Endocrinology

Question 1

DM type I

Answer 1

• onset: slow in adults, rapid in children, autoimmune, Finland/Sardinia (by Italy)
• Type 1A: immune mediated, HLA associated, white, no FHx, autoantibody (+)
• Type 1B: idiopathic, AA/Asian, autoantibody (-), FHx
• sxs: 3Ps (polyuria, polydipsia, polyphagia), wt loss, infxn, nocturia, blurry vision
• dx: autoimmune markers, GAD65 autoAbs, islet cell autoAbs, insulin autoAbs, C-peptide low (no active insulin in body)
• tx: insulin pen, vial and basal bolus with carb counting, check gluc at least 4x daily

Question 2

DM type II

Answer 2

• insulin resistance: hyperinsulin at first, then hypoinsulinemic
• insulin resistance doesnt change - insulin secretion changes, B-cell decline gradual, def of amylin, def of GLP-1: stops glucagon, satiety, inc insulin release, postprandial gluc increases over time
• RF: first deg relative, age, obesity
• sxs: blurred vision, 3Ps, WIN, Acanthosis nigricans, ketonuria and wt loss (rare), fatigue, pruritus, recurrent candidal vaginitis, blurred vision, poor wound healing
• dx: randome glucose >200 (w/ sxs), fasting >126 (2+ occasions), HbA1C >6.5%, OGTT if fasting 100-125, diabetic dyslipidemia (high TGs, low HDL, altered LDL)
• tx: diet, exercise, wt loss, metformin
• goal of HbA1C = 6-6.5, FBS goal = 100-124, 1-2 PP (<180), screen annually

Question 3

dawn phenomenon and somogyi phenomenon

Answer 3

• dawn phenomenon: increased resistance to insulin in the early morning d/t counter-reg hormones
  
  • tx: increase overnight basal insulin, exercise, metformin, TZD
• somogyi phenomenon: rebound fasting hyperglyc following undetected hypoglyc overnight, excess hunger, wt gain, worsening hyperglyc
  
  • tx: dec overnight basal insulin or eat a snack at bedtime

Question 4

hyperthyroidism

Answer 4

• associated: afib
• subclinical hyperthyroidsim = low TSH, normal T3/T4
• sxs: anxiety, insomnia, irritability, palps, wt loss, heat intolerance, sweating, D, increased freq, oligomen, tremor, hyperactivity, tremulousness
• signs: moist skin, tachycardia, hyperreflexia, flushed, diaphoretic, wide pulse pressure
• dx: Primary hyperthyroid - TFTs (TSH low, total T3 high, free T4 high)
  
  • ​autoantibody tests (antithyroid peroxidase Ab, TS-immunoglob
  • scintigraphy (thyroid scan) - if etiology unclear after initial labs
• tx: propranolol, methimazole, propylthiouracil (can . use in preg and thyroid storm), RAI tx, thyroidectomy

Question 5

hypothyroid

Answer 5

• primary: failure of thyroid to produce sufficient T3 (iatrogenic - prior tx of hyper thyroid, hashimotos)
• secondary: hypothyroid dt pituitary dz, low TSH/free T4
• tertiary: dt hypothal dz (TRH def), low TSH/free T4
• associated: carpal tunnel syndrome
• sxs: constipation, fatigue, lethargy, weakness, wt gain, depression, menorrhagia, cold intolerance, cramps, slow mentation, inability to concentrate, dull expresion, m weakness, arthralgias, hoarseness
• signs: dry, rough skin, coarse hair, palpable enlarged thyroid, brittle nails, puffy face and eyelids, yellowing of skin (carotenemia), decreased DTRs
• dx: thyroid fn tests
  
  • primary: high TSH (most sensitive)
  • secondary: low TSH
  • tertiary: low TSH
  • free T4 low in clinically overt
  • Ab testing, CBC (normocytic anemia MC)
• tx: levothyroxine (T4) → effects in 2-4wk →monitor TSH and clinical state periodically

Question 6

Grave’s dz (diffuse toxic goiter)

Answer 6

• 80%, metabolically active gland, MCC of hyperthyroidism, mostly younger women with other autoimmune conditions, Autoimmune (thyroid stimulating IgG Ab binds TSH receptors on surface o f thyroid cells triggering synthesis of excess thyroid hormone)
• sxs: pretibial myxedema, exophthalmos (periorbital edema, diplopia, or proptosis), thyroid bruit, diffusely enlarged, symmetric, nontender gland
• dx: measurement of thyroid Abs (anti-TPO high, TSI high), scintigraphy (diffuse uptake)
• tx: antithyroid meds, radioactive iodine preferred, saline eye drops and tight fitting sunglasses, high dose steroids with orbital decompresison surgery and ocular radiation tx for severe exophthalmos

