ERM 1.1 Midterm

hypothalamus function? pineal gland?

• releasing/inhibiting hormones (CRH, GnRH, TRH, GHRH, DA) → ant. pit. → target endocrine gland → hormone into circ. → (-) feedback loop

  • body energy thermostat → integrate hormonal signal from gut + fat to maintain balance

  • NPY/AgRP (hunger) + POMC (satiety) systems

• melatonin → controls circadian rhythm + inhibit sec. of gonadotropins (LH + FSH)

pars intermedia products? pars nervosa? pars distalis?

• contain nissl bodies + herring bodies

• post. (neural ectoderm) → oxytocin (paraventricular) + ADH/vasopressin (supraoptic)

• ant. (rathke pouch) → FLAT PEG (FSH, LH, ACTH, TSH, prolactin, endorphin, GH)

primary vs secondary excess? deficiency?

• primary → inc. gland hormone (hypothalamus and pituitary low via -feedback)

  • deficiency = opposite

• secondary → inc. pituitary hormone (gland high and hypothalamus low)

  • deficiency = opposite

anterior pituitary hormone (GH, ACTH, prolactin) function?

• GH → IGF (inhibits GHRH + GH)→ muscle/bone formation, protein syn., dec. glucose uptake (adipose/muscle), neuronal survival, myelin synthesis

  • GH inhibited via somatostatin

  • GHRH stim. via sleep, hypoglycemia, stress

• stress → CRH → PVN sec. into HPS → corticotroph → ACTH

  • CRH + ACTH inhibited via cortisol

• dopamine + TRH (inc. via hypothyroidism)→ lactotroph → prolactin (dev. of mammary glands, syn. of milk) via inc. estrogen

  • prolactin inhibited via dopamine

  • prolactin inhibits GnRH → dec. FSH/LH

hypopituitarism?

• inadequate pituitary hormones leading to hormone deficiency

• craniopharyngioma, sheehan, empty sella syn. (Tx w/ hormone replacement)

craniopharyngioma cause? microscopy?

• compressive force (adenoma in adult)

• coronal MRI → expansive supra-sellular mass from rathke pouch remnants eroding surrounding structure

• microscopy → cystic space, squamoid cell nest, dystrophic calcification

sheehan syndrome (postpartum hypopituitarism) cause? symptoms? treatment?

• pregnancy induced infarction of pituitary gland (gland enlarges, but blood supply is same = lack of O2)

• amenorrhea + poor lactation, pubic hair loss, hypothyroidism, low BP, low blood sugar, breast shrinkage; shock

• Tx w/ lifelong hormone replacement therapy

empty sella syndrome cause? partial vs total? primary vs secondary?

• CSF in subarachnoid space herniates into sella turcica → appears empty = space enlarged w/ flat/shrunk gland

• less than ½ full of CSF + gland 3-7 mm; more than ½ full of CSF + gland 2 mm or less

• PES (no identified cause); SES (via cerebral trauma + pp pit. necrosis, post. pit. surgery, etc.)

somatotroph and lactotroph stain? thyrotroph, corticotroph, and gonadotroph?

• somatotroph (GH, PIT-1) + lactotroph (prolactin, PIT-1 + ERa) → acidophilic (attract acid) = yellow on masson’s trichrome + pink on H&E

• thyrotroph (TSH, PIT-1 + GATA2), corticotroph (ACTH, TPIT), gonadotroph (LH, FSH, GATA2, SF1, ERa) → basophilic (attract basic) = pink on masson’s trichrome + blue on H&E

null cell adenoma hormone? symptoms? labs? treatment?

• none

• mass effect → headache, nausea, vomit, bitemporal hemianopsia, cavernous sinus syndrome

• Dx w/ MRI of pit. gland for tumor

• surgery + chemo, pit. hormone replacement

pinealoma hormone? symptoms? labs? treatment?

• melatonin

• benign or malignant; high melatonin = messed up sleep cycle + precocious puberty

• N/A

gonadotroph adenoma hormone? symptoms? labs? treatment?

