Endo

Question 1

Chronic Adrenal Insufficiency primary vs secondary defintion

Answer 1

*adrenal gland does not produce enough hormones

Hypothalamus (CRH) 🡪 pituitary (ACTH) 🡪 adrenal (cortisol)
RAAS 🡪 aldosterone

Primary (Addison Disease): adrenal gland destruction
*lack of cortisol & aldosterone
Etiologies:
*autoimmune MCC in the US
*infection (TB, HIV) MCC in developing countries
*vascular: thrombosis or hemorrhage 🡪 Waterhouse-Friderichsen
*others: trauma, metastatic disease, meds (ketoconazole)

Secondary: pituitary failure of ACTH secretion
*lack of cortisol ONLY; aldosterone intact due to RAAS
Etiologies:
*hx of exogenous glucocorticoid use MCC overall
*hypopituitarism

Question 2

Chronic Adrenal Insufficiency sx

Answer 2

Sxs due to lack of cortisol:
*weakness, myalgias, fatigue
*GI: weight loss, anorexia, N/V/D, abdominal pain
*HA, sweating, abnormal menstruation
*mild hyponatremia, salt craving
*hypotension, hypoglycemia

Addison: sxs due to lack of sex hormones & aldosterone
*hyperpigmentation (↑ ACTH stimulates melanocyte-stimulating hormone secretion)
*orthostatic hypotension
*women: loss of libido, amenorrhea, loss of axillary/pubic hair

Question 3

Chronic Adrenal Insufficiency dx and tx

Answer 3

Baseline labs: 8am ACTH, cortisol, renin
*↑ renin (esp. w/ primary)
*cortisol <3µg/dL = (+) adrenal insufficiency
*Primary: ↑ ACTH
*Secondary: ↓ ACTH

Labs:
*hypoglycemia

Addison:
*hyponatremia, hyperkalemia
*non-anion gap metabolic acidosis

Screening: high-dose ACTH (Cosyntropin)
*no rise in cortisol 🡪 Addison (primary)
*destroyed adrenal gland = no response
*normal rise in cortisol 🡪 secondary
*adrenal gland in intact = responds

tx
Glucocorticoid replacement:
*hydrocortisone first line
*dexamethasone

Addison 🡪 (+) mineralocorticoid
*fludrocortisone

Illness, surgery, high fever, stress:
*3x the normal PO dose

Question 4

Adrenal (Addisonian) Crisis definition, sx, dx, tx

Answer 4

*sudden worsening of sxs
*precipitated by a “stressful” event (illness, surgery, trauma, volume loss, hypothermia, MI, fever, sepsis, hypoglycemia, steroid withdrawal, etc.)

Etiologies:
*abrupt withdrawal of steroids (w/o tapering) MCC
*previously undiagnosed + subject to stress
*diagnosed + no increase in meds during stress
*bilateral adrenal infarction (hemorrhage)

sx
Shock:
*hypotension
*hypovolemia

Profound weakness, severe abdominal pain, peripheral vascular collapse, electrolyte abnormalities, shock

dx
Labs:
*hyponatremia
*hyperkalemia
*hypoglycemia

*cortisol, aldosterone, ACTH, renin, CBC

tx
*isotonic fluids (NS or D5NS) plus
*IV hydrocortisone
*dexamethasone if undiagnosed

*reversal of electrolyte disorders
*fludrocortisone

Question 5

Diabetes Insipidus central vs nephrogenic definition

Answer 5

*inability of the kidney to concentrate urine, leading to production of large amounts of dilute urine

2 TYPES:
Central: no production of ADH (MC)
*idiopathic MCC, destruction of posterior pituitary, head trauma, CNS tumor, infection

Nephrogenic: partial or complete renal insensitivity to ADH
*lithium, amphotericin B, hypokalemia, hypercalcemia, acute tubular necrosis, hyperparathyroidism

Question 6

Diabetes Insipidus sx, dx, tx

Answer 6

sx
*polyuria + polydipsia
*high-volume nocturia

Neurologic sxs of hypernatremia
*confusion, lethargy, disorientation
*seizures, coma

PE:
*dehydration, hypotension, rapid vascular collapse

dx
*increased serum osmolarity
*decreased urine osmolality & specific gravity
*increased urine volume

Fluid deprivation test: *establishes dx
*continued production of large amounts of dilute urine (low urine osmolality)

ADH stimulation test: *distinguishes central v. nephro
*central: responds to ADH
*nephrogenic: continued production of large amounts of dilute urine (no response to ADH)

tx
Central:
*desmopressin (DDAVP) first line
*carbamazepine second line

Nephrogenic:
*correct underlying cause
*hydrochlorothiazide, indomethacin, or amiloride is sxs persist
*sodium & protein restriction

Question 7

DM Type 1 defintion

Answer 7

90% autoimmune – pancreatic β cells fail to respond to stimuli & undergo autoimmune destruction

Onset: usually <30 (3/4 diagnosed in childhood)
*peaks at 4-6y then again at 10-14y
*NOT associated w/ obesity

Type 1A: autoimmune (MC); HLA-DR3 & HLA-DR4 association
Type 1B: non-autoimmune β cell destruction

Main RF: family hx (first-degree relative)

Diabetic Ketoacidosis (DKA):
*infection MCC – others: D/C or inadequate insulin therapy, undiagnosed DM, MI, CVA, pancreatitis

Question 8

DM Type 1 sx

Answer 8

3 initial presentations:
*Classic new onset: polydipsia, polyuria, & weight loss + hyperglycemia & ketonemia (or kentonuria)
*DKA
*Silent (asymptomatic) incidental discovery

*perineal candidiasis – common in young children/girls
*acute visual disturbances

DKA: sxs evolve rapidly over 24h
Child appears acutely ill & suffers from moderate to profound dehydration
*polyuria, polydipsia
*fatigue, HA, AMS
*N/V, abdominal pain

PE: tachycardia, tachypnea, hypotension, ↓ skin turgor
*fruity (acetone) breath
*Kussmaul respirations (deep, labored breathing)

DM1 Associations & Solutions:
Dawn Phenomenon: normal glucose until 2-8am when it rises; results from ↓ insulin sensitivity & a nightly surge of counter-regulatory hormones during nighttime fasting
TX: bedtime injection of NPH to blunt morning hyperglycemia; avoid carbs late at night

Somogyi Effect: nocturnal hypoglycemia followed by rebound hyperglycemia d/t surge in growth hormone
TX: ↓ nighttime NPH dose or give bedtime snack

Insulin Waning: a progressive rise in glucose from bed to morning
TX: change of insulin dose to bedtime

Question 9

DM Type 1 dx

Answer 9

Criteria: one of the following
1) Fasting plasma glucose ≥126mg/dL on >1 occasion
2) Random plasma glucose ≥200mg/dL + classic s/sxs of hyperglycemia
3) OGTT – plasma glucose ≥200mg/dL after 2hr
4) HbA1C ≥6.5% confirmed by repeat testing

Autoantibodies: GAD65, IA2, insulin
*any (+) autoantibodies 🡪 assume DM1

LOW insulin & C-peptide

*urine: glucose, ketones

DKA:
*BG >250mg/dL (usually <800mg/dL)
*acidic pH <7.3, anion gap usually >20mEq/L
*bicarb <15-18
*(+) urine/serum ketones

Potassium: total body K is depleted, but serum K is normal/elevated (K shift from intracellular fluid to extracellular fluid)

Question 10

DM Type 1 tx

Answer 10

INSULIN THERAPY!!
*Multiple Daily Injections (MDI): long-acting insulin injections 1-2x/d + rapid or short-acting insulin before each meal/snack
*Insulin Pump: delivers continuous SC infusion of rapid or short-acting insulin + supplemented boluses before each meal/snack

DKA: SIPS – saline, insulin (regular), potassium repletion, search for underlying cause

Saline: isotonic 0.9% (normal saline) until hypotension & orthostasis resolves
*then switch to ½ NS (0.45%)
*once serum glucose reaches ~200-250, add dextrose (to prevent hypoglycemia from insulin)

Insulin: for pts w/ K ≥3.3mEq/L – regular insulin continuous infusion; 2 regimens
*0.1units/kg IV bolus then continuous IV infusion 0.1units/kg/h
*NO BOLUS, start continuous IV infusion 0.14units/kg/h
*if serum glucose doesn’t fall by at least 50-70mg/dL in the first hour, DOUBLE rate of insulin infusion

Potassium: regardless of serum K, pts have a large total body K deficit
*K <3.3mEq/L – HOLD INSULIN; give IV KCl 20-40mEq/L until K above 3.3mEq/L
*K 3.3-5.3mEq/L – give KCl 20-30mEq/L IV fluid
*maintain SERUM K 4-5mEq/L
*K >5.3mEq/L – DO NOT GIVE K; check serum K q2h & delay KCl admin until serum K <5.3mEq/L

Sodium Bicarbonate: ONLY GIVEN TO PTS W/ pH <6.90 (admin associated w/ complications of overcorrection & increased cerebral edema)

Question 11

DM Type II defintion, sx, dx, tx

Answer 11

Combination of insulin insensitivity (resistance) & relative impairment of insulin secretion

Risk Factors: obesity greatest RF, decreased physical activity, family hx, metabolic syndrome

Hyperosmolar Hyperglycemic State (HHS): seen in older patients, associated w/ more severe dehydration; no ketosis or acidosis

sx
3 Ps: polyuria, polydipsia, polyphagia
*poor wound healing
*increased infections

HHS: s/sxs develop more insidiously
*polyuria, polydipsia, weight loss, profound dehydration
*NEURO SXS – mental obtundation, coma, seizures
*fatigue, weakness, N/V

PE: tachycardia, hypotension, ↓ skin turgor, ↑ capillary refill time

dx
Criteria: one of the following
1) Fasting plasma glucose ≥126mg/dL on >1 occasion
2) Random plasma glucose ≥200mg/dL + classic s/sxs of hyperglycemia
3) OGTT – plasma glucose ≥200mg/dL after 2hr
4) HbA1C ≥6.5% confirmed by repeat testing

HIGH insulin & C-peptide

HHS:
*BG >600mg/dL, often >1000mg/dL
*Plasma osmolality >320
*pH >7.3, bicarb >18
*ketones: small

tx
Initial: diet, exercise, lifestyle changes
Asymptomatic:
*metformin MC initial
*intolerance/CI: GLP-1 receptor agonists, SGLT2 inhibitors
Symptomatic: insulin indicated as initial therapy

HHS: fluids most important management!!
*start IV fluids – 0.9% NaCl at 1L/h
*once glucose ~300mg/dL 🡪 5% dextrose w/ 0.45% NaCl at 150-250mL/h

Insulin: 0.1units/kg bolus then 0.1units/kg/h continuous IV infusion

Potassium: same guidelines as in DM1

Question 12

DMT1 medications: rapid acting and long acting

Answer 12

rapid acting
aspart
lispro
glulisine

long acting
detemir
glargine
degludec

Question 13

DMT2 medications: Biguanides MOA, CI

Answer 13

metformin- first line

MOA: Decreased hepatic glucose production

CI: Severe renal or hepatic impairment
- held before giving iodinated contrast, resumed 48hrs after

Question 14

DMT2 medications: Sulfonylureas MOA

Answer 14

2nd gen: glipizide, glyburide, glimepiride
1st gen: tolbutamide, chlorpropamide

MOA: Stimulates pancreatic beta cell insulin release

Question 15

DMT2 medications: GLP-1 Agonists MOA, CI

Answer 15

Iiraglutide, semaglutide, dulaglutide

MOA: Increased glucose-dependent insulin secretion

CI: Hx of gastroparesis or pancreatitis
Medullary thyroid cancer

Question 16

DMT2 medications: SGLT-2 Inhibitors MOA

Answer 16

empagliflozin
canagliflozin
dapagliflozin

MOA: Lowers renal glucose threshold, leading to increased urinary glucose excretion

Question 17

Hyperthyroidism defintion: Graves and Thyroid storm

Answer 17

Causes:
*Grave’s Disease (MC)
*toxic multinodular goiter (Plummer’s Disease)
*toxic adenoma
*TSH secreting pituitary adenoma
*amiodarone

Grave’s: autoimmune – TSH receptor antibodies cause ↑ thyroid hormone synthesis, release, & thyroid gland growth worse w/ stress (pregnancy, illness)

Thyrotoxic Crisis (Thyroid Storm): potentially fatal complication of untreated thyrotoxicosis usually after a precipitating event

Question 18

Hyperthyroidism sx

Answer 18

Clinical hyperthyroidism – diffuse, enlarged thyroid
*↑ metabolic rate (except menstrual flow which ↓)
*heat intolerance
*weight loss (despite ↑ appetite)
*skin warm, moist, soft
*fine hair, alopecia, easy bruising
*hyperactivity: anxiety, tremors, nervousness, fatigue, weakness, increased sympathetic
*diarrhea, hyperdefecation
*tachycardia, palpitations
*high-output heart failure

Grave’s:
*ophthalmopathy: lid lag, exophthalmos/proptosis
*pretibial myxedema: nonpitting, edematous, pink-brown plaques/nodules on skin
*thyroid bruits

TMG/TA:
*no skin/eye changes
*compressive sxs: dyspnea, dysphagia, stridor, hoarseness
-due to laryngeal compression

TSH secreting pituitary adenoma:
*bitemporal hemianopsia
-due to compression of optic chiasm
*HA, mental disturbances

Thyroid Storm:
*hyperthyroid sxs (exaggerated) & hypermetabolic state
-high fever (104-106F)
-CV dysfunction (palpitations, AFIB, CHF)
-CNS dysfunction (delirium, psychosis, coma)

Question 19

Hyperthyroidism dx and tx

Answer 19

dx
TFTs:
*Grave’s, TMG/TA: ↑ FT4/FT3, ↓ TSH
*TSH secreting pituitary adenoma: ↑ FT4/FT3, ↑ TSH

RAIU:
*Grave’s: ↑ diffuse uptake
*TMG: patchy areas of both ↑ & ↓ uptake
*TA: ↑ local uptake (hot nodule)
*TSH secreting pituitary adenoma: ↑ diffuse uptake

Grave’s: + TSH-receptor Ab (hallmark)
+/- thyroid peroxidase, anti-TG Ab

TSH secreting pituitary adenoma:
*pituitary MRI: adenoma

tx
Grave’s:
- radioactive iodine (MC therapy)
- methimazole or PTU
*PTU preferred in pregnancy
- BBs (propranolol) for sxs relief
- thyroidectomy
- ophthalmopathy: glucocorticoids

TMG/TA:
- radioactive iodine (MC therapy)
- subtotal thyroidectomy
- methimazole or PTU
- BBs for sxs of thyrotoxicosis

TSH secreting pituitary adenoma:
- transsphenoidal surgery to remove

Thyroid Storm:
- IV fluids
- propranolol
- PTU; 1hr later 🡪 IV sodium iodide
- IV glucocorticoids
- antipyretics (AVOID ASPIRIN)

Question 20

Hypothyroidism definition Hashimoto and myxedema coma

Answer 20

Causes:
*Hashimoto (Chronic Lymphocytic) – MC
*medications: amiodarone, lithium, alpha interferon

Hashimoto: autoimmune thyroid cell destruction by anti-thyroid peroxidase & anti-thyroglobulin antibodies

Myxedema Coma: extreme form of hypothyroidism usually d/t an acute precipitating factor – MC seen in elderly women in winter

Question 21

Hypothyroidism sx

Answer 21

sx
Clinical hypothyroidism – painless, enlarged thyroid
*↓ metabolic rate (except menstrual flow which ↑)
*cold intolerance
*weight gain (despite ↓ appetite)
*dry, thick roughened skin
*loss of outer 1/3 eyebrow
*hypoactivity: fatigue, sluggishness, memory loss, depression, ↓ DTR
*hoarseness of voice
*constipation, anorexia
*bradycardia, decreased CO
*pericardial effusion

Hashimoto:
*myxedema: nonpitting (periorbital, peripheral)

Medication-induced:
*thyrotoxicosis 🡪 hypothyroid (depends when they present)

Myxedema Coma: exaggerated hypothyroidism
*bradycardia
*hypothermia
*hypotension

Question 22

Hypothyroidism dx and tx

Answer 22

dx
TFTs: ↓ FT4/FT3, ↑ TSH

Hashimoto:
*(+) anti-thyroid peroxidase &/or anti-TG Ab
*bx: lymphocytes, germinal follicles

tx
Hashimoto:
- levothyroxine
*monitor TSH @ 6wk intervals
*ADRs: adverse CV effects, osteoporosis

Medication-Induced:
- often returns to euthyroid when D/C
- corticosteroids

Myxedema Coma:
- IV levothyroxine
- supportive: warming, IV fluids
- IV glucocorticoids

Question 23

Hyperparathyroidism definition, sx, dx, tx

Answer 23

Excess PTH

Etiologies:
*parathyroid adenoma MCC; parathyroid hyperplasia or enlargement
*lithium
*MEN I & IIa

sx
Signs of hypercalcemia: “stones, bones, abdominal groans, psychiatric moans”
*nephrolithiasis
*painful bones, fractures
*ileus, constipation, N/V
*weakness, ↓ DTRs

dx
Triad: hypercalcemia + ↑ PTH + ↓ phosphate

*↑ 24hr urine calcium excretion, ↑ vitamin D

Ancillary: may have osteopenia on bone scan; imaging studies to detect parathyroid adenoma (U/S or nuclear scanning)

tx
Parathyroidectomy
*Cinacalcet if not surgical candidate
Very high calcium:
*IV fluids, furosemide, calcitonin

Question 24

Hypoparathyroidism definition, sx, dx, tx

Answer 24

Etiologies:
*post neck surgery & autoimmune MCC
*radiation therapy
*hypomagnesemia

sx
Signs of hypocalcemia
*carpopedal spasm
*perioral numbness
*Trousseau & Chvostek signs
*increased DTRs

dx
Triad: hypocalcemia + ↓ PTH + ↑ phosphate
EKG: prolonged QT interval

tx
*calcium supplementation + vit D (calcitriol)
Acute symptomatic hypocalcemia:
*IV calcium gluconate

Question 25

Acute Thyroiditis MCC, sx, dx, tx

Answer 25

Etiology: staph aureus MC

sx
PAINFUL, fluctuant thyroid
*usually very ill (chills, pharyngitis), febrile

dx
Leukocytosis, ↑ ESR
TFTs usually normal
FNA w/ gram stain & culture
U/S

tx
- abx
- surgical drainage if fluctuant

Question 26

Pheochromocytoma definition

Answer 26

*catecholamine-secreting adrenal tumor (chromaffin cells)
*rare (causes 0.1-0.5% HTN) but MC adrenal tumor in adults
*may be associated w/ MEN II, neurofibromatosis type I, & von Hippel-Lindau disease

90% benign; rule of 10s – 10% malignant, 10% bilateral, 10% seen in children, 10% extra-adrenal (paraganglioma)

PATHO:
*secretes norepinephrine, epinephrine, & dopamine autonomously & intermittently – triggers include surgery, exercise, pregnancy, meds (TCAs, opiates, metoclopramide, glucagon, histamine)

Question 27

Pheochromocytoma sx, dx, tx

Answer 27

sx
HTN most consistent finding – may be temporary or sustained

PHE:
*Palpitations
*Headache
*Excessive sweating

*chest or abdominal pain, weakness, fatigue, weight loss (despite appetite), & pallor

dx
Biochemical testing: plasma fractionated metanephrines confirmed by 24hr urinary fractionated catecholamines including metabolites
*↑ metanephrines
*↑ vanillylmandelic acid

MRI or CT of abdomen & pelvis

MIBG scanning: nuclear isotope that can detect tumors outside of the adrenal gland if CT or MRI is negative

tx
Complete adrenalectomy after at least 1-2wks of medical therapy

Medical therapy:
*nonselective alpha blockade: phenoxybenzamine or phentolamine 1-2wks 🡪 BB/CCBs to control BP prior to surgery

Do NOT initiate therapy w/ beta-blockade to prevent unopposed alpha constriction during catecholamine release triggered by surgery or spontaneously, which could lead to life-threatening HTN crisis

Question 28

Cushing’s Syndrome definition sx, dx, tx

Answer 28

*s/sxs related to cortisol excess

Etiologies:
*long-term high-dose steroid therapy MCC overall
*exogenous
*Cushing’s Disease: pituitary ACTH overproduction
*endogenous (MCC)
*ectopic ACTH-producing tumor (SCLC) *endogenous
*adrenal tumor (adenoma) *endogenous

dx
Fat redistribution:
*central obesity, “moon facies”
*buffalo hump, supraclavicular fat pads
*thin extremities

Skin:
*thin skin (atrophy), striae (red or purple, 1cm wide)
*easy bruising, ↓ wound healing
*hyperpigmentation if ↑ ACTH

Acanthosis nigricans: epidermal hyperplasia & thickening of the skin esp. around neck/armpit w/ hyperinsulinemia
Androgen excess: hirsutism, acne, oily skin

dx
Screening tests:
(1) 24hr urinary-free cortisol (most specific)
(2) nighttime salivary cortisol
(3) low-dose (1mg) overnight dexamethasone suppression test
*elevated cortisol/no suppression = (+) syndrome
Differentiating tests: ACTH + high-dose dex suppression test
*Cushing’s Disease: ↑ ACTH + SUPPRESSION
*Ectopic ACTH-producing tumor: ↑ ACTH + no suppression
*Adrenal tumors, steroids: ↓ ACTH + no suppression

Labs: hyperglycemia, dyslipidemia, leukocytosis, hypokalemia, metabolic alkalosis

Cushing’s Disease 🡪 pituitary MRI
Adrenal tumor 🡪 abdominal CT
Ectopic ACTH-producing lung tumor 🡪 CXR

tx
Corticosteroid use:
*gradual taper to prevent Addisonian crisis

Cushing’s Disease:
*transsphenoidal resection
*inoperable 🡪 radiation, Pasireotide

Adrenal tumor: tumor excision

Ectopic tumor: resection
*unresectable 🡪 Ketoconazole, Metyrapone