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PA31.1-3 | Thyroid: Goiter, Thyroiditis & Thyroid Function Disorders — SDL Guide (Part 4)

Hypothyroidism — Causes, Clinical Features & Laboratory Findings (PA31.3)

Hypothyroidism is deficient thyroid hormone action on tissues. It is classified by level of axis failure:

Primary hypothyroidism (>99% of cases — thyroid itself is deficient):
1. Hashimoto thyroiditis — most common in iodine-replete regions (autoimmune destruction)
2. Iodine deficiency — most common worldwide (impaired synthesis)
3. Post-radioiodine/post-surgical — iatrogenic ablation
4. Dyshormonogenesis — congenital enzyme defects (e.g., thyroid peroxidase mutations)
5. Goitrogens — dietary (cassava, cabbage — thiocyanates), drugs (lithium, amiodarone, PTU overdose)

Secondary hypothyroidism (pituitary failure → ↓TSH → thyroid underactivation)
Tertiary hypothyroidism (hypothalamic failure → ↓TRH)

Clinical manifestations — "metabolic slowdown":
• Cardiovascular: bradycardia, low-voltage ECG, pericardial effusion
• Neurological: lethargy, cognitive slowing, depression, cerebellar ataxia
• Metabolic: weight gain (not due to true obesity — mainly myxoedema fluid), cold intolerance, ↑ LDL cholesterol
• Skin/hair: dry coarse skin, hair loss, non-pitting myxoedema (mucin deposition in dermis), puffy face, macroglossia, hoarse voice
• Reproductive: menorrhagia, infertility, elevated prolactin (TRH also stimulates PRL)
• Neuromuscular: delayed relaxation of deep tendon reflexes ("hung-up" reflexes), carpal tunnel syndrome

Special form — Congenital hypothyroidism (cretinism): Iodine deficiency or thyroid agenesis in utero → irreversible intellectual disability + stunted growth. Neonatal TSH screening (Guthrie card) enables early thyroxine replacement and prevents neurological damage.

Laboratory findings:
• Primary: ↑TSH (most sensitive early marker), ↓ free T4
• Secondary/tertiary: ↓TSH, ↓ free T4
• Dyslipidaemia: ↑ LDL-C, ↑ triglycerides
• ↑ CK (muscle myopathy), ↑ serum prolactin

Myxoedema coma: End-stage severe hypothyroidism — hypothermia, bradycardia, CO2 retention, altered consciousness; medical emergency.

Two-panel diagram: left panel shows a clinical illustration of a patient's face with myxoedematous hypothyroidism highlighting periorbital puffiness, facial oedema, dry coarse skin, and eyebrow thinning; right panel shows a vertical flowchart of the myxoedema mechanism from hypothyroidism to TSH-driven fibroblast activation, dermatan sulphate and hyaluronate deposition, and resultant non-pitting oedema. — **Panel A:** Periorbital puffiness (swollen eyelids), facial oedema (non-pitting, rounded cheeks), dry coarse skin (stippled texture), lateral eyebrow thinning, dull expressionless facies, scalp hair thinning. **Panel B:** Primary hypothyroidism → ↓T3/T4 → ↑TSH (lost negative feedback) → fibroblast activation → dermatan sulphate deposition + hyaluronate deposition → hygroscopic GAG water retention → non-pitting myxoedematous oedema.

