Extra Endocrine Flashcards
3 classic symtoms of prlactinoma
Galactorrhea, amenorrhea (females)
Impotence (males)
why does prolactinoma cause amenorreha
Prolactin inhibits GnRH
Secondary complication of growth cella denoma (besides growth) and its mechanism
Diabetes Mellitus, because growth hormone is gluconeogenic
Diagnostic test for GH adenoma
Failure of glucose to suppress GH
bone condition seen in women with prolactinoma and its mechanism
Osteoporosis
Prolactin inhibits GnRH = no estrogen = increased osteoclast activity
Defect in dwarfism
Defective GH receptors
Elevated GH and low IGF-1 in serum
what endocrine disease can cause a prolactinoma
Primary Hypothyroid
TSH backs up, TRH backs up, TRH stimulates Prolactin release
Woman gives birth, begins breast feeding and then a week later she notices loss of pubic hair and difficulty with breast feeding
Sheehan syndrome
Sheenan syndrome pathogenesis
During pregnancy, pituitary swells 2x but doesnt increase blood flow. If blood is lost during labor, pituitary infarcts
Empty sella syndrome defect
Herniation of arachnoid and CSF into the sella, destroying the pituitary
Sudden onset severe headache and bitemporal hemianopsia and diplopia
Pituitary apoplexy
Major risk that central DI patients have
life threating dehydration
Herediatry cause of nephrogenic DI
Mutation in neurophysin gene
2 drugs that cause neprhogenic DI
Lithium
Demococlyine
Most common site of ectopic ADH production
Small Cell Lung Cacner
2 lab values that distinguish SIADH from DI
Sodium and serum osmolality
SIADH is hyponatremic, low osmolality, the others are hypernatremic, high osmolality
Midline anterior neck mass in a child
Thyroglossal duct cyst
how to differentiate thyroglossal duct cyst from branchial cleft cyst
Thyroglossal duct cysts move with tongue and while swallowing.
Brachial cleft cysts dont move and are on the lateral neck
Child with mass at the base of the tongue
Lingual thyroid
What is lingual thyroid composed of
Normal thyroid tissue
2 receptors that mediate symptoms of hyperthyroidism
NaK pump –> increased BMR
B1 receptors –> increased SNS activity
3 endocrine changes with hyperthyroid
Hypercalcemia (increased bone resorption)
Hyperglycemia (increased gluconeogenesis/glycogenolysis)
Hypocholesterolemia
Graves disease defect
IgG stimulates TSH receptor
3 PE findings of Graves
Goiter
Exopthalmos
Myxedema
Mechanism of GOiter in graves
Constant TSH = thyroid hyperplasia
mechanism of exopthalmos and pretibial myxedema
T cells stimulate Fibroblasts release to glycosaminoglycans –> increases osmotic swelling and adipocyte size –> exopthalmos
2 major cell types involved in exopthalmos
Fibroblasts
T cells
2 specific glycosaminoglycans
Chondroitin sulfate
Hyaluronic acid
Histology of graves
Tall follicular cells with colloid scalloping
Scalloped colloid looks like little tombstones –> like…GRAVES
Thiomide MOA
Blocks thyroid peroxidase
Patient with hyperthyroidism undergoes a surgery under general anesthesia. When they wake up they develop severe hyperthermia, Delerium, tachycardia and arrhythmias
Thyroid Storm
Toxic multinodular goiter defect
Nodules secreating hormone independent of TSH
Are hot nodules benign or malignant
Benign
Jod Basedow phenomenon
Patient with iodide deficiency is pumped full of iodide, and then they have thyrotoxicosis
opposite of wolff chaikoff
Infant with pot bellly, swollen face, protruding umbilicul, tongue falling out of mouth
Cretinism –> congential hypothyroid
6 Ps of cretinism
Pot belly Protruding umbilicus Protouding tongue Pale Puffy Face Poor brain development
Dyshormonogenetic goiter defect
It is one of the causes of cretinsm.
