-
Axial skeleton:
15 % of skel mass; verts, pelvis, skull; majority of cancellous bone (most of Ca efflux from this); 80 % of metabolic activity
-
Appendicular Skeleton
85 % of skel mass; long bones; majority of cortical bone; 20 % of metabolic activity
-
Hypercalcemia S/S
serum Ca >10.5 mg/dL; altered mentation, N/V; polyuria, polydipsia, stones
-
Hypercalcemia pathogenesis
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)
-
Hypercalcemia: causes
inc skeleton resorption (primary hyperPTH; malig); inc GI absorption (milk-alk syn); both inc skel resorp & GI absorption (granulomatous: sarcoid, TB, fungal);
-
Primary hyperPTH mnemonic
Bones, stones, moans & groans
-
Primary hyperPTH evolving clin spectrum
more recently, less about stones & bone dz, more asymptomatic
-
Hypercalcemia: nonpharm tx
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
-
Hypercalcemia: Pharm tx: Inhibit osteoclastic resorption:
bisphosphonates (pamidronate IV; zoledronic acid for malig-related hypercalc); calcitonin (transient benefit d/t tachyphylaxis); cinacalcet; Last line: plicamycin, gallium nitrate
-
Hypercalcemia: Pharm tx: Inhibit osteoclast resorption/reduce GI absorption:
Glucocorticoids (prednisone; solumedrol)
-
Chvostek sx =
twitching of face and upper lip in response to tapping inferior to TMJ joint
-
Trousseau sx =
inflate BP cuff, leave it there; pt gets carpal spasm
-
If suspect pt is hypocalcemic, measure 1,25-D?
No; measure 25-OH D
-
Acute Hypocalcemia S/S
tetany, twitching, paresthesia; Chvostek sx; Trousseau sx; seizures; laryngo or bronchospasm; long QT; arrhythmia; hypotension
-
Chronic Hypocalcemia S/S
ectopic calcification (basal ganglia); EPS; parkinsonism; dementia; cataracts; abnml teeth; dry skin
-
Most common cause of hypocalcemia
surgically induced hypoPTH
-
Hypocalcemia Tx
Vit D (25 OH D deficiency): Calcium (2000-4000 mg/day); ergocalciferol / cholecalciferol if 25 OH D deficient; Calcitriol if 25 OH D sufficient
-
Osteomalacia =
Defective bone matrix mineralization d/t: inadequate Ca & phosphorus; deficient mineralizn mechm in presence of normal Ca / phosphorus
-
Osteomalacia in childhood is:
rickets
-
Osteomalacia symptoms
diffuse bone pain (esp pelvis), waddling gait, mx weakness, fractures & pseudofractures (Looser’s zones) of long bones, ribs, pelvis
-
Osteomalacia: causes
Vitamin D disorders; Hypophosphatemia (inherited disorders); Mineralization disorders
-
Osteomalacia: Tx
Vitamin D (25 OH D def): Ca (1500-2000 mg/day); ergocalciferol (D2-Drisdol) cholecalciferol (D3); Calcitriol (for hypophosphatemic osteomalacia)
-
Paget’s Disease =
Localized disorder of bone remodeling
-
Paget’s Dz: initiating lesion is:
inc bone resorption (giant multicellular osteoclasts); bone formation and mineralization is normal, though of irregular woven type
-
Paget’s Dz: most commonly affects:
pelvis, femur, spine, skull and tibia
-
Paget’s Dz: Sx
pain, bowing, fracture, HA, hearing loss; elevated alk phos (hallmark); bone turnover markers often elevated
-
Paget’s Dz: Tx
Inhibit osteoclast resorption/ bone formation: bisphosphonates; calcitonin
-
More abundant; precursor to T3
T4
-
exerts majority of thyroidal hormone effects:
T3
-
Circulating T3 & T4
most is pro-bound; unbound = regulator for negative feedback inhibition mechanism
-
Thyroid hormones control:
O2 consumption CHO & protein metabolism, electrolyte mobilization & conversion of carotene to Vitamin A; also lipid synth & metab
-
Thyroid & insulin req in DM
Hypo: dec insulin req, inc chol/TG; hyper = inc insulin req, dec chol/TG
-
Amt TBG affects:
amt serum T3 & T4 (not physiologic thyroid status, which is affected by free hormone)
-
TBG can be measured:
directly or by T3 uptake
-
Factors increasing TBG
Estrogens (inc serum TBG, so low T3 uptake value)
-
Factors decreasing TBG