• FSH + LH

• ovarian hyperstimulation → ovarian cyst, infertility, amenorrhea, endometrial hyperplasia

• Dx w/ rare hormone secretion; might have high LH, FSH + a subinit

• Tx w/ surgery + chemo

cushing disease hormone? symptoms? labs? treatment?

• ACTH

• corticotroph adenoma (= inc. ACTH); high cortisol effect (inc. BIG, dec. FIB)

• Dx w/ high ACTH + cortisol, pit. MRI, +PAS, +DST

• Tx w/ ketaconazole, fluconazole (steroid syn. inhibitors)

hyperthyroidism hormone? symptoms? labs? treatment?

• TSH

• high body temp., high HR, high met. rate

• Dx w/ high TSH (2ndary), T4+T3 (primary), pit. MRI

• Tx w/ methimazole, propylthiouracil (PTU) (thiomides)

prolactinoma hormone? symptoms? labs? treatment?

• prolactin

• women → amenorrhea via dec. GnRH, LH, FSH; galactorrhea, infertility, low libido, dec. bone density

• men → gynecomastia, erectile dysfxn, infertility, low libido, dec. body/facial hair

• Dx w/ high prolactin → inhibit GnRH → dec. FSH + LH; TFs: ERa, PIT-1

• Tx w/ bromocriptine or cabergoline (dopamine agonist)

kallman syndrome hormone? symptoms? labs? treatment?

• GnRH

• Dx @ puberty → lack sexual dev. = hypogonadism, incomplete sexual mat., anosmia

• Tx w/ hormone replacement therapy

gigantism hormone? symptoms? labs? treatment?

• GH

• high HGH b4 puberty (>97th percentile) → impaired glucose tolerance/diabetes

• Dx w/ high serum IGF1, -oral glucose tolerance test (OGTT), pit. MRI

• Tx w/ surgery + chemo, octreotide or lanreotide (somatostatin), cabergoline (dopamine)

acromegaly hormone? symptoms? labs? treatment?

• GH

• high HGH after puberty → enlarged hands feet, jaw, organs; inc. hat size, nose/eye ridge, HTN impaired glucose tolerance/diabetes

• Dx w/ high serum, IGF1, -oral glucose tolerance test (OGTT), pit. MRI

• Tx w/ surgery + chemo, octreotide or lanreotide (somatostatin), cabergoline (dopamine)

dwarfism hormone? symptoms? labs? treatment?

• GH

• low HGH b4 puberty (<3rd percentile) → can be via turner syndrome

• Dx w/ low serum IGF1, -insulin tolerance test (ITT)

• Tx w/ somatropin (synthetic GH)

primary polydipsia hormone? symptoms? labs? treatment?

• ADH/vasopressin

• drink excessive water (via psych illness or hypothalamic lesion) → polyuria, polydipsia, dilute urine, serum hypoNa

• Dx w/ (+)water deprivation test (= inc. urine osmolality)

• Tx underlying disorder

central diabetes insipidus hormone? symptoms? labs? treatment?

• ADH/vasopressin

• dec. ADH prod. (tumor, trauma) → polyuria, polydipsia, dilute urine, serum hyperNa

• Dx w/ (-)water deprivation test + (+)desmopressin test (= inc. urine osmolality)

• Tx w/ desmopressin (ADH analog)

nephrogenic diabetes insipidus hormone? symptoms? labs? treatment?

• ADH/vasopressin

• dec. V2 receptors, renal resistance to ADH, Li/demeclocycline → polyuria, polydipsia, dilute urine, serum hyperNa

• Dx w/ (-)water deprivation test + (-)desmopressin test (both minimal)

• Tx w/ low salt/protein diet, NSAIDs + diuretics (thiazides) → paradoxical

SIADH hormone? symptoms? labs? treatment?

• ADH/vasopressin (via HEELD)

• inc. ADH → oligouria, euvolemia, serum hypoNa, cerebral edema (=neuro dysfxn, headaches, nausea)

  • body responds w/ dec. aldosterone + inc. ANP/BNP = inc. Na urinary sec.

