Emergency Medicine Rotation: Endocrinology (Smarty PANCE)

What is the most common cause of primary adrenal insufficiency (Addison disease) in the developed world?

Autoimmune adrenalitis (~80% of cases); associated with anti-21-hydroxylase antibodies; bilateral adrenal destruction leads to deficiency of cortisol, aldosterone, and androgens

What is the classic triad of chronic primary adrenal insufficiency?

Fatigue/weakness, hyperpigmentation (ACTH-driven MSH effect on melanocytes), and orthostatic hypotension; also: hyponatremia, hyperkalemia, hypoglycemia

What electrolyte pattern distinguishes primary from secondary adrenal insufficiency?

Primary: hyponatremia + hyperkalemia (aldosterone deficiency); Secondary (pituitary): hyponatremia only (ACTH loss → cortisol loss; aldosterone preserved via RAAS)

What is an adrenal crisis and how does it present in the ED?

Life-threatening acute cortisol deficiency: severe hypotension/shock refractory to fluids/pressors, nausea/vomiting, abdominal pain, fever, hypoglycemia, hyponatremia, hyperkalemia

What is the gold standard diagnostic test for adrenal insufficiency?

ACTH (cosyntropin) stimulation test: cortisol level <18 mcg/dL at 60 minutes after 250 mcg IV/IM cosyntropin = abnormal (insufficient adrenal reserve)

What is the emergency treatment of adrenal crisis?

Hydrocortisone 100 mg IV bolus STAT, then 50–100 mg IV q6–8h; aggressive IV normal saline (1–2 L); dextrose for hypoglycemia; do NOT delay treatment for confirmatory testing

What lab findings are classically seen with adrenal insufficiency?

Hyponatremia, hyperkalemia, hypoglycemia, eosinophilia, lymphocytosis, elevated BUN (prerenal); low morning cortisol (<3 mcg/dL is diagnostic)

What are the most common causes of secondary adrenal insufficiency?

Exogenous glucocorticoid use (most common worldwide), pituitary tumors, Sheehan syndrome, traumatic brain injury, pituitary apoplexy

What is the classic biochemical signature of Cushing syndrome?

Elevated 24-hour urinary free cortisol, elevated late-night salivary cortisol, and failure to suppress AM cortisol to <1.8 mcg/dL after 1 mg overnight dexamethasone suppression test

What differentiates Cushing disease from Cushing syndrome?

Cushing disease = pituitary ACTH-secreting adenoma (most common cause of endogenous Cushing); Cushing syndrome = any cause of excess cortisol (includes adrenal tumors, ectopic ACTH, exogenous steroids)

What are the classic clinical features of Cushing syndrome? Use mnemonic CUSHINGS

Central obesity, Ulcers/poor wound healing, Striae (purple), Hypertension, Infections (immunosuppression), Neuropsychiatric (depression/psychosis), Glucose elevation (DM), Skin thinning/easy bruising

What is the most common cause of Cushing syndrome overall?

Exogenous (iatrogenic) glucocorticoid use; most common endogenous cause is Cushing disease (pituitary adenoma)

Which test best differentiates pituitary from ectopic ACTH production in Cushing syndrome?

High-dose dexamethasone suppression test (8 mg): pituitary source suppresses cortisol >50%; ectopic ACTH source (e.g., small cell lung cancer) does NOT suppress

What electrolyte abnormality is most associated with ectopic ACTH syndrome (e.g., small cell lung cancer)?

Severe hypokalemia (cortisol acts on mineralocorticoid receptors); also metabolic alkalosis; much more rapid onset than pituitary Cushing

What is the imaging of choice for Cushing disease vs. adrenal Cushing?

Cushing disease: MRI pituitary (may be too small to visualize); adrenal Cushing: CT adrenal glands; ectopic ACTH: CT chest/abdomen

What is central (neurogenic) diabetes insipidus and what causes it?

Deficiency of ADH (vasopressin) secretion from posterior pituitary; causes: idiopathic, head trauma, neurosurgery, pituitary tumors, Sheehan syndrome, sarcoidosis, meningitis

What is nephrogenic diabetes insipidus and its most common causes?

