Endocrinology 5

15 % of skel mass; verts, pelvis, skull; majority of cancellous bone (most of Ca efflux from this); 80 % of metabolic activity

85 % of skel mass; long bones; majority of cortical bone; 20 % of metabolic activity

serum Ca >10.5 mg/dL; altered mentation, N/V; polyuria, polydipsia, stones

accel bone resorption by osteoclasts (PTH, 1,25 (OH)D, IL-1, IL-6, TNF-alpha); enhanced GI absorption of Ca (vit D); hypercalcemia represents eclipsed renal capacity to excrete Ca load ( ie, hypercalciuria also present)

inc skeleton resorption (primary hyperPTH; malig); inc GI absorption (milk-alk syn); both inc skel resorp & GI absorption (granulomatous: sarcoid, TB, fungal);

Bones, stones, moans & groans

more recently, less about stones & bone dz, more asymptomatic

Tx underlying cause; enhance calciuresis: Fluids (2-3 L / day po for mild; IV saline for severe / Ca > 13); loop diuretics (only after volume repletion); furosemide

bisphosphonates (pamidronate IV; zoledronic acid for malig-related hypercalc); calcitonin (transient benefit d/t tachyphylaxis); cinacalcet; Last line: plicamycin, gallium nitrate

Glucocorticoids (prednisone; solumedrol)

twitching of face and upper lip in response to tapping inferior to TMJ joint

inflate BP cuff, leave it there; pt gets carpal spasm

No; measure 25-OH D

tetany, twitching, paresthesia; Chvostek sx; Trousseau sx; seizures; laryngo or bronchospasm; long QT; arrhythmia; hypotension

ectopic calcification (basal ganglia); EPS; parkinsonism; dementia; cataracts; abnml teeth; dry skin

surgically induced hypoPTH

Vit D (25 OH D deficiency): Calcium (2000-4000 mg/day); ergocalciferol / cholecalciferol if 25 OH D deficient; Calcitriol if 25 OH D sufficient

Defective bone matrix mineralization d/t: inadequate Ca & phosphorus; deficient mineralizn mechm in presence of normal Ca / phosphorus

rickets

diffuse bone pain (esp pelvis), waddling gait, mx weakness, fractures & pseudofractures (Looser’s zones) of long bones, ribs, pelvis

Vitamin D disorders; Hypophosphatemia (inherited disorders); Mineralization disorders

Vitamin D (25 OH D def): Ca (1500-2000 mg/day); ergocalciferol (D2-Drisdol) cholecalciferol (D3); Calcitriol (for hypophosphatemic osteomalacia)

Localized disorder of bone remodeling

inc bone resorption (giant multicellular osteoclasts); bone formation and mineralization is normal, though of irregular woven type

pelvis, femur, spine, skull and tibia

pain, bowing, fracture, HA, hearing loss; elevated alk phos (hallmark); bone turnover markers often elevated

Inhibit osteoclast resorption/ bone formation: bisphosphonates; calcitonin

T4

T3

most is pro-bound; unbound = regulator for negative feedback inhibition mechanism

O2 consumption CHO & protein metabolism, electrolyte mobilization & conversion of carotene to Vitamin A; also lipid synth & metab

Hypo: dec insulin req, inc chol/TG; hyper = inc insulin req, dec chol/TG

amt serum T3 & T4 (not physiologic thyroid status, which is affected by free hormone)

directly or by T3 uptake

Estrogens (inc serum TBG, so low T3 uptake value)

Androgens or adrenocorticosteroid, low protein states (nephrotic syndrome or hepatic failure): dec serum TBG, so high T3 uptake value

indirect measure of pt’s Total T4; the higher the T3 uptake, the higher the pt’s T4 level

Hyper: high T3 uptake; hypo: low T3 uptake

total T4 x T3 uptake; FTI low: hypo; FTI high: hyperthyroid

FTI (takes into account both absolute hormone level & binding capacity of TBG)

