What is the diagnosis and treatment for a patient with primary hypothyroidism, elevated TSH, low T3, and high T4?

Diagnosis: Primary Hypothyroidism (Hashimoto's Thyroiditis)

This patient has severe overt primary hypothyroidism with a TSH of 157 mIU/L, low T3 (<43), elevated free T4 (4.25), and positive thyroid antibodies (EVIGG positive), requiring immediate levothyroxine therapy. 1

Understanding the Laboratory Pattern

The combination of markedly elevated TSH (>100 mIU/L chronically), low T3, and paradoxically elevated T4 with positive thyroid antibodies confirms autoimmune thyroiditis (Hashimoto's disease) as the underlying diagnosis. 1, 2

• The positive thyroid antibodies (EVIGG) identify an autoimmune etiology and predict ongoing thyroid destruction, with a 4.3% annual progression risk to complete thyroid failure. 1, 2
• The extremely elevated TSH (157 mIU/L) indicates the thyroid gland is failing despite maximal pituitary stimulation, defining this as severe overt hypothyroidism requiring treatment. 1
• The low T3 (<43) reflects inadequate peripheral conversion and tissue hypothyroidism, explaining clinical symptoms. 2
• The elevated T4 (4.25) in the setting of very high TSH is paradoxical but can occur in severe hypothyroidism when the failing thyroid gland produces predominantly T4 with impaired T3 conversion. 2

Critical diagnostic point: Negative pituitary imaging rules out secondary (central) hypothyroidism, confirming this is primary thyroid gland failure. 1

Immediate Treatment Protocol

Start levothyroxine immediately at 1.6 mcg/kg/day for patients under 70 years without cardiac disease, or 25-50 mcg/day for elderly patients or those with cardiac risk factors. 1, 3

Dosing Algorithm Based on Patient Characteristics:

• If patient is <70 years old AND has no cardiac disease: Start full replacement dose of 1.6 mcg/kg/day (typically 100-125 mcg daily for average adult). 1
• If patient is >70 years old OR has any cardiac disease/multiple comorbidities: Start conservatively at 25-50 mcg/day and titrate gradually every 6-8 weeks. 1, 3
• If patient has coronary artery disease specifically: Start at 12.5-25 mcg/day to avoid unmasking cardiac ischemia. 1, 4

Critical Safety Consideration Before Starting Treatment:

Rule out concurrent adrenal insufficiency BEFORE initiating levothyroxine, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1, 2

• Check 8 AM cortisol or perform cosyntropin stimulation test if patient has unexplained hypotension, hyponatremia, hyperpigmentation, or unexplained fatigue beyond what hypothyroidism explains. 1
• If adrenal insufficiency is present, start physiologic dose corticosteroids (hydrocortisone 15-20 mg/day) at least 1 week before initiating levothyroxine. 1, 2

Monitoring Protocol

Recheck TSH and free T4 in 6-8 weeks after starting therapy or any dose adjustment, as this represents the time needed to reach steady state. 1, 5

• Target TSH range: 0.5-4.5 mIU/L with normal free T4 levels. 1, 5
• Adjust levothyroxine dose in 12.5-25 mcg increments based on TSH response. 1
• Once stable, monitor TSH annually or sooner if symptoms change. 1

Dose Adjustment Guidelines:

• If TSH remains >10 mIU/L after 6-8 weeks: Increase levothyroxine by 25 mcg (or 12.5 mcg in elderly/cardiac patients). 1
• If TSH is 4.5-10 mIU/L: Increase by 12.5-25 mcg to normalize into reference range. 1
• If TSH drops <0.1 mIU/L: Decrease dose by 25-50 mcg immediately to prevent cardiac and bone complications. 1

Common Pitfalls to Avoid

Never start treatment based on a single TSH value without confirmation testing—but with TSH chronically >100 mIU/L, this patient clearly requires immediate treatment without waiting for repeat testing. 1, 4

• Undertreatment risk: Persistent hypothyroid symptoms, adverse cardiovascular effects, abnormal lipid metabolism, and impaired quality of life. 1
• Overtreatment risk: Approximately 25% of patients on levothyroxine are unintentionally maintained on excessive doses, increasing risk for atrial fibrillation (5-fold increased risk), osteoporotic fractures, and cardiac complications. 1, 5
• Missing transient thyroiditis: While this patient's positive antibodies and chronic elevation indicate permanent hypothyroidism, always consider whether thyroid dysfunction could be temporary (post-viral thyroiditis, medication-induced) to avoid unnecessary lifelong treatment. 1, 4

Special Considerations for This Patient

The combination of positive thyroid antibodies with TSH >100 mIU/L indicates this is permanent autoimmune hypothyroidism requiring lifelong treatment. 1, 2

• The normal CBC and other lab work rule out other causes of fatigue and confirm hypothyroidism as the primary issue. 2
• The elevated protein (46) may reflect chronic inflammation from autoimmune thyroiditis but is not clinically significant for treatment decisions. 2
• Monitor for development of other autoimmune conditions annually, as patients with Hashimoto's thyroiditis have increased risk of concurrent autoimmune diseases (adrenal insufficiency, celiac disease, type 1 diabetes). 1

Expected Clinical Response

Symptoms should begin improving within 2-4 weeks of starting adequate levothyroxine therapy, with full normalization of TSH taking 6-8 weeks. 1, 5

• Fatigue typically improves first (within 2-3 weeks). 5
• Weight, cold intolerance, and constipation improve more gradually (4-8 weeks). 5
• If symptoms persist despite normalized TSH, consider checking T3 levels or evaluating for other causes of symptoms. 2, 6