Common questions asked in seminar presentations on myxedema and thyrotoxicosis
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Common Seminar Questions: Myxedema & Thyrotoxicosis
Below is a structured list of the questions most commonly asked during clinical seminar presentations on these two topics, with concise, examiner-ready answers drawn from Goldman-Cecil Medicine, Rosen's Emergency Medicine, Tintinalli's Emergency Medicine, Goodman & Gilman's Pharmacological Basis of Therapeutics, Harrison's Principles of Internal Medicine 22E, and others in the medical library.
PART 1: MYXEDEMA / HYPOTHYROIDISM
Definitions & Classification
Q: What is the difference between hypothyroidism, myxedema, and myxedema coma?
- Hypothyroidism = insufficient thyroid hormone production causing slowed cellular metabolism.
- Myxedema = clinically overt hypothyroidism with characteristic non-pitting, mucopolysaccharide-laden skin changes; the term is sometimes used loosely for severe hypothyroidism.
- Myxedema coma = the extreme decompensated form: hypothyroidism + depressed mental status + precipitating event. It is a medical emergency with mortality up to 30% even with optimal treatment. - Rosen's Emergency Medicine
Q: How do you classify hypothyroidism by etiology?
- Primary (thyroid gland failure): Hashimoto's thyroiditis (most common), post-radioiodine therapy, post-thyroidectomy, iodine deficiency, drug-induced (amiodarone, lithium, interferon-α, immune checkpoint inhibitors), infiltrative disease (sarcoidosis, amyloidosis, hemochromatosis), transient (postpartum/silent thyroiditis, subacute thyroiditis).
- Secondary (pituitary TSH deficiency): hypopituitarism, Sheehan's syndrome, drugs (bexarotene).
- Tertiary (hypothalamic failure): TRH deficiency, tumors, infiltrative disease.
- Congenital: absent/ectopic thyroid, dyshormogenesis, TSH receptor mutations. - Harrison's Principles 22E
Clinical Features
Q: What are the classical symptoms and signs of hypothyroidism?
| System | Features |
|---|---|
| General/metabolic | Cold intolerance, fatigue, weight gain with decreased appetite |
| Skin | Dry coarse skin, alopecia, lateral eyebrow thinning, cool extremities, pallor, carotenemia (yellow tinge) |
| Neurological | Slow mentation and speech, impaired memory, lethargy, delayed relaxation of deep tendon reflexes (hung-up reflex), carpal tunnel syndrome, sensorineural hearing loss |
| Cardiovascular | Sinus bradycardia, diastolic heart failure, long QT interval, pericardial effusion |
| Muscular | Proximal myopathy, pseudohypertrophy (Hoffmann syndrome), elevated muscle enzymes |
| GI | Constipation, macroglossia |
| Reproductive | Menorrhagia, oligomenorrhea, infertility |
| Psychiatric | Depression, psychosis ("myxedema madness") |
- Rosen's Emergency Medicine, Kaplan & Sadock's Psychiatry
Q: What is the "hung-up" reflex and why does it occur?
Delayed relaxation phase of deep tendon reflexes (particularly the ankle jerk) due to impaired ATP-dependent calcium uptake by the sarcoplasmic reticulum, slowing muscle relaxation. It is a highly specific sign of hypothyroidism.
Q: What is Hoffmann syndrome?
Proximal myopathy with muscular pseudohypertrophy (muscle enlargement due to glycosaminoglycan deposition), elevated CK, and slow movements seen in severe hypothyroidism.
Myxedema Coma Specifics
Q: What are the cardinal features of myxedema coma?
- Altered consciousness / stupor / coma
- Hypothermia (often severe - a key distinguishing feature from other comas)
- Respiratory depression (hypercapnia, hypoxia - due to depressed central respiratory drive)
- A concomitant precipitating event
- Goodman & Gilman's, Rosen's Emergency Medicine
Q: What precipitates myxedema coma?
- Infection (most common, especially pneumonia/UTI/sepsis)
- Exposure to cold weather
- Surgery / trauma
- CNS depressants (opioids, sedatives, antipsychotics)
- Stroke, myocardial infarction, GI bleeding
- Stopping thyroid replacement medication
- Rosen's Emergency Medicine
Q: How do you diagnose myxedema coma?
- Diagnosis is clinical - do not wait for lab results to treat.
- Supportive labs: elevated TSH (primary), low free T4, elevated serum CK, hyponatremia, hypoglycemia, hypercholesterolemia, normochromic anemia, hypercapnia on ABG.