Depressed TSH; Elevated FT4, T3 Uptake, FTI

Elevated TSH; Depressed FT4, T3 Uptake, FTI

Sl low TSH; Free T4 nml or sl high; low T3 Uptake

TSH variable; Total T4 low to normal; Elevated T3 Uptake

entire thyroid-pituitary-hypothalamus feedback loop

primary hypopituitarism & states of altered thyroid homeostasis

IgG Ab vs thyroid cell TSH rec's; 78% Graves pts are pos; test to monitor tx; titers rise with relapse

euthyroid sick syndrome

USPSTF: no recs; ATA: TSH screen start at 35 yo & q5 yrs (sooner if risk factors or sx)

autoimmune thyroiditis

autoimmune thyroiditis

small goiter (decreases w/thianamides); FT3 predominance; neg TSI titer

exercise, hypoglycemia hi protein diet, acute starvation & oral contraceptives (secondary to estrogen)

obesity & corticosteroid therapy

CT or MRI of brain to evaluate sella turcica

GH on fasting AM samples (often not diagnostic); GH Stimu tests (hyperglycemia normally suppresses GH secretion); GH remains elevated in acromegaly

pit tumor (1/3); pit damage (1/3); Pure GH deficiency (1/3)

Useful to compare IGF-1 levels to GH; IGF-1 is low whenever GH is deficient; IGF1 more stable than GH; mediate GH fx on sk mx

nutrition (low levels in malnutrition)

automatic/constant unless inhibited

Prolactinomas

rarely measured directly (d/t lability)

Alters the permeability of renal collecting tubules to water; Causes vasoconstriction

285 mOsm/L

Hypothalamic origin; ADH production or release is deficient

Kidneys fail to respond to normal or even elevated levels of ADH

usually unmeasurable; 2.3-3.1 pg/mL

urine osmo: <300 mOsmkg (nml pt; ovenight urine is ≥800)

Central DI: urine osmo will increase; Nephrogenic DI: urine osmo will not change

excessive levels of ADH active material of non-pituitary origin

low serum osmolality, low serum sodium & high urine osmolality

DI: H2O deprivation; SIADH: water loading test

(1L H2O; hourly urine/serum x 5 hrs) Normal: urine osmo < serum osmo; SIADH: urine osmo > serum osmo

can measure Ca, PO4, Mg, PTH directly; Alk phos assoc w/osteocyte activity (higher in growing kids, M>F, or mets)

responsible for absorption of dietary calcium & phosphate in intestines; enhance PTH fx on mobilization of skeletal Ca & PO4

can directly measure Vit D & metabolites

IGF’s mediate the effect of GH on skeletal muscle

zona glomerulosa

reabsorption of sodium and excretion of potassium; prevention of hypovolemia & hyperkalemia

counters fx of insulin; anti-inflam

in AM; in stress & exercise

AKA Addison dz; all 3 zones of adrenal (so potl insuff of cortisol & aldost)

considering the abruptness of disease onset

Adrenal hemorrhage, necrosis, thrombosis; meningococcal sepsis (Waterhouse-Friderichsen Syn); pseudo; coag dz; mets ca w/ bleed

Auto-immune Adrenalitis; infxs Adrenalitis; Mets ca; congenital Adrenal Hyperplasia (CAH); Adrenomyeloneuropathy

Hyperpigmentation (due to xs ACTH); Salt craving; Hyponatremia; Hyperkalemia; Vitiligo, pallor; auto-immune thyroid dz; CNS sx in adrenomyeloneuropathy

Pit tumor / surgery / rad; Craniopharyngioma ; Isolated ACTH def; Megace (glucocorticoid-like action); LT g’corticoid tx; Sarcoidosis; Hypothalamic tumor

>18: r/o AI; <3: R/I AI; btw this range: need dynamic testing

250 mcg Cosyntropin; measure cortisol before & 30 & 60 min after injxn; pre or post >18: R/O AI

AM cortisol (low); ACTH stim (low); plasma ACTH (>100: primary AI) (nml: 5-45 R/O primary AI; find cause of secondary/tert AI)

Tx HYPOTENSION w/ volume (2 to 3 L of NS or D5NS); Give IV DEXAMETHASONE 4mg or IV HYDROCORTISONE 100mg (Dex preferred bc it won’t interfere w/ further dx testing & is long acting)

Hydrocortisone 20mg AM / 10mg PM; Dex; prednisone

aldosterone: Fludrocortisone; check for postural HypoTN, orthostasis, serum K, renin; poss inc dose summer (inc persp Na loss) & dec dose in HTN (do not d/c altogether); NO K sparing diuretics for anti-HTN Rx

