GAGAGG(GluArg) 3 GAAAAG(GluLys)] is associated with altered GC sensitivity, anthropometric parameters, cardiovascular risk factors, and sex steroid hormones. In a subgroup of 202 healthy elderly subjects of the Rotterdam Study, we identified 18 heterozygotes (8.9%) for the 22/23EK allele (ER22/23EK carriers). In the highest age group, the number of ER22/23EK carriers was higher (67-82 years, 12.9%) than in the youngest age group (53-67 years, 4.9%; P < 0.05). Two dexamethasone (DEX) suppression tests with 1 and 0.25 mg DEX were performed, and serum cortisol and insulin concentrations were compared between ER22/ 23EK carriers and noncarriers. After administration of 1 mg DEX, the ER22/23EK group had higher serum cortisol concentrations (54.8 ؎ 18.3 vs. 26.4 ؎ 1.4 nmol/l, P < 0.0001), as well as a smaller decrease in cortisol (467.0 ؎ 31.7 vs. 484.5 ؎ 10.3 nmol/l, P < 0.0001). ER22/23EK carriers had lower fasting insulin concentrations (P < 0.001), homeostasis model assessment-insulin resistance (IR) (index of IR, P < 0.05), and total (P < 0.02) and LDL cholesterol concentrations (P < 0.01). Our data suggest that carriers of the 22/ 23EK allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than noncarriers, resulting in a better metabolic health profile. Diabetes 51:3128 -3134, 2002

show abstract

Spontaneous Hypercortisolism without Cushing's Syndrome

Cited by 155 publications

References 14 publications

Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes

Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes

A mutation of the glucocorticoid receptor in primary cortisol resistance.

A Polymorphism in the Glucocorticoid Receptor Gene, Which Decreases Sensitivity to Glucocorticoids In Vivo, Is Associated With Low Insulin and Cholesterol Levels

Contact Info

Product

Resources

About