PHARMACOLOGY TBL - COMPLETE CASE DISCUSSION NOTES

Case: 40-year-old woman with hyperthyroidism (Graves Disease)

STEP 1: PATIENT'S PROBLEM

A. Patient Characteristics

• 40-year-old female
• 4-month history of progressive symptoms
• Family history of thyroid disease (maternal aunt)
• No exophthalmos, no pretibial myxedema (incomplete Graves triad)

B. Pertinent Findings

• Increased sweating (hyperhidrosis)
• Palpitations
• Weight loss of 7 kg in 6 months (despite presumably normal/increased appetite)
• Oligomenorrhea (lighter periods but regular - classic thyrotoxicosis effect on menstrual cycle)
• Nervousness and agitation
• Family history of thyroid disease

• Tachycardia: pulse 106/min (sinus tachycardia from excess thyroid hormone)
• BP 130/60 (wide pulse pressure - high systolic, low diastolic due to increased cardiac output and peripheral vasodilation)
• Diffuse, non-tender, smooth thyroid enlargement (diffuse goiter)
• Thyroid bruit (highly significant - indicates increased vascularity from TSH receptor stimulation)
• Fine finger tremor (beta-adrenergic overstimulation)
• Nervous, agitated affect

• T3: 4.8 nmol/L (NR 0.8-2.4) - markedly ELEVATED (2x upper normal)
• T4: 48 nmol/L (NR 9-23) - markedly ELEVATED (>2x upper normal)
• TSH: 0.29 mU/L (NR 0.4-5 mU/L) - SUPPRESSED (primary hyperthyroidism confirmed)

C. Diagnosis: Graves Disease (Autoimmune Hyperthyroidism)

1. Clinical criteria - classic triad signs: diffuse thyroid enlargement + thyrotoxicosis symptoms (note: no ophthalmopathy or dermopathy in this case but not required for diagnosis)
2. Biochemical criteria - elevated T3 and T4 with suppressed TSH = primary hyperthyroidism
3. Diffuse smooth goiter with bruit - pathognomonic of Graves disease; bruit indicates hypervascular gland from TSH-receptor antibody (TRAb/TSI) stimulation
4. Autoimmune pathogenesis - IgG autoantibodies against the TSH receptor stimulate thyroid follicular cells independent of endogenous TSH, causing unregulated hormone production (Robbins & Kumar Basic Pathology)
5. Demographics - peak incidence 20-40 years, women 7x more affected than men; genetic predisposition (HLA alleles, CTLA4 genes) explains familial clustering (Robbins & Kumar)

Note on absent features: No exophthalmos and no focal skin thickening (pretibial myxedema) - these unique features of Graves are present only in a subset of patients; their absence does not exclude the diagnosis.

STEP 2: THERAPEUTIC OBJECTIVE

A. Curative

• Achieve permanent euthyroid state by inducing immunological remission with antithyroid drugs (18-month course of carbimazole)
• OR if remission fails: definitive treatment with radioactive iodine (RAI/I-131) or total thyroidectomy
• Goal: normalize free T3, free T4, and eventually TSH levels

B. Symptomatic

• Control adrenergic symptoms (palpitations, tremor, sweating, anxiety) using a beta-blocker (propranolol) as adjunct therapy
• Propranolol 10-40 mg TID/QID: reduces sympathomimetic effects of excess thyroid hormone; also has the added benefit of reducing peripheral conversion of T4 to T3 (at higher doses)
• Relief expected within days of starting beta-blocker

C. Preventive

• Prevent thyroid storm (thyrotoxic crisis) - a life-threatening emergency
• Prevent cardiovascular complications: atrial fibrillation, heart failure (from persistent tachycardia and high output state)
• Prevent bone loss (osteoporosis risk from prolonged hyperthyroidism)
• Monitor for and prevent agranulocytosis from carbimazole therapy

STEP 3: TREATMENT CHOICE

A. Standard Treatment Based on Available Evidence

• 12-18 months of continuous therapy (shorter courses have higher relapse rates)
• Remission rates: <50% overall; ~40% in women, ~20% in men
• Relapse typically occurs within 3-6 months of stopping - offer definitive therapy then

B. Drug-Drug Interaction: Carbimazole + Propranolol (Beta-blocker)

1. Carbimazole + Warfarin (if needed): Carbimazole increases anticoagulant effect of warfarin because hyperthyroidism increases clotting factor catabolism; as patient becomes euthyroid, warfarin dose may need reduction.
2. Propranolol (non-selective beta-blocker) interactions:
   • Reduces heart rate - monitor for bradycardia
   • Can mask hypoglycemia signs in diabetics
   • Avoid in patients with asthma/bronchospasm (bronchoconstriction)
   • No major direct pharmacokinetic interaction with carbimazole
3. Carbimazole + Digoxin: If digoxin is used (e.g., for AF), hyperthyroidism accelerates digoxin clearance; as patient becomes euthyroid on carbimazole, digoxin levels may rise - monitor.

STEP 4: START TREATMENT

A. Doctor's Order

MEDICATION ORDERS:
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1. Carbimazole 30 mg PO OD (once daily)
   - Rationale: Severe disease (T3 and T4 >2x upper limit)
   - Titrate down to 5-10 mg/day once euthyroid (fT4 normal)

2. Propranolol 40 mg PO TID (three times daily)
   - Rationale: Symptomatic control of tachycardia, palpitations, tremor
   - Check HR before each dose; hold if HR <60 bpm
   - Taper and stop once carbimazole achieves euthyroid state

3. Check FBC (full blood count/CBC) BEFORE starting carbimazole (baseline)
4. Check LFTs (liver function tests) baseline

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ALLERGIES: None known

B. Continue, Adjust, or Stop

C. Prescription for Amlodipine (for context - blood pressure/HR management if needed as home medication)

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PRESCRIPTION

Patient: [Name], 40 y/o Female
Date: ___________

Rx:
    Amlodipine 5 mg tablet
    Take 1 tablet by mouth once daily
    Quantity: 30 tablets (30-day supply)
    Refill: 0 (reassess after euthyroid state achieved)

Instructions to patient:
- Take at same time each day
- Monitor BP and HR at home
- Report ankle swelling, flushing, or worsening palpitations

Prescriber: _______________  Lic. No.: ___________
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D. Monitoring While on Medication

• CBC with differential - baseline, then promptly if ANY fever, sore throat, or mouth ulcers occur (screen for agranulocytosis)
• Thyroid function tests (fT3, fT4, TSH) - every 4-6 weeks initially, then every 8-12 weeks once controlled
• Liver function tests (LFTs) - baseline; if jaundice, right upper quadrant pain, or nausea develops, repeat immediately (hepatotoxicity)
• Heart rate - before each propranolol dose; aim HR 60-90
• Blood pressure - monitor during follow-up
• Symptoms diary - ask patient to track tremor, sweating, palpitations, weight

STEP 5: PATIENT INFORMATION AND INSTRUCTIONS

• This medicine slows down your thyroid from making too many hormones
• Take it every day at the same time - do NOT skip doses
• It will take 3 to 4 weeks before you feel significantly better - this is normal
• You will need to take it for at least 12-18 months

If you develop a sore throat, fever, mouth ulcers, or any signs of infection while taking carbimazole, STOP the tablet immediately and go to the emergency room or your doctor the same day for a blood test. This is because carbimazole can rarely cause a dangerous drop in your white blood cells (agranulocytosis) which leaves you unable to fight infection. This side effect is rare (0.2-0.5%) but serious.

• Skin rash or itching (common, may need dose adjustment)
• Yellow skin or eyes, dark urine, stomach pain (liver problem - rare but serious - stop and seek care)
• Joint pain or swelling

• This controls your fast heartbeat, trembling, and sweating while waiting for carbimazole to work
• Take it with or without food, three times a day
• Do NOT stop this tablet suddenly
• Do NOT take if you have asthma or breathing problems - tell your doctor
• May cause dizziness - rise slowly from sitting or lying position

• Avoid iodine-rich foods in excess (seaweed, kelp supplements, high-dose iodine vitamins) as they can worsen thyroid overactivity
• No smoking - smoking worsens Graves eye disease (ophthalmopathy)
• Keep all follow-up appointments - blood tests are needed regularly
• Tell all other doctors/dentists you are on carbimazole before any procedures
• Women of childbearing age: If you plan to become pregnant, inform your doctor BEFORE conceiving - the medication may need to be switched to propylthiouracil in the first trimester (carbimazole carries a small risk of scalp defects in the newborn)
• If you feel your symptoms are getting much worse suddenly (extreme agitation, very high fever, rapid heart rate) - go to the emergency room immediately (thyroid storm)

• Watch for and report any signs of infection (fever, sore throat) - these need same-day medical attention
• Encourage regular medication and follow-up
• Be patient - the medicine takes weeks to work fully

STEP 6: MONITOR TREATMENT

A. Drug Effect Monitoring

B. Laboratory Tests to Monitor

C. Other Factors to Monitor

• Weight - expect gradual weight gain back toward baseline as euthyroid is restored
• Heart rate - aim for resting HR <90 bpm; document at each visit
• Blood pressure - wide pulse pressure (130/60) should normalize as cardiac output normalizes
• Tremor - should resolve with beta-blocker and with euthyroid state
• Menstrual cycle - oligomenorrhea should normalize with euthyroidism
• Anxiety/agitation/nervousness - should improve as hormone levels normalize
• Goiter size - a shrinking goiter correlates with improved remission likelihood (Scott-Brown's, Vol 1)
• Eyes - although no proptosis initially, monitor for development of ophthalmopathy at each visit (Graves ophthalmopathy can develop or worsen independently of thyroid status)
• Skin - check for pretibial myxedema (glycosaminoglycan skin deposits) at each visit

• Cardiac function - persistent tachycardia increases risk of high-output heart failure; if AF develops, anticoagulation and rate control are needed
• Liver function - especially if patient reports any GI symptoms on carbimazole
• Bone health - prolonged thyrotoxicosis accelerates bone resorption; ensure adequate calcium/vitamin D intake
• Compliance assessment - if large doses are still required without adequate response, suspect poor adherence (Scott-Brown's, Vol 1)

PHARMACOLOGY QUICK REFERENCE SUMMARY

References (as specified in your file)

1. Goodman and Gillman's Pharmacological Basis of Therapeutics, 13th Edition
2. Harrison's Principles of Internal Medicine, 20th Edition
3. Robbins & Kumar Basic Pathology (Graves Disease pathogenesis and morphology)
4. Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Vol 1 (carbimazole dosing, side effects, Graves management)
5. UpToDate.com - Hyperthyroidism management
6. MIMS Philippines - local drug formulary
7. WHO.int - essential medicines list