Give pre-op hydrocortisone / continue 24 hrs; cut dose by 50% after first 24 h; cut dose by 50% each day until return to maint level (small procedures: give single dose of HC IV before procedure)

Adrenal lesion: next step is adrenal CT; exogenous source; Plasma ACTH level is low (< 5 pg/mL)

Plasma ACTH level is normal or high (>15 pg/mL); Either ectopic production OR Pituitary adenoma = Cushing dz

CRH-Stimulation test; HD Dex suppression; Petrosal Sinus Sampling; Octreotide scintigraphy to localize ectopic source; MRI

Surg Resection; Transphenoidal microsurgical removal (if sure Cushing dz); Bilateral Adrenalectomy (uncommon); Pharmacologic adrenal blockade

Idiopathic (Familial); PCOS; Androgen-secreting adrenal adenomas or carcinoma; Ovarian tumors; Glucocorticoid resistance

Congenital Adrenal Hyperplasia; ACTH-dependent Cushing Syn

>2.0 common

Rare; high serum androgen conc remain elevated despite Dex suppression

More common than adenomas

usu > 5 cm at dx; Very high DHEA, DHEA sulfate; No response to HD Dex Suppression

Serum testost (total & free); androstenedione (>1000: ovar adrenal neoplasm); DHEAS (>700: adrenal source of androgen xs; Need adrenal CT to detn if hyperplasia or ca)

Pelvic Exam & US; Abd CT (esp adrenal glands/ fine cuts): adenoma / ca / hypertrophy

Enzyme defects in adrenal steroid hor synth -> insuff cortisol +/-mineralocorticoid; classically with an assoc androgen excess

Salt-wasting form; Virilizing Syndromes

Late-onset: women = hirsutism & menstrual irreg which can mimic PCOS; Men/boy: androgen excess can be asymptomatic

Stop any offending meds; Med tx options; Interventional tx options (Postmeno F can undergo lap bilat oophorectomy, if scans are nml; small hilar cell tumors of ovary may not be visible on scans

Oral Contraceptives (beware DVT); Metformin; Anti-androgen ( if NOT PG): Aldactone (spironolactone), Finasteride, Flutamide

Hypertension; Mx Sx (d/t hypokalemia): cramping, weakness, periodic paralysis; Often few clinical findings at all (often suspected after lab abnormalities)

Chem7 (Hypokalemia, Metab alkalosis); Serum renin & aldosterone ( Aldo/renin ratio >20 is suspicious); 24-hr urine aldost (high in setting of low renin (<5mcg/dL) suspicious); Saline-loading; 18-OH corticosterone

indicative of aldosterone producing adenoma (APA)

Abd CT (esp of adrenals); Adrenal vein sampling: for localization (cath of left an&d right adrenal veins & the IVC, looking for lateralization of elevated aldosterone level

S/b off Aldactone; CCB; ACEI (consider in-house eval); At least 150mEq of sodium intake daily (to suppress aldosterone prodn)

APA (Conn’s); Bilateral Hyperplasia of the Zona Glomerulosa (if bilat, need remove both); Primary adrenal hyperplasia; Adrenal carcinoma

surgical (effective only in patients with unilateral disease)

med tx: Mineralocorticoid receptor antagonists: Spironolactone (DOC) or Eplerenone; CCB; ACEI

dz of adrenal medulla (site of catecholamine prodn)

pain; pallor (ortho hypoTN); palpitations; pressure (HTN); perspiration

10% of dz are: extra-adrenal; bilateral; familial; malignant; not assoc w/ HTN

24 hr urine (for Catecholamines & Metabolites: Metanephrines / VMA); Serum metanephrines/ plasma catecholamines; Imaging

Alpha Adrenergic-Blockade first; Beta-blockade next if nec; NEVER start before alpha-blockade (can lead to worsened hypertensive crises); CCB (may be better tolerated than alpha-blockade)

Surgical resection is tx of choice (May req open lap); Need adequate a-blockade pre-op; Watch for post-op comps(Labile BP; Post-resection hypoTN/ shock; Hypoglycemia)

inc by estrogen, decreased by androgen

Severe illness or starvation decrease total T3 and free T3, increase rT3, no change of free T4 (euthyroid sick syndrome)

