🦋 Thyroid Disorders

💉 Diabetes Mellitus

🌟 Adrenal Disorders

🧠 Pituitary Disorders

⚖️ Metabolic Disorders

💊 Other Disorders

🦋 Thyroid

Hypothyroidism

NICE 2024 ATA 2023 AACE 2023

Diagnostic Criteria

Primary Hypothyroidism: • TSH >4.5-5.0 mIU/L with low FT4
• TSH 4.5-10 mIU/L with normal FT4 = Subclinical
• Consider TPO antibodies for autoimmune etiology
Clinical Features: • Fatigue, cold intolerance, weight gain
• Constipation, dry skin, hair loss
• Bradycardia, delayed reflexes
• Cognitive impairment, depression

Treatment Algorithm Grade A

Initial Treatment:
Levothyroxine 1.6 mcg/kg/day (ideal body weight)
Elderly or cardiac disease: Start 25-50 mcg/day
Titration:
Check TSH every 6-8 weeks
Adjust dose by 12.5-25 mcg increments
Target TSH: 0.5-2.5 mIU/L
Maintenance:
Monitor TSH annually once stable
Take medication on empty stomach, 30-60 min before breakfast

Monitoring & Follow-up

Laboratory Monitoring: TSH every 6-8 weeks until stable, then annually
Clinical Assessment: Symptoms, weight, heart rate, reflexes
Drug Interactions: Iron, calcium, PPI, soy products (separate by 4 hours)

Red Flags & Complications

⚠️ Myxedema coma: Hypothermia, altered mental status, hypotension
⚠️ Pregnancy: Increase dose by 30-50% immediately
⚠️ Over-treatment: Risk of atrial fibrillation, bone loss
🦋 Thyroid

Hyperthyroidism & Thyrotoxicosis

ATA 2016 ETA 2024

Diagnostic Workup

Initial Tests: • TSH <0.1 mIU/L with elevated FT4 and/or FT3
• TSH receptor antibodies (TRAb) for Graves' disease
• Thyroid ultrasound for nodular disease
Etiology-Specific Tests: • Radioactive iodine uptake (RAIU) to differentiate causes
• High RAIU: Graves', toxic nodular goiter
• Low RAIU: Thyroiditis, exogenous thyroid hormone

Treatment Options Grade A

Methimazole (MMI): 10-30 mg/day divided
First-line for most patients (not pregnancy 1st trimester)
Propylthiouracil (PTU): 200-400 mg/day divided TID
Use in 1st trimester pregnancy, thyroid storm
Duration: 12-18 months typical course
Remission rate: 30-50% after treatment cessation
Indications:
• Definitive treatment for Graves' disease
• Toxic nodular goiter
• Contraindications: Pregnancy, breastfeeding, active ophthalmopathy
Dose: 10-15 mCi I-131 typical
Expect hypothyroidism in 80% within 3-6 months
Total Thyroidectomy Indications:
• Large goiter with compressive symptoms
• Suspected thyroid cancer
• Pregnancy (2nd trimester if needed)
• Patient preference

Thyroid Storm - Medical Emergency

⚠️ Fever >38.5°C, tachycardia >140 bpm, altered mental status
Treatment: PTU 500-1000mg loading → 250mg q4h + Propranolol + Hydrocortisone + Supportive care
💉 Diabetes

Type 2 Diabetes Mellitus

ADA 2025 EASD 2024 AACE 2024

Diagnostic Criteria (ADA 2025)

Any ONE of the following:
• HbA1c ≥6.5% (NGSP certified method)
• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L)
• 2-hour plasma glucose ≥200 mg/dL during OGTT
• Random glucose ≥200 mg/dL with classic symptoms
*Confirm with repeat testing unless symptomatic
Prediabetes:
• HbA1c 5.7-6.4%
• Fasting glucose 100-125 mg/dL
• 2-hour OGTT 140-199 mg/dL

Comprehensive Management Algorithm Grade A

Baseline Assessment:
• HbA1c, lipid panel, eGFR, UACR
• Screen for ASCVD, heart failure, CKD
• Assess for obesity (BMI, waist circumference)
Initial Therapy (ADA/EASD 2025):
All patients: Metformin + Lifestyle modification
Metformin 500mg daily → titrate to 2000mg/day
Add-on Therapy - Risk-Based Approach:
🫀 ASCVD or High CV Risk:
→ GLP-1 RA with proven CV benefit (semaglutide, liraglutide, dulaglutide)
→ OR SGLT2i with CV benefit (empagliflozin, canagliflozin)
🫘 CKD (eGFR <60 or UACR ≥30):
→ SGLT2i (empagliflozin, dapagliflozin, canagliflozin)
→ OR GLP-1 RA if SGLT2i not tolerated
💓 Heart Failure:
→ SGLT2i (empagliflozin, dapagliflozin) - FIRST CHOICE
⚖️ Obesity (BMI ≥27 kg/m²):
→ GLP-1 RA (semaglutide 2.4mg weekly preferred)
→ OR Dual GIP/GLP-1 RA (tirzepatide) - superior weight loss
If HbA1c Still Above Target:
• Triple therapy: Add DPP4i, TZD, or insulin
• Basal insulin if HbA1c >10% or symptomatic hyperglycemia

🧮 HbA1c to Average Glucose Calculator

Treatment Targets & Monitoring (ADA 2025)

Glycemic Targets:
• HbA1c <7.0% for most adults
• <6.5% if achieved safely without hypoglycemia
• <8.0% for older adults with comorbidities
Blood Pressure: <130/80 mmHg
Lipids: Statin therapy for all T2DM 40-75 years
LDL target <70 mg/dL if ASCVD
CGM Recommendation (NEW 2025):
Consider CGM for adults with T2DM on glucose-lowering agents (not just insulin)

