← all disease traces
21-hydroxylase deficiency (classic salt-wasting CAH)
CYP21A2OMIM 201910do(cortisol ↓)
loss-of-function of adrenal 21-hydroxylase -> impaired cortisol (and aldosterone) synthesis; loss of cortisol negative feedback raises ACTH.
plasma adrenocorticotropic hormone (corticotropin) concentration ↑HPO: Increased circulating ACTH levelHP:0003154
comparative-statics (steady-state) net: ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑
plasma cortisol concentration ↓ →(-) hypothalamic corticotropin-releasing hormone concentration ↑ →(+) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑
plasma cortisol concentration ↓ →(-) circulating tumor necrosis factor alpha concentration ↑ →(+) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotroph ACTH secretion rate ↑ ↠(production +) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑
plasma cortisol concentration ↓ →(-) hypothalamic corticotropin-releasing hormone concentration ↑ →(+) anterior-pituitary corticotroph ACTH secretion rate ↑ ↠(production +) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑
plasma aldosterone concentration ↓HPO: Decreased circulating aldosterone concentrationHP:0004319
comparative-statics (steady-state) net: ?
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑
plasma cortisol concentration ↓ →(-) hypothalamic corticotropin-releasing hormone concentration ↑ →(+) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑
plasma cortisol concentration ↓ →(-) hypothalamic corticotropin-releasing hormone concentration ↑ →(+) anterior-pituitary corticotroph ACTH secretion rate ↑ ↠(production +) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑
plasma cortisol concentration ↓ →(-) hypothalamic corticotropin-releasing hormone concentration ↑ →(-) hypothalamic gonadotropin-releasing hormone concentration / pulse drive ↓ →(+) anterior-pituitary luteinizing-hormone secretory output (rate) ↓ →(+) plasma luteinizing hormone concentration ↓ →(+) plasma 17-beta-estradiol concentration ↓ →(-) adipose (fat) tissue mass ↑ →(+) plasma insulin concentration ↑ →(-) plasma potassium concentration ↓ →(+) plasma aldosterone concentration ↓
plasma cortisol concentration ↓ →(-) hypothalamic corticotropin-releasing hormone concentration ↑ →(-) hypothalamic gonadotropin-releasing hormone concentration / pulse drive ↓ →(+) anterior-pituitary luteinizing-hormone secretory output (rate) ↓ →(+) plasma luteinizing hormone concentration ↓ →(+) plasma 17-beta-estradiol concentration ↓ →(-) adipose (fat) tissue mass ↑ →(+) plasma insulin concentration ↑ →(-) plasma potassium concentration ↓ →(+) adrenal zona glomerulosa cell aldosterone secretion rate ↓ ↠(production +) plasma aldosterone concentration ↓
plasma sodium concentration ↓HPO: HyponatremiaHP:0002902
comparative-statics (steady-state) net: ?
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(-) antidiuretic hormone (vasopressin) concentration ↓ →(-) plasma sodium concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(-) water intake (drinking / thirst-driven ingestion) ↓ →(-) plasma sodium concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) antidiuretic hormone (vasopressin) concentration ↓ →(-) plasma sodium concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(-) antidiuretic hormone (vasopressin) concentration ↓ →(-) plasma osmolality ↑ →(+) water intake (drinking / thirst-driven ingestion) ↑ →(-) plasma sodium concentration ↓
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(-) water intake (drinking / thirst-driven ingestion) ↓ →(-) plasma osmolality ↑ →(+) antidiuretic hormone (vasopressin) concentration ↑ →(-) plasma sodium concentration ↓
plasma potassium concentration ↑HPO: HyperkalemiaHP:0002153
comparative-statics (steady-state) net: ?
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) antidiuretic hormone (vasopressin) concentration ↓ →(-) plasma osmolality ↑ →(+) plasma potassium concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) antidiuretic hormone (vasopressin) concentration ↓ →(-) plasma sodium concentration ↑ →(+) plasma osmolality ↑ →(+) plasma potassium concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) plasma renin activity ↓ →(+) plasma angiotensin II concentration ↓ →(+) antidiuretic hormone (vasopressin) concentration ↓ →(-) plasma osmolality ↑ →(+) plasma potassium concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) plasma renin activity ↓ →(+) plasma angiotensin II concentration ↓ →(+) water intake (drinking / thirst-driven ingestion) ↓ →(-) plasma osmolality ↑ →(+) plasma potassium concentration ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) plasma renin activity ↓ →(+) plasma angiotensin II concentration ↓ →(+) baroreflex sympathetic outflow ↓ →(-) plasma insulin concentration ↑ →(-) plasma potassium concentration ↓
mean arterial pressure ↓HPO: HypotensionHP:0002615
comparative-statics (steady-state) net: ?
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) total peripheral resistance ↓ =(identity +) mean arterial pressure ↓
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) total peripheral resistance ↓ →(-) cardiac output ↑ =(identity +) mean arterial pressure ↑
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) plasma renin activity ↓ →(+) plasma angiotensin II concentration ↓ →(+) total peripheral resistance ↓ =(identity +) mean arterial pressure ↓
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) plasma renin activity ↓ →(+) plasma angiotensin II concentration ↓ →(+) antidiuretic hormone (vasopressin) concentration ↓ →(+) total peripheral resistance ↓ =(identity +) mean arterial pressure ↓
plasma cortisol concentration ↓ →(-) anterior-pituitary corticotropin (ACTH) secretory output (rate) ↑ →(+) plasma adrenocorticotropic hormone (corticotropin) concentration ↑ →(+) plasma aldosterone concentration ↑ →(+) renal tubular sodium and water reabsorption ↑ →(+) blood volume ↑ →(+) atrial natriuretic peptide concentration ↑ →(-) plasma renin activity ↓ →(+) plasma angiotensin II concentration ↓ →(+) total peripheral resistance ↓ →(-) cardiac output ↑ =(identity +) mean arterial pressure ↑
↑ increased ↓ decreased ? magnitude-dependent (SCC). →(+) positive edge, →(−) negative, ▷ cross-scale constitutive lift. Endophenotypes are real HPO directional terms. Draft for domain review.