Due to low levels of thryoid peroxidase
Myxedema cause
accumulation of glycosaminoglycans in skin and soft tissue
Patent states they’ve been gaining weight despite not eating more, feels fatigued and has noticed deepening of voice and feels like their tongue is larger than normal
Hypothryoidism
Why do hypothryoid patients have deeper voices/large tongues
Glycosaminoglycan deposition
Hashimoto defect (3 Ab)
IgG ab against thryoid peroxidase
IgG against thyroglobulin
Antimicrosomal Ab
HLA association with hashimoto
HLA DR5
classic paradox in lab findings in hashimoto
Patients initially present with elevated T4 levels and SSx of hyperthyroid, then come back and have SSx of hypothyroid
Why do T4 levels initially increase in hashimoto
follicle damage causes release of T4
2 unique histology findings of hashimoto
1- Germinal center formation (appears like a lymph node)
2- hurthle cells
hurthle cell description
Eosinophlic metaplasia that lines the follicles
which cancer does hashimotos increase risk for? why?
Diffuse large B cell lymphoma b/c germinal cells are being formed
Patient has an upper respiratory infection, then develops periodic episodes of tachycardia, sweating, increased appetite. C/o Jaw pain and anterior neck pain.
Subacute granulomatous Thyroiditis
Subacute granulomatous thyroiditis labs
Elevated ESR
SGT clinical course
Hyperthyroidism that may progress to hypothyroid
SGT biopsy
Granulomatous inflammation w/ giant cells
20 year old presents with dysphagia and wheezing. Thyroid is firm when palpated but not painful, and it doesnt move when palpated.
Riedel fibrosing thyroiditis
What must be r/o in fibrosing thyroitis? how?
Anaplastic thyroid cancer.
RF is in young patients, cancer is older. RF lacks malignant cells
how does I 131 uptake help distinguish hyperthyroid/toxic goiter from cacner
Cancer is a cold nodule (doesn’t take up I 131)
5 classic cancers of the thyroid
Follicular Adenoma Follicular Carcinoma Papillary carcinoma Medullary carcinoma Anaplastic carcinoma
Hallmark of follicular adenoma on gross exam/histology
Follicles are surrounded by a thick fibrous capsule
CLassic risk factor for developing papillary carcinoma of thyroid
Radition to the head and neck area as a child
Papillary carcinoma histology (2 unique features)
Empty nuclei with central clearing (orphan annie cells)
Psammoma bodies
Papillary = Psammoma and Pupils (eyes)
Pap. Carcinoma spread and progonisis
Cervical llymph nodes
Good prognosis
Follicular carcinoma mutation
RAS
Follicular carcinoma spread and prognosis
HEMATOGENOUS SPREAD. it forgot its a carcinoma
Good prognosis
Why can’t fine needle aspiration differentiate b/w follicular adenoma and carcinoma
FNA only sample cells and not the capsule.
Entire capsule needs to be visualized under microscope to ensure no invasion
Medullary carinoma is a malignancy of
Calcitonin secreting parafollicular C cells
medullary carcinoma labs
Hypocalcemia w/ hypercalciuria (b/c calcitonin increases renal excretion of Ca)
Classic medullary carcinoma histology
sheets of cells in an amyloid (pink) stroma
Medullary carcinoma mutation
RET mutation (MEN2a 2b)
What should be done if pt has RET mutation?
Prophylactic thyroidectomy
What is the amyloid made of in med. carcinoma?
Calcitonin deposition
70yo pt presents with neck mass, dysphagia, hoarseness
Anaplastic carcinoma
Patient presents with asymptomatic hypercalcemia
Primary hyperparathyroidism
classic GI symptom that arrises in primary hyperPTH patients
Acute pancreatitis –> Ca is an enzyme activator!
4 main symptoms of hypercalcemia
“Stones, bones, groan, psychiatric overtones”
Kidney stones
Osteitis fibrosis cystica
Constipation, abdominal pain, pancreatitis
Depression
serum alk phos level in primary hyperPTH. Why?
Elevated b/c PTH activates osteoblasts, which secrete alk phos b/c it needs an alkaline environment to make bone
Osteitis fibrosa cystica cause
excessive bone resorption by overactive osteoclasts
OFC gross and Xray appearance
Cysts full of brown fibrous tissue
Multiple cystic spaces on Xray
Why is the cyst brown?
