Describe the normal axis of thyroid hormone production
1) hypothalamus makes TRH stimulates anterior pituitary to make TSH
2) TSH increases the production of T3 and T4
3) Rising levels of T3 and T4 inhibits TRH release by the hypothalamus and TSH levels by the anterior pituitary
Describe the 5 avenues of investigation we have available to us in investigating the thyroid
1) PE (HR, sweating, fine tremor, hair loss)
2) Palpation of thyroid
3) Labs (fT3, fT4, TSH, thyroid autoantibodies)
5) Iodine uptake scan
How does thyroid hormone increase BMR? (2)
1) increases synthesis of Na-K-ATPase pumps
2) Increases SNS by increasing expression of Beta1 receptors
6 Causes of hyperthyroidism Investigations to confirm each.
1) Autoimmune: Graves (most common; TSH receptor antibodies), Hashimoto's (transient; anti Tb and Tg antibodies)
2) autonomy of the thyroid (not TSH dependent; uptake scan, absence of abs)
3) Exogenous hyperthyroid (too many pills; Hx)
4) Thyroid cancer (rare; uptake, U/S)
5) Pituitary dysfunction (high TSH)
6) Amiodarone therapy
Describe Hashimoto's Thyroiditis (4)
1) initial hyperthyroid (release of stored T4) and then hypo (tissue is destroyed)
2) Look for high antithyroglobilin (Tg-abs) and anti-thyroperoxidase (TPO-abs) (these are the destructive antibodies causing the damage)
3) infiltration of lymphocytes
4) Heurthel cells
Describe the pathophysiology of Graves' disease
IgG (TSI) stimulates the TSH receptors which causes the overproduction of thyroid hormone in the thyroid. In addition it increases GAG production in fibroblasts behind the eyes and on the shins causing the proptosis and tibial myxedema, respectively.
Describe the labs that you see in Graves' disease and what inflammatory disorder gives similar results
first line meds for controlling BP in a diabetic patient?
ACEi or ARB
What causes DKA?
absolute insulin deficiency and a trigger (e.g. infection, trauma, etc)
triggers high counterregulatory hormone production (cortisol, glucagon, etc) which breaks down glycogen, proteins, fats which produces ketones and acids.
Causes dehydration due to diuresis
Lab findings include for DKA 3 categories
1) hyperglycemia (>14)
2) Ketoacidosis: Increased Ion gap metabolic acidosis; ketonemia; ketonuria
3) Dehydration electrolytes: elevated Cr/urea; usually hyperkalemia due to insulin deficiency
Treatment for DKA (3 things)
When should you stop tmt?
IV fluids (NS; they are dehydrated)
potassium (prevent hypokalemia as the insulin drives the K intracellularly; wait until urine is being produced)
insulin (to correct hyperglycemia; wait until K levels are 3.3-5.5 before giving; usually in conjunction with IV glucose once stabalized)
Stop Insulin when:
-Anion gap normal
-patient is eating/drinking without vomiting
-Kenotemia/ketonuria is resolved
similarities (2) and difference (3) b/n hyperosmolar hyperglycemic state (HHS) and DKA?
similarities: severe volume depletion; hyperglycemia
difference: no ketoacidosis (no DKA manifestations, no increased ion gap MA, no ketonuria/ketonemia); K+ is usually normal (both due to this only being a RELATIVE insulin deficiency); patients are usually 2x as dehydrated
-Osteoporosis (decreased bone prod, increased resorption)
What 2 screening tests do we use to test cortisol levels in SK?
1) 24 hour urine free cortisol and Cr: should not be 3x normal upper limite
2) Low dose dex suppression test: 1 mg dex at 11pm should suppress cortisol at 8am (< 50). Dex is not detected in assay. If it is still high then cortisol levels are TRULY elevated and this is not just regular variability
How do you manage cushings Synd?
1) What is causing this excess production
-Adrenal source (ACTH < 5)
-ACTH-dependent (ACTH >15)
2) If ACTH-dependent use high dose dex test and imaging to figure out pituitary or ectopic source (high dose dex will slap the pituitary and decrease ACTH levels, no response in tumor)
3) Manage Sx: Blood sugars, BP, infections, bone health
What is Conn's syndrome?
hyperaldosteronism due to an adrenal adenoma
What are the effects of aldosterone?
sodium reabsorption (water follows)
What are the main clinical presentations in primary hyperaldosteronism (conn's)? (2) Renin/aldo relationship?
