IM12.1-14 | Thyroid Dysfunction — Graded Quiz

Correct. At 24 weeks (second trimester), the carbimazole embryopathy risk window (first trimester organogenesis) has passed. PTU's risk of hepatotoxicity with prolonged use makes switching to carbimazole at the start of the second trimester the standard practice. The high TRAb titre (6.2 IU/L) is critically important: TRAb crosses the placenta and can cause neonatal Graves thyrotoxicosis or neonatal hypothyroidism (from antithyroid drug passage). Neonatal thyrotoxicosis risk is increased when maternal TRAb exceeds approximately 3× the upper limit of normal — this patient's TRAb is elevated and requires specialist monitoring, fetal surveillance, and neonatal team alerting. Radioiodine is absolutely contraindicated throughout pregnancy.

Pregnancy antithyroid drug strategy: PTU trimester 1 (carbimazole embryopathy risk) → switch to carbimazole trimester 2 (PTU hepatotoxicity risk). High maternal TRAb (>3× ULN) predicts neonatal thyrotoxicosis — alert neonatology. TRAb should be checked at booking, 18–22 weeks, and 30–34 weeks. Radioiodine absolutely contraindicated in pregnancy.

At 24 weeks (second trimester), switch from PTU to carbimazole is appropriate because the carbimazole embryopathy window is past and PTU hepatotoxicity becomes the dominant concern. High TRAb (6.2 IU/L, more than 3× ULN) predicts risk of neonatal Graves thyrotoxicosis — the neonate must be monitored. Radioiodine is absolutely contraindicated in pregnancy.

Correct. Hyperthyroidism accelerates the catabolism (metabolic clearance) of vitamin K-dependent clotting factors (II, VII, IX, X). In the hyperthyroid state, clotting factors are broken down rapidly, so a given warfarin dose achieves moderate anticoagulation. When carbimazole treats the hyperthyroidism and thyroid hormone levels normalise, factor catabolism slows — the same warfarin dose now acts on a larger pool of clotting factors, producing disproportionately higher anticoagulation (rising INR). This interaction is clinically important: warfarin dose must be reduced proactively when antithyroid treatment is initiated, and INR must be monitored closely during the transition to euthyroidism.

Drug interaction: hyperthyroidism + warfarin. Hyperthyroidism accelerates clotting factor catabolism (requires higher warfarin dose). Treating thyrotoxicosis restores normal factor catabolism — warfarin dose must be reduced as euthyroidism is achieved or INR will overshoot. Monitor INR weekly during the first 4–6 weeks of antithyroid therapy.

In hyperthyroidism, vitamin K-dependent clotting factors are catabolised more rapidly — hyperthyroid patients require higher warfarin doses to achieve target INR. When euthyroidism is restored with carbimazole, factor catabolism normalises, factor concentrations rise, and the existing warfarin dose produces supra-therapeutic INR. This is a pharmacokinetic interaction: reduced factor catabolism, not direct carbimazole-warfarin drug interaction. Warfarin dose reduction and close INR monitoring are required during antithyroid therapy.

Correct. The Bethesda System for Reporting Thyroid Cytopathology: Category I = non-diagnostic; Category II = benign (risk of malignancy 0–3%); Category III = atypia of undetermined significance (risk ~5–15%); Category IV = follicular neoplasm or suspicious for follicular neoplasm (risk ~15–30%); Category V = suspicious for malignancy (risk ~60–75%); Category VI = malignant (risk ~97–99%). Bethesda IV indicates a follicular patterned lesion where FNAC cannot distinguish follicular adenoma from follicular carcinoma — the distinction requires histological assessment of capsular and vascular invasion. The recommended management is diagnostic surgical lobectomy. The suspicious ultrasound features (hypoechoic, irregular margins, microcalcifications, taller-than-wide) are independently concerning but the cytology category IV does not itself confirm malignancy.

