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Thyroid Disorders

EndocrineGraves' diseaseHypothyroidismThionamides

30-Second Snapshot

What it is:The thyroid sets the body's metabolic thermostat by secreting T4 and T3. Too much hormone is thyrotoxicosis (usually Graves' disease). Too little is hypothyroidism (usually Hashimoto's). Same gland, same axis, opposite direction, and almost every drug you'll use just pushes the thermostat one way or the other.

The core problem:Thyroid hormone touches nearly every organ system, so both extremes present as vague, multisystem complaints (fatigue, weight change, temperature intolerance, bowel habit change) that are easy to blame on something else. TSH is what actually tells you which direction the patient is drifting, almost always before the patient can tell you themselves.

What you do about it:Hyperthyroidism: shut off hormone production or destroy the gland (thionamide, radioactive iodine, or surgery), and use a beta blocker for symptom control while you wait. Hypothyroidism: replace with levothyroxine and titrate to a normal TSH. That's almost the whole chapter.

Worth knowing

Think of TSH as a thermostat reading in reverse. A high TSH means the pituitary is shouting at a cold house (hypothyroid, needs more hormone). A suppressed TSH means the pituitary has gone silent because the house is already too hot (hyperthyroid, too much hormone). You almost never need to memorize which way T4 goes if you can reason it out from what TSH is doing.

Thyroid Physiology - The Axis You'll Keep Coming Back To

Every drug and every lab value in this chapter maps onto one pathway. Learn it once and the rest is just "which step did this drug or disease hit."

The HPT axis

Hypothalamus releases TRH, which drives the anterior pituitary to release TSH, which drives the thyroid follicular cell to make and release T4and T3. Circulating T3 and T4 then feed back and suppress both TRH and TSH. It's a closed loop, so a problem anywhere in the loop shows up as an abnormal TSH somewhere else in the loop.

Building the hormone

The number that explains levothyroxine dosing

The thyroid secretes T4 almost exclusively. Less than 20% of circulating T3 comes directly from the gland; the rest is made peripherally when 5'-deiodinase strips one iodine off T4. That's why you can replace a failed thyroid with T4 alone (levothyroxine) and the body converts what it needs on its own, on physiologic demand. It's also why the physiologic T4:T3 ratio the body targets is roughly 14-16:1, a number that matters later when you see why 4:1 combination products (liotrix, desiccated thyroid) are considered non-physiologic.

T3 is the biologically active hormone at the receptor and is substantially more potent than T4 (DiPiro cites roughly 5x). T4 can also be deiodinated at a different position to form reverse T3, which is biologically inert, essentially a decompression valve. Both T3 and T4 travel bound to thyroid-binding globulin (TBG), transthyretin, and albumin; only the tiny unbound (free) fraction is active and regulates TSH.

Hyperthyroidism / Thyrotoxicosis - Causes

Thyrotoxicosisis the umbrella term for any tissue exposure to excess thyroid hormone. Hyperthyroidismis the specific subset where the gland itself is overproducing. The distinction matters because it changes both the workup (RAIU) and the treatment (you can't shut down a gland that isn't actually the problem).

CauseMechanismKey clue
Graves' disease(most common, 60-80% of thyrotoxicosis)Autoimmune. Thyroid-stimulating antibodies (TSAb/TRAb) bind the TSH receptor and activate adenylate cyclase just like TSH does, but with no negative feedback shutoffDiffuse goiter, exophthalmos, pretibial myxedema, thyroid acropachy, possible bruit over the gland
Toxic adenomaBenign nodule making hormone autonomously, independent of TSH. Usually needs to be >3 cm before it makes enough hormone to matterSingle hot nodule on scan
Toxic multinodular goiterSome follicles go rogue and function autonomously while others stay normal or quietPatchy uptake on thyroid scan
Subacute (de Quervain) thyroiditisUsually post-viral gland inflammation that leaks preformed hormone; the gland isn't overproducing, it's leakingPainful, tender, firm gland plus fever/malaise/myalgia
Painless (silent/postpartum) thyroiditisSame leak mechanism as subacute, presumed autoimmune, but no painDiffusely enlarged, non-tender gland; antiTG/antiTPO antibodies up in >50%
Thyrotoxicosis factitiaExogenous thyroid hormone ingestion (misuse, overdose, or surreptitious)Low RAIU andlow serum thyroglobulin (nothing is being made or destroyed)
TSH-secreting pituitary tumor(rare)Autonomous TSH release, unresponsive to feedbackElevated or "inappropriately normal" TSH in a thyrotoxic patient
Amiodarone-induced37% iodine by weight can either flood synthesis (type 1) or cause destructive thyroiditis (type 2) in a susceptible glandCauses thyrotoxicosis in 2-3% and hypothyroidism (overt 5%, subclinical 25%) of patients on it
Why RAIU is the tiebreaker

