IM12.1-14 | Thyroid Dysfunction — Glossary

American College of Radiology Thyroid Imaging Reporting and Data System; a scoring system for thyroid nodule ultrasound features (composition, echogenicity, shape, margin, echogenic foci) producing categories TR1–TR5 with associated malignancy risk and size thresholds for FNA recommendation.

Absolute neutrophil count <0.5 × 10⁹/L; an idiosyncratic, life-threatening adverse effect of thionamide drugs (carbimazole, PTU) occurring in 0.1–0.5% of patients; presents with fever, sore throat, and mouth ulcers; requires immediate drug cessation and urgent CBC.

An idiosyncratic adverse effect of carbimazole or PTU in which absolute neutrophil count falls below 0.5 × 10⁹/L; occurs in 0.1–0.5% of patients, typically within 3 months of starting therapy; presents with fever, sore throat, and oral ulcers; managed by immediate drug cessation, hospitalisation, and G-CSF in severe cases.

Thyrotoxicosis caused by amiodarone, which contains ~37% iodine by weight; two types: Type I (jod-Basedow — iodine excess activating pre-existing autonomous nodules; low/normal RAIU; treat with antithyroid drugs) and Type II (amiodarone-induced destructive thyroiditis — drug toxicity releasing stored hormone; RAIU near zero; treat with corticosteroids).

Autoantibodies directed against thyroid peroxidase; the most sensitive serological marker of autoimmune thyroid disease; present in >90% of Hashimoto thyroiditis and ~75% of Graves disease patients; elevated anti-TPO without thyroid dysfunction predicts future hypothyroidism.

A variant of thyrotoxicosis seen primarily in elderly patients, characterised by weight loss, new-onset AF, and heart failure without the typical adrenergic features (tremor, anxiety, heat intolerance); often attributed to diminished adrenergic responsiveness with ageing; frequently missed clinically.

A six-category cytopathological reporting system for thyroid FNAC: I (non-diagnostic), II (benign), III (atypia of undetermined significance), IV (follicular neoplasm), V (suspicious for malignancy), VI (malignant); guides management decisions on surgery vs surveillance.

A treatment strategy for Graves hyperthyroidism in which a full blocking dose of antithyroid drug (carbimazole 20–40 mg/day) is maintained throughout, with levothyroxine added simultaneously to prevent drug-induced hypothyroidism; achieves stable thyroid hormone levels but exposes the patient to higher antithyroid drug doses and more adverse effects compared with the titration regimen.

A validated scoring tool for diagnosing thyroid storm; assigns points for temperature, heart rate, atrial fibrillation, heart failure, altered consciousness, GI symptoms, and precipitating event; score ≥45 = thyroid storm; 25–44 = impending storm; <25 = thyroid storm unlikely.

A prodrug antithyroid thionamide converted to methimazole in the body; inhibits TPO (blocking organification of iodine and coupling of MIT/DIT); standard first-line antithyroid drug for hyperthyroidism outside first-trimester pregnancy; initial dose 20–40 mg/day; associated with carbimazole embryopathy in first trimester (aplasia cutis, choanal atresia).

A pattern of congenital anomalies associated with carbimazole/methimazole exposure in the first trimester of pregnancy: aplasia cutis (absent scalp skin), choanal atresia, oesophageal atresia, and other midline defects; the basis for recommending PTU instead of carbimazole during the first trimester.

Risk stratification tool for stroke in atrial fibrillation: Congestive heart failure (1), Hypertension (1), Age ≥75 (2), Diabetes (1), Stroke/TIA (2), Vascular disease (1), Age 65–74 (1), Sex category female (1); score ≥2 in men or ≥3 in women indicates anticoagulation benefit; used to guide anticoagulation in thyrotoxic AF.

Beat-to-beat alternation in QRS complex axis or amplitude on ECG; caused by the heart swinging within a large pericardial effusion, altering its orientation with each beat; a specific sign for haemodynamically significant pericardial effusion or tamponade; requires echocardiographic confirmation.

Irreversible syndrome of intellectual disability, deaf-mutism, and spasticity resulting from severe iodine deficiency during pregnancy; fetal brain development depends on maternal thyroid hormones during the first trimester before the fetal thyroid becomes functional; the most devastating consequence of IDD.

