Week 1 - Endocrine Flashcards
Group 1 Hormones
steroids, thyroid
lipophilic, transported bound to proteins
long plasma half life
intracellular receptors (thyroid=nuclear, steroid=cytoplasmic) - act on transcription/translation
Group 2 Hormones
Peptides, proteins, glycoproteins, catecholamines
hydrophilic, transported freely
short half-life
plasma-bound receptors
mediators: cAMP, cGMP, Ca, metabolites, kinases
Origin of pituitary components
hypophyseal diverticulum (Rathke's pouch) anterior wall= pars distalis superior extension= pars tuberalis posterior wall= pars intermedia Infundibulum= stalk + pars nervosa
Origin of thyroid components
thyroid diverticulum (endoderm)= thyroid follicular cells Neural crest= parafollicular cells Dorsal wing of pharyngeal arch 3,4 (endoderm)= parathyroid principal cells
Primary germ layer origin of glands
pituitary= ectoderm thyroid/parathyroid= endoderm adrenal= mesoderm
Hyperprolactinemia
Causes:
-prolactinoma (most common)
-drugs (metoclopramide, risperidone, D2 antagonists)
-infundibular stalk compression (from larger pituitary mass)
-pregnancy, lactation, stress, sleep
Sx: women have menstrual abn, galactorrhea, men have ED and hypogonad
Tx: dopamine agonists (cabergoline, bromocriptine), very effective
Acromegaly
excess growth hormone (GH)
GH stimulated by GHRH, inhibited by somatostatin and IGF-1(feedback from liver)
Sx: skull and extremity growth, thick skin, etc
Dx: serum IGF-1, or oral glucose tolerance test
Tx: surgery, radiation, octreotide, lanreotide, pegvisomant
Things pituitary releases
Anterior: ACTH- glucocorticoids (stim by CRH) TSH- T3,T4 (stim by TRH) GH- IGF-1 (stim by GHRH, inhi by somatostatin,IGF-1) Prolactin- (inhib by dopamine) Gonadotropins- FSH and LH (stim by GnRH) Posterior: vasopressin(ADH), oxytocin
Growth hormone deficiency
Sx: in neonate= hypoglycemia,, in child= fat, microphallus, delayed puberty, short
Tx: rGH, check IGF-1 to dose
PTH feedback loop
low Ca - PTH secretion -
- kidney: Ca reabsorption, convert 25 to 1,25 vitD
- Intestine: Ca absorption
- Bone: Ca resorption (and P)
Calcium sensing receptor (CaSR)
expressed in parathyroid and kidney
loss of fxn= familial hypocalciuric hypercalcemia (FHH)
gain of fxn= autosomal dominant hypocalcemia (ADH)
Primary hyperparathyroidism
hypercalcemia (PTH dep)
usually sporadic, single tumor
MEN (multiple endocrine neoplasias)
Familial isolated hyperparathyroidism
Familial hypocalciuric hypercalcemia (FHH)
ectopic PTH (rare)
Sx: hyperparaosteitis, brown tumor (bone), thinning of bone cortex
Familial hypocalciuric hypercalcemia (FHH)
CaSR loss of fxn (usually, not always) autosomal dom asymptomatic, lifelong PTH not suppressed use 24hr urine Ca and creatinine to rule out
PTH independent hypercalcemia
PTH is low malignancy calcitriol-mediated (granulomatous, sarcoid) -excess vitD hyperthyroidism (inc bone resorbtion) immobilization milk --PTHrP
Tx of hypercalcemia
fluids, loop diuretics (furosemide)
bisphosphonates (inhibit osteoclasts)
Hypocalcemia lab findings ddx
primary hypoparathyroid: PO4 up/n, PTH down/n, vitD n
Pseudohyperparathyroid (PTH resistant): PO4 up/n, PTH up, vitD n
Mg depletion: PO4 n, PTH down/n, vitD n
secondary hyperparathyroid: PO4 down/n, PTH up, vitD down
Hypoparathyroidism
hypocalcemia, PO4 up
either genetic or autoimmune or infiltrative
Sx:basal ganglia calcification, hypocalcemic tetany (hand contraction)
Pseudohyperparathyroidism
PTH resistance
GNAS mutation
Albright’s Hereditary Osteodystrophy= short, round face, short 4th metacarpals, ossifications
Hypocalcemia flow chart
PTH down or nl= probable hypoparathyroidism, r/o Mg def
PTH up with high phos= PTH resistance, renal insuff
PTH up with low/n phos= vitD def, occult malabsorption ,, measure 25vitD and 24hr urine Ca and creatinine, check for celiac ds, check BMD
FGF23
-made by osteocytes
Intestine: decreased Ca and PO4 absorbtion by decreased 1,25vitD production
Kidney: increased PO4 excretion
Bone: decreased mineralization due to hypophos and low 1,25vitD
