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System 06 · ~7% of exam

Endocrine

Pattern recognition lives here. Hyper vs hypo for each gland. Classic lab signatures. DKA/HHS, thyroid storm, myxedema coma, adrenal crisis are the emergencies.

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Chief complaints

BUILD THE DIFFERENTIAL

Vignettes enter through one of these doors. Each complaint lays out the full differential, marks the can't-miss diagnoses, and tells you the next right action for each.

Polyuria & polydipsiaThyroid symptomsWeight change
CHIEF COMPLAINT · HIGH-YIELD

Polyuria & polydipsia

Diabetes mellitus, diabetes insipidus, or primary polydipsia.

Approach

Check glucose first. If normal, serum and urine osm, water deprivation test. DM: hyperglycemia with osmotic diuresis. Central DI: low urine osm, responds to desmopressin. Nephrogenic DI: low urine osm, no response to desmopressin. Primary polydipsia: dilute urine with normal or low-normal serum Na.

The differential
Diagnosis Key features / clues Next step
Diabetic ketoacidosis Type 1 DM, abdominal pain, vomiting, Kussmaul breathing, fruity breath, polyuria/polydipsia. Glucose > 250, anion gap > 12, ketones, pH < 7.3. IV fluids (NS bolus then maintenance with KCl if K < 5.3) · IV insulin drip · monitor K Q2 hr · transition to SC when gap closed
Hyperosmolar hyperglycemic state Type 2 DM, severe hyperglycemia (> 600), hyperosmolar, minimal ketones, severe dehydration, altered mental status. Aggressive IV fluids (often 6–10 L) · insulin drip (lower rate) · K replacement
New-onset DM Polyuria, polydipsia, weight loss, fatigue. Random glucose > 200 with symptoms, or A1c ≥ 6.5, or FPG ≥ 126, or OGTT ≥ 200. Confirm diagnosis · lifestyle · metformin for type 2 · insulin for type 1 or severe
Central DI Large volume dilute urine, hypernatremia, recent pituitary surgery or trauma, craniopharyngioma. Water deprivation test · desmopressin responds · MRI pituitary
Nephrogenic DI Lithium, chronic hypercalcemia, hypokalemia, genetic. No response to desmopressin. Remove offending agent · thiazide (paradoxically reduces urine output)
Primary polydipsia Psychiatric patient, excessive fluid intake, dilute urine. Fluid restriction · treat underlying psychiatric condition
⚑ = can't-miss diagnosis · rule out first
Classic vignette
Exam-style stem
A 16-year-old girl with 2 days of nausea, vomiting, polyuria, and fatigue. Kussmaul breathing. Glucose 480, pH 7.12, HCO3 8, anion gap 24, K 5.4, Na 132, ketones positive.
Next step in management?
Answer › Normal saline bolus (15–20 mL/kg over 1 hour), then insulin drip 0.1 U/kg/hr (after fluids start to avoid cerebral edema). Hold insulin if K < 3.3 until replaced. Add dextrose when glucose < 200 to continue insulin until gap closes.
Pearls
Pearl
In DKA, K is often falsely elevated from the acidosis (shift). Total body K is depleted. Replace aggressively once urine output is adequate.
Pearl
Resolution of DKA is defined by closure of the anion gap, not normalization of glucose. Add dextrose to IV fluids when glucose drops to 200.
Pearl
Cerebral edema in pediatric DKA: change in mental status during treatment. Slow fluid resuscitation and consider mannitol or hypertonic saline.
CHIEF COMPLAINT · HIGH-YIELD

Thyroid symptoms

Hyperthyroid (heat intolerance, tachycardia, weight loss, tremor) vs hypothyroid (cold intolerance, bradycardia, weight gain, fatigue).

Approach

TSH is the first test. Low TSH → high free T4 = primary hyperthyroid. High TSH → low free T4 = primary hypothyroid. Radioiodine uptake helps differentiate hyperthyroid causes.

