wek 4- endo 1

Question 1

• Hypothalamus basic fxn:

Answer 1

o secrete hormones to ant pituitary thru portal vessels to control thyroid, adrenals, gonads, growth
o direct neural connection to post pituitary, storage for ADH and oxytocin

Question 2

• 1st, 2nd, 3rd endocrine dos:

Answer 2

o 1: originates in peripheral endocrine gland
o 2: dt ↑ or ↓stim by pituitary
o 3: dt ↑ or ↓stim by HTH

Question 3

• Hyper- and hypo-fxn of HTH:

Answer 3

o Hyper: ↑ stim by pituitary; hyperplasia/neoplasia of gland; ectopic hormone production (hormone-secreting neoplasia); exogenous hormone administration; auto-Abs (eg Grave’s dz)
o Hypo: ↓ stim by pituitary; AI, tumor, toxins, CA, vascular dos w/in gland; Genetic; Hormone resistance

Question 4

• Endocrine cc hx:

Answer 4

o Ssx mb insidious and nonspecific! 1+ glands mb involved, broad ssx: metabolism, growth, energy, sexual fxn
o HPI, ROS: HA, heat/cold intolerance, response to exercise, Changes in menses, erectile fxn, skin, vision, weight
o FHx endo dos, CA, AI

Question 5

• Endo cc PE, labs, image:

Answer 5

o PE: vitals, growth charts in kids, HEENT, genitalia exams, neuro/MSE
o Lab: peripheral & regulating hormone. Effects on circadian rhythms. Serum, urine, salivary samples. Dynamic testing (stimulation or suppression tests)
o Imaging: MRI or CT often needed, US, scans

Question 6

• Pituitary dos:

Answer 6

o Anterior: empty sella, hypofxn (apoplexy, infarction/Sheehan syndrome, dwarfism), hyperfxn (hyperprolactinemia, acrmegaly & gigantism), adenoma, other masses
o Posterior: Central DI (or neurogenic), hyperfxn (SIADH)

Question 7

• Empty Sella, 2 types

Answer 7

o radiographic finding; enlarged sella turcica not entirely filled w pituitary tissue
o 1st: defect diaphragm sella allows ↑CSF pressure to ↑ sella, compress and flatten pituitary (congenital or 2nd to injury); mb hormone def
o 2nd: mass (mb adenoma) enlarges the sella. →Hypopituitarism, or infarction. Pit tumor may secrete GH, prolactin, ACTH →hyperpituitarism

Question 8

• Empty sella epidem, ssx, image:

Answer 8

o F > M, obese, HTN, post-injury (surgery, head trauma, ischemia after childbirth)
o SSX: mb asx, HA, visual field defects. ↑ or ↓hormonal secretion
o Imaging: x-ray skull and MRI brain. mass > 1cm requires hormonal testing for ↑ or ↓secretion

Question 9

• Hypofunction of Ant Pit, causes

Answer 9

o Partial or total loss of anterior lobe fxn
o Causes: pit tumors (adenomas, CA), infiltrative lesions, cranio-pharyngiomas, sarcoidosis, arterial aneurysms, thromboses, postpartum shock (Sheehan’s), TBI, ischemic stroke, subarachnoid hemorrhage; HTH dos {mass, lung or breast CA mets, iatrogenic (radiation tx), infx like TB meningitis}

Question 10

• AP hypofxn ssx:

Answer 10

o depends on hormones affected
o GH def: ↓ serum glucose, mb asx in adult; In kids: → ↓ growth, maturation
o ↓ GN (LH and FSH) → ↓ sex fxn; F: amenorrhea, oligomenorrhea, ↓ libido, infertility. M: erectile dysfxn, testicular atrophy, ↓ libido, infertility
o TSH def: facial puffiness, bradycardia, cold intolerance. Newborn: cretinism
o ACTH def (Addison’s): fatigue, hypotension, intolerance to stress

Question 11

• AP hypofxn work-up:

