Endocrine Flashcards
What is the most common tumor of the adrenal gland?
Benign cortical adenoma
What organ requires fetal cortisol for complete development?
Lungs - stimulates Type 2 Pneumocytes to secrete surfactant beginning in week 34
What hormones are secreted from the anterior pituitary?
FSH, LH, ACTH, TSH, prolactin, GH
Which hormones share a common a subunit?
TSH, LH, FSH, hCG
What is oxytocin used for clinically?
To induce labor or prevent postpartum hemorrhage (induced uterine contractions)
What hormones are secreted from the a, B, and d cells of the pancreas?
a - glucagon
B - insulin
d - SST
What 3 tissues secrete SST and what is it’s function in those tissues?
Pancreas (d cells) - decrease insulin secretion
GI mucosa (D cells) - decrease motility and splanchnic blood flow (Tx bleeding esophageal varies)
CNS - decrease pituitary hormone secretion (TSH and GH)
What does FSH do in females and males? What molecule exerts negative feedback?
Females - stimulate Granulosa cell estrogen release (follicular development)
Males - stimulate Sertoli cell spermatogenesis
Inhibin
What does LH do in females and males? What molecule exerts negative feedback?
Females - Theca cell testosterone release, stimulates ovulation
Males - Leydig cell testosterone release
Sex hormones
What are the different types of glucose transporters and what tissues are they found in?
GLUT1 (low Km) - RBC, brain, cornea
GLUT2 (high Km) - pancreatic B cells, liver
GLUT4 (insulin dependant) - adipose, skeletal muscle
GLUT5 (fructose) - GI
What influences prolactin release? What hypothalamic/pituitary hormones does prolactin influence?
DA inhibits and TRH stimulates prolactin
Prolactin inhibits GnRH (and thus LH/FSH) - prolactin release during breastfeeding causes natural family spacing by inhibiting ovulation, prolactinomas can cause amenorrhea and osteoporosis
What drug can be used to treat a prolactinoma?
Bromocriptine (DA agonist)
Which hormones confer insulin resistance?
Cortisol, GH
What hypothalamic nucleus synthesizes ADH?
Supraoptic nuclei
How does nicotine, opiates, and alcohol affect ADH secretion?
Nicotine, opiates - increase ADH (water retention)
Alcohol - decrease ADH (diuresis)
What is the most common cause of Congenital Adrenal Hyperplasia? How do girls and boys present (if not caught with the newborn 17-OH-progesterone screen?
21-Hydroxylase deficiency
Girls - virulization (seen early)
Boys - salt wasting (caught later, no obvious virulization)
What hormones are elevated in 17a-hydroxylase deficiency, 21-hydroxylase deficiency and 11B-hydroxylase deficiency?
17a-hydroxylase deficiency - Pregnenolone and progesterone
21-hydroxylase deficiency - Progesterone and 17-OH-progesterone
11B-hydroxylase deficiency - 11-deoxy-corticosterone and 11-deoxy-cortisol
What drug and hormone affect Desmolase activity?
Ketoconazole (decreases activity) and ACTH (increases activity)
What drug inhibits 5a-Reductase? What is it’s clinical use?
Finasteride
BPH, male-patterned baldness
Which forms of Congenital Adrenal Hyperplasia will result in ambiguous genitalia in males? Females?
Males - 17-hydroxylase (low androgens)
Females - 21-hydroxylase and 11a-hydroxylase (high androgens = virulization)
What clinical feature is found in all causes of CAH?
Adrenal hyperplasia (all have low cortisol, thus high ACTH causes hyperplasia for the Zona Fasciculata)
What is the DIT shortcut for CAH clinical presentations?
First digit is a 1 = HTN
Second digit is a 1 = Masculinization
What aldosterone precursor has minor mineralocorticoid activity? Which form of CAH has accumulation of this causing HTN?
11-deoxy-corticosterone
11-hydroxylase deficiency
If a patient is in septic shock and BP does not increase with pressers, what may be deficient?
Cortisol - upregulates a1 Rs on arterioles, increasing NE/Epi sensitivity
What abnormality can be seen on CBC with Cushing Syndrome and why?