Key Updates 2025 & Red Flags

✨ NEW: CGM expanded to non-insulin users on other glucose-lowering meds
✨ NEW: Emphasis on resistance training with weight-loss medications
⚠️ Cannabis use increases DKA risk - counsel patients
⚠️ Medication shortages: Have backup plans for GLP-1 RA alternatives
🌟 Adrenal

Primary Aldosteronism

Endocrine Society 2025 ESC 2024

Screening & Diagnosis (Updated 2025)

ESC 2024: Screen ALL adults with diagnosed hypertension Grade A
High-Risk Groups (Priority Screening):
• Hypertension + hypokalemia (spontaneous or diuretic-induced)
• Resistant hypertension (≥3 drugs including diuretic)
• Young-onset hypertension (<40 years)
• Hypertension + adrenal incidentaloma
• Hypertension + sleep apnea
• First-degree relative with PA
Screening Test:
Aldosterone/Renin Ratio (ARR)
• Positive if ARR >20-40 (lab dependent) AND aldosterone >10 ng/dL
• Morning sample, seated position
• Liberalize salt intake before testing

Confirmatory Testing & Subtype Classification

Confirmatory Tests (choose one):
• Oral sodium loading test
• Saline infusion test
• Fludrocortisone suppression test
• Captopril challenge test
Subtype Differentiation:
• CT/MRI adrenal imaging
• Adrenal vein sampling (AVS) if surgical candidate
• Unilateral disease → Surgery
• Bilateral disease → Medical therapy

Treatment

Unilateral Aldosterone-Producing Adenoma:
→ Laparoscopic adrenalectomy (curative in 30-60%)
Bilateral Disease or Non-surgical Candidates:
First-line: Mineralocorticoid receptor antagonists
• Spironolactone 12.5-50 mg/day (titrate to max 400 mg/day)
• Eplerenone 25-100 mg/day (fewer side effects)
Add if needed: Amiloride, thiazide, CCB

Clinical Pearls & Complications

💡 PA is vastly underdiagnosed - maintain high index of suspicion
⚠️ Higher CV risk than essential HTN (MI, stroke, atrial fibrillation)
⚠️ Increased renal damage risk - screen for CKD
🧠 Pituitary

Acromegaly

Endocrine Society 2014

Diagnostic Workup

Screening Test:
• IGF-1 level (age and sex-adjusted)
• Elevated IGF-1 → proceed to confirmatory testing
Confirmatory Test:
• Oral glucose tolerance test with GH measurement
• Acromegaly: GH >1 ng/mL (or >0.4 ng/mL with sensitive assays) after 75g glucose
• Normal: GH suppression to <1 ng/mL
Imaging:
• Pituitary MRI with gadolinium
• Identify adenoma size, extension

Treatment Algorithm Grade A

First-line Treatment:
Transsphenoidal surgery (TSS)
• Cure rate: 60-90% for microadenomas
• 40-50% for macroadenomas
Medical Therapy (if surgery unsuccessful or not candidate):
Somatostatin Analogs (first-line medical):
• Octreotide LAR 10-40 mg IM monthly
• Lanreotide 60-120 mg SC monthly
• Normalizes IGF-1 in 50-70% of patients
Second-line Medical Options:
• Pegvisomant (GH receptor antagonist) 10-30 mg SC daily
• Cabergoline (dopamine agonist) 0.25-3.5 mg/week
• Combination therapy for resistant cases
Radiation Therapy:
Reserved for persistent disease after surgery + medical therapy

Monitoring & Complications

Biochemical Monitoring: IGF-1, GH every 3-6 months until controlled
Screen for Comorbidities:
• Colonoscopy (increased polyp risk)
• Echocardiogram (cardiomyopathy)
• Sleep study (sleep apnea)
• Glucose tolerance, lipids
⚖️ Metabolic

Obesity Management

ADA 2025 Obesity Society 2024

Classification & Assessment

BMI Categories:
• Normal: 18.5-24.9 kg/m²
• Overweight: 25-29.9 kg/m²
• Obesity Class I: 30-34.9 kg/m²
• Obesity Class II: 35-39.9 kg/m²
• Obesity Class III: ≥40 kg/m²
NEW 2025: Body Fat Distribution (ADA):
Use in addition to BMI:
• Waist circumference (>40" men, >35" women)
• Waist-to-hip ratio
• Waist-to-height ratio
Measure annually

Comprehensive Management Strategy

Lifestyle Interventions (Foundation):
• 500-750 kcal/day deficit
• ≥150 min/week moderate aerobic activity
• NEW 2025: Resistance training 2-3x/week (maintain lean body mass)
Pharmacotherapy (BMI ≥27 with comorbidities or ≥30):
First-line agents (superior efficacy):
• Semaglutide 2.4 mg SC weekly (15-20% weight loss)
• Tirzepatide 5-15 mg SC weekly (15-22% weight loss) - BEST
Alternative agents:
• Liraglutide 3.0 mg SC daily (5-10% weight loss)
• Phentermine/topiramate ER (7-10% weight loss)
• Naltrexone/bupropion SR (5-6% weight loss)
• Orlistat 120 mg TID (3-5% weight loss)
Bariatric Surgery (BMI ≥40 or ≥35 with comorbidities):
• Roux-en-Y gastric bypass (25-30% weight loss)
• Sleeve gastrectomy (20-25% weight loss)
• Adjustable gastric banding (15-20% weight loss)
2025 Note: Maintain resistance training post-surgery

🧮 BMI Calculator

2025 Updates & Key Points

✨ Resistance training crucial for lean body mass preservation
✨ GLP-1 RAs have CV and renal benefits beyond weight loss
💡 Reassess if insufficient weight loss - consider increasing dose or adding therapy
⚖️ Metabolic

Dyslipidemia Management

AACE 2025 ACC/AHA 2024

Lipid Panel Targets

Risk Stratification:
• Extreme risk (ASCVD + multiple events): LDL <55 mg/dL
• Very high risk (ASCVD): LDL <70 mg/dL
• High risk (diabetes, CKD): LDL <70-100 mg/dL
• Moderate risk: LDL <100 mg/dL
• Low risk: LDL <130 mg/dL
NEW 2025: AHA PREVENT Calculator
Replaces race with ZIP code (social deprivation index)
Includes kidney function (eGFR) and HbA1c in risk prediction