Normal 24-hour radioactive iodine uptake (RAIU) is 10-30%. High RAIUmeans the gland is genuinely overproducing (Graves, toxic adenoma, toxic MNG). Low (<2%) RAIUmeans the excess hormone is coming from somewhere other than active synthesis, either the gland is leaking stored hormone (thyroiditis) or the hormone isn't from the gland at all (factitia, struma ovarii). This single test tells you whether an antithyroid drug will do anything at all.

Hyperthyroidism - Clinical Presentation

Almost everything about the presentation is "the body running too hot." Once you see it that way the list stops being a memorization exercise.

SystemFindings
Neuro/psychNervousness, irritability, anxiety, emotional lability, fine tremor of outstretched hands and protruded tongue, hyperactive deep tendon reflexes
CardiacPalpitations, resting tachycardia, widened pulse pressure, systolic ejection murmur, atrial fibrillation
MetabolicHeat intolerance, sweating, weight loss despiteincreased appetite
GIIncreased bowel frequency, diarrhea
MusculoskeletalProximal muscle weakness (noticed on stairs or standing from a chair)
Skin/nailsWarm, smooth, moist skin; fine hair; onycholysis (nail separating from the bed)
ReproductiveScanty or irregular menses, occasional gynecomastia in men
EyesLid retraction and lid lag on all causes; exophthalmos and pretibial myxedema are Graves'-specificand don't occur with other causes
The pairing that's a classic distractor

Lid laghappens in any thyrotoxicosis, it's just excess sympathetic tone on the eyelid. Exophthalmos (proptosis)is specific to Graves' because it's driven by the same autoimmune process infiltrating the retro-orbital tissue, not by hormone level. A hyperthyroid patient with bulging eyes is Graves' until proven otherwise; lid lag alone tells you nothing about the cause.

Thyroid storm is a different presentation entirely

Decompensated thyrotoxicosis: high fever (often >39.4°C/103°F), marked tachycardia, tachypnea, dehydration, and CNS changes ranging from agitation to coma, plus nausea/vomiting/diarrhea. This is not "bad hyperthyroidism," it's a distinct emergency. See the dedicated section below.

Diagnosis - Labs for Both Directions

One panel, read in both directions. Learn the normal ranges once.

Total T4Free T4Total T3TSH
Normal4.5-10.9 mcg/dL0.8-2.7 ng/dL60-181 ng/dL0.5-4.7 mIU/L
Hyperthyroid↑↑↑↑↑↑↑ (disproportionate)↓↓
Hypothyroid↓↓↓↓↓ (often preserved longer)↑↑
↑ TBG(pregnancy, estrogen)NormalNormal
Why TSH moves first and moves most

The pituitary is exquisitely sensitive to tiny changes in free T4, so TSH is the first lab to become abnormalin both directions and the single most sensitive screening test. In early primary hypothyroidism, TSH rises while free T4 is still technically "normal" (compensated/subclinical hypothyroidism). T3 tends to hang on longer than T4 as hypothyroidism progresses, which is why an isolated low T3 is a poor early marker.