Hemosiderin form macrophages
2 most common causes of secondary hyperPTH
chronic renal failure
Hypovitaminosis D
Really, anything that causes low Ca or high Phos
Muscle effects of hypocalcemia
Muscle spasms and fatigue
2 PE findings for hypocalcemia
Chovestek sign (tap on facial nerve = twitch) Trousseau (occlude brachail artery = carpal spasm)
3 most common causes of hypoparathyroid
Surgical excision of thyroid
Autimmune
DiGeorge!
spatial relationship of alpha and beta cells
Alpha cells surround the beta cells
hypersensitivity type of DM type 1
Type 4 –> T cells against beta cells
DM 1 histology vs DM 2
DM1 = inflammatory cells in the islet
DM2= Amyloid deposition in islet
Polyuria, polydipsia and glycosuria are due to
Hyperglycemia causing osmotic diuresis
WEight loss, decreased muscle mass and polyphagia are due to
Unopposed GLUCAGON. –> Does everything opposite of insulin
Increases lipolysis, protein breakdown, gluconeogenesis (which worsens the hyperglycemic symptoms)
SSx of DKA
DKA is Deadly
Delerium
Kusmaull respiration
Abdominal pain (N/V)
Dehydration
+ Fruity breath
why does DKA occur during illness?
Epinephrine is released –> epi causes glucagon release –> overactive lipolysis, glycogenolysis and gluconeogenesis
Mechanism for ketone body generation (3 steps)
Increaesd liposlysis –> increase FFA production –> liver converts FFAs to ketone bodies
2 reasons for hyperkalemia in DKA
No insulin = transcellular shift out of cells
AG Metabolic Acidosis = transcellular shift out of cells
TOTAL body K levels in DKA
Decreased, even though theyre hyperkalemic (all the K is in the blood. none is in the cells)
3 Tx for DKA
Insulin (treat hyperK and lower glucose)
K+ so they dont become hypokalemic
Glucose so they dont become hypoglycemic
Why is DKA not seen in DM2?
Endogenous insulin prevents excess lipolysis (less FFAs = less ketone bodies)
how does obesity lead to DM 2
Adipose down regulates insulin receptors on cells
Stronger genetic predisposition b/w DM1 or DM2
DM2
HLA association in 1 and 2
DM1- HLA DR3 and DR4
DM2- none
progression of serum insulin in DM2. Why?
INitially elevated due to hyperglycemia, but progressively decline as the beta cells burn out
3 diagnostic criteria for DM
Fasting BGL > 126
Random BGL >200
BGL > 200 2hrs after glucose load
hyperosmolar hyperglycemic non ketotic coma mechanism (3 steps)
Hyperglycemia –> osmotic diuresis –> dehydration
who is HHNS seen in ?
Elderly people who DONT DRINK WATER
HHNS ssx
Polyuria
Thirst
Lethargy
Seizures/neuro defecits
HHNS serum osmolarity, glucose and pH
Hyperglycemia low osmolarity (water loss) normal pH (no ketone bodies)
Non enzymatic Glycosylization causes which class of comlications
Small vessel disease (retinopathy, nephropathy, neuropathy)
Large vessel disease (CAD, PVD, gangrene)
Osmotic damage causes which 4 complications
Peripheral neuropathy
Impotence
Blindness
Cataracts
3 cell types/tissues where osmotic damage occurs
Schwann cells
Pericytes of retinal blood vessels
Lens of the eye
Mechanism of osmotic damage
Accumulation of sorbitol in tissue = osmotic damage
2 enzymes responsible for osmotic damage
Elevated aldose reductase
Decreased sorbitol dehydrogenase
DM can cause cataracts blindness and glaucoma. how are the mechanisms different?
Cataracts = osmotic damage to lens Blindness = osmotic damage to pericytes Glaucoma= non enzymatic glycoslylation of retina
Type of arteriolosclerosis seen in DM
Hyaline (just like HTN)
inheritance of MEN syndromes
Autosomal dominant. “MEN are Dominant”
MEN1 mutation
menin, a tumor supressor on Ch11
MEN1 SSx
Pituitary adenoma
Pancreatic tumor (ZE, gastrinoma, insulinoma)
Parathyroid adenoma
MEN2a SSx
Parathyroid adenoma
Pheochromocytoma
Medullary Carcinoma of thyroid
MEN2b SSx
Pheochromocytoma
Medullary carcinoma of thyroid
Mucosal neuromas
Marfanoid habitus
MEN2 defect and pathogenesis
RET mutation, which codes for receptor tyrosine kinase
embryonic origin of the cells affected by RET mutatino
Nueral Crest
SSx of Insulinoma
Episodic hypoglycemia and AMS that resolves with glucose administration
4 SSx of Somatostatinoma
Steatorrhea, gallstones (no CCK or secretin)
Glucose intolerance
Achlorhydria (n ogastrin)
VIPoma ssx (3)
Diarrhea (high VIP = relaxed bowel)
Hypokalemia (diarrhea…may also have NAGMA)
Achlorhydria (VIP inhibits gastrin)
Glucagonoma ssx (5)
Dermatitis Diabetes DVT Declining weight Depression
MCC of primary hyperaldosteronism
Bilateral adrenal hyperplasia Adrenal adenoma (conn)
MCC of secondary hyperaldosteronism
Renal artery stenosis
CHF
ANything decreasing perfusion to the kidney
How to differentiate b/w primary and secondary hyperaldo
Primary = Low Renin w/o edema Secondary = High Renin + Edema
Child with HTN, hypokalemia, elevated aldosterone with low renin
Glucocorticoid remediable aldosteronism (GRA)
GRA defect
Overactive expression of aldosterone synthase
confirmatory test for GRA
dexamethasone suppression
Liddle Syndrome defect
loss of ENAC channels = hyponatremia
how does Liddle and GRA presentation differ?