Thyrotoxicosis vs. Hypothyroidism — Integrated Comparison

This comparison table is your rapid-revision anchor. Examiners love asking you to distinguish the two:

Feature	Thyrotoxicosis	Hypothyroidism
Heart rate	Tachycardia, AF	Bradycardia
Weight	Loss (↑ appetite)	Gain (↓ appetite)
Temperature tolerance	Heat intolerance, sweating	Cold intolerance, dry skin
Skin	Warm, moist, fine	Dry, coarse, myxoedematous
Hair	Fine, brittle, diffuse loss	Coarse, brittle, outer third eyebrow loss
Deep tendon reflexes	Hyperreflexia, fast relaxation	Hyporeflexia, delayed relaxation
Bowel	Diarrhoea, hyperdefecation	Constipation
Menstruation	Oligomenorrhoea	Menorrhagia
TSH	↓↓ (primary) or ↑ (TSH-oma)	↑↑ (primary) or ↓ (secondary)
Free T4	↑↑	↓↓
RAIU	↑ (Graves) or ↓ (thyroiditis)	↓ (not used diagnostically)
Cholesterol	↓ LDL	↑ LDL
Most common cause	Graves disease	Hashimoto thyroiditis (iodine-replete) / iodine deficiency (worldwide)

Memory hook for reflexes: In hyperthyroidism, everything is fast — fast heart, fast gut, fast reflexes. In hypothyroidism, everything is slow — but the reflex relaxation phase is disproportionately slow (hallmark sign on physical examination).

Side-by-side infographic comparing hyperthyroid (left, warm red tones) and hypothyroid (right, cool blue tones) patient silhouettes, with organ-specific leader-line labels covering heart rate, weight change, skin/hair findings, bowel motility, deep tendon reflexes, and a bottom TSH/T4 summary strip. — **Panel A:** Hyperthyroid silhouette (warm red/orange): tachycardia ↑HR, weight loss ↓ with downward arrow, warm-moist skin / heat intolerance, fine tremor, exophthalmos, goiter, ↑ bowel motility (diarrhea), brisk hyperreflexia DTRs, fine thin hair, anxiety/restlessness label. **Panel B:** Hypothyroid silhouette (cool blue/gray): bradycardia ↓HR, weight gain ↑ with upward arrow, dry-cold-coarse skin / cold intolerance / myxedema, periorbital edema, loss of outer eyebrow, goiter or atrophic gland, ↓ bowel motility (constipation), delayed hung-up DTRs, coarse brittle hair loss, hoarse voice, carpal tunnel icon. **Bottom strip:** Two-column TSH/fT4/fT3 value summary: Hyperthyroid TSH↓ fT4↑ fT3↑ | Hypothyroid TSH↑ fT4↓ fT3↓.

Laboratory & Imaging Interpretation in Thyroid Disorders

Thyroid Function Tests — interpretation framework:

Step 1: TSH — the most sensitive screening test for primary thyroid dysfunction
• TSH ↑ → primary hypothyroidism (or recovery phase of thyroiditis)
• TSH ↓ → hyperthyroidism (or central hypothyroidism — rare)
• TSH normal → euthyroid in most circumstances

Step 2: Free T4 (and free T3 if indicated)
• Confirms and quantifies the degree of dysfunction
• Free T3 is useful in T3-toxicosis (autonomous nodules may preferentially secrete T3)

Step 3: Antibodies
• Anti-TPO ↑↑ → Hashimoto (or Graves overlap)
• TRAb/TSI positive → Graves disease (>95% sensitivity)
• Anti-thyroglobulin → less specific

RAIU (Radioactive Iodine Uptake):
• Measures gland's iodine-trapping capacity (reflects TSH stimulation or autonomous activity)
• Technique: administer 123I tracer; measure uptake at 6 h and 24 h
• High RAIU + homogeneous scan → Graves
• High RAIU + focal "hot" nodule → toxic adenoma
• High RAIU + patchy, nodular → toxic MNG
• Low/suppressed RAIU → thyroiditis, factitious, iodine excess (Wolff-Chaikoff effect)

Thyroid Ultrasound:
• Graves: diffusely enlarged, hypoechoic gland, markedly ↑ vascularity on Doppler ("thyroid inferno")
• MNG: multiple nodules of varying echogenicity ± cystic change ± calcification
• Hashimoto: heterogeneous, hypoechoic parenchyma with echogenic fibrous septa, ↓ vascularity