Bethesda System: I = non-diagnostic, II = benign, III = AUS/FLUS, IV = follicular neoplasm (needs lobectomy), V = suspicious for malignancy, VI = malignant. The key Bethesda IV point: FNAC cannot distinguish follicular adenoma from follicular carcinoma — histology needed for capsular/vascular invasion assessment. Thyroid FNAC is the first-line investigation for any thyroid nodule >1 cm with suspicious ultrasound features.

Bethesda Category IV = follicular neoplasm/suspicious for follicular neoplasm (malignancy risk 15–30%). FNAC cannot distinguish follicular adenoma from carcinoma because the distinction requires demonstrating capsular or vascular invasion — only possible on surgical histology. Recommended management is diagnostic hemithyroidectomy (lobectomy). Bethesda V = suspicious for malignancy; Bethesda VI = malignant.

Correct. This patient has agranulocytosis — the most dangerous adverse effect of thionamide drugs (carbimazole and PTU), occurring in 0.1–0.5% of patients. Agranulocytosis is defined by absolute neutrophil count <0.5 × 10^9/L. It typically occurs within the first 3 months and presents with fever, sore throat, and mouth ulcers. Management: (1) STOP carbimazole IMMEDIATELY — dose reduction is insufficient and switching to PTU is NOT safe because cross-reactivity agranulocytosis can occur; (2) urgent admission for IV broad-spectrum antibiotics (febrile neutropenia protocol); (3) haematology consultation; (4) G-CSF may be used but is not standard first line without specialist input. Every patient on thionamides must be counselled at initiation to stop the drug immediately and seek emergency assessment if they develop fever or sore throat.

Carbimazole/methimazole/PTU agranulocytosis: 0.1–0.5% incidence, most common in first 3 months. ANC <0.5 × 10^9/L. ACTION: stop drug immediately (do NOT switch between thionamides — cross-reactivity occurs), admit, IV broad-spectrum antibiotics, haematology. Patient education at prescription is mandatory: stop drug immediately if fever or sore throat develops.

Agranulocytosis (ANC <0.5 × 10^9/L) is the most dangerous adverse effect of thionamide drugs. Management: stop the drug IMMEDIATELY (dose reduction is inadequate; do NOT switch to PTU — cross-reactivity is documented); admit for IV broad-spectrum antibiotics under febrile neutropenia protocol; haematology review. All patients starting thionamides must receive explicit counselling to stop the drug and attend emergency if they develop fever or sore throat during the first 3 months.

Correct. Severe hypothyroidism produces characteristic ECG changes reflecting reduced cardiac output, pericardial effusion, and metabolic effects on myocardial conduction: (1) sinus bradycardia (reduced chronotropic drive), (2) low-voltage QRS complexes (from pericardial effusion or reduced myocardial contractility), (3) flattened or inverted T waves (metabolic myocardial dysfunction), and (4) prolonged QT interval (risk of torsades de pointes). In contrast, hyperthyroidism causes sinus tachycardia or atrial fibrillation. Atrial fibrillation in hyperthyroidism is managed with rate control and antithyroid therapy; cardioversion is attempted only after euthyroidism is restored. S1Q3T3 is a pattern of pulmonary embolism, not thyroid disease.

Hypothyroidism ECG: bradycardia, low-voltage QRS, T-wave flattening/inversion, prolonged QT (torsades risk). Hyperthyroidism ECG: sinus tachycardia, AF (10–15% of hyperthyroid patients, especially elderly — may be first presentation). AF in hyperthyroidism: rate control + antithyroid therapy first; cardioversion only after euthyroidism restored.

Hypothyroidism ECG findings: sinus bradycardia + low-voltage QRS (pericardial effusion) + flattened/inverted T waves + prolonged QT. Hyperthyroidism causes sinus tachycardia or AF, NOT bradycardia. Low-voltage ECG + sinus bradycardia in a patient with hypothyroid features should prompt urgent TFT, TTE for pericardial effusion assessment, and levothyroxine initiation.

