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USMLE Step 3 high yield psychiatry neurology must know 2025 2026

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USMLE Step 3 - High-Yield Psychiatry & Neurology

PSYCHIATRY

1. Schizophrenia & Psychotic Disorders

DSM-5-TR Criteria for Schizophrenia (must know all 5):

A - At least 2 of: delusions, hallucinations, disorganized speech, disorganized/catatonic behavior, negative symptoms -- at least 1 must be delusions, hallucinations, or disorganized speech
B - Functioning impaired (work, self-care, relationships)
C - Duration ≥ 6 months (including prodrome/residual)
D/E - Rule out schizoaffective, substance, or medical causes

Key Distinctions:

Diagnosis	Duration	Mood Episode
Brief psychotic disorder	1 day - 1 month	None
Schizophreniform	1-6 months	None
Schizophrenia	≥ 6 months	None
Schizoaffective	≥ 6 months	Present for majority of illness
Delusional disorder	≥ 1 month	None

Antipsychotic Selection:

First-line: Atypical antipsychotics (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone)
Clozapine: Reserve for treatment-resistant schizophrenia (failed ≥ 2 adequate trials); requires ANC monitoring (agranulocytosis risk ~1-2%)
- Baseline ANC > 1500/µL required; monitor weekly x 6 months, then biweekly x 6 months, then monthly
Metabolic monitoring for all atypicals: weight, BMI, fasting glucose, lipids at baseline and regularly

Antipsychotic Side Effects - High Yield:

Drug	Key Side Effect
Clozapine	Agranulocytosis, seizures, myocarditis
Olanzapine	Most metabolic syndrome
Quetiapine	Sedation, metabolic effects
Ziprasidone	QTc prolongation (least weight gain)
Risperidone	Highest prolactin elevation
Haloperidol	EPS, NMS, tardive dyskinesia

EPS Management:

Acute dystonia → benztropine or diphenhydramine IM
Akathisia → propranolol or benzodiazepine (not anticholinergics)
Tardive dyskinesia → discontinue or switch to clozapine/quetiapine; valbenazine or deutetrabenazine
NMS: High fever, rigidity, autonomic instability, elevated CPK → STOP antipsychotic, dantrolene, bromocriptine, ICU

2. Mood Disorders

Major Depressive Disorder (MDD):

≥ 5 symptoms (SIG E CAPS) for ≥ 2 weeks, with depressed mood OR anhedonia required; impaired function
First-line: SSRIs (sertraline, escitalopram); SNRIs second-line
Mild-moderate: psychotherapy (CBT) ± medication
Severe/psychotic: medication required; ECT for severe treatment-resistant, catatonic, or suicidal with failure to treat medically
Always screen for bipolar before starting antidepressants (manic switch risk)

Bipolar Disorder:

	Bipolar I	Bipolar II	Cyclothymia
Mania	Full (≥ 7 days or hospitalized)	Hypomania only (≥ 4 days)	Hypomanic + depressive sx, never full criteria
Duration	Any	Any	≥ 2 years

Treatment of Bipolar:

Acute mania: Lithium, valproate, or atypical antipsychotic (olanzapine, quetiapine, aripiprazole); haloperidol for acute severe agitation
Acute bipolar depression: Quetiapine, lurasidone, or lamotrigine + lithium; avoid antidepressant monotherapy
Maintenance: Lithium (gold standard, also suicide prevention), valproate, lamotrigine, or atypical antipsychotics

Lithium Monitoring (must know):

Therapeutic level: 0.6-1.2 mEq/L (acute mania: 0.8-1.2; maintenance: 0.6-0.8)
Toxicity: tremor, nausea, ataxia, confusion, seizures, coma (levels > 1.5 mEq/L)
Monitor: renal function (BUN/Cr), TFTs, EKG (T-wave flattening), CBC -- at baseline and every 3-6 months
NSAIDs, thiazides, ACE inhibitors → increase lithium levels (reduce renal clearance)
Renally cleared; reduce dose in renal impairment
Pregnancy category D (Ebstein's anomaly risk, though risk is small)

3. Anxiety Disorders

Key diagnoses:

Disorder	Key Feature
GAD	≥ 6 months excessive worry, ≥ 3 symptoms (muscle tension, fatigue, poor concentration, irritability, sleep disturbance, restlessness)
Panic Disorder	Recurrent unexpected panic attacks + worry about future attacks
Social Anxiety	Fear of scrutiny/embarrassment in social situations
PTSD	Re-experiencing, avoidance, negative cognitions/mood, hyperarousal after traumatic event; ≥ 1 month
OCD	Intrusive obsessions + compulsions; ego-dystonic

First-line treatment for most anxiety disorders: SSRIs or SNRIs + CBT

PTSD: Sertraline or paroxetine (FDA-approved); CBT/prolonged exposure is preferred psychotherapy; prazosin for nightmares
OCD: SSRIs (high dose) + ERP (exposure & response prevention therapy)
Panic: SSRIs/SNRIs; benzodiazepines short-term only
Social anxiety: SSRIs; beta-blocker (propranolol) for performance anxiety

4. Substance Use Disorders

Alcohol:

Withdrawal: tremors (6-24h) → seizures (24-48h) → delirium tremens (48-72h; fever, autonomic instability, hallucinations)
Treatment: Benzodiazepines (CIWA-Ar protocol); chlordiazepoxide or diazepam preferred; lorazepam if hepatic disease
Wernicke's: confusion, ataxia, ophthalmoplegia → IV thiamine FIRST before glucose
Korsakoff's: anterograde amnesia, confabulation (late; often irreversible)
Maintenance: Naltrexone (reduce cravings), acamprosate (reduce PAWS), disulfiram (aversion therapy)

Opioid Use Disorder:

Withdrawal: yawning, lacrimation, rhinorrhea, piloerection, diarrhea, myalgias (not life-threatening)
Overdose: pinpoint pupils, respiratory depression, coma → naloxone (0.4-2 mg IV/IM/IN)
MAT (medication-assisted treatment): Methadone (opioid agonist, clinic-only), buprenorphine/naloxone (Suboxone, office-based), naltrexone (for abstinence maintenance)

Stimulants (cocaine, amphetamines):

Intoxication: tachycardia, HTN, euphoria, mydriasis
Overdose management: benzodiazepines for agitation/seizures; avoid beta-blockers (unopposed alpha → HTN)
Withdrawal: crash - fatigue, hypersomnia, depression (no specific pharmacotherapy needed)

5. Suicidality & Capacity

Risk factors for suicide: Male sex, prior attempt (single best predictor of future attempt), access to firearms, older age, living alone, unemployment, substance use, chronic illness, hopelessness

Hospitalization indications: Active SI with plan/intent/means; SI with poor insight; homicidal ideation; inability to care for self; psychosis with dangerous behavior; severe alcohol/benzo withdrawal

Decision-Making Capacity (4 elements):

Understand information
Appreciate relevance to their situation
Reason through options
Express a consistent choice

Capacity is decision-specific and can fluctuate. A patient refusing treatment must have capacity assessed. Competency is a legal determination (court); capacity is a clinical determination (physician).