The differential
Diagnosis Key features / clues Next step
Thyroid storm Severe hyperthyroid with fever, tachycardia, delirium, GI symptoms, HF. Precipitant: surgery, infection, iodine load. Beta-blocker (propranolol) · PTU or methimazole · iodine (1 hr after thionamide) · steroids · cooling · treat precipitant
Myxedema coma Severe hypothyroid with hypothermia, bradycardia, hypotension, hyponatremia, AMS. IV levothyroxine + stress-dose steroids (until adrenal insufficiency ruled out) · supportive
Graves disease Diffuse goiter, ophthalmopathy, pretibial myxedema. Elevated TSI. Diffuse high uptake on RAIU. Methimazole (PTU in pregnancy T1) · radioactive iodine · thyroidectomy · beta-blocker for symptoms
Toxic multinodular goiter / toxic adenoma Older patient, nodular thyroid. Patchy or focal uptake on RAIU. Radioactive iodine or surgery
Subacute thyroiditis (de Quervain) Tender thyroid, recent viral illness, elevated ESR. Low uptake on RAIU. NSAIDs · beta-blocker · steroids if severe · usually self-limited
Hashimoto thyroiditis Hypothyroid, elevated anti-TPO antibodies, sometimes goiter. Levothyroxine
Subclinical thyroid disease Abnormal TSH with normal free T4. Subclinical hypo (high TSH, nl T4) or subclinical hyper (low TSH, nl T4). Treat subclinical hypo if TSH > 10 or symptomatic or pregnant or high CV risk
⚑ = can't-miss diagnosis · rule out first
Pearls
Pearl
Amiodarone can cause either hypothyroidism (iodine-induced, more common in iodine-sufficient areas) or hyperthyroidism (types 1 and 2).
Pearl
Pregnancy: PTU in first trimester (methimazole teratogenic), methimazole in second and third.
Pearl
Thyroid storm needs propranolol AND thionamide AND iodine (delayed 1 hr after thionamide). Iodine first would feed the thyroid.
CHIEF COMPLAINT

Weight change

Unintentional weight loss: malignancy, thyroid, DM, depression, GI. Weight gain: endocrine, medications, psych.

Approach

Age-appropriate cancer screening is the first step in unexplained weight loss. Thyroid, diabetes, depression screen. Adrenal, hypogonadism. Cushing features. Check medications (steroids, atypicals, insulin).

The differential
Diagnosis Key features / clues Next step
Malignancy Weight loss, fatigue, anemia, night sweats, constitutional symptoms. Age-appropriate screening · directed evaluation
Cushing syndrome Central obesity, moon face, buffalo hump, striae, bruising, HTN, hyperglycemia, proximal weakness. 24-hour urine cortisol, late-night salivary cortisol, low-dose dex suppression · ACTH · source imaging
Addison disease Weight loss, fatigue, hyperpigmentation, hyponatremia, hyperkalemia, hypotension. Morning cortisol + ACTH · cosyntropin stim · hydrocortisone
Depression Weight change (either), anhedonia, sleep/appetite changes, fatigue. PHQ-9 · SSRI and/or therapy
⚑ = can't-miss diagnosis · rule out first
Pearls
Pearl
Unexplained weight loss of > 5% over 6 months warrants workup. Age-appropriate cancer screening, TSH, CBC, metabolic panel, CXR, FOBT.
✦

Disease deep dives

DEFINITIVE DX

Once you've identified the likely diagnosis from the chief complaint, these pages give you the presentation, workup, management, and exam pearls in depth.

Type 2 Diabetes Mellitus
Insulin resistance + relative insulin deficiency. A1c-based diagnosis and targets. SGLT2i and GLP-1 are now first-line for CV and renal benefit.
Diabetic Ketoacidosis
Absolute insulin deficiency with ketoacidosis. Fluids → insulin → potassium → find precipitant.
Hyperthyroidism
Graves is the most common cause. RAIU differentiates hyperthyroid etiologies.
Hypothyroidism
Hashimoto thyroiditis is the most common cause in iodine-sufficient areas. Levothyroxine replacement.
Adrenal Insufficiency
Primary (Addison) vs secondary. Hyponatremia, hyperkalemia, hypoglycemia, hyperpigmentation in primary.
Hypercalcemia
Primary hyperparathyroidism (outpatient) and malignancy (inpatient) account for 90%. Symptoms at Ca > 12.
DISEASE DEEP DIVE

Type 2 Diabetes Mellitus

Insulin resistance + relative insulin deficiency. A1c-based diagnosis and targets. SGLT2i and GLP-1 are now first-line for CV and renal benefit.