• Dx w/ low urine output, low serum osmolality, high urine osmolality, high urine Na conc.

• Tx w/ conivaptan or tolvaptan (ADH antagonist), fluid restriction (1st line) + hypertonic IV

mecasermin MOA, indication, AE?

• recombinant IGF-1

• IGF-1 deficiency that is not responsive to exogenous GH

• hypoglycemia, intracranial HTN, hepatotoxicity

somatotropin MOA, indication, AE?

• recombinant GH

• dwarfism → GH deficiency, wasting in HIV infection, short bowel syndrome

• pseudotumor cerebri, slipped capital femoral epiphysis, edema, hyperglycemia + progression of scoliosis

octreotide, lanreotide MOA, indication, AE?

• somatostatin agonist, inhibits GH production

• acromegaly, esophageal varices (GI bleed), carcinoid tumor (flushing, diarrhea, vomiting)

  • dec. portal venous pressure + blood flow

• gallstones, bradycardia, cardiac conduction problems

pegvisomant MOA, indication, AE?

• blocks GH receptors (ameliorates effects of excess GH production)

• acromegaly (alt. to octreotide or lanreotide)

• hepatotoxic, monitor pituitary adenoma growth

leuprolide MOA, indication, AE?

• GnRH agonist

  • intermittent admin → inc. LH + FSH sec.

  • continuous admin → dec. LH + FSH sec.

• ovarian suppression, controlled ovarian stim., central precocious puberty, prostate cancer, endometriosis, breast cancer

• headache, nausea

ganirelix MOA, indication, AE?

• blocks GnRH receptors, reduce endogenous LH, FSH

• prevent premature LH surge during controlled ovarian stim

• headache, nausea

follitropin alpha MOA, indication, AE?

• act. FSH receptors

• controlled ovarian stim., infertility due to hypogonadotropic hypogonadism in men

• multiple pregnancies, gynecomastia in men

hCG MOA, indication, AE?

• agonist at LH receptor

• MHH, initiation of final oocyte maturation and ovulation during controlled ovarian stim.

• depression

bromocriptine, carbergoline MOA, indication, AE?

• act. dopamine D2 receptors, suppress prolactin + GH

• prolactinoma, acromegaly, PD

• GI, orthostatic hypotension, psychosis, vasospasm

oxytocin MOA, indication, AE?

• act. Gq-IP-DAG Ca

• uterine tone, induce labor, PPH

• fetal distress, uterine rupture

desmopressin MOA, indication, AE?

• ADH analog → V2 agonist, Gs-cAMP

• central DI, enuresis, hemophilia A + von willebrand disease

• GI, hyponatremia

conivaptan, tolvaptan MOA, indication, AE?

• ADH antagonist → V1 + V2 antagonist

• SIADH → hyponatremia

• infusion rxn

thyroid hormone synthesis? screening? 2nd messengers?

• TRH → TSH → active iodide uptake via NIS + forms TGB → iodine (in lumen via TPO) + tyrosine on TGB in lumen = iodination/organification (via TPO) → iodotyrosine = MIT + DIT → T3/T4

• TSH → useful for thyroid disorders

• TRH → IP3, TSH → cAMP, T3/T4 → IC receptor

how to administer thyroid hormone? changes in populations? how to monitor dose?

• T4 alone > mix of T3/T4 (T4 converted to T3 in target cells/liver/kidney + T3 more potent)

• start low/gradual dose inc. in elderly → CVS (thyroid hormone inc. myocardial O2 demand → induce arrhythmias, angina pectoris, MI)

• pregnancy = higher demands (inc. TBG)

• children > adults dose

• monitor T4 + TSH levels; if TBG altered → dose adjustment

graves category? etiology? symptoms? labs?

• hyperthyroid

• TSI antibodies (TSAb) bind TSHR, mimics TSH

• exophthalmos, pre-tibial myxedema (via T cell activated fibroblasts = GAG release), fever, delirium, tachycardia

  • thyroid storm (untreated hyperTH → inc. catecholamines)

• dec. TSH, inc. T3/T4, RAIU (speed of iodine uptake) = diffuse

toxic multinodular goiter (TMG) category? etiology? symptoms? labs?