NEUROLOGY

6. Stroke

Ischemic Stroke Management:

IV tPA (alteplase) window: 0-3 hours (extended to 4.5 hours in select patients: age < 80, no prior stroke + DM, no anticoagulation, NIHSS < 25, no large MCA infarct)
Mechanical thrombectomy: Up to 24 hours for large vessel occlusion (anterior circulation) with favorable imaging (DAWN/DEFUSE-3 criteria)
Contraindications to tPA: active bleeding, recent surgery (< 14 days), BP > 185/110 (treat first), recent head trauma, prior hemorrhagic stroke, platelets < 100k, INR > 1.7, glucose < 50 or > 400
BP management in ischemic stroke: Do NOT lower unless > 220/120 (or > 185/110 if giving tPA)

Hemorrhagic Stroke:

ICH: Reverse anticoagulation immediately; BP < 140 if presenting between 150-220 is reasonable; neurosurgery consult
SAH: Berry aneurysm rupture - "worst headache of life" + meningismus; CT without contrast first; LP if CT negative (xanthochromia); nimodipine for vasospasm; neurosurgery for clipping or coiling

Secondary Prevention:

Cardioembolic (Afib) → anticoagulation (warfarin or DOAC)
Non-cardioembolic → antiplatelet therapy (aspirin, clopidogrel, or aspirin+dipyridamole)
Dual antiplatelet (aspirin + clopidogrel) for 21 days after minor ischemic stroke or high-risk TIA (POINT/CHANCE trials), then single antiplatelet

TIA: Imaging (MRI-DWI), vascular imaging (CTA/MRA), echo, telemetry; ABCD2 score for risk stratification; aspirin + clopidogrel x 21 days if high-risk

7. Seizures & Epilepsy

Classification:

Focal (partial): Simple (aware) vs. complex (impaired awareness)
Generalized: tonic-clonic, absence, myoclonic, atonic

Drug of Choice by Seizure Type:

Type	First-Line
Focal	Levetiracetam, lamotrigine, carbamazepine
Generalized tonic-clonic	Valproate, levetiracetam, lamotrigine
Absence	Ethosuximide (preferred), valproate
Juvenile myoclonic	Valproate, levetiracetam
Women of childbearing age	Lamotrigine (avoid valproate - teratogenic)

Status Epilepticus (SE):

Definition: > 5 minutes of continuous seizure OR ≥ 2 seizures without return to baseline
Step 1 (0-5 min): ABCs, IV access, glucose check, thiamine if alcohol history
Step 2 (5-20 min): Benzodiazepine - lorazepam 0.1 mg/kg IV (preferred); diazepam or midazolam IM if no IV
Step 3 (20-40 min): Second-line agent - fosphenytoin, levetiracetam, or valproate IV
Step 4 (> 40 min, refractory SE): Intubation + IV anesthetic (propofol, midazolam, pentobarbital); EEG monitoring

(Katzung's Basic & Clinical Pharmacology; Tintinalli's Emergency Medicine)

8. Dementia & Delirium

Delirium vs. Dementia:

Feature	Delirium	Dementia
Onset	Acute (hours-days)	Gradual (months-years)
Attention	Severely impaired	Intact until late
Consciousness	Fluctuating	Usually clear
Reversible	Yes (if cause treated)	Generally not
Hallucinations	Visual > auditory	Less common

Delirium workup (reversible causes - "I WATCH DEATH"): Infections, Withdrawal, Acute metabolic, Trauma, CNS pathology, Hypoxia, Deficiencies (B12, thiamine), Endocrine, Acute vascular, Toxins/drugs, Heavy metals

Dementia Types:

Type	Key Feature
Alzheimer's	Most common; amyloid plaques + tau tangles; gradual memory loss first
Vascular	Stepwise progression; risk factors = HTN, DM, hyperlipidemia
Lewy body	Visual hallucinations, parkinsonism, fluctuating cognition, REM sleep behavior disorder; avoid antipsychotics (severe sensitivity)
Frontotemporal	Personality/behavior change, language problems, disinhibition; early age onset
NPH	Wet, wacky, wobbly (incontinence, dementia, gait disturbance); responds to LP drainage

Alzheimer's pharmacotherapy:

Mild-moderate: Donepezil (AChEI), rivastigmine, galantamine
Moderate-severe: Add memantine (NMDA antagonist)

9. Headache

Type	Features	Treatment
Migraine	Unilateral, pulsating, 4-72h, nausea/vomiting, photophobia/phonophobia, aura in ~30%	Acute: triptans (5-HT1B/1D agonists) or NSAIDs; Prophylaxis: propranolol, topiramate, amitriptyline, CGRP antagonists
Cluster	Unilateral periorbital, severe, autonomic features (lacrimation, Horner's), 15-180 min, clusters	Acute: high-flow O₂ or sumatriptan SC; Prophylaxis: verapamil
Tension	Bilateral, band-like, mild-moderate, no autonomic sx	NSAIDs, acetaminophen
SAH	Thunderclap "worst headache of life"	CT head → LP → neurosurgery
Meningitis	Headache + fever + stiff neck + photophobia	LP → empiric antibiotics (do not wait)

Red flag headaches (SNOOP4): Systemic symptoms, Neurologic deficits, Onset sudden, Onset after age 50, Postural change, Papilledema, Progressive worsening

10. Movement Disorders

Parkinson's Disease:

Triad: resting tremor (pill-rolling), bradykinesia, rigidity (cogwheel)
Dopamine deficit in substantia nigra
Lewy bodies (alpha-synuclein)
Treatment: Levodopa/carbidopa (most effective); dopamine agonists (pramipexole, ropinirole) for younger patients to delay levodopa; MAO-B inhibitors (selegiline, rasagiline) as adjuncts
Complications: motor fluctuations ("wearing off"), dyskinesias, hallucinations; adjust timing/dosing or add COMT inhibitor (entacapone)

Essential Tremor:

Kinetic/action tremor (not resting), bilateral hands; improves with alcohol
Treatment: propranolol (first-line), primidone

11. Multiple Sclerosis

Most common in young women, white, northern latitudes
Relapsing-remitting (85% at onset): McDonald criteria require dissemination in time AND space (MRI)
Typical presentations: optic neuritis (painful vision loss), INO (internuclear ophthalmoplegia - MLF lesion), Lhermitte's sign, transverse myelitis
Acute relapse: IV methylprednisolone (speeds recovery, doesn't change overall disability)
Disease-modifying therapy (DMT): IFN-beta, glatiramer acetate (mild-moderate); natalizumab, ocrelizumab, alemtuzumab (high-efficacy/aggressive)
Uhthoff's phenomenon: worsening with heat

12. Meningitis

Empiric Treatment (don't delay antibiotics for LP if clinical signs present):

Age	Organisms	Treatment
Neonate	GBS, E. coli, Listeria	Ampicillin + cefotaxime
1 month - 50 yrs	N. meningitidis, S. pneumoniae	Ceftriaxone + vancomycin
> 50 yrs / immunocompromised	Above + Listeria	+ Ampicillin
All ages	Add dexamethasone (S. pneumo)	Reduces hearing loss / mortality

CSF Findings:

	Bacterial	Viral	Fungal/TB
WBC	Neutrophils (> 1000)	Lymphocytes (< 500)	Lymphocytes
Protein	Very elevated	Normal/slightly elevated	Elevated
Glucose	Very low (< 45)	Normal	Low
Opening pressure	Elevated	Normal/mildly elevated	Very elevated

Encephalitis: HSV most common cause in adults - fever, personality change, temporal lobe seizures → acyclovir immediately (don't wait for MRI or PCR)

13. Peripheral Neuropathy & GBS

Guillain-Barre Syndrome (GBS):

Ascending flaccid paralysis, areflexia, post-infectious (Campylobacter, EBV, CMV)
CSF: albuminocytologic dissociation (high protein, normal WBC)
Complications: respiratory failure (monitor FVC - intubate if FVC < 15-20 mL/kg or < 20 cmH₂O negative inspiratory force), autonomic instability
Treatment: IVIG or plasmapheresis (equivalent efficacy); steroids NOT effective
NOT corticosteroids