Presentation

Often asymptomatic at diagnosis, detected on screening. Symptoms: polyuria, polydipsia, fatigue, blurred vision, recurrent infections.

Workup
  1. Diagnosis. A1c ≥ 6.5, FPG ≥ 126, OGTT 2-hr ≥ 200, or random ≥ 200 with symptoms. Confirm with repeat unless unambiguous.
  2. Screening. All adults 35+ every 3 years. Earlier if BMI ≥ 25 with risk factors.
  3. Complications. Annual: A1c every 3–6 months, lipid panel, urine ACR, creatinine, dilated eye exam, foot exam.
Management
  1. Lifestyle. Weight loss (even 5–10%), Mediterranean or DASH diet, 150 min moderate exercise per week.
  2. Metformin. First-line unless contraindicated (eGFR < 30). Start 500 mg daily with meal, titrate.
  3. Second agent based on comorbidities. ASCVD → GLP-1 RA (semaglutide, liraglutide) or SGLT2i. HF → SGLT2i (empagliflozin, dapagliflozin). CKD → SGLT2i (primary) or GLP-1 RA. Weight loss priority → GLP-1 RA or SGLT2i.
  4. A1c targets. < 7% for most. < 6.5% if young and healthy. < 8% if elderly, frail, or limited life expectancy.
  5. BP and lipid targets. BP < 130/80. Statin for all DM > 40.
  6. Insulin. If A1c > 10% at diagnosis with symptoms, or if failing multi-drug therapy. Basal first (glargine, detemir, degludec), then prandial (aspart, lispro).
Pearls
Pearl
Metformin cautions: lactic acidosis in renal failure, hepatic disease, alcohol, severe HF. Hold for contrast, reintroduce after Cr stable.
Pearl
GLP-1 RA side effects: nausea (transient), pancreatitis (rare), gallbladder disease, thyroid C-cell tumors (contraindicated if MEN2 or MTC history).
Pearl
SGLT2i side effects: genital mycotic infections, euglycemic DKA (hold before surgery), volume depletion, Fournier gangrene (rare).
Classic vignette
Exam-style stem
A 58-year-old man with T2DM on metformin has A1c 8.4. History of MI 2 years ago. eGFR 68.
Answer › Add a GLP-1 RA or SGLT2 inhibitor, both have proven CV benefit post-MI. Semaglutide or empagliflozin are reasonable choices.
DISEASE DEEP DIVE

Diabetic Ketoacidosis

Absolute insulin deficiency with ketoacidosis. Fluids → insulin → potassium → find precipitant.

Presentation

Polyuria, polydipsia, nausea, vomiting, abdominal pain, Kussmaul breathing, fruity (acetone) breath, altered mental status.

Workup
  1. Glucose, BMP, ABG. Glucose > 250, anion gap > 12, pH < 7.3, HCO3 < 18. Ketones in urine and serum (beta-hydroxybutyrate).
  2. Precipitant workup. Infection (CBC, cultures, CXR, UA), MI (ECG, troponin), medication non-adherence, new-onset DM.
Management
  1. Fluids. NS 15–20 mL/kg bolus, then 250–500 mL/hr. Switch to 0.45% NS after initial resuscitation if corrected Na is normal or high. Add D5 when glucose < 200 to keep insulin running.
  2. Insulin. 0.1 U/kg IV bolus (optional) then 0.1 U/kg/hr drip. Do not start insulin until K ≥ 3.3.
  3. Potassium. K < 3.3: hold insulin, replace K. K 3.3–5.3: add K to fluids. K > 5.3: hold K, recheck Q2 hr.
  4. Bicarbonate. Only if pH < 6.9.
  5. Transition. When anion gap closed, HCO3 ≥ 15, pH > 7.3, patient eating: overlap IV insulin with subcutaneous for 2 hours.
Pearls
Pearl
The most common precipitants: infection, non-adherence, MI, new-onset DM. Always look for a trigger.
Pearl
Euglycemic DKA: SGLT2 inhibitors. Glucose may be normal or minimally elevated but ketoacidosis is present. Hold SGLT2 perioperatively.
Pearl
Cerebral edema in children with DKA: change in neurologic status during treatment. Slower fluids and mannitol or hypertonic saline.
DISEASE DEEP DIVE