131-Iodine Uptake; Measured at 24 hours; Normal 15-30%

Thyroid scan (99m Tc); US (good for nodules); CT; MRI; PET

Auto-antibody reacting with the TSH receptor (TSI, 80-95% pos)

Symmetric non-tender goiter (80%) (bruit is pathognomonic); Ocular findings (30%); Pretibial myxedema; TSH, Free T4, Free T3; Thyroid uptake and scan

de Quervain’s

Hashitoxicosis

hyperthy (1-3 mo); then hypothy (1-3 mo); then euthyroid

2% of US F (0.2% US M); 1 in 4000 newborns

Primary; goitrous; central

cytotoxic anti-thy Ab's (80-90% antithyroglobulin); >50 yo

multicell autonomic fn

>50 yo; lg irreg nod thy; TSH, FT4, FT3, uptake & scan; Rx RAI

activation of TSH receptors via rec gene mutation

30-40 yo; lg irreg nod thy; onycholysis; TSH, FT4, uptake & scan; Rx RAI

TH leak d/t viral infxn -> thy gland destn

Fever; lg irreg very tender thy; TSH, FT4, FT3, thyroglobulin, ESR, uptake & scan(result: zero)

ASA/ NSAIDs; prednisone

transient autoimmune dysfn (often post-partum); sudden onset of hyperthyroid

lg nod thy; TSH, FT4, FT3, anti-thy Ab (30%), uptake & scan; Rx beta blocker

Osteoporosis; Inc cardiac contractility; Inc risk of A-fib; Allergic rxn dye in tablets

2-4% prev in iodine-sufficient areas; F 5-15 x M; multifactorial; genetic cause?

thyroxine suppression of TSH; surg if obstruction

benign hx; s/s hypo or hyper; tender nod; FH hypo, nod, or goiter

TSH; US (80%); FNA. Scan = no value

PTU (esp for PG/BF)(TID); Tapazole (qd)

T3 drug

inc cardiotoxicity risk

Unpredictable hormonal stability; allerg rxn risk; Lacks bioequivalence among brands

17 weeks

6 wks (w/fewer AE)(QD dosing, so better compliance than PTU TID)

Benign rash; potl agranulocytosis; hepatotoxicity

pts with obstructions, malignancy, pregnancy in 2nd trimester, or those with contraindications to RAI or thioamides

radioactive I ablation (CI in PG)

beta-blockers; c'steroids (dec action of thy hormone & imm response in Graves); Iodine (blocks thy hor release)

take as soon as remember. Double up doses if necessary!

PTU; Propranolol; Corticosteroid; Iodide; Supportive measures; mortality 20%

Emergency: elderly in winter; Hypothermia; Resp depression; Unconsciousness

stat IV levothyroxine; then check labs

Liotrix 4:1; thyroglobulin 2.5:1; armour = not consistent

<45 yo 100%; > 45 or LT/severe dz 50%; CVD or >65 25%; PG: inc dose by 50%

TT4 & FTI after 4-6 wks; after change in tx; then q 6-12 mo (for RAI: TSH/FT4 qmo)

24 hr urine cortisol (AKA urine free cortisol)

24 hr urine cortisol

5 mL (frozen, fridge, or preservative) within 4 hr of collection

High: Addison; low: secondary AI

Cushing dz; Addison; ectopic ACTH-producing tumors

adrenal tumor; steroid medication; hypopituitarism

Low cortisol; Hyperkalemia; Hyponatremia; Elevated BUN; Hypoglycemia

24 hr urine cort; Dex suppression test; high PM cortisol

Plasma ACTH level; HD Dex supp test; CRH stimulation test; Imaging (CT, MRI, US)

More common than primary; usu d/t renal artery stenosis (curable by surg/angioplasty)

levels rise following assumption of an upright position

tumor or hyperplasia of adrenal cortex

look for calcifications (poss d/t TB)

evaluate the size & shape of the adrenal glands & pituitary

detn cause of Cushing’s syn

Hyperglycemia; Glycosuria; Leukocytosis; Lymphocytopenia; Hypokalemia

ectopic ACTH secretion

Inc plasma & urine 17-KS; inc plasma ACTH

peppers

useful in dx & f/u of pheochromocytoma; present in larger amts than other catecholamines