Answer 11

o Labs: Hormones: 8am serum cortisol: > 3mcg/dl but lt 18 → measure ACTH (↓in hypopit); ↓cortisol & ↑ACTH = adrenal insuff
o ↓TSH, fT4
o GNs: M: ↓ T, LH. F: premenopausal w a/oligomenorrhea: Check FSH, LH, E2
o GH: ↓ IGF-1
o Provocative tests: GHRH, CRH, TRH, GnRH given together IV. Measure glucose, cortisol, GH, TSH, prolactin, LH, FSH, ACTH at intervals > 3 hrs
o Imag: CT or MRI
o DDX: anorexia nervosa, alcoholic liver dz, myotonia dystrophica, polyglandular AI dz

Question 12

• Pituitary apoplexy, ssx, PE, comp, dx, px:

Answer 12

o =Sudden hemorrhage of pit adenoma → edema and hypofxn
o SSX: sudden onset severe HA, stiff neck, visual field defects (bitemporal hemianopsia dt pressure on optic chiasm, diplopia dt pressure on occulomotor nerves)
o PE: ↓BP; HEENT, visual fields by confrontation
o Comp: really big → coma, death, esp ACTH, cortisol def → hypotension. Less severe: sudden hypopit sxs
o Dx: MRI; mb blood in CSF
o Px: spontanteously resolve or w surgical decompression

Question 13

• Pituitary Infarction, or Sheehan syndrome, path

Answer 13

o Aka: postpartum hypopituitarism or postpartum pituitary necrosis, dt hemorrhage & hypovolemic shock
o Path: 1) Hypertrophy and hyperplasia of lactotroph cells during pg → enlarged ant pit, w/o ↑blood supply
o 2) defect in ant pit ↓P portal venous system (post pit usu not affected dt direct arterial supply)

Question 14

• Sheehan ssx, work-up:

Answer 14

o SSX: mb asx; Severe (life-threatening): lethargy, anorexia, weight loss, inability to lactate. Less severe: failure to lactate, menses doesn’t resume, ↓ sexual hair
o Workup: full hx, PE
o Lab: serum hormones: May affect 1+ (→ panhypopituitarism); ↓ prolactin
o Imag: x-ray sella turcica (empty sella syndrome or tumor present); uss CT or MRI

Question 15

• Pituitary dwarfism (short stature)

Answer 15

o ↓ GH from pit or HTH dz. (may → ↓GH only or in panhypopit)
o Causes: Idiopathic, emotional deprivation, hereditary
o PE: plot body measurements Growth charts: ↓, w norm proportions = hallmark; ↓Height velocity; Puberty mb normal if def is GH, abn if panhypopit
o Lab/Dx: ↓ IGF-1 & GH (but st borderline norm)
o Imag: x-ray hands for bone age (delayed)
o DDX: usu genetic or dt physiological delay rather than GH def (familial, Constitutional Delay in Growth and Puberty CDGP, idiopathic short stature ISS)
o Pathologic: Undernutrition, Crohn’s, Celiac, Juvenile RA, CF, chronic kidney dz, skeletal dysplasias, hypothyroid, precocious puberty, Cushing’s

Question 16

• Hyperfunctioning Anterior Pituitary

Answer 16

o Adenomas over-secrete hormones (or commonly none): PRL, GH, ACTH
o SSX depend on hormones: usu 1 affected, rest are ↓. Mb ↑intracranial P sxs if a mass (check for papilledema)

Question 17

• Hyperprolactinemia

Answer 17

o Causes: mc adenomas, drugs (methyldopa, anti-depressants, cimetidine, phenothiazines, antihypertensives, opioids, methadone) stress, pg. ↑ Prolactin → inhibit LH/FSH secretion
o SSX: General: HA, visual change; Pre-m F: persistent lactation after pg, amenorrhea, menstrual abn, infertility, galactorrhea; Post-m F: HA, ↓vision; M: ↓libido, ED, infertility, gynecomastia, Osteopenia, mb galactorrhea
o PE: HEENT, visual fields, ssx of hypothyroid, hypogonad
o Lab: ↓ prolactin (N: 5-20; mb > 200ng/ml w tumors); If ↑: check E&P
o Imag: MRI (adenoma). DEXA (↓low bone mineral density)
o Tx: Depends on severity of ssx. DA agonist drugs (bromocriptine). radiation or surgery