Hyperthyroidism

Graves is the most common cause. RAIU differentiates hyperthyroid etiologies.

Presentation

Heat intolerance, weight loss, palpitations, anxiety, tremor, hyperdefecation, oligomenorrhea, hyperreflexia. Graves: ophthalmopathy, pretibial myxedema, diffuse goiter.

Workup
  1. TSH. Suppressed in primary hyperthyroid.
  2. Free T4 and T3. Elevated (T3 toxicosis can have isolated T3 elevation).
  3. TSI / TSH receptor antibodies. Elevated in Graves.
  4. RAIU. Diffuse high uptake: Graves. Nodular: toxic multinodular or toxic adenoma. Low uptake: thyroiditis, exogenous, iodine-induced.
Management
  1. Beta-blocker. Propranolol for symptomatic control. Also blocks T4 to T3 conversion at high doses.
  2. Thionamides. Methimazole (first-line for most). PTU in first trimester of pregnancy and thyroid storm (inhibits T4→T3).
  3. Radioactive iodine. Definitive treatment for Graves and toxic nodules. Contraindicated in pregnancy, breastfeeding, severe ophthalmopathy.
  4. Surgery. For large goiters, pregnancy (if needed), severe ophthalmopathy, refractory cases.
Pearls
Pearl
Methimazole side effects: agranulocytosis (check CBC if fever or sore throat), hepatotoxicity, rash. PTU: hepatotoxicity more severe, ANCA-associated vasculitis.
Pearl
Graves ophthalmopathy does not improve with hyperthyroid treatment and can worsen with radioactive iodine. Steroids if active.
Pearl
Amiodarone-induced thyrotoxicosis: type 1 (Jod-Basedow, iodine-induced in predisposed) treat with thionamide; type 2 (destructive thyroiditis) treat with steroids.
DISEASE DEEP DIVE

Hypothyroidism

Hashimoto thyroiditis is the most common cause in iodine-sufficient areas. Levothyroxine replacement.

Presentation

Cold intolerance, fatigue, weight gain, constipation, dry skin, hair loss, bradycardia, menorrhagia, depression. Severe: myxedema (non-pitting edema, hoarseness).

Workup
  1. TSH. Elevated in primary hypothyroid.
  2. Free T4. Low confirms overt hypothyroid. Normal with high TSH = subclinical.
  3. Anti-TPO antibodies. Positive in Hashimoto.
Management
  1. Levothyroxine. Start 1.6 mcg/kg/day in young healthy; lower in elderly or CAD. Titrate based on TSH every 6 weeks.
  2. Target TSH. Upper half of normal range for most. Suppressed in thyroid cancer.
  3. Pregnancy. Increase dose by 25–30% at positive pregnancy test. Target TSH < 2.5 first trimester.
  4. Subclinical hypothyroid. Treat if TSH > 10, symptomatic, positive anti-TPO, pregnant, infertility.
Pearls
Pearl
Myxedema coma: hypothermia, bradycardia, hypotension, hyponatremia, hypoglycemia, AMS. IV levothyroxine + hydrocortisone (until adrenal insufficiency excluded) + supportive ICU care.
Pearl
Levothyroxine absorption is reduced by calcium, iron, PPIs, and soy. Separate by 4 hours.
Pearl
If T4 is low and TSH is normal or low: consider central hypothyroidism (pituitary/hypothalamic disease). Check full pituitary workup.
DISEASE DEEP DIVE

Adrenal Insufficiency

Primary (Addison) vs secondary. Hyponatremia, hyperkalemia, hypoglycemia, hyperpigmentation in primary.

