Lecture 92, 94 - Adrenal Disorders + Adrenal Steroid Pharm Flashcards
labs of primary adrenal insufficeincy
Low cortisol;
High ACTH, CRH
etiologies of acute adrenal insufficiency
massive hemorrhage
Tumors
Drugs (ketoconazole, Etomidate)
abrupt withdrawal of glucocorticoids
etiolgoes of chronic adrenal insuffieicny
TB Adrenalitis
Auto immune (APS 1 – APECED, APS 2)
XLALD
CAH
what is APECED (APS1)
defect to what gene?
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
AIRE gene
what is APS2?
Genes: AD with incomplete penetrance
More Common than APS1
Hallmark: Adrenal Insufficiency + Thyroid Disease (Hypo or Hyper)
what is XLADL
manifestation
XL genetic mutation to ATP binding casettes which code for proteins necessary to break down long chain fatty acids
CNS, AI
what is the most common defect of Congential Adrenal Hyperplasia
how may it presetnt early in life?
21 Alpha Hydroxylase
most common cause of salt wasting adrenal crisis in the first two weeks of life
in 21 alpha hydroxylase deficincey – what features may present in females
virulizing effects
labs of secondary adrenal failure
Labs: Low Cortisol; Low ACTH (CRH)
what is the most common etiology for secondary adrenal failure?
Pituitary/Hypothalamic Tumor
hyperpigmentation is present in ______ adrenal fuction.. why?
If Primary AI – Hyperpigmentation (bc ACTH –> MSH)
serum electrolyte values of AI
what changes to the CBC?
Low adolsterone –
Hyponatremia
Hyperkalemia
Hypoglycemia
Hypercalcemia – cortisol nomrally decreases intestinal calcium
Eosinophilia (cortisol is toxic to eosinophils)
gold standard for diagnosis of AI
other good test ?
ACTH Stimulation Test – GOLD STANDARD
Primary – no rise in cortisol
Secondary – some response to cortisol
Morning cortisol check:
Cortisol should be high in the morning. If Low, check ACTH to determine if primary or secondary
Treatment for AI
Hydrocortisone – but this is short acting and requires multiple injections per day
Fludrocortisone – Mineralocorticoid and Glucocortisol effects
DHEA – replacement of Androgens for Women
what is cushing’s syndrome
what is cushing’s disease
syndrome – excess cortisol production
Disease – ACTH producing adenoma
Causes of Cushing’s Syndrome
Unilateral Adrenal Adenoma;
Bilateral Adrenal Hyperplasia (usually bilateral)
three tests to help dx cushing’s
Dexamethasone Suppression Test (ACTH doesn’t decrease)
24 hour urine – increased
Late night salivary cortisol – higher than it should be
clinical features of cushing’s
muscle weakness and thin extremitiis
Moon facies, buffalo hump, truncal obesity
high insulin
abdominal stira
HTN
Osteoporsis
Immune suppression; poor wound healing
Hyperaldosteronism
what is conn syndrome?
what is the most common cause?
Most common cause: bilateral adrenal hyperplasia
Conn syndrome – adrenal adenoma over producing aldosterone
Clinical presesntation of hyperaldosterone
hypernatremia; HTN
Hypokalemia
weakness, cramps, periodic paralysis
best way to diagnose and locate hyperaldosterone
CT – 1/3 of time its unilateral; if B
Adrenal Vein Sampling – -the gold standard
treamtnet for hyperaldosterone
unilateral vs bilateral
Surgery – if unilateral
If Bilateral -- Medical: Spironolactone, Eplerenone
what is a pheochromocytoma
Catecholamine producing tumor of the adrenal medulla
“attacks” of release of catecholamines;
Symptoms can be paroxysmal
classic triad of symptoms of pheo
other sx:
HA, Diaphoresis, Palpitations
HTN, Diaphoresis, Palpitations
diagnosis of pheo
measure Metanephrines
Clonidine suppression test
4 familial forms of pheo
VHL
NF1
MEN2A
MEN2B
MEN 2a vs MEN2B –
what is the associated mutation
RET gene
Treatment of Pheo –
alpha and beta blockers A before B)
CCBs
Metyrosine
Surgery
which glucocorticoid agonist has the highest anti-inflammatory potency ?
whaich has the highest NA retntion potency?
anti-inflammatory Dexamethasone
9 alpha Fluorocortisol – highest Na Retention potency;
indications for glucocorticoid use
Hormone Replacement Therapy
Suppress Inflammation and Immune Responses
what are the primary targets of Cortisol in the periphery
Liver and Kidneys –
what is the difference between 11B HSD 1 and 11B HSD 2
Glucocorticoid Receptor Rich Tissues: Express High level of 11 Beta HSD Type 1: converts cortisol to active form (cortisone –> Cortisol)
Mineralocorticoid Receptor Rich Tissues: Express High level of 11 Beta HSD Type 2: converts cortisol to inactive form (cortisone)
indications for glucocorticoid antagonists
Severe Hypercoretisolism
Persistent Hypercortisolism following surgery
Cushings disease
Synthesis inhibitors of Glucocorticoids
Ketoconazole –
Mitotane –
Metyrapone
Mineralocorticoid Receptor Agonists
Fludrocortisone
MR Antagonists
Spironolactone (+ Eplerenone) –