14. Spinal Cord Emergencies

Cauda Equina Syndrome (CES) vs. Conus Medullaris:

Feature	Cauda Equina	Conus Medullaris
Lesion level	Below L1-L2	L1-L2 (conus)
Weakness	LMN only (flaccid)	Mixed UMN + LMN
Reflexes	Absent	Variable
Bowel/bladder	Overflow incontinence, urinary retention	Similar
Back pain	Severe radicular	Less prominent
Management	Emergency MRI → surgery	Emergency MRI

Spinal Cord Compression: Back pain + bilateral weakness/sensory loss below a level + bowel/bladder dysfunction → MRI spine stat → dexamethasone → oncology/neurosurgery

STEP 3-SPECIFIC TIPS

CCS (Clinical Case Simulations): Order workup AND initiate treatment simultaneously for emergencies (don't wait for results before treating stroke, status epilepticus, meningitis, or GBS)
Rule out organic cause before psychiatric diagnosis - always consider thyroid, B12, syphilis, HIV, substance intoxication/withdrawal
Competence vs. capacity - physicians assess capacity; courts determine competency
Informed consent components: Diagnosis, proposed treatment, risks/benefits, alternatives, right to refuse
Mandatory reporting: Child abuse, elder abuse, certain communicable diseases, threats to identifiable third parties (Tarasoff), impaired drivers (varies by state) - report even without patient consent
Confidentiality exceptions: Imminent threat to self or others, child/elder abuse, court orders
Biostatistics on Step 3: Know sensitivity/specificity, PPV/NPV, NNT, absolute vs. relative risk reduction, intention-to-treat analysis

Sources: Kaplan & Sadock's Comprehensive Textbook of Psychiatry; The Maudsley Prescribing Guidelines in Psychiatry (15th ed.); Bradley & Daroff's Neurology in Clinical Practice; Katzung's Basic & Clinical Pharmacology (16th ed.); Tintinalli's Emergency Medicine

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USMLE Step 3 - High-Yield Pediatrics

1. Neonatal Resuscitation & Newborn Care

APGAR Score (assessed at 1 and 5 minutes):

Sign	0	1	2
Appearance	Blue/pale all over	Blue extremities, pink body	Pink all over
Pulse	Absent	< 100	≥ 100
Grimace	No response	Grimace	Cry/cough/sneeze
Activity	Limp	Some flexion	Active motion
Respiration	Absent	Weak/irregular	Strong cry

Score 7-10: normal; 4-6: intermediate; < 4: intervention needed
Do not delay resuscitation to calculate APGAR - assess tone, breathing, and HR first
Newborn resuscitation: warm/dry/stimulate → position/clear airway → PPV if HR < 100 or apneic → chest compressions if HR < 60 despite 30 sec PPV → epinephrine if no response

Routine Newborn Prophylaxis (must know all 3):

Erythromycin eye ointment - prevents gonococcal ophthalmia neonatorum
Vitamin K IM - prevents hemorrhagic disease of the newborn (VKDB)
Hepatitis B vaccine - first dose within 24 hours of birth (if mother HBsAg-negative)
- If mother HBsAg-positive: give both HepB vaccine AND HBIG within 12 hours of birth

Newborn Screening: PKU, congenital hypothyroidism, galactosemia, sickle cell, CAH, hearing screen, CCHD (pulse oximetry before discharge)

2. Neonatal Jaundice (Hyperbilirubinemia)

Physiologic vs. Pathologic:

Feature	Physiologic	Pathologic
Onset	> 24 hours of life	< 24 hours (always pathologic)
Peak bilirubin	Term: < 12 mg/dL	Any level requiring treatment
Type	Indirect (unconjugated)	Depends on cause
Resolution	1-2 weeks (term), 3 weeks (preterm)	Variable

Causes of early jaundice (< 24h): Rh/ABO incompatibility, G6PD deficiency, spherocytosis

Causes of prolonged jaundice: Hypothyroidism, breast milk jaundice, biliary atresia (direct hyperbilirubinemia - always pathologic; conjugated bili > 2 mg/dL or > 20% of total)

Direct (conjugated) hyperbilirubinemia - always pathologic: Biliary atresia (clay-colored stools, hepatomegaly - confirm with HIDA scan; treat with Kasai procedure before 60 days), neonatal hepatitis, choledochal cyst, sepsis

Management:

Monitor with transcutaneous or serum bilirubin, plot on Bhutani nomogram
Phototherapy: Blue light (460-490 nm) converts bilirubin to water-soluble isomers; most common treatment
Exchange transfusion: For severe hyperbilirubinemia unresponsive to phototherapy or with acute bilirubin encephalopathy (Kernicterus: lethargy, hypotonia → opisthotonus, seizures → auditory/visual impairment)

3. Respiratory Distress in Newborns

Condition	Features	CXR	Management
RDS (HMD)	Premature infant, grunting, nasal flaring, intercostal retractions; onset within hours	Ground glass, air bronchograms, low lung volumes	Surfactant, CPAP/mechanical ventilation; Prevent with antenatal corticosteroids (betamethasone)
TTN	Term infant, C-section (no labor squeeze), mild distress, self-limited (< 24h)	Perihilar streaking, fluid in fissures	Supportive oxygen, resolves spontaneously
Meconium Aspiration	Post-term infant, stained amniotic fluid, respiratory distress	Patchy infiltrates, hyperinflation	Suction if depressed; surfactant, HFOV, inhaled NO for PPHN
Pneumothorax	Sudden deterioration, absent breath sounds, shift of trachea	Hyperlucent area, mediastinal shift	Needle decompression → chest tube

PPHN (Persistent Pulmonary Hypertension): Right-to-left shunting through PDA/PFO → severe hypoxia; treat with inhaled nitric oxide, HFOV, ECMO if refractory

4. Congenital Heart Disease

Key Rule: Cyanosis not responsive to 100% O₂ = cardiac cause (hyperoxia test: PaO₂ < 150 on 100% O₂ = cardiac right-to-left shunt)

Acyanotic (Left-to-Right Shunts):

Lesion	Key Feature	Murmur	Management
VSD	Most common CHD; often closes spontaneously	Holosystolic at LLSB	Watch; surgical closure if large
ASD	Fixed split S2; recurrent URI	Systolic ejection + fixed S2 split	Catheter-based or surgical closure
PDA	Continuous "machine" murmur; premature infants	L subclavicular	Indomethacin (preterm); surgical ligation if needed
Coarctation of Aorta	HTN in arms, decreased pulses in legs, rib notching on CXR; associated with Turner syndrome and bicuspid aortic valve	Systolic; back	Balloon dilation or surgery

Cyanotic ("5 T's and more"):

Lesion	Key Feature	CXR	Immediate Treatment
Tetralogy of Fallot	Most common cyanotic CHD after infancy; Tet spells (hypercyanotic)	Boot-shaped heart, decreased pulmonary vascularity	Tet spell: knee-chest position, O₂, morphine, phenylephrine, propranolol; Surgical repair
Transposition of Great Arteries (TGA)	Most common cyanotic CHD in neonates; parallel circulations	Egg on a string	Prostaglandin E1 (PGE1) to keep PDA open → Rashkind balloon atrial septostomy → arterial switch surgery
Tricuspid Atresia	No tricuspid valve	Left axis deviation on EKG	PGE1 + Fontan procedure
Truncus Arteriosus	Single great vessel from both ventricles	Cardiomegaly, increased pulmonary vascularity	Surgery
Total Anomalous Pulmonary Venous Return (TAPVR)	All pulmonary veins drain to RA	Snowman/figure-8 heart (supracardiac type)	Surgery