Question 7

thyroid storm

Answer 7

• rare, life-threatening complication of thyrotoxicosis, acute exacerbation of hyperthyroidism
• precipitating factors: infxn, DKA, stress (trauma, surgery, illness, labor)
• sxs: marked fever, agitation, psychosis, confusion, nausea, vomiting, diarrhea, signs: tachycardia
• tx: supportive tx, antithyroid agents (PTU q2h, iodine), BB, dexameth (generates peripheral T3 from T4, adrenal support
• high mortality (20%)

Question 8

hashimoto’s thyroiditis

Answer 8

• MCC: autoimmune thyroid disorder and MCC hypothyroidism
• MC in F, genetics + FH common, slow decline in thyroid fn
• sxs: puffiness of face and . eyelides: periorbital myxedema, thinning of outer halves of eyebrows, goiter (MC feature) - hard, nonpainful, nontender, multinodular, irregular, asymmetric
• dx: antiperoxidase Abs (90% +), anti thyroglobulin . Ab, antimicrosomal Ab high, irregular I-131 on thyroid scan (not required to DX)
• tx: levothyroxine (T4)

Question 9

myxedema coma

Answer 9

• rare condition, precipitating factors (cold exposure, infxn, trauma, narcotics)
• sxs: depressed state of consciousness, profound hypothermia, resp depression
• tx: supportive tx for BP and breathing, IV thyroxine, IV hydrocortisone
• high mortality rate (50-75%)

Question 10

primary adrenal insufficiency (addison dz)

Answer 10

• chronic adrenocortical insufficiency
• adrenal gland does not produce cort, aldosterone, or sex hormones (retain no sodium), primary adrenal failure from autoimmune adrenalitis
• sxs: hyperpig dt increased ACTH, MSH (POMC), anorexia, abdominal pain, N, V, wt loss, lethargy, confusion, psychosis, weakness, malaise, postural HoTN, dizziness, salt craving
• signs: hypotension (orthostasis)
• dx: electrolytes (hyponat, hyperkalemia, hypoglycemia, hypercalcemia, elevated SCr), low serum cort, high ACTH, low aldo and high renin
  
  • cosyntropin test = definitive (cort will not elevate sufficiently → test also known as astandard ACTH test
• tx: daily oral steroids (hydrocort, prednisone), daily fludrocort (mineralocort)

Question 11

secondary adrenal insufficiency

Answer 11

• long-term steroid therapy - most common cause overall, dysfunciton of hypothalamic pituitary . component of HPA axis: only steroid and androgen deficiency present
• sxs: hx of prior use of oral steorids shuts down adrenal axis and causes acute adrenal crisis when stopped (weakness, malaise, postural HoTN, lethargy, confusion, psychosis)
• sings: alabaster pale skin
• dx: electrolytes (hyponat, hyperkalemia, hypoglyc, serum cort low, serum ACTH low, nl aldosterone and renin, ACTH test → cort will not respond at all)
• tx: only daily steroid required

Question 12

addisonian (adrenal) crisis

Answer 12

• HoTN refractory to IV fluids or acutely ill pts with chronic steroid use (moon facies, buffalo hump), any stress can precipitate adrenal crisis
• sxs: fatigue, anorexia, generalized aches, weakness, lethargy, abd pain, N, V
• signs: severe HoTN (orthostasis)
• dx: hyponatremia, hyperK, hypoglyc, elevated SCr, metabolic acidosis, acute renal failure, cortisol low, ACTH stim test or cosyntropin test (cort will not elevate sufficiently)
• tx: IV hydrocortisone, fludrocortisone, IV fluids, monitor fluid intake and output, and serum K levels frequently

Question 13

primary aldosteronism (Conn syndrome)

Answer 13

• benign adenoma of the adrenal cortex (makes aldosterone, retian sodium)
• sxs: pt on no meds with HTN
• dx: hypokalemia (unprovoked), hypernatremia

Question 14

cushing syndrome

Answer 14

• excessive exogenous cort, MCC = iatrogenic dt prescribed prenisone, androgen excess absent (exog steroids suppress production by adrenals), second MCC = ACTH secreting adenoma (AKA cushing dz) →bilateral adrenal hyperplasia (androgen excess common)
• sxs: striae, buffalo hump, central obesity, moon facies, lanugo, acne, easy bruising, proximal muscle weakness and wasting, osteoporosis, AVN of fem head, HA, depression, mani
• signs: HTN, DM, menstrual irreg, infertility, Cushing dz only = masculinization
• dx: HD dexamethasome suppression test, midnight serum cortisol, late night salivary cort, urinary free cort, CT or MRI, sustained elevated cort, hypoK, hyperglyc, glucosuria
• tx: if iatrogenic → taper steroids, if ACTH secreting adenoma, transphenoidal resection of tumor, adrenal adenoma → pit radiation, med adrenalectomy, bilateral adrenalectomy, ectopic ACTH production (2/3 SCC from lungs)