Question 18

• Acromegaly and Gigantism

Answer 18

o ↑GH secretion: usu dt pit adenoma
o SSX: Kids (rare): ↑long bone growth → ↑ height (gigantism); Adults: suspect if (slow developing) macrognathia, ↑hands and feet (shoes, gloves, rings no longer fit); coarse facial features, upper incisors separate; CVD, sleep apnea, DM 2, HA, vision loss, carpal tunnel
o PE: Organomegaly, enlarged tongue
o LAB: ↑IGF-1; OGT fails to ↓GH to lt 2 ng/ml in 2 hrs
o Imag: X-ray: thick bone, ↑ sinuses, eroded sella, tufted phalanges, thick soft tissue; MRI pit (mb mass). If norm, Chest & abd CT for extra-pit GH-secreting mass
o Tx: Somatostatin analogs meds which block GH release. Pit surgery

Question 19

• Pituitary Adenoma

Answer 19

o Seen on MRI:
o Grade 0: intrapit microadenoma ( ≤ 1cm)
o Grade 1: intrapit microademoma, focal bulging of sellar wall
o Grade 2: intrasellar macroadenoma, diffusely enlarged sella, no invasion
o Grade 3: macroadenoma, localized sellar invasion
o Grade 4: macroadenoma, extensive sellar invasion/destruction
o tests for ↑ or ↓ hormones: PRL, IGF-1, fT4, Dexamethasome suppression test

Question 20

• Other pit masses

Answer 20

o cysts, mets, lymphocytic hypophysitis (lymphocytic infiltration often in late pg →HA and hypopit)

Question 21

• Central DI (or neurogenic) (vs. nephrogenic DI), etio, ssx:

Answer 21

o def ADH → ↑ dilute urine, ↑ thirst
o types: chronic, complete, partial, temporary; 1st or 2nd. mb ingest and excrete 5-30 L fluids/d w rapid dehydration if stop drinking!
o Causes: HTH or post pit dz (infx, tumors, vascular dos), idiopathic, familial, AI
o SSX: usu abrupt onset. Idiopathic: only polyuria ( > 3L/d), polydipsia, nocturia. 2nd: ssx of causative dz. Dry skin, dry mucus membranes, irritability

Question 22

• Central DI work-up:

Answer 22

o FHx, Hx renal dos
o PE: Tachycardia, weak pulse; neuro status, dehydration status
o Labs: Water restriction test: urine volume & osmolality every hr, plasma Na and Osm every 2 hrs (4-18 hrs); Norm: ↑plasma osm → ↓volume conc urine. DI: urine more dilute ( lt 200 mOsm/kg) than plasma (↑). Psychogenic polydipsia: both very dilute
o Other labs: FBG, UA: SG lt 1.005, no glucosuria; electrolytes: Ca, BUN, creatinine
o DDX: Polyuria: renal dos (nephrogenic polyuria), BPH, hyperglycemia; psychogenic polydipsia: emotional upset, little or no nocturia or nighttime thirst

Question 23

• SIADH (Syndrome of inappropriate secretion of ADH)

Answer 23

o = ADH secretion w/o appropriate stimulus
o Causes: stroke, head trauma, small cell carcinoma, drugs (SSRIs, methotrexate, opiates, NSAIDS, etc), pneumonia, HIV
o SSX: Lethargy, HA, difficult concentrate, gait disturbance, falls, N/V, coma, sz, fluid overload; Concomitant ssx of etio
o PE: Tachycardia, HTN, ↑weight
o LAB: ↓ serum Na, urine Na > 40mEq/L. U osm > serum ( U > 100mOsmol/kg). N serum K, acid-base balance, BUN, creatinine. mb screen for HIV
o Imag: CXR to r/o infx or mass, MRI to r/o CNS lesion
o DDX (↓ urine output): renal dz, urinary blockage, heart dz

