Hypothyroidism
Most common endocrine disorder. Hashimoto's thyroiditis is the #1 cause in iodine-sufficient areas. Levothyroxine replacement -simple in concept, nuanced in practice.
🔍 Overview
Overview
Hypothyroidism = insufficient thyroid hormone production. Primary (> 95%): thyroid gland failure -TSH high, FT4 low. Central (< 5%): pituitary or hypothalamic disease -TSH low/normal, FT4 low. Hashimoto's thyroiditis (chronic autoimmune) is the #1 cause in iodine-sufficient countries. Other causes: post-RAI, post-thyroidectomy, post-radiation, medications (amiodarone, lithium, checkpoint inhibitors), iodine deficiency (worldwide), infiltrative (sarcoidosis, hemochromatosis). Prevalence: 5-10% (overt + subclinical). Subclinical hypothyroidism: TSH elevated (4.5-10), FT4 normal. Treatment controversial -treat if: TSH > 10, symptoms, positive TPO antibodies with TSH > 7, or a raised TSH confirmed on repeat when planning pregnancy. In pregnancy itself, the decision turns on timing (see Management). Symptoms: fatigue, cold intolerance, weight gain, constipation, dry skin, hair loss, menorrhagia, depression, myalgias, delayed DTRs.
🧪 Workup
Workup
- TSH -most sensitive test. Elevated in primary hypothyroidism. Normal/low in central hypothyroidism (misleading -always check FT4 if clinical suspicion).
- Biotin interference -high-dose biotin (hair/skin/nail supplements, 5 mg or more) makes TSH falsely low and FT4 falsely high on biotin-streptavidin immunoassays. In a patient on levothyroxine this looks like overreplacement and prompts an unneeded dose cut, so ask about supplements and repeat after holding biotin at least 48 h before changing the dose (see biotin and thyroid tests).
- Free T4 -low confirms hypothyroidism. TSH high + FT4 low = primary overt hypothyroidism. TSH high + FT4 normal = subclinical.
- TPO antibodies (anti-thyroid peroxidase) -positive in Hashimoto's (~95%). Useful for: (1) confirming etiology, (2) predicting progression from subclinical → overt, (3) informs treatment decisions in subclinical hypothyroidism.
- Anti-thyroglobulin antibodies -positive in ~60% of Hashimoto's. Less specific than TPO.
- Lipid panel -hypothyroidism causes hyperlipidemia (elevated LDL). May normalize with treatment. Don't start statins until euthyroid.
- CBC -normocytic or macrocytic anemia is common
- BMP -hyponatremia (impaired free water excretion), elevated Cr (decreased renal perfusion)
- CK -elevated from hypothyroid myopathy (can be markedly elevated, mimicking rhabdomyolysis)
- If central hypothyroidism suspected: check FT4 (not just TSH), pituitary MRI, assess other pituitary axes (ACTH/cortisol, FSH/LH, GH, prolactin). Must rule out adrenal insufficiency before starting T4 (same principle as myxedema coma).
🚨 Management
Management
- Levothyroxine (T4): Standard replacement. Full dose: 1.6 mcg/kg/day. Start lower in elderly or cardiac patients: 12.5-25 mcg daily → increase by 12.5-25 mcg q6-8 weeks.
- How to take: On empty stomach, 30-60 min before breakfast (or at bedtime, ≥ 3h after last meal). Separate from calcium, iron, PPIs, soy, coffee by ≥ 4 hours (all impair absorption).
- Dose adjustments:
- Check TSH at 6-8 weeks (TSH has a long half-life -don't recheck sooner).
- Target TSH 0.5-2.5 mIU/L for most adults. Elderly (> 70): target 3-6 (higher TSH is protective, over-replacement → AF + osteoporosis).
- Pregnancy: keep TSH within the pregnancy range and below 2.5 mU/L, a margin against the rising demand; without a local trimester-specific range, the first-trimester range is about 0.1 to 4.0. Needs climb about 25% by week 12 and 50% by week 20. ATA, 2026
What changed in the ATA 2026 pregnancy guideline (replaces 2017):- CHANGED Timing decides subclinical hypothyroidism. Levothyroxine started after about the first trimester has not improved pregnancy or child outcomes (CATS, 2012, Casey (NIH), 2017), so subclinical disease found later is not started on treatment; found in the first trimester, treat or recheck by shared decision, starting at 25 to 75 mcg/day.
- CHANGED Recheck a mild raised TSH (below 6) before treating, because it normalizes in about half within weeks; overt hypothyroidism with TSH 6 or more is always treated (1.5 to 1.7 mcg/kg/day plus 20 to 30%).
- CHANGED TPO antibodies no longer guide treatment, and euthyroid TPO positivity is not treated even with infertility or prior miscarriage (TABLET, 2019).
