Thyroid Disorders — Clinical Case

DCE Long Case

Patient profile

Mrs K is a 58-year-old bookkeeper presenting to the endocrine outpatient clinic with a four-month history of palpitations, heat intolerance, and a 7 kg weight loss despite an increased appetite. She has also noticed her eyes bulging and double vision when looking to the side. [1]

Presenting concern: For four months she has had a racing, irregular heartbeat that wakes her at night, intolerance of warm weather, a fine shake of her hands, three loose bowel motions daily, and a 7 kg weight loss. Over the past two months her eyes have become more prominent, with redness, watering and double vision on lateral gaze, and she has been anxious and irritable. [1]

Past medical history: Hypertension (on amlodipine 5mg), cholecystectomy, no known cardiac disease, no prior thyroid disease. Menopause at age 54. [1]

Medications: amlodipine 5mg daily, multivitamin. No over-the-counter thyroid supplements or iodine. [1]

Family history: Mother with hypothyroidism; sister with type 1 diabetes. No known thyroid cancer. [1]

Social: Bookkeeper, married, two adult children. Current smoker of 15 cigarettes per day (30 pack-years). Alcohol 4 standard drinks per week. No illicit drugs. [1]

Examination:

• Alert, thin, mildly anxious. Temperature 37.0. Pulse 128 irregularly irregular. Blood pressure 152/70 (wide pulse pressure). Respiratory rate 18. SpO2 98% room air.
• Hands: warm, moist palms, palmar erythema, fine tremor of outstretched fingers, onycholysis (Plummer nails). Proximal muscle strength 4/5 in shoulder abduction bilaterally.
• Eyes: lid retraction (sclera visible above the iris), lid lag on downward gaze, bilateral proptosis (Hertel exophthalmometry 22mm bilaterally), chemosis and conjunctival injection, diplopia on lateral gaze (limited abduction bilaterally), visual acuity 6/6 bilaterally, Ishihara plates normal (no colour desaturation), no relative afferent pupillary defect, fundi normal (no disc swelling). Clinical activity score 4 out of 7.
• Neck: a diffuse, smooth, firm, non-tender goitre approximately twice the normal size, moving on swallowing, with the lower border palpable. An audible bruit over the gland. No cervical lymphadenopathy. No retrosternal dullness. No thyroidectomy scar. No pretibial myxoedema.
• Cardiovascular: irregularly irregular pulse, no murmurs, no signs of heart failure.
• Reflexes: brisk, with normal relaxation. Neurology otherwise normal. [1]

Investigations:

• TSH less than 0.01 mIU/L (reference 0.4 to 4.0); free T4 42 pmol/L (reference 10 to 20); free T3 14 pmol/L (reference 3.5 to 6.5).
• TSH receptor antibody markedly elevated (positive).
• Anti-TPO strongly positive.
• FBC normal; LFTs normal; calcium and PTH normal; vitamin D 38 nmol/L (low).
• ECG: atrial fibrillation, ventricular rate 128, no ischaemic changes.
• Echocardiogram: normal left ventricular size and systolic function (ejection fraction 60%), no valvular disease.
• Thyroid ultrasound: diffusely enlarged heterogeneous gland with increased vascularity on colour-flow Doppler, no discrete nodules.
• Orbital MRI: enlarged inferior and medial rectus muscles bilaterally, with fat expansion and active inflammation; no optic nerve compression. [1]

Candidate's opening statement (SASPOP)

"This is Mrs K, a 58-year-old bookkeeper presenting 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 — a diffuse smooth goitre with a bruit, lid lag and bilateral orbitopathy with enlarged extraocular muscles on MRI — together with the positive TSH receptor antibody, is diagnostic of Graves disease. Her main problems are the thyrotoxic state driving the atrial fibrillation, the active eye disease that constrains the definitive-treatment choice, her ongoing smoking which worsens the orbitopathy, the thromboembolic risk of her thyrotoxic atrial fibrillation, and the need to engage her in a shared decision on definitive therapy. My priorities are to control her symptoms and her cardiac rate, anticoagulate her, render her euthyroid with antithyroid drugs, treat the active orbitopathy with intravenous methylprednisolone and urgent smoking cessation, and then decide on definitive therapy together." [1]