-Severe HTN on 3 agents or hypokalemia (Use the BP Cuff in Conn's)
-electrolyte changes: hypernatremia, met alk, ALMOST ALWAYS HYPOKALEMIA
-There will be high aldo and low renin
What stimulates renin release? (1)
1) low sodium
3) decreased renal blood flow
4) low aldo
Most specific test for primary hyperaldosteronism? Why not straight to MRI?
1) salt loading test: sodium bolus decreases aldo in a normal person but does not change anything with someone with primary hyperaldosteronism. Confirm with MRI.
2) Too many people have adrenal incidentalomas (10%) which will give falkse +ves
How do you treat Conn's? (2)
Definitive tmt is surgery
Medically manage with spirinolactone (aldo antagonist)
Three things you can test in screening for androgen excess
How do you confirm adrenal adenoma is the cause of hirsutism. Why is it important to diagnose early?
MRI of adrenals after biochemical suspicion
important to diagnose early because hair that has converted to dark terminal hair will not revert back after tumor is excised.
What are the rule of 10 for pheo? (7)
10% are extramedullary
10% in kids
10% incidentally discovered
10% re-occur after removal
10% familial (more like 20%)
Describe three associations with pheo
-MEN 2A and 2B
How do you screen for pheo?
24 hour urine looking for metanephrines and chatechols. (+ve if >2x upper limit)
Drugs and stress (OSA included) can cause false +ves
3 ways to confirm a +ve 24 hour urine pheo test?
3) MIBG scan (attaches to these specific tumor cells)
What is the best tmt for pheo? What do we always give first? Why? second line tmt?
always give phenoxybenzamine (irreversible alpha blocker) so that when you disturb the gland and release all the catacholamines the patient doesn't die on you
If they cant tolerate surgery, give them beta blockers
Based on size, how to differentiate adrenal adenoma from adrenal carcinoma? Best Dx test, what must you do first?
Cancer is large (>4.5) adenoma is small (<4.5 cm)
Diagnose by biopsy, BUT MUST RULE OUT PHEO BEFORE JAMMING A NEEDLE IN THERE!!!
Describe, by order of prevalence the types of adrenal adenoma
non-functioning (most common)
Describe addison's disease. Describe the skin manifestations
AI destruction cortical glucocorticoid and mineralocorticoid layers. People get hyperpigmentation and vitiligo (if they have concurrent hash. thyroiditis)
How do you diagnose addison's?
Pull 8am cortisol levels ( best screening)
if low then do a cosyntropin (ACTH analog) stimulation test. +ve test if no corresponding rise in cortisol (best diagnostic)
when do you see emergency or urgent HTN
Why is it unlikely that a patient with pheo has MEN? (2)
80%+ of pheo's are non-familial
MEN is autosomal dominant, so she would need a parent with the disease
How do you manage acute adrenal emergency? When should you initiate tmt? What shoiuld you switch to for long term?
-1-3 L of NS over 24 hours
-glucocorticoids (e.g. dex) IV
DO NOT WAIT FOR TESTS TO COME BACK!
use mineralocorticoid replacement (fludrocortisone) for replacement
Describe the 5 major anterior pituitary hormones and the positive and negative feedback hormones for each
ACTH: CRH (+ve), cortisol (-ve)
GH: GRHR, somatostatin
LH/FSH: pulsatile GnRH, constant GnRH, estrogen
TSH: TRH, T4, T3
Prolactin: progesterone, under constant dopamine inhibition
Most common pituitary mass effect? Other visual effect?
bitemporal hemianopsia usually. can get a homonymous hemianopsia if post-optic chiasm compression
Describe what you would do if you found a pituitary adenoma incidentally based on size (2,3 for each)
If macroadenoma (>1cm):
-evaluate for hyper/hypofunctioning
-if <2cm and no Sx-> close followup
If microadenoma (<1cm):
-evaluate for hyper/hypofunctioning
-followup if non-functioning
-reassure patient (95% do not enlarge over 4-6 years of observation)
describe pituitary apoplexy
-acute infarct/hemorrhage of pituitary tumor
-an emergency!!! need transphenoidal decompression
What do you see in GH deficiency? How would you investigate?
-Children: (justin fontaine), reduced muscle mass, chubby/cherubic facial features
-adults: baldness, fatigue, reduced muscle/bone mass
-NOT random GH (pulsatile hormone)
-IGF-1 (would be low)
-Stimulated GH (Insulin Tolerance Test (hypoglycemia))
What tests should you order to investigate for central hypothyroidism?
TSH (normal to low), free T4 (markedly low)
if this was primary hypothyroid TSH would be markedly elevated
Describe how hypogonadotrophic hypogonadism presents. One genetic cause