Thyroid Disorders

Thyroid disease is extremely common and often presents with vague, nonspecific symptoms, so a high index of suspicion combined with a low threshold for TSH testing is what actually catches most affected patients.^[1] Hypothyroidism is a state of thyroid hormone deficiency — most often autoimmune (Hashimoto thyroiditis) in an iodine-sufficient country like Canada — treated with lifelong levothyroxine replacement dosed and monitored to normalize TSH. Hyperthyroidism (thyrotoxicosis) is a state of thyroid hormone excess, most often Graves disease, managed with thionamides, radioactive iodine, or surgery depending on patient factors and preference.^[2] Both conditions range from mild, largely asymptomatic biochemical abnormalities (subclinical disease) to true endocrine emergencies — myxedema coma and thyroid storm — and both need individualized management across pregnancy, older age, and cardiac disease. This chapter focuses on hypothyroidism and hyperthyroidism; thyroid nodules and goitre are a separate clinical pathway not covered here.

Symptoms of both hypothyroidism and hyperthyroidism are frequently nonspecific and develop gradually, so patients — and sometimes clinicians — often attribute them to aging, stress, or another chronic condition rather than the thyroid.

Subclinical disease is common and, by definition, produces few or no symptoms — an elevated TSH with a normal free T4 defines subclinical hypothyroidism, and a suppressed TSH with normal free T3/T4 defines subclinical hyperthyroidism (see Assessment & Diagnosis for when to treat).

• Female sex, and a personal or family history of autoimmune thyroid disease or another autoimmune condition (type 1 diabetes, celiac disease, vitiligo, pernicious anemia).
• Prior thyroid surgery, radioactive iodine therapy, or prior external neck/upper-chest irradiation.
• The postpartum period — postpartum thyroiditis can cause a transient hyperthyroid phase, a transient hypothyroid phase, or both in sequence.
• Drugs that can cause hypothyroidism: amiodarone, lithium, iodinated contrast agents, sulfonylureas, and immune checkpoint inhibitors or other immunotherapy.
• Drugs and exposures that can cause or unmask hyperthyroidism: excess iodine intake, including amiodarone, iodinated contrast, and kelp/seaweed supplements — and, rarely, overtreatment with thyroid hormone itself.
• Iodine deficiency (rare in Canada) or iodine excess.
• Older age — a risk factor for thyroid dysfunction generally, and a population where the threshold to treat subclinical hyperthyroidism is lower given atrial fibrillation and bone risk.
• Pregnancy and the immediate postpartum period, given the physiologic rise in thyroid-binding globulin and hCG-driven TSH suppression in the first trimester.

History and physical examination

Ask specifically about the symptom clusters above, the pace of onset, family history of thyroid or other autoimmune disease, current medications (amiodarone, lithium, biotin-containing supplements), pregnancy status/plans, and — for suspected hyperthyroidism — eye symptoms and any recent iodine exposure (contrast, amiodarone). Examine for goitre, nodules, tremor, reflexes, heart rate and rhythm, and — when Graves disease is suspected — orbitopathy and pretibial skin changes.

Laboratory testing

TSH alone is the correct initial test for suspected primary thyroid dysfunction — it is far more sensitive than free T4 for picking up mild disease, and is the single test needed to screen. Add free T4 (and free T3 for suspected hyperthyroidism) only once TSH is abnormal.^[1]

Order anti-TPO antibodies only when the result will actually change management (for example, confirming an autoimmune cause when it affects a shared decision about treating subclinical disease) — do not order it reflexively with every abnormal TSH.

Order thyrotropin receptor antibodies (TRAb) when the cause of confirmed thyrotoxicosis is not clear on history and exam; a clearly positive TRAb in a patient with typical Graves features can substitute for a radioactive iodine uptake scan. Thyroid scintigraphy and radioactive iodine uptake are contraindicated in pregnancy and lactation.

Discontinue biotin supplements at least 48 hours before thyroid testing — biotin interferes with many common immunoassay platforms and can produce a falsely low TSH with falsely elevated free T4/T3, mimicking hyperthyroidism.

When testing is not indicated

Routine population screening for thyroid dysfunction in asymptomatic, average-risk, nonpregnant adults is not recommended — reserve testing for patients with symptoms, risk factors, or a specific indication such as preconception or early pregnancy assessment.^[3] A thyroid scan is rarely needed when TSH is normal or high, since scintigraphy is a test for the cause of thyrotoxicosis, not for hypothyroidism.