Diffuse or multinodular enlargement of the thyroid due to chronic iodine deficiency; results from compensatory TSH-driven follicular cell proliferation in response to inadequate hormone synthesis; the most visible manifestation of iodine deficiency disorders (IDD).

Forward displacement of the eyeball beyond the orbital rim, measurable by exophthalmometry (Hertel >21 mm or >3 mm asymmetry); specific to Graves disease due to TRAb-mediated orbital fibroblast activation causing glycosaminoglycan deposition and intraorbital volume expansion; distinguished from lid retraction which occurs in any thyrotoxicosis.

Ultrasound-guided sampling of thyroid nodule cells for cytological analysis; reported using the Bethesda System for Reporting Thyroid Cytopathology (6 categories: I non-diagnostic, II benign, III/IV indeterminate, V suspicious for malignancy, VI malignant); the primary investigation for thyroid nodules meeting size and TIRADS criteria for biopsy.

The unbound, biologically active fraction of circulating thyroxine (~0.03% of total T4); preferred over total T4 for assessment of thyroid status as it is not affected by changes in binding protein concentrations.

A cytokine (filgrastim) that stimulates bone marrow granulopoiesis; used to accelerate neutrophil recovery in thionamide-induced agranulocytosis when ANC is severely suppressed with concurrent sepsis; reduces time to neutrophil recovery but evidence for mortality benefit is limited.

Transient thyrotoxicosis in early pregnancy caused by HCG cross-reacting with the TSH receptor; typically associated with hyperemesis gravidarum; TSH suppressed with normal or mildly elevated FT4; self-limiting; distinguished from true Graves disease by the absence of TRAb and the resolution by the second trimester.

Enlargement of the thyroid gland beyond normal size (~20–25 g in adults); classified by WHO as Grade 0 (not palpable/visible), Grade 1 (palpable but not visible with neck in normal position), or Grade 2 (visible with neck in normal position); may be diffuse or nodular, and may occur in hypo-, hyper-, or euthyroid states.

The most common cause of hyperthyroidism in iodine-sufficient populations; an autoimmune disease in which stimulatory TSH receptor antibodies (TRAb/TSI) constitutively activate the TSH receptor, producing autonomous T4/T3 excess; associated with diffuse goitre, ophthalmopathy, and pretibial myxoedema; HLA-DR3 associated.

Autoimmune orbital disease specific to Graves disease, caused by TRAb-mediated activation of TSH receptors on orbital fibroblasts causing glycosaminoglycan accumulation and orbital inflammation; graded by NOSPECS criteria; active moderate-to-severe ophthalmopathy is a contraindication to radioiodine (which can worsen it) — surgery preferred.

The most common cause of hypothyroidism in iodine-sufficient populations; an autoimmune disease characterised by CD8+ T-cell-mediated destruction of thyroid follicles, lymphocytic infiltration with germinal centres, and production of anti-TPO and anti-thyroglobulin antibodies; HLA-DR4/DR5 associated.

A transient hyperthyroid phase that occasionally occurs early in Hashimoto thyroiditis when inflammatory destruction of follicles releases preformed T4/T3 into the circulation; RAIU is low (passive hormone leak, not active synthesis); self-limiting, managed with beta-blockers.

Loss of the outer third of the eyebrows; a classic sign of hypothyroidism, thought to result from thyroid hormone deficiency impairing hair follicle cycling in the lateral brow.

Delayed relaxation phase of tendon reflexes, most easily demonstrated at the ankle; a sensitive clinical sign of hypothyroidism caused by slowed muscle relaxation from decreased sarcoplasmic reticulum calcium uptake; the foot plantar-flexes promptly but returns slowly.

Hypocalcaemia due to inadvertent removal or devascularisation of parathyroid glands during thyroidectomy; transient (5–10% of total thyroidectomies) or permanent (1–2%); presents with perioral and fingertip tingling, positive Trousseau and Chvostek signs, muscle cramps, and severe hypocalcaemic tetany; treated with oral/IV calcium and calcitriol (active vitamin D).

The neuroendocrine regulatory hierarchy comprising TRH from the hypothalamus, TSH from the anterior pituitary, and T4/T3 from the thyroid gland; negative feedback from thyroid hormones maintains T4/T3 within a narrow physiological range.

A radioactive iodine isotope with 13-hour half-life that emits only gamma rays; preferred for diagnostic RAIU testing and thyroid scintigraphy because of its low radiation dose compared with ¹³¹I.

A radioactive iodine isotope with 8-day half-life that emits both gamma rays (for imaging) and tissue-destructive beta particles; used therapeutically for hyperthyroidism (radioiodine ablation) and differentiated thyroid cancer.

Iodine-induced hyperthyroidism occurring when a large iodine load (amiodarone, contrast media, iodine supplements) is given to a patient with autonomous thyroid nodules or pre-existing subclinical hyperthyroidism; iodine excess enables autonomous tissue to produce excess thyroid hormone without TSH regulation.

Synthetic T4 used as the standard pharmacological replacement for hypothyroidism; oral absorption 70–80% fasting; half-life ~7 days (steady-state in 4–6 weeks after dose change); dosing: 1.6 µg/kg/day for healthy adults, 25–50 µg/day starting dose for elderly or cardiac disease patients.

Iatrogenic subclinical hyperthyroidism from excessive levothyroxine dosing in patients on thyroid hormone replacement; detected by suppressed TSH with normal FT4; associated with increased bone loss (osteoporosis risk) and AF risk; requires dose reduction to achieve TSH in low-normal range.

The upper eyelid lags behind the downward-moving globe during downgaze; a sign of any thyrotoxicosis due to sympathetic overactivation of the superior tarsal muscle.

Scleral show above the iris due to overactivation of the superior tarsal muscle (Müller muscle) by sympathetic tone; occurs in any cause of thyrotoxicosis; distinguished from proptosis which is specific to Graves disease.

QRS amplitude <5 mm in all limb leads and <10 mm in all precordial leads; seen in pericardial effusion (electrical signal dampened by fluid), myxoedematous infiltration of the myocardium, or diffuse oedema; the most consistent ECG finding in significant pericardial effusion.

A solution of iodine and potassium iodide; used pre-operatively in thyroid surgery (reduces vascularity via Wolff-Chaikoff effect, decreasing operative blood loss) and in thyroid storm (blocks thyroglobulin proteolysis, reducing hormone release); must be given AFTER antithyroid drug in thyroid storm to prevent providing iodine substrate to an unblocked gland.

The most severe form of hypothyroidism; a medical emergency characterised by hypothermia, bradycardia, hypotension, hypoventilation (CO₂ retention), altered consciousness, and myxoedematous features; may be precipitated by stopping levothyroxine, infection, cold exposure, sedatives; treated with IV levothyroxine plus IV hydrocortisone.

India's public health programme (renamed from National Goitre Control Programme in 1992) targeting iodine deficiency disorders through universal salt iodisation at ≥15 ppm iodine at retail level; monitored by total goitre rate, urinary iodine concentration, and neonatal TSH screening.

Separation of the nail from the nail bed at its distal free edge; associated with thyrotoxicosis, particularly Graves disease; caused by rapid nail growth outpacing the underlying nail bed.

Autoimmune destruction of gastric parietal cells leading to intrinsic factor deficiency and consequent vitamin B12 malabsorption; associated with other organ-specific autoimmune diseases including Hashimoto thyroiditis; presents with macrocytic megaloblastic anaemia, peripheral neuropathy, and subacute combined degeneration of the spinal cord.

Administration of Lugol's iodine solution or SSKI for 10–14 days before thyroid surgery to reduce gland vascularity and operative blood loss; the Wolff-Chaikoff effect causes gland involution and reduced blood flow; used after the patient has been rendered euthyroid with antithyroid drugs.

Orange-peel textured, non-pitting, indurated plaques or nodules on the anterior shins; caused by TRAb-mediated glycosaminoglycan deposition in cutaneous fibroblasts; specific to Graves disease; misleadingly named as it occurs in hyperthyroidism, not hypothyroidism.

A thionamide antithyroid drug with two mechanisms: (1) inhibition of TPO (same as carbimazole); (2) inhibition of peripheral T4→T3 deiodination; preferred over carbimazole in the first trimester of pregnancy and in thyroid storm; dosed every 8 hours (shorter half-life); associated with rare but serious hepatotoxicity.

A nuclear medicine test measuring the percentage of administered ¹²³I or ¹³¹I taken up by the thyroid at defined time intervals; exploits the NIS-mediated iodine trapping property of thyroid follicular cells; high RAIU indicates active synthesis (Graves, toxic nodular goitre); low RAIU indicates thyroiditis or factitious thyrotoxicosis.

Oral administration of iodine-131 for therapeutic destruction of thyroid follicular cells; beta particles emitted by ¹³¹I cause radiation thyroiditis and gland involution; used for Graves disease (renders patient hypothyroid as the intended endpoint), toxic adenoma, TMNG, and differentiated thyroid cancer; contraindicated in pregnancy, breastfeeding, and active severe Graves ophthalmopathy.

A complication of thyroidectomy caused by injury or division of the RLN, resulting in unilateral vocal cord paralysis (hoarseness), bilateral RLN injury (airway emergency); occurs in approximately 1–2% of cases in experienced surgical hands; a primary risk that patients must be counselled about preoperatively.

Hypothyroidism due to insufficient TSH secretion from the pituitary (or TRH from hypothalamus); characterised by low TSH and low FT4 (TSH-FT4 dissociation from normal pattern); always associated with other evidence of hypopituitarism; cortisol replacement must precede thyroid hormone replacement.

Altered TFTs in acutely ill patients without primary thyroid disease; cytokines suppress the HPT axis causing low FT3 (reduced peripheral conversion), low or normal TSH, and sometimes low FT4; do not treat with thyroid hormone — recheck after recovery.

A pattern of altered thyroid function tests seen in acutely ill patients without intrinsic thyroid disease; characterised by low serum T3 (reduced peripheral conversion), low/normal T4, and low/normal TSH; caused by cytokines suppressing the HPT axis; usually resolves with recovery from the primary illness.

A membrane transporter on the basal surface of thyroid follicular cells that actively concentrates iodide from the bloodstream into the cell; energised by the Na+/K+-ATPase gradient; the molecular target of radioactive iodine uptake.

A painful, self-limiting inflammatory thyroid condition following a viral upper respiratory tract infection; characterised by a painful, tender thyroid, elevated ESR, low RAIU (passive hormone leak), and transient thyrotoxicosis followed by hypothyroidism and then recovery; treated with NSAIDs and beta-blockers.

Suppressed TSH (<0.4 mIU/L, often <0.1 mIU/L) with normal free T4 and T3; associated with increased risk of atrial fibrillation and bone loss; treatment indicated if TSH <0.1 in patients over 65, those with cardiac disease, or postmenopausal women with osteoporosis.

Elevated TSH (typically 4–10 mIU/L) with normal free T4 and T3; patient may be asymptomatic; treatment threshold is TSH >10 mIU/L, or lower if symptomatic, anti-TPO positive, pregnant, or cardiovascular risk factors present; risk of progression to overt hypothyroidism ~5% per year with positive anti-TPO.

A form of overt hyperthyroidism in which TSH is suppressed, free T4 is normal, but free T3 is elevated; the gland preferentially secretes T3; requires FT3 measurement for diagnosis; would be misclassified as subclinical hyperthyroidism if FT3 is not checked.

A large glycoprotein secreted by thyroid follicular cells into the colloid; serves as the scaffold for thyroid hormone synthesis and storage; serum thyroglobulin is a tumour marker after total thyroidectomy for differentiated thyroid cancer.

A midline neck cyst arising from a remnant of the thyroglossal duct (the embryological migration path of the thyroid from the foramen caecum to the anterior neck); characteristically moves both on swallowing AND on tongue protrusion — the defining clinical feature distinguishing it from a thyroid mass or lymph node.

A continuous low-pitched murmur auscultated over the thyroid gland, reflecting markedly increased intrathyroidal vascularity; pathognomonic of Graves disease; distinguished from carotid bruit (lateral, systolic, obliterates on vessel compression) and cardiac murmur (transmitted from precordium).

A discrete lesion within the thyroid gland, palpable or identified incidentally on imaging; ~5–10% are malignant; risk stratified by ACR-TIRADS on ultrasound; Bethesda classification on FNAC cytology; a solitary cold nodule (non-functioning on scintigraphy) carries higher malignancy risk than a hot nodule.

The enzyme responsible for iodide oxidation and organification of thyroglobulin tyrosine residues; catalyses both MIT/DIT formation and coupling to form T4 and T3; the target antigen for anti-TPO autoantibodies in Hashimoto thyroiditis and Graves disease.

Life-threatening exacerbation of thyrotoxicosis characterised by fever >38.5°C, tachycardia >140 bpm, altered mental status, vomiting, and cardiovascular decompensation; diagnosed clinically using the Burch-Wartofsky score (≥45 = highly likely); requires emergency treatment with PTU/carbimazole, iodine solution, beta-blockers, corticosteroids, and supportive care.

A life-threatening exacerbation of thyrotoxicosis with extreme metabolic derangement; diagnosed clinically using the Burch-Wartofsky Point Scale (score ≥45 = storm); characterised by hyperpyrexia, extreme tachycardia, heart failure, altered consciousness, GI dysfunction; treatment: PTU → Lugol's iodine (≥1h after PTU) → propranolol → hydrocortisone → supportive care.

Glycoprotein hormone secreted by anterior pituitary thyrotrophs in response to TRH; the principal regulator of thyroid hormone synthesis and secretion; the most sensitive biochemical marker of thyroid status in primary thyroid disease.

The main secretory product of the thyroid gland, containing four iodine atoms; a prohormone converted to the biologically active triiodothyronine (T3) by peripheral deiodinase enzymes; predominantly protein-bound in plasma.

The principal plasma carrier protein for T4 and T3 (~70% binding); synthesised in the liver; levels increase with oestrogen (pregnancy, OCP), affecting total T4 without changing free T4 concentrations.

An approach to diagnostic testing in which each test's result determines whether and what the next test is; avoids unnecessary testing by using sensitive screening tests first (TSH) and only adding confirmatory or aetiological tests (FT4, TRAb, RAIU) when the screening result is abnormal.

ACR classification system for risk-stratifying thyroid nodules on ultrasound using five features (composition, echogenicity, shape, margin, echogenic foci); scores TR1–TR5 guide management (no FNA vs FNA based on size threshold for each category).

A treatment strategy for Graves hyperthyroidism in which the antithyroid drug dose is reduced stepwise as FT4 normalises, guided by monitoring of TFTs every 4–6 weeks; uses lower overall drug doses than the block-replace regimen; the most commonly used regimen in India.

A benign autonomous thyroid nodule that produces T3/T4 independently of TSH due to a somatic activating mutation of the TSH receptor; on scintigraphy it appears as a 'hot nodule' with suppression of the surrounding normal thyroid tissue.

Hyperthyroidism arising from multiple autonomous nodules within a long-standing multinodular goitre; more common in older patients and in iodine-deficient regions; may be precipitated by iodine load (amiodarone, contrast agents — jod-Basedow effect).

The biologically active thyroid hormone, containing three iodine atoms; binds nuclear thyroid hormone receptors (TR-α, TR-β) with greater affinity than T4; produced largely by peripheral deiodination of T4.

IgG autoantibodies that bind to the TSH receptor on thyroid follicular cells; in Graves disease, stimulatory TRAb (thyroid-stimulating immunoglobulins, TSI) activate the receptor constitutively, driving autonomous hormone production independent of TSH.

The strategy of iodising all edible salt for human and animal consumption to prevent iodine deficiency disorders; the primary intervention of NIDDCP; regulated by FSSAI to ≥15 ppm iodine at retail level.

Transient inhibition of thyroid hormone synthesis caused by acute iodine excess, due to autoregulatory blockade of organification; most individuals escape this effect within days; susceptible individuals (those with Hashimoto thyroiditis or neonates) may develop prolonged iodine-induced hypothyroidism.