Treatment Algorithm (AACE 2025)

High-Intensity Statins (First-line):
• Atorvastatin 40-80 mg daily
• Rosuvastatin 20-40 mg daily
Target: 50% LDL reduction
Add Ezetimibe if LDL not at goal:
10 mg daily (additional 15-20% LDL reduction)
PCSK9 Inhibitors (if still not at goal):
• Evolocumab 140 mg SC q2weeks or 420 mg monthly
• Alirocumab 75-150 mg SC q2weeks
Additional 50-60% LDL reduction
NEW 2025: Bempedoic Acid:
180 mg daily if statin intolerant
20-25% LDL reduction + CV benefit demonstrated
Triglycerides >500 mg/dL:
• Icosapent ethyl 2g BID with statin (if TG 135-500)
• Fibrates if TG >500 (pancreatitis risk)
💊 Other

Vitamin D Deficiency

Endocrine Society 2024

Classification

25(OH)D Levels:
• Deficiency: <20 ng/mL (<50 nmol/L)
• Insufficiency: 20-30 ng/mL (50-75 nmol/L)
• Sufficiency: ≥30 ng/mL (≥75 nmol/L)

Treatment (ES 2024 Guidelines)

Deficiency (<20 ng/mL):
50,000 IU vitamin D2/D3 weekly x 8 weeks
Then maintenance 1000-2000 IU daily
Maintenance (prevent deficiency):
• Adults: 600-800 IU daily
• Adults >70 years: 800-1000 IU daily
• Obesity: May need 2-3x higher doses

Important Updates 2024

⚠️ No evidence for routine vitamin D supplementation for disease prevention in general population
💡 Target deficiency treatment in high-risk groups: osteoporosis, malabsorption, CKD
💉 Diabetes

Type 1 Diabetes Mellitus

ADA 2025 Endocrine Society 2024

Diagnosis & Staging

Diagnostic Criteria:
• Hyperglycemia (same as T2DM criteria) PLUS
• Autoantibodies: GAD65, IA-2, ZnT8, insulin autoantibodies
• C-peptide low/absent
• Typically presents with DKA or severe hyperglycemia
NEW 2025: Staging System
Stage 1: Autoimmunity + normal glucose
Stage 2: Autoimmunity + dysglycemia (abnormal glucose but not diabetes)
Stage 3: Clinical diabetes with symptoms
NEW 2025: Screening for At-Risk Individuals
• Screen first-degree relatives with autoantibodies
• Consider teplizumab (Tzield) for Stage 2 disease (age ≥8 years)

Insulin Therapy Grade A

Multiple Daily Injections (MDI):
• Basal insulin: Glargine, degludec, or detemir once/twice daily
• Prandial insulin: Rapid-acting (aspart, lispro, glulisine) before meals
• Correction factor for high blood sugars
Continuous Subcutaneous Insulin Infusion (CSII/Pump):
• Preferred for many patients
• Basal rate programming + bolus calculator
• Better flexibility and control
NEW 2025: Automated Insulin Delivery (AID) Systems:
• Hybrid closed-loop systems (adjust basal automatically)
• Recommended for most T1DM patients
• Requires CGM integration
• Examples: Medtronic 780G, Tandem Control-IQ, Omnipod 5
Initial Insulin Dose:
• Total daily dose: 0.5-0.6 units/kg/day
• 50% basal, 50% prandial (divided among 3 meals)
• Honeymoon phase: May need less (0.2-0.3 units/kg/day)

Technology & Monitoring (ADA 2025)

Continuous Glucose Monitoring (CGM):
• Offer at diagnosis for ALL patients with T1DM Grade A
• Real-time CGM preferred (Dexcom G7, FreeStyle Libre 3)
• Target: >70% time in range (70-180 mg/dL), <4% time below range
HbA1c Targets:
• Adults: <7.0% (individualize based on hypoglycemia risk)
• Pregnant women: <6.0%
• Children/adolescents: <7.0%
Self-Management Education:
• Carbohydrate counting
• Insulin-to-carb ratios
• Correction factors
• Exercise management
• Sick day rules

Complications & Special Situations

⚠️ Hypoglycemia Awareness: Screen for impaired awareness, adjust targets
⚠️ DKA Risk: Never stop basal insulin, ketone monitoring during illness
💡 Pregnancy: Pre-conception HbA1c <6.5%, intensive monitoring required
✨ NEW 2025: Teplizumab can delay onset in Stage 2 T1DM by ~2 years
💉 Diabetes

Diabetic Ketoacidosis (DKA)

ADA 2025 AACE 2023

Diagnostic Criteria

Required:
• Glucose >250 mg/dL (or known diabetes)
• pH <7.3 OR bicarbonate <18 mEq/L
• Ketonemia/ketonuria (β-hydroxybutyrate >3 mmol/L)
Severity Classification:
Mild: pH 7.25-7.30, bicarb 15-18
Moderate: pH 7.0-7.24, bicarb 10-14
Severe: pH <7.0, bicarb <10
Precipitating Factors:
• Insulin omission (most common)
• Infection (pneumonia, UTI)
• New-onset T1DM
• MI, stroke, pancreatitis
• NEW 2025: SGLT2 inhibitors, cannabis use

