Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor

Table 2 Clinical manifestations and diagnostic evaluation of primary generalized glucocorticoid resistance or Chrousos Syndrome

Clinical presentation	Diagnostic evaluation
Apparently normal glucocorticoid function	Absence of clinical features of Cushing syndrome
Asymptomatic	Normal or elevated plasma ACTH concentrations
Hypoglycemia	Elevated plasma cortisol concentrations
Chronic fatigue (glucocorticoid deficiency?)	Increased 24-hour urinary free cortisol excretion
Mineralocorticoid excess	Normal circadian and stress-induced pattern of cortisol and ACTH secretion
Hypertension	Resistance of the HPA axis to dexamethasone suppression
Hypokalemic alkalosis	Thymidine incorporation assays: Increased resistance to dexamethasone-induced suppression of phytohemaglutinin-stimulated thymidine incorporation compared to control subjects
Androgen excess	Dexamethasone-bindings assays: Decreased affinity of the glucocorticoid receptor for the ligand compared to control subjects
Children: Ambiguous genitalia at birth*, premature adrenarche, precocious puberty	Molecular studies: Mutations/deletions of the glucocorticoid receptor
Females: Acne, hirsutism, male-pattern hair loss, menstrual irregularities, oligo-anovulation, infertility
Males: Acne, hirsutism, oligospermia, adrenal rests in the testes, infertility
Increased HPA axis activity (CRH/ACTH hypersecretion)
Anxiety
Adrenal rests

Modified from References [28] and [29].
* This is the only case of ambiguous genitalia documented in a child with 46,XX karyotype who also harbored a heterozygous mutation of the 21-hydroxylase gene.

ISSN: 1472-6823