Critical rule for Step 3: Any cyanotic duct-dependent lesion (TGA, pulmonary atresia, hypoplastic left heart) → start PGE1 immediately while arranging definitive management

5. Pediatric GI Emergencies

Condition	Age	Presentation	Dx	Tx
Hypertrophic Pyloric Stenosis	2-8 weeks (first-born males)	Projectile non-bilious vomiting, hungry after vomiting, olive-shaped mass RUQ, hypochloremic hypokalemic metabolic alkalosis	Ultrasound (elongated pyloric channel > 14mm, thickness > 4mm)	Correct electrolytes FIRST, then pyloromyotomy
Intussusception	6 months - 2 years	Colicky abdominal pain, currant jelly stools, sausage-shaped mass RUQ, "lead point" in older children (Meckel's, polyp, lymphoma)	Ultrasound (target/donut sign)	Air or contrast enema (diagnostic + therapeutic); surgery if peritonitis/perforation
Hirschsprung Disease	Neonates/infants	Failure to pass meconium in first 24-48h, chronic constipation, abdominal distension, "ribbon stools"	Barium enema (transition zone), rectal biopsy (absent ganglion cells - gold standard)	Surgical resection of aganglionic segment
Malrotation/Volvulus	Neonates	Bilious vomiting + abdominal distension = surgical emergency	Upper GI series (duodenal obstruction, "corkscrew" sign)	Emergency surgery
Meckel Diverticulum	Any age, usually < 2 years	Painless rectal bleeding (most common presentation); rule of 2s: 2 inches long, 2 feet from ileocecal valve, 2% of population, 2:1 male	Technetium-99m pertechnetate scan (Meckel scan)	Surgical resection
NEC	Premature infants	Abdominal distension, bloody stools, feeding intolerance, pneumatosis intestinalis on XR	AXR (pneumatosis intestinalis, portal venous gas)	NPO, NG suction, IV antibiotics; surgery for perforation

6. Pediatric Infectious Disease

Fever in Neonates (< 28 days):

Full sepsis workup (blood/urine/CSF cultures) regardless of appearance
Empiric treatment: Ampicillin + Gentamicin (covers GBS, Listeria, E. coli)
Add acyclovir if HSV suspected (skin vesicles, seizures, hepatitis)

Fever in Infants 1-3 months:

If well-appearing and low-risk criteria met → blood/urine culture, close follow-up; consider LP
If ill-appearing: full workup + empiric antibiotics

Bacterial Meningitis - Age-Based Empiric Treatment:

Age	Common Organisms	Treatment
0-28 days	GBS, E. coli, Listeria, HSV	Ampicillin + Cefotaxime (+ Acyclovir)
1-3 months	GBS, E. coli, S. pneumo, N. meningitidis	Ampicillin + Cefotaxime
3 months - 18 years	S. pneumo, N. meningitidis	Ceftriaxone + Vancomycin

Add dexamethasone before or with first antibiotic dose for S. pneumoniae meningitis (reduces hearing loss)

Epiglottitis vs. Croup:

Feature	Epiglottitis	Croup (Laryngotracheobronchitis)
Age	Any (classically 2-7 yrs)	6 months - 3 years
Cause	H. influenzae type b (now rare post-vaccine); also Staph aureus	Parainfluenza virus
Onset	Rapid, toxic-appearing	Gradual, prodromal URI
Drooling	Yes (can't swallow)	No
Posture	Tripod position, sniffing	-
CXR/X-ray	Thumb sign (epiglottis)	Steeple sign (subglottic narrowing)
Treatment	Do NOT examine throat; secure airway in OR first; IV antibiotics (ceftriaxone)	Racemic epinephrine + dexamethasone; humidified air

Pertussis (Whooping Cough): Bordetella pertussis; classic: catarrhal (URI, 1-2 wks) → paroxysmal (inspiratory whoop, post-tussive vomiting, 2-4 wks) → convalescent; Dx: nasopharyngeal PCR; Tx: azithromycin (or clarithromycin, TMP-SMX); prophylaxis for close contacts; prevent with DTaP

Kawasaki Disease: Fever ≥ 5 days + 4 of 5 criteria: Conjunctival injection (bilateral, non-exudative), Rash (polymorphous), Adenopathy (cervical, unilateral ≥ 1.5 cm), Lips/mouth changes (strawberry tongue, cracked lips, pharyngeal erythema), Extremity changes (erythema of palms/soles, periungual desquamation)

Complication: coronary artery aneurysms (most serious)
Treatment: IVIG (2 g/kg single dose) + aspirin (high-dose during acute phase, then low-dose)

7. Pediatric Respiratory - Asthma & Beyond

Asthma Severity & Step-Up Therapy:

Severity	Symptoms	SABA Use	Nighttime Awakenings	FEV₁	Treatment
Intermittent	≤ 2 days/wk	≤ 2 days/wk	≤ 2x/month	> 80%	SABA PRN only
Mild persistent	> 2 days/wk	> 2 days/wk	3-4x/month	> 80%	Low-dose ICS
Moderate persistent	Daily	Daily	> 1x/week	60-80%	Medium ICS + LABA
Severe persistent	Continuous	Continuous	Nightly	< 60%	High ICS + LABA ± oral steroids

Acute Asthma Exacerbation: SABA (albuterol) + ipratropium + systemic corticosteroids; IV magnesium for severe exacerbation; intubation if respiratory failure; Heliox for severe obstruction

Bronchiolitis: RSV most common (age < 2 years); fever, wheezing, crackles; Dx: clinical; Tx: supportive only (O₂, nasal suctioning, hydration) - bronchodilators, steroids, and antibiotics are NOT recommended; Palivizumab (RSV prophylaxis for high-risk: premature < 29 weeks, hemodynamically significant CHD, chronic lung disease)

8. Child Development & Milestones (High-Yield for Step 3)

Language milestones (most tested):

2 months: social smile, cooing
6 months: babbling, rolls over
9 months: "mama/dada" (non-specific), pincer grasp developing
12 months: 1-2 words (specific "mama/dada"), walks with support, pincer grasp complete
18 months: 10-20 words, walks independently
24 months: 50+ words, 2-word phrases, runs
3 years: 3-word sentences, rides tricycle, knows age/gender
4 years: 4-word sentences, hops on one foot
5 years: 5-word sentences, skips, ties shoes

Red flags (automatic referral):

No babbling by 12 months, no words by 16 months, no 2-word phrases by 24 months
Any loss of language at any age (always pathologic)

9. Child Abuse

Physical Abuse - High-Yield Findings:

Classic fractures: Posterior rib fractures (pathognomonic for squeezing/shaking), metaphyseal "bucket handle" or "corner" fractures, spiral fractures of long bones in non-ambulatory child
Shaken Baby Syndrome (Abusive Head Trauma): Retinal hemorrhages, subdural hematoma, no external signs of trauma; bulging fontanelle, irritability, lethargy
Bruising in non-mobile infants, bruising in unusual locations (trunk, ears, neck), multiple bruises in different stages of healing
Management: Skeletal survey (all children < 2 years suspected abuse), ophthalmology consult, head CT/MRI, notify child protective services (mandatory reporting - no parental consent needed)

Sexual Abuse: Physical exam often normal; STI in a child (gonorrhea, syphilis) = sexual abuse until proven otherwise; report to CPS; interview child alone; forensic evidence collection if recent assault

