Random Organ systems - endo Flashcards
What is the function of CRH of HPA? clinical notes?
increase ACTH, MSH, Beta-endorphin
CRH is decreased in chronic exogenous steroid use
What is the function of Dopamine of HPA? clinical notes?
decrease prolactin
Dopamine antagonists (antipsychotics) can cause galactorrhea
What is the function of GnRH of HPA? clinical notes?
increase FSH & LH
regulated by prolactin;
Tonic GnRH suppresses HPA axis
Pulsatile GnRH leads to puberty & fertility
What is the function of Prolactin of HPA? clinical notes?
decreases GnRH
Pituitary prolactinoma leads to amenorrhea & osteoporosis
What is the function of somatostatin of HPA? clinical notes?
decrease GH & TSH
Analogs used to treat acromegaly
What is the function of TRH of HPA?
increase TSH & prolactin
Name the neuroendocrine glands controlled by the medulla
Posterior pituitary => ADH & OT
Adrenal medulla => catecholamines
Hypothalamus => releasing hormones
What increases or decreases cholesterol desmolase action to convert cholesterol to pregnenolone?
increases => ACTH
decreases => ketoconzale
WRT calcium homeostasis, an increase in pH will cause what Sx?
increase in pH leads to increase affinity of albumin (neg charge) to bind to Ca+ causing hypocalcemia symptoms of cramps, pain, paresthesias, carpopedal spasm
What endocrine signaling pathways use cAMP?
FLAT ChAMP
FSH; LH, ACTH, TSH
CRH, hCG, ADH (V2 receptor), MSH, PTH
calcitonin, GHRH, glucagon
What endocrine signaling pathways use cGMP?
ANP & NO (EDRF) => think vasodilators
What endocrine signaling pathways use IP3?
GOAT HAG
GnRH, Oxytocin, ADH (V1 receptor), TRH;
Histamine (H1-receptor), AT-II, Gastrin
What endocrine signaling pathways use steroid receptor (intracellular action)?
VETTT CAP
Vit D, Estrogen, Testosterone, T3/T4;
Cortisol, Aldosterone, Progesterone
What endocrine signaling pathways use intrinsic tyrosine kinase?
MAP kinase pathway => think growth factors
Insulin, IGF-1, FGF, PDGF, EGF
What endocrine signaling pathways use receptor associated tyrosine kinase?
JAK/STAT pathway => think acidophiles & cytokines
PIG
Prolactin, Immunomodulators, GH
IL-2, IL-6, IL-8, IFN
Steroid hormones are lipophilic & bound to SHBG. Describe the increase & decrease in SHBG in men & women
men=> increase SHBG lowers free testosterone causing gynecomastia
women=> increase SHBG is found in OCPs & pregnancy but free estrogen is unchanged;
decreased SHBG raises free testosterone leading to hirsutism
What does T3/T4 do to the heart?
increases B1 receptors leading to increased CO, HR, SV, contractility
What does T3/T4 do to the BMR?
increases BMR via increase in Na/K ATPase activity causing more O2 consumption, increased RR & body temp
What causes a decrease in TBG? increase in TBG?
hepatic failure;
pregnancy or OCP use along w/ estrogen
What converts T4 to T3 in the periphery?
5’-deiodinase
What is the role peroxidase of thyroid hormones?
Peroxidase responsible for oxidation & organification of iodide; couples MIT & DIT
What is the Wolff chaikoff effect?
excess iodine temporarily inhibits thyroid peroxidase leading to decreased T3/T4 production
Differentiate the Rx used for hyperthyroidism
Propylthiourcil inhibits both peroxidase & 5’-deiodinase
Methimazole inhibits peroxidase only
Treatment for prolactinoma
DA agonists => bromocriptine or cabergoline
Tx for acromegaly
Try to resect
If not cured then octreotide (somatostatin analog) or pegvisomant (GH receptor antagonist)
Differentiate DI based on water restriction test
Central DI will show > 50% increase in urine osmolarity
Nephrogenic DI while show no change in urine osmolarity
Tx for central DI
Intranasal DDAVP & hydration
Tx for nephrogenic DI
HCTZ, indomethacin, amiloride;
Hydration
What are secondary causes of Nephrogenic DI?
hypercalcemia; lithium, demeclocycline (ADH antagonist that is former antibiotic rarely used)
What can cause SIADH?