Androgens or adrenocorticosteroid, low protein states (nephrotic syndrome or hepatic failure): dec serum TBG, so high T3 uptake value
-
T3 uptake =
indirect measure of pt’s Total T4; the higher the T3 uptake, the higher the pt’s T4 level
-
Thyroid state & T3 uptake:
Hyper: high T3 uptake; hypo: low T3 uptake
-
FTI (T7) =
total T4 x T3 uptake; FTI low: hypo; FTI high: hyperthyroid
-
Most common calculation method for free hormone
FTI (takes into account both absolute hormone level & binding capacity of TBG)
-
Hyperthyroidism labs
Depressed TSH; Elevated FT4, T3 Uptake, FTI
-
Hypothyroidism labs
Elevated TSH; Depressed FT4, T3 Uptake, FTI
-
Euthyroid, High TBG (eg, PG)
Sl low TSH; Free T4 nml or sl high; low T3 Uptake
-
Euthyroid, Low TBG (eg nephrotic syn)
TSH variable; Total T4 low to normal; Elevated T3 Uptake
-
ThRH stimulating test evaluates:
entire thyroid-pituitary-hypothalamus feedback loop
-
TSH levels don’t rise in:
primary hypopituitarism & states of altered thyroid homeostasis
-
TSI test
IgG Ab vs thyroid cell TSH rec's; 78% Graves pts are pos; test to monitor tx; titers rise with relapse
-
hypometabolism with low T3/T4; +/- low FTI & nml TSH; If reverse T3 (inactive product from T4 metabolic breakdown) is elevated =
euthyroid sick syndrome
-
Thyroid screening
USPSTF: no recs; ATA: TSH screen start at 35 yo & q5 yrs (sooner if risk factors or sx)
-
Thyroglobulin Ab >1:100 suggestive of:
autoimmune thyroiditis
-
Microsomal Ab >1:32 titer correlates with:
autoimmune thyroiditis
-
Graves dz: predictors of remission
small goiter (decreases w/thianamides); FT3 predominance; neg TSI titer
-
GH stimuli include:
exercise, hypoglycemia hi protein diet, acute starvation & oral contraceptives (secondary to estrogen)
-
GH deficiency seen in:
obesity & corticosteroid therapy
-
Pituitary adenoma diagnosed by:
CT or MRI of brain to evaluate sella turcica
-
GH lab testing
GH on fasting AM samples (often not diagnostic); GH Stimu tests (hyperglycemia normally suppresses GH secretion); GH remains elevated in acromegaly
-
3 causes of pituitary dwarfism:
pit tumor (1/3); pit damage (1/3); Pure GH deficiency (1/3)
-
pituitary dwarfism: IGF-1 & GH
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
-
IGF-1 levels influenced by:
nutrition (low levels in malnutrition)
-
Prolactin prodn driven by:
automatic/constant unless inhibited
-
Most common disorder involving excess pituitary secretion
Prolactinomas
-
ACTH measurement
rarely measured directly (d/t lability)
-
2 actions of ADH
Alters the permeability of renal collecting tubules to water; Causes vasoconstriction
-
ADH is secreted when serum osmo exceeds:
285 mOsm/L
-
Central DI:
Hypothalamic origin; ADH production or release is deficient
-
Nephrogenic DI:
Kidneys fail to respond to normal or even elevated levels of ADH
-
ADH measurement
usually unmeasurable; 2.3-3.1 pg/mL
-
Pt ADH deficient, urine osmo: ≤300 mOsmkg
urine osmo: <300 mOsmkg (nml pt; ovenight urine is ≥800)
-
H2O deprivation test: fx of exogenous ADH
Central DI: urine osmo will increase; Nephrogenic DI: urine osmo will not change
-
SIADH caused by:
excessive levels of ADH active material of non-pituitary origin
-
SIADH labs:
low serum osmolality, low serum sodium & high urine osmolality
-
ADH problems: tests
DI: H2O deprivation; SIADH: water loading test
-
Water loading study results
(1L H2O; hourly urine/serum x 5 hrs) Normal: urine osmo < serum osmo; SIADH: urine osmo > serum osmo
-
PTH labs
can measure Ca, PO4, Mg, PTH directly; Alk phos assoc w/osteocyte activity (higher in growing kids, M>F, or mets)
-
Vit D metabolites
responsible for absorption of dietary calcium & phosphate in intestines; enhance PTH fx on mobilization of skeletal Ca & PO4
-
Vit D labs
can directly measure Vit D & metabolites
-
IGF's fn:
IGF’s mediate the effect of GH on skeletal muscle
-
Aldosterone made in:
zona glomerulosa
-
Aldosterone fn
reabsorption of sodium and excretion of potassium; prevention of hypovolemia & hyperkalemia
-
Cortisol fn
counters fx of insulin; anti-inflam
-
Cortisol level highest:
in AM; in stress & exercise
-
Primary AI involves:
AKA Addison dz; all 3 zones of adrenal (so potl insuff of cortisol & aldost)
-
Addison dz: Ddx can be narrowed by:
considering the abruptness of disease onset
-
Primary AI: abrupt onset: etiology
Adrenal hemorrhage, necrosis, thrombosis; meningococcal sepsis (Waterhouse-Friderichsen Syn); pseudo; coag dz; mets ca w/ bleed
-
Primary AI: slow onset: etiology
Auto-immune Adrenalitis; infxs Adrenalitis; Mets ca; congenital Adrenal Hyperplasia (CAH); Adrenomyeloneuropathy
-
Primary AI: clin findings
Hyperpigmentation (due to xs ACTH); Salt craving; Hyponatremia; Hyperkalemia; Vitiligo, pallor; auto-immune thyroid dz; CNS sx in adrenomyeloneuropathy
-
Secondary/tert AI: slow onset: etiology
Pit tumor / surgery / rad; Craniopharyngioma ; Isolated ACTH def; Megace (glucocorticoid-like action); LT g’corticoid tx; Sarcoidosis; Hypothalamic tumor
-
AM cortisol results:
>18: r/o AI; <3: R/I AI; btw this range: need dynamic testing
-
ACTH stim test
250 mcg Cosyntropin; measure cortisol before & 30 & 60 min after injxn; pre or post >18: R/O AI
-
AI dx: labs
AM cortisol (low); ACTH stim (low); plasma ACTH (>100: primary AI) (nml: 5-45 R/O primary AI; find cause of secondary/tert AI)
-
Adrenal crisis tx
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)
-
Chronic AI: maint tx
Hydrocortisone 20mg AM / 10mg PM; Dex; prednisone
-
Tx chronic primary AI: besides cortisol, must also tx insuff of:
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
-
AI Prophylaxis: Steroids in Surgery
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)
-
Cushing syn: ACTH-indept:
Adrenal lesion: next step is adrenal CT; exogenous source; Plasma ACTH level is low (< 5 pg/mL)
-
Cushing syn: ACTH-dependent:
Plasma ACTH level is normal or high (>15 pg/mL); Either ectopic production OR Pituitary adenoma = Cushing dz
-
Diagnosis: ACTH-dept: distinguish btw ectopic vs pituitary:
CRH-Stimulation test; HD Dex suppression; Petrosal Sinus Sampling; Octreotide scintigraphy to localize ectopic source; MRI
-
Cushing syn: tx
Surg Resection; Transphenoidal microsurgical removal (if sure Cushing dz); Bilateral Adrenalectomy (uncommon); Pharmacologic adrenal blockade
-
Hirsutism / virilization: etiology
Idiopathic (Familial); PCOS; Androgen-secreting adrenal adenomas or carcinoma; Ovarian tumors; Glucocorticoid resistance
-
Hirsutism / virilization: etiology: ACTH-dependent causes
Congenital Adrenal Hyperplasia; ACTH-dependent Cushing Syn
-
PCOS LH:FSH ratio
>2.0 common
-
Androgen-secreting adrenal adenomas
Rare; high serum androgen conc remain elevated despite Dex suppression
-
Androgen-secreting adrenal ca prevalence
More common than adenomas
-
Androgen-secreting adrenal carcinomas
usu > 5 cm at dx; Very high DHEA, DHEA sulfate; No response to HD Dex Suppression
-
Hirsutism / virilization: lab eval
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)
-
Hirsutism / virilization: Imaging
Pelvic Exam & US; Abd CT (esp adrenal glands/ fine cuts): adenoma / ca / hypertrophy
-
CAH
Enzyme defects in adrenal steroid hor synth -> insuff cortisol +/-mineralocorticoid; classically with an assoc androgen excess
-
CAH: classical forms
Salt-wasting form; Virilizing Syndromes
-
CAH: nonclassical forms
Late-onset: women = hirsutism & menstrual irreg which can mimic PCOS; Men/boy: androgen excess can be asymptomatic
-
Hirsutism / virilization: Tx
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
-
PCOS Tx options
Oral Contraceptives (beware DVT); Metformin; Anti-androgen ( if NOT PG): Aldactone (spironolactone), Finasteride, Flutamide