Correct. RAIU measures the thyroid's iodine-trapping capacity, which reflects active hormone synthesis. High RAIU (≥35%, and especially >65%) = active hormone overproduction (Graves disease or toxic nodular goitre — elevated TSH receptor stimulation drives iodine uptake). Low or near-zero RAIU = thyrotoxicosis from hormone RELEASE rather than synthesis (subacute thyroiditis, postpartum thyroiditis, factitious thyrotoxicosis, iodine load, amiodarone-induced type II). In subacute thyroiditis, the gland is destroyed/inflamed and not synthesising hormone — preformed hormone leaks into the circulation (thyrotoxic phase) but the damaged thyrocytes cannot trap iodine. This distinction is clinically critical: low-RAIU thyrotoxicosis is treated supportively (NSAIDs, steroids) not with thionamides, as there is no synthesis to block.

RAIU diagnostic interpretation: high (35–65%+) = synthesis-driven thyrotoxicosis (Graves, TMNG) → treat with thionamides/RAI/surgery; low (<5%) = release-driven thyrotoxicosis (subacute thyroiditis, postpartum thyroiditis, factitious, amiodarone type II) → supportive (NSAIDs, steroids); thionamides useless. This is the primary diagnostic use of RAIU.

RAIU high (>35–65%) = active synthesis is the cause of thyrotoxicosis (Graves, TMNG). RAIU low (near zero) = hormone release not synthesis (subacute thyroiditis, postpartum thyroiditis, factitious). Patient A with 68% RAIU = active synthesis = Graves (or TMNG). Patient B with 2% RAIU = release-type = subacute thyroiditis (damaged/inflamed gland leaks preformed hormone). Low-RAIU thyrotoxicosis: thionamides are NOT effective — treat with NSAIDs/prednisolone for the inflammatory thyroiditis; support only for factitious.

Correct. Radioiodine (I-131) is absolutely contraindicated in: (1) pregnancy (causes fetal thyroid ablation — fetal thyroid concentrates iodine from 10–12 weeks gestation), and (2) breastfeeding (I-131 is excreted in breast milk in significant concentrations and would irradiate the infant's thyroid). Breastfeeding must be stopped and cannot be resumed after radioiodine therapy (I-131 has a physical half-life of 8 days but biological clearance takes weeks). A waiting period of 6 months after radioiodine before attempting conception is recommended. Moderate Graves orbitopathy is a RELATIVE contraindication (radioiodine may worsen ophthalmic disease; prophylactic steroids can be given). Large goitre is not a contraindication but surgery may be preferred. Relapse after carbimazole is a common INDICATION for radioiodine.

Radioiodine absolute contraindications: pregnancy (fetal thyroid ablation, uptake starts 10–12 weeks) and breastfeeding (I-131 in breast milk → infant thyroid irradiation; breastfeeding cannot be resumed after RAI). Relative contraindications: moderate-severe active Graves orbitopathy (worsens in 15–20%, use prophylactic prednisolone), desired pregnancy within 6 months. Preferred indication: Graves relapse after thionamides, TMNG, toxic adenoma.

Absolute contraindications to radioiodine: pregnancy (causes fetal thyroid ablation) and breastfeeding (I-131 excreted in breast milk, irradiates infant thyroid — breastfeeding must be permanently stopped, not merely paused). Moderate Graves orbitopathy is a relative contraindication (may worsen ophthalmopathy — mitigate with corticosteroids). Relapse after carbimazole is an indication for RAI. Patients must also avoid pregnancy for 6 months after RAI.

