Hypothyroidism Study Guide

📖 Core Concepts Hypothyroidism – inadequate production of thyroid hormones (mainly T₄) by the thyroid gland. Primary vs Central Primary: disease resides in the thyroid (most common). Central: pituitary (secondary) or hypothalamic (tertiary) failure to stimulate the thyroid. Overt vs Subclinical Overt: ↑ TSH, ↓ free T₄ (symptomatic). Subclinical: ↑ TSH, normal free T₄ (often asymptomatic). Negative‑feedback loop – circulating T₃/T₄ suppress hypothalamic TRH and pituitary TSH; loss of hormone → TSH rises. Key hormones & enzymes T₄ (thyroxine) – major secreted hormone, peripheral conversion to T₃ (triiodothyronine) by iodothyronine deiodinases (Se‑dependent). Iodine & tyrosine – substrates for hormone synthesis; iodine deficiency → most common global cause. Autoimmune Hashimoto’s thyroiditis – lymphocytic infiltration + anti‑TPO, anti‑TG, anti‑TSH‑R antibodies; most common cause in iodine‑sufficient regions. Myxedema coma – severe, life‑threatening decompensation (hypothermia, bradycardia, altered mental status). --- 📌 Must Remember Epidemiology Overt hypothyroidism ≈ 0.3–0.4 % (U.S.); up to 1 % in iodine‑sufficient adults. Subclinical hypothyroidism ≈ 4–10 %, higher in women & >60 y. ≈1 billion people worldwide are iodine‑deficient. Lab thresholds Overt primary: TSH > 10 mIU/L or persistently >5 mIU/L with symptoms + low free T₄. Subclinical pregnancy: TSH 2.5–10 mIU/L (first trimester < 2.5 mIU/L). Central: low/normal TSH with low free T₄. Treatment triggers Overt hypothyroidism → always treat. Subclinical → treat if TSH > 10 mIU/L, pregnancy, or clear symptoms. Levothyroxine dosing Full replacement ≈ 1.6 µg/kg/day (young, healthy). Start ½–¾ dose in elderly or cardiac disease. Increase dose 30–50 % in pregnancy; ≈25 % after ≥10 % weight gain. Monitoring Check TSH & free T₄ 4–8 weeks after any dose change, then every 6 months once stable. Myxedema coma – give IV levothyroxine (200‑400 µg) or liothyronine, rewarm, give fluids, vasopressors, stress‑dose steroids. --- 🔄 Key Processes Thyroid Hormone Synthesis Iodide uptake → organification with tyrosine on thyroglobulin → coupling → T₄/T₃ stored in colloid → proteolysis releases hormones. Peripheral Conversion Type 1 & 2 deiodinases remove an outer‑ring iodine → T₄ → active T₃. Negative‑Feedback Loop ↓T₃/T₄ → ↑TRH (hypothalamus) → ↑TSH (pituitary) → ↑ thyroid output. Diagnostic Algorithm Step 1: Measure serum TSH. Step 2: If TSH ↑, obtain free T₄. Free T₄ ↓ → overt primary. Free T₄ normal → subclinical. If TSH low/normal + free T₄ ↓ → central. Levothyroxine Initiation & Titration Calculate weight‑based dose → give in the morning, empty stomach → re‑check labs 4‑8 weeks → adjust by 12‑25 % increments. Myxedema Coma Management (stepwise) Warm patient, secure airway, give IV levothyroxine (or liothyronine), IV glucocorticoids, fluid/electrolyte support, treat precipitating cause. --- 🔍 Key Comparisons Primary vs Central Hypothyroidism TSH: ↑ (primary) vs low/normal (central). Cause: thyroid gland disease vs pituitary/hypothalamic dysfunction. Overt vs Subclinical Free T₄: ↓ (overt) vs normal (subclinical). Symptoms: often evident (overt) vs often absent/minimal (subclinical). Levothyroxine vs Liothyronine vs Desiccated Thyroid Levothyroxine: synthetic T₄, standard first‑line, long half‑life. Liothyronine: synthetic T₃, short half‑life, not routinely recommended alone. Desiccated thyroid: mixture of T₄/T₃, variable potency → not guideline‑recommended. Iodine‑Deficiency vs Autoimmune (Hashimoto) Geography: endemic in