Thyroid Issues: Understanding Fatigue and Other Symptoms

Thyroid Physiology

Thyroid (butterfly-shaped, neck) produces T4 (thyroxine, prohormone) and T3 (triiodothyronine, active). Regulated by hypothalamic-pituitary-thyroid axis: TRH → TSH → T4/T3. T4→T3 conversion (deiodinases) in liver, kidney, brain, muscle. 99% protein-bound; free hormone is bioactive.

Hypothyroidism (Underactive)

• Primary (95%): Hashimoto’s thyroiditis (autoimmune), post-ablative (RAI, surgery), iodine deficiency, drugs (lithium, amiodarone, checkpoint inhibitors).
• Secondary/Central: Pituitary/hypothalamic disease.
• Symptoms: Fatigue, cold intolerance, weight gain (modest), constipation, dry skin, hair loss, menorrhagia, bradycardia, hoarseness, myxedema, cognitive slowing, depression.
• Labs: ↑ TSH, ↓ free T4 (overt); ↑ TSH, normal free T4 (subclinical).
• Treatment: Levothyroxine 1.6 mcg/kg/day; empty stomach, 30–60 min before food/meds; monitor TSH 6–8 wks after dose change.

Hyperthyroidism (Overactive)

• Causes: Graves’ disease (TSI antibodies), toxic multinodular goiter, toxic adenoma, thyroiditis (subacute, postpartum, amiodarone), excess levothyroxine.
• Symptoms: Heat intolerance, weight loss despite ↑ appetite, tachycardia, palpitations, tremor, anxiety, insomnia, diarrhea, menstrual irregularity, exophthalmos (Graves’), pretibial myxedema.
• Labs: ↓ TSH (<0.01), ↑ free T4/T3; TSI+, RAIU pattern.
• Treatment: Thionamides (methimazole first-line), RAI (definitive), thyroidectomy (large goiter, pregnancy, suspicion malignancy). Beta-blockers for symptom control.

Thyroid Nodules & Cancer

• Palpable in 5–10%; US-detected 50–65%.
• TI-RADS scoring guides FNA (≥1 cm solid, ≥1.5 cm mixed).
• Papillary (80%), follicular (15%), medullary (3%), anaplastic (1%).
• Excellent prognosis (20-yr survival >95% differentiated).

Special Populations

• Pregnancy: TSH targets trimester-specific (1st: 0.1–2.5; 2nd: 0.2–3.0; 3rd: 0.3–3.0 mIU/L). LT4 dose ↑ 25–50% by 4–6 wks. Monitor q4wks.
• Elderly: Atypical presentation (apathy, falls, AFib); lower treatment thresholds for subclinical.

Key Takeaway

Thyroid dysfunction is common, treatable, and often masquerades as fatigue, mood, or metabolic issues. Screen TSH with reflex free T4 in symptomatic, high-risk, or pregnant patients.