Thyroid Disorders — Viva Defence

Long Case Viva Defence

The scenario

A 58-year-old woman presents to the endocrine clinic with four months of palpitations, heat intolerance, a 7 kg weight loss despite an increased appetite, and progressive bulging of her eyes with double vision on looking to the side. She is a current smoker of 15 cigarettes per day. On examination: pulse 128 irregularly irregular, blood pressure 152/70, warm moist palms, a fine tremor, lid lag, bilateral proptosis with chemosis and diplopia on lateral gaze, and a diffuse smooth goitre with an audible bruit. TSH suppressed, free T4 42 pmol/L, free T3 14 pmol/L. ECG confirms atrial fibrillation. [1]

Opening statement (SASPOP)

"This is Mrs K, a 58-year-old woman presenting to the endocrine clinic with a four-month history of biochemically overt thyrotoxicosis, complicated by atrial fibrillation with a rapid ventricular response and moderate-severe active Graves orbitopathy with diplopia. The clinical picture — diffuse goitre with a bruit, lid lag and bilateral orbitopathy — is diagnostic of Graves disease. Her main problems are the thyrotoxic state driving the atrial fibrillation, the active eye disease that constrains definitive-treatment choice, her ongoing smoking, and the need for anticoagulation. My priorities are to control her symptoms and her cardiac rate, confirm the cause biochemically, render her euthyroid with antithyroid drugs, treat the active orbitopathy with intravenous methylprednisolone and urgent smoking cessation, anticoagulate her for the thyrotoxic atrial fibrillation, and then engage her in a shared decision on definitive therapy." [1]

Problem list (numbered, prioritised)

1. Overt Graves thyrotoxicosis — needs cause confirmation (TRAb) and definitive treatment
2. Atrial fibrillation with rapid ventricular response — thromboembolic risk, rate control, anticoagulation
3. Moderate-severe active Graves orbitopathy with diplopia — constrains radioiodine, needs urgent combined care
4. Smoking — strongest modifiable risk factor for orbitopathy; worsens treatment response
5. Symptomatic hyperadrenergic state — palpitations, tremor, weight loss
6. Perimenopausal osteoporosis risk from untreated thyrotoxicosis [1]

Integrated management plan

Pillar 1 — Confirm the cause: "The clinical picture is diagnostic of Graves, but I would confirm with serum TSH receptor antibody — a positive TRAb confirms Graves and obviates the need for a radioactive iodine uptake scan [1]. I would also send anti-TPO, FBC, LFTs, bone profile, and organise an orbital MRI to grade the eye disease."

Pillar 2 — Immediate symptom and rate control: "Propranolol 40 mg three times daily — controls the sympathetic features and, at this dose, inhibits T4-to-T3 conversion. This will also control her ventricular rate. I would anticoagulate her with a direct oral anticoagulant — thyrotoxic atrial fibrillation carries a higher thromboembolic risk than non-thyrotoxic AF, and her CHA2DS2-VASc is at least 2. I would continue anticoagulation until she has been biochemically euthyroid for several months and the AF has reverted or been cardioverted." [1]

Pillar 3 — Antithyroid drug therapy: "Carbimazole 30 mg daily in a titration regimen, rechecking TFTs at 4 to 6 weeks and titrating down to a maintenance dose. I would counsel her explicitly and in writing on agranulocytosis — stop the drug and present urgently with fever, sore throat or mouth ulceration, particularly in the first three months. I would check baseline FBC and LFTs. A block-replace regimen is a reasonable alternative if frequent titration is impractical." [1]

Pillar 4 — Graves orbitopathy: "She has moderate-severe active disease — proptosis, chemosis and diplopia. The first action is smoking cessation — non-negotiable, it is the strongest modifiable risk factor and improves treatment response. Per the 2016 EUGOGO guidelines [4], I would treat with intravenous methylprednisolone, cumulative dose 4.5 g over 12 weeks (for example 500 mg weekly). I would refer urgently to a combined endocrine-ophthalmology clinic. I would specifically look for sight-threatening disease — optic nerve compression or corneal breakdown — which needs urgent high-dose IV methylprednisolone (up to 1 g weekly) and urgent orbital decompression if no response. Radioactive iodine is relatively contraindicated here because it worsens active orbitopathy; if it were ever used, prophylactic oral prednisolone would be required."

Pillar 5 — Definitive therapy, shared decision: "The three definitive options are roughly equivalent in outcome. Given her active orbitopathy and smoking, my recommendation is antithyroid drugs first-line aiming for remission, combined with aggressive treatment of the eye disease, reserving surgery or radioiodine for relapse or intolerance. I would present the options honestly, document her preference, and review." [1]

Probing questions the examiner would ask

Q: Why is radioactive iodine relatively contraindicated in this patient, and what would you do if she insisted on it? [1]

A: "Radioactive iodine worsens active Graves orbitopathy in about 15% of patients within the first year after treatment, by releasing antigen and amplifying the autoimmune orbital inflammation. Her active moderate-severe disease makes this risk unacceptable without mitigation. If radioiodine were genuinely her preference, I would first ensure smoking cessation, then give prophylactic oral prednisolone 0.3 to 0.5 mg/kg/day started at the time of radioiodine and tapered over three months, and monitor the orbitopathy closely [1]. I would also counsel her that radioiodine commits her to lifelong levothyroxine, that she must avoid pregnancy for 6 to 12 months, and that she may need a second dose. In her case, with active diplopia and chemosis, I would strongly prefer antithyroid drugs or surgery."

Q: How would you counsel her on agranulocytosis, and how would you manage it if it occurred? [1]

A: "I would tell her in writing that carbimazole can, rarely, cause a dangerous fall in white blood cells. The warning is specific: if she develops fever, sore throat or mouth ulceration, particularly in the first three months, she must stop the drug immediately and present to the emergency department for a full blood count. I do not recommend routine FBC monitoring because the yield is too low and the onset can be rapid between tests. If agranulocytosis occurs (neutrophils below 0.5), I would stop the carbimazole, give broad-spectrum antibiotics covering gram-negatives and oral flora, admit her, and arrange a different definitive therapy — radioiodine or surgery once euthyroid. I would NOT substitute propylthiouracil because there is significant cross-reactivity between the thionamides for agranulocytosis." [1]

Q: She re-presents in three months with worsening dyspnoea and orthopnoea. Echocardiogram shows a dilated left ventricle with an ejection fraction of 35%. How does this change your management? [1]

A: "She has developed thyrotoxic cardiomyopathy with heart failure with reduced ejection fraction. This is an indication for urgent definitive therapy rather than continued antithyroid drugs. The 2016 ATA guidelines recommend that patients who develop heart failure from thyrotoxicosis proceed promptly to definitive treatment — total thyroidectomy is often preferred because it achieves euthyroidism most rapidly and avoids the delay of radioiodine. I would optimise her medically first — continue carbimazole to render her euthyroid, stop or reduce the beta-blocker (which may worsen HFrEF — propranolol is problematic in HFrEF; a cardioselective agent or low-dose careful use is needed), start GDMT for HFrEF (ACE inhibitor, beta-blocker once stable, MRA, SGLT2 inhibitor), and diurese for volume. I would arrange urgent anaesthetic and surgical review for total thyroidectomy once euthyroid. Thyrotoxic cardiomyopathy often recovers substantially once euthyroidism is achieved." [1]

Q: How would your management differ if she were 28 years old and 10 weeks pregnant? [1]

A: "Three changes. First, propylthiouracil replaces carbimazole as first-line in the first trimester, because carbimazole is teratogenic (aplasia cutis, choanal atresia, tracheo-oesophageal fistula, omphalocele). I would switch to carbimazole from 16 weeks to limit PTU hepatotoxicity. Second, radioactive iodine is absolutely contraindicated in pregnancy — it ablates the fetal thyroid. Third, I would measure TSH receptor antibody at 20 to 24 weeks because TRAb crosses the placenta and can cause fetal and neonatal hyperthyroidism — monitor the fetus for tachycardia, growth restriction and goitre. The beta-blocker would be limited to a short course for severe symptoms because long-term propranolol is associated with fetal growth restriction. If she were uncontrolled on PTU, surgery in the second trimester would be the next step. Her levothyroxine — if she were hypothyroid — would be increased by 25 to 30% at confirmation of pregnancy." [1]

Q: She asks whether radioactive iodine causes cancer or infertility. How do you respond? [1]

A: "I would reassure her with the evidence. Decades of follow-up of patients treated with I-131 for hyperthyroidism show no increase in overall cancer mortality or infertility compared with the general population. There is a small, age-dependent increase in the risk of radiation-attributable secondary cancers, but the absolute risk is low. I would explain that radioiodine is taken up almost exclusively by thyroid tissue, the radiation dose to the gonads is minimal, and contraception is recommended for 6 to 12 months only to avoid a pregnancy during the early hypothyroid phase — it does not impair future fertility. I would address her specific fears directly and offer written information, and if her concern remained a barrier, antithyroid drugs or surgery remain excellent alternatives." [1]

Communication and shared decision-making

"I would frame Graves disease as a treatable autoimmune condition with three equivalent definitive options that we would choose together. I would explain that her eye disease is the active, treatable phase and that smoking cessation is the single most impactful action she can take for it. I would be honest about the risk of agranulocytosis and what to do. I would discuss contraception and future pregnancy planning, given the implications of each treatment option. And I would align the plan with what matters to her — controlling her symptoms, preserving her vision, avoiding hospital admissions, and managing her AF. I would document the shared decision and review it as the clinical picture evolves." [1]

Short Case Discussion — Thyroid Examination

Instruction: "Examine this patient's neck and thyroid." [1]

Systematic examination routine

1. End of bed — observe for obvious goitre, proptosis, periorbital puffiness, cachexia or obesity, scars from prior surgery, demeanour (agitation vs lethargy).
2. Hands — warm moist palms (thyrotoxic), cool dry palms (hypothyroid), palmar erythema, onycholysis (Plummer nails), fine tremor of outstretched hands with a sheet of paper on them, thyroid acropachy (Graves), proximal muscle strength.
3. Pulse and blood pressure — tachycardia, atrial fibrillation, wide pulse pressure (hyperthyroid); bradycardia, diastolic hypertension (hypothyroid).
4. Eyes — lid retraction (sclera visible above the iris on forward gaze), lid lag (the lid lags behind the globe on downward gaze), exophthalmometry for proptosis, extraocular movements for ophthalmoplegia and diplopia, conjunctiva for chemosis and injection, visual acuity and colour vision (Ishihara) for optic nerve compression, fundoscopy for disc swelling.
5. Neck (inspection from the front and side) — ask the patient to swallow a sip of water — a goitre moves on swallowing (thyroid, thyroglossal). Inspect for scars, masses, distended veins (suggest retrosternal extension).
6. Neck (palpation from behind) — stand behind the patient, place both hands on the neck with the patient's neck slightly flexed. Palpate the thyroid: size, consistency (smooth = Graves; nodular = multinodular goitre or adenoma; hard, fixed = malignancy), tenderness (subacute thyroiditis), mobility on swallowing, lower border (can you get below it — retrosternal extension if not). Palpate for a thrill.
7. Percussion — percuss the sternum for dullness (retrosternal extension).
8. Auscultation — listen for a bruit over the goitre (hypervascularity in Graves).
9. Cervical lymph nodes — palpate the cervical chain for lymphadenopathy (malignancy, Hashimoto).
10. Reflexes — delayed relaxation of the ankle jerks in hypothyroidism; hyperreflexia in thyrotoxicosis.
11. Pretibial region — pretibial myxoedema (Graves dermopathy). [1]

Presentation template

"I have examined this patient's thyroid. On inspection from the end of the bed, there is bilateral proptosis with lid retraction. The hands are warm and moist with a fine tremor. The pulse is irregularly irregular at 110. On inspection of the neck there is a diffuse swelling that moves on swallowing. On palpation from behind, the thyroid is smoothly enlarged to approximately twice normal size, firm but not hard, non-tender, mobile on swallowing, with the lower border palpable and no retrosternal extension. There is an audible bruit over the gland. There is no cervical lymphadenopathy. There is lid lag on downward gaze and diplopia on lateral gaze. The ankle jerks are brisk. These findings — a diffuse smooth goitre with a bruit, eye signs, and thyrotoxic features — are consistent with Graves disease with Graves orbitopathy." [1]

Discussion questions

Q: What is the significance of a bruit over the thyroid? [1]

A: "A bruit indicates increased vascularity of the gland, which is characteristic of Graves disease — the TSH receptor stimulating antibody drives both hormone synthesis and hypertrophy of the gland with increased blood flow. A bruit is not present in toxic multinodular goitre, toxic adenoma or the thyroiditides, so it is a useful discriminator when the cause of thyrotoxicosis is unclear at the bedside. I would confirm with a TSH receptor antibody and, if negative, a radioactive iodine uptake scan." [1]

Q: How do you distinguish Graves disease from subacute thyroiditis at the bedside? [1]

A: "The discriminators are pain and the goitre. Subacute (de Quervain) thyroiditis is painful — the patient has anterior neck pain often radiating to the jaw, and the gland is tender on palpation [5]. The goitre is typically small, firm and tender. There are no eye signs and no bruit. The patient often has a recent viral upper respiratory tract infection and may have fever, malaise and a raised ESR. Graves disease, by contrast, has a painless, smooth, non-tender diffuse goitre, often a bruit, and may have orbitopathy and dermopathy. The investigation discriminator is the radioactive iodine uptake — high in Graves, low or suppressed in subacute thyroiditis — but TRAb will be positive in Graves and negative in thyroiditis, making it the modern first-line test."

Q: What do you look for in a thyroid nodule that raises the suspicion of malignancy? [1]

A: "The concerning features at the bedside are: a hard, fixed nodule; rapid growth; a history of neck irradiation; a family history of familial medullary thyroid carcinoma or MEN2; recurrent laryngeal nerve palsy (hoarseness); cervical lymphadenopathy; and the patient being at the extremes of age (under 20 or over 60). On ultrasound, the high-risk features are hypoechogenicity, microcalcifications, irregular margins, a taller-than-wide shape and extrathyroidal extension [3]. A nodule with any of these features needs FNA reported by the Bethesda System, and management is dictated by the Bethesda category [6]."

Q: What is the significance of delayed relaxation of the ankle jerks? [1]

A: "Delayed relaxation of the deep tendon reflexes, particularly the ankle jerks, is a classic sign of hypothyroidism — the muscle contraction-shortening cycle is slowed by the hypometabolic state. It is one of the few signs that can be elicited reliably at the bedside and, with bradycardia, cool dry skin and periorbital puffiness, supports a clinical diagnosis of hypothyroidism. It is reversed with levothyroxine replacement [2]."