ADRENAL DISORDERS

Cushing Syndrome

Risk Factors: Adrenal tumor (primary), pituitary ACTH tumor/Cushing disease, ectopic ACTH, exogenous steroids
Symptoms: Central obesity, moon facies, buffalo hump, purple striae, dorsal fat pad, proximal muscle weakness, Hypertension
Diagnosis: ≥2 positive screening tests needed: 24-hr urine cortisol, late-night salivary cortisol, or low-dose dex suppression test; then ACTH level + high-dose dex suppression test to differentiate source
Treatment: Treat underlying cause—surgery for tumor, discontinue steroids if exogenous

Cushing Disease (Pituitary ACTH-secreting adenoma)

Symptoms: Same as Cushing syndrome
Diagnosis: High ACTH + suppression on high-dose dex test (suppresses ACTH unlike ectopic source)
Treatmelectent: Transsphenoidal surgery (first line); radiation/adrenolytic agents if failed

Pheochromocytoma

Risk Factors: MEN 2A/2B, neurofibromatosis, family history
Symptoms: Classic triad—episodic severe headache, diaphoresis, palpitations/tachycardia; anxiety, tremor
Diagnosis: 24-hr urine metanephrines or plasma metanephrines; imaging (CT/MRI) to localize Treatment: Alpha-blockade first (phenoxybenzamine) → then beta-blockade → surgery (critical: prevent hypertensive crisis)

Primary Adrenal Insufficiency (Addison Disease)

Symptoms: Fatigue, weight loss, hyperpigmentation (primary ONLY), hypotension, GI complaints, hypoglycemia
Electrolytes: Hyponatremia, hyperkalemia (hallmark of primary), hypovolemia
Diagnosis: High ACTH + low cortisol; low sodium + high potassium + low aldosterone + high renin; cosyntropin stimulation test confirms
Treatment: Glucocorticoid (hydrocortisone/prednisone) PLUS mineralocorticoid (fludrocortisone)
Addisonian Crisis: Hypotension + shock + N/V + abdominal pain + hypoglycemia/hyponatremia → IV hydrocortisone + normal saline IMMEDIATELY (don’t delay for labs, no pressors)

Secondary Adrenal Insufficiency

Symptoms: Fatigue, hypotension (no electrolyte changes, no hyperpigmentation)
Labs: Low ACTH + low cortisol; normal electrolytes
Treatment: Hydrocortisone/prednisone ONLY (no mineralocorticoid needed)
Causes: Chronic steroid use, pituitary/hypothalamic disease


PARATHYROID DISORDERS

Primary Hyperparathyroidism

Risk Factors: Parathyroid adenoma (85%), hyperplasia, carcinoma; MEN syndromes
Symptoms: “Stones, bones, groans, psychiatric moans” (hypercalcemia effects)—nephrolithiasis, osteoporosis, GI, psychiatric symptoms Labs: High calcium + high PTH + low phosphate
Diagnosis: Elevated calcium with normal/high PTH (PTH suppressed = malignancy instead) Surgery indications: Symptomatic OR age ≤50 OR Ca >1 mg/dL above normal OR osteoporosis OR nephrolithiasis OR GFR decline
Treatment: Surgery (definitive); cinacalcet/bisphosphonates if non-surgical

Secondary Hyperparathyroidism

Causes: CKD, vitamin D deficiency
Symptoms: Low calcium drives high PTH
Labs: Low calcium + high PTH

Hypoparathyroidism

Risk Factors: Thyroid surgery (most common), autoimmune, genetic **
Symptoms: Tetany, perioral numbness, paresthesias, seizures, QT prolongation, Chvostek/Trousseau signs (hypocalcemia)
Labs: Low calcium + high phosphate + low PTH Treatment:** Calcium + active vitamin D (calcitriol)


PITUITARY DISORDERS

Prolactinoma (Most common functional pituitary adenoma)

Symptoms: Galactorrhea, amenorrhea, sexual dysfunction, infertility, headache, bitemporal hemianopsia (vision changes) Diagnosis: Prolactin >200 ng/mL (highly specific); MRI pituitary Treatment: Dopamine agonists (cabergoline preferred > bromocriptine); surgery NOT first line

Acromegaly / Gigantism

Symptoms: Enlarged hands/feet, coarse features, prognathism, macroglossia, arthralgias, cardiomegaly, sleep apnea, carpal tunnel Labs: Elevated IGF-1 (screens); oral glucose suppression test (confirms—normal GH should suppress <1 ng/mL) Diagnosis: IGF-1 elevated + failure to suppress GH on glucose tolerance test; MRI localizes Treatment: Transsphenoidal surgery (first line); bromocriptine, somatostatin analogs (octreotide), GH antagonist (pegvisomant)

Cushing Disease (Pituitary ACTH tumor)

Clinical: Same as Cushing syndrome (central obesity, moon facies, purple striae, dorsal fat pad, proximal weakness) Diagnosis: High ACTH + high-dose dex suppression suppresses ACTH (differentiates from ectopic ACTH which won’t suppress) Treatment: Transsphenoidal surgery (first line); radiation/medical if failed

General Pituitary Adenoma

Symptoms: Vision loss (bitemporal hemianopsia), headache, endocrine dysfunction (hormone-specific) Risk Factors: MEN-1, sporadic mutations Diagnosis: MRI pituitary, hormone level screening Treatment: Surgery, radiation, medical therapy (dopamine agonists, somatostatin analogs, GH antagonist)

Hypopituitarism (Hormone Deficiency)

Symptoms: Fatigue, amenorrhea, may have hypothyroidism/secondary AI symptoms Causes: Non-functioning adenoma, surgery/radiation, apoplexy, Sheehan syndrome (postpartum hemorrhage) Critical Pearl: If low TSH AND low ACTH, replace cortisol FIRST (prevent AI crisis)

Pituitary Apoplexy (EMERGENCY)

Symptoms: Sudden severe “thunderclash” headache, vision loss, AMS, hypotension; may have known pituitary tumor Treatment: IV hydrocortisone + neurosurgical consult immediately

Diabetes Insipidus

Central (ADH deficiency):

  • Polyuria, polydipsia, dehydration
  • High sodium, dilute urine
  • Treatment: Desmopressin
  • Causes: Head trauma, surgery, tumors

Nephrogenic (kidney resistance to ADH):

  • Polyuria, polydipsia, dehydration
  • High sodium, dilute urine
  • Treatment: Thiazides, NSAIDs, amiloride
  • Causes: Lithium, genetic, hypercalcemia

Memory: DI = “Dry” = desmopressin (central); or dry/dilute urine in both types

SIADH (Syndrome of Inappropriate Antidiuretic Hormone)

Symptoms: Hyponatremia manifestations—lethargy, confusion, seizures (euvolemic, NO edema) Labs: Low sodium + low osmolality + inappropriately HIGH urine osmolality + euvolemia
Causes: Lung cancer, CNS disease, medications (SSRIs, carbamazepine), pneumonia, post-op Treatment: Fluid restriction (first line); hypertonic saline if severe symptomatic; vaptans; treat underlying cause Memory: SIADH = “Swelled” = stop drinking water


METABOLIC SYNDROME

Diagnostic Criteria: ≥3 of 5:

  • Increased waist circumference (men >40”, women >35”)
  • High triglycerides ≥150 mg/dL (or on treatment)
  • Low HDL (men <40, women <50)
  • Elevated BP ≥130/85 mmHg (or on antihypertensive)
  • Fasting glucose ≥100 mg/dL (or on glucose-lowering medication)

Pearl: Being on meds for any criterion = criterion is met

Mechanism: Visceral fat → pro-inflammatory cytokines → insulin resistance → hyperglycemia + atherogenic dyslipidemia + hypertension + prothrombotic state

Associated Risks: Type 2 DM, CAD, CKD, MASLD

Treatment: Lifestyle first (weight loss 5-10%); treat individual components with guideline-directed therapy

Common Mistakes: DM not required for diagnosis; LDL not part of criteria; BMI not part of criteria


NEOPLASMS & MEN SYNDROMES

MEN1 (3 P’s)

  • Parathyroid carcinoma (MC) → hyperparathyroidism → hypercalcemia
  • Pituitary adenoma → prolactinoma (MC) → galactorrhea, amenorrhea
  • Pancreatic carcinoma → gastrinoma (MC) → peptic ulcers; insulinoma → hypoglycemia/Whipple’s triad

MEN2A

  • Medullary thyroid carcinoma (MC)
  • Pheochromocytoma
  • Parathyroid carcinoma

MEN2B (more aggressive, presents very young)

  • Medullary thyroid carcinoma
  • Pheochromocytoma
  • Neuromas

Primary Endocrine Malignancies

  • Thyroid carcinomas: Papillary (MC) → thyroidectomy ± RAI
  • Parathyroid carcinoma: Hypercalcemia
  • Adrenocortical carcinoma: Large mass (>4-6cm), often causes Cushing (↑cortisol, ↓ACTH) → adrenalectomy + mitotane
  • Pancreatic NETs: Insulinoma, gastrinoma; often MEN1