- CHANGED The dose increase on a positive test is tailored: a blanket two-extra-tablets rule overtreats women whose pre-pregnancy TSH was below 1.5 or dose above 100 mcg/day.
- UNCHANGED TSH below 2.5 as the treatment target; switch liothyronine or desiccated thyroid to levothyroxine before conception, because the fetal brain depends on maternal T4.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Levothyroxine (T4) | 1.6 mcg/kg/day (full dose); start 25-50 mcg in elderly | PO | Standard of care. Empty stomach, 30-60 min before breakfast. Separate from Ca, Fe, PPI by 4h. Half-life 7 days → steady state in 6 wk. ATA, 2014 |
| Liothyronine (T3) | 5-25 mcg daily (divided BID-TID) | PO | NOT routine. Short half-life → TID dosing. Consider only if persistent symptoms on adequate T4 with normal TSH. Variable absorption. |
| IV levothyroxine | 50-100% of oral dose | IV | For patients who cannot take PO (ICU, post-surgical). 100% bioavailable vs ~70% PO. For myxedema coma: loading dose 200-400 mcg. |
🏥 Rounds
Pimp Questions
❓ Why must you wait 6-8 weeks to recheck TSH after a levothyroxine dose change?
Levothyroxine has a half-life of 7 days. It takes approximately 5 half-lives (35 days) to reach steady state. Checking TSH sooner gives a misleading result because the new dose hasn't equilibrated yet. If you increase dose and recheck at 2 weeks, the TSH may still appear elevated → you increase again → overcorrection → iatrogenic hyperthyroidism.
❓ What medications interfere with levothyroxine absorption?
Must separate by ≥ 4 hours: (1) Calcium (supplements and antacids), (2) Iron, (3) PPIs/H2 blockers (need gastric acid for T4 absorption), (4) Soy products, (5) Cholestyramine (binds T4 in gut), (6) Sucralfate, (7) Coffee (reduces absorption by ~30%). Practical advice: take levothyroxine first thing in morning with water only, eat/take other meds ≥ 30-60 min later.
❓ When do you treat subclinical hypothyroidism?
Always treat: TSH > 10, goiter, and a raised TSH confirmed on a repeat 4 to 6 weeks later when planning pregnancy. Pregnancy is no longer a blanket indication (ATA 2026): found in the first trimester, treat or recheck by shared decision; found later, levothyroxine has not improved outcomes (CATS, NIH trial), so recheck rather than start, treating if it progresses to overt hypothyroidism. Strongly consider treating: TSH 7-10 with positive TPO antibodies (high progression rate to overt hypothyroidism, ~5% per year), symptoms suggestive of hypothyroidism, hyperlipidemia that may improve with treatment. Observe: TSH 4.5-7 without symptoms or risk factors. Elderly > 70: higher TSH may be physiologically normal -treating can cause harm (AF, fractures).
❓ Why should levothyroxine dose be increased in pregnancy?
Pregnancy increases T4 demand by 25-50% due to: (1) increased TBG (estrogen-mediated → more T4 bound, less free), (2) increased plasma volume (dilution), (3) placental deiodinase (degrades T4), (4) fetal thyroid doesn't function until week 12 -fetus depends entirely on maternal T4 for neurodevelopment. Maternal hypothyroidism → lower fetal IQ, neurodevelopmental delay. Increase the dose as soon as pregnancy is confirmed, by raising the daily dose or adding 2 tablets a week, but tailor it: ATA 2026 notes the fixed rule overtreats women whose pre-pregnancy TSH was below 1.5 or dose above 100 mcg/day. ATA, 2026
❓ What is the #1 cause of persistently elevated TSH in a patient on levothyroxine?
Non-compliance. Before increasing the dose, always ask: (1) Are you taking it daily? (2) On empty stomach, 30-60 min before eating? (3) Are you taking calcium, iron, or PPIs near the dose? (4) Any new medications? A common pattern: patient takes T4 intermittently, TSH remains elevated → dose is increased → patient takes it consistently for a few days before the lab → TSH normalizes temporarily → cycle repeats.
Clinical Examples
📋 Case 1, New Diagnosis of Hashimoto's Hypothyroidism
Patient: 38F with fatigue, weight gain (12 lb/6 months), constipation, cold intolerance, and menorrhagia. TSH 62 mIU/L, FT4 0.3 ng/dL. TPO Ab 580 IU/mL. No goiter.
Key findings: Overt primary hypothyroidism (elevated TSH + low FT4). Hashimoto thyroiditis confirmed by strongly positive TPO antibodies. Symptomatic.