10. Pediatric Renal & Hematology

Urinary Tract Infection (UTI):

Most common bacterial infection in young children
Girls > Boys (except uncircumcised males age < 1 year)
E. coli most common organism
Dx: catheter specimen (not bag); UA + urine culture
Tx: antibiotics; obtain renal ultrasound after first febrile UTI in all children < 2 years; VCUG to evaluate for VUR

Nephrotic vs. Nephritic:

	Nephrotic	Nephritic
Protein	Massive (> 3.5 g/day)	Mild
Hematuria	Minimal	Prominent (RBC casts)
BP	Normal or low	Hypertension
BUN/Cr	Normal	Elevated
Classic pediatric cause	Minimal change disease (responds to steroids)	Post-strep GN (follows pharyngitis or impetigo by 2-3 weeks)

Minimal Change Disease: Most common nephrotic syndrome in children 2-8 years; treat with prednisone; excellent prognosis

Henoch-Schonlein Purpura (IgA Vasculitis): Palpable purpura on lower extremities/buttocks + arthritis/arthralgias + colicky abdominal pain + nephritis; preceded by URI; self-limited; treat symptomatically; steroids for severe GI/renal involvement

Sickle Cell Disease - Key Complications:

Complication	Management
Vaso-occlusive crisis (pain crisis)	IV fluids, analgesics (NSAIDs + opioids)
Acute chest syndrome (fever, chest pain, new infiltrate, hypoxia)	O₂, antibiotics (ceftriaxone + azithromycin), exchange transfusion if severe
Splenic sequestration	Rapid splenomegaly, anemia, shock → transfusion
Stroke	Exchange transfusion acutely; chronic transfusions for prevention
Aplastic crisis	Parvovirus B19; transfuse as needed
Infection	Encapsulated organisms (S. pneumo, H. flu, N. meningitidis) due to functional asplenia

Prophylaxis: Penicillin VK starting at 2 months until age 5; PCV vaccine; hydroxyurea (reduces HbS, increases HbF)

11. Common Pediatric Ambulatory Conditions

Otitis Media (AOM):

Most common in 6-24 months; S. pneumo, H. flu, M. catarrhalis
Dx: bulging tympanic membrane with erythema and opacification
Tx: Amoxicillin (high-dose 80-90 mg/kg/day) first-line; amoxicillin-clavulanate if failed amoxicillin or recent antibiotic use
Watchful waiting acceptable in mild disease in children ≥ 2 years (unilateral, no severe symptoms)

Streptococcal Pharyngitis:

Centor criteria: tonsillar exudate, tender anterior cervical lymphadenopathy, fever, absence of cough
Dx: rapid strep test; throat culture if negative (children)
Tx: Penicillin V (10 days) or amoxicillin; azithromycin if PCN-allergic
Goal: prevent rheumatic fever (NOT prevent nephritis - that cannot be prevented)

Febrile Seizure:

Simple (most common): generalized, < 15 min, does not recur within 24h; in febrile child 6 months - 6 years
Complex: focal, > 15 min, or recurs within 24h
Simple febrile seizure: no LP, no EEG, no imaging required if well-appearing after seizure
LP if < 12 months with first febrile seizure (consider meningitis), any meningeal signs, or prolonged postictal state
No prophylactic anticonvulsants for simple febrile seizures; reassure parents

Iron Deficiency Anemia:

Most common nutritional deficiency in children; toddlers (12-24 months) drinking excess cow's milk
Labs: low MCV, low Hgb, low ferritin, high TIBC, low serum iron
Tx: oral iron supplementation (3-6 mg/kg/day elemental iron); dietary changes; recheck CBC in 4 weeks

12. Vaccines - High-Yield for Step 3

Routine childhood schedule (landmark doses):

Birth: HepB #1
2 months: DTaP, IPV, Hib, PCV15/20, RV, HepB #2
6 months: Influenza annually (starting 6 months)
12-15 months: MMR #1, Varicella #1, HepA #1
4-6 years: DTaP #5, IPV #4, MMR #2, Varicella #2
11-12 years: Tdap booster, HPV series (2-3 doses depending on age started), MenACWY

Live attenuated vaccines (cannot give to immunocompromised or pregnant): MMR, Varicella, LAIV (FluMist), Rotavirus, Yellow Fever, BCG, Oral typhoid

Contraindications:

MMR/Varicella: immunocompromised, pregnancy, anaphylaxis to gelatin or neomycin, recent blood product (wait 3-11 months)
DTaP: progressive neurologic disorder, encephalopathy within 7 days of prior DTaP
Egg allergy is NOT a contraindication to influenza vaccine (give in any setting with monitoring)

13. Lead Poisoning

Universal screening at 12 and 24 months (or 36-72 months if not previously screened)
Sources: old paint (pre-1978 homes), dust, soil, imported toys/jewelry
Symptoms (high levels > 45 µg/dL): abdominal pain, constipation, encephalopathy, irritability, cognitive impairment; Basophilic stippling on peripheral smear
Level 3.5-44 µg/dL: environmental investigation + nutritional counseling (calcium, iron, vitamin C)
Level ≥ 45 µg/dL: chelation therapy (succimer/DMSA oral; EDTA IV for severe/encephalopathy); BAL (dimercaprol) if encephalopathy

14. Developmental & Behavioral Pediatrics

ADHD:

Inattention and/or hyperactivity-impulsivity present in ≥ 2 settings for > 6 months; onset before age 12
Dx: clinical (DSM-5); obtain parent and teacher behavior rating scales
Age 4-5: behavioral therapy first (parent training); medication if inadequate response
Age ≥ 6: Stimulants first-line (methylphenidate, amphetamine salts); non-stimulants (atomoxetine, guanfacine, clonidine) if stimulants contraindicated or fail
Monitor: growth, BP, HR

Autism Spectrum Disorder (ASD):

Persistent deficits in social communication + restricted/repetitive behaviors; onset in early developmental period
Red flag: No back-and-forth sharing of sounds/smiles by 9 months; no words by 16 months; no 2-word phrases by 24 months; any regression
Dx: clinical (DSM-5); M-CHAT-R screening at 18 and 24 months
Tx: Applied behavioral analysis (ABA), speech/OT/PT; no proven pharmacologic cure; risperidone or aripiprazole for irritability/aggression

CCS Tips - Pediatrics

Any cyanotic newborn: Start PGE1 immediately while arranging echo and cardiology consult
Bilious vomiting in a neonate = surgical emergency (malrotation/volvulus) until proven otherwise
Suspected child abuse: Mandatory report to CPS regardless of certainty; skeletal survey for < 2 years
Fever in neonate < 28 days: Always full workup + empiric antibiotics; no "well-appearing" exceptions
Pyloric stenosis: Correct metabolic alkalosis with IV normal saline before surgery
Meningococcemia (petechial/purpuric rash + fever + shock): Give ceftriaxone immediately, do not wait for LP
Simple febrile seizure: Reassure - no workup needed in child > 12 months with no meningeal signs

Sources: The Harriet Lane Handbook (23rd ed., Johns Hopkins Hospital); Red Book 2021 (AAP Committee on Infectious Diseases); Tintinalli's Emergency Medicine; Robbins & Kumar Basic Pathology; Goldman-Cecil Medicine

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USMLE Step 3 high yield endocrinology must know diabetes thyroid adrenal 2025

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Excellent - I have strong textbook backing across all major endocrine topics. Here is the full high-yield Step 3 Endocrinology review:

USMLE Step 3 - High-Yield Endocrinology

1. Diabetes Mellitus - Diagnosis

Diagnostic Criteria (any one of the following):