FNAC (Fine Needle Aspiration Cytology):
• Standard for evaluating thyroid nodules (Bethesda classification)
• Hashimoto: lymphocytes, Hürthle cells, sparse follicular cells
• Graves: hyperplastic follicular cells with scant colloid (may raise concern for follicular neoplasm — clinical correlation crucial)

Decision tree diagram interpreting serum TSH and free T4 results: low TSH branches to overt hyperthyroidism (Graves disease or toxic MNG) or subclinical hyperthyroidism; high TSH branches to Hashimoto thyroiditis or central hypothyroidism; right column shows RAIU scan pattern icons for each diagnosis ranging from diffuse high uptake in Graves to low uptake in central hypothyroidism. — **Panel A:** Decision tree nodes: SERUM TSH (entry) → three branches TSH Low / Normal / High → FREE T4 diamond nodes → terminal diagnosis boxes: Graves Disease, Toxic Multinodular Goiter, Subclinical Hyperthyroidism, Euthyroid, Hashimoto Thyroiditis / Primary Hypothyroidism, Central (Secondary) Hypothyroidism. **Panel B1:** Graves Disease RAIU pattern — diffuse homogeneous orange-red fill >35% at 24 h. **Panel B2:** Toxic MNG RAIU pattern — patchy heterogeneous uptake with discrete hot nodules on cool background. **Panel B3:** Hashimoto Thyroiditis RAIU pattern — low variable grey-blue uptake in enlarged thyroid outline. **Panel B4:** Central Hypothyroidism RAIU pattern — uniform low pale-blue uptake reflecting absent TSH stimulation.

CLINICAL PEARL

Amiodarone and thyroid dysfunction — the CBME clinical link: Amiodarone (anti-arrhythmic) contains 37% iodine by weight. It causes thyroid dysfunction in up to 30% of patients via two mechanisms:
• Amiodarone-induced hypothyroidism (AIH): Wolff-Chaikoff effect — excess iodine acutely inhibits thyroid peroxidase → blocks T3/T4 synthesis; more common in Hashimoto patients (impaired escape mechanism)
• Amiodarone-induced thyrotoxicosis Type 1 (AIT-1): Iodine load drives excess hormone synthesis in underlying MNG or Graves (Jod-Basedow)
• AIT-2: Direct toxic destructive thyroiditis from amiodarone → colloid leakage → RAIU suppressed

Distinguishing AIT-1 vs AIT-2 guides treatment (antithyroid drugs vs. steroids). This is a real exam favourite in combined pharmacology–pathology questions.

SELF-CHECK

A 32-year-old woman presents with 6 months of palpitations, 5 kg weight loss, heat intolerance, and protrusion of both eyes. Examination reveals a diffusely enlarged smooth thyroid with a bruit, lid lag, and tremor. Labs: TSH undetectable, free T4 markedly elevated, TRAb strongly positive. RAIU at 24 hours = 68% (normal 15–35%). Which finding on thyroid histology would you expect?

A. Dense lymphocytic infiltrate with germinal centres and Hürthle cell metaplasia

B. Granulomas with central colloid and multinucleated giant cells

C. Tall crowded columnar follicular cells with papillary infoldings and scalloped pale colloid

D. Paucicellular dense hyaline fibrosis extending into perithyroidal tissues

Reveal Answer

Answer: C. Tall crowded columnar follicular cells with papillary infoldings and scalloped pale colloid

This is classic Graves disease: diffuse goiter + bruit (high vascularity) + bilateral proptosis + undetectable TSH + high free T4 + strongly positive TRAb + high RAIU (TSI drives active iodine trapping). The hallmark histology is option C — tall crowded columnar cells with papillary infoldings (pseudopapillae, not true papillae) and scalloped pale colloid from active endocytosis. Option A is Hashimoto (lymphocytes, germinal centres, Hürthle cells). Option B is de Quervain (granulomas). Option D is Riedel (paucicellular fibrosis).