Presentation

Fatigue, weight loss, hypotension (especially orthostatic), hyperpigmentation (primary only), salt craving, nausea. Crisis: hypotension, shock, AMS, hyponatremia, hyperkalemia, hypoglycemia.

Workup
  1. Morning cortisol. < 5 highly suggestive; > 15 rules out.
  2. Cosyntropin stimulation. Low cortisol with inadequate rise (< 18 at 30 or 60 min) confirms.
  3. ACTH. High in primary (end-organ failure), low or inappropriately normal in secondary.
  4. Etiology. Autoimmune (most common), TB, adrenal hemorrhage, metastases, meds (ketoconazole, etomidate).
Management
  1. Crisis. IV hydrocortisone 100 mg bolus, then 50 mg Q6h. IV fluids. Treat precipitant. Do not delay steroids for confirmatory testing.
  2. Chronic primary. Hydrocortisone 15–25 mg/day in divided doses + fludrocortisone 0.05–0.2 mg/day.
  3. Chronic secondary. Hydrocortisone only (fludrocortisone not needed, intact RAAS).
  4. Stress dosing. Double or triple normal dose for illness, surgery, trauma. Avoid crisis.
Pearls
Pearl
Hyperpigmentation in primary adrenal insufficiency is from elevated ACTH (POMC derivative). Absent in secondary.
Pearl
Hyperkalemia only in primary (aldosterone deficiency). Secondary preserves aldosterone.
Pearl
All patients on chronic steroids > 3 weeks get stress-dose coverage for surgery or serious illness.
DISEASE DEEP DIVE

Hypercalcemia

Primary hyperparathyroidism (outpatient) and malignancy (inpatient) account for 90%. Symptoms at Ca > 12.

Presentation

Stones, bones, groans, thrones, psychiatric overtones. Polyuria, polydipsia, constipation, fatigue, confusion, nephrolithiasis.

Workup
  1. Ionized Ca or corrected Ca. Confirm true hypercalcemia. Corrected Ca = measured + 0.8 × (4 − albumin).
  2. PTH. High or inappropriately normal: primary hyperparathyroidism, familial hypocalciuric hypercalcemia, lithium. Low: malignancy, vitamin D toxicity, sarcoidosis, thiazides.
  3. If PTH low. PTHrP (humoral hypercalcemia of malignancy), 1,25-OH vitamin D (granulomatous, lymphoma), SPEP/UPEP (myeloma).
  4. 24-hr urine Ca. Low in FHH, high in primary hyperparathyroidism.
Management
  1. Volume resuscitation. Normal saline aggressively (3–6 L in first 24 hours), volume depletion from polyuria.
  2. Bisphosphonate. Zoledronic acid or pamidronate. Onset 24–48 hours, lasts weeks.
  3. Calcitonin. Acute but tachyphylaxis in 48 hours. Bridge to bisphosphonate.
  4. Denosumab. For refractory cases or renal failure (where bisphosphonates contraindicated).
  5. Steroids. For granulomatous disease and lymphoma.
  6. Dialysis. If severe or renal failure.
  7. Primary hyperparathyroidism. Surgery if symptomatic, Ca > 1 above ULN, age < 50, nephrolithiasis, eGFR < 60, T-score < -2.5.
Pearls
Pearl
Avoid loop diuretics in hypercalcemia unless volume overloaded. Old teaching of 'furosemide for hypercalcemia' is wrong, volume depletion worsens it.
Pearl
PTH-independent hypercalcemia in a cancer patient: PTHrP (squamous cell, breast, renal), bony mets, lymphoma (vitamin D), myeloma.
Pearl
FHH (familial hypocalciuric hypercalcemia) mimics primary hyperparathyroidism but does not need surgery. Low urine Ca/Cr clearance ratio distinguishes.
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