Renal resistance to ADH; causes: lithium toxicity (most common drug), hypercalcemia, hypokalemia, chronic kidney disease, hereditary (V2 receptor mutation)

What are the classic lab findings in diabetes insipidus?

Hypernatremia, serum osmolality >295 mOsm/kg, inappropriately dilute urine (urine osmolality <300 mOsm/kg, urine specific gravity <1.005), polyuria (>3 L/day), polydipsia

What is the water deprivation test and how does it differentiate DI types?

Withhold water until urine osmolality plateaus, then give desmopressin (DDAVP): Central DI → urine osmolality increases >50% after DDAVP; Nephrogenic DI → minimal response (<10%); Psychogenic polydipsia → urine concentrates before DDAVP

What is the treatment for central vs. nephrogenic DI?

Central DI: intranasal or IV desmopressin (DDAVP); Nephrogenic DI: treat underlying cause, low-salt/low-protein diet, thiazide diuretics (paradoxically), NSAIDs

What is the emergency management of severe hypernatremia in DI?

Calculate free water deficit; replace with hypotonic fluids (D5W or 0.45% NS); correct no faster than 0.5 mEq/L/hour (max 10–12 mEq/L per 24h) to prevent cerebral edema

What are the diagnostic criteria for Type 2 DM?

Any ONE of: fasting glucose ≥126 mg/dL (×2), 2-hour OGTT glucose ≥200 mg/dL, HbA1c ≥6.5% (×2), or random glucose ≥200 mg/dL WITH classic symptoms (polyuria, polydipsia, weight loss)

What is the first-line pharmacologic treatment for Type 2 DM without contraindications?

Metformin (biguanide); mechanism: decreases hepatic glucose production, improves insulin sensitivity; contraindicated in eGFR <30, active liver disease, active/risk of lactic acidosis

What are the diagnostic criteria for DKA vs. HHS?

DKA: glucose >250, pH <7.3, bicarb <18, anion gap >12, positive ketones; HHS: glucose >600, pH >7.3, bicarb >18, osmolality >320 mOsm/kg, minimal/no ketones

What microvascular complications of DM are screened for and how?

Retinopathy: annual dilated eye exam; Nephropathy: urine albumin-to-creatinine ratio (microalbuminuria >30 mg/g); Neuropathy: 10-g monofilament exam + ankle reflexes annually

Which SGLT-2 inhibitors and GLP-1 agonists have proven cardiovascular and renal benefit in DM?

SGLT-2 inhibitors (empagliflozin, canagliflozin, dapagliflozin): reduce CV events + renal progression; GLP-1 agonists (semaglutide, liraglutide): reduce MACE events; preferred in DM + ASCVD or CKD

What is the triad of DKA?

Hyperglycemia (>250 mg/dL) + Anion gap metabolic acidosis + Ketonemia/ketonuria; caused by insulin deficiency + glucagon excess → uncontrolled lipolysis → ketone production

What are the most common precipitants of DKA? Use the 6 I's

Infection (most common), Insulin non-compliance/Inadequate dosing, Infarction (MI, stroke), Intoxication, Iatrogenic (steroids, SGLT-2 inhibitors), Initial presentation of new T1DM

What are the steps in DKA management in the ED?

1) IV fluids: 1–2 L NS bolus, then 250–500 mL/hr; 2) Insulin: regular insulin 0.1 unit/kg/hr infusion (after K+ ≥3.5); 3) Potassium replacement (target 3.5–5.5 mEq/L); 4) Monitor glucose hourly, BMP q2–4h

When should insulin infusion be started in DKA and why is potassium critical first?

Do NOT start insulin if K+ <3.5 mEq/L — insulin drives K+ intracellularly, worsening hypokalemia → fatal arrhythmia; replace K+ to ≥3.5 before initiating insulin

When should dextrose be added to IV fluids in DKA management?