Test	Diabetes	Pre-diabetes
Fasting glucose	≥ 126 mg/dL	100-125
2-hr OGTT	≥ 200 mg/dL	140-199
HbA1c	≥ 6.5%	5.7-6.4%
Random glucose + symptoms	≥ 200 mg/dL	-

Asymptomatic: must confirm with two separate tests (same test or different test on different days)
Symptomatic + random glucose ≥ 200: one test sufficient

Type 1 vs. Type 2:

	Type 1	Type 2
Pathophysiology	Autoimmune beta-cell destruction; anti-GAD, anti-islet cell antibodies	Insulin resistance + relative insulin deficiency
Age	Usually < 30 yrs (but any age)	Usually > 40 yrs (increasing in youth)
Body habitus	Normal/thin	Usually obese
Onset	Acute, can present in DKA	Insidious
Insulin	Required	Initially not required

2. Diabetes - Glycemic Management

HbA1c Goals:

General target: < 7% (most non-pregnant adults)
Less stringent (< 8%): elderly, multiple comorbidities, limited life expectancy, hypoglycemia unawareness
More stringent (< 6.5%): young, newly diagnosed, no CVD, long life expectancy - if achievable without hypoglycemia

Step-Up Pharmacotherapy for Type 2 DM:

Step 1 - Metformin (first-line for ALL patients unless contraindicated):

Mechanism: decreases hepatic gluconeogenesis, increases insulin sensitivity
Benefits: weight neutral/loss, low hypoglycemia risk, CV benefit, cheap
Contraindications: eGFR < 30 mL/min (hold if < 45 for new starts), IV contrast (hold day of), severe hepatic disease, alcohol use disorder
Side effects: GI (start low, titrate), lactic acidosis (rare)

Add-on agents - choose based on comorbidities:

Drug Class	Example	Key Benefit	Key Concern
GLP-1 RA	Semaglutide, liraglutide	CV mortality ↓, weight loss, ASCVD/HF benefit	Nausea, pancreatitis risk
SGLT-2 inhibitor	Empagliflozin, dapagliflozin	CV mortality ↓, HF hospitalization ↓, renal protection	UTI/genital yeast, DKA (euglycemic)
DPP-4 inhibitor	Sitagliptin	Weight neutral, safe in renal disease	Possible pancreatitis, saxagliptin → HF
Sulfonylurea	Glipizide, glimepiride	Cheap, effective	Hypoglycemia, weight gain
TZD	Pioglitazone	Insulin sensitizer, NASH benefit	Weight gain, fluid retention/HF, fractures, bladder cancer (pioglitazone)
Insulin	Basal (glargine), prandial	Most potent	Hypoglycemia, weight gain

Step 3 MUST-KNOW algorithm:

ASCVD or high CV risk → add GLP-1 RA or SGLT-2 inhibitor regardless of HbA1c
Heart failure or CKD → SGLT-2 inhibitor first
Weight loss priority → GLP-1 RA
Hypoglycemia avoidance → DPP-4i, GLP-1 RA, SGLT-2i (all low hypoglycemia risk)

3. DKA vs. HHS

Feature	DKA	HHS (Hyperosmolar Hyperglycemic State)
Type	Usually T1DM (also T2DM)	T2DM
Glucose	> 250 mg/dL (often 300-600)	> 600 mg/dL
pH	< 7.3	Normal (> 7.3)
Bicarbonate	< 18 mEq/L	Normal or slightly low
Anion gap	Elevated (ketoacidosis)	Normal
Ketones	Positive (serum + urine)	Negative or trace
Osmolality	Mildly elevated	> 320 mOsm/kg
Sensorium	Variable	Marked obtundation/coma
Mortality	~1-2%	~15% (older, dehydrated)

DKA Treatment (must know sequence):

IV fluids first - Normal saline 1-2 L bolus (most important initial step; correct hypovolemia)
Potassium - Check K+ before starting insulin; if K+ < 3.5 mEq/L, hold insulin and replete K+ first; if K+ 3.5-5.5, add 20-40 mEq/L to IV fluids
Insulin - Regular insulin 0.1 unit/kg IV bolus then 0.1 unit/kg/hr infusion (or 0.14 unit/kg/hr without bolus)
Add dextrose (D5W) when glucose < 200 mg/dL - keep glucose 150-200 until acidosis resolves
Transition to SQ insulin when: anion gap closed, pH > 7.3, patient eating - overlap SQ with IV for 1-2 hours before stopping drip
Treat precipitating cause (infection most common - check UA, CXR, blood cultures)

Monitoring: Glucose hourly; BMP every 2-4 hours; expect potassium to drop as insulin drives K+ into cells

4. Hypoglycemia

Whipple's Triad: Symptoms + low glucose (< 70 mg/dL) + relief with glucose correction

Fasting hypoglycemia workup: Measure glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate simultaneously during episode

Elevated insulin + elevated C-peptide → Insulinoma (endogenous; C-peptide present with insulin)
Elevated insulin + low C-peptide → Exogenous insulin administration (factitious)
Elevated insulin + elevated C-peptide + sulfonylurea screen positive → Sulfonylurea ingestion

Insulinoma: Best localized with EUS (endoscopic ultrasound); treat with surgical resection; diazoxide for medical management

5. Thyroid Disorders

Hypothyroidism

Primary hypothyroidism: High TSH, low free T4

Most common cause: Hashimoto's thyroiditis (autoimmune; anti-TPO antibodies, anti-thyroglobulin antibodies)
Symptoms: fatigue, cold intolerance, weight gain, constipation, bradycardia, dry skin, hair loss, depression, delayed DTRs, myxedema, menorrhagia
Treatment: Levothyroxine (T4) - start low, titrate to normalize TSH; monitor TSH every 6-8 weeks while adjusting, then annually
Monitor TSH (not free T4) for adequacy of replacement

Myxedema Coma: Severe decompensated hypothyroidism; decreased consciousness, hypothermia, hypoventilation, bradycardia; triggered by infection, cold exposure, medications

Treatment: IV T3 (liothyronine) or T4 + IV hydrocortisone (rule out/treat concurrent adrenal insufficiency first), supportive care, ICU

Important: Always treat adrenal insufficiency before starting levothyroxine - levothyroxine increases cortisol clearance and can precipitate adrenal crisis if concurrent AI is untreated

Hyperthyroidism

Primary hyperthyroidism: Low TSH, high free T4/T3

Cause	Distinguishing Feature	RAIU
Graves' disease	Most common; diffuse goiter, exophthalmos, pretibial myxedema; anti-TSH receptor (TSI) antibodies	Diffusely increased
Toxic multinodular goiter	Multiple nodules, older patients	Multiple hot spots
Toxic adenoma	Single hot nodule	Single hot spot, rest suppressed
Subacute thyroiditis (de Quervain's)	Post-viral, painful thyroid, self-limited	Very low (destructive release)
Postpartum thyroiditis	Post-delivery, painless, self-limited	Very low

Graves' Treatment options:

Antithyroid drugs (ATD): Methimazole (first-line; 1x/day dosing); PTU only in 1st trimester pregnancy or thyroid storm (blocks T4→T3 conversion also)
- Risk: agranulocytosis (0.3%; check WBC if fever/sore throat), hepatotoxicity (PTU > methimazole)
Radioactive iodine (RAI, I-131): Preferred definitive therapy in non-pregnant adults; follow with levothyroxine
Surgery (thyroidectomy): Large goiter, compressive symptoms, malignancy concern, pregnancy planning