Ectopic ADH from small cell lung CA;
CNS d/o or head trauma;
Pulmonary disease;
Drugs => cyclophosphamide
Tx for SIADH?
fluid restrict; IV hypertonic saline;
Conivaptan, tolvaptan, demeclocycline
Tx for hypopituitarism
HRT => corticosteroids, thryoxine, sex steroids, GH
What 2 blood disorders can occur due to hyperthyroidism?
hypocholesterolemia => increased LDL receptor expression
hyperglycemia => gluconeogenesis & glycogenolysis
What are the labs associated w/ the most common cause of hyperthyroidism?
Graves disease
increased total & free T4;
decreased TSH;
hypocholesterolemia (increased LDL expression)
increased serum glucose
Tx for Graves disease
Beta-blockers
Thioamide (blocks peroxidase)
Radioiodine ablation
Patient comes w/ elevated catecholamines after birth with arrhythmia, hyperthermia, vomiting & hypovolemic shock. What is the treatment?
Thyroid storm
Give PTU, beta-blockers, steroids
What is the association of the most common type of hypothyroidism?
Hashimoto thyroiditis => AI destruction of thyroid gland assoc w/ HLA-DR5
What AI Ab are present in Hashimoto thyroiditis?
Antithyroglobulin & antimicrosomal Ab => markers that damage has occurred
What are the labs assoc with Hashimoto thyroiditis?
decreased T4 => controls # of TRH receptors which controls amount of TSH produced => always opposite
increased TSH
What type of cancer is assoc w/ hashimoto thyroiditis?
B cell lymphoma => marginal cell lymphoma
Young woman comes in with tender thyroid after viral infection. What is Dx & Px?
Subacute (deQuervain) Granulomatous thyroiditis
self limited transient hyperthyroidism w/ NO progression to hypothyroidism
young female patient presents w/ nontender, hard thyroid w/ hypothyroidism. What is Dx & what is at risk? What would be the Dx if the patient was older?
Reidel fibrosing thyroiditis => fibrosis may extend to local structures such as airway
anaplastic thyroid
increased I radioactive up results in what Dx? decreased?
increased in Graves or nodular goiter
decreased in adenoma & carcinoma (do FNA Bx)
What are the 4 types of thyroid carcinoma?
papillary, follicular, medullary, anaplastic
What is the MC thyroid CA? What is a major risk factor?
papillary Ca => ionizing radiation in childhood (severe acne)
What typically defines papillary CA of the thyroid?
nuclear features of orphan-annie eyes, psammoma bodies, nuclear grooves
What is oncogenes are mutated in papillary CA of thyroid?
RET & BRAF
Px of papillary CA after lymph node spread?
excellent
Tx for thyroid cancer? complications of treatment?
remove the thyroid
Hoarseness (recurrent laryngeal nerve damage);
hypocalcemia (removal of parathyroid glands);
transection of inferior thyroid artery
Hallmark of follicular CA of thyroid
malignant proliferation of follicles w/ invasion through the capsule
Why cannot FNA Bx distinguish between follicular adenoma & follicular CA?
needle insertion will only see follicular proliferation as seen in both
invasion through the capsule distinguishes them & not seen on FNA
How does follicular CA of thyroid spread?
hematogenously
What are the CA that like to spread via blood?
Renal cell CA;
follicular CA of thyroid
hepatocellular CA;
ChorioCA
FNA Bx done and see malignant cells in amyloid stroma
medullary CA => malignant proliferation of C cells
What are the Sx related to of medullary CA?
high levels of calcitonin produced by tumor lead to hypocalcemia
Calcitonin often deposits w/in tumor as amyloid
what are the familial cases of medullary CA of thyroid associated w/?
MEN 2A & 2B => mutations in RET oncogene
Mutation in RET oncogene warrants what procedure?
prophylactic thryoidectomy
Older person presents w/ dysphagia & respiratory compromise w/ swollen neck. what is Dx & Px?
anaplastic CA of thyroid => undifferentiated malignant tumor
Poor Px
What is MCC of primary hyperparathyroidism?
parathyroid adenoma => benign neoplasm
What are the results of primary hyperparathyroidism?
Stones, bones, groans, psych overtones nephrolithiasis; nephrocalcinosis; CNS disturbances; Constipation, PUD, acute pancreatitis; Osteitis fibrosa cystica
Define osteitis fibrosa cystica
cystic bone spaces w/ brown fibrous tissue => bone pain
Labs of primary hyperparathyroidism
increased serum PTH, Ca+, alk phos (due to osteoblast turned on)
decreased serum phosphate
increased urinary cAMP (PTH stimulates Gs receptor)
What is MCC of secondary hyperparathyroidism?
chronic renal failure => excess PTH extrinsic to parathyroid gland
Labs of secondary hyperparathyroidism
increased PTH, phosphate, alk phos
decreased serum Ca+
What are causes of hypoparathyroidism?
AI damage, surgical excision, DiGeorge syndrome
Presentation of hypoparathyroidism?
numbness/tingling & muscle spasms (tetany) => Trousseau’s sign (BP cuff), Chavsofic sign (tap on jaw)
Labs for hypoparathyroidism
low PTH & low serum Ca+
What is the cause of pseudohypoparathyroidism?
organs not responding to PTH so hypocalcemia w/ elevated PTH
The end organ resistance of pseudohypoparathyroidism is due to what?
AD mutation in Gs protein assoc w/ short stature & short 4th & 5th digits
What causes type I DM? What is it associated with?
autoimmune destruction of Beta cells of T lymphocytes => Ab against insulin leading to inflammation of islets
Assoc w/ HLA-DR3 & DR4
What are the clinical features of a type I DM patient in DKA?
hyperglycemia (>300)
anion gap metabolic acidosis due to ketoacids in blood
hyperkalemia but getting losses in urine so ends in low body potassium bc it is not in cells
Kussmaul respirations, mental change, fruity breath
Tx of DKA
fluids,
insulin
replacement of electrolytes w/ K+
What is the mechanism of insulin resistance in type II DM?
decreased numbers of insulin receptors on skeletal muscle & adipose tissue
How does insulin concentration change during the course of type II DM?
rises due to resistance then very decreased bc of Beta cell exhaustion
amyloid deposits
Tx of type II DM
weight loss (1st always);
Rx to counter insulin resistance;
end stage is insulin dependent
What is a risk for uncontrolled type II DM? How does it present?
hyperosmolar non-ketotic coma => very very high glucose leading to life threatening diuresis causing hypoTN & coma w/ absent ketones (small amounts of insulin counteracts glucagon)
Vascular complications of DM?
NEG of vascular BM =>
NEG of large/medium vessels leads to atherosclerosis;
NEG of small vessels leads to hyaline arteriosclerosis;
NEG of Hgb leads to HbA1c (marker of glycemic control)
What cells/structures are at risk for osmotic damage due to high sugar?
Schwann cells => basis of neuropathy in diabetics
Pericytes in retina blood vessels => aneurysm causing rupture to blindness
lens
Pancreatic endocrine tumors are associated with what?
MEN 1 => parathyroid hyperplasia & pituitary adenoma
How does an insulinoma present? what relieves Sx? What are the labs?
episodic hypoglycemia w/ mental changes relieved by glucose
low glucose;
high insulin & C peptide
Patient w/ Treatment resistant PUD. what is Dx?
