Endocrine Pathology

ekadar's version from 2016-03-13 07:42

Adrenal Pathologies

Question Answer
Cushing's Syndrome causesincreased cortisol due to: exogenous steroids (↓ ACTH), pituitary adenoma (Cushing's Disease, ↑ACTH), adrenal problem (adenoma/carcinoma/hyperplasia--> ↓ ACTH), or ectopic source (small cell lung cancer, ↑ACTH)
ACTH-independent causes of cushing’sexogenous source (iatrogenic steroids) or adrenal adenoma (pituitary adenoma and ectopic source are both ACTH-dependent causes) i
Cause of cushing’s that does not suppress cortisol in response to low and high dose dexamethasoneectopic ACTH producing tumor (small cell carcinoma), and cortisol-producing tumor
Dexamethasone is asynthetic glucocorticoid- used to i.d. cause of Cushing’s
if decreased serum ACTH in Cushingssuspect adrenal tumor
Findings in CushingsHTN, wt. gain, truncal obesity, buffalo hump, striae, osteoporosis
Cause Cushing's DiseaseACTH pituitary adenoma, will be suppressed in high dose Dexamethasone test
Acute adrenocortical insufficiency due to adrenal hemorrhage from n. meningitidis septicemiawaterhouse-friderichsen syndrome
Chronic adrenal insufficiency from adrenal atrophy or destruction by diseaseAddison’s- deficiency of aldo/cortisol causing hypotension, hyperkalemia, acidosis and hyperpigmentation (lots of ACTH-->MSH), involves all 3 layers of cortex
Secondary adrenal insufficiencypituitary problem w/ ↓ ACTH production (no hyperpigmentation or hyperkalemia as in primary chronic adrenal insufficiency, ie. addison’s)
How to diagnose adrenal insufficiencymeasure ACTH or give metyrapone which blocks last step of cortisol synthesis. normal response is increase in ACTH, in insufficiency ACTH remains low
Primary hyperaldosteronism and txi.e. Conn’s syndrome – aldo secreting tumor--> HTN/hypokalemia/metabolic alkalosis/low plasma renin, can be uni or bilateral- tx with spironolactone (k-sparing aldo antagonist)
Secondary hyperaldosteronismkidney perception of low intravascular volume (CHF, renal failure, renal a. stenosis, nephrotic syndrome, cirrhosis) results in overactive RAS--->high plasma renin
How to diagnose between Conn's and secondaryConn's increase aldo and decrease renin, secondary increase aldo and increase renin
Pheomost common tumor of adrenal medulla in adults, from chromaffin cells from neural crest- secretion of epi/NE/DA
5P's: Pressure (episodic HTN), Pain (HA), Perspiration, Palpitations, Pallor
Rule of 10s for pheo10% malignant/bilateral/extra-adrenal/calcify/kids/familial
Tx of pheoalpha blocker (phenoxybenzamine-->irreversible alpha blocker)
Pheo associated with what other conditions?MEN2a/b, neurofibromatosis
Pheo dxelevated plasma catecholamines and urinary VMA (breakdown product of NE)
Catecholamine synthesisPhenylalanine-->tyrosine-->L-dopa-->DA (to HVA)-->NE (to VMA)-->epi (to metanephrine)
Most common tumor of adrenal medulla in kidsneuroblastoma- can happen anywhere along sympathetic chain, N-myc oncogene. Crosses the midline in contrast to Wilms tumor
Neuroblastoma dxHVA (byproduct of DA) in urine

Thyroid Pathologies

Question Answer
Symptoms specific to Gravespretibial myxedema and periorbital edema
Hashimotosmost common cause hypothyroidism (can be hyperthyroid in early course during follicular rupture), anti-microsomal and anti-thyroglobulin Ab's, painless!!!
Hashimotos histologylymphocytic infiltrate with germinal centers, hurthle cells
Hashimotos AssociationsHLA-DR5, ↑ risk of non-Hodgkin's lymphoma
Cretinismfrom severe fetal hypothyroidism, defect in T4 formation or developmental failure of thyroid formation; can occur in areas where there is lack of iodine
Cretinism findingspot-beliied, pale puffy-faced child, protruding umbilicus, protuberant tongue
Subacute granulomatous thyroiditisself-limited hypothyroidism following flulike illness, ↑ ESR, jaw pain, early inflammation, painful thyroid gland
subacute thyroditis and iodine uptakedecreased because there is not an exessive production
course of subacute thyroiditisearly can be hyperthyroid (T4 spills out from damaged thyroid), then hypothyroidism
Thyroid replaced by fibrous tissue, can compress adjacent structuresriedel’s thyroiditis- present with fixed/hard painless goiter
Hyperthyroidism with thyroid stimulating/TSH receptor AbsGrave’s- will see exophthalmos (proptosis and EOM swelling due to deposits), pretibial myxedema, diffuse goiter, often presents during stress
Stress-induced catecholamine surgeThyroid storm - can lead to death by arrhythmia; may see ↑ ALP due to ↑ bone turnover
Toxic multinodular goiterfocal patches of hyperfunctioning follicular cells working independently of TSH from mutation in TSH receptor--> ↑ release of T3/T4, nodules aren’t malignant
Thyrotoxicosis if pt. w/ iodine def. goiter is made iodine replete and then given iodineJod-Basedow phenomenon
what drug can cause hypothyroidismamiodarone
subacute lymphocytic thyroditistransient hyperthyroidism that is painful

