Hypothalamic-Pituitary Relationships and Biofeedback Pt 2 Flashcards
Actions of cortisol
- Secreted predominantly from the zona fasciculata
- Longer-acting stress-response steroid hormone
- Suppresses the immune system via an anti-inflammatory action
- Stimulates gluconeogenesis in the liver to increase plasma glucose (diabetogenic effect)
- Promotes protein catabolism w/in muscles
- Promotes lipolysis w/in adipose tissue
Regulation of aldosterone secretion
- Main stimulus is decreased Na+ or increased K+ in blood, decreased blood volume or decreased BP through the renin-angiotensin-aldosterone axis
- Can also be stimulated by adrenocorticotrophic hormone
Actions of aldosterone
- Targets distal kidney tubules to increase absorption of Na+ and, secondarily, water, as well as, increasing K+ excretion –> increases blood volume and BP
- Steroid hormone that alters the transcription/translation of protein channels and pumps
- Secreted from the zona glomerulosa
Signs/symptoms of Cushing’s syndrome/Disease
- Hypercorticolism
- Truncal/central obesity
- Round face
- “Buffalo hump” –> excess fat on back of neck
- Easy bruising/poor wound healing
- Osteoporosis
- Purple striae
- HTN
- Edema
- Weakness
- Osteoporosis
- Hirsutism
- Acne
- Virilization
- Diabetes
- Immunosuppression
- Cognitive effects
Dexamethasone suppression test: Low dose
- Provide a low-dose of synthetic glucocorticoid at night –> measure cortisol and ACTH lvls in morning b/c it should inhibit adrenocorticotropic hormone and corticotropin releasing hormone secretion by acting like cortisol in negative feedback
- Differentiates pts w/ Cushing’s syndrome versus Cushing’s disease –> If there is no ACTH suppression it indicates Cushing’s Disease (ACTH-dependent hypercorticolism)
Dexamethasone suppression test: High dose
-When identified pt has Cushing’s Disease (ACTH-dependent hypercortisolism), we can administer high lvls of synthetic glucocorticoid to distinguish the source of the elevated ACTH lvls:
a) Anterior pituitary ACTH-secreting tumor –> high lvls will negatively feedback and cause decreased ACTH
b) Ectopic ACTH-secreting tumor –> no negative feedback effect and therefore will continue to see elevated ACTH
Consequences of glucocorticoid excess
- Overall diabetogenic effect
- promotes visceral obesity
- Osteoporosis
- Protein catabolism/collagen breakdown
- Anti-inflammatory immunosuppression
- Salt & water retention –> HTN b/c has cross reactivity w/ mineralocorticoid receptors at high lvls
Etiologies of Cushing’s syndrome (hypercortisolism)
- Exogenous glucocorticoid excess
- Pseudo-Cushing’s syndrome (major depression, anxiety, acute/chronic illness)
- ACTH-dependent (Cushing’s disease, ectopic ACTH-secreting tumors, CRH-secreting tumors)
- ACTH-independent (adrenal adenoma vs adrenal carcinoma)
How do the normal lab values (CRH, ACTH, Cortisol) compare to values seen in Cushing’s syndrome caused by: adrenal tumor
primary disorder:
- decreased CRH
- decreased ACTH
- increased cortisol lvls
How do the normal lab values (CRH, ACTH, Cortisol) compare to values seen in Cushing’s syndrome caused by: ectopic ACTH-secreting tumor
- decreased CRH
- INCREASED ACTH (very abnormally high) –> hyperpigmentation
- increased cortisol
How do the normal lab values (CRH, ACTH, Cortisol) compare to values seen in Cushing’s syndrome caused by: ACTH-secreting pituitary tumor
secondary disorder:
- decreased CRH
- Increased ACTH (but not as much as an ectopic tumor) –> hyperpigmentation
- increased cortisol
How do the normal lab values (CRH, ACTH, Cortisol) compare to values seen in Cushing’s syndrome caused by: excess exogenous glucocorticoid drugs
- decreased CRH
- decreased ACTH
- decreased cortisol (but drugs mimic cortisol actions and pt has symptoms of excess)
How do the normal lab values (CRH, ACTH, Cortisol) compare to values seen in: primary adrenal insufficiency (Addison’s disease)
- increased CRH
- increased ACTH –> hyperpigmentation
- decreased cortisol
How do the normal lab values (CRH, ACTH, Cortisol) compare to values seen in: secondary adrenal insufficiency
- Increased CRH
- decreased ACTH
- decreased cortisol
- Normal levels of aldosterone b/c renin-angiotensin-aldosterone axis maintained
How do the normal lab values (CRH, ACTH, Cortisol) compare to values seen in: tertiary adrenal insufficiency
- decreased CRH
- decreased ACTH
- decreased cortisol
- Normal levels of aldosterone b/c renin-angiotensin-aldosterone axis maintained
How does increased ACTH cause hyperpigmentation?
-When there is a loss of feedback on the HPA axis causing supraphysiological lvls of ACTH, it can bind to low-affinity MC1R on melanocytes in skin to increase melanin synthesis and dispersal –> skin darkening
Explain how the cosyntropin stimulation test detects adrenal gland insufficiency
- Cosyntropin is a synthetic ACTH analog
1) Measure cortisol @ 8 am:
a. if pt has >15 microgram/dL –> r/o adrenal insufficiency
b. if pt has < 3 microgram/dL –> adrenal insufficiency confirmed (see step 2)
c. if pt has 3-15 micrograms/dL –> administer cosyntropin and measure cortisol lvls in 30 min to see if able to produce it –> if lvls are WNL (>/= 18), AI r/o but if they are less than normal (<18), AI confirmed
2) AI confirmed –> measure ACTH lvls:
a. if low/normal –> secondary or tertiary AI
b. if elevated –> primary AI
Primary vs secondary hyperaldosteronism
- Primary due to excessive release of aldosterone from adrenal cortex (Conn’s syndrome = alderosterone-secreting adenoma in zona glomerulosa of adrenal cortex)
- Secondary due to excessive renin secretion by juxtaglomerular cells in kidney
Signs/symptoms of Addison’s Disease (primary adrenocortical insufficiency)
Primary deficiency of cortisol and aldosterone due to adrenal cortex atrophy
- Hypoglycemia
- Anorexia, weight loss, nausea, vomiting
- Weakness
- Hypotension
- Hyperkalemia
- Metabolic acidosis
- Decreased pubic and axillary hair in females
- Hyperpigmentation
Explain how we can use the ratio of plasma aldosterone concentration (PAC) / plasma renin activity (PRA) to detect primary hyperaldosteronism
- Hypertension and hypokalemia –> hyperaldosteronism
- decreased PRA and increased PAC –> ratio of >/= 20 AND PAC >/= 15 ng/dL
- Since the primary problem is elevated aldosterone lvls, it is increasing BP and therefore decreasing activity of the renin system
21beta-hydroxylase deficiency
- Blocks cortisol and mineralocorticoid production, therefore increasing production of androgens
- Hypotension due to salt wasting, hypoglycemia, masculinization of external genitalia (penis-like clitoris and scrotum-like labia) in females, early appearance of pubic/axillary hair (precocious puberty), suppression of gonadal function, early acceleration of linear growth, virilization
- ACTH lvls will be elevated due to low cortisol lvls –> adrenal hyperplasia
17alpha-hydroxylase deficiency
- Blocks glucocorticoid and androgen production –> impaired formation of secondary sex characteristics and overproduction of mineralocorticoids
- Symptoms of glucocorticoid deficiency (hypoglycemia)
- Symptoms of mineralocorticoid excess (HTN, hypokalemia, metabolic alkalosis) –> will also have decreased aldosterone lvls b/c of HTN negative feedback on renin-angiotensin-aldosterone system
- Lack of pubic/axillary hair in females, undescended testes in males
- ACTH lvls will be elevated due to low cortisol lvls –> adrenal hyperplasia
11beta-hydroxylase deficiency
- blocks cortisol production and mineralocorticoid products downstream of 11-deoxycorticosterone (DOC)
- increased levels of DOC cause symptoms of mineralocorticoid excess –> HTN, hypokalemia, metabolic alkalosis
- Also causes an increase in androgen production (masculinization)
- ACTH lvls will be elevated due to low cortisol lvls –> adrenal hyperplasia
Expected levels of mineralocorticoids, cortisol, androgens, BP, [K+], and other labs compared to normal in pts w/:
17alpha-hydroxylase deficiency
- increased mineralocorticoids
- decreased cortisol
- decreased androgens
- increased BP
- decreased [K+]
- decreased androstenedione
Expected levels of mineralocorticoids, cortisol, androgens, BP, [K+], and other labs compared to normal in pts w/:
21beta-hydroxylase deficiency
- decreased mineralocorticoids
- decreased cortisol
- increased androgens
- decreased BP
- increased [K+]
- increased renin activity and increased 17-hydroxy-progesterone
Expected levels of mineralocorticoids, cortisol, androgens, BP, [K+], and other labs compared to normal in pts w/:
11beta-hydroxylase
- decreased aldosterone, increased DOC (increased BP)
- decreased cortisol
- increased androgens
- increased BP
- decreased [K+]
- decreased renin activity (negative feedback)
Classic symptoms of pheochromocytoma
Increased catecholamine release causing:
- HTN
- Headaches
- palpitations
- sweating