iodine‑poor regions vs common in iodine‑replete areas. Lab: antibodies present in autoimmune; absent in pure deficiency. --- ⚠️ Common Misunderstandings “Normal TSH = normal thyroid function.” Central hypothyroidism can present with normal/low TSH; always check free T₄ when suspicion exists. “All subclinical cases need treatment.” Treatment is reserved for TSH > 10 mIU/L, pregnancy, or clear symptomatology. “Free T₄ is the best test in pregnancy.” Pregnancy alters binding proteins; total T₄ (or trimester‑specific reference ranges) is preferred. “Desiccated thyroid is superior to levothyroxine.” Lack of consistent dosing and evidence; guidelines favor levothyroxine. “Liothyronine monotherapy is safer.” Higher side‑effect profile, no proven superiority; generally discouraged. --- 🧠 Mental Models / Intuition Thermostat Analogy: The thyroid axis is a thermostat. Low hormone → “heater” (TSH) turns up; high hormone → heater turns down. TSH‑Free T₄ Grid: Visualize a 2‑by‑2 table (TSH high/low vs Free T₄ high/low) to instantly categorize primary vs central and overt vs subclinical. Weight‑Based Dosing Rule: 1.6 µg/kg/day ≈ full replacement; think “1 µg per kg for a gentle start, add 0.6 µg/kg for full dose.” --- 🚩 Exceptions & Edge Cases Pregnancy – lower TSH targets (≤2.5 mIU/L first trimester, ≤3.0 mIU/L later) and total T₄ monitoring. Elderly / Cardiac disease – start at ½‑¾ of full replacement to avoid angina/AF. Iodine excess – can precipitate or worsen autoimmune hypothyroidism (Jod‑Basedow phenomenon). Medication interactions – calcium, iron, PPIs ↓ levothyroxine absorption; separate dosing by ≥4 h. Weight change – ↑ dose ≈25 % if body weight ↑ > 10 %. --- 📍 When to Use Which Levothyroxine – first‑line for all primary and central hypothyroidism (including overt, most subclinical). Liothyronine (T₃) – only in rare cases of proven deiodinase deficiency or patient‑driven trial after shared decision‑making; not routine. Combination T₄/T₃ – discouraged; consider only in a controlled trial setting with persistent symptoms despite normalized TSH. Desiccated thyroid – avoid; reserve for patients refusing synthetic therapy after thorough counseling. Imaging – order thyroid ultrasound only if goiter, nodules, or neck mass is palpable or if surgery/radiation is contemplated. Anti‑TPO antibody testing – useful when autoimmune etiology is suspected or to risk‑stratify subclinical disease. --- 👀 Patterns to Recognize High TSH + low free T₄ → classic overt primary hypothyroidism. High TSH + normal free T₄ → subclinical; look for risk factors (female, >60 y, antibodies). Low/normal TSH + low free T₄ → central hypothyroidism; consider pituitary/hypothalamic pathology. Myxedema coma clues: hypothermia without shivering, bradycardia, altered mental status, hyponatremia. Lipid panel: unexplained ↑ LDL, total cholesterol often points toward hypothyroidism. --- 🗂️ Exam Traps “TSH normal → euthyroid.” – Missed central disease or early overt hypothyroidism with “inappropriately normal” TSH. “All subclinical hypothyroidism needs levothyroxine.” – Only TSH > 10 mIU/L, pregnancy, or symptomatic cases require therapy. “Free T₄ is the test of choice in pregnant women.” – Total T₄ (or trimester‑adjusted reference) is preferred due to binding‑protein changes. “Desiccated thyroid is recommended by guidelines.” – Major societies favor synthetic levothyroxine; desiccated thyroid is not guideline‑endorsed. “Myxedema coma is treated with oral levothyroxine.” – Requires IV administration (rapid effect) plus supportive measures. ---