Excess= hypophosphatemia, rickets, osteomalacia
Decreased= hyperphosphatemia, tumoral calcinosis
Pituitary adenomas
women more than men, 30-60yo
prolactinoma most common, non-secreting second-most
well-circumscribed, one cell type, destruction of normal reticulin pattern
Sheehan’s syndrome
postpartum pituitary necrosis
bc gland enlarges during pregnancy, more susceptible to ischemia
obstetrical hemorrhage or shock can make it worse
results in hypopituitarism
Rathke cleft cyst
may be asymptomatic
columnar/cuboidal cells with cilia
thin-walled cyst under pituitary
Craniopharyngioma
kids: adamantinomatous (palisading squamous epithelium with keratin)
adults: papillary (no keratin)
Sx: optic chiasm probs, hypopituitary
Bone disease in hyperparathyroidism
osteitis fibrosa cystica= osteoclasts, thin cortex, fibrosis of marrow
Brown tumor= osteoclasts, giant cells, hemorrhage, like giant cell tumor
Parathyroid adenoma
solitary nodule in single gland
sheets of chief cells, decreased stromal fat
rim of normal parathyroid at edge
Parathyroid carcinoma= super rare, fibrous adhesions
Renin angiotensin aldosterone system
decrease blood pressure- kidney makes renin- renin activates angiotensinogen to AngI- ACE converts to AngII- causes vasoconstriction and adrenals to make aldosterone- Aldo causes renal water and Na retention and K and H secretion- increased blood pressure
Renin system drugs
Renin inhibitors: aliskiren
ACE inhibitors: -pril
Angiotensin receptor blockers (ARBs): -sartan
Mineralocorticoid (aldo) receptor antagonists: spironolactone, eplerenone
Primary hyperaldosteronism
hypertension, hypokalemia
high plasma aldo, low plasma renin activity (ratio high)
also secreting adrenocortical adenoma
bilateral hyperplasia of zona glomerulosa
Tx: adrenalectomy
Secondary hyperaldosteronism
renal ischemia
decreased intravascular volume
Na wasting disorders
Apparent mineralocorticoid excess
11BHSD2 deficiency
that protein converts cortisol to cortisone in the kidney, so if it isn’t there then cortisol can act like aldosterone
Liddle’s Syndrome
mutation in amiloride sensitive ENaC
Tx: amiloride, triamterene (K-sparking diuretics)
Pheochromocytoma
tumor of chromaffin cells (neuroendocrine) of adrenal medulla
secrete both epi and norepi
can be metastatic or benign
“zellballen” cell balls, abundant cytoplasm, granular, basophilic
Paragangliomas: extra-adrenal tumor secrete mostly norepi
Sx: tachycardia, HTN, sweating, headaches, etc (Paroxysmal events)
Dx: 24hr urine catecholamines and plasma metanephrines
Tx: begin alpha block, then beta-block, hydration, surgery
Cortisol-Cortisone shuttle
cortisol is active, cortisone is not
11B-HSD2 in kidney converts cortisol to cortisone
11B-HSD1 in liver converts it back to cortisol
Adrenal Insufficiency (low cortisol)
Sx: fatigue, anorexia, weight loss, increased skin pigmentation, salt craving(primary)
Hyponatremia,, (hyperkalemia in primary)
Causes: critical illness (TB), pituitary injury(secondary), withdrawl from corticosteroids, narcotics, mifepristone, malignancy, hemorrhage
Drugs that cause it: ketoconazole, metyrapone, mitotane, etomidate
Genetic: congenital adrenal hyperplasia (170HP), Adrenoleukodystrophy (accumulate long chain fatty acids)
Tests: ACTH (Cosyntropin) cortisol response, or juct check them both in the AM
Most common= autoimmune adrenalitis (Addison’s)
Tx: glucocorticoid and mineralocorticoid(fludrocortisone) replacement for primary,, just gluco for secondary
Primary= high ACTH, high renin, low aldo
Secondary= low/n ACTH, norm renin, norm aldo
Cushing’s Syndrome
ACTH-dependent hyperaldosteronism
ACTH-secreting tumor (in pituitary or ectopic)
Sx: weight gain, hump, osteoporosis, inc BP, hypogonad, androgen excess, easy bruise
Tests: late-night salivary cortisol, overnight DST, 24hr urine cortisol
If ACTH is low, then get adrenal CT for primary tumor
If ACTH is high/n, get MRI of pituitary and petrosal sinus sample to determine where the tumor is
