Endocrine - to midterm Flashcards
3 questions to always ask about pituitary tumors
- Functional (makes hormones)?
- Mass effects?
(ie: bitemporal hemianopsia or erosion into sinuses) - Production of other hormones affected?
Types of Hormone Receptors
- Cell Membrane Rs: amt hormone => response size
2. Cytoplasmic/Nuclear Rs: #Rs => response size
Common causes of hyperprolactinemia
- prolactinoma (in pituitary, often large)
- pituitary stalk damage
- chest wall trauma
- kidney failure
- drugs (esp. antipsychotics)
- hypothyroidism (=> high TRH)
Treatment for hyperprolactinemia
1. dopamine agonist –> decreases secretion AND shrinks prolactinomas!
- surgery if unresponsive
* none if mild
metabolic consequences of GH-producing pituitary tumors
- excess DNA, RNA & protein synth
- FA mobilization
- insulin resistance (use fat more than glucose)
* irreversible bone changes
Diagnosis for acromegaly
high IGF-1 & GH >1ug after oral glucose load,
Xrays (skull, hand, feet)
Pituitary MRI or CT
Iodine deficiency
- where?
- why does it matter?
- low iodine in soil @ places far from ocean (comes down in rain)
- need iodine for thyroid hormone synthesis (100ug/day)
(thyroglobulin + tyrosine + Iodine => T4 & T3)
*TSH binding to THR increases thyroid uptake of Iodine!
Function of T3 hormone
(binds to TRE –> histone acetylation –> activate transcription)
- Metabolic:
- increase O2 consumption, heat production
- increase metabolic rate (ie: food, drugs, anesthesia)
- increase protein/fat/cholest. synth & degrad. - increase SNS tone
- normal brain dvpt in infants (need!)
Congenital Hypothyroidsim
= Cretinism, due to failed thyroid dvpt.
Sx: lethargy, mental retardation, failure to grow/feed/gain weight
Adult hypothyroidism
Thyroid hormone deficit,
Causes: autoimmune, thyroid damage (radioactive I, surg, drugs); low TSH (secondary)
Sx: fatigue, cold intolerance, low HR/contractility, HTN, infertility, slow reflex relaxation
Thyrotoxicosis
too much thyroid hormone
(due to hyperthyroidism or thyroiditis)
Sx: heat intolerance, weight loss, stare & proptosis, high HR, A-fib., tremor
Grave’s disease
familial, autoimmune stimulation of thyroid; 10x F>M.
* most common cause of hyperthyroidsim
Dx: high radioiodine uptake, low TSH, high T3/T4
Treatment for hyperthyroidism
- radioactive iodine
- anti-thyroid hormone drugs (methimazole, PTU)
- surgery (only if Large goiters, bleeding, etc.)
Thyroiditis
destruction of thyroid follicle epithelial cells
=> initially thyrotoxic bc leak T3/T4, but then hypothyroid bc damaged.
Causes: viral, autoimmune, radiation, drugs (amiodarone, iodine)
Aldosterone secretion stimulated by:
- Angiotensin II (from RAAS)
- Renin (low Na delivery to distal conv. tubule)
- SNS activity
- K+ & ACTH
Effects of Cortisol
- metabolic: promote gluconeogen & liver glycogen storage
- -> insulin resistance, weight gain (stim. appetite)
- anti-inflammatory
- mineralcorticoid (retain Na+)
Effects of aldosterone
- retain Na+ (mineralcorticoid)
2. increase excretion of K+ & H+ (in urine)
effects of DHEA
- maintains axillary & pubic hair,
* normal levels decrease w/ increasing age
* deficit => female virilization
Adrenal insufficiency (Dx, Tx)
= cortisol deficit
Dx: ACTH stim test (<18)
Tx: Cortisol
Primary vs. Secondary adrenal insufficiency
causes & signs
Primary: adrenalitis, TB, carcinoma met or adrenal hemorrhage
- high ACTH, low cortisol; hyperpigmentation.
Secondary: pituitary trauma/postpart. apoplexy, tumor/radiation
- low ACTH & cortisol; pallor.
Cushing’s Syndrome (causes, Sx)
Excess cortisol;
Causes: adrenal adenoma/carcinoma, ACTH-prod. pituitary tumor
Sx: weight gain/round face, HTN, amenorrhea, hirsutism, growth retardation (in kids only)
Cushing’s Syndrome Dx & Tx
= excess cortisol.
Dx:
- Screen: bedtime salivary cortisol, 24 hr urine free cortisol, overnight dexamethasone suppression test (am plasma cort.>2)
- Localize: plasma ACTH, high dose dexameth. suppression test
Tx:
- surgery (adrenal tumor) - pasireotide (pit. tumor)
- decrease dose (exog. glucocorticoids)
primary hyperaldosteronism
excess aldosterone production ==> HTN
Causes: adrenal adenoma or bilat adrenal hyperplasia (rare)
Dx: plasma Aldosterone/Renin activity RATIO >30
Tx: surgery (if adenoma), Spironolactone (if hyperplasia)
Congenital Adrenal Hyperplasia
bc 21-hydroxylase deficiency => Low cortisol synth.
Dx: serum 17-hydroxyprogesterone
Tx: replacement doses of cortisol (or prednisone, dexamethasone)
Pheochromocytoma
tumor of adrenal medulla that secretes catecholamines
Sx: SNS activation – tremor, high HR, palpitations, sweating, etc.
Dx: urine or plasma metanephrines
Tx: surgical excision
Familial combined hyperlipidemia
excess ApoB produced by liver
=> varied presentation in family & individual over time
(high TG, high cholesterol OR both)
Familial hypercholesterolemia
AD => LDL R mutation bc over-expressed enzyme
High risk:
severe hypercholesterolemia, tendinous xanthomas, atherosclerosis
familial hypertriglyceridemia
defective ApoC or deficit of LPL (lipoprotein lipase)
–> strong familial trend of high TGs
Remnant Disease
defective ApoE = reduced clearance by remnants & LDL Rs
physical exam signs of hyperlipidemia (5)
- corneal arcus (choles., age milky retinal blood vessels)
- central obesity
how to Dx hyperlipidemia
fasting TG and LDL, HDL, & total cholesterol…
a) TG < 400: LDL = total - (HDL + TG/5) (*TG/5 = VLDL)
b) TG > 400: non-HDL chol. = total - HDL
* refer to treatment guidelines for Dx values
When to start treatment for hyperlipidemia
Start treatment with a statin IF…
a) known CV disease
b) LDL =190+
c) LDL = 70-189 & DM & age 40-75
d) LDL = 70-189 & 10 yr CV risk > 7.5% (no DM)
Drugs that cause overproduction of lipids
- EtOH
- diuretics
- beta blockers
- steroids
- retinoic acid
- HIV drugs
Diseases that associated with secondary hyperlipidemia
Over-production: diabetes, liver disease, nephrotic syndrome
Under-excretion: Renal failure, hypOthyroidism
ApoE (where? why?)
on remnants (not LDLs), = LDL remnant R ligand *mutated in Remnant Disease
ApoCII (where, why?)
on chylomicrons coming from liver,
= LPL cofactor! (needed for breakdown)
*mutated in familial HyperTGemia
ApoB100
on liver LDLs,
1 ApoB per particle OTHER than HDL
=> if high = high # particles; low = fewer, large particles.
*mutated in familial hyperCHOLesterolemia
ApoA1
on HDLs
–> tag for heading back to liver for recycling