When glucose falls to 200–250 mg/dL — switch to D5-0.45% NS; continue insulin until anion gap closes (not until glucose normalizes); goal is to clear ketones, not just lower glucose

What are the criteria for DKA resolution?

Glucose <200 mg/dL, serum bicarb ≥15 mEq/L, anion gap ≤12, and pH >7.3; transition to subcutaneous insulin with 1–2 hour overlap before stopping insulin infusion

Why can serum potassium be normal or elevated on presentation in DKA despite total body K+ depletion?

Acidosis drives K+ out of cells (H+/K+ exchange); insulin deficiency further impairs cellular K+ uptake; total body K+ is depleted due to osmotic diuresis (urinary loss)

What is euglycemic DKA and what causes it?

DKA with glucose <250 mg/dL; most commonly caused by SGLT-2 inhibitors (empagliflozin, canagliflozin, dapagliflozin); also pregnancy, fasting, alcohol; high clinical suspicion required — check ketones/pH regardless of glucose

What is the most common cause of heat intolerance in the context of endocrine disease?

Hyperthyroidism (excess thyroid hormone increases BMR and heat production); also consider pheochromocytoma (episodic), menopause (hot flashes/vasomotor), and carcinoid syndrome

What is the most common cause of cold intolerance in endocrine disease?

Hypothyroidism (decreased BMR, decreased thermogenesis); also consider adrenal insufficiency, anemia (non-endocrine), and autonomic dysfunction

What clinical features distinguish heat intolerance of hyperthyroidism from pheochromocytoma?

Hyperthyroidism: constant heat intolerance, weight loss despite increased appetite, tachycardia, tremor; Pheochromocytoma: episodic "spells" of headache + diaphoresis + palpitations + hypertension (classic triad + HTN)

What is the diagnostic workup for pheochromocytoma as a cause of heat/sympathetic symptoms?

24-hour urine fractionated metanephrines and catecholamines OR plasma free metanephrines (most sensitive); imaging (CT/MRI adrenal) after biochemical confirmation

What electrolyte abnormality causes heat intolerance and muscle cramps and is associated with hypoparathyroidism?

Hypocalcemia: tetany, cramps, Chvostek sign (facial twitch with CN VII tap), Trousseau sign (carpal spasm with BP cuff inflation); hypoparathyroidism → low Ca2+, high phosphate

What is the most common cause of primary hyperparathyroidism?

Solitary parathyroid adenoma (~85%); less common: hyperplasia (10–15%), parathyroid carcinoma (<1%); associated with MEN1 (parathyroid + pituitary + pancreas) and MEN2A

What are the classic symptoms of hypercalcemia from hyperparathyroidism? Use mnemonic Stones, Bones, Groans, Thrones, Psychic Moans

Stones (nephrolithiasis, nephrocalcinosis), Bones (osteitis fibrosa cystica, subperiosteal resorption), Groans (nausea, vomiting, constipation, pancreatitis), Thrones (polyuria, polydipsia), Psychic Moans (depression, cognitive impairment)

What lab pattern is diagnostic of primary hyperparathyroidism?

Elevated PTH (inappropriately normal or high) + hypercalcemia + hypophosphatemia + hyperchloremia + elevated urine calcium; 24-hr urine Ca helps exclude familial hypocalciuric hypercalcemia (FHH)

What calcium level requires emergency treatment and what is the treatment?

Symptomatic or Ca2+ >14 mg/dL: IV NS (2–4 L aggressive hydration), IV furosemide (after rehydration), IV bisphosphonates (zoledronic acid or pamidronate — onset 2–4 days), IV calcitonin (fastest onset, 4–6 hours, tachyphylaxis)

What is the difference between primary, secondary, and tertiary hyperparathyroidism?

Primary: autonomous PTH secretion (adenoma/hyperplasia); Secondary: compensatory PTH elevation due to chronic hypocalcemia (CKD, vitamin D deficiency); Tertiary: autonomous PTH secretion developing from long-standing secondary (post-renal transplant)

What is the most common cause of hyperthyroidism?