Question 24

• Adrenal cortex hypofxn dos:

Answer 24

o 1st adrenal def (Addison’s)

o 2nd adrenal def w ↓cortisol

Question 25

• Primary adrenal def (Addison’s), etio, ssx, PE:

Answer 25

o Etio: 70% idiopathic (AI) atrophy of adrenal gland
o Other: gland destruction by viral infx, sarcoidosis, granuloma, neoplasm, amyloid, inflame, iatrogenic
o 4/100,000, all ages, sexes
o Tends to manifest w metabolic stress and trauma
o Ssx: Insidiously progressive. weak, fatigue, anorexia, N/V, diarrhea or constipation, abd pain, cold intolerance, dizzy, fainting, low resistance to infx/stress, salt craving, muscle or jt pn, gait disturbance, difficult concentrate
o PE: hypotension, ↓wt, signs of dehydration. Skin: hyperpigmentation (diffuse, mouth), vitiligo. Ear: auricular calcification (rare). Small heart in later stages

Question 26

• Addison’s labs:

Answer 26

o Electrolytes: Serun: ↓ Na+ & Cl-, ↑K (→ dehydration, ↓blood vol, hypotension, circulatory collapse), ↑Ca; Urine: ↑Na, ↓K
o ↓ am serum cortisol lt 3mcg/dl (hypotension, disturbed CHO, fat, protein metabolism). → ↑ACTH → hyperpigmentation, vitiligo
o Insulin hypersensitivity, hypoglycemia (FBG)
o ↓serum ALD
o CBC: mb anemia, eosinophilia
o ↑ BUN
o ↓ urine cortisol metabolites: ↓ 17-hydroxy-ketosteroids
o ACTH stimulation test (gold standard): IV cosyntropin, cortisol measured at baseline, 30, 60 min. if lt 18 mcg/dl, measure ACTH. If ↑: 1st adrenal insuff. If N/↓: adrenal insuff 2nd to pit insuff

Question 27

• Adrenal crisis:

Answer 27

o MEDICAL EMERGENCY! profound weakness, peripheral vascular collapse, renal failure/azotemia, pain in legs, back, abd
o Crisis usu dt infx, trauma, surgery, salt loss dt heavy sweating

Question 28

• Addison’s ddx:

Answer 28

o renal dz, diuretic use, SIADH and salt wasting nephritis. (All can cause ↓Na, usua assoc w edema but NO hyperpigmentation or ↑K)

Question 29

• 2nd Adrenal def w ↓cortisol:

Answer 29

o 2nd to ↓ACTH stim dt destructive adrenal or pit lesion or prolonged ( > 4 wks) suppression w cortisone
o SSX: like 1st, but no hyperpigmentation.
o Labs: ACTH stim test: N or ↓ ACTH. CMP (N K and BUN, mb ↓Na dt dilution). Low serum cortisol. mb ↓ thyroid and sex hormones
o Imag: MRI or CT

Question 30

• Adrenal cortex hyperfxn, dos:

Answer 30

o	Hypersecretion of 1+ adrenal hormones, compensatory or acquired
o	Congenital Adrenal Hyperplasia (CAH)
o	Cushing’s dz and syndrome
o	1st Hyperaldosteronism (Conn syndrome)
o	2nd Hyperaldosteronism

Question 31

• Congenital Adrenal Hyperplasia (CAH)

