Lecture 36 Hypothalamus-Pituitary-Adrenal Axis Conditions Flashcards
(15 cards)
Fx of Adrenal Glands
located on top of each kidneys
Medulla (10% of gland) - catecholamines, primary stimulus for secretion is neural (SNS)
Cortex (90% of gland) - secretes mineralocorticoids, glucocorticoids, androgens
Cortisol function
regulates enzyme levels for metabolism
may act to limit inflammation and immune responses
permissive role in BP maintenance
stress stimulates secretion above basal levels
gives negative feedback to anterior pituitary and release of ACTH as well as hypothalamus and release of CRH
How are adrenal disorders categorized?
either hyper or hypofunction of the gland ⇒ Hyper: Cushing’s syndrome (hypercortisolism), hyperaldosteronism
Hypo: Addison’s disease (adrenal insufficiency), genetic abnormalities of steroidogenesis
over or under production of gland hormones can have significant consequences as they regulate BP, metabolism, immune response, stress response, bodily fxn
What is adrenocortical insufficiency, categories?
Primary: destruction or dysfunction of adrenal cortex aka Addison’s Disease
most cases (80-90%) are caused by autoimmune dysfunction, can also be infection (tuberculosis), trauma, surgery
30-60 cases per 1,000,000
more common in women
results in deficiencies in cortisol, aldosterone, androgen levels
Secondary: deficient secretion of adrenocorticotropic hormone (ACTH), glucocorticoid therapy (important if tx is stopped or reduced) due to negative feedback on the system (ex. prednisone > 20 mg daily for more than 3 weeks)
What is the clinical presentation of adrenocortical insufficiency?
weakness, lethargy, fatigue, anorexia, weight loss, abdominal sx (N/V, ab pain), hypoglycemia, hyperpigmentation of skin (only in primary insufficiency from excessive ACTH), mineralocorticoid deficiency - hypotension, dehydration, hyponatremia, hyperkalemia
How do plasma ACTH and glucocorticoid levels look in adrenocortical insufficiency, and what test can be run to check for insufficiency?
morning plasma cortisol levels (06:00-09:00) < 80 nmol/L when normal morning levels are around 138-635 nmol/L
ACTH will be high in primary insufficiency and low in secondary insufficiency
corticotropin (or cosyntropin) stimulation test - measure plasma cortisol at baseline ⇒ admin 250 mcg synthetic ACTH (IV or IM) ⇒ repeat cortisol in 30 and 60 mins ⇒ >500 nmol/L rules out primary adrenal insufficiency,, however some drugs like oral contraceptives increase cortisol-binding globulin resulting in elevated cortisol levels (should be taken into consideration)
What regimen for steroids may be the best when it comes to primary adrenocortical insufficiency?
Glucocorticoid: 2/3 dose in morning and 1/3 dose in late afternoon ⇒ HC 15-25 mg/day (may also use cortisone or prednisone)
Mineralocorticoid: fludrocortisone 0.05-0.1 mg qd
What dose stress dosing refer to in primary adrenocortical insufficiency management?
pt unable to mount normal cortisol response (increase BP and BG levels) to stressful events
increase dose of glucocorticoid during major illness or injury - increased dose individualized, pt should have own plan, in general the dose is doubled during febrile illness, continue with increased dose until feeling better
injectable HC may be required if pt is experiencing diarrhea or vomiting (oral tabs not providing sufficient cortisol replacement)
if pt using mineralocorticoid this will also have to be increased (2-3x dose) for hot weather, strenuous exercise (where sweating or fluid loss may occur), watch for fluid retention and HTN
How should secondary adrenocortical insufficiency be managed?
pt may need glucocorticoid replacement but not mineralocorticoid replacement - adrenal cortex isn’t damaged, aldosterone production and release managed by different pathway (RAAS)
dose of corticosteroid will depend on sx, ACTH levels, and response to corticotropin stimulation test
most pt will require stress dose steroids,,, counselling on tapered withdrawal of corticosteroids important - abrupt withdrawal or rapid dose reduction can cause adrenal crisis
What is adrenal excess?
Cushing syndrome describes clinical condition resulting from chronic excessive levels of endogenous cortisol or exogenous corticosteroids - most common cause is drug-related (prolonged use of high dose or high potency glucocorticoids), other causes include adrenal adenomas, adrenal carcinomas, and ectopic ACTH secretion (ex. neuroendocrine tumours)
Cushing disease refers to excessive cortisol levels caused by overproduction and release of ACTH from pituitary tumour - 1.2-1.7 per 1,000,000
What is the clinical presentation of adrenal excess?
fatigability and weakness, increased body weight, redistribution of body fat - centripetal obesity, facial rounding, thin extremities
HTN, hirsutism, amenorrhea, muscle wasting, thinning of skin, easy bruising
What lab tests can be done to establish hypercortisolism?
measure level of cortisol - 24 hour urine collection to measure urinary free cortisol, midnight plasma or salivary cortisol to see if diurnal pattern intact
dexamethasone suppression test - 1 mg admin po qhs, morning cortisol on next day ⇒ < 50 nmol/L rules out Cushing syndrome, > 50 nmol/L confirms Cushing syndrome
neither test will help identify etiology of this
false positive results: exogenous glucocorticoid admin (systemic, inhaled, topical), acute illness, pregnancy, oral contraceptive use
How should adrenal excess be managed?
in Cushing disease: surgery or pituitary radiation to reduce size of tumour
pharmacologic tx: GOAL: to normalize cortisol levels and alleviate sx, also helps with preoperative management or as adjunct tx to surgery/radiation if sx persist
enzyme inhibitors (decrease cortisol synthesis) - ketoconazole - need to monitor liver tests (ALT, AST, total bilirubin, ALP, INR)
mitotane (Lysodren) - can also block synthesis of thyroxine
modulate ACTH secretion from pituitary - cabergoline (dopamine agonist), pasireotide (somatostatin analogue)
What is hyperprolactinemia (clinical manifestations, demographic, drugs that can contribute)?
state of persistent elevated these levels, secretion is regulated primarily by tonic inhibition of dopamine
Manifestations: galactorrhea, hypogonadism ⇒ irregular menses, sexual dysfunction, infertility, osteoporosis
usually affects women of reproductive age (24-35 yrs, 24 cases per 1000 person years)
the reference range in non-pregnant women is 4-23 mcg/L
most commonly caused by these secreting tumours
Drugs: that antagonize dopamine - antipsychotics, antidepressants (through elevated 5-HT which is strong stimulator of this release), metoclopramide and domperidone (dopa receptor antag)
Less Common: elevated TRH or estrogen stimulating lactotrophs
How should hyperprolactinemia be managed?
stop meds that antagonize dopamine
use dopamine agonists for prolactinomas - cabergoline, bromocriptine
monitor for effectiveness by following conc levels