Management Protocol Grade A

Fluid Resuscitation:
• 0.9% NaCl 1-1.5 L/hr initial bolus (15-20 mL/kg/hr)
• Then 250-500 mL/hr based on hydration status
• Switch to 0.45% NaCl when sodium corrected/normal
• Add dextrose when glucose <200 mg/dL
Insulin Therapy:
• Regular insulin 0.1 units/kg/hr IV continuous infusion
• OR 0.14 units/kg/hr if no bolus given
• Goal: Decrease glucose 50-75 mg/dL/hr
• When glucose <200, reduce insulin to 0.02-0.05 units/kg/hr
• Continue until anion gap closes
Potassium Replacement:
• If K+ <3.3: Hold insulin, give 40 mEq/hr until >3.3
• If K+ 3.3-5.2: Add 20-30 mEq to each liter IV fluid
• If K+ >5.2: Hold K+, check every 2 hours
Bicarbonate (Controversial):
• Consider if pH <6.9
• 100 mmol NaHCO3 in 400 mL H2O over 2 hours
Transition to Subcutaneous Insulin:
• When anion gap normalized AND patient eating
• Give SC insulin 1-2 hours before stopping IV
• Overlap essential to prevent recurrence

Monitoring During Treatment

Hourly: Glucose, vitals, mental status
Every 2-4 hours: Electrolytes, BUN, creatinine, venous pH
Calculate: Anion gap, corrected sodium
Resolution Criteria: Glucose <200, pH >7.3, bicarb ≥18, anion gap ≤12

Complications & Special Considerations

⚠️ Cerebral Edema: Headache, altered mental status (especially children) - Mannitol/hypertonic saline
⚠️ Hypokalemia: Most common electrolyte complication - aggressive replacement
⚠️ Euglycemic DKA: Can occur with SGLT2 inhibitors - check ketones even with normal glucose
✨ NEW 2025: Cannabis use increases DKA risk - counsel all patients
💉 Diabetes

Hypoglycemia Management

ADA 2025 Endocrine Society 2023

Classification & Definitions

ADA 2025 Hypoglycemia Thresholds:
• Level 1 (Alert): 54-70 mg/dL - Take action
• Level 2 (Serious): <54 mg/dL - Requires immediate action
• Level 3 (Severe): Any glucose level with altered mental/physical status requiring assistance
Causes:
• Insulin/sulfonylurea excess
• Missed meals, increased exercise
• Alcohol consumption
• Impaired hypoglycemia awareness
• Renal/hepatic impairment

Acute Management Grade A

Conscious Patient (Level 1 or 2):
Rule of 15:
• 15 grams fast-acting carbohydrate
• Wait 15 minutes
• Recheck glucose
• Repeat if still <70 mg/dL

15g carb options:
• 4 oz juice or regular soda
• 1 tablespoon sugar/honey
• Glucose tablets (3-4 tablets)
Unconscious/Unable to Swallow (Level 3):
• Glucagon:
- Intranasal: 3 mg (Baqsimi) - 1 spray in nostril
- Injectable: 1 mg IM/SC (Glucagon Emergency Kit)
- Turn patient on side (vomiting risk)
• Call 911
• Give carbs when patient wakes
Hospital Setting:
• Dextrose 50% (D50): 25 grams (50 mL) IV push
• If no IV access: Glucagon 1 mg IM
• D10 infusion if recurrent

Prevention & Long-term Management

Adjust Therapy:
• Reduce insulin doses by 10-20%
• Consider insulin pump or AID system
• Switch from sulfonylurea to safer agents
CGM Benefits:
• Alerts for impending hypoglycemia
• Reduces severe hypoglycemia by 40-60%
• Recommended for all with Level 2/3 hypoglycemia
Screen for Hypoglycemia Unawareness:
• Gold score or Clarke questionnaire
• If present: Relax glycemic targets temporarily
• Hypoglycemia avoidance training

High-Risk Populations

⚠️ Older Adults: Higher risk of falls, cardiac events
⚠️ CKD: Reduced insulin clearance - dose reduction needed
💡 NEW 2025: Screen for fear of hypoglycemia and anxiety annually
💡 Educate family on glucagon use - prescribe rescue glucagon for all at risk
🦋 Thyroid

Thyroid Nodules

ETA 2023 ATA 2015 AACE 2023

Initial Evaluation

When to Evaluate:
• Palpable nodule
• Incidental finding on imaging
• Risk factors: radiation exposure, family history MTC/MEN2
Step 1: TSH Level
• If TSH suppressed → Thyroid scintigraphy
• Hyperfunctioning nodule → Usually benign, no FNA needed
Step 2: Thyroid Ultrasound
• Assess size, echogenicity, margins, calcifications
• Use standardized system: EU-TIRADS or ACR-TIRADS
• Determines FNA indication

FNA Indications (EU-TIRADS 2023)

High Suspicion (EU-TIRADS 5):
FNA if ≥1 cm
Features: Solid hypoechoic, irregular margins, taller-than-wide, microcalcifications
Intermediate Suspicion (EU-TIRADS 4):
FNA if ≥1.5 cm
Low Suspicion (EU-TIRADS 3):
FNA if ≥2 cm or symptomatic
Very Low Suspicion (EU-TIRADS 2):
FNA rarely indicated (only if >2 cm and growing)
Purely Cystic:
FNA not needed unless symptomatic

Management Based on Bethesda Classification

Bethesda I (Nondiagnostic): Repeat FNA with ultrasound guidance
Bethesda II (Benign): Surveillance with US in 1-2 years
Bethesda III (AUS/FLUS): Repeat FNA or molecular testing (risk 10-30%)
Bethesda IV (Follicular Neoplasm): Surgery vs molecular testing (risk 25-40%)
Bethesda V (Suspicious for Malignancy): Surgery recommended (risk 50-75%)
Bethesda VI (Malignant): Surgery (risk >95%)

Red Flags for Malignancy

⚠️ Rapid growth, voice changes, dysphagia
⚠️ Fixed, hard nodule with lymphadenopathy
⚠️ History of head/neck radiation in childhood
⚠️ Family history of MTC or MEN2 (check calcitonin)
💡 Molecular testing (Afirma, ThyroSeq) can help avoid unnecessary surgery
🦋 Thyroid