Answer 31

o Etio: Defects in cortisol hydroxylation w accumulation of cortisol precursors (21-hydroxylase def) → permanent ↑ACTH. ↑ or ↓ androgens depending on area of block
o SSX: F: masculinization of fetus in utero, ambiguous genitalia. M: “infant Hercules” syndrome. Children may grow rapidly, premature growth plate closure. Infants may have adrenal crisis as early as 2 wks dt salt loss
o Lab: ↑ serum 17-hydroxyprogesterone. ↑ serum/urine 17-ketosteroids, ↓17-OHCS, ↑T, also measure serum cortisol, androstenedione, DHEA

Question 32

• Cushing’s dz and syndrome

Answer 32

o Remember: Stress signals HTH to ↑CRH release → ↑ACTH from pit → ↑cortisol from adrenals (~ 20mg/d = ~2 mg/d cortisone). Some fxs of cort: ↑BG, mobilize fats and protein, potent anti-inflammatory
o Dz: ↑ ACTH → hyperpigmentation, 80% dt pit tumors or ectopic ACTH production (eg small cell lung CA), ↑endogenous cort
o Syndrome: usu dt long term tx w corticosteroids (↑exogenous cort); mb dt cort-secreting tumors but ↓ACTH dt feedback inhibition. NO hyperpigmentation

Question 33

• Cushing’s ssx, work-up, ddx:

Answer 33

o SSX: (usu present many yrs before dx) moon facies, plethora, buffalo hump, truncal obesity w skinny limbs, easy bruising, purple striae (abdomen, arms), poor wound healing, renal calculi, osteoporosis, glucose intolerance, abn menses, ↓ libido, psychiatric disturbances
o PE: Vitals: HTN. Abd: purple striae, truncal obesity. Skin: atrophy, acne, hirsutism. Cardio: mb cardiomyopathy
o Lab: ↑plasma and urine free cortisol (UFC) and metabolites (17-OHCS, 17-KS). ↑midnight salivary cortisol. CMP: Hyperglycemia, ↑ ALP, plts, cholesterol, TG. CBC: ↑ PMNs. ↓ACTH or undetectable. Dexamethasone suppression test (gold standard): (+) if plasma cort > 5mg/dL (fails to suppress)
o Imag: CT or MRI adrenals, CT chest/abd if ectopic ACTH production to r/o neoplasm of lung, kidney, pancreas. DEXA scan
o DDX for hypercortisolism: physical stress (infxs), obesity, PCOS, psych stress, psych dos, chronic alcoholism. Other: metabolic syndrome (HTN, DM, truncal obesity)

Question 34

• Primary Hyperaldosteronism (Conn syndrome)

Answer 34

o Remember: ALD retains Na, secrete K and H in DTs
o Etio: adrenal adenoma or adrenal hyperplasia → ↑ALD → ↑ intravascular vol, HTN. Na, DA inhibit RAAS (no ALD)
o SSX: hypervolemia, muscle weakness, paresthesias, transient paralysis, personality disturbances
o PE: high diastolic BP, neuro exam, MSE
o Lab: Hypokalemia, mild hypernatremia, hypokalemic alkalosis, hyperchlorhydria, Hyperglycemia, hypomagnesemia, ↓renin, glycosuria, ↑serum & 24hr urine aldosterone
o Imag: CT
o DDX: renal dz, myasthenia gravis, 2nd hyperaldosteronism, use of K-losing diuretics

Question 35

• 2nd Hyperaldosteronism

Answer 35

o Causes: massive hemorrhage, dehydration (severe V/D), renal dz, CHF, cirrhosis
o SSX: edema
o Labs: ↑renin, ↓ serum Na, ↑ ALD

Question 36

• Pheochromocytoma etio, ssx:

Answer 36

o Etio: Tumor of sympathetic ganglia or adrenal medulla, w ↑ catecholamines (epi, NE, DA). 5% have adrenal malignancy (esp if mult chain-like tumor). “Attack” mb precipitated by palpation of tumor, postural changes, abd compression, anesthesia, emotional trauma, beta blockers, micturation, tyramine foods, histamine
o SSX: sudden (sustained or paroxysmal) ↑ BP, severe HA, diaphoresis, flushing, cold clammy skin, angina, palpitations, tremor, N/V, epigastric pan, visual dos, dyspnea, paresthesias, constipation, panic attack-type sxs