Thyroid Histology

Question Answer
follicular hyperplasia with tall cells forming intracellular papillary projectionspapillary carcinoma
branching papillary projections with interspersed calcified bodiespapillary carcinoma
mixed, cellular infiltration with occassional multinucleated giant cellsgranulomatous thyroditis
mononuclear, parenchymal infiltration with well-developed germinal centershashimoto
extensive stromal fibrosis extending beyond thyroid capsulereidel thyroditis

Thyroid Cancer

Question Answer
MC Thyroid cancer?Papillary carcinoma s
Papillary carcinoma: Orphan Annie nuclei
- Empty nuclei with central clearing

[ Papi like Daddy Warbucks ]
Papillary carcinoma: Psamomma bodies

[Mama and Papi]
RET and BRAF mutationsPapillary carcinoma
What is the treatment for Papillary carcinoma?Sorafenib: Kinase inhibitor
2nd MC thyroid cancer?Follicular carcinoma
How does Follicular carcinoma invade?Through the thyroid capsule
How does Follicular carcinoma metastasize?Hematogenously!! Prone to mets especially lung and bones
RAS and PAX8-PPAR1Follicular carcinoma
Associated with MEN2A and MEN 2B RET mutationsMedullary carcinoma
Medullary carcinoma is derived from which cells?Parafollicular c cells
Calcitonin: causes HypocalcemiaMedullary carcinoma: proliferation of parafollicular C cells
Medullary Carcinoma: Sheets of cells in aMyloid stroma
What type of thyroid cancer has the worst prognosis?Undifferentiated / Anaplastic carcinoma
Rock hard thyroid in older patientsUndifferentiated / Anaplastic carcinoma
Which type of cancer is associated with Hashimoto thyroiditis?B Cell Lymphoma
What are common complications of thyroidectomy?1. Hypocalcemia: remove parathyroid glands
2. Hoarseness: damage laryngeal nerves
Activation of receptor tyrosine kinase?Papillary and Medullary


Question Answer
What are common causes of Primary Hyperparathyroid?Parathyroid Adenoma (MC)
↑Ca++ ↑PTH ↑ALP ↑cAMP in urinePrimary hyperparathyroid
Why is cAMP high in the urine with primary hyperparathyroid?PTH stimulates Gs → AC: ATP→cAMP
What are the key findings of Primary hyperparathyroid?Hypercalcemia:
Psychiatric overtones
What kind of renal stones develop in Primary hyperparathyroid?Calcium oxalate (due to ↑Ca++ in the urine
What bone deformities develop in Primary hyperparathyroid?Osteitis fibrosa cystica
- Cystic bone space filled with brown fibrous tissue
↓Ca++ ↑PO4- ↑PTH ↑ALPSecondary Hyperparathyroidism
What is the cause of Secondary Hyperpara?Chronic Renal Insufficiency
- No vitamin D: ↓Ca++
- Can't excrete PO4 → PO4- binds free Ca++
Acute pancreatitisHyperparathyroidism: ↑Ca++ stimulates pancreatic enzymes
What is the most common congenital cause of Hypoparathyroid?DiGeorge
- Failure to form the 3rd and 4th pharyngeal pouch!
What are common causes of Hypopara?Surgical excision
↓Ca++ ↓PTHHypoparathyroidism
What are signs of Hypopara?Chvostek (hypocalcemia). facial muscle contractions
Trousseau (hypocalcemia). carpal tunnel spasm
↓Ca++ ↑PTHPseudo-Hypoparathyroidism
Contraction when tapping facial nerveChvostek Sign: Hypoparathyroidism
Carpal spasm when brachial artery is occludedTrousseau sign: Hypoparathyroidis
What lung cancer release PTH related hormonesquamous cell carcinoma of the lung
labs of pseudohypoparamentally retarded child with low serum calcium, high serum phosphate, high PTH and shortened metacarpals
pathogenesis of pseudohypoparadecreased expression Gs in erythrocytes