-
Primary hyperaldosteronism: clin findings
Hypertension; Mx Sx (d/t hypokalemia): cramping, weakness, periodic paralysis; Often few clinical findings at all (often suspected after lab abnormalities)
-
Primary hyperaldosteronism: labs
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
-
Primary hyperaldosteronism: labs: 18-OH corticosterone
indicative of aldosterone producing adenoma (APA)
-
Primary hyperaldosteronism: imaging
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
-
Primary hyperaldosteronism: issues in eval
S/b off Aldactone; CCB; ACEI (consider in-house eval); At least 150mEq of sodium intake daily (to suppress aldosterone prodn)
-
Primary hyperaldosteronism: presenting forms
APA (Conn’s); Bilateral Hyperplasia of the Zona Glomerulosa (if bilat, need remove both); Primary adrenal hyperplasia; Adrenal carcinoma
-
Primary hyperaldosteronism: Tx: Aldosterone Producing Adenoma:
surgical (effective only in patients with unilateral disease)
-
Primary hyperaldosteronism: Tx: IHA or poor surgical candidate:
med tx: Mineralocorticoid receptor antagonists: Spironolactone (DOC) or Eplerenone; CCB; ACEI
-
Pheochromocytoma =
dz of adrenal medulla (site of catecholamine prodn)
-
Pheochromocytoma: 5 P’s
pain; pallor (ortho hypoTN); palpitations; pressure (HTN); perspiration
-
Pheochromocytoma; rule of 10
10% of dz are: extra-adrenal; bilateral; familial; malignant; not assoc w/ HTN
-
Pheochromocytoma: Dx
24 hr urine (for Catecholamines & Metabolites: Metanephrines / VMA); Serum metanephrines/ plasma catecholamines; Imaging
-
Pheochromocytoma: Tx : First:
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)
-
Pheochromocytoma: Tx:
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)
-
TBG is increased / decreased by:
inc by estrogen, decreased by androgen
-
Fx of illness on T3 / T4
Severe illness or starvation decrease total T3 and free T3, increase rT3, no change of free T4 (euthyroid sick syndrome)
-
Thyroid functional assessment
131-Iodine Uptake; Measured at 24 hours; Normal 15-30%
-
Thyroid imaging
Thyroid scan (99m Tc); US (good for nodules); CT; MRI; PET
-
Graves dz: etiology
Auto-antibody reacting with the TSH receptor (TSI, 80-95% pos)
-
Graves dz: eval
Symmetric non-tender goiter (80%) (bruit is pathognomonic); Ocular findings (30%); Pretibial myxedema; TSH, Free T4, Free T3; Thyroid uptake and scan
-
Subacute thyroiditis (early) AKA:
de Quervain’s
-
Silent or painless thyroiditis (early) AKA:
Hashitoxicosis
-
thyroiditis (early): course:
hyperthy (1-3 mo); then hypothy (1-3 mo); then euthyroid
-
hypothyroid prevalence
2% of US F (0.2% US M); 1 in 4000 newborns
-
Hypothyroid etiology (3)
Primary; goitrous; central
-
Hashimoto etiology
cytotoxic anti-thy Ab's (80-90% antithyroglobulin); >50 yo
-
toxic multinodular goiter etiology
multicell autonomic fn
-
toxic multinodular goiter exam & Tx
>50 yo; lg irreg nod thy; TSH, FT4, FT3, uptake & scan; Rx RAI
-
Toxic nodule: etiology
activation of TSH receptors via rec gene mutation
-
Toxic nodule: exam
30-40 yo; lg irreg nod thy; onycholysis; TSH, FT4, uptake & scan; Rx RAI
-
subacute thyroiditis etio
TH leak d/t viral infxn -> thy gland destn
-
subacute thyroiditis: exam
Fever; lg irreg very tender thy; TSH, FT4, FT3, thyroglobulin, ESR, uptake & scan(result: zero)
-
subacute thyroiditis: Tx
ASA/ NSAIDs; prednisone
-
silent thyroiditis: etio
transient autoimmune dysfn (often post-partum); sudden onset of hyperthyroid
-
silent thyroiditis: exam & Tx
lg nod thy; TSH, FT4, FT3, anti-thy Ab (30%), uptake & scan; Rx beta blocker
-
levothyroxine AE
Osteoporosis; Inc cardiac contractility; Inc risk of A-fib; Allergic rxn dye in tablets
-
Multinodular goiters
2-4% prev in iodine-sufficient areas; F 5-15 x M; multifactorial; genetic cause?