Confirming the cause once thyrotoxicosis is established

Confirming hypothyroidism and its cause

A counseling detail worth knowing before you order labs

High-dose vitamin B6 supplementation can interfere with the T4 binding assay and produce a false hypothyroid-looking result. Have patients hold B6 supplements for about a week before thyroid labs if you're troubleshooting an unexpected result.

Hyperthyroidism - Treatment Overview

Goals:eliminate the excess hormone, control symptoms, prevent long-term consequences (bone loss, cardiac strain), and individualize by cause, age, and prior response. There are three definitive options (thionamides, radioactive iodine, surgery) plus symptomatic beta blockade layered on top of whichever one you pick.

OptionBest forTradeoff
Thionamides(methimazole, PTU)First-line for most patients; only option in pregnancy/children; used pre-op or pre-RAI to get euthyroid firstLow cure rate alone (~40-50% durable remission), adverse drug reactions, adherence-dependent
Radioactive iodine (RAI, I-131)Graves', toxic adenoma, toxic multinodular goiter; cheapest option long-termPermanent hypothyroidism is nearly inevitable eventually; can worsen Graves' ophthalmopathy; absolutely contraindicated in pregnancy
Surgery (thyroidectomy)Very large glands (>80 g), severe ophthalmopathy, suspicious coexisting nodule, patients who refuse RAI, pregnancy 2nd trimester if drug-intolerantMost invasive; recurrent laryngeal nerve injury and hypoparathyroidism are real risks; permanent hypothyroidism common
Thyroiditis is managed differently from everything else

Subacute and painless thyroiditis are notoverproduction states, so thionamides do nothing (there's no synthesis to block). Treatment is symptomatic: beta blockers for adrenergic symptoms and NSAIDs (or steroids for severe pain in subacute thyroiditis). It's self-limited and typically resolves over the triphasic course (thyrotoxic → hypothyroid → recovery).

Pre-surgical prep, the sequence matters

If thyroidectomy is planned: give methimazole until the patient is biochemically euthyroid (usually 6-8 weeks), thenadd iodides (500 mg/day) for 10-14 days before surgery to shrink the gland and reduce its vascularity, so the surgeon isn't operating on a bleeding, hyperemic organ. Propranolol is often layered on for several weeks preop and 7-10 days postop to keep resting HR under 90 bpm.

Dosing Table

DrugStarting doseNotes
Thionamides - Hyperthyroidism
Methimazole, mild-moderate5-20 mg/day dividedMaintenance 5-30 mg/day; ~10x more potent than PTU
Methimazole, severe20-40 mg/day divided
PTU, mild-moderate150-300 mg/day dividedMaintenance 50-300 mg/day
PTU, severe300-900 mg/day dividedDiPiro range: 300-600 mg/day initial
Iodides
SSKI3-10 drops/day (120-400 mg)38 mg iodide/drop; give 3-7 days afterRAI, never before
Lugol solutionProduct-specific, ~100 mg elemental iodine/day typical6.3 mg iodide/drop
Beta blocker (symptom control)
Propranolol20-40 mg PO QIDUp to 240-480 mg/day in younger or more severely toxic patients; goal HR <90
Levothyroxine - Hypothyroidism
Nonpregnant adult, otherwise healthy~1.6 mcg/kg/dayFull weight-based replacement dose
Older adult or known/suspected cardiac disease25 mcg/day (12.5-25 mcg in frail/cardiac elderly)Titrate by 25 mcg increments every 3-4 weeks
Subclinical, TSH <1050 mcg/dayTitrate by 25 mcg every 6 weeks to TSH goal 0.35-5.5 mIU/L
Subclinical, TSH ≥10Full weight-based (~1.6 mcg/kg/day)Treat like overt hypothyroidism
Average adult maintenance~75-125 mcg/day, individualized to TSH
Other thyroid replacement
Liothyronine (T3)~37.5 mcg/day average; dosed BID-TID (t½ ~1.5 days)
Liotrix (T4:T3, 4:1)Thyrolar-1 = 50 mcg T4 / 12.5 mcg T3
Desiccated thyroid (Armour, etc)1 grain (~60-65 mg) ≈ 38 mcg T4 + 9 mcg T3; when switching to levothyroxine, cut the dose by half a grain-equivalent