Neutropenia - cortisol decreases leukocyte adhesion to vessel walls
What infections are patients with Cushing Syndrome most susceptible to and why?
TB reactivation and Candidiasis - cortisol blocks IL2 production (T cell proliferation)
What are the features of Cushing Syndrome?
BAM, CUSHINGOID
Buffalo hump, acne, moon facies, Crazy (phychosis), ulcer (PUD), skin changes (purple striae, poor wound healing), HTN, infection, necrosis of the femoral head, glaucoma, osteoporosis, immunesuppression, diabetes
How does PTH increase Ca bone resorption?
PTH stimulates osteoblasts to secrete RANKL, which binds RANK on osteoclasts to stimulate bone resorption
What malignant tumors can secrete PTHrp? (3)
Squamous cell lung CA, renal cell CA, breast CA
How does low Mg affect PTH? What are 4 common causes of hypoMg?
Low Mg = stimulate PTH, very low Mg = inhibit PTH
Diuretics, diarrhea, aminoglycosides (can bind CaRs on presynaptic neurons to cause neuromuscular block, behaves like Ca), alcohol abuse
How does alkalosis affect Ca levels?
HypoCa - Ca primarily binds albumin in serum because strongly negative charge (many COOH), H is kicked off in alkalosis giving more negative locations for Ca to bind (same Ca content, more is bound)
Trousseau and Chvostek signs indicate what?
HypoCa
What cell type secretes Calcitonin? What cell type did it originate from?
Parafollicular C cells of the thyroid medulla
What cancer has a tumor marker that is turned into amyloid?
Medullary thyroid CA - tumor of parafollicular C cells, secretes calcitonin that forms an amyloid stroma
What are the signs/symptoms of primary hyperparathyroidism? (Stones, Bones, Groans, Psychiatric overtones)
Stones - renal stones, nephrocalcinosis
Bones - osteoporosis, osteitis fibrosa cystica (subperiosteal bone resorption on radial middle phalanges, bone cysts, brown tumor)
Groans - constipation (excessive SMC tone), peptic ulcers (Ca increases gastrin secretion), pancreatitis
Psych - fatigue, psychosis, coma
What is the most common cause of hyperCa?
Solitary parathyroid adenoma
Which endocrine hormones modulate cAMP signaling? (FLAT ChAMP)
FSH, LH, ACTH, TSH
CRH, hCG, ADH (V2), MSH, PTH
Which endocrine hormones modulate IP3 signaling? (GOAT)
GnRH, Oxytocin, ADH (V1), TRH
What endocrine hormones modulate R-associated Tyrosine Kinases?
Prolactin, GH
What is the Wolff-Chaikoff effect?
Excess Iodine inhibits thyroid Peroxidase (organification) to paradoxically decrease thyroid hormone levels
What are two physiologic effects of thyroid hormone and what is the mechanism?
Increase basal metabolic rate = increase Na/K ATPase synthesis
Increase sympathetic tone = increase B adrenergic Rs
What is the mechanism of pretrial myxedema and exophthalmos in Grave’s Disease?
Thyroid Stimulating Immunoglobulins (TSIs) stimulate TSHRs on dermal and retro-orbital fibroblasts to secrete GAGs
What metabolic changes are seen in hyperthyroidism and why?
Hypocholesterolemia - increased LDLR expression
Hyperglycemia - activation of gluconeogenesis AND glycogenolysis
What histological findings are seen in Grave’s Disease?
Hyperplastic follicles with scalloped colloid
How does thyroid storm present? How would you treat it?
Arrhythmia, hyperthermia, hypovolemic shock
PTU, B blocker, corticosteroids
What drugs can induce Hyperthyroidism if the patient has undetected non-functioning multi nodular goiter?
Contrast and amiodarone (both have high I content)
Non-functional multi nodular goiter occurs when patches of thyroid become relatively I deficient = hyperplasia under increased TSH stimulation. Thus if given a high I dose it will turn back on quickly due to the hyperplasia
What HLA gene is associated with Hashimoto Thyroiditis?