Pearl: Medullary TC produces calcitonin; may present as hypercalcemia—differentiate from parathyroid origin by checking PTH (low in medullary TC)


DIABETES MELLITUS

Diagnostic Criteria

Diabetes (ANY ONE):

  • A1c ≥6.5%
  • Fasting glucose ≥126 mg/dL
  • 2-hr OGTT ≥200 mg/dL
  • Random glucose ≥200 + symptoms (sufficient alone if symptomatic)

Prediabetes:

  • A1c 5.7–6.4%
  • Fasting glucose 100–125 mg/dL

Type 1 vs Type 2 (likely question stem)

Type 1: Kid/teen, thin, weight loss, DKA, autoimmune history; GAD65 antibody (MC)
Type 2: Adult, overweight, metabolic syndrome, no DKA

First-line Treatments

  • Type 1: Insulin, always
  • Type 2: Lifestyle → metformin → insulin; except DKA/HHS (start insulin immediately)

Metformin: Decreases hepatic gluconeogenesis, no hypoglycemia, GI side effects, ↓B12 long-term, contraindicated eGFR <30

Diabetic Emergencies

DKA:

  • Ketones, Kussmaul respirations, N/V, fruity breath, acidosis

HHS:

  • Glucose >600, NO acidosis (pH >7.3), AMS, severe dehydration

Treatment Order:

  1. IV fluids
  2. Check potassium
  3. Insulin
    • If K+ very low → give K+ before insulin
    • If K+ midrange → give K+ with insulin
    • If K+ high → monitor closely

Medication Pearls

  • IV insulin: Regular insulin only
  • SGLT-2 inhibitors (-gliflozin): ↑ urinary glucose, CV/renal benefit, genital infections, euglycemic DKA (hold before surgery)
  • GLP-1 agonists (-tide): ↑ insulin, ↓ glucagon, weight loss, avoid in medullary thyroid CA/MEN2/pancreatitis (hold before surgery)
  • Sulfonylureas: ↑ insulin, risk hypoglycemia/weight gain

Chronic Complications

  • Microvascular: Retinopathy, nephropathy, neuropathy
  • Macrovascular: CAD, PAD, stroke
    • Tight control decreases microvascular complications

Screening & Prevention

  • Annual urine albumin-to-creatinine ratio
  • ACE/ARB for diabetic nephropathy (even if normotensive)
  • Statin for all age 40-75 (diabetes = ASCVD risk equivalent); don’t avoid if cholesterol “normal”

ADDITIONAL PITUITARY/HYPOTHALAMIC DISORDERS

Dwarfism (GH Deficiency)

Symptoms: Short stature, delayed growth, immature facies, hypoglycemia
Labs: Low IGF-1, failure to rise with GH stimulation tests
Treatment: Recombinant GH replacement


KEY PANCE EXAM PEARLS

Adrenal:

  • Hyperpigmentation = primary adrenal insufficiency ONLY
  • High K+ = think primary insufficiency
  • Alpha-block before beta-block in pheochromocytoma (prevent hypertensive crisis)
  • Don’t delay steroids if adrenal crisis suspected

Parathyroid:

  • High calcium → first test is PTH
  • High Ca + suppressed PTH = malignancy (not hyperparathyroidism)
  • Correct calcium for low albumin

Pituitary:

  • Bitemporal hemianopsia → think prolactinoma
  • Prolactin >200 = highly specific for prolactinoma
  • If low TSH AND low ACTH → replace cortisol FIRST
  • DI = “Dry”; SIADH = “Swelled”
  • SIADH: Low sodium + low osmolality + high urine osmolality

Diabetes:

  • Single random glucose ≥200 + symptoms = sufficient for diagnosis + treat
  • Tight control decreases microvascular complications (retinopathy, nephropathy, neuropathy)
  • DM = ASCVD risk equivalent → statin age 40-75

Thyroid: (see separate thyroid review in PowerPoint)

  • TSH alone CANNOT diagnose
  • T3 NOT used to diagnose hypothyroidism
  • RAI uptake: HOT = benign, COLD = cancer
  • Treat symptoms first (beta-blocker), then disease

SUMMARY TABLE: Key Lab Patterns

ConditionCalciumPTHPhosphateACTHCortisol
Primary Hyperparathyroidism
Hypoparathyroidism
Malignancy (PTHrP)
Cushing Syndrome
Cushing Disease (Pituitary)↑ (suppresses on high-dose dex)
Ectopic ACTH↑↑↑ (NO suppression on high-dose dex)
Primary Adrenal Insufficiency↑↑
Secondary Adrenal Insufficiency