Management:
- Levothyroxine 1.6 mcg/kg/day (full replacement dose in young, healthy patient), ~88 mcg daily
- Take on empty stomach, 30-60 min before breakfast. Avoid calcium, iron, PPI within 4 hours
- Recheck TSH in 6-8 weeks (steady state requires 5-6 half-lives; T4 t½ = 7 days)
- Goal TSH 0.5-2.5 mIU/L (lower half of normal range for symptomatic patients)
- Screen for associated autoimmune conditions: celiac (10% co-occurrence), B12 deficiency, adrenal insufficiency
Teaching point: In young, healthy patients, start full replacement dose immediately. In elderly or cardiac patients, start low (25-50 mcg) and titrate slowly, rapid correction can precipitate angina or arrhythmia.
📋 Case 2, Hypothyroidism in Pregnancy
Patient: 32F with known Hashimoto's on levothyroxine 75 mcg daily. Newly pregnant (6 weeks). Pre-pregnancy TSH 1.8. Current TSH 4.2, FT4 0.8 ng/dL.
Key findings: TSH above the pregnancy treatment target (below 2.5) and the first-trimester range (about 4.0), with a low-normal free T4 (ATA 2026). The fetal thyroid does not function until about week 12, so the fetus depends on maternal T4 for neurodevelopment.
Management:
- Increase levothyroxine now by about 25 to 30%: 2 extra tablets a week (75 mcg × 9 per week instead of 7). That suits her, since her pre-pregnancy TSH was 1.8 and her dose 75 mcg, outside the groups ATA 2026 flags for overtreatment (TSH below 1.5, dose above 100 mcg/day) ATA, 2026
- Target TSH within the pregnancy range and below 2.5 mU/L
- Recheck TSH and free T4 every 4 weeks through mid-pregnancy, because requirements climb fastest then (about 25% by week 12, 50% by week 20)
- Maternal hypothyroidism → lower fetal IQ and neurodevelopmental delay
- Postpartum: return to the pre-pregnancy dose and recheck TSH at 6 weeks; women who were not on a full dose before pregnancy, or gained a lot of weight, may need more
Teaching point: Pregnancy raises T4 demand through higher TBG, plasma volume expansion and placental deiodinase. Two extra tablets a week is a practical way to add about 30% at once, but ATA 2026 asks you to tailor it to the pre-pregnancy TSH and dose rather than apply it to everyone.
📋 Case 3, Myxedema Coma
Patient: 72F brought by EMS. Found unresponsive at home. Temp 33.2°C, HR 42, BP 82/50, RR 8. Known hypothyroidism, ran out of levothyroxine 3 months ago. Na 118, glucose 48.
Key findings: Myxedema coma: hypothermia + bradycardia + AMS + hypotension in the setting of severe hypothyroidism. Precipitated by medication non-compliance. Mortality 30-60%.
Management:
- IV levothyroxine 200-400 mcg loading dose → 1.6 mcg/kg/day IV (gut absorption unreliable in critical illness)
- Stress-dose hydrocortisone 100 mg IV q8h (must rule out concurrent adrenal insufficiency before giving T4, T4 increases cortisol clearance)
- Passive rewarming only (active warming → vasodilation → cardiovascular collapse)
- D50 for hypoglycemia, hypertonic saline only if Na < 120 with seizures
- ICU admission, intubate if GCS ≤ 8, avoid sedatives (prolonged metabolism)
Teaching point: Always give stress-dose steroids BEFORE or WITH IV levothyroxine in myxedema coma. If undiagnosed adrenal insufficiency coexists (Schmidt syndrome), T4 alone can precipitate adrenal crisis.
Sample Presentation
Mrs. Johnson is a 45-year-old woman with 6 months of fatigue, 10 lb weight gain, constipation, cold intolerance, and hair thinning. PMH: nothing. No medications. Exam: dry skin, periorbital puffiness, bradycardia (HR 56), delayed DTR relaxation. No goiter. Labs: TSH 48 mIU/L (elevated), Free T4 0.4 ng/dL (low), TPO Ab 420 IU/mL (strongly positive).
Key Points: Classic overt primary hypothyroidism from Hashimoto's thyroiditis (positive TPO antibodies). Start levothyroxine ~100 mcg daily (estimated 1.6 × 65 kg). Fasting, 30-60 min before breakfast. Recheck TSH in 6-8 weeks. Target TSH 0.5-2.5. Also check lipids (likely elevated -will improve with treatment).
- TSH at 6-8 weeks after any dose change -do NOT recheck sooner (TSH equilibration takes 4-6 weeks). Adjust by 12.5-25 mcg increments.
- Annual TSH once stable on appropriate dose
- Pregnancy: TSH every 4 weeks through mid-pregnancy; raise the dose on the positive test, since needs climb about 25% by week 12 and 50% by week 20, and return to the pre-pregnancy dose at delivery. ATA, 2026
- Central hypothyroidism: Monitor Free T4 (NOT TSH -TSH is unreliable when the pituitary is the problem). Target FT4 in upper half of reference range.