HLA-DR5
What antibodies are produced in Hashimoto Thyroiditis?
Anti-thyroglobulin and anti-microsomal
What histology is seen in Hashimoto Thyroiditis?
Chronic inflammation, germinal centers, and Hurthle cells (follicular epithelium with bright pink cytoplasm)
What pathology would cause a patient with long-standing Hashimoto Thyroiditis to have newly-enlarging thyroid?
Marginal B cell lymphoma
What presents with hypothyroid + painful goiter? What type of inflammation is present?
Subacute de Quervian Thyroiditis
Granulomatous inflammation
What presents with hypothyroid + painless goiter? What type of inflammation is present?
Hashimoto thyroiditis - lymphocytic inflammation
Riedel thyroiditis ("hard as wood thyroid") - eosinophils + macrophages/fibrosisThyroid fibrosis that extends into local structures
Riedel thyroiditis - young females
Anaplastic CA - older pts
Ovarian mass + hyperthyroid
Struma ovarii (teratoma with thyroid tissue)
What would you give someone with radioactive I exposure?
Potassium-iodide - competes for uptake/organification (faster than drugs)
Whats the mechanism for sampling thyroid tissue?
Fine needle aspiration
What surgical complications are unique to thyroidectomy?
Parathyroidectomy, recurrent laryngeal nerve damage (horseness)
What histological features are unique to papillary thyroid CA?
Orphan annie nuclei (central clearing), nuclear grooves (dark purple needles), psammoma bodies
What is the difference between follicular adenoma and CA? How can you determine this clinically?
CA has invaded through the fibrous capsule.
FNA cannot distinguish the two! Must see gross specimen to inspect the entire capsule
Which 4 CAs spread hematogenously?
Follicular CA, chorioCA, renal cell CA, HCC
What genetic mutation is associated with medullary thyroid CA?
RET mutations (associated with MEN2A and 2B)
What is the strongest risk factor for papillary thyroid CA?
Childhood head/neck radiation
What are 3 causes of nephrogenic diabetes insidious?
HyperCa (nephrocalcinosis), Li, demeclocycline (tetracycline abx)
What 3 medications are used to treat nephrogenic DI?
HCTZ - worsens volume depletion enough to stimulate greater Na/water resorption in the proximal tubule
Indomethacin - blocks PG vasodilation of afferent arteriole = decrease RBF
Amiloride (if due to Li) - blocks Na channel in the collecting duct that Li uses to enter (blocks ADH R from inside the cell)
How does PTH affect urine cAMP?
Increases urine cAMP - PTH R on renal tubular cells activates Gs signaling pathway to increase cAMP which modulates Na/Ca channels in the distal tubule
How does PTH affect ALP? Why?
Increased ALP - marker for osteoBLAST activity, which is directly activated by PTH to release RANKL which stimulates osteoCLASTs
What is the most common cause of secondary hyperparathyroidism? What is the mechanism to elevate PTH?
Chronic renal failure - decreased PO4 excretion = binds free Ca = decreased free Ca concentration = increased PTH
HypoCa, short stature, short 4th/5th digits
Pseudohyperparathyroidism - autosomal dominant mutation in Gs intracellular signaling protein causes tissues to become unresponsive to PTH.
What are the 4 most common causes of Cushing Syndrome?
- Exogenous steroids - bilateral atrophy
- Functional adrenal adenoma - unilateral atrophy
- Cushing Disease (ACTH-secreting pituitary adenoma) - bilateral hyperplasia
- Paraneoplastic ACTH (small cell lung CA) - bilateral hyperplasia
How would you differentiate Cushing Disease from paraneoplastic ACTH?
High dose dexamethasone test - ACTH-secreting pituitary adenoma (Cushing Disease) will be suppressed (more like the original tissue) than the ectopic ACTH-secreting tumor
What are the 3 most common causes of chronic adrenal insufficiency?
Autoimmune destruction, TB, bilateral metastases (especially lung CA)
How would you grossly differentiate a pheochromocytoma from a cortical adrenal adenoma?
Pheochromocytoma is brown, cortical tumors are yellow (high cholesterol content)
How frequently are pheochromocytomas outside the adrenal gland? Where are they most commonly located?
10% extra-adrenal
Classically in the bladder wall = symptoms associated with urination
What 4 genetic diseases are associated with pheochromocytoma?
MEN2A, MEN2B, von Hippel-Lindau diasease, Neurofibromatosis type 1
What NT breakdown products will be increased in pheochromocytoma?
Metanephrine, normetanephrine, VMA - breakdown products of NE and Epi via MAO
What NT breakdown products will be increased in neuroblastoma?
Homovanillic acid (HVA) - breakdown product of DA
What 4 tumors can secrete EPO?
Pheochromocytoma, RCC, hemangioblastoma, HCC
What antibody is seen in T1DM?
Anti-glutamic acid decarboxylase
What HLA genes are associated with T1DM?
HLA-DR3 and HLA-DR4
What enzyme converts glucose to sorbitol? What tissues are missing the enzyme that converts sorbitol to fructose?
Aldose reductase Schwann cells (peripheral neuropathy), lens (cataracts), retina, kidneys = osmotic swelling and damage
What are the components of metabolic syndrome?
Waist circumference, TGs, HDL, BP, fasting serum glucose
How is K affected by DKA?
Serum hyperK (acidosis causes K/H pump to pump K out of cells) but total body K depletion (osmotic diuresis pulls K with it)
What infections are DKA patients more susceptible to?
Mucor and rhizopus - fungi proliferate in blood vessel walls with excess glucose and ketones. Penetrate cribriform plate = cerebral abscesses, facial black eschar
If hyperglycemia is not the major concern in DKA, why is insulin given?
Although insulin and hypeglycemia are the initiators, ketone buildup and acidosis is what causes DKA. Still give insulin to inhibit lipolysis (decreasing Acetyl-CoA available for ketogenesis) - give glucose if necessary to continue giving insulin until metabolic gap closes. Lipolysis is stimulated to glucagon
What is different about Hyperosmotic Hyperglycemic State (T2DM) when compared to DA (T1DM)?
Insulin is present, thus lipolysis doesn’t occur and no ketones are made. Symptoms are caused by extreme hyperglycemia. Give insulin until serum glucose normalizes
What is the Whipple triad?
Insulinoma - low blood glucose, symptoms of hypoglycemia (lethargy, syncope, diplopia), and symptom resolution when given glucose
What is the mechanism of Metformin? What is the major side effect?
Decreases gluconeogenesis in the liver Lactic acidosis (stop if getting contrast because renal failure increases risk)
What is the mechanism of Sulfonylureas (Gli-)? What is the major side effect?
Closes K channels in B cell to stimulate insulin secretion (requires some beta cell function to work)
Hypoglycemia
What is the mechanism of TZDs (-glitazone)? What is the major side effect?
Increase insulin sensitivity in peripheral tissue by binding PPAR TF
Edema (contraindicated in CHF)
What is the mechanism of DPP4 inhibitors (-gliptin)? What is the major side effect?
DPP4 inhibits the endogenous Encretin system that augments insulin secretion, drugs inhibit DPP4 to activate the Encretin system
No major side effects
What is the mechanism of GLP1 agonists (-tide)? What is the major side effect?
Analog of encretin system molecules = augments insulin secretion in a glucose-dependent manner
Acute pancreatitis
What is the mechanism of SGLT2 inhibitors (-liflozin)? What is the major side effect?
Inhibits glucose reabsorption in the kidneys
Recurrent UTI
What vitamin deficiency is seen in Carcinoid Syndrome?
Pellagra (Tryptophan is used to make the 5HT, less available to make Niacin)
Leptin modulates which hypothalamic nuclei?
Inhibits lateral (hunger) and stimulates ventromedial (satiety) "Lateral likes lunch"
What is the serious side effect associated with PTU and Methimazole? What other side effect is associated with only PTU? Only Methimazole?
Both - agranulocytosis
PTU - hepatotoxicity
Methimazole - teratogen