Gastrinoma => ZE syndrome
can be multiple & extend into jejunum
Patient w/ low stomach pH along with gallstones & steatorrhea. Dx? Why the Sx?
Somatostatinoma
inhibits gastrin so achlorhydria
inhibits CCK => cholelithiasis & steatorrhea
Patient w/ watery diarrhea, hypokalemia, achlorhydria. Dx?
VIPoma
How does cortisol raise the blood sugar? What are the effects of the elevated blood glucose?
breakdown muscle causing weakness w/ thin extremities;
insulin is released to store fat on face, back, trunk
What is the mechanism of abdominal striae in Cushings?
ruptured blood vessels due to collagen damage
How does stress or any increase in cortisol raise HTN?
upregulate alpha-1 receptors on arterioles thus increasing effect of catecholamines (esp NE)
What are the 3 mechanisms by which cortisol leads to immune suppression?
1) inhibits phospholipase A2 => cannot produce arachidonic acid metabolites
2) inhibits IL-2
3) inhibits histamine release from mast cells
What are the 4 major causes of cushing syndrome?
MCC=> exogenous corticosteroids;
Primary adrenal adenoma, hyperplasia, or CA (one large & one atrophic adrenal gland)
ACTH secreting pituitary adenoma (hyperplastic adrenals);
paraneoplsatic ACTH secretion (bilateral hyperplastic adrenals)
Prolonged exogenous corticosteroids will result in what grossly?
atrophy of both adrenals
How would ATCH pituitary adenoma be differentiated from paraneoplastic ACTH secretion?
High dose dexamethasone (cortisol analog) then measure cortisol levels
If ACTH is suppressed then pituitary adenoma;
If no ACTH suppression then small cell lung CA
What is the MCC of primary hyperaldosteronism? how is it characterized?
MCC is adrenal adenoma
high aldosterone & low renin (high flow)
What is the cause of secondary hyperaldosteronism? how is it characterized?
activation of RAAS => high aldosterone & high renin due to sensing less flow
Define congenital adrenal hyperplasia
excess sex steroids w/ hyperplasia of both adrenal glands
What is the mechanism of pathology in 21 hydroxylase deficiency?
knock out mineral & gluco-corticoids leading to shunting to sex steroids (F: clit enlarge; M: precocious pub)
lack of cortisol will have life threatening hypoTN & excess ACTH (lack of inhibition) leading to hyperplasia of both adrenals;
Salt wasting & hyperkalemia & hypovolemic
Differentiate 11 vs 21 hydroxylase deficiency
There will not be salt wasting in 11 deficiency
What is the findings in 17 deficiency?
excess mineralocorticoids;
no sex hormones so look like opposite of genotype;
excess ACTH
What is the acute cause of adrenal insufficiency?
waterhouse-friderichsen syndrome => N. meningitides after DIC then massive hypoTN
Look for sack of blood of adrenals
Define chronic adrenal insufficiency and give 3 MCC
progessive destruction of adrenal glands
AI destruction of adrenals;
TB;
metastatic CA
What cancer loves the adrenal?
lung
Why is hyper pigmentation assoc w/ adrenal insufficiency or any increase in ACTH?
ACTH is derived from POMC which makes melanocyte stimulating hormone
Where do the chrommafin cells of adrenals come from embryologically?
neural crest cells
How does a pheochromocytoma present grossly?
brown tumor due to chrommafin cells in adrenal medulla being brown
How is pheochromocytoma diagnosed?
increased serum metanephrines & 24 hr urine metanephrines & VMA
For the 10% of pheochromocytomas that are not in the adrenal medulla, where is the MC location? how will it present?
bladder wall => pt urinates causing HTNive episode
What are the genetic association of pheochromocytomas?
MEN 2A & B;
VHL disease;
NF type 1
