Endocrinology & Family Medicine & Endocrine Surgery
Goiter
A goiter is any enlargement of the thyroid gland beyond normal values, regardless of cause or associated thyroid function. Normal adult thyroid volume is 6-20 mL in women and 8-25 mL in men, measured by ultrasound. Classically, a distinction is made between simple (or euthyroid, diffuse or nodular, without thyroid dysfunction), multinodular goiter (with or without hyperthyroidism), inflammatory goiter (Hashimoto's thyroiditis, De Quervain's thyroiditis) and diffuse toxic goiter (Graves' disease). Iodine deficiency, the world's leading cause of goiter, has been virtually eliminated in Canada thanks to the mandatory iodization of table salt since 1949. In Quebec, goiters are therefore mainly autoimmune (Hashimoto's), benign nodular or linked to thyroid dysfunction. Assessment is based on TSH, thyroid antibodies and thyroid ultrasound - classically complemented by ultrasound-guided fine-needle cytopuncture (FNC) for any suspicious nodule. Treatment varies according to etiology, size, thyroid function and the presence of compressive symptoms.
Pathophysiology, classification and etiologies
- Mechanisms of goiter development : the thyroid increases in volume by three main, often interrelated mechanisms: diffuse hyperplasia: prolonged stimulation of thyreocytes by TSH (iodine deficiency + goitrogens + resistance to thyroid hormones) → increase in the number and size of follicles → diffuse goiter + focal hypertrophy (nodulogenesis) : clonal expansion of groups of thyreocytes with somatic mutations conferring an advantage in growth or functional autonomy (TSH receptor mutations - TSHR + Gsα mutations + BRAF/RAS alterations in case of malignant transformation) → benign nodules (adenomas) or malignant nodules (carcinomas) + inflammatory or fibrous infiltration : Hashimoto's thyroiditis (lymphoid infiltrate + progressive fibrosis) + De Quervain's thyroiditis (granulomatous inflammation) + Riedel's thyroiditis (extensive fibrosis - rare); role of iodine in goitrogenesis: iodine is the essential substrate for thyroid hormone synthesis (T3 + T4) → iodine deficiency → drop in free T4 → reflex increase in TSH (hypothalamic-pituitary axis) → stimulation of thyroidocyte growth → initially diffuse euthyroid goiter → multinodularity with age → recommended iodine intake (WHO): 150 µg/d in adults + 250 µg/d during pregnancy and breastfeeding → dietary sources: iodized salt + dairy products + eggs + sea fish + seaweed + dietary goitrogens: substances interfering with thyroid hormone synthesis → cabbage + broccoli + cauliflower (isothiocyanates) + manioc + soy (isoflavones) → negligible effect at usual dietary intakes except pre-existing iodine deficiency
- Etiological classification of goitres : simple diffuse (euthyroid) goiter: absence of nodules + normal thyroid function + absence of significant antibodies → causes : iodine deficiency (rare in Canada - isolated rural areas + immigrant populations) + puberty + pregnancy (increased iodine requirements) + goitrogenic drugs (lithium + amiodarone + carbimazole + propylthiouracil - inhibits thyroid hormone synthesis) + genetic factors (familial - familial simple goiter); multinodular goiter (GMN): presence of multiple thyroid nodules of various sizes and structures + most frequent in clinical practice in middle-aged and elderly adults + two forms: euthyroid (non-toxic) GMN: normal thyroid function + benign nodules + ultrasound monitoring + toxic GMN (GMNT): one or more secretory autonomous nodules (toxic adenomas) → hyperthyroidism → collapsed TSH + elevated T3/T4 → thyroid scintigraphy: «hot» nodules (hypercaptans) + the rest of the thyroid is suppressed → treatment: radioactive iodine (¹³¹I) or surgery; Hashimoto's thyroiditis: autoimmune chronic lymphocytic thyroiditis → anti-TPO (anti-thyroperoxidase) + anti-thyroglobulin (anti-Tg) antibodies → lymphoid infiltration + fibrosis → firm + irregular goiter + progressive hypothyroidism → most common cause of autoimmune hypothyroidism and goiter in Quebec + prevalence: 5-10 % of adult female population → treatment: levothyroxine if hypothyroidism; Graves' disease: toxic diffuse goiter → TSH receptor stimulating antibodies (TSI or TRAb) → constitutive thyroid stimulation → hyperthyroidism + vascular diffuse goiter + triad: goiter + ophthalmopathy (exophthalmos) + dermopathy (pretibial myxedema - rare) → TRAb positive → treatment: synthetic antithyroid drugs + radioactive iodine + surgery; cervical goiter with endothoracic extension (plunging): goiter descending behind the sternum into the anterior mediastinum → often bulky multinodular goiter → tracheal compression + superior cava syndrome if bulky + cervicothoracic CT scan obligatory → often surgical indication.
- Clinical presentation and compressive signs: asymptomatic goiter (most frequent): fortuitous discovery on clinical examination or during cervical imaging (ultrasound + CT + MRI) → TSH often normal → monitoring + symptomatic goiter: local functional symptoms: dysphagia (oesophageal compression) + dyspnoea (tracheal compression - inspiratory stridor) + hoarseness (compression of the recurrent laryngeal nerve → cordial paralysis → ENT opinion + laryngoscopy) + «ball» sensation in the throat + chronic postural cough + cervical discomfort + Pemberton sign: elevation of arms above head → cervical venous congestion + facial erythema + vertigo → compressive endothoracic goiter → urgent thoracic CT scan + associated systemic symptoms: hyperthyroidism if toxic goiter (palpitations + emaciation + tremors + diarrhea + heat intolerance + tachycardia) + hypothyroidism if Hashimoto's (asthenia + weight gain + frilosity + constipation + bradycardia) + acute neck pain : De Quervain's thyroiditis (viral - granulomatous inflammation) → pain radiating to jaw and ears + fever + very high SV (>100 mm/h) + transient thyrotoxicosis → endocrinology opinion + signs suggestive of malignancy in a nodular goiter: rapidly growing nodule + hard cervical adenosathies + persistent hoarseness + stony consistency of nodule + history of cervical irradiation + familial MEN2 syndrome + ultrasound-guided CAF if suspicious
Diagnosis, clinical forms and management
| Clinical situation | Diagnosis and assessment | Treatment and follow-up |
|---|---|---|
| Initial goiter assessment TSH - antibodies - ultrasound - TI-RADS classification |
The initial workup of a newly diagnosed goiter follows a structured algorithm combining thyroid biology and imaging; 1st-line biological workup: ultrasensitive TSH (TSHus): reference test for assessing thyroid function - normal TSH: 0.4-4.0 mIU/L → collapsed TSH (4.5 mIU/L) → hypothyroid goiter → assay free T4 + anti-TPO antibodies + anti-Tg antibodies → normal TSH : euthyroid goiter → measure anti-TPO antibodies (Hashimoto's screening) + thyroid-specific antibodies: anti-TPO (anti-thyroperoxidase): marker of thyroid autoimmunity → positive in Hashimoto's (95 % of cases) + Graves' disease (70 %) + postpartum thyroiditis + TRAb (TSH receptor antibodies): specific for Graves' disease → sensitivity 95 % + specificity 99 % → positive TRAb + low TSH = Graves' disease almost certain → monitoring during antithyroid treatment (guides decision to stop) → serum calcitonin: to be measured if thyroid nodule suspected → marker of medullary thyroid carcinoma (MTC) → basal calcitonin >100 pg/mL → MTC almost certain → genetic work-up (RET proto-oncogene) + pentagastrin stimulation test if calcitonin 10-100 pg/mL (limited availability in Canada) + thyroglobulin (Tg): not useful in initial diagnosis → follow-up marker for differentiated thyroid cancer after total thyroidectomy; thyroid ultrasound: reference morphological examination → perform systematically in the presence of any palpated goiter → measure thyroid volume (ellipsoid formula: L × W × H × 0.524 for each lobe) → characterization of nodules: size + echogenicity + contours + presence of microcalcifications + Doppler vascularization + cervical adenopathies → ACR TI-RADS classification (Thyroid Imaging Reporting and Data System - Tessler 2017): score 1-5 according to ultrasound features + recommendations for CAF according to score and size: TI-RADS 1-2: benign → no CAF + TI-RADS 3: slightly suspicious → CAF if ≥2.5 cm + TI-RADS 4: moderately suspicious → CAF if ≥1.5 cm + TI-RADS 5: highly suspicious → CAF if ≥1.0 cm | 2nd-line examinations according to clinical orientation: thyroid scintigraphy (⁹⁹ᵐTc-pertechnetate or ¹²³I): indicated if TSH low or collapsed + nodular goiter → identifies «hot» nodules (autonomous - hypercaptant) + «cold» nodules (hypocaptant - higher risk of malignancy if cold) → allows diagnosis of GMNT (toxic multinodular goiter) + Graves' disease (diffuse intense homogeneous uptake) → NB: not indicated if TSH normal (cold nodule in this context → same risk of malignancy as any nodule → evaluate by TI-RADS + CAF); Cervico-thoracic CT with injection: indicated if: endothoracic plunging goiter + dyspnoea or dysphagia + positive Pemberton sign → precise mapping of extension + tracheal compression (measurement of tracheal diameter - stenosis if <9 mm) + vascular compression + surgical planning → caution: iodine from the contrast medium can precipitate hyperthyroidism in a GMNT (Jod-Basedow phenomenon) → inform the endocrinologist + discuss premedication + cervico-thoracic MRI: non-irradiating alternative - useful for mediastinal extension and surgical planning → no interference with future radioactive iodine; ultrasound-guided fine-needle cytopunction (FNC): outpatient procedure + optional local anesthesia → cell sampling of suspicious nodule → Bethesda classification (thyroid cytopathology reporting system - 2023): Bethesda I: non-diagnostic → repeat + Bethesda II: benign (70-80 % of CAFs) → surveillance + Bethesda III: atypia of undetermined significance (AUS/FLUS) → molecular (ThyroSeq + Afirma) or surgery + Bethesda IV: follicular neoplasm → surgery (lobectomy) + Bethesda V: suspected malignancy → surgery + Bethesda VI: malignant → total thyroidectomy + extension workup. |
| Multinodular euthyroid goiter Surveillance - TI-RADS - CAF - surgical criteria |
Euthyroid multinodular goiter is the most common form of goiter in adults over 50 in Quebec - it is most often benign and requires surveillance only; epidemiology: ultrasound prevalence of thyroid nodules: 20-76 % depending on age and sex (more frequent in women and with age) → palpable: 5-7 % of the adult population + risk of malignancy of a thyroid nodule: 5-15 % (all sizes combined) → nodules <1 cm have a risk of malignancy 20 % or new suspicious feature → repeat CAF; criteria for surgery in euthyroid GMN: compressive symptoms (dysphagia + dyspnea + hoarseness) + large goiter (>80-100 mL) + endothoracic extension + suspicion of malignancy (CAF Bethesda IV-VI) + patient preference after full information + cosmetic (very large cervical goiter) → surgical indication discussed in multidisciplinary team (endocrinologist + endocrine surgeon); goiter surgery: total thyroidectomy (if large bilateral goiter) or lobectomy (if unilateral goiter or isolated nodule) → risks: transient or permanent hypoparathyroidism (hypocalcemia) + recurrent laryngeal nerve paralysis (hoarseness) + bleeding → high-volume surgical center → permanent complication rate: <2 % in expert centers → post-operative hypothyroidism: almost constant after total thyroidectomy → lifetime levothyroxine | Radiofrequency ablation (RFA) of benign nodules: non-surgical interventional technique → radiofrequency probe introduced into the nodule under ultrasound guidance → heat → coagulative necrosis of the nodule → volume reduction 50-80 % in 6-12 months → indications: symptomatic (compressive + cosmetic) benign nodule + Bethesda II confirmed + patient refusing or unable to undergo surgery → advantages: ambulatory + no induced hypothyroidism + preserves thyroid function + rapid recovery → availability in Quebec: university centers specializing in interventional endocrinology (CHUM + CHU de Québec - check current availability) → efficacy data: Ha 2021 meta-analysis (Thyroid): mean volume reduction 76 % at 12 months → European Thyroid Association recommends RFA as an alternative to surgery for symptomatic benign nodules (ETA 2020) + ethanol ablation (PEI - Percutaneous Ethanol Injection): reserved for cystic or mixed nodules (fluid predominant) → puncture + cyst emptying + pure ethanol injection + success rate: 85-95 % for pure cysts; long-term follow-up of GMN: risk of progression to GMNT (toxic multinodular goiter) with age → annual TSH → if TSH low → scintigraphy → if warm nodules → hyperthyroidism treatment + risk of malignancy in GMN: low but not zero → any ultrasound or clinical change → repeat CAF + iodine recommendation: do not supplement iodine in established GMN (risk of Jod-Basedow if subclinical autonomous nodules) → sufficient normal dietary iodine |
| Hashimoto's goiter (chronic lymphocytic thyroiditis) Anti-TPO - hypothyroidism - levothyroxine - target TSH |
Hashimoto's thyroiditis is the most common cause of hypothyroidism and autoimmune goiter in Canada - its management is well codified; clinical presentation and diagnosis: moderate + firm + irregular goiter («bumpy» or «rubbery» appearance) + sometimes tender + asymptomatic or symptoms of progressive hypothyroidism → biology: anti-TPO: elevated (>35 IU/mL) in 95 % of cases → titer correlated with inflammatory activity + anti-Tg: elevated in 60-80 % + TSH: normal in the euthyroid stage → progressively elevated with hypothyroidism → free T4: lowers as hypothyroidism progresses → natural evolution: euthyroid phase (sometimes initial transient thyrotoxicosis - «hashitoxicosis» → release of preformed hormones from destroyed thyreocytes → 5-10 % of Hashimoto's → transient low TSH → elevated free T4 → disappears in 2-4 months → distinguish Graves' disease: TRAb negative + scintigraphy: uptake collapsed) → subclinical hypothyroidism (TSH 4.5-10 mIU/L + normal free T4) → frank hypothyroidism (TSH >10 mIU/L + low free T4); peculiarity of Hashimoto's thyroiditis + thyroid cancer: primary thyroid lymphoma (MALT type - Mucosa-Associated Lymphoid Tissue) → rare but well-documented complication → risk ×60-80 compared with general population → to be evoked if sudden increase in volume of a Hashimoto's goiter + cervical adenopathies → CAF + surgical biopsy if doubt → papillary thyroid carcinoma: slight increase in risk (×1.5-3) in Hashimoto's thyroiditis → justifies ultrasound follow-up | Treatment of Hashimoto's thyroiditis: treatment of hypothyroidism with levothyroxine (L-T4): indication: TSH >10 mUI/L → quasi-systematic treatment + TSH 4.5-10 mUI/L (subclinical hypothyroidism) → treatment discussed: consensus indications: symptoms of hypothyroidism + pregnancy or desire for pregnancy + positive anti-TPO (risk of progression to frank hypothyroidism) + ischemic heart disease (target TSH 1-2.5 mUI/L) + child or adolescent → comfort treatment if asymptomatic : discussed + initial dosage of L-T4: young adult without comorbidity: 1.6 µg/kg/d full dose + elderly or cardiopathic adult: start at 12.5-25 µg/d and increase in increments of 12.5-25 µg/d every 4-6 weeks → avoid rapid increases (risk of angina or tachyarrhythmia) + target TSH: general adult population: 0.5-2.5 mUI/L + pregnancy: TSH <2.5 mUI/L in 1st trimester + 75 years: 1.0-4.0 mUI/L (avoid over-substitution → arrhythmias + osteoporosis + dementia) → take on an empty stomach in the morning, 30-60 min before meal (or 4h after calcium + iron + PPI supplements which reduce absorption) + TSH monitoring at 6-8 weeks after each dose adjustment + anti-TPO monitoring: do not monitor regularly (does not guide treatment); goiter reduction on L-T4: L-T4 can reduce goiter volume by partially suppressing TSH → modest effect → do not aim for TSH <0.5 mIU/L to reduce goiter (risk of atrial fibrillation + osteoporosis) → if compressive goiter persists on L-T4 → surgery or RFA |
| Toxic goiter - Graves' disease and GMNT TRAb - antithyroid drugs - radioactive iodine - surgery |
Toxic (hyperthyroid) goiters represent a spectrum ranging from Graves' disease to toxic multinodular goiter - their management is specific; Graves' disease: most frequent cause of hyperthyroidism in women aged 20-50 + pathophysiology: IgG antibodies to TSH receptor (TRAb) → constitutive stimulation of adenylcyclase → excessive production of T3 + T4 → TSH suppression → Graves' triad: diffuse vascular goiter (murmur on auscultation) + ophthalmopathy (exophthalmos ± chemosis ± diplopia) + dermopathy (pretibial myxedema - rare) + biology: collapsed TSH (60 years + pre-existing multinodular goiter + often progressive, moderate hyperthyroidism + collapsed TSH + elevated T4/T3 + negative TRAb + scintigraphy: multiple hot nodules + suppressed inter-nodular tