Hyperthyroidism: Definition, Causes, Diagnosis & Stepwise Management Guide [MMI, PTU]

1️⃣. Definition and Pathophysiology

Hyperthyroidism = overproduction of thyroid hormones (T3, T4) by the thyroid gland → suppressed TSH.

Thyrotoxicosis = clinical syndrome of excess circulating thyroid hormone, regardless of cause (e.g., Graves, thyroiditis, toxic nodular goiter).

Pathophysiology summary:

↑ T3/T4 → ↑ basal metabolic rate
↑ β-adrenergic receptor sensitivity → palpitations, tremor
Feedback inhibition → ↓ TSH from pituitary

2️⃣. Common Causes

Category	Disease	Mechanism
Autoimmune	Graves’ disease	TRAb stimulates TSH receptor → overproduction
Toxic nodular disease	Toxic multinodular goiter, Toxic adenoma	Autonomous hormone production
Inflammatory	Subacute thyroiditis, Silent thyroiditis, Postpartum thyroiditis	Destruction of follicles → hormone leakage
Iatrogenic	Amiodarone, excess levothyroxine, iodine exposure	Overreplacement / iodine-induced
Rare	TSH-secreting pituitary adenoma, Struma ovarii	Ectopic production

3️⃣. Diagnosis — Lab Interpretation

Parameter	Normal Range	Hyperthyroid Pattern
TSH	0.4 – 4.0 mIU/L	↓ (often < 0.01)
Free T4 (FT4)	0.8 – 1.8 ng/dL (10–23 pmol/L)	↑
Free T3 (FT3)	2.3 – 4.2 pg/mL (3.5–6.5 pmol/L)	↑↑ (sometimes disproportionately high → T3 toxicosis)

🔹 T3 toxicosis: TSH ↓, FT3 ↑, FT4 normal → early Graves or toxic nodular goiter 🔹 Subclinical hyperthyroidism: TSH ↓, FT3/FT4 normal → mild or early disease

4️⃣. Confirming the Cause (Etiologic Workup)

Test	Purpose	Findings
TSH receptor antibody (TRAb)	Confirm Graves’ disease	Positive = Graves
Thyroid peroxidase antibody (Anti-TPO)	Autoimmune marker	+ in Graves or Hashimoto
RAI Uptake Scan	Identify pattern of activity	Diffuse uptake = Graves Patchy = Toxic MNG Low uptake = Thyroiditis
Thyroid Ultrasound with Doppler	Assess structure and vascularity	"Thyroid inferno" pattern in Graves
Baseline labs	Safety before drugs	CBC, LFT, Pregnancy test (if female)

5️⃣. Management — Overview

🎯 Goals:

Control symptoms (tachycardia, tremor)
Normalize thyroid hormone levels
Prevent complications (thyroid storm, arrhythmia, osteoporosis)
Treat the underlying cause

6️⃣. Stepwise Management Algorithm

A. Symptomatic Control

Drug	Dose	Purpose
Propranolol	20–40 mg PO every 6–8 hours	Control palpitations, tremor, anxiety; inhibits T4→T3 conversion
Alternative (asthma)	Atenolol 25–50 mg PO daily	Cardioselective option

B. Definitive Control of Hormone Synthesis

🩸 1. Antithyroid Drugs (First-Line for Most)

Drug	Adult Dose	Notes
Methimazole (MMI)	Mild: 10 mg/dayModerate: 20–30 mg/daySevere: 40 mg/day (divided 2–3 times daily)*	Preferred (longer half-life, safer)
Propylthiouracil (PTU)	Initial: 100 mg PO tidMaintenance: 50 mg tid	Use in 1st trimester pregnancy or thyroid storm
Duration:	12–18 months	Monitor TSH, FT4 q4–6 weeks
Monitor:	CBC, LFT	Risk: agranulocytosis, hepatotoxicity
Warning:	Stop immediately if fever/sore throat (→ CBC to check WBC).

✅ Once euthyroid achieved → reduce MMI to 5–10 mg/day maintenance.