Class-by-Class Detail

Thionamides (methimazole & PTU) - mechanism, timeline, and the adverse effects that actually change management

Both drugs block TPO, so they stop organification of iodide onto tyrosine and stop the coupling step that builds T3 and T4. PTU has one extra trick: at large doses it also blocks peripheral 5'-deiodinase, so it partially blocks T4-to-T3 conversion outside the thyroid too. That extra mechanism is exactly why PTU (not methimazole) is preferred in thyroid storm, where you want every possible brake on circulating T3.

Timeline:because these drugs block newsynthesis, not the hormone already stored in the gland, expect 4-8 weeks before symptoms and labs meaningfully improve. Make dose changes monthly, not weekly, since it takes about that long for endogenous T4 to reach a new steady state. Continue therapy 12-24 months for the best shot at durable remission; if relapse occurs, guidelines favor moving to RAI over trying a second drug course, though long-term low-dose methimazole is also reasonable in select patients.

The adverse effects that change your next move
  • Agranulocytosis(granulocyte count <250/mm³): rare but life-threatening, usually hits in the first 3 months, and comes on suddenly, which is exactly why routine WBC monitoring doesn't catch it in time. What you actually do is tell the patient to call immediately for fever, sore throat, or mouth sores, then check a WBC/ANC on symptoms, not on a schedule.
  • Hepatotoxicity, higher risk with PTU: discontinue if LFTs run 3x above normal. This is exactly why PTU carries a boxed warning and lost first-line status for both adults and children.
  • Minor reactions(pruritic rash, arthralgia, fever, transient leukopenia <4000/mm³) don't require stopping therapy outright; you can often switch to the other thionamide, though cross-sensitivity between the two occurs in about 50% of patients, so it isn't a guaranteed fix.
The 3 exceptions where PTU beats methimazole

Despite PTU's worse hepatotoxicity profile, guidelines carve out three situations where PTU is still preferred: (1) first trimester of pregnancy(methimazole-associated embryopathy risk in that window is judged worse than PTU's hepatotoxicity risk), (2) methimazole intolerance, and (3) thyroid storm(for the extra T4→T3 blockade). Outside those three, methimazole is first-line.

Iodides - the fast-acting bridge drug with one big trap

Iodide at pharmacologic doses acutely blocks hormone release, interferes with intrathyroidal iodide utilization, and shrinks gland size and vascularity. It works fast, symptom improvement in 2-7 days, faster than a thionamide alone, which is why it's used as a bridge: preoperatively (7-14 days before surgery), in severely thyrotoxic patients with cardiac decompensation who need rapid control, or after RAI to blunt hormone release from dying follicles.

Sequencing is everything with iodide

Give iodide aftera thionamide is already on board, never before or without one. Iodide alone can actually feedsynthesis in a gland with autonomous tissue (the Jod-Basedow phenomenon), which is exactly why iodide is contraindicated in toxic multinodular goiter. Around RAI, the order flips the other way: iodide must come 3-7 days afterRAI, never before, or it competes with the radioactive iodine for uptake and blunts the treatment.

Adverse effects:hypersensitivity reactions (rash, drug fever, rhinitis/conjunctivitis), salivary gland swelling, gynecomastia, and "iodism," metallic taste, burning mouth and throat, sore teeth/gums, cold-like symptoms, sometimes GI upset.

Beta blockers - what they do and don't do

Beta blockers control the adrenergic symptoms, palpitations, tremor, anxiety, heat intolerance, but do nothingto actual hormone production, don't reduce TSAb, and don't prevent thyroid storm. Propranolol and nadolol partially block peripheral T4-to-T3 conversion, but that contribution is small and not the reason you're using them.

They're adjunctivetherapy layered on top of a thionamide, RAI, iodides, or surgical prep, in every cause of thyrotoxicosis except one: thyroiditis, where beta blockade isthe primary therapy since there's no overproduction to block.

