Glucocorticoid resistance is an autosomal dominant or recessive disorder caused by mutations of the glucocorticoid receptor. It is characterized by elevated cortisol levels and without any signs of Cushing disease.
In 1976, the disease was first described by Vingerhoeds in a man with a homozygous glucocorticoid receptor mutation as Spontaneous hypercortisolism without Cushing's syndrome.[Error: Macro 'ref' doesn't exist]
The suppression of morning ACTH levels can be achieved by midnight dexamethason. The dose started with 1mg/d should be titrated down as long as aldosterone and androgens remain normal. Some patients end up with doses as low as 0.25mg/d. Hyperaldosteronism is best treated with aldosterone anatgonists whose potassium sparing and antiandronenic effects are particularly beneficial in this disorder.
Hypertension | |
Hyperaldosteronism-like Hypertension is the most prominent clinical symptom of patients with glucocorticoid resistance. |
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Hypokalemia | |
Hypokalemia is the direct consequence of hyperaldosteronism. |
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Virilization | |
Hyperandrogenism causes virilization in females in whom most of the androgens are produced ACTH-dependently by the adrenals. As in in men the androgen production is predominantly maintained by the testes adrenal hyperandrogenism has no clinical effect. |
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Hyperandrogenism | |
Virilization becomes apparent in female patients only. |
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Hirsutism | |
Hirsutism develops as a result of Hyperandrogenism and leads in women to male type body hair. |
1. |
Hurley DM et al. (1991) Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. |
2. |
Chrousos GP et al. (1982) Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms. |
3. |
Nawata H et al. (1987) Decreased deoxyribonucleic acid binding of glucocorticoid-receptor complex in cultured skin fibroblasts from a patient with the glucocorticoid resistance syndrome. |
4. |
Donner KM et al. (2013) Generalized glucocorticoid resistance caused by a novel two-nucleotide deletion in the hormone-binding domain of the glucocorticoid receptor gene NR3C1. |
5. |
Charmandari E et al. (2008) Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder. |
6. |
Huizenga NA et al. (2000) Five patients with biochemical and/or clinical generalized glucocorticoid resistance without alterations in the glucocorticoid receptor gene. |
7. |
Karl M et al. (1993) Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. |
8. |
Chrousos GP et al. (1983) Primary cortisol resistance: a family study. |
9. |
Chrousos GP et al. (1982) Primary cortisol resistance in man. A glucocorticoid receptor-mediated disease. |
10. |
Iida S et al. (1985) Primary cortisol resistance accompanied by a reduction in glucocorticoid receptors in two members of the same family. |
11. |
Lamberts SW et al. (1986) Familial cortisol resistance: differential diagnostic and therapeutic aspects. |
12. |
Brönnegård M et al. (1986) Primary cortisol resistance associated with a thermolabile glucocorticoid receptor in a patient with fatigue as the only symptom. |
13. |
Lipsett MB et al. (1985) The defective glucocorticoid receptor in man and nonhuman primates. |
14. |
Vingerhoeds AC et al. (1976) Spontaneous hypercortisolism without Cushing's syndrome. |
15. |
Bray PJ et al. (2003) Variations of the human glucocorticoid receptor gene (NR3C1): pathological and in vitro mutations and polymorphisms. |
16. |
Orphanet article Orphanet ID 786 |
17. |
OMIM.ORG article Omim 615962 |