Beta-blockers (propranolol): Symptomatic relief only (palpitations, tremor); does NOT treat underlying hyperthyroidism but blocks T4→T3 conversion at high doses

Thyroid Storm: Life-threatening hyperthyroid emergency; fever > 40°C, tachycardia/arrhythmia, agitation/psychosis/coma, N/V/D; Burch-Wartofsky score

Treatment (give in order): PTU (blocks synthesis + conversion) → then iodine/SSKI (1 hour after PTU; blocks hormone release) → propranolol → hydrocortisone (blocks T4→T3; addresses adrenal insufficiency) → treat precipitant

6. Adrenal Disorders

Cushing Syndrome (Hypercortisolism)

Causes:

Cushing's disease: Pituitary ACTH-secreting adenoma (most common cause of endogenous Cushing's, 70%)
Ectopic ACTH: Small cell lung cancer, carcinoid (very high ACTH, very high cortisol)
Adrenal adenoma/carcinoma: Low ACTH (ACTH-independent)
Exogenous steroids: Most common overall cause (iatrogenic)

Symptoms: Central obesity, moon facies, buffalo hump, purple striae (> 1 cm), proximal muscle weakness, hypertension, hyperglycemia, osteoporosis, hirsutism, menstrual irregularity, easy bruising

Diagnostic Workup (step-by-step):

Confirm hypercortisolism (screening): 24-hour urinary free cortisol OR late-night salivary cortisol OR 1 mg overnight dexamethasone suppression test (most commonly used on Step 3)
- Abnormal = cortisol > 1.8 mcg/dL after 1 mg dexamethasone at midnight
Determine ACTH level:
- Low ACTH (< 5 pg/mL) → adrenal source → CT adrenals
- High ACTH (> 20 pg/mL) → ACTH-dependent → go to step 3
Distinguish pituitary vs. ectopic ACTH:
- MRI pituitary first
- High-dose dexamethasone suppression test: Cortisol suppresses ≥ 50% → pituitary (Cushing's disease); NO suppression → ectopic
- Inferior petrosal sinus sampling (IPSS): gold standard for differentiating pituitary vs. ectopic

Treatment:

Cushing's disease → Transsphenoidal surgery (first-line)
Adrenal adenoma → adrenalectomy
Ectopic ACTH → treat primary tumor; medical therapy (ketoconazole, metyrapone, mifepristone) while awaiting

Adrenal Insufficiency (Addison's Disease)

Primary AI (Addison's): Destruction of adrenal cortex (autoimmune most common; also TB, metastases, hemorrhage)

Deficiency: cortisol + aldosterone + androgens
Unique features: hyperpigmentation (elevated ACTH/MSH), hyponatremia, hyperkalemia, hypotension, hypoglycemia

Secondary AI: Pituitary ACTH deficiency (most commonly from long-term exogenous steroid use)

Aldosterone intact (no hyper-K, less salt wasting)
No hyperpigmentation (ACTH is low)

Diagnosis:

8 AM cortisol: if < 3 mcg/dL → highly suggestive; if > 18 mcg/dL → rules out
ACTH (cosyntropin) stimulation test: Gold standard; cortisol should rise to > 18-20 mcg/dL at 30-60 min; subnormal response = AI
If AI confirmed → check ACTH level: high = primary; low/normal = secondary

Adrenal Crisis (Acute AI): Hypotension, abdominal pain, fever, altered mental status; precipitated by illness/surgery/trauma in patient on chronic steroids or with known AI

Treatment: IV hydrocortisone 100 mg stat then 50-100 mg q8h + aggressive IV fluids (normal saline) + treat precipitant
Fludrocortisone added for primary AI (mineralocorticoid replacement)

Chronic replacement: Hydrocortisone 15-20 mg/day (2/3 AM, 1/3 PM) + fludrocortisone 0.1 mg/day (primary AI only); stress dosing (double/triple dose) for illness/surgery/procedure

Pheochromocytoma

Catecholamine-secreting tumor of adrenal medulla (paraganglioma if extra-adrenal)
"Rule of 10s": 10% malignant, 10% bilateral, 10% extra-adrenal, 10% pediatric, 10% familial
Associated with MEN 2A, MEN 2B, Von Hippel-Lindau, neurofibromatosis, SDH mutations
Symptoms: Hypertensive crises (episodic or sustained), headache, diaphoresis, palpitations ("5 H's: HTN, Headache, Hyperhidrosis, Hyperglycemia, heart pounding")

Diagnosis: 24-hour urinary metanephrines (preferred); or plasma free metanephrines (most sensitive)

CT/MRI adrenals for localization after biochemical confirmation

Treatment:

Alpha-blockade FIRST (phenoxybenzamine or doxazosin) for 10-14 days pre-op
Then beta-blockade (only after adequate alpha-blockade - never beta first, causes hypertensive crisis from unopposed alpha)
Surgical resection (adrenalectomy)

MEN 2 rule: If medullary thyroid carcinoma + MEN 2 diagnosed → always rule out pheochromocytoma before surgery (measure 24-hr urinary metanephrines); undiagnosed pheo + surgery = potentially fatal hypertensive crisis

7. Calcium Disorders

Hypercalcemia:

Causes - "CHIMPANZEES" (high-yield mnemonics):

Most common overall: Primary hyperparathyroidism (outpatient) and malignancy (inpatient)
Others: granulomatous disease (sarcoidosis, TB), thiazide diuretics, vitamin D toxicity, immobilization, milk-alkali syndrome, Addison's disease

Distinguishing primary hyperPTH vs. malignancy:

	Primary Hyperparathyroidism	Malignancy
PTH	High (hallmark)	Low/suppressed
PTHrP	Normal	Often elevated (humoral hypercalcemia)
ALP	Normal or slightly elevated	Often elevated
Chronicity	Asymptomatic, months-years	Symptomatic, acute

Symptoms of hypercalcemia: "Bones, groans, moans, and psychic overtones"

Bones: bone pain, fractures, subperiosteal resorption (classic of hyperPTH)
Stones: nephrolithiasis (calcium oxalate/phosphate)
Groans: N/V, constipation, pancreatitis, peptic ulcer
Moans: depression, lethargy, confusion

Treatment of hypercalcemia:

Mild (< 12 mg/dL), asymptomatic: Hydration, treat underlying cause
Moderate-severe or symptomatic: IV saline (mainstay) → IV bisphosphonates (zoledronic acid, pamidronate; onset 2-4 days, maximal effect 4-7 days) → calcitonin (rapid onset, tachyphylaxis) → dialysis for refractory/renal failure
Glucocorticoids for granulomatous disease or vitamin D toxicity

Hypocalcemia:

Causes: hypoparathyroidism (post-thyroidectomy most common surgical cause), hypomagnesemia (refractory hypocalcemia until Mg corrected), pseudohypoparathyroidism, vitamin D deficiency, pancreatitis
Symptoms: Chvostek's sign (tapping facial nerve → twitching), Trousseau's sign (inflating BP cuff → carpal spasm), QT prolongation, perioral numbness, tetany, seizures
Treatment: IV calcium gluconate for acute; oral calcium + vitamin D for chronic; correct Mg first if low

8. Pituitary Disorders

Prolactinoma

Most common pituitary adenoma
Causes hyperprolactinemia → galactorrhea, amenorrhea, infertility in women; decreased libido, erectile dysfunction, infertility in men
Elevated prolactin causes: MADS - Medications (antipsychotics, metoclopramide, methyldopa, verapamil, TCAs), Adenoma, Drugs, Stress/physiologic (pregnancy, breastfeeding, hypothyroidism, renal failure)
Workup: serum prolactin, TSH, MRI pituitary
"Hook effect": Very large adenoma may give falsely low prolactin by immunoassay; dilute sample