Contraindications:decompensated heart failure (unless the HF is purely rate-driven), sinus bradycardia, concurrent MAOI or TCA use, spontaneous hypoglycemia. When beta blockade can't be used, centrally-acting sympatholytics (clonidine) or non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are reasonable substitutes for symptom control.

Radioactive iodine (I-131) - the details that trip people up

Oral I-131 concentrates in the thyroid the same way stable iodine does, then disrupts hormone synthesis and, over subsequent weeks, causes necrosis and fibrosis of the follicles that took it up. A single dose (4000-8000 rad) achieves a euthyroid state in about 60% of patients by 6 months; if the patient is still hyperthyroid at that point, a second dose is given.

Why cardiac and elderly patients get pretreated first

RAI initially increaseshormone levels transiently, since dying follicles dump their stored hormone before they die off completely. In a patient with underlying cardiac disease, that transient surge can be dangerous, so those patients often get a thionamide first to get euthyroid before RAI. The flip side: don't restart antithyroid drugs immediatelyafter RAI, doing so is associated with higher rates of persistent or recurrent hyperthyroidism, presumably because it blunts the ablative effect.

Absolute contraindication: pregnancy.Radiation crosses to fetal thyroid tissue. Pregnancy should be deferred 6-12 months after treatment, and breastfeeding is out entirely.

Other notes:beta blockers can be given any time around RAI without interfering with it. Lithium as an adjunct can increase cure rate, shorten time to cure, and blunt the post-treatment hormone surge. RAI can worsen Graves' ophthalmopathy, so a short prednisone course (4-6 months) is sometimes used to attenuate that risk. Hypothyroidism months to years after RAI is the expected long-term outcome, essentially the price of ablating the gland, not a treatment failure.

Hypothyroidism - Causes, Presentation, Diagnosis

Causes

CategoryCause
Primary (thyroid itself fails), the vast majority of casesChronic autoimmune (Hashimoto) thyroiditisaccounts for roughly 80%. Also: iatrogenic (post-RAI, post-thyroidectomy, excess thionamide dosing), iodine deficiency, enzyme defects, thyroid hypoplasia, goitrogen ingestion, and drugs (lithium, amiodarone, iodine excess, antithyroid drugs)
Secondary (pituitary fails), uncommonPituitary tumor destroying thyrotrophs, pituitary surgery or radiation, postpartum pituitary necrosis (Sheehan syndrome), trauma, infiltrative disease (metastatic tumor, TB, sarcoidosis)

Hashimoto's mechanism:a defect in suppressor T-lymphocyte function lets a mutant clone of helper T cells survive and attack thyroid membrane antigens, which then drives B cells to make thyroid antibodies (anti-TPO). This is the autoimmune mirror image of Graves', one attacks the receptor and turns it on, the other destroys the gland and turns it off.

Clinical presentation

The opposite of hyperthyroidism, almost point for point: everything runs cold and slow instead of hot and fast.

SystemFindings
Neuro/psychLethargy, depression, fatigue, loss of ambition/energy, difficulty concentrating and poor memory, delayed relaxation phase of deep tendon reflexes
CardiacBradycardia
MetabolicCold intolerance, weight gain despite poor appetite
GIConstipation
MusculoskeletalWeakness (proximal > distal), muscle cramps, myalgia, stiffness
Skin/hairDry, coarse skin and hair, periorbital puffiness, hoarse or slowed speech
ReproductiveMenorrhagia, later oligo/amenorrhea, infertility
Neuro syndromesReversible carpal tunnel syndrome, polyneuropathy, cerebellar dysfunction
The "magic number" for treatment decisions

TSH >10 mIU/L with a lowfree T4 = overt hypothyroidism, treat. TSH >10 mIU/L with a normalfree T4 = subclinical, still treat. TSH 5-10 mIU/L with normal free T4 = subclinical, generally just watch unless the patient has symptoms, a goiter, or is young/middle-aged with a compelling reason to treat. Most patients with subclinical disease and no symptoms can simply be monitored.