• hyperthyroid

• goiter w/ nodules → abundant follicular cells

• asymptomatic + discovered incidentally

• dec. TSH, inc. T3/T4, RAIU = patchy

subacute (deQuervain) category? etiology? symptoms? labs?

• hyperthyroid

• post-viral granulomatous inflammation

• painful goiter, transient hyper- → hypothyroidism

• inc. ESR, dec. RAIU

hypothyroidism category? etiology? symptoms? labs?

• hypothyroid

• primary (autoimmune, iodine def., post-ablation) vs 2ndary (pituitary or hypothalamic failure)

• fatigue, weight gain, cold intolerance, hoarseness, myxedema, carpal tunnel syndrome

• inc. TSH, dec. T3/T4

  • 2ndary = dec. TSH, dec. T3/T4

hashimoto thyroiditis category? etiology? symptoms? labs?

• hypothyroid

• autoimmune (anti-TPO or anti-TG), hurthle cells w/ extensive lymph filtration

  • variant → silent lymphocytic thyroiditis (hyper)

• fatigue, weight gain, cold intolerance, hoarseness, myxedema, carpal tunnel syndrome

• inc. TSH, dec. T3/T4

congenital hypothyroidism category? etiology? symptoms? labs?

• hypothyroid

• thyroid dys(hormono)genesis → iodine def.

• intellectual disability, coarse features (cretinism); 6Ps (poor brain dev., protuberant tongue, pot belly, protruding umbilici, pale/puffy face)

• inc. TSH, dec. T3/T4

riedel thryoiditis category? etiology? symptoms? labs?

• euthryoid (inc. TH → dec. TH)

• extensive fibrosis w/ lympocytic infiltration

• hard/fixed goiter, compressive symptoms, hoarseness

• normal TSH + T3/T4

hyperparathyroidism category? etiology? symptoms? labs?

• parathyroid

• primary → adenoma, hyperplasia, carcinoma

  • inc. PTH, inc. Ca, dec. Ph

• 2ndary → CKD + vitD def.

  • inc. PTH, dec. Ca, inc. Ph

• stones, bones, groans, psychiatric overtones (inc. Ca primary)

hypoparathyroidism category? etiology? symptoms?

• parathyroid

• surgical injury, autoimmune, digeorge

• tetany/cramps, +chvostek/trousseau, elongated QT

• inc. PTH, dec. Ca, inc. Ph

pseudohypoparathyroidism category? etiology? symptoms?

• parathyroid

• end-organ resistance to PTH

• short stature, round face, brachydactyly

• inc. PTH, dec. Ca, inc. Ph

levothyroxine (T4), liothyronine (T3) class? MOA? indications? AE?

• thyroid hormones

• act. nuclear receptors → inc. RNA formulation, protein synthesis

• hypothyroidism

• hyperthyroidism, levothyroxine (empty stomach w/ water)

propylthiouracil (PTU), methimazole class? MOA? indications? AE?

• thioamides (delayed onset)

• PTU (prevents T4 → T3), Met (inhibit TPO organification, iodotyrosine)

• hyperthyroidism (avoid met during pregnancy, PTU ok)

• hypothyroidism, nausea, GI disturbance, rash, hepatotoxic (PTU), agranulocytosis

radioactive iodine class? MOA? indications? AE?

• radioisotopic

• radiation-induced destruction of thyroid parenchyma → emits B-particles

• hyperthyroidism; pts should be on euthyroid or B blockers b4; avoid in pregnancy and nursing

• hypothyroidism, sore throat

potassium iodide-lugol solution class? MOA? indications? AE?

• iodides (acute onset)

• inhibit iodine organification + hormone release

• dec. size/vascularity of thyroid prior thryoidectomy

• avoid b4 radioactive treatment bc thyroid will absorb iodine instead of radiation

propranolol class? MOA? indications? AE?