Liddle has low aldo and low renin
GRA has HIGH aldo and low rening
Mechanism of thin extremities in cushing
Cortisol causes proteolysis to get AAs for gluconeogenesis
Mechanism of obesity in cushing
High insulin and and glucose cause lipogenesis
Mechanism of striae in cushing
Cortisol inhibits fibroblast prolferation and collagen production
major eelectroloyte imbalance in cushing
Hypokalemia
Classic triad of symptoms that aren’t related to physical appearance in cushings
HTN, hypokalemia and metabolic alkalosis
Mechanism for HTN inc ushings
cortisol increases catecholamine sensitivity in vessels –> vasoconstriction
Cortisol can increase Na reabsorption by acting like aldo
mechanism for hyhpokalemia/metabolic alkalosis in cushings
at very high doses, cortisol can actually bind to the aldosterone receptor (K and H secretion, Na reabsorption, HTN)
Basis for high dose dex suppression test
Pituitary cushings is suppressed with high dose dex
Ectopic cushings is not
Basis for CRH stimulation test in cushings
If ACTH increases when CRH is administered, it is pituitary cushings
If ACTH doesnt increase with CRH, it is ectopic production
imaging findings for exogenous steroid induced cushings
bilateral adrenal atrophy
2 causes of bilateral adrenal hypertrophy
Pituitary Cushings
Ectopic Cushings
major cause of unilateral adrenal hypertrophy and atrophyy of the opposite gland
Adrenal adenoma
2 DDx for Hyperpigmentation of the skin in a person with adrenal dysfunction
Adrenal insufficiency
Congential adrenal hyperplasia
Anything causing low cortisol = high ACTH
major way to distinguish b/w 21OH and 11OH deficiency
21OH = hypotension , hyponatremia, hyperkalemia
11OH= Hypertension, hypernatremia, hypokalemia
21OH vs 17OH def (sexual appearance)
21OH is precocious puberty in males, ambiguous in females
17OH is amenorrhea in females and ambiguous in males
screening test of choice for any type of congential drenal hyperplasia
17-hydroxyprogesterone
17OHprogesterone screening results in each case
21OH- elevated
11OH - elevated
17OH- decreased
complication of over treating someone with cushings
they can develop adrenal insufficiency
why must corticosteroids must be tapered?
Acute withdrawal can lead to acute adrenal failure!
SSx of acute adrenal insufficiency
acute drop in BP to the point they can’t perfuse organs
progressive onset of orthostatic hypotension, salt/sugar cravings, fatigue, weight loss
addison dz
2 MCC of addison disease
autoimmune destruction of the gland (DM)
TB in developing countries
how to differentiate primary vs secondary adrenal insufficiency
Primary causes hyperpigmentation due to high ACTH
Secondary doesn’t affect skin b/c ACTH is low
which cancer can cause adrenal insufficiency?
Lung cancer! remember, lung cancers met to the adrenals
Basis for metyropone stimulation test
Metyropone inhibits 11-deoxycortisol –> cortisol
Less cortisol should stimulate an increase in ACTH and 11-deoxycoritsol production
Metyropone test in primary ad. insuff.
ACTH increases, but 11-deoxycortisol does not
Metyropone test in secondary/tertiary ad. insuff
ACTH and 11deoxycortisol both remain low (b/c pituitary cant make more ACTH in response to the low cortisol)
Cell type and embryologic derivative of the adrenal medulla
Chromaffin cells
derived from neural crest
Pheochromocytoma is a tumor of
chromaffin cells
Classic presentation of pheo.