Don't anchor on TSH if the story doesn't fit

A patient with a "normal" TSH can still have real symptoms from something else entirely: adrenal insufficiency, liver disease, anemia, B12 or iron deficiency, chronic kidney disease, vitamin D deficiency, mononucleosis or other viral illness, or a mood/anxiety disorder. Don't chase the TSH indefinitely if the clinical picture doesn't line up with thyroid disease.

Hypothyroidism - Treatment

Goals:restore normal tissue hormone levels, relieve symptoms, prevent neurologic deficits in newborns and children, and normalize TSH.

Levothyroxine is the drug of choice, full stop

It's chemically stable, cheap, effective orally, non-antigenic, and has uniform potency. Because the body converts T4 to T3 on physiologic demand via 5'-deiodinase, giving pure T4 lets the body regulate its own T3 supply rather than you trying to guess it. Half-life is about 7 days, which is why it's dosed once daily and why you wait 4-6 weeks before rechecking labs after any dose change.

Dosing strategy - start slow in anyone with a heart

Healthy, younger patients can generally start at a full weight-based replacement dose (~1.6 mcg/kg/day). Older patients or anyone with known or suspected cardiac diseaseshould start much lower, 25 mcg/day (some sources allow up to 50 mcg), and titrate by 25 mcg increments every 3-4 weeks. The reason isn't subtle: ramping metabolism up too fast increases myocardial oxygen demand and can precipitate angina, arrhythmia, or MI in a heart that hasn't seen that much demand in a while.

Absorption is fragile - this is where real-world failures happen

Take levothyroxine on an empty stomach, ideally 30-60 minutes before breakfast with water only (a consistent bedtime dosing routine, at least 2 hours after the last meal, is also acceptable if mornings don't work for the patient). Separate by 2 hours from calcium and ironsupplements. Drugs and foods that impair absorption include cholestyramine, calcium carbonate, sucralfate, aluminum hydroxide, ferrous sulfate, soy formula, fiber supplements, espresso, and acid suppression (H2RAs, PPIs). Rifampin, carbamazepine, and phenytoin increase non-deiodinative clearance of T4. Selenium deficiency and amiodarone can impair T4-to-T3 conversion. If a patient's TSH suddenly drifts after being stable for years, ask about a new PPI, calcium supplement, or coffee habit before you assume the dose is wrong.

Special populations

Alternatives to levothyroxine, and why they're rarely the answer

What it isWhy it's not first-line
Liothyronine (Cytomel)Synthetic T3Short half-life (~1.5 days) means peaks and troughs, requires multiple daily doses, more cardiac adverse effects, harder to monitor with standard labs, and more expensive
Liotrix (Thyrolar)Synthetic T4:T3 in a fixed 4:1 ratioStable and predictable, but 4:1 is far more T3-heavy than the body's own physiologic ~14-16:1 ratio, so it risks iatrogenic T3 toxicosis, and there's no real pharmacologic rationale since the body already converts T4 to T3 as needed
Desiccated thyroid(Armour, Nature-Throid, WP Thyroid)Porcine-derived T4:T3, ratio ~4.2:1Same non-physiologic T3 ratio problem as liotrix, plus potential antigenicity and tablet-to-tablet potency variation between manufacturers. ATA/AACE recommend against routine use
The combination-therapy debate, as it was actually taught

Combined T4/T3 therapy is popular online and controversial in practice. More than 85% of patients do perfectly well on T4 alone. Most of the trials that failed to show benefit from combination therapy used a supraphysiologic 4:1 ratio instead of the body's actual ~14-16:1 ratio, so the negative trials may have simply been testing the wrong ratio. If combination therapy is tried, it's generally reserved for patients with persistent symptoms and elevated TSH despite maximized levothyroxine, especially those with a history of thyroidectomy or RAI, and T3 needs to be dosed twice daily given its short half-life. Well-designed, blinded outcome trials at a truly physiologic ratio are still lacking.