Correct. Subclinical hypothyroidism (raised TSH, normal FT4) management depends on the TSH level. At TSH 7.8 mIU/L (between 4.5 and 10 mIU/L): repeat TFTs in 3–6 months to confirm persistence (transient TSH elevations occur with illness recovery, drug effects). If persistent TSH 4.5–10 mIU/L: treatment is recommended if the patient has symptoms, positive anti-TPO antibodies (predicts progression to overt hypothyroidism), cardiovascular risk factors, or is pregnant. If TSH persistently >10 mIU/L: most guidelines recommend treatment regardless of symptoms, as this TSH level is associated with increased cardiovascular risk. Thyroid biopsy plays no role in this decision. Immediate full-dose levothyroxine in a 70-year-old risks precipitating angina — in elderly patients, start low (25–50 µg) and titrate.

Subclinical hypothyroidism treatment thresholds: TSH 4.5–10 — confirm persistence, treat if symptomatic, anti-TPO+, cardiovascular risk, or pregnant. TSH >10 — treat all. Elderly patients: start levothyroxine 25–50 µg (not full replacement dose — risk of precipitating angina). Subclinical hypothyroidism with anti-TPO+ progresses to overt hypothyroidism at 2–5% per year.

Subclinical hypothyroidism management: TSH 4.5–10 mIU/L — confirm persistence with repeat TFTs in 3–6 months; treat if symptoms present, anti-TPO positive, cardiovascular risk, or pregnancy. TSH persistently >10 mIU/L — treat regardless of symptoms (cardiovascular risk increased). In elderly patients, start levothyroxine at low dose (25–50 µg) to avoid precipitating cardiac ischaemia — NOT full replacement dose from the outset.

Correct. Pemberton sign tests for thoracic inlet obstruction by a large or retrosternal goitre. Technique: ask the patient to raise both arms above the head for 30–60 seconds. A positive sign is the development of facial plethora, congestion, distension of neck veins, and in severe cases, stridor and respiratory distress — caused by the goitre obstructing venous return and/or the trachea through the thoracic inlet when the arms are raised. This is an important clinical finding as it indicates the need for urgent cross-sectional imaging (CT thorax) and surgical assessment, regardless of the thyroid function status.

Pemberton sign: raise both arms above head → positive if facial plethora + neck vein distension + stridor = thoracic inlet obstruction by large or retrosternal goitre. Requires CT thorax and surgical referral regardless of TFT status. Other thyroid examination signs: tracheal deviation (large goitre), thyroid bruit (Graves), Joffroy sign (absent forehead wrinkling on upward gaze — Graves), von Graefe sign (lid lag).

Pemberton sign: patient raises both arms above head. Positive = facial congestion, neck vein distension, possible stridor due to thoracic inlet obstruction by a large or retrosternal goitre. Relevant to ANY large goitre, not specific to a particular thyroid disease aetiology. A positive Pemberton sign indicates need for CT thorax to assess retrosternal extension and surgical evaluation.

Correct. Amiodarone-induced thyrotoxicosis (AIT) has two subtypes distinguished by mechanism and Doppler vascularity: Type I (increased synthesis) — occurs in patients with pre-existing thyroid disease (nodular goitre), excess iodine from amiodarone drives autonomous hormone synthesis; Doppler shows normal or increased vascularity; RAIU may be low-normal (paradoxical); treat with thionamides ± potassium perchlorate. Type II (destructive thyroiditis) — amiodarone causes direct destructive thyroiditis, hormone is released from damaged follicles; Doppler shows absent/reduced vascularity; treat with prednisolone (30–40 mg/day, taper over 3 months). The absent vascularity on Doppler in this case confirms Type II destructive thyroiditis. However, in practice many cases are mixed, and combined treatment may be necessary.

Amiodarone-induced thyrotoxicosis: Type I = excess synthesis (pre-existing nodular disease) → Doppler vascularity increased → treat with thionamides + potassium perchlorate. Type II = destructive thyroiditis → Doppler vascularity absent/reduced → treat with prednisolone 30–40 mg tapering. Mixed (unclear) = treat both. RAIU unhelpful (amiodarone iodine load suppresses uptake). Amiodarone has 8-week half-life — thyroid effects persist long after stopping.

AIT Type I = increased synthesis in pre-existing nodular thyroid → normal/increased Doppler vascularity → treat with thionamides. AIT Type II = destructive thyroiditis → absent/reduced vascularity → treat with prednisolone 30–40 mg/day (not thionamides — no synthesis to block). Absent vascularity on colour Doppler confirms Type II here. Amiodarone contains ~37% iodine by weight — it has complex effects on thyroid (inhibits T4-to-T3 conversion, can cause both hypothyroidism and thyrotoxicosis). Cannot use RAIU in amiodarone-treated patients as the iodine load suppresses uptake regardless of type.

Correct. In patients with ischaemic heart disease, starting at full replacement levothyroxine dose risks increasing myocardial oxygen demand abruptly in a heart that has adapted to the reduced metabolic rate of hypothyroidism. This can precipitate angina or myocardial infarction. The appropriate strategy is to start low (25 µg/day) and titrate upward slowly in 25 µg increments every 4–6 weeks, guided by symptom tolerance and TSH. Full replacement can be achieved safely over months. IV levothyroxine is reserved for myxoedema coma (impaired consciousness/coma). Deferring treatment entirely is inappropriate — untreated hypothyroidism itself worsens cardiac function (pericardial effusion, reduced contractility, dyslipidaemia).

Levothyroxine dosing in ischaemic heart disease: start 25 µg/day, titrate 25 µg every 4–6 weeks. Full replacement (1.6 µg/kg/day) is the eventual target but must be reached gradually in cardiac patients. Healthy adults: can start at 50 µg and titrate. Young/healthy: may start at full dose. Elderly without cardiac disease: start 50 µg. Elderly with IHD: always 25 µg start.

In hypothyroid patients with ischaemic heart disease, start levothyroxine at 25 µg/day and titrate gradually (25 µg increments every 4–6 weeks). Abrupt full-dose replacement increases myocardial oxygen demand in a heart adapted to a lower metabolic state — risk of angina or MI. IV levothyroxine is reserved for myxoedema coma only. Deferring treatment is wrong — hypothyroidism itself worsens cardiac outcomes (pericardial effusion, dyslipidaemia, reduced contractility).

Correct. This is subacute thyroiditis (de Quervain thyroiditis) — the classic presentation is: (1) preceding viral URTI, (2) tender goitre with anterior neck pain radiating to jaw/ear, (3) thyrotoxic phase (high FT4, suppressed TSH), (4) markedly elevated ESR, and (5) very low RAIU (<5%) — the damaged inflamed gland cannot trap iodine despite releasing preformed hormone. The course is typically: thyrotoxic phase (4–8 weeks) → euthyroid phase → transient hypothyroidism → recovery (usually 95%+ recover normal function). Treatment: NSAIDs for mild pain; prednisolone 30–40 mg/day tapered over 6–8 weeks for severe pain. Antithyroid drugs are ineffective as there is no new hormone synthesis to block. The low RAIU confirms destructive (release-type) thyrotoxicosis.

Subacute thyroiditis (de Quervain) hallmarks: post-viral + tender thyroid + elevated ESR + thyrotoxic TFTs + RAIU near-zero. Treatment: NSAIDs → prednisolone if needed. Do NOT use thionamides. Course: thyrotoxic → euthyroid → hypothyroid (transient) → recovery (95%). Annual TFT follow-up recommended. Differentiate from suppurative thyroiditis (bacterial, systemic sepsis, absent ESR spike without systemic features).

Subacute (de Quervain) thyroiditis: post-viral, tender thyroid, elevated ESR, thyrotoxic TFTs with near-zero RAIU (release not synthesis). Treatment: NSAIDs for mild; prednisolone 30–40 mg/day for severe/refractory. Thionamides are NOT used — no synthesis to block. Condition is self-limiting; 95% recover normal function. Transient hypothyroid phase follows the thyrotoxic phase — levothyroxine may be needed temporarily.