💉 2. Radioactive Iodine (RAI-131)

Definitive treatment for most adults.
Contraindicated in:
- Pregnancy / breastfeeding
- Severe ophthalmopathy (worsens after RAI)
Goal: destroy thyroid tissue → hypothyroidism (then lifelong levothyroxine).

🩺 3. Surgery (Total or Subtotal Thyroidectomy)

Indications:

Large goiter / compressive symptoms
Suspicious or malignant nodule
Drug intolerance / relapse after MMI
Pregnancy (2nd trimester only)

Pre-op preparation:

Achieve euthyroid with MMI/PTU
Add potassium iodide 5 drops PO bid × 10 days before surgery to prevent thyroid storm.

C. Supportive Care

Measure	Purpose
Adequate hydration	Replace increased metabolic losses
Nutrition	High-protein, high-calorie diet
Avoid excess iodine	E.g., seaweed, multivitamins
Stress control	Prevent adrenergic flare
Smoking cessation	Reduces risk of Graves’ ophthalmopathy

7️⃣. Follow-up & Monitoring

Parameter	Timeline	Purpose
TSH, FT4, FT3	Every 4–6 weeks initially	Guide dose adjustment
CBC & LFT	Baseline, then if symptomatic	Detect agranulocytosis or hepatotoxicity
TRAb	At 12–18 months	Predict relapse or remission
After remission	Monitor yearly for relapse or hypothyroidism

8️⃣. Complications to Monitor

Untreated	From Drugs
Thyroid storm (fever, tachycardia, delirium)	Agranulocytosis (neutropenia)
Atrial fibrillation	Hepatotoxicity (esp. PTU)
Osteoporosis, muscle wasting	Hypothyroidism (from overtreatment)

9️⃣. Special Considerations

Condition	Preferred Drug	Notes
Pregnancy (1st trimester)	PTU	Avoid MMI (teratogenic)
Pregnancy (2nd–3rd trimester)	MMI	PTU hepatotoxic
Thyroid storm	PTU + Propranolol + Steroid + Iodine	PTU preferred (blocks T4→T3)

🔢 10. Drug Dosing Summary Table

Drug	Starting Dose	Maintenance Dose	Max Dose	Route	Notes
Methimazole (MMI)	10–30 mg/day	5–15 mg/day	40 mg/day	PO	Preferred; once daily ok
Propylthiouracil (PTU)	100 mg tid	50 mg tid	600–900 mg/day	PO	Use in 1st trimester, thyroid storm
Propranolol	20–40 mg q6h	10–20 mg q6h or PRN	160 mg/day	PO	Symptom control
Potassium iodide	5 drops bid (SSKI)	Short-term pre-op	—	PO	Given after PTU in thyroid storm

📉 11. Example Interpretation and Management (Your Case)

Parameter	Result	Interpretation
TSH	0.027 ↓	Suppressed
FT3	7.82 ↑	Markedly elevated
FT4	2.02 ↑	Elevated
→ Diagnosis: Primary hyperthyroidism (likely Graves’)

Start:

Methimazole 20 mg/day PO (moderate case)
Propranolol 20 mg PO q6h
Baseline CBC, LFT
TRAb ± Ultrasound if not done
Follow-up in 4–6 weeks

🧭 12. Treatment Targets

Phase	Goal
Initial (4–6 wks)	Normalize FT4 (TSH may remain low for months)
Maintenance (3–6 mo)	Stable FT4 and TSH within range
Long-term (12–18 mo)	Attempt drug withdrawal if TRAb negative and patient euthyroid

📚 Guideline References

American Thyroid Association (ATA): Hyperthyroidism and Other Causes of Thyrotoxicosis, 2016.
European Thyroid Association (ETA) Guideline 2018.
Thai Endocrine Society Clinical Practice Guideline for Thyrotoxicosis (2021).

🩺 Keys for Exam

✅ MMI preferred (once-daily, less hepatotoxic). ✅ PTU only for pregnancy 1st trimester or thyroid storm. ✅ Always check CBC + LFT before starting. ✅ TRAb optional for diagnosis, essential for predicting remission. ✅ Follow FT4, not TSH, in early follow-up. ✅ If symptoms controlled but FT4 high → increase MMI dose. ✅ If FT4 normal but TSH still low → keep same dose, recheck in 6 wks.