• B-blocker (rapid onset)

• inhibits B receptors + T4 → T3 conversion

• thyroid storm, adjunct to control tachycardia, HTN, A-fib

• asthma, AV blockade, hypotension, bradycardia

thyroglossal duct cyst characteristics? management?

• midline neck; can cause 2ndary infection, abscess, rare papillary carcinoma

  • histology → pseudostratified ciliated or squamous epithelium; thyroid follicles in wall

• surgical excision

branchial cleft cyst characteristics? management?

• lateral neck; congenital anomaly, not thyroid-derived; can cause 2ndary infection

  • histology → squamous or ciliated columnar epithelium; lymphoid tissue

• surgical excision

heterotopic thyroid tissue characteristics? management?

• ectopic thyroid tissue (normal histology), often lingual → mass effect → dysphagia, airway obstruction

  • absence of normal thyroid gland

• surgery + hormone replacement

thyroid nodule characteristics? diffuse goiter? multinodular goiter?

• discrete swelling, mostly benign

• iodine def. → enlarged thyroid/follicles filled w/ colloid → compression → swallow/resp. issues

• from long-standing goiter → more irregular enlargement → hyperthyroidism, plummer syndrome

thyroid nodule, diffuse goiter, and multinodular goiter management?

• FNA for evaluation

• iodine supplementation

• surgery if symptomatic

follicular adenoma characteristics? management?

• encapsulated neoplasm penetrating into follicular cells/surrounding thyroid; benign, non functional

  • hurthle cell adenoma (oncocytic): variant → eosinophilic granular cytoplasm w/ small round nuclei

• FNA, observation, lobectomy

follicular carcinoma characteristics? management?

• same as adenoma but w/ capsular/vascular invasion + hematogenous spread (bone, lung, liver) = malignant

• thyroidectomy + radioactive iodine

papillary carcinoma characteristics? management?

• via BRAF or RET mut., involves lymphatic spread; recurrence but good prognosis

  • histology → papillae, ground glass/orphan Annie nuclei, psammoma bodies (concentric calc.), nuclear inclusions

• thyroidectomy + radioactive iodine

medullary carcinoma characteristics? management?

• C cell neuroendocrine tumor; ass. w/ RET mut. or MEN2A/2B + FMTC syndromes

  • histology → polygonal cells; amyloid; calcitonin + CEA sec. → paraneoplastic syndromes

• thyroidectomy; RET-targeted therapy

anaplastic thyroid carcinoma characteristics? management?

• from PTC or FTC; hoarseness; pleomorphic spindle cells; undifferentiated/aggressive → rapid prog., fatal

• surgery, radiation, chemo

teriparatide MOA, use, AE?

• acts through PTH receptors → inc. bone formation

• osteoporosis, hypoPTH

• hypercalcemia, hypercalciuria

cholecalciferol, calcitriol MOA, use, AE?

• regulated gene transcription via VitD receptor to produce effects

• osteoporosis, VitD deficiency, osteomalacia, psoriasis, hypo parathyroid, 2nd + tertiary hyperPTH

• hypercalcemia, hyperphosphatemia, hypercalciuria

calcitonin MOA, use, AE?

• inhibits bone resorption

• osteoporosis

• rhinitis

calcium, phosphate MOA, use, AE?

• bone mineralization

• osteoporosis, osteomalacia, Ca + P deficiencies, hypoPTH

• constipation

alendronate (bisphosphonate) MOA, use, AE?

• inhibit osteoclast mediated bone resorption

• osteoporosis, paget’s disease

• esophageal irritation, ONJ

denosumab MOA, use, AE?

• binds RANKL, prevent it form stimulating osteoclast diff. and fxn; mimics OPG

• osteoporosis, hyperparathyroidism

• osteonecrosis of the jaw, risk of infeection

raloxifene MOA, use, AE?

• estrogen agonist effect in bone + antagonist in breast and endometrium

• osteoporosis in postmenopausal women

• hot flashes, thromboembolism

cinacalcet MOA, use, AE?

• activates Ca sensing receptors (dec. PTH + Ca)

• hyperparathyroidism + osteolysis

• hypocalcemia