- Elderly (> 70): Target TSH 3-6. Do NOT over-replace -subclinical hyperthyroidism from excess T4 → AF, osteoporosis, fractures.
- Drug interactions: Reassess dose when starting/stopping calcium, iron, PPIs, estrogen (increases TBG → need more T4), phenytoin/carbamazepine (increase T4 metabolism).
- Lipid panel -recheck 3-6 months after achieving euthyroidism (hyperlipidemia often normalizes).
📋 Summary
Summary
Diagnose on TSH First
A raised TSH with a low free T4 is primary hypothyroidism. Hashimoto thyroiditis is the commonest cause in iodine-sufficient regions, confirmed by TPO antibodies. A low or inappropriately normal TSH with a low free T4 means central hypothyroidism, which needs pituitary imaging and assessment of the other axes.
Check Cortisol Before Thyroid Hormone in Suspected Central Disease
Treating hypothyroidism in an unrecognized adrenal insufficiency precipitates adrenal crisis, because thyroid hormone increases cortisol clearance and metabolic demand. In panhypopituitarism, give the glucocorticoid first.
Dose and Give It Properly
Levothyroxine 1.6 mcg/kg/day as a full replacement dose. Start at 25 to 50 mcg in the elderly and in coronary disease, since a full dose can precipitate angina or arrhythmia. Take it on an empty stomach, 30 to 60 min before breakfast, and separate it by 4 hours from calcium, iron, proton pump inhibitors and bile acid sequestrants, which block absorption. Poor absorption from mistimed dosing is the commonest reason a TSH will not come down.
Recheck at 6 Weeks, Not Sooner
Levothyroxine has a 7-day half-life, so a steady state takes about 6 weeks. Checking earlier gives a number that has not equilibrated and leads to unnecessary dose changes. Titrate by 12.5 to 25 mcg and recheck after another 6 weeks.
T3 Is Not Routine
Combination T4 and T3 has not shown consistent benefit in trials, and liothyronine has a short half-life needing TID dosing with supraphysiologic peaks. Consider it only for persistent symptoms with a normalized TSH, after excluding the other causes of fatigue, and never as first-line therapy. Desiccated thyroid extract has an unphysiologic T4:T3 ratio and is not recommended.
Treat Subclinical Disease Selectively
Raised TSH with a normal free T4. Treat when TSH is above 10, when TPO antibodies are positive with symptoms, when trying to conceive (once a repeat TSH confirms it), and in goiter. Pregnancy is no longer a blanket indication (ATA 2026): found in the first trimester, treat or recheck by shared decision; found later, levothyroxine has not improved outcomes, so it is not started. Observe when TSH is 4.5 to 10 in an asymptomatic older adult, where a mildly raised TSH may be an age-appropriate finding and treating it adds no benefit.
Pregnancy Changes Everything
Requirements rise by roughly 30% and the increase is needed early, so instruct a known hypothyroid patient to increase the dose as soon as pregnancy is confirmed (commonly by two extra tablets a week, less if the pre-pregnancy TSH was below 1.5) and check TSH immediately. The target is a TSH below 2.5, inside a pregnancy range that is lower than usual, and untreated maternal hypothyroidism impairs fetal neurodevelopment, which is why this is one of the few settings where treatment is urgent.
Know Why the TSH Will Not Normalize
Non-adherence is the commonest reason, followed by mistimed dosing with food or interacting drugs, malabsorption (celiac disease, atrophic gastritis, bariatric surgery), and drug interference from amiodarone, lithium, checkpoint inhibitors, estrogen and rifampin. A suppressed TSH means over-replacement, which is not benign: it causes atrial fibrillation and bone loss, especially in the elderly. Do not chase the TSH in acute illness: euthyroid sick syndrome produces abnormal results that resolve on recovery, so retest after the illness rather than treating the number.
📄 One Pager
Text version
One-Pager
Hypothyroidism
Simple drug, nuanced dosing
Levothyroxine Rules
1.6 mcg/kg/day. Empty stomach, 30-60 min before food. Separate Ca/Fe/PPI by 4h. Start low in elderly/cardiac (25 mcg). Recheck TSH at 6-8 weeks. Target 0.5-2.5.
Subclinical Decision
TSH > 10 → treat. TSH 7-10 + TPO+ → treat. Pregnant: TSH ≥ 6 → treat; milder → recheck, or treat if first trimester (target < 2.5). Elderly → often observe (higher TSH may be normal).
Trials
ATA Hypothyroidism Guidelines 2014 · ATA Thyroid in Pregnancy 2026 · CATS 2012 · Casey (NIH) 2017