Structured problem list (numbered, prioritised)

1. Overt Graves thyrotoxicosis — confirmed by positive TRAb; needs definitive treatment after symptomatic control.
2. Atrial fibrillation with rapid ventricular response — high thromboembolic risk in thyrotoxicosis; needs rate control and anticoagulation.
3. Moderate-severe active Graves orbitopathy with diplopia — constrains radioiodine; needs urgent combined endocrine-ophthalmology care and intravenous glucocorticoid.
4. Current smoking (30 pack-years) — strongest modifiable risk factor for orbitopathy; worsens treatment response; needs cessation support.
5. Symptomatic hyperadrenergic state — palpitations, tremor, weight loss, anxiety; needs beta-blockade.
6. Vitamin D deficiency — contributes to the perimenopausal osteoporotic risk of untreated thyrotoxicosis; needs replacement.
7. Hypertension — needs ongoing management; may improve with control of the thyrotoxicosis. [1]

Integrated management plan

Step 1 — Confirm the cause and complete the workup: [1]

The cause is already confirmed — the positive TSH receptor antibody in a thyrotoxic patient with the classic clinical picture is diagnostic of Graves disease, and no radioactive iodine uptake scan is needed [1]. The orbital MRI confirms active disease with muscle enlargement but no optic nerve compression. I would arrange a DEXA scan (she is postmenopausal and thyrotoxic, at high osteoporotic risk) and a formal ophthalmology assessment of her eye disease.

Step 2 — Immediate symptomatic and rate control: [1]

• Propranolol 40mg three times daily — controls the sympathetic symptoms and, at this dose, also inhibits peripheral T4-to-T3 conversion; it will also control her ventricular rate. I would review her blood pressure (the beta-blocker and the carbimazole may both reduce it; her amlodipine may need downward titration).
• Anticoagulation — assess her thromboembolic risk with CHA2DS2-VASc (female, age 58, hypertension — score 2). Thyrotoxic atrial fibrillation carries a higher thromboembolic risk than non-thyrotoxic AF, so I would anticoagulate with a direct oral anticoagulant (apixaban 5mg twice daily) unless contraindicated by bleeding risk, continuing until she has been biochemically euthyroid for several months and the AF has reverted or been cardioverted. [1]

Step 3 — Antithyroid drug therapy: [1]

• Carbimazole 30mg daily in a titration regimen, rechecking thyroid function at 4 to 6 weeks and titrating down toward a maintenance dose of 5 to 10mg daily once euthyroid.
• Counselling on agranulocytosis — in writing, she must stop the drug and present urgently with fever, sore throat or mouth ulceration, particularly in the first three months, for a full blood count. I do not recommend routine FBC monitoring.
• Baseline FBC and LFTs done and normal. A block-replace regimen is an alternative if titration proves difficult. [1]

Step 4 — Graves orbitopathy management: [1]

• Smoking cessation is non-negotiable — it is the strongest modifiable risk factor for orbitopathy and reduces the response to all treatments. I would refer her to a smoking cessation service, offer nicotine replacement therapy and varenicline, and reinforce at every visit.
• Intravenous methylprednisolone — cumulative 4.5g over 12 weeks (for example 500mg weekly), as first-line for moderate-severe active disease per the 2016 EUGOGO guidelines [4]. Higher doses (up to 8g cumulative) are used for sight-threatening disease; cumulative doses above 8g are associated with hepatic and cardiovascular toxicity and should be avoided.
• Urgent combined endocrine-ophthalmology referral. I have already screened for sight-threatening disease — her visual acuity is preserved, colour vision is normal, there is no relative afferent pupillary defect and no disc swelling, and the MRI shows no optic nerve compression. If any of these developed, she would need urgent high-dose IV methylprednisolone (up to 1g weekly) and urgent orbital decompression if no response within two weeks.
• Radioactive iodine is relatively contraindicated while her orbitopathy is active, because it worsens the eye disease; if it were ever used, prophylactic oral prednisolone would be required.

Step 5 — Definitive therapy, shared decision: [1]

The three definitive options — antithyroid drugs, radioactive iodine, and surgery — are roughly equivalent in long-term 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 as the clinical picture evolves [1].

Step 6 — Other problems: [1]

• Vitamin D deficiency — colecalciferol 1000 IU daily (or a loading regimen), recheck in 3 months.
• Osteoporosis risk — DEXA scan; if osteopenic or osteoporotic, treat with calcium, vitamin D and a bisphosphonate as appropriate; the thyrotoxicosis itself accelerates bone loss and this will improve as she becomes euthyroid.
• Hypertension — continue amlodipine, review as her thyroid status normalises. [1]

Step 7 — Communication, follow-up and safety: [1]

• I would frame Graves disease as a treatable autoimmune condition with three equivalent definitive options that we would choose together, address her anxiety about the eye disease directly, counsel on contraception (avoid pregnancy on carbimazole), warn on agranulocytosis, and arrange follow-up at 4 to 6 weeks with TFTs and review of the orbitopathy.
• Refer to an endocrine nurse specialist, a dietitian (for the weight loss and bone health), and the ophthalmologist.
• Document and share the plan with her GP. [1]

Probing questions the examiner would ask

Q: What is her thromboembolic risk, and how long would you anticoagulate her? [1]

A: "Her CHA2DS2-VASc is 2 — female sex and hypertension. But thyrotoxic atrial fibrillation is a special case: it carries a higher thromboembolic risk than non-thyrotoxic AF, and the guidelines anticoagulate more readily. I would anticoagulate her with a direct oral anticoagulant (apixaban or rivaroxaban) from now. I would continue anticoagulation until she has been biochemically euthyroid for at least several months and the AF has reverted to sinus rhythm (or has been cardioverted after a period of stable euthyroidism). If she remains in AF despite euthyroidism, I would re-assess her long-term stroke risk by CHA2DS2-VASc and decide on lifelong anticoagulation accordingly." [1]

Q: How would your management change if her orbitopathy became sight-threatening? [1]

A: "Sight-threatening Graves orbitopathy — optic nerve compression (reduced visual acuity, colour desaturation, relative afferent pupillary defect, disc swelling) or corneal breakdown — is an endocrine-ophthalmological emergency. I would admit her, give urgent high-dose intravenous methylprednisolone 500mg to 1g weekly (up to a cumulative dose that avoids the hepatic and cardiovascular toxicity above 8g), involve ophthalmology and orbital surgery urgently, and if there is no improvement within two weeks of the high-dose glucocorticoid, proceed to urgent orbital decompression. Radioactive iodine is absolutely contraindicated in active sight-threatening disease. In parallel, I would optimise her thyrotoxicosis control — continuing carbimazole and considering urgent total thyroidectomy to rapidly achieve euthyroidism." [1]

Q: She asks whether she should have her thyroid removed. When is surgery preferred over drugs or radioiodine in Graves disease? [1]

A: "Surgery is preferred when there is a large compressive goitre with pressure symptoms (stridor, dysphagia), a coexisting suspicious or confirmed malignant thyroid nodule, pregnancy with disease uncontrolled on antithyroid drugs, a coexisting parathyroid lesion needing surgery, severe active orbitopathy where rapid permanent control of the hyperthyroidism is desired, patient preference for definitive cure, or intolerance of antithyroid drugs (for example agranulocytosis or severe hepatotoxicity). Total or near-total thyroidectomy is now the standard operation for Graves. I would render her euthyroid pre-operatively with carbimazole, give Lugol's iodine 5 to 7 drops three times daily for the 10 days before surgery to reduce gland vascularity, and continue beta-blockade. The risks to discuss are recurrent laryngeal nerve injury (1 to 2% permanent hoarseness), hypoparathyroidism (transient in up to 20%, permanent in 1 to 5%), haematoma (an airway emergency), and the certainty of permanent hypothyroidism needing lifelong levothyroxine." [1]

Q: Six months later, her TFTs are normal on carbimazole 5mg daily, her orbitopathy is inactive and her AF has reverted to sinus rhythm. You stop the carbimazole after an 18-month course. Six weeks later her TSH is suppressed and free T4 elevated again. What are her options now? [1]

A: "She has relapsed — which happens in 50 to 60% of Graves patients after a course of antithyroid drugs. Her options now are a second course of antithyroid drugs (with a lower likelihood of remission), radioactive iodine (now that her orbitopathy is inactive, with prophylactic prednisolone to protect against reactivation of the eye disease, and she must avoid pregnancy for 6 to 12 months), or total thyroidectomy. I would present these options honestly with her — a young, working woman may prefer to avoid the hospital admission of surgery and the hypothyroidism commitment, while a patient wanting definitive certainty may prefer surgery. I would document the shared decision. The relapse rate after a second course of antithyroid drugs is high, so for most patients a definitive option is preferred at this point." [1]

Q: How would your management differ if the cause were amiodarone-induced thyrotoxicosis in a 70-year-old man with ischaemic cardiomyopathy? [1]

A: "The principles change. First, I would use colour-flow Doppler to distinguish type 1 (iodine-induced synthesis in an abnormal gland, with increased vascularity) from type 2 (destructive folliculitis in a normal gland, with absent vascularity), per the 2018 ETA guidelines [6]. Type 1 is treated with a thionamide (carbimazole), often combined with potassium perchlorate for a few weeks to deplete the iodine pool. Type 2 is treated with oral glucocorticoids (prednisolone 40 to 60mg daily tapering over months). Mixed forms are treated with both. The decision to stop amiodarone is individualised and shared with cardiology — withdrawal is often impractical for life-threatening arrhythmias, and the long tissue half-life means stopping has a limited short-term effect. In cases of haemodynamic deterioration or failure of medical therapy, urgent thyroidectomy is indicated. Anticoagulation and beta-blockade are used cautiously given the underlying cardiomyopathy."

Communication and shared decision-making

"I would frame Mrs K's 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 in the active, treatable phase — smoking cessation is the single most impactful action she can take for it, and I would support her with a structured cessation programme. I would be honest about the risk of agranulocytosis and exactly what to do. I would discuss contraception and future pregnancy planning, given that carbimazole is teratogenic and radioiodine requires a delay. I would address her anxiety about the eye disease and the double vision directly, explaining that intravenous methylprednisolone can reduce the inflammation and that the disease has a phasic course that often burns out. And I would align the plan with what matters to her — controlling her symptoms, preserving her vision, managing her palpitations and AF, and returning to work. I would document the shared decision and review it as the clinical picture evolves." [1]

DCE Short Case — 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, scars from prior surgery, body habitus, demeanour (agitation vs lethargy).
2. Hands — warm moist palms vs cool dry; palmar erythema; onycholysis (Plummer nails); fine tremor of outstretched hands with a sheet of paper; thyroid acropachy; proximal muscle strength.
3. Pulse and blood pressure — rate and rhythm (tachycardia, AF, wide pulse pressure in thyrotoxicosis; bradycardia, diastolic hypertension in hypothyroidism).
4. Eyes — lid retraction (sclera visible above the iris on forward gaze), lid lag (lid lags behind the globe on downward gaze), exophthalmometry for proptosis, extraocular movements for ophthalmoplegia and diplopia, conjunctiva for chemosis, 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 thyroid swelling moves on swallowing. Inspect for scars, masses, distended neck veins (retrosternal extension).
6. Neck palpation (from behind) — stand behind the seated patient, place both hands on the lower neck with the patient's neck slightly flexed. Palpate: size, consistency (smooth = Graves; nodular = multinodular goitre or adenoma; hard and fixed = malignancy), tenderness (subacute thyroiditis), mobility on swallowing, whether the lower border is palpable (if not, suspect retrosternal extension). Feel for a thrill.
7. Percussion — percuss the sternum for dullness (retrosternal extension).
8. Auscultation — listen with the diaphragm over each lobe for a bruit (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; brisk reflexes in thyrotoxicosis.
11. Pretibial region — pretibial myxoedema (Graves dermopathy). [1]

Key physical signs the patient demonstrates (for this case)

• Bilateral proptosis with lid retraction and lid lag, chemosis, diplopia on lateral gaze (Graves orbitopathy)
• Diffuse, smooth, firm, non-tender goitre with an audible bruit (Graves)
• Warm moist palms, fine tremor, palmar erythema, onycholysis (thyrotoxicosis)
• Irregularly irregular pulse (atrial fibrillation)
• Brisk reflexes (thyrotoxicosis) [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 and onycholysis. The pulse is irregularly irregular at 110 beats per minute. 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 the 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. On eye examination there is lid lag on downward gaze, bilateral proptosis with chemosis and diplopia on lateral gaze, with preserved visual acuity, normal colour vision and no relative afferent pupillary defect. The reflexes are brisk with normal relaxation. These findings are consistent with Graves disease with Graves orbitopathy, complicated by atrial fibrillation." [1]

Discussion questions

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

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

Q: How would you distinguish this goitre from a multinodular goitre at the bedside? [1]

A: "A Graves goitre is diffuse, smooth and often has a bruit. A multinodular goitre is asymmetric, with one or more palpable nodules of varying size, often larger, and may extend retrosternally (the lower border may not be palpable and there may be sternal dullness on percussion, distended neck veins, or stridor). A toxic multinodular goitre typically presents in an older patient with subclinical or apathetic thyrotoxicosis rather than the florid adrenergic picture and orbitopathy of Graves. The investigation discriminator is the radioactive iodine uptake scan — diffusely increased in Graves, patchy in toxic multinodular goitre — but TRAb is the first-line test and will be positive in Graves and negative in toxic multinodular goitre [1]."

Q: What signs would make you concerned about malignancy in a thyroid nodule? [1]

A: "At the bedside: a hard, fixed nodule; rapid growth; a history of childhood neck irradiation; a family history of medullary thyroid carcinoma or MEN2; hoarseness from recurrent laryngeal nerve palsy; cervical lymphadenopathy; and age at the extremes (under 20 or over 60). On ultrasound, the high-risk features are hypoechogenicity, microcalcifications, irregular margins, a taller-than-wide shape and extrathyroidal extension. A nodule with any of these features needs ultrasound-guided FNA reported by the Bethesda System, and management is dictated by the Bethesda category — Bethesda III and IV are the zones of greatest uncertainty, with malignancy risks of 10 to 30% and 25 to 40% respectively, and Bethesda V and VI go to surgery [3]."

Q: How would you screen for sight-threatening Graves orbitopathy at the bedside? [1]

A: "I would specifically assess for optic nerve compression and corneal breakdown. Optic nerve compression presents with reduced visual acuity, colour desaturation (the Ishihara test is sensitive — loss of colour vision precedes loss of acuity), a relative afferent pupillary defect, and disc swelling on fundoscopy. Corneal breakdown presents with severe eye pain, redness and photophobia from lagophthalmos (the lids cannot close over the proptotic globe). Any of these is an emergency — I would arrange urgent high-dose intravenous methylprednisolone and urgent combined ophthalmology review, with orbital decompression if no response within two weeks [4]."

Q: How would you examine for hypothyroid signs if the patient were hypothyroid? [1]

A: "I would look for bradycardia and diastolic hypertension; cool, dry, pale skin; periorbital puffiness and loss of the outer third of the eyebrows; a hoarse voice; delayed relaxation of the ankle jerks (a classic sign); a slow mental tempo; and signs of associated autoimmune disease (vitiligo, addisonian pigmentation). I would also look for a goitre (Hashimoto can produce a firm, pebbly goitre) or an atrophic gland, and for complications such as a pericardial effusion (distant heart sounds, raised JVP) or pleural effusions [2]."