Tx: surgery, remove tumor,, Pasireotide= somatostatin agonist, Metyrapone= 11B hydroxylase inhibitor, Mifepristone= glucocorticoid inhibitor
Structure of adrenal glands
Cortex: -zona glomerulosa= mineralocorticoids -zona fasciculata= glucocorticoids -zona reticularis= estrogen and androgen Medulla: chromaffine cells= catecholamines
Adrenocortical hyperplasia
bilateral thickenening of adrenal cortex
mostly faciculata cells= clear cells= make glucocorticoids
can be diffuse or multi-nodular
Adrenocortical Adenoma
yellow, encapsulated
can be functional or non-functional (most non)
mostly faciculata cells
Adrenocortical carcinoma
rare, large, invasive
necrosis and hemorrhage
lymph node metastasis
can be well or poorly differentiated
SIADH
common
hyponatremia due to excess H2O retention
causes: lung ds, brain ds, drugs, misc
low Na, hypotonic serum, euvolemic, high urine osmolarity and Na
Dx: exclusion, R/O hypothyroid and adrenal insuff
Tx: fluid restrict, IV salt, AVP receptor antagonists (conivaptan and talvaptan), loop diuretics, Demeclocycline
Be sure to slowly correct the serum Na to avoid bad brain stuff
Diabetes Insipidus (DI)
Deficient ADH (thus polyuria, hypernatremia) central(neurogenic): autoimmune, trauma, tumors, infiltrative of pituitary/hypopthalamus Nephrogenic: x-linked recessive, hypokalemia, hypercalcemia, renal ds, drugs, lithium high Na, euvolemic, variable urine Na polyuria, low urine osmolality, abnormal water restriction test Tx: central= DDAVP/desmopressin,, nephrogenic= low salt diet, thiazide diuretic, NSAIDs
Congenital hypothyroidism
more common in girls, hispanics
mostly from dysgenesis, some from dyshormonogenesis, iodine def is rare here
occasionally from central hypothyroid (MPHD) or transient
Sx: asymptomatic at birth, then lethargy, macroglossia, large fontanels, jaundice, etc,, brain damage less common after age 3
Newborn screening often just measures TSH, can miss central hypothyroid
Tx: levothyroxine
Chronic Lymphocytic Thyroiditis (Hashimoto’s)
autoimmune, own lymphocytes against thyroglobulin, thyroid peroxidase, or TSH receptor
cytokines and inflammation destroys the gland
diffuse enlargement, lymphocytic inflammation, germinal centers, Hurthle cell change
Hypothyroidism
Most common= Hashimoto’s
causes: infiltrative, infxn, dysgenesis, iodine def, iodine excess(Wolff-Chaikoff), drugs, lithium
viral=painful, self-limited
fibrous=hard and fixed, painless
Secondary: tumors, trauma, drugs, dopamine
Sx: fatigue, weight gain, constipation, hypothermia, periorbital puffiness, bradycardia
Dx: serum TSH
Tx: levothyroxine
Graves Disease
hyperthyroidism due to autoimmune which stimulates thyroid via TSI thyroid stimulating immunoglobulin
increased rad-I uptake uniform and bilateral
-irregular follicles, scalloped colloid
Hyperthyroidism (Thyrotoxicosis)
Sx: nervousness, palpitations, weight loss, heat intolerance, tremor, sweating, proptosis, tachycardia
Proptosis: eyeball extrusion due to antibody cross-react with muscles behind eye
pretibial myxedema: thickeneing of the skin, mucopolysaccharide deposition
-Graves
-Solitary toxic nodule
-Toxic multinodular goiter
Tx: Methimazole (blocks oxidation of iodine in thyroid), propylthiouracil (for pregnant), Iodide (pre-surgery), I-131 (thyroid destruction)
-Thyroid I uptake is low in destructive thyroiditis (give b-blocker)
Follicular adenoma (of thyroid)
benign, various appearances
most non-functional, but some can produce thyrotoxicosis
do NOT progress to carcinoma
have fibrous capsule, smaller follicles
Thyroid carcinoma
uncommon, more women
risk: ionizing radiation
Papillary: most common, BRAF mutation, younger age, lymphatic spread, good prognosis, nuclear features are key
Follicular: RAS mutation, older age, vascular spread, worse prognosis, invasion
Medullary: RET mutation, neuroendocrine parafollicular C-cells, secrete calcitonin, MEN-2, amyloid stroma
Anaplastic: p53 mutation, super bad, undifferentiated, distant metastasis, variable, pleomorphic