Thyroiditis

ATA 2023 ETA 2024

Types of Thyroiditis

Hashimoto's Thyroiditis (Chronic Autoimmune):
• Most common cause of hypothyroidism
• TPO antibodies positive (90-95%)
• Thyroglobulin antibodies may be present
• Goiter may be present
• Treatment: Levothyroxine if hypothyroid
Subacute Thyroiditis (De Quervain's):
• Painful thyroid, often post-viral
• Elevated ESR, CRP
• Triphasic: Thyrotoxic → Hypothyroid → Recovery
• Low radioiodine uptake
• Self-limited (2-6 months)
Postpartum Thyroiditis:
• Occurs within 12 months postpartum
• Similar triphasic course
• TPO antibodies often positive
• 20-30% develop permanent hypothyroidism
Painless/Silent Thyroiditis:
• Similar to postpartum but not related to pregnancy
• Autoimmune etiology
• Low uptake scan distinguishes from Graves'

Management by Type

Hashimoto's Thyroiditis:
• Levothyroxine if TSH >10 mIU/L or symptomatic
• Consider treatment if TSH 4.5-10 with positive antibodies
• Monitor TSH every 6-12 months
Subacute Thyroiditis:
Thyrotoxic Phase:
• Beta-blockers for symptoms (propranolol 20-40 mg TID)
• NSAIDs or corticosteroids for pain
• NO antithyroid drugs (not producing hormone)
Hypothyroid Phase:
• Levothyroxine if symptomatic or prolonged
• Usually temporary - attempt withdrawal after 6-12 months
Postpartum Thyroiditis:
• Beta-blockers if thyrotoxic
• Levothyroxine if hypothyroid and symptomatic
• Monitor TSH at 6 and 12 months postpartum
• Screen in future pregnancies

Diagnostic Testing

Laboratory: TSH, FT4, TPO antibodies, ESR/CRP
Radioiodine Uptake: Low in all types during thyrotoxic phase
Ultrasound: Heterogeneous, hypoechoic in Hashimoto's; normal/decreased vascularity in subacute

Clinical Pearls

💡 Painful thyroid + elevated ESR = Subacute thyroiditis
💡 Hashimoto's increases risk of thyroid lymphoma (rare)
⚠️ Pregnancy: Screen for postpartum thyroiditis if TPO antibodies positive
💡 Drug-induced thyroiditis: Amiodarone, lithium, interferon-alpha, checkpoint inhibitors
🌟 Adrenal

Cushing's Syndrome

Endocrine Society 2024

Clinical Features & Screening

Classic Features:
• Central obesity, facial plethora, supraclavicular fat pads
• Purple striae (>1 cm wide)
• Proximal muscle weakness
• Hypertension, glucose intolerance
• Osteoporosis, easy bruising
• Psychiatric symptoms
Who to Screen:
• Multiple progressive features
• Young patients with osteoporosis/hypertension
• Adrenal incidentaloma
• Children with decreasing growth velocity and weight gain

Diagnostic Algorithm Grade A

Step 1: Screen for Hypercortisolism (2 abnormal tests):
• 24-hour urinary free cortisol (≥3x upper limit)
• Late-night salivary cortisol (≥2 samples elevated)
• 1 mg overnight dexamethasone suppression test (cortisol >1.8 mcg/dL)
• Low-dose dexamethasone (2 mg/day x 48 hr): cortisol >1.8 mcg/dL
Step 2: ACTH Level (Determine Etiology):
ACTH <5 pg/mL: ACTH-independent (Adrenal cause)
→ Adrenal CT/MRI
→ Adenoma vs. carcinoma vs. bilateral hyperplasia

ACTH ≥20 pg/mL: ACTH-dependent
→ Proceed to Step 3
Step 3: Differentiate Pituitary vs. Ectopic:
• Pituitary MRI
• High-dose dexamethasone suppression test (8 mg)
• CRH stimulation test
• Bilateral inferior petrosal sinus sampling (BIPSS) - Gold standard

Treatment

Pituitary Cushing's (70%):
• Transsphenoidal surgery - First-line
• Radiation if surgery fails
• Medical therapy: Pasireotide, osilodrostat
Adrenal Cushing's (15-20%):
• Unilateral adrenalectomy for adenoma
• Bilateral adrenalectomy for bilateral disease
• Mitotane for adrenal carcinoma
Ectopic ACTH (10-15%):
• Resect source if identified
• Medical therapy: Ketoconazole, metyrapone, etomidate

Important Considerations

⚠️ Exclude exogenous glucocorticoids (most common cause of "Cushing's")
⚠️ Pseudo-Cushing's: Alcoholism, depression, obesity - Can have mildly elevated cortisol
💡 Post-op: Monitor for adrenal insufficiency - May need hydrocortisone temporarily
🌟 Adrenal

Addison's Disease (Primary Adrenal Insufficiency)

Endocrine Society 2024 ESE 2023

Clinical Presentation

Symptoms:
• Fatigue, weakness, weight loss
• Hyperpigmentation (skin creases, mucosa)
• Hypotension, orthostasis
• Salt craving
• Nausea, vomiting, abdominal pain
• Hyponatremia, hyperkalemia
Etiology:
• Autoimmune (80% in developed countries)
• Tuberculosis, HIV
• Adrenal hemorrhage/infarction
• Metastatic disease
• Medications (ketoconazole, etomidate)

Diagnostic Testing Grade A

Morning Cortisol (8 AM):
• <3 mcg/dL: Diagnostic of AI
• >15 mcg/dL: Rules out AI
• 3-15 mcg/dL: Perform ACTH stimulation test
ACTH Stimulation Test (Cosyntropin 250 mcg IV/IM):
• Measure cortisol at 0, 30, and 60 minutes
• Normal: Peak cortisol >18-20 mcg/dL
• AI: Peak <18 mcg/dL
ACTH Level (Differentiate Primary vs. Secondary):
Primary AI: ACTH elevated (>2x normal)
Secondary AI: ACTH low or inappropriately normal
Additional Tests for Primary AI:
• 21-hydroxylase antibodies (autoimmune)
• Adrenal CT (infection, hemorrhage, metastases)
• Screen for other autoimmune diseases