EPISODIC
Anxiety/panic
palpitations
headaches
sweating
screening test for pheo
Vannilylmandelic acid (VMA) and catecholamines in the urine and serum
2 Tx for pheo, and the appropriate order
Phenoxybenzamine/phentolamine followed by Bblocker
2 Classic extra medullary site for pheochromocytoma
Inferior mesenteric artery
Bladder wall
Neuroblastoma origin and location
chromaffin cells in kids
neural crest origin
CLassic neuroblastoma presentation
abdominal distention
IRREGULAR shaped mass that CROSSES MIDLINE
HTN +/-
Myoclonus or Opsoclonus (eyes)
how to differentiate neuroblastoma from nephroblastoma (wilms)
Wilms is smooth and unilateral
Histology of neuroblastoma
Homer wright rosettes, just like medulloblastoma
Neuroblastoma gene defect
overexpression of N-myc
2 things that suppress GH secretion
Somatostatin
GLucose
buzzword for the facial apperance of hyperthyroidism
“frightened appearance”
Refers to staring gaze with lid lag (eyes wide open)
mechanism of hypocholesterolemia in hyperthyroidism
Thyroid hormone increases LDL receptor synthesis in the liver –> decreases serum cholesterol
can increase risk of gallstones!!
effect of free T3/ rT3 in hypothyroidism
Can be low or normal
There is a lot of variability on the effects of T3 b/c it is made peripherally. So in early hypothyroid, T4 will be low, but the T3 can be normal because there isn’t much of it around anyway. But in late disease, T3 will drop b/c T4 is severely low
Histology of orbital muscles in exopthalmos will show what 2 features?
Inflammation (T cells)
Increased Adipocytes
4 Tx for thyroid storm
PTU
Prednisone
Propanolol
Potassium Iodine
LIgation of superior laryngeal artery during thyroidectomy. Complication?
Damage to superior laryngeal nerve –> loss of cricothyroid function (deepening of voice)
Ligation of inferior thyroid artery. Post surgical complication?
Damage to recurrent laryngeal nerve –> hoarseness
Hypocalcemia effects on ECG
QT Prolongation
what is most likely to be seen in a kidney biopsy in a patient with Primary Hyperparathyroidism?
Nephrocalcinosis of the renal tubules
HyperCa = metastatic calcification
Knuckle Knuckle Dimple Knuckle sign
Turners
Knuckle Knuckle Dimple Dimple sign
Pseudohypoparathyroidism (Albright heriditary dystrophy)
What is the specific defect in PsHP?
Defective Gs protein in the renal tubular cells –> kidney doesn’t respond to PTH
(PsHP is to PTH as Nephrogenic DI is to ADH)
Which parent is responsible for passing on PsHP? Why?
Mom because of genetic imprinting
Pseudopseudohypoparathyroidism presentation
Look like albrights (short stature, short 4th/5th digits) but don’t have end organ PTH resistance…PTH and Ca levels are normal
Which parent causes PsPsHP?
Father
Familial Hypocalciuric Hypercalcemia defect
Defective Ca Sensing receptor in the PTH means body can’t respond to high Ca
FHH Labs (serum/urine Ca, PTH)
High serum Ca
High PTH
Low urine Ca
Relationship of Prolactinoma and Bone ina woman
Increases risk for osteoporosis
Prolactin inhibits GnRH = low estrogen = increased osteoclasti activity
2 enzymes implicated in Osmotic damage in diabetes
Aldose reductase
ABSENCE of sorbitol dehydrogenase
Insulinoma Labs (glucose, insulin, Cpeptide)
Low glucose
High Insulin
High C peptide
Screening test (besides cpeptide) for insulinoma
Symptoms resolve after giving glucose, but then come back several hours later
Screening test for gastrinoma
Gastrin levels remain elevated after secretin administration
Potassium levels in primary vs secondary adrenal insufficiency. Why?
Low in Primary b/c entire adrenal is dead
Normal in secondary b/c ACTH doesn’t directly stimulate the zona glomerulosa!!
Basis for CRH stimulation test in adrenal insufficiency
If CRH stimulates the production of new cortisol, the Dx is Secondary/tertiary adrenal insufficiency (b/c the pituitary wasn’t releasing ACTH)
This is the same logic as in pituitary cushings vs ectopic ACTH production
Muscle disease in hypo vs hyperthyroid? how to differentiate?
Both get proximal muscle wekness
Hypothyroid = Increased CK Hyperthyroid = Normal CK