Question 37

• Pheochromocytoma work-up, ddx:

Answer 37

o PE: Vitals: HTN, tachycardia, tachypnea, ↓ wt. appears hyperkinetic. mb papilledema
o Lab: Plasma free metanephrines (normetanephrines >2.5 pmol/ml or metanephrines > 1.4 pmol/ml). 24 hr urinary metanephrines: elevated VMA and HVA. Increased ESR, leukocytosis, hyperglycemia
o Imaging: Scintigraphy with iodine 131-I MIBG to localize extra abdominal mass; MRI of abdomen
o DDX: Severe stress response, Panic disorder, sympathomimetic drugs (cocaine, amphetamines, etc), hyperthyroidism, carbohydrate intolerance, hypoglycemia, labile hypertension

Question 38

• Hypoparathyroidism, etio, ssx, work-up:

Answer 38

o =hyposecretion of PTH leading to hypocalcemia
o Causes: decreased blood supply during thyroidectomy, or removal of the glands with thyroidectomy, congenital, autoimmune, idiopathic. May be associated with Addison’s disease.
o Other causes of hypocalcemia: vitamin D deficiency, decreased sun exposure, intestinal malabsorption, Vit D-dependent rickets, renal tubular disease, acute pancreatitis, hypoproteinemia, sepsis, magnesium depletion.
o SSX: may be asymptomatic. Tetany, numbness, tingling, carpo-pedal spasm, laryngeal stridor, seizure, psychiatric findings (depression, anxiety, confusion, psychosis)
o PE: hypotension. Skin: dry and course. Neuro: (+)Trousseau (inflate BP cuff over systolic for 3 min, watch for hand configuration). (+)Chvostek (tap CN7 at jaw → ipsilateral facial mm twitch) Cataracts; Papilledema if severe
o Lab: ↓serum Ca ( lt 8.5mg/d, lt 7 w tetany), ↓blood PTH, ↑ serum PO4, N ALP, Hypomagnesemia

Question 39

• Pseudohypoparathyroidism:

Answer 39

o dt end organ (kidney) insensitivity to PTH. ↓ stim effect of PTH on renal tubular Ca reabsorption
o Lab: hypercalciuria
o Risk nephrolithiasis

Question 40

• 1st Hyperparathyroidism

Answer 40

o ↑PTH secretion → ↑serum Ca, ↓PO4, bone resorption (osteitis fibrosa cystica)
o Causes: PTH-producing carcinoma (RCC), familial hypercalcemia, hyperthyroidism, Vit D or A intoxication, long term immobilization, sarcoidosis
o If dt parathyroid adenoma: mb other endo dysfxn w AD MEN syndrome.
o SSX: kidney stones, constipation, anorexia, N/V w abd pain and ileus, muscular weakness, renal impairment (nocturia, polyuria, polydipsia.), PUD and pancreatitis assoc w hypercalcemia. Severe: (serum Ca > 11-12mg/d): profound mental impairment, confusion, delirium, psychosis, sz, coma
o PE: abd, MSE, neuro
o Labs: ↑ serum Ca (ionized), ↓ PO4, N ALP, ↑Cl; ↑PTH-C terminal assay; ↑ Urine Ca and PO4, ↓ SG
o Imag: DEXA, X-ray (bone lesions), US parathyroid, US kidneys to r/o RCC
o DDX: myeloma (anemia, azotemia, ↑ Ca), hyperthyroidism, milk alkali syndrome (↑intake Ca), Addison’s,, renal failure, mets

Question 41

• 2nd hyperparathyroidism

Answer 41

o ↑PTH dt ↓serum Ca, (Eg, in renal dz)

o Labs: ↑Serum PO4, ↓Cl