Thyroid Storm

A rare, life-threatening exaggeration of thyrotoxicosis, not just "worse hyperthyroidism" but a distinct decompensated state. Mortality runs roughly 10-30%. It develops in patients with longstanding, often undertreated hyperthyroidism and is typically triggered by an acute stressor: thyroid or nonthyroidal surgery, trauma, infection, an acute iodine load, or abrupt withdrawal from antithyroid drugs.

Presentation:high fever (often >39.4°C/103°F), marked tachycardia, tachypnea, dehydration, and CNS dysfunction ranging from agitation and delirium to psychosis, stupor, or coma, plus nausea, vomiting, and abdominal pain.

Four simultaneous therapeutic targets

TargetDrugRegimenWhy this one
1. Stop synthesisPTU (preferred) or methimazolePTU 500-1000 mg loading, then 250 mg q4h (or 900-1200 mg/day divided); methimazole 60-120 mg/day dividedPTU also blocks peripheral T4→T3 conversion; methimazole's longer duration of action is a theoretical advantage but doesn't offset PTU's extra mechanism here
2. Stop releaseIodide (SSKI or Lugol's, or IV sodium iodide)Sodium iodide up to 2 g/day IV; Lugol's 5-10 drops TID; SSKI 1-2 drops TIDMust be given afterthe thionamide is on board (at least ~1 hour after), otherwise you hand the gland raw material to make even more hormone
3. Antiadrenergic controlEsmolol (preferred) or propranololPropranolol 40-80 mg q6h if usedEsmolol's ultra-short half-life makes it safer in patients with pulmonary disease or at risk for cardiac failure, since its effects reverse quickly if things go wrong
4. CorticosteroidsDexamethasone, hydrocortisone, prednisone, or methylprednisoloneDexamethasone 5-20 mg/day; hydrocortisone 100-400 mg/day IVAlso blunts peripheral T4→T3 conversion; covers for possible relative adrenal insufficiency; provides antipyretic effect and hemodynamic stabilization
Acetaminophen only, never aspirin

Aspirin and other NSAIDs displace thyroid hormone from its binding proteins, which raises the free(active) hormone fraction and can make storm worse. Use acetaminophen for fever control instead. Round out supportive care with fluid/electrolyte replacement, sedatives as needed, and management of any precipitating illness.

Myxedema Coma

The hypothyroid mirror image of thyroid storm: a rare, severe decompensation of longstanding hypothyroidism with a genuinely high mortality rate historically cited in the 30-70% range depending on the series. It demands immediate, aggressive treatment, not a slow taper toward normal.

Hallmarks:decreased mental status (delirium to coma) and hypothermia are the two defining features. Also expect bradycardia, hypotension, hyponatremia, hypoglycemia, and hypoventilation.

Management

Expected response:consciousness and vital signs typically start improving within 24 hours of appropriate treatment. If they don't, look harder for an unaddressed precipitant.

Monitoring - What, When, Why

ParameterWhenWatching for
TSH(both directions)4-6 weeks after any dose change or product switch, then every 6-12 months once stableMost sensitive and specific marker; guides every dose adjustment
Free T4Alongside TSH, especially early in hypothyroid treatment or if noncompliance is suspectedUseful for catching malabsorption, nonadherence, or a bioequivalence issue after a product switch
CBC/WBC on thionamidesOn symptoms only (fever, sore throat, mouth sores), not routinely scheduledAgranulocytosis, onset is sudden so scheduled monitoring won't catch it in time
LFTs on thionamidesBaseline and with any symptoms of hepatotoxicityDiscontinue if LFTs run 3x above normal, especially on PTU
Heart rateEvery visit while thyrotoxic or on beta blockadeTarget <90 bpm on propranolol during active hyperthyroidism
RAIU/thyroid scanAt diagnosis if cause is unclearConfirms whether true overproduction or a leak/exogenous source is driving thyrotoxicosis
Clinical euthyroid statusMonthly until euthyroid, then every 6-12 monthsWatch for either persistent thyrotoxicosis or overshoot into hypothyroidism after any definitive therapy