Pituitary Pathologies

Question Answer
Most likely Pituitary adenomamost likely prolactinoma
Prolactinoma findingsamenorrhea, galactorrhea, low libido, infertility- possible impingement on optic chiasm-->bitemporal hemianopia
Prolactinoma txDA agonists = bromocriptine and cabergoline tend to shrink adenoma so don’t usually need sx
Acromegaly findingsdue to excess GH in adults-->large jaw, deep furrows/deep voice, large hands/feet, large tongue, coarse facial features, impaired glucose tolerance (insulin resistance)
GH excess in kids?gigantism- linear bone growth
Tx of GH excesspituitary adenoma resection, then octreotide (somatostatin analog)
Dx GH excessscreen for high serum IGF1, dx with given glucose, glucose supposed to suppress GH, but in tumors increases GH
GH increases in what states?stress, exercise, and hypoglycemia
Postpartum hypopituitarism = ?Sheehans- enlarge anterior pituitary (increased lactotrophs) without increased blood supply-->high risk of infarction of pituitary following severe bleeding/hypoperfusion during delivery
Sheehan’s clinicalfatigue, anorexia, poor lactation, loss of pubic/axillary hair
Empy sella syndromeatrophy of pituitary --> hypopituitarism, fills w/ CSF
Intense thirst and polyuria, unable to concentrate urinediabetes insipidus- central (no ADH from tumor/trauma/sx/histiocytosis x) or nephrogenic (can’t respond to ADH- hereditary or secondary to hypercalcemia, lithium, demeclocycline = ADH antagonists)
Dx Diabetes insipiduswater deprivation test-->urine still doesn’t [ ] even when water is deprived
response to desmopressin distinguishes the 2: central responds, nephrogenic doesn’t
Tx DIfor central give desmopressin (ADH analog), for nephrogenic give HCTZ, indomethacin, or amiloride
SIADHinappropriate ADH: excessive water retention, hyponatremia, urine osmolarity>serum osmolarity
SIADH txwater restriction or demeclocycline
SIADH causesectopic ADH (small cell lung cancer), CNS disorders/head trauma, pulmonary disease, drugs (cyclophosphamide)
Complications of correcting low Na+ too fastcentral pontine myelinolysis


Question Answer
Tests for DMfasting serum glucose, A1c, glucose tolerance test
Acute clinical DMpolydipsia, polyuria, polyphagia, weight loss, DKA (type 1), hyperosmolar coma (type 2), unopposed secretion of GH and epi
Chronic clinical DMdue to nonenzymatic glycosylation
Nephropathynodular sclerosis, progressive proteinuria, chronic renal failure, HTN, Kimmelstiel-Wilson nodules
Why is there increased sorbitol in Schwann cells, lens, retina and kidneybecause glucose converts to sorbitol which converts to fructose via sorbitol dehydrogenase. in diabetes too much sorbitol to convert so it builds up
Genetics and HLA association in DM1 vs 2HLADR3/DR4 for DM1 and weak genetic disposition, no HLA association for DM2 however strong genetic predisposition (polygenic)
Beta cells and serum insulin in DM1 vs 2in 1 beta cell numbers decrease as is serum insulin, 2- variable beta cells/insulin levels
Primary defect in DM1 vs 21- viral/AI destruction of beta cells, 2- increased resistance to insulin
Histology for DM1 vs 21 - islet leukocytic infiltrate
2 - islet amyloid deposit
DKAcomplication of DM1- due to increased insulin requirements in times of stress-->excess fat breakdown and more ketones/free FAs-->ketone bodies, usually insulin is around to inhibit hormone sensitive lipase but when insulin is too low, lots of fat & ketone bodies
Signs of DKAkussmaul respirations (rapid deep breathing), fruity breath, n/v, ab pain, dehydration, delirium/psychosis
Labs for DKAhigh anion gap metabolic acidosis, hyperglycemia, high H+ low HCO3, high blood ketones (β-hydroxybutyrate > acetoacetate), leukocytosis, hyperkalemia (***transcellular shift from ICM-->ECM due to insulin depletion)
Tx DKAfluids, K (replete intracellular stores), admin of insulin causes rapid drop of K so don’t want pt to become hypokalemic), then insulin, also give glucose to prevent hypoglycemia and also give phosphate to prevent respiratory paralysis
dermatitis, diabetes, DVT and depressionglucagonoma
Describe the mechanism of the release of insulin from beta cells of the pancreasa high ATP to ADP ratio within beta cells causes the closure of potassium channels (KATP). When these channels close beta cells depolarize, and voltage gated calcium channels open. High intracellular calcium leads to insulin release.
Defects of the KATP channel result intype 2 diabetes as there is an inadequate insulin response to glucose
what happens to peripheral nervesendoneural arteriole hyalinization

Tumor Syndromes

Question Answer
Carcinoid syndromerare from carcinoid tumors- neuroendocrine cells of GI tract, especially small bowel metastatic tumors--> secrete high 5-HT
Carcinoid syndrome sxsBFDR (bronchospasm, flushing, diarrhea, right-sided heart tumor)
Dx/tx carcinoidhigh urine 5-HIAA, give octreotide
What happens if carcinoid tumor is limited to GI tractno sxs due to 5-HT undergoing 1st pass effect
ZE syndromegastrin-secreting tumor of pancreas or duod, recurrent ulcers, can be associated with MEN1 (3 Ps)
MEN13 Ps- pancreatic, pituitary, parathyroid, commonly presents with stomach ulcers/kidney stones
MEN1 pancreatic endocrine tumorsZE syndrome, insulinoma, VIPoma, glucagonomas
MEN2apheo, parathyroid hyperplasia, medullary thyroid carcinoma
Men2bpheo,medullary thyroid carcinoma, mucosal neuromas
ret mutationMEN2A and MEN2B
MEN syndrome inheritanceauto dom