Subclinical disease — definitions and when to treat

Subclinical hypothyroidism is an elevated TSH with a normal free T4. Treatment is not routinely recommended for most adults, since randomized evidence does not show a consistent symptom or outcome benefit — but treatment should be considered specifically for a TSH over 10 mU/L, significant hypothyroid symptoms, an abnormal lipid profile, or a patient who is pregnant or planning pregnancy.^[4]

Subclinical hyperthyroidism is a suppressed TSH with normal free T3 and free T4. It is a recognized risk factor for atrial fibrillation and for bone loss, so treatment is generally indicated for older or frail patients, those with other atrial fibrillation risk factors, those with osteoporosis, or those with hyperthyroid symptoms — even though free hormone levels are technically normal.^[2]

Recognizing the two emergencies clinically

Myxedema coma and thyroid storm are clinical diagnoses made at the bedside — there is no single lab value that confirms either one, and severe biochemical hypothyroidism or hyperthyroidism can exist without either syndrome being present. The Burch-Wartofsky point scale is a validated bedside scoring tool that can support, but not replace, the clinical diagnosis of thyroid storm when the picture is ambiguous.^[5]

• Normalize TSH (and free T4/T3 in hyperthyroidism) and resolve symptoms — in pregnancy, target free hormone levels and trimester-specific TSH ranges rather than the standard non-pregnant reference range.
• Avoid overtreatment in both directions — over-replaced hypothyroidism causes iatrogenic thyrotoxicosis and, in older adults, increased fracture risk; under-treated hyperthyroidism risks thyroid storm, arrhythmia, and bone loss.
• Prevent, and promptly recognize, the two thyroid emergencies — myxedema coma and thyroid storm.
• Protect fertility and fetal/neonatal outcomes in patients who are pregnant or planning pregnancy.
• Select a definitive strategy for hyperthyroidism — long-term thionamide, radioactive iodine, or surgery — that matches the patient's goals, orbitopathy status, and pregnancy plans.

• Reinforce consistent levothyroxine timing and, where possible, a consistent product/manufacturer — switching between brand and generic (or between generics) can shift bioavailability enough to warrant a TSH recheck after any switch.
• Counsel on iodine intake: adequate but not excessive. Discourage high-dose iodine or kelp/seaweed supplements, especially in Graves disease, since excess iodine can worsen or trigger thyrotoxicosis.
• Smoking cessation is a specific, high-yield counselling point in Graves orbitopathy — smoking significantly worsens the severity and treatment response of thyroid eye disease, more than for almost any other modifiable factor.
• Advise patients with mild Graves orbitopathy to discuss selenium supplementation with their eye-care specialist as an adjunct — see Drug Tables.
• Discuss fitness to drive if fatigue, impaired concentration, or tremor is significant enough to impair judgment or motor skills.
• Educate every patient started on a thionamide, before symptoms occur, about the specific warning symptoms — sore throat, fever, mouth sores, jaundice, dark urine — that require stopping the drug and seeking immediate care.
• Support adherence counselling for lifelong levothyroxine therapy — hypothyroidism symptoms often return gradually enough that patients underestimate the impact of missed doses.

Breastfeeding

Levothyroxine is safe during breastfeeding at usual replacement doses. For hyperthyroidism, methimazole is preferred over propylthiouracil during breastfeeding — the reverse of the first-trimester-pregnancy preference — because of propylthiouracil's hepatotoxicity risk with more prolonged use; propylthiouracil can still be used if methimazole is not tolerated. Radioactive iodine is contraindicated while breastfeeding and must be postponed until breastfeeding has stopped.

Older adults

Start levothyroxine low (12.5-25 mcg/day) and titrate slowly regardless of cardiac history, since subclinical coronary disease is common in this group. Treat subclinical hyperthyroidism more readily than in younger adults, given the added atrial fibrillation and osteoporosis risk. Watch specifically for over-replacement, since a suppressed TSH from excess levothyroxine is itself linked to increased fracture risk in older patients.

Cardiac disease

Start levothyroxine at the lowest end of the dosing range (as low as 12.5 mcg/day) with slow titration to avoid precipitating angina or arrhythmia. Use beta-blockers cautiously in decompensated heart failure. Untreated hyperthyroidism itself drives high-output heart failure and atrial fibrillation, so undertreatment carries its own real cardiac risk — the goal is careful, monitored correction in either direction, not avoidance of treatment.

Renal and hepatic impairment

Reduce the propylthiouracil dose in significant renal impairment. Use thionamides cautiously in hepatic impairment given their intrinsic hepatotoxicity risk, and obtain baseline liver function tests before starting either agent.

Pediatrics

Newborn levothyroxine replacement — for example, in congenital hypothyroidism — is dosed much higher per kilogram than in adults, at about 10-15 mcg/kg/day. Methimazole is preferred over propylthiouracil in children of any age; propylthiouracil should be avoided in children given its hepatotoxicity risk relative to the benefit in this population.

For hypothyroidism, recheck TSH 6-8 weeks after starting levothyroxine or after any dose change, then at least annually once stable, or sooner if new symptoms arise. In pregnancy, recheck every 4 weeks in the first trimester, then every 6 weeks to about 32 weeks gestation, and 4-6 weeks after any dose adjustment.

For hyperthyroidism, obtain a baseline CBC and liver function tests (ALT, bilirubin) before starting a thionamide. Routine periodic repeat testing for neutropenia or hepatic injury is not required in an asymptomatic patient, but suspect either complication — and check immediately — within the first 3-4 months of starting therapy, or whenever fever, sore throat, or jaundice develops. Hepatic enzymes are frequently mildly elevated in untreated hyperthyroidism itself, independent of any drug effect. Monitor TSH, free T3, and free T4 every 4-6 weeks until stable, then every 3 months; expect TSH to remain suppressed for some time even after free hormone levels normalize, so trend free T4/T3 rather than TSH early in treatment.

Reassess fitness to drive at follow-up if cardiac, neurologic, or muscular symptoms remain uncontrolled.

1. Confirm adherence and correct administration technique first — empty stomach, correct timing before food, and adequate spacing from calcium, iron, antacids, and bile-acid resins — before assuming the dose itself is wrong; this is the most common reason for an apparently inadequate response to levothyroxine.
2. Review the medication list for a new interacting drug or supplement (a new proton pump inhibitor, iron supplement, estrogen product, anticonvulsant, or rifampin) that could have changed requirements since the last stable dose.
3. Confirm the patient has been on a consistent product/manufacturer since the last TSH — a brand or generic switch can shift bioavailability enough to need retesting.
4. If dose requirements are unusually high despite confirmed adherence and no interacting drug, consider a malabsorptive cause — untreated celiac disease, Helicobacter pylori infection, atrophic gastritis, or prior bariatric surgery.
5. For hyperthyroidism not controlled on an adequate thionamide dose, confirm adherence first, then consider a dose increase, re-evaluate for a coexisting or alternative cause of thyrotoxicosis, and discuss definitive therapy (radioactive iodine or surgery) if control remains difficult.
6. If TSH remains persistently out of target range despite working through the steps above, refer to endocrinology rather than continuing to empirically adjust the dose.

• Taking levothyroxine with food, coffee, or too close to calcium, iron, or a proton pump inhibitor — the single most common preventable cause of an apparently inadequate response.
• Rechecking TSH before 6 weeks after a dose change and over-adjusting based on a value that has not yet reached a new steady state.
• Continuing propylthiouracil past the first trimester of pregnancy without revisiting the option of switching back to methimazole.
• Dismissing a sore throat or fever in a patient on a thionamide as just a cold instead of stopping the drug and getting an immediate CBC.
• Treating subclinical hypothyroidism reflexively in every patient with a mildly elevated TSH, without checking the TSH threshold, symptoms, lipid profile, or pregnancy status first.
• Using liothyronine alone as thyroid hormone replacement in pregnancy — it does not cross the placenta.
• Giving iodine solution before the thionamide in thyroid storm — giving it first, or without a thionamide already on board, can worsen thyrotoxicosis by providing substrate for new hormone synthesis; it must follow the thionamide dose by at least 1 hour.
• Using ASA or another NSAID for fever in thyroid storm — these displace protein-bound thyroid hormone and raise free hormone levels; use acetaminophen instead.
• Ordering thyroid function tests without asking about biotin supplement use, risking a falsely reassuring or falsely alarming result.

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Thyroid hormones

Antithyroid agents (thionamides)

Beta-blockers

Used adjunctively for adrenergic symptom control in every hyperthyroid patient without a contraindication; taper once thyrotoxicosis has improved rather than stopping abruptly.

Corticosteroids (thyroid emergencies)

Reserved for emergency adjunctive management, in conjunction with specific antithyroid therapy - not used in routine, non-emergency hypo- or hyperthyroidism.

Iodine, selenium, and antipyretics

The Database's existing iodine, iodide, and selenium monograph slugs are formulation mismatches for this chapter and are intentionally not linked here - see the class note in each row.

Drug interactions with levothyroxine

Levothyroxine has one of the richest interaction profiles a pharmacist will counsel on - most interactions are absorption interactions that are entirely preventable with correct spacing, which makes this a genuinely high-yield counselling point at every dispense and every medication review.

Evidence note: Drug inventory, dosing, adverse effects, and comments reflect current ATA hypothyroidism and hyperthyroidism guideline recommendations and standard Canadian critical-care practice for the two thyroid emergencies.^[1][2][5]