Graves disease (~80%): autoimmune; TSH receptor-stimulating antibodies (TRAb/TSI) → diffuse thyroid stimulation; classic triad: diffuse goiter + exophthalmos (proptosis) + pretibial myxedema

What are the classic clinical features of hyperthyroidism?

Heat intolerance, weight loss with increased appetite, palpitations/tachycardia/afib, tremor, anxiety/irritability, diarrhea, menstrual irregularities, warm moist skin, hair loss, lid lag/stare

What TSH and T4/T3 pattern confirms hyperthyroidism?

Low TSH (<0.1 mIU/L) + elevated free T4 and/or free T3; subclinical hyperthyroidism = low TSH + normal free T4/T3

What is thyroid storm and how is it managed?

Life-threatening hyperthyroidism: HR>140, hyperthermia >40°C, altered mental status, N/V, heart failure; Treatment order: 1) PTU (blocks synthesis AND T4→T3 conversion), 2) Iodine (Lugol's, 1 hour after PTU), 3) Beta-blocker (propranolol), 4) Steroids (hydrocortisone/dexamethasone), 5) Treat precipitant

What is the Burch-Wartofsky score used for?

Scoring system to diagnose thyroid storm (score ≥45 = highly likely): assesses thermoregulatory dysfunction, CNS effects, GI-hepatic dysfunction, heart rate, afib, heart failure, and precipitant history

What are the first-line and second-line treatments for Graves hyperthyroidism?

First-line: antithyroid drugs (methimazole preferred; PTU in pregnancy first trimester); Radioactive iodine (RAI/I-131) is also first-line in US; Surgery (thyroidectomy) for large goiter, malignancy concern, or RAI failure; Beta-blockers for symptom control

Why is PTU preferred over methimazole in specific clinical scenarios?

PTU preferred in: thyroid storm (blocks peripheral T4→T3 conversion), first trimester pregnancy (methimazole teratogenic — aplasia cutis, choanal atresia), thyrotoxic crisis

What is the most common cause of hypothyroidism in developed countries?

Hashimoto thyroiditis (chronic lymphocytic thyroiditis): autoimmune; anti-TPO antibodies (most sensitive) + anti-thyroglobulin antibodies; most common cause worldwide is iodine deficiency

What are the classic clinical features of hypothyroidism?

Cold intolerance, weight gain, fatigue, constipation, bradycardia, dry skin, coarse/thinning hair, periorbital edema, hoarseness, delayed DTRs (hung-up reflexes), menorrhagia, depression, myxedema

What TSH and free T4 pattern confirms primary hypothyroidism?

Elevated TSH + low free T4 = overt hypothyroidism; Elevated TSH + normal free T4 = subclinical hypothyroidism; Central hypothyroidism (pituitary): low/normal TSH + low free T4

What is myxedema coma and how is it treated emergently?

Severe decompensated hypothyroidism: hypothermia, altered mental status/coma, bradycardia, hypoventilation, hypotension, hyponatremia; Treatment: IV T4 (levothyroxine 200–400 mcg loading dose) ± IV T3, hydrocortisone (concurrent adrenal insufficiency), rewarming, supportive care

What medications commonly cause hypothyroidism?

Amiodarone (iodine-rich — can cause both hypo and hyperthyroidism), lithium (blocks thyroid hormone release), interferon-alpha, tyrosine kinase inhibitors, immunotherapy (checkpoint inhibitors), excessive iodine (Wolff-Chaikoff effect)

What is the treatment for hypothyroidism and how is it monitored?

Levothyroxine (T4) PO daily on empty stomach; start low and go slow in elderly/cardiac patients; recheck TSH in 6–8 weeks after initiation or dose change; target TSH 0.5–2.5 mIU/L (lower target in pregnancy)

What is Hashimoto thyroiditis and what antibodies are associated?

Autoimmune destruction of thyroid by lymphocytic infiltration; associated with anti-TPO antibodies (>90%, most sensitive) and anti-thyroglobulin antibodies; can cause transient hyperthyroidism (hashitoxicosis) before hypothyroidism

What is hyperglycemic hyperosmolar state (HHS) and what population does it affect?

Severe hyperglycemia (>600 mg/dL) + hyperosmolality (>320 mOsm/kg) + altered mental status WITHOUT significant ketoacidosis; occurs in elderly type 2 DM; mortality 10–20% (higher than DKA)

What is the pathophysiology of HHS vs. DKA?

HHS: enough residual insulin to suppress lipolysis/ketogenesis but NOT glucose uptake → no ketones; DKA: absolute/near-absolute insulin deficiency → uncontrolled lipolysis → ketones; both have osmotic diuresis and profound dehydration

What is the fluid deficit in HHS and how is it replaced?

Fluid deficit averages 8–10 L (greater than DKA); initial resuscitation: 1 L NS bolus, then calculated free water deficit replacement over 24–48 hours; switch to 0.45% NS once hemodynamically stable

What is the insulin strategy in HHS?

Fluid resuscitation is the primary treatment; insulin infusion (0.1 unit/kg/hr) started AFTER initial fluids; glucose falls more readily with fluids alone in HHS vs. DKA; add dextrose when glucose <300 mg/dL

What are the neurological complications of HHS and why do they occur?

Cerebral edema (especially if corrected too rapidly), focal seizures, hemiplegia, and altered mental status due to profound hyperosmolality; correct sodium and osmolality no faster than 3–8 mOsm/kg/hr

What is the corrected sodium formula used in HHS management?

Corrected Na = measured Na + 1.6 mEq/L per 100 mg/dL glucose above 100; helps assess true sodium status; as glucose normalizes, sodium should rise (if corrected Na was normal, true hypernatremia will emerge)

What are the most common endocrine causes of palpitations in the emergency setting?

Hyperthyroidism (sinus tachycardia, afib), pheochromocytoma (paroxysmal HTN + palpitations + diaphoresis + headache), hypoglycemia (catecholamine surge), and carcinoid syndrome (flushing + diarrhea + wheezing)

What is the classic presentation of pheochromocytoma causing palpitations?

Paroxysmal "spells": severe hypertension + palpitations + diaphoresis + headache (classic triad); triggered by physical exertion, anesthesia, medications (beta-blockers can worsen); associated with MEN2A, MEN2B, VHL, NF1

What is the most dangerous medication to give a patient with pheochromocytoma causing hypertensive crisis?

Beta-blockers without alpha-blockade first — causes unopposed alpha-adrenergic stimulation → severe hypertension/hypertensive emergency; always give alpha-blockade (phentolamine IV, or phenoxybenzamine pre-op) FIRST

How does hypoglycemia cause palpitations and what are the associated findings?

Hypoglycemia (<70 mg/dL) triggers catecholamine surge → tachycardia, palpitations, diaphoresis, tremor, anxiety; Whipple's triad: hypoglycemic symptoms + low glucose + relief with glucose administration

What ECG findings are associated with endocrine causes of palpitations?

Hyperthyroidism: sinus tachycardia, atrial fibrillation; Hyperkalemia (Addison's): peaked T waves → PR prolongation → wide QRS → sine wave; Hypocalcemia (hypoparathyroidism): prolonged QT; Hypomagnesemia: torsades de pointes

How should new-onset afib in the ED be evaluated for an endocrine cause?

Always check TSH in new-onset afib — hyperthyroidism is a reversible cause; if TSH suppressed, treat the thyroid disease first; rate control with beta-blockers (or CCBs if beta-blockers contraindicated); cardioversion after thyroid disease treated

What is Hashimoto thyroiditis and how can it cause transient hyperthyroidism (hashitoxicosis)?

Autoimmune lymphocytic destruction of the thyroid; initial inflammatory destruction releases stored thyroid hormone → transient hyperthyroidism (hashitoxicosis); eventually leads to hypothyroidism; RAI uptake is LOW (distinguishes from Graves)

What is subacute (de Quervain) thyroiditis and its classic presentation?