Patient Counseling - What You'll Actually Say

  • Levothyroxine timing:"Take this first thing in the morning, on an empty stomach, with just water, and wait 30 to 60 minutes before you eat breakfast. If mornings don't work for you, taking it at bedtime, at least 2 hours after your last meal, works just as well, just be consistent about which one you do."
  • Spacing from other pills:"Keep your calcium and iron supplements at least 2 hours away from your thyroid pill; they'll block how much of it you actually absorb."
  • Setting expectations on dose changes:"We don't recheck your levels for about 4 to 6 weeks after any dose change, because it takes that long for your body to settle into the new dose. Don't get discouraged if you don't feel different right away."
  • Brand consistency:"Try to stay on the same brand or generic manufacturer each time you refill. If your pharmacy switches you to a different one, let us know so we can recheck your levels."
  • Thionamide safety net:"If you get a fever, sore throat, or mouth sores while on this medication, call us immediately and don't just wait it out, we need to check your blood count that same day."
  • PTU liver warning:"Call right away if your skin or eyes turn yellow, your urine gets dark, or you're unusually tired and it doesn't make sense, those can be signs this medication is affecting your liver."
  • Don't stop antithyroid drugs cold turkey:"Even if you're feeling better, don't just stop this medication on your own. Stopping suddenly can trigger a dangerous flare called thyroid storm."
  • Beta blocker for symptoms:"This won't fix the thyroid problem itself, it just calms the racing heart and shakiness while the other medication or treatment does the real work."
  • Iodine sources to watch:"Some cough syrups, contrast dye for CT scans, kelp or seaweed supplements, and the heart medication amiodarone all contain a lot of iodine and can throw your thyroid off. Mention your thyroid condition before any of those."
  • Lab prep detail:"If you take a B6 or B-complex vitamin, stop it about a week before your thyroid labs, it can throw off the results and make you look more hypothyroid than you actually are."

High-Yield Recall Sheet

  • TSH moves first and moves mostin both directions; it's the single most sensitive screening test.
  • RAIU normal 10-30%.High RAIU = true overproduction (Graves, toxic adenoma/MNG). Low RAIU (<2%) = leak or exogenous source (thyroiditis, factitia).
  • Exophthalmos and pretibial myxedema are Graves'-specific.Lid lag alone happens in any thyrotoxicosis.
  • Methimazole and PTU both block TPO.Only PTU also blocks peripheral T4→T3 conversion.
  • PTU wins in exactly 3 situations:first trimester pregnancy, methimazole intolerance, thyroid storm. Otherwise methimazole is first-line.
  • Agranulocytosishits suddenly, usually within 3 months; monitor by symptoms (fever, sore throat), not routine scheduled labs.
  • Give iodide after a thionamide, not before(feeds an autonomous gland otherwise). Give iodide 3-7 days afterRAI, never before.
  • Iodide is contraindicated in toxic multinodular goiter(Jod-Basedow risk).
  • Beta blockers control symptoms only; they don't touch hormone production or prevent storm, except in thyroiditis where they ARE primary therapy.
  • RAI is contraindicated in pregnancy, absolute; defer conception 6-12 months after treatment.
  • Hypothyroidism after RAI is expected, not a failure.
  • Start levothyroxine low (25 mcg) in elderly or cardiac patientsto avoid provoking angina/arrhythmia/MI.
  • Levothyroxine half-life is 7 days: once-daily dosing, recheck labs no sooner than 4-6 weeks after any change.
  • Physiologic T4:T3 ratio is ~14-16:1, not the 4:1 found in liotrix and desiccated thyroid, why those are considered non-physiologic.
  • >85% of hypothyroid patients do fine on T4 alone.Combination T4/T3 is reserved for persistent symptoms despite maximized levothyroxine.
  • Thyroid storm: PTU + iodide (after) + esmolol/propranolol + corticosteroid + acetaminophen (never aspirin).
  • Myxedema coma: IV levothyroxine ± liothyronine + IV hydrocortisone + aggressive supportive care.Expect improvement within 24 hours.