Question 15

hyperparathyroidism etiology and sxs

Answer 15

• Primary: one or more glands produce inappropriate PTH relative to Ca2+
  
  • MCC: parathyroid adenoma
• secondary: high PTH and low or nl Ca2+
  
  • MCC: chronic renal failure, vitD def, renal hypercalciuria, most found incidentally by hypercalcemia on routine labs, most F>50
• sxs: most asxatic; stones, bones, groans, psychiatric overtones
  
  • stones: nephrolithiasis, frequent urination
  • bones: body aches and pains, osteitis fibrosa cystica (brown tumors - predisposes to fx), weakness
  • groans: abdominal pain, constipation, N/V/A
  • psychiatric overtones: depression, fatigue, anorexia, sleep disturbance, anxiety, lethargy
• signs: HTN, dec DTRs

Question 16

hyperparathyroidism dx and tx

Answer 16

• dx: serum Ca2+ HIGH, serum phosphate LOW, serum PTH HIGH (first line)
  
  • total and ionized Ca2+ high, alb low, urine caAMP high
  • XR: subperiosteal bone resorption, osteopenia
• tx: if serum Ca2+ >12 - IV fluid resuscitation; otherwise follow up
  
  • primary: BB, k-phos supplement, dietary calcium restriction, bisphosphonates, calcimimetic agents (calcinet), parathyroidectomy
  • secondary: 400IU vitD (calcitriol) daily for vitD deficiency (annual Ca and Cr measurements, annual KUB for stones, DEXA q2-3y), PO Ca, dietary phos restriction for renail failure

Question 17

pheochromocytoma etiology, sxs

Answer 17

• rare, secrete catecholamines from adrenal medulla, arise from chromaffin cells (adrenal medulla) or from sympathetic ganglia (extrarenal)
• associated with MEN 2A and MEN 2B, von recklinghausen neurofibromatosis, von hippellindau dz
• sxs: paroxysms of HA, profuse sweating, palps, wt loss, feelings of warmth along with episodic (later sustained) hypertension, sometimes severe, feeling of impending doom
• signs: tachycardia

Question 18

pheochromocytoma dx and tx

Answer 18

• dx: 24h urine metanephrines, plasma mets > urine mets, CT or MRI, glucosuria, hyperlip, hypokalemia, hypercalcemia
• tx: give clonidine if equivocal results, tumor resection with ligation of venous drainage (laparoscopic adrenalectomy) - alpha blockers (phenoxybenzamine x10-14d prior to surgery to control BP and replete intravascular volume), beta blockers - propranolol 2-3d prior to surgery to control HR
  
  • fatal if left undiagnosed and treated

Question 19

thyroid nodules

Answer 19

• cancer found in 4-10% of investigated nodules
• sxs: fixed nodule without mvmt on swallowing (firm, irregular), hx of radiation tx to neck or family hx, rapid progression, obstructive sxs = vocal cord paralysis, dysphagia, odynophagia
• signs: must be >1cm to be palpable on exam
• dx: thyroid tests (TSH, T3, T4, serum calcitonin high), thyroid US (only differentiates solid vs cystic), FNA bx (even if clinically and chem euthyroid, if palpable or >1.5cm, only reliable test that differentiates benign vs malig, reliable for all cancers, except follicular - if indeterminate - RAI uptake
• tx: benign - observe 1y, fu with US, radioactive iodine tx (prefer if <40y and reliable for lifetime T4 - levothyroxine; for overactive thyroid w/o risk of subsequent cancer, leukemia, or other malig), thyroidectomy (cold nodules)

Question 20

thyroid cancer - differentiated papillary thyroid carcinoma

Answer 20

• F>M 3:1
• MC type (80-90%), least aggressive, slow growth and spread
• RF: hx of radiation to head/neck, papillary cancers are characterized histologically by psammoma bodies
• sxs: typically found incidentally on exam - thyroid nodule
• dx: TSH normal, T3/T4 normal, thyroid US differentiates solid vs cystic, FNA required for dx (psammoma bodies), RAI uptake +
• tx: total thyroidectomy with limited cervical lymph node removal
  
  • complications: vocal cord paralysis, hypoparathyroidism (hypocalcemia), hypothyroid
  • postop radioactive iodine ablation tx
  • spreads via lymphatics in neck, metastasizes to cervical lymph nodes

Question 21

medullary thyroid carcinoma

Answer 21

• neuroendocrine tumor of the parafollicular or C cells of the thyroid gland, 3-5% of thyroid carcinomas
• associated with familial syndromes in about 1/3 of the cases (MEN 2A or 2B)
• sxs: dysphagia, hoarseness, diarrhea, facial flushing
• signs: palpable solitary thyroid nodule (MC presentation) in upper portion of thyroid lobe, cervical lymph nodes palpable
• dx: US of neck (hypoechoic microcalcifications), labs (calcitonin elevated, CEA), FNA bx (diagnostic), genetic testing for germline RET mutations
• tx: total thyroidectomy most commonly recommended
  
  • thyroxine tx started immediately post-op to maintain euthyroidism
• health maintenance: measure serum calcitonin and CEA 2-3mos after surgery to ro residual dz (if undetectable, measure levels twice yearly x2y, then annually if stable, neck US 6-12mo postop

Question 22

hypoparathyroidism

Answer 22

• MCC: head and neck surgery - thyroidectomy, parathyroidectomy; nonsurgical is rare
• sxs: numbness and tingling - fingers, toes, tip of nose
  
  • tetany (hyperactive DTRs), rickets, osteomalacia, cataracts
• signs: chvostek sign (tap facial nerve, contraction of muscles), trousseau sign (carpal spasms with inflating BP cuff higher than systolic BP x3 min)
• dx: EKG QT prolongation, PTH low, Ca low, phosphate high, urine Ca low, nl alk phos
• tx: mild to mod - PO calcium supplements, vit D (calcitriol) - too high can cause stones
  
  • severe: IV Ca gluconate

Question 23

Diabetes insipidus

Answer 23

• Diabetes insipidus - excretion of large volume of dilute urine
• sxs: polyuria, nocturia, polydipsia
• dx: hypernatremia, 24h urine collection, urine osmolality LOW, water restriction test = confirmatory (differentiates central DI from primary polydipsia)

Question 24

Primary polydipsia

Answer 24

• Primary polydipsia (psychogenic, middle aged women with psych illness, carbamazepine, thiazides - hyponatremia) - DONT treat with antidiuretics - eliminating polyuria does not eliminate urge to drink

Question 25

central diabetes insipidus

Answer 25

• neurohypophyseal - deficient secretion of ADH resulting in variable degree of polyuria
• SODIUM IS HIGH IN CENTRAL DI
• idiopathic, possibloy autoimmune injury to ADH producing cells, MC type
• sxs: polyuria, abrupt, excretion of dilute colorless urine, polydipsia, nocturia
• dx: hypernat, urine osmolality LOW, water restriction and desmopressin test inc urine osmolality by 300, ADH LOW
• tx: desmopressin PO, nasal spray, or injection, chlorpropamide increases ADH secretion and enhances effect of ADH

Question 26

Nephrogenic Diabetes insipidus

Answer 26

• normal ADH secretion, but varying renal resistance to water-retaining effect
• children: x-linked; acquired from drug exposure (chronic lithium use, amphotericin B, metabolic conditions - hypercalcemia, hypokalemia), or renal damage
• sxs: polyuria (gradual), nocturia
• dx: hypernatremia, urine osmolality low, water restriction and desmopressin test: will not increase urine osmolality, ADH nl to high

Question 27

Paget disease of the bone (osteitis deformans) etiology and sxs

Answer 27

• MC sx: bone pain
• Age 60+, M=F, rare before age 40
• viral: paramyxovirus (measles, RSV, canine distemper virus)
• genetic: familial
• localized disorder of accelerated bone remodeling
• sxs: asxatic in 70-90%, bone pain (pelvis, lumbar, spine, skull, prox femur - mild to severe, not related to physical activity), periarticular pain (hip, knee, spine), neuro sxs (nonspecific HA, deafness)
• signs: mixed conductive and sensory hearing loss, frontal bossing of forehead or maxilla
• complications: chalk stick fractures, osteosarcoma, chondrosarcoma, fibrosarcoma, nephrolithiasis, gout

Question 28

paget dz of the bone dx and tx

Question 29

pituitary adenoma

Answer 29

• tumors arising in the anterior pituitary - compresses pituitary, then optic chiasm - cavernous sinus - third ventricle, temporal lobes, posterior fossa
  
  • 60-70% PRL secreting, 10-15% growth hormone, small amnt ACTH
• sxs: HA, complete or partial bitemporal hemianopia, oculomotor palsy
• complications: DI, somnolence, CSF rhinorrhea, seizures
• dx: MRI with gadolinium
• tx: transsphenoidal surg or stereotactic radiosurgery

Question 30

acromegaly

Answer 30

• broadening of skeleton due to excess GH after epiphyseal closure
• MCC: 10% caused by GH secreting pit adenoma
• MCC death: cardiovasc dz
• prior to puberty, oversecretion of GH leads to gigantism
• sxs: growth promotion (soft tissue and skeletal overgrowth, coarse facial features, abnly large hands/feet, organomegaly, arthralgias, prognathism), metabolic disturbances (diabetes, hyperhidrosis), parasellar manifestations (HA, bitemporal hemianopsia, cavernous sinus compression, sphenoid sinus invasion, HTN and OSA)
  
  • complications: hypertrophic CM
• dx: GH elevated, IGF-1 very high, OGTT fails to suppress GH, MRI, random GH level NOT USEFUL
• tx: octreotide, bromocriptine, transsphenoidal surg (1st line), radiation

Question 31

hypernatremia

Answer 31

• MC in elderly owing to inadequate water intake and loss
• sxs: muscle weakness, pain, tachycardia, hypotension
  
  • complications: rhabdomyolysis, obtundation, coma
• dx: Na >145, calculate free water deficit (TBW x Na(measured) - Na(desired))
• tx: acute hypernatremia - occurs within <48h, correct rapidly (hypotonic saline solution - 0.45% NSS)
  
  • chronic hypernatremia - correct slowly over 48-72h

Question 32

Hyponatremia

Answer 32

• excess of total body water in relation to Na, primarily a disorder of H2O homeostasis
• sxs: N/V, confusion, lethargy, disorientation, weakness, cramps, severe = szs, coma, death
• signs: decreased DTRs
• complications: central pontine myelinolysis occurs if you correct too quickly
• dx: serum osmolality Na <135, serum glucose
• tx: presence, absence, or severity of sxs determines urgency of tx
  
  • hyponat >48h puts pt at risk for osmotic demyelination syndrome - corrected by >10-12mM in first 24h
  • response to hypertonic saline or vasopressin antagonists requires frequent monitoring of Na (q2-4h)

Question 33

hypocalcemia

Answer 33

• increased neuromuscular irritability
• associated: rickets and osteomalacia, basal ganglia calcifications
• sxs: asxatic, numbness, tingling - circumoral in fingers, toes, face (periorbital, tip of nose), tetany, grand mal seizures
• signs: hyperactive DTRs, chvostek sign - tapping a facial nerve leads to a contraction (twitching) of facial muscles, trousseau sign - inflate BP cuff to a pressure higher than the pts systolic BP x3min - elicits carpal spasms
• dx: EKG arrhythmias, QT prolongation, BUN/Cr, Mg, albumin, ionized Ca, amylase, lipase, LFTs, serum PO4 high in renal insuff and hypopara, PTH, hypoparathyroidism = low; vit D def = high, pseudohypoparathyroidism = very high
• tx: if sxatic IV Ca gluconate, long term = oral CaCO3 and vitD, PTH def - replace with vitD and high oral Ca intake, thiazide diuretics lower urinary Ca and prevent urolithiasis, correct hypomag - very difficult to correct Ca if you dont correct magnesium first

Question 34

hypercalcemia

Answer 34

• Children - hypotonicity, muscle weakness, apathy, mood swings, bizarre behavior, N/V, abd pain
• signs: hyperextensibility of joints, hypertension, bradycardia, cardiac anomalies, short QT interval, intractable peptic ulcer, pancreatitis, decreased DTRs
• dx: draw same labs as for hypocalcemia (serum Ca > 11, slit lamp exam (band keratopathy - deposits in cornea or conjunctiva), radioimmunoassay of PTH high, bone scan or bone surgery for lytic lesions, urinary cAMP - elevated in primary PTH
• tx: inc urinary excretion (vigorous hydration - IV normal saline = first step, loop diuretics)
  
  • inhibit bone resorption in pts with malignancy, bisphosphonates, calcitonin, give steroids if vitamin D related and multiple myeloma, hemodialysis for renal failure

Question 35

complications of hypercalcemia

Answer 35

• Stones: nephrolithiasis, nephrocalcinosis
• Bones: bone aches/pains, osteitis fibrosa cystica (brown tumors)
• Grunts and groans: muscle pain and weakness, pancreatitis, PUD, gout, constipation
• psychiatric overtones: depression, fatigue, anorexia, sleep distubances, anxiety, lethargy
• other findings: polydipsia, polyuria, HTN, wt loss, short QT