Post-viral inflammatory thyroiditis: painful, tender thyroid gland, fever, preceded by URI; phases: hyperthyroid → euthyroid → hypothyroid → euthyroid; elevated ESR/CRP; LOW radioactive iodine uptake; self-limited

What is the treatment for subacute granulomatous (de Quervain) thyroiditis?

NSAIDs or aspirin for mild cases; prednisone for severe pain/systemic symptoms; beta-blockers for symptomatic hyperthyroidism (no antithyroid drugs — not synthesis-driven); disease is self-limited (weeks to months)

What is silent (painless) thyroiditis and who is most commonly affected?

Autoimmune subacute thyroiditis without pain; most common in postpartum women (postpartum thyroiditis — occurs 1–6 months post-delivery); same triphasic course as de Quervain; low RAI uptake; anti-TPO antibodies present

How do you differentiate the hyperthyroid phase of thyroiditis from Graves disease?

Both: low TSH + high T4/T3; Distinguishing test: radioactive iodine uptake (RAIU): Thyroiditis → LOW/absent uptake (no synthesis, just release); Graves → HIGH uptake (active synthesis); also: thyroiditis is painful (de Quervain) or painless

What is Riedel thyroiditis?

Rare fibrosing thyroiditis: dense fibrosis replaces thyroid and invades adjacent structures → "rock hard" woody thyroid, dysphagia, hoarseness, stridor; associated with IgG4-related disease; treat with steroids ± tamoxifen

What is amiodarone-induced thyroiditis and how does it present?

Amiodarone (iodine-rich drug) causes: Type 1 = iodine-induced hyperthyroidism (treat with thionamides); Type 2 = destructive thyroiditis releasing preformed hormone (treat with steroids); difficult to distinguish; thyroid function must be checked before and during amiodarone

What are the most common causes of tremor in endocrine disease?

Hyperthyroidism (fine resting/postural tremor), hypoglycemia (catecholamine-mediated tremor + diaphoresis), pheochromocytoma (paroxysmal tremor + HTN + diaphoresis), medication-induced (lithium, corticosteroids, levothyroxine overdose), Wilson disease

How does the tremor of hyperthyroidism differ from Parkinson tremor?

Hyperthyroid tremor: fine, fast (8–12 Hz), postural/action tremor, bilateral, associated with tachycardia/weight loss/heat intolerance; Parkinson tremor: slow (4–6 Hz), resting "pill-rolling," unilateral onset, improves with movement (action)

What is the mechanism of tremor in hypoglycemia and what glucose level triggers it?

Blood glucose <70 mg/dL → catecholamine (epinephrine) surge → adrenergic symptoms: tremor, diaphoresis, palpitations, anxiety, tachycardia; neuroglycopenic symptoms (confusion, seizure, coma) occur at lower levels (<50 mg/dL)

What is the treatment of hypoglycemia-induced tremor/neuroglycopenic symptoms in the ED?

Conscious patient: 15–20 g fast-acting oral glucose (juice, glucose tablets — "Rule of 15"); Unconscious or unable to swallow: D50W 25 g (50 mL) IV push OR glucagon 1 mg IM/SQ (if no IV access); recheck glucose in 15 minutes

What endocrine cause of tremor is associated with elevated urinary catecholamines and episodic HTN?

Pheochromocytoma; diagnosis: plasma free metanephrines (most sensitive, best for high-risk patients) or 24-hour urine fractionated metanephrines/catecholamines; never start beta-blocker without alpha-blockade first

What is essential tremor and how does it relate to thyroid disease clinically?

Essential tremor: bilateral, postural/kinetic, high-frequency (6–12 Hz), worsens with action, improves with alcohol; can mimic hyperthyroid tremor — always check TSH to rule out thyroid etiology before diagnosing essential tremor

What medication-related tremors are relevant in endocrine/EM contexts?

Lithium (used in bipolar) → tremor + hypothyroidism + nephrogenic DI; corticosteroid excess → proximal myopathy + tremor; levothyroxine overdose mimics hyperthyroidism; valproic acid → postural tremor (non-endocrine but common EM differential)