info on Chrousos syndrome:
An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature
An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature.
“Glucocorticoid resistance, also named Chrousos syndrome, is a rare, sporadic or familial condition characterized by biochemically proven hypercortisolism without the clinical stigmata of Cushing syndrome, and by partial or generalized insensitivity to glucocorticoids. Due to this insensitivity, and thereby inadequate negative feedback, serum ACTH, and therefore cortisol production were compensatory stimulated. The chronic excess of ACTH results in an overstimulated steroid biosynthesis, including increased production of adrenal steroids with androgenic and/or mineralocorticoid activity [8, 9]. The clinical spectrum ranges from a completely asymptomatic form [10] to severe, life threatening conditions such as severe hypokalaemia, alkalosis or hypoglycaemia. In addition, hyperandrogenism (acne, hirsutism, infertility, oligo-amenorrhea in females, oligospermia and infertility in males, precocious puberty in children) [11] and mineralocorticoid excess (hypertension and hypokalemic alkalosis) [12] can also be observed. Fatigue is the most common sign of the disease [10]. The diagnosis is based on a detailed evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. Measurement of serum cortisol levels in samples collected in the morning under fasting conditions, at midnight and after dexamethasone administration, together with evaluation of 24 h urinary-free cortisol excretion, are mandatory investigations for diagnosis. Serum cortisol and 24 h urinary free cortisol excretion remain elevated after administration of low dose dexamethasone [13]. Contrary to Cushing’s syndrome, in patients with Chrousos syndrome, the HPA axis preserves its circadian rhythm [13].”
This is pretty alarming. The article also mentions later on the there is increased adrenal DHEA -as also mentioned by Danny Roddy in his article
The Danny Roddy Weblog
Primary Generalized Glucocorticoid Resistance or Chrousos Syndrome
Primary Generalized Glucocorticoid Resistance or Chrousos Syndrome - Endotext - NCBI Bookshelf
"Clinical manifestations of androgen excess include ambiguous genitalia in a karyotypic female at birth and gonadotropin-independent precocious puberty in children of either gender; acne, hirsutism and decreased fertility in both sexes; male-pattern hair loss, menstrual irregularities and oligo-anovulation in females; and oligospermia in males (Table 1). The impaired fertility in both sexes has been attributed in part to the feedback inhibition of gonadotropin secretion by the elevated androgen concentrations, while the profound anxiety observed in some subjects is probably due to compensatory increases in hypothalamic CRH and AVP secretion. The latter might also predispose the patients to the development of an ACTH-secreting pituitary adenoma. Finally, the elevated circulating ACTH concentrations may be responsible for the observed growth of intra-testicular adrenal rests and oligospermia (47-58).
The clinical spectrum of Chrousos syndrome is broad, ranging from most severe to mild forms, and a number of patients may be asymptomatic, displaying biochemical alterations only (47-58) (Table 1). This variable clinical phenotype is due to variations in the tissue sensitivity of the glucocorticoid, mineralocorticoid and/or androgen receptor signaling pathways; variations in the activity of key hormone-inactivating or -activating enzymes, such as the 11β-hydroxysteroid dehydrogenase (61) and 5α-reductase (62); and other genetic or epigenetic factors, such as the presence of insulin resistance and visceral obesity (58)."
An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature
An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature.
“Glucocorticoid resistance, also named Chrousos syndrome, is a rare, sporadic or familial condition characterized by biochemically proven hypercortisolism without the clinical stigmata of Cushing syndrome, and by partial or generalized insensitivity to glucocorticoids. Due to this insensitivity, and thereby inadequate negative feedback, serum ACTH, and therefore cortisol production were compensatory stimulated. The chronic excess of ACTH results in an overstimulated steroid biosynthesis, including increased production of adrenal steroids with androgenic and/or mineralocorticoid activity [8, 9]. The clinical spectrum ranges from a completely asymptomatic form [10] to severe, life threatening conditions such as severe hypokalaemia, alkalosis or hypoglycaemia. In addition, hyperandrogenism (acne, hirsutism, infertility, oligo-amenorrhea in females, oligospermia and infertility in males, precocious puberty in children) [11] and mineralocorticoid excess (hypertension and hypokalemic alkalosis) [12] can also be observed. Fatigue is the most common sign of the disease [10]. The diagnosis is based on a detailed evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. Measurement of serum cortisol levels in samples collected in the morning under fasting conditions, at midnight and after dexamethasone administration, together with evaluation of 24 h urinary-free cortisol excretion, are mandatory investigations for diagnosis. Serum cortisol and 24 h urinary free cortisol excretion remain elevated after administration of low dose dexamethasone [13]. Contrary to Cushing’s syndrome, in patients with Chrousos syndrome, the HPA axis preserves its circadian rhythm [13].”
This is pretty alarming. The article also mentions later on the there is increased adrenal DHEA -as also mentioned by Danny Roddy in his article
The Danny Roddy Weblog
Primary Generalized Glucocorticoid Resistance or Chrousos Syndrome
Primary Generalized Glucocorticoid Resistance or Chrousos Syndrome - Endotext - NCBI Bookshelf
"Clinical manifestations of androgen excess include ambiguous genitalia in a karyotypic female at birth and gonadotropin-independent precocious puberty in children of either gender; acne, hirsutism and decreased fertility in both sexes; male-pattern hair loss, menstrual irregularities and oligo-anovulation in females; and oligospermia in males (Table 1). The impaired fertility in both sexes has been attributed in part to the feedback inhibition of gonadotropin secretion by the elevated androgen concentrations, while the profound anxiety observed in some subjects is probably due to compensatory increases in hypothalamic CRH and AVP secretion. The latter might also predispose the patients to the development of an ACTH-secreting pituitary adenoma. Finally, the elevated circulating ACTH concentrations may be responsible for the observed growth of intra-testicular adrenal rests and oligospermia (47-58).
The clinical spectrum of Chrousos syndrome is broad, ranging from most severe to mild forms, and a number of patients may be asymptomatic, displaying biochemical alterations only (47-58) (Table 1). This variable clinical phenotype is due to variations in the tissue sensitivity of the glucocorticoid, mineralocorticoid and/or androgen receptor signaling pathways; variations in the activity of key hormone-inactivating or -activating enzymes, such as the 11β-hydroxysteroid dehydrogenase (61) and 5α-reductase (62); and other genetic or epigenetic factors, such as the presence of insulin resistance and visceral obesity (58)."