Replacement Therapy

Glucocorticoid Replacement:
• Hydrocortisone 15-25 mg/day divided 2-3 times
• Typical regimen: 10 mg AM, 5 mg noon, 5 mg 4 PM
• OR Prednisone 3-5 mg once daily
• OR Dexamethasone 0.25-0.5 mg once daily (longer-acting)
Mineralocorticoid Replacement (Primary AI Only):
• Fludrocortisone 0.05-0.2 mg once daily
• Monitor: BP, electrolytes, plasma renin activity
Stress Dosing (Sick Day Rules):
• Minor illness: Double or triple usual dose
• Major illness/surgery: Hydrocortisone 100 mg IV q8h
• Taper to maintenance over 3-5 days as patient improves

Adrenal Crisis - EMERGENCY

⚠️ Presentation: Shock, hypotension, acute abdomen, confusion, hypoglycemia
⚠️ Treatment:
• IV fluids: 0.9% NaCl 1-2 L rapidly
• Hydrocortisone 100 mg IV bolus → 50-100 mg q6-8h
• DO NOT delay treatment for testing
• Treat precipitant (infection, trauma)
💡 All patients should carry emergency ID and injectable hydrocortisone
💡 Patient education on stress dosing is critical
🌟 Adrenal

Pheochromocytoma & Paraganglioma

Endocrine Society 2014

Clinical Presentation & Screening

Classic Triad (occurs in 50%):
• Episodic headaches
• Sweating
• Tachycardia/palpitations
Who to Screen:
• Paroxysmal hypertension
• Resistant hypertension
• Hypertensive crisis during anesthesia/procedures
• Adrenal incidentaloma
• Family history of pheochromocytoma/paraganglioma
• Hereditary syndromes: VHL, MEN2, NF1, SDH mutations

Diagnostic Testing Grade A

Biochemical Testing (First-line):
• Plasma free metanephrines OR
• 24-hour urine metanephrines + catecholamines

Positive: >2x upper limit of normal
Sensitivity >95%, Specificity 85-90%
Imaging (Once Biochemically Confirmed):
• Adrenal CT or MRI (first-line)
• If negative, functional imaging:
- 123I-MIBG scintigraphy
- PET scan with 18F-FDOPA or 68Ga-DOTATATE
Genetic Testing:
• Recommended for ALL patients
• 30-40% have germline mutation
• Test for: VHL, RET, NF1, SDHx genes

Preoperative Management & Surgery

Alpha-Blockade (Essential):
• Phenoxybenzamine 10-20 mg BID → titrate to max 1-2 mg/kg/day
• Start 10-14 days before surgery
• Goal: Control BP, normalize volume
Beta-Blockade (Only AFTER alpha-blockade):
• Add if persistent tachycardia
• Propranolol or metoprolol
• NEVER give beta-blocker first (unopposed alpha = hypertensive crisis)
Surgery:
• Laparoscopic adrenalectomy - Preferred
• Experienced surgical team essential
• Monitor for hypotension post-resection

Critical Points

⚠️ Rule of 10s: 10% bilateral, 10% extra-adrenal, 10% malignant, 10% familial
⚠️ Never give beta-blocker before alpha-blockade
💡 Metastatic disease in 10-15% - No reliable markers except metastases
💡 Lifelong surveillance needed (recurrence possible)
🧠 Pituitary

Prolactinoma

Endocrine Society 2023

Clinical Presentation

Women:
• Galactorrhea
• Amenorrhea or oligomenorrhea
• Infertility
• Decreased libido
Men:
• Erectile dysfunction
• Decreased libido
• Gynecomastia (less common)
• Infertility
• Often present late with mass effects
Mass Effects (Macroadenomas):
• Headache
• Visual field defects (bitemporal hemianopsia)
• Hypopituitarism

Diagnostic Workup

Serum Prolactin:
• Mild elevation (20-50 ng/mL): Many causes
• Moderate (50-100 ng/mL): Likely prolactinoma or other pituitary disease
• Markedly elevated (>200 ng/mL): Macroprolactinoma
• Check for macroprolactin (false elevation)
Rule Out Other Causes:
• Pregnancy test
• Medications: Antipsychotics, metoclopramide, SSRIs
• Hypothyroidism (TSH)
• Renal failure
• Chest wall lesions
Pituitary MRI:
• Microadenoma: <10 mm
• Macroadenoma: ≥10 mm
• Assess chiasm compression
Assess Pituitary Function:
• IGF-1, ACTH, cortisol
• TSH, FT4
• LH, FSH, testosterone/estradiol
• Visual fields if macroadenoma

Treatment Grade A

First-line: Dopamine Agonists

Cabergoline (Preferred):
• Start 0.25 mg twice weekly
• Titrate by 0.25 mg/week every 4 weeks
• Usual dose: 0.5-1.5 mg twice weekly (max 3 mg/week)
• Better tolerated, more effective, taken less frequently

Bromocriptine:
• Start 1.25 mg at bedtime with food
• Titrate to 2.5-15 mg/day divided BID
• Safe in pregnancy (preferred if conception planned)
When to Treat:
• Microadenoma: If symptomatic OR desiring fertility
• Macroadenoma: Always treat
• Monitor prolactin, MRI to assess response
Surgery (Second-line):
• Dopamine agonist resistance/intolerance
• Visual field compromise not improving on medication
• CSF leak from tumor
• Transsphenoidal approach

Monitoring & Special Situations

Response Assessment: Prolactin every 3 months until normal, then every 6-12 months
MRI: At 1 year, then as clinically indicated
Pregnancy:
• D/C cabergoline, continue bromocriptine only if large tumor
• Monitor symptoms (not prolactin)
• MRI if visual symptoms develop

Important Considerations

💡 Most prolactinomas shrink dramatically with dopamine agonists (60-90%)
⚠️ Side effects: Nausea, orthostasis, impulse control disorders (rare)
💡 Can attempt withdrawal after 2+ years if prolactin normalized and MRI shows no tumor
🧠 Pituitary

Hypopituitarism

Endocrine Society 2016

Etiology & Clinical Features

Common Causes:
• Pituitary adenoma (mass effect)
• Post-surgical or radiation
• Traumatic brain injury
• Sheehan's syndrome (postpartum hemorrhage)
• Infiltrative diseases (hemochromatosis, sarcoidosis)
• Lymphocytic hypophysitis
Hormone Deficiency Pattern:
• GH and gonadotropins typically first
• TSH, ACTH usually later
• Posterior pituitary (ADH) rarely affected unless stalk/posterior lesion

Diagnostic Testing

ACTH/Cortisol Axis:
• Morning cortisol (8 AM)
• If <3 mcg/dL: Secondary AI
• If 3-15 mcg/dL: ACTH stimulation test
• ACTH will be low-normal (inappropriately low)
TSH/Thyroid Axis:
• FT4 and TSH
• Secondary hypothyroidism: Low/normal FT4 with inappropriately normal/low TSH
• Do NOT use TSH alone for diagnosis
Gonadotropin Axis:
Men: Low testosterone with low/normal LH, FSH
Women: Oligo/amenorrhea, low estradiol with low/normal LH, FSH
Postmenopausal: Low/normal FSH (should be elevated)
GH/IGF-1 Axis:
• IGF-1 level
• If low → GH stimulation test (insulin tolerance test or glucagon)
• Peak GH <5 mcg/L suggests deficiency
Posterior Pituitary:
• If polyuria/polydipsia: Check serum/urine osmolality
• Water deprivation test if diabetes insipidus suspected
Imaging:
• Pituitary MRI with gadolinium
• Assess for mass, empty sella, hemorrhage

Hormone Replacement Therapy

Glucocorticoid (MOST URGENT):
• Hydrocortisone 15-25 mg/day divided
• 10 mg AM, 5 mg noon, 5 mg afternoon
• OR Prednisone 3-5 mg once daily
• Stress dosing protocols essential
Thyroid:
• Levothyroxine (start AFTER glucocorticoid)
• Initial: 1.6 mcg/kg/day (can start full dose)
• Monitor FT4 (NOT TSH)
• Target: FT4 in upper half of normal range
Sex Hormones:
Men: Testosterone replacement
• Injections, gel, or patch
• Target: Mid-normal testosterone

Women: Estrogen/progesterone (if premenopausal)
• Transdermal estradiol preferred
• Add progesterone if uterus present
Growth Hormone:
• Consider in adults with severe deficiency
• Start low: 0.2-0.4 mg/day SC
• Titrate based on IGF-1 levels
• Benefits: Body composition, bone density, QOL
ADH (if diabetes insipidus):
• Desmopressin 0.1-0.4 mg/day PO or 10-40 mcg intranasal
• Monitor sodium (hyponatremia risk)

Critical Management Points

⚠️ ALWAYS replace glucocorticoids BEFORE thyroid hormone (risk of adrenal crisis)
⚠️ Do NOT use TSH to monitor secondary hypothyroidism - use FT4
💡 Educate on stress dosing - essential for preventing adrenal crisis
💡 Annual screening for new hormone deficiencies
💊 Other

Male Hypogonadism

Endocrine Society 2024

Classification & Diagnosis

Primary Hypogonadism (Testicular):
• Low testosterone + High LH/FSH
• Causes: Klinefelter's, orchitis, trauma, chemotherapy
Secondary Hypogonadism (Hypothalamic-Pituitary):
• Low testosterone + Low/normal LH/FSH
• Causes: Pituitary tumor, hyperprolactinemia, medications, obesity
Diagnostic Criteria:
• Morning total testosterone <300 ng/dL (on 2 separate occasions)
• PLUS symptoms:
- Decreased libido
- Erectile dysfunction
- Fatigue
- Decreased muscle mass
- Decreased bone density

Testosterone Replacement Therapy

Contraindications (Screen First):
• Prostate cancer or high PSA
• Breast cancer
• Hematocrit >48%
• Untreated severe sleep apnea
• Heart failure (relative contraindication)
• Fertility desired (use hCG/clomiphene instead)
Formulations:
Injections (Most cost-effective):
• Testosterone cypionate/enanthate 100-200 mg IM every 1-2 weeks
• Testosterone undecanoate 750 mg IM every 10 weeks

Transdermal (More physiologic):
• Gel 1%: 50-100 mg applied daily to shoulders/arms
• Patch: 4 mg applied nightly

Buccal/Nasal:
• Less commonly used

Oral (Avoid methyltestosterone - hepatotoxic):
• Testosterone undecanoate oral available in some countries

Monitoring on Testosterone Therapy

3-6 months after initiation, then annually:
• Testosterone level (target: 400-700 ng/dL mid-normal)
• Hematocrit (hold if >54%, consider phlebotomy)
• PSA (if >50 years or high risk)
• Digital rectal exam (controversial)
Bone density: If osteoporosis at baseline, repeat in 1-2 years
Symptoms: Libido, energy, erectile function

Special Considerations

⚠️ Testosterone therapy causes infertility - Use hCG if fertility desired
⚠️ CV risk: Controversial - individualize decision, especially in older men with CV disease
💡 Obesity/metabolic syndrome: Weight loss may improve testosterone
💡 Clomiphene citrate: Alternative for secondary hypogonadism preserving fertility
💊 Other

Polycystic Ovary Syndrome (PCOS)

Endocrine Society 2023 ESHRE 2023

Rotterdam Criteria (2 of 3 Required)

1. Oligo-ovulation or Anovulation:
• <8 menses per year
• Irregular cycles (>35 days or <21 days)
2. Hyperandrogenism:
Clinical: Hirsutism, acne, male-pattern baldness
Biochemical: Elevated total/free testosterone or DHEAS
3. Polycystic Ovaries on Ultrasound:
• ≥20 follicles (2-9 mm) per ovary OR
• Ovarian volume >10 mL
Exclusions:
Rule out: Pregnancy, thyroid dysfunction, hyperprolactinemia, congenital adrenal hyperplasia, Cushing's syndrome, androgen-secreting tumors

Comprehensive Management

Lifestyle Modification (Foundation):
• Weight loss 5-10% improves ovulation, insulin sensitivity
• Diet: Low glycemic index preferred
• Exercise: 150 min/week moderate activity
Metabolic Management:
Metformin 1500-2000 mg/day:
• Improves insulin sensitivity
• Modest improvement in menstrual regularity
• May aid weight loss
• Start 500 mg daily, titrate weekly

Screen for:
• Diabetes/prediabetes (OGTT or HbA1c)
• Dyslipidemia
• NAFLD
• Sleep apnea
Menstrual Regulation & Contraception:
Combined oral contraceptives (COCs):
• First-line for menstrual irregularity
• Reduces androgens, prevents endometrial hyperplasia
• Choose low androgenic progestin

If COCs contraindicated:
• Cyclic progestins (medroxyprogesterone 10 mg x 10-14 days/month)
Hirsutism Treatment:
• COCs (first-line)
• Add spironolactone 50-200 mg/day if inadequate response
• Eflornithine cream 13.9% for facial hirsutism
• Cosmetic measures: Laser, electrolysis
Infertility Treatment:
First-line: Letrozole 2.5-7.5 mg days 3-7
Second-line: Clomiphene citrate 50-150 mg days 3-7
If resistant: Gonadotropins, IVF
Consider: Metformin adjunct, ovarian drilling

Long-term Screening & Monitoring

Annually:
• Glucose tolerance (OGTT or HbA1c)
• Lipid panel
• Blood pressure
• Weight, waist circumference
Endometrial Protection:
• If oligomenorrhea, induce period every 3 months minimum
• Screen for endometrial hyperplasia if prolonged amenorrhea

Important Considerations

⚠️ Increased risk: T2DM (40-50%), metabolic syndrome, cardiovascular disease
💡 PCOS is a lifelong condition requiring ongoing management
💡 Mental health: Higher rates of depression, anxiety - screen regularly
✨ Newer agents: GLP-1 RAs showing promise for weight loss and metabolic improvement
⚖️ Metabolic

Osteoporosis

AACE 2024 Endocrine Society 2023

Diagnosis & Screening

WHO Criteria (DEXA Scan - T-score):
• Normal: T-score ≥-1.0
• Osteopenia: T-score -1.0 to -2.5
• Osteoporosis: T-score ≤-2.5
• Severe osteoporosis: T-score ≤-2.5 + fragility fracture
Screening Recommendations:
• Women ≥65 years
• Men ≥70 years
• Postmenopausal women <65 with risk factors
• Men 50-69 with risk factors
• Adults with fragility fracture
• NEW 2024 ADA: Diabetes patients ≥65 years (higher fracture risk)
Sites to Measure:
• Lumbar spine (L1-L4)
• Total hip
• Femoral neck
Use lowest T-score for diagnosis

Fracture Risk Assessment

🧮 FRAX Score

Calculate 10-year fracture probability at: FRAX Tool

Treatment Thresholds (NOF):
• 10-year hip fracture risk ≥3% OR
• 10-year major osteoporotic fracture risk ≥20%
→ Consider pharmacotherapy

Management Algorithm Grade A

Universal Measures:
• Calcium 1000-1200 mg/day (diet + supplement)
• Vitamin D 800-1000 IU/day (target 25(OH)D >30 ng/mL)
• Weight-bearing exercise
• Fall prevention
• Avoid smoking, excessive alcohol
First-line Pharmacotherapy (Most Patients):
Bisphosphonates:
• Alendronate 70 mg PO weekly
• Risedronate 35 mg PO weekly OR 150 mg monthly
• Ibandronate 150 mg PO monthly OR 3 mg IV q3months
• Zoledronic acid 5 mg IV yearly

Take on empty stomach, stay upright 30-60 min
Contraindicated if CrCl <30-35 mL/min
Alternative Agents:
Denosumab (Prolia) 60 mg SC q6months:
• No renal dose adjustment
• Risk: Rebound fractures if stopped

Raloxifene 60 mg daily:
• SERM - for postmenopausal women only
• Reduces spine fractures, breast cancer risk
• Increases VTE risk
Anabolic Therapy (Severe Osteoporosis):
Indications:
• T-score ≤-3.5
• Multiple vertebral fractures
• Fracture on antiresorptive therapy

Options:
• Teriparatide 20 mcg SC daily x 2 years max
• Abaloparatide 80 mcg SC daily x 2 years max
• Romosozumab 210 mg SC monthly x 1 year

Follow with antiresorptive (bisphosphonate/denosumab)

Monitoring & Duration

DEXA: Repeat in 1-2 years after starting therapy, then every 2 years
Bone Turnover Markers: Optional - CTX, P1NP
Duration of Therapy:
• Oral bisphosphonates: 3-5 years, then drug holiday if low risk
• IV zoledronic acid: 3-6 years
• Denosumab: No drug holiday (rebound risk)
• Reassess fracture risk at each interval

Secondary Causes & Complications

💡 Screen for Secondary Causes:
Vitamin D deficiency, hyperparathyroidism, hyperthyroidism, Cushing's, hypogonadism, celiac disease, multiple myeloma
⚠️ Atypical femoral fractures: Rare with long-term bisphosphonates
⚠️ Osteonecrosis of jaw: Rare - dental hygiene, avoid invasive procedures
✨ Diabetes & fracture risk: DEXA may underestimate risk - consider treating at higher T-scores