Treatment:

Dopamine agonists (cabergoline or bromocriptine) = first-line for all prolactinomas (even macroadenomas); cabergoline preferred (more effective, fewer side effects)
Surgery (transsphenoidal) if: resistant/intolerant to DA, apoplexy, visual field defects not responding

Acromegaly (Growth Hormone Excess)

Pituitary GH-secreting adenoma in adults (> 90%)
Symptoms: enlargement of hands, feet, jaw (prognathism), tongue; coarsening of facial features; carpal tunnel syndrome, arthritis, sleep apnea, hypertension, hyperglycemia, organomegaly; if childhood onset → gigantism
Diagnosis: IGF-1 (screening) → confirm with oral glucose tolerance test (GH should suppress to < 1 ng/mL; failure to suppress confirms acromegaly) → MRI pituitary
Treatment: Transsphenoidal surgery (first-line); octreotide/lanreotide (somatostatin analogues) for residual/unresectable; pegvisomant (GH receptor blocker) for resistant cases; cabergoline may help

Panhypopituitarism / Central DI

Central Diabetes Insipidus: ADH deficiency → polyuria (hypotonic, dilute urine), polydipsia, hypernatremia

Urine osmolality low (< 300 mOsm/kg) despite high serum osmolality
Water deprivation test: urine does not concentrate → confirm with desmopressin (DDAVP): urine concentrates with DDAVP = central DI; no response = nephrogenic DI
Treatment: DDAVP (desmopressin) for central DI; thiazide diuretics + low-salt/protein diet for nephrogenic DI (lithium-induced most common cause)

9. SIADH (Syndrome of Inappropriate ADH Secretion)

Diagnostic criteria (all must be met):

Hyponatremia (< 135 mEq/L) with hypo-osmolality (serum Osm < 275 mOsm/kg)
Urine osmolality inappropriately concentrated (> 100, usually > 300 mOsm/kg)
Urine sodium elevated (> 20 mEq/L)
Euvolemic (no edema, no dehydration)
Normal thyroid, adrenal, renal function

Common causes: CNS disease (stroke, meningitis, SAH), pulmonary disease (pneumonia, TB, SIADH), malignancy (small cell lung cancer most classic), drugs (SSRIs, carbamazepine, cyclophosphamide, NSAIDs, PPIs), postoperative

Treatment of SIADH:

Mild/chronic: Fluid restriction (800-1000 mL/day) ± salt tablets
Moderate: Add demeclocycline (causes nephrogenic DI) or vaptans (tolvaptan - V2 receptor antagonist)
Severe symptoms (seizures, coma): 3% hypertonic saline

Critical rule - rate of correction: Correct Na+ by no more than 8-10 mEq/L per 24 hours (max 18 mEq/L per 48 hours) to avoid osmotic demyelination syndrome (ODS/central pontine myelinolysis) - especially in chronic hyponatremia

10. Multiple Endocrine Neoplasia (MEN)

	MEN 1 ("3 P's")	MEN 2A	MEN 2B
Gene	MEN1 (menin)	RET proto-oncogene	RET proto-oncogene
Components	Pituitary adenoma + Parathyroid hyperplasia + Pancreatic tumors (gastrinoma, insulinoma, VIPoma, glucagonoma)	Medullary thyroid carcinoma + Pheochromocytoma + Parathyroid hyperplasia	Medullary thyroid carcinoma + Pheochromocytoma + Mucosal neuromas + Marfanoid habitus
Most common presentation	Hyperparathyroidism (90%)	Medullary thyroid carcinoma	Medullary thyroid carcinoma
Screening gene test	MEN1 sequencing	RET mutation testing	RET mutation testing

Key Step 3 rules for MEN:

MEN 1 + recurrent peptic ulcers → Zollinger-Ellison syndrome (gastrinoma); measure fasting gastrin; secretin stimulation test (paradoxical rise in gastrin)
MEN 2 + thyroid mass → measure calcitonin; rule out pheochromocytoma BEFORE thyroid surgery
Prophylactic thyroidectomy recommended for RET mutation carriers (timing based on specific mutation)

11. Thyroid Nodule & Cancer

Workup of Thyroid Nodule:

Check TSH
- Low TSH → RAIU scan (look for hot/hyperfunctioning nodule - unlikely malignant)
- Normal/high TSH → proceed to ultrasound
Ultrasound - assess size and features
FNA biopsy for nodules > 1 cm with suspicious features (microcalcifications, irregular margins, taller-than-wide, hypoechoic, vascularity)

Thyroid Cancer Types:

Type	Key Features	Treatment
Papillary (85%)	Most common; psammoma bodies, ground glass "Orphan Annie eyes" nuclei; excellent prognosis; spread to lymph nodes	Surgery ± RAI
Follicular (10%)	Vascular invasion; spread hematogenously (bone, lung); no lymph node spread	Surgery ± RAI
Medullary (5%)	Calcitonin-secreting C cells; associated with MEN 2; amyloid deposits	Surgery; genetic testing of family; check pheochromocytoma first
Anaplastic (< 1%)	Elderly, rapidly fatal; poor prognosis	Palliative

12. Adrenal Incidentaloma

Adrenal mass found incidentally on imaging done for another reason
Workup ALL incidentalomas:
1. Biochemical: 1 mg overnight DST (Cushing's), plasma metanephrines (pheo), aldosterone/renin ratio if hypertensive (Conn's)
2. Imaging characteristics: > 4 cm, heterogeneous, high HU value → concerning for malignancy
Surgery if: biochemically active, > 4 cm, imaging concerning for malignancy, or growing on surveillance
Non-functioning, < 4 cm, benign appearance → repeat imaging at 6-12 months

Quick Reference - Hormone Arrows

Condition	Glucose	Na+	K+	ACTH	Cortisol	TSH	fT4
Addison's	Low	Low	High	High	Low	-	-
Cushing's (pituitary)	High	High	Low	High	High	-	-
Primary hypothyroid	-	-	-	-	-	High	Low
Secondary hypothyroid	-	-	-	-	-	Low	Low
Primary hyperPTH	-	-	-	-	-	-	-
SIADH	-	Low	Normal	-	-	-	-
DI (central)	-	High	-	-	-	-	-

CCS Tips - Endocrinology

DKA: Always check K+ BEFORE starting insulin; replete if < 3.5 mEq/L first
Adrenal crisis: Give IV hydrocortisone immediately - do NOT wait for cortisol results
Pheochromocytoma: Alpha-block FIRST (10-14 days), THEN beta-block; never beta-block alone
MEN 2 + surgery: Always check 24-hr urine metanephrines/plasma metanephrines before any neck surgery
Hyponatremia correction: Never exceed 8-10 mEq/L/24h to prevent osmotic demyelination
Thyroid storm: PTU first → iodine (1 hour after PTU) → propranolol → hydrocortisone
Levothyroxine + suspected adrenal insufficiency: Treat adrenal insufficiency first to avoid precipitating crisis

Sources: Harrison's Principles of Internal Medicine (22nd ed.); Goodman & Gilman's Pharmacological Basis of Therapeutics; Katzung's Basic & Clinical Pharmacology (16th ed.); Lippincott Illustrated Reviews - Pharmacology; The Washington Manual of Medical Therapeutics; Goldman-Cecil Medicine; Rosen's Emergency Medicine

Step 3 high yield must know for exam

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