-
Multinodular goiters: tx
thyroxine suppression of TSH; surg if obstruction
-
Thy nodule/neoplasia: exam
benign hx; s/s hypo or hyper; tender nod; FH hypo, nod, or goiter
-
Thyroid nodule: eval for neoplasm
TSH; US (80%); FNA. Scan = no value
-
Tx for Graves dz
PTU (esp for PG/BF)(TID); Tapazole (qd)
-
-
Cytomel AE
inc cardiotoxicity risk
-
Armour thyroid: problems
Unpredictable hormonal stability; allerg rxn risk; Lacks bioequivalence among brands
-
PTU works within:
17 weeks
-
Tapazole works within:
6 wks (w/fewer AE)(QD dosing, so better compliance than PTU TID)
-
PTU & Tapazole AE:
Benign rash; potl agranulocytosis; hepatotoxicity
-
Surgery for hyperthyroid: subtotal or total thyroidectomy: indicated in:
pts with obstructions, malignancy, pregnancy in 2nd trimester, or those with contraindications to RAI or thioamides
-
Tx of choice for hyperthyroid in US:
radioactive I ablation (CI in PG)
-
Hyperthyroid tx adjuncts:
beta-blockers; c'steroids (dec action of thy hormone & imm response in Graves); Iodine (blocks thy hor release)
-
PTU / Tapazole: If miss a dose:
take as soon as remember. Double up doses if necessary!
-
Tx for thyroid storm
PTU; Propranolol; Corticosteroid; Iodide; Supportive measures; mortality 20%
-
Myxedema Coma: findings
Emergency: elderly in winter; Hypothermia; Resp depression; Unconsciousness
-
Myxedema Coma: tx
stat IV levothyroxine; then check labs
-
hypothyroid Tx: T4/T3 ratios
Liotrix 4:1; thyroglobulin 2.5:1; armour = not consistent
-
thyroid replacement tx dosing
<45 yo 100%; > 45 or LT/severe dz 50%; CVD or >65 25%; PG: inc dose by 50%
-
Hyperthyroid tx monitoring
TT4 & FTI after 4-6 wks; after change in tx; then q 6-12 mo (for RAI: TSH/FT4 qmo)
-
test used to evaluate overall cortisol production
24 hr urine cortisol (AKA urine free cortisol)
-
preferred test for Cushing syn
24 hr urine cortisol
-
24 hr urine cortisol specimen
5 mL (frozen, fridge, or preservative) within 4 hr of collection
-
ACTH levels indicate:
High: Addison; low: secondary AI
-
Increased ACTH d/t:
Cushing dz; Addison; ectopic ACTH-producing tumors
-
Decreased ACTH d/t:
adrenal tumor; steroid medication; hypopituitarism
-
Acute AI: lab findings
Low cortisol; Hyperkalemia; Hyponatremia; Elevated BUN; Hypoglycemia
-
Cushing: lab dx
24 hr urine cort; Dex suppression test; high PM cortisol
-
Cushing: to detn cause of xs cortisol:
Plasma ACTH level; HD Dex supp test; CRH stimulation test; Imaging (CT, MRI, US)
-
Secondary hyperaldosteronism
More common than primary; usu d/t renal artery stenosis (curable by surg/angioplasty)
-
Renin & aldosterone: body position
levels rise following assumption of an upright position
-
Elevation of 17-KS indicates:
tumor or hyperplasia of adrenal cortex
-
adrenal x-rays to:
look for calcifications (poss d/t TB)
-
adrenal CT/MRI to:
evaluate the size & shape of the adrenal glands & pituitary
-
17-OCHS & 17-KS useful to:
detn cause of Cushing’s syn
-
Cushing other findings
Hyperglycemia; Glycosuria; Leukocytosis; Lymphocytopenia; Hypokalemia
-
17-OCHS very high in:
ectopic ACTH secretion
-
Hirsutism/virilization labs:
Inc plasma & urine 17-KS; inc plasma ACTH
-
interfering substance in urine metanephrine analysis
peppers
-
VMA
useful in dx & f/u of pheochromocytoma; present in larger amts than other catecholamines
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