- The Myxedema Coma Scoring Tool (Rosen's) stratifies risk and guides treatment decisions.
- ECG: sinus bradycardia, low-voltage complexes, flattened/inverted T-waves, prolonged QT.
Q: How is myxedema coma treated?
Treatment must begin immediately without awaiting confirmation:
| Step | Action |
|---|---|
| Thyroid hormone | IV levothyroxine loading dose 200-300 µg, then 1.6 µg/kg IV every 24 hours. Add IV T3 (5-10 µg every 8-12 hours) since T4→T3 conversion may be impaired |
| Glucocorticoids | Hydrocortisone 100 mg IV every 6 hours BEFORE thyroid hormone (to prevent precipitating adrenal crisis) |
| Hypothermia | Passive rewarming only (active rewarming causes vasodilation and further hypotension) |
| Ventilatory support | Mechanical ventilation if respiratory failure |
| Fluid/electrolytes | Cautious fluid resuscitation; correct hyponatremia |
| Treat precipitant | Broad-spectrum antibiotics if infection suspected |
- Goldman-Cecil Medicine, Goodman & Gilman's
Q: Why give hydrocortisone BEFORE levothyroxine in myxedema coma?
Severe hypothyroidism causes relative adrenal insufficiency (reduced cortisol reserve). Giving thyroid hormone first increases metabolic demand and can precipitate an adrenal crisis. Glucocorticoids protect the adrenal axis until insufficiency is excluded.
Q: Why use passive rather than active rewarming in myxedema coma?
Active rewarming causes peripheral vasodilation, which reduces venous return and worsens the already compromised cardiac output, precipitating cardiovascular collapse.
Investigations
Q: What is the single best test for primary hypothyroidism?
Serum TSH - it is elevated (high sensitivity for primary hypothyroidism). Free T4 confirms the diagnosis and grades severity.
Q: What is subclinical hypothyroidism and when do you treat it?
Mildly elevated TSH with normal free T4. Treatment is indicated if:
- TSH > 10 mIU/L
- TSH 5-10 mIU/L with symptoms, elevated LDL cholesterol, or positive thyroid peroxidase antibodies
- Evidence suggests no benefit from treatment in asymptomatic patients >65 years. - Goldman-Cecil Medicine
PART 2: THYROTOXICOSIS / THYROID STORM
Definitions & Classification
Q: What is the difference between hyperthyroidism and thyrotoxicosis?
- Hyperthyroidism = excess thyroid hormone production by the gland.
- Thyrotoxicosis = excess thyroid hormone effect on tissues - a broader term that includes exogenous intake (factitious thyrotoxicosis) or hormone release from a damaged gland without increased synthesis (e.g., thyroiditis).
Q: What are the causes of thyrotoxicosis?
- Increased production: Graves' disease (most common), toxic multinodular goiter, toxic adenoma, TSH-secreting pituitary adenoma, gestational thyrotoxicosis (hCG-mediated), trophoblastic disease.
- Destructive/release: subacute thyroiditis (de Quervain's), postpartum thyroiditis, silent thyroiditis, amiodarone-induced.
- Exogenous: factitious (thyroid hormone ingestion), iodine excess (Jod-Basedow effect), iodinated contrast.
Q: What is the pathophysiology of Graves' disease?
Autoimmune production of TSH-receptor stimulating antibodies (TRAb/TSI) that chronically activate the TSH receptor, causing unregulated thyroid hormone synthesis and secretion, thyroid gland hypertrophy, and characteristic extra-thyroidal manifestations (exophthalmos, pretibial myxedema).
Clinical Features
Q: What are the clinical features of thyrotoxicosis?
| System | Features |
|---|---|
| General | Heat intolerance, weight loss despite increased appetite, fatigue |
| Cardiovascular | Tachycardia (often out of proportion to fever), palpitations, atrial fibrillation, wide pulse pressure, high-output heart failure |
| Neurological | Tremor, anxiety, emotional lability, hyperreflexia, restlessness |
| Skin | Warm moist skin, sweating, hair thinning, onycholysis (Plummer's nails), pretibial myxedema (Graves') |
| GI | Diarrhea/increased bowel frequency, weight loss, vomiting |
| Eyes (Graves') | Exophthalmos, lid lag, lid retraction, chemosis, ophthalmoplegia |
| Reproductive | Oligomenorrhea, reduced fertility, gynaecomastia |
| Muscular | Proximal myopathy, periodic paralysis (especially in Asian males) |
| Metabolic | Mild hypercalcemia (bone resorption), hyperglycemia |
Thyroid Storm
Q: Define thyroid storm. What is the mortality?
Thyroid storm (thyrotoxic crisis) is a rare, life-threatening hypermetabolic state representing acute, extreme exacerbation of thyrotoxicosis with multiorgan dysfunction. Untreated mortality approaches 100%; with treatment, mortality is 10%-30% (some sources cite up to 50% depending on cardiovascular involvement). - Rosen's, Braunwald's Heart Disease, Tintinalli's
Q: What precipitates thyroid storm?
- Infection (most common)
- Surgery (especially thyroid surgery in an unprepared patient)
- Trauma
- Iodine load (radiocontrast, amiodarone)
- Acute myocardial infarction, pulmonary embolism
- DKA, severe emotional stress
- Parturition
- Abrupt cessation of antithyroid drugs
Q: What are the clinical features of thyroid storm?
The four major systems involved:
- Thermoregulatory: Hyperpyrexia (104-106°F / 40-41°C)
- Cardiovascular: Extreme tachycardia often >140 bpm (disproportionate to fever), atrial fibrillation, high-output heart failure, cardiovascular collapse
- CNS: Agitation → delirium → psychosis → seizures → coma
- GI-Hepatic: Nausea, vomiting, diarrhea, abdominal pain; cholestatic jaundice (poor prognosis)
- Rosen's, Tintinalli's
Q: How is thyroid storm diagnosed? What is the Burch-Wartofsky Point Scale (BWPS)?
Thyroid storm is a clinical diagnosis - do not delay treatment for lab confirmation. The Burch-Wartofsky Point Scale (1993) quantifies likelihood:
| Feature | Points |
|---|---|
| Fever | 5 (99°F) to 30 (≥104°F) |
| Tachycardia | 5 (90-109 bpm) to 25 (≥140 bpm) |
| Mental status | 0 (normal) to 30 (coma/seizure) |
| GI dysfunction | 10 (moderate) to 20 (jaundice) |
| CHF | 5 (mild) to 25 (refractory) |
| Atrial fibrillation | 10 (present) |
| Precipitant identified | 0 (absent) to 10 (present) |
-
Score ≥45: thyroid storm
-
Score 25-44: impending storm
-
Score <25: unlikely storm
-
Rosen's Emergency Medicine
Q: Outline the treatment of thyroid storm (the "5 aims").
| Aim | Drug / Action |
|---|---|
| 1. Block new hormone synthesis | PTU 200-250 mg every 4h PO/NG or methimazole 20-30 mg every 6h |
| 2. Block hormone release | Lugol's iodine 8-10 drops every 6-8h (given ≥1 hour AFTER thionamide) or potassium iodide |
| 3. Block peripheral effects | Propranolol 60-80 mg every 4h PO or IV (also blocks T4→T3 conversion) |
| 4. Block T4→T3 peripheral conversion | Glucocorticoids: hydrocortisone 300 mg IV then 100 mg every 8h, OR dexamethasone 2 mg every 6h; PTU (preferred over methimazole) |
| 5. Supportive care | IV fluids, paracetamol (NOT salicylates), cooling blankets, treat precipitant |
Note: PTU is preferred over methimazole in thyroid storm because PTU also blocks peripheral T4→T3 conversion. - Tintinalli's Emergency Medicine
Q: Why are salicylates contraindicated in thyroid storm?
Aspirin displaces thyroid hormone from thyroid-binding globulin (TBG), acutely raising the level of free T3 and T4, thereby worsening the storm.
Q: Why must iodine be given AFTER thionamides in thyroid storm?
If iodine is given first, it provides substrate for new hormone synthesis, potentially worsening the storm. Thionamides must first block the organification step so that the iodine-induced inhibition of hormone release (Wolff-Chaikoff effect) is not overcome.
Q: What is cholestyramine's role in thyroid storm?
It interrupts the enterohepatic circulation of thyroid hormone by binding it in the gut, reducing reabsorption. Used as an adjunct when thionamides are insufficient or contraindicated. Dose: 4 g every 6 hours. - Tintinalli's
Q: What is the role of lithium in thyroid storm?
Used when iodine is contraindicated (e.g., amiodarone-induced thyrotoxicosis). Lithium inhibits thyroid hormone release and synthesis. Dose: 300 mg every 8h; monitor serum levels (target 0.6-1.0 mEq/L) to avoid toxicity.
Q: When is plasmapheresis used?
In thyroid storm refractory to conventional treatment, or when thionamides and iodine are both contraindicated. Directly removes circulating thyroid hormones. - Tintinalli's
Comparative & High-Yield Cross-Questions
Q: Compare thyroid storm vs. myxedema coma.
| Feature | Thyroid Storm | Myxedema Coma |
|---|---|---|
| Temperature | Hyperpyrexia (>40°C) | Hypothermia |
| Heart rate | Extreme tachycardia | Bradycardia |
| CNS | Agitation → seizure → coma | Stupor → coma |
| BP | Initially elevated, then shock | Low-normal or hypotensive |
| Skin | Warm, moist, sweating | Cool, dry, coarse |
| Reflexes | Hyperreflexia | Delayed ("hung-up") reflexes |
| TSH | Very low/suppressed | Very elevated (primary) |
| Free T4 | Very elevated | Very low |
| Key drug | PTU / propranolol | IV levothyroxine + hydrocortisone |
| Avoid | Salicylates; iodine before thionamide | Active rewarming |
Q: What cardiac manifestation is shared by both conditions but opposite in nature?
Both can cause heart failure - thyroid storm causes high-output failure (tachycardia-mediated), while hypothyroidism/myxedema causes low-output diastolic failure (reduced contractility, pericardial effusion).
Q: Why does myxedema cause hypercholesterolemia?
Thyroid hormone normally upregulates LDL receptors in the liver. In hypothyroidism, LDL receptor expression falls, reducing LDL clearance, resulting in elevated LDL cholesterol.
Q: What is the Jod-Basedow phenomenon?
Iodine-induced thyrotoxicosis occurring when a patient with an autonomous thyroid nodule or iodine-deficient multinodular goiter is exposed to a large iodine load (e.g., radiocontrast dye, amiodarone). The autonomous tissue suddenly has substrate to massively increase hormone synthesis.
Q: What is pretibial myxedema and what causes it?
Non-pitting, indurated, "orange-peel" plaques over the anterior shin, seen in Graves' disease. Despite the name, it is a feature of hyperthyroidism, not hypothyroidism. Caused by TSH receptor antibody-stimulated fibroblast proliferation and glycosaminoglycan deposition in the dermis.
Q: What eye signs are specific to Graves' disease vs. general thyrotoxicosis?
- General thyrotoxicosis: lid retraction, lid lag (von Graefe's sign) - due to adrenergic stimulation of Müller's muscle.
- Graves' specific: proptosis/exophthalmos, chemosis, periorbital oedema, ophthalmoplegia - due to immune-mediated orbital fibroblast activation, independent of thyroid status.
Pharmacology Questions
Q: What is the mechanism of PTU vs. methimazole?
Both are thionamides that inhibit thyroid peroxidase (TPO), blocking organification of iodide and coupling of iodotyrosines to form T3/T4. PTU additionally blocks peripheral deiodination (T4→T3 conversion). Methimazole has a longer half-life and is generally preferred except in thyroid storm, first trimester of pregnancy, and thyrotoxic crisis.
Q: Which thionamide is preferred in pregnancy and why?
- First trimester: PTU (methimazole associated with aplasia cutis and choanal atresia).
- Second/third trimester: Switch to methimazole (PTU has hepatotoxicity risk).
Q: What are the serious adverse effects of thionamides?
- Agranulocytosis (0.1-0.5%) - most feared; can be life-threatening. Patients must stop the drug and seek urgent CBC if sore throat/fever develops.
- PTU-specific: hepatotoxicity, ANCA-associated vasculitis.
- Methimazole-specific: aplasia cutis (teratogenic), cholestatic jaundice.
Q: What is the mechanism of radioactive iodine (RAI) therapy?
I-131 is taken up by thyroid follicular cells and emits beta radiation that destroys thyroid tissue over weeks to months, reducing hormone production. Primary treatment for Graves' disease and toxic nodular disease. Contraindicated in pregnancy and moderate-to-severe active Graves' ophthalmopathy.
Sources
- Goldman-Cecil Medicine International Edition, 26th Ed. - Myxedema Coma section
- Rosen's Emergency Medicine 10th Ed. - Chapter 117 (Thyroid & Myxedema)
- Tintinalli's Emergency Medicine 9th Ed. - Chapter 229 (Thyroid Storm treatment aims)
- Goodman & Gilman's Pharmacological Basis of Therapeutics 14th Ed. - Thyroid pharmacology
- Harrison's Principles of Internal Medicine 22E (2025) - Causes of hypothyroidism table
- Braunwald's Heart Disease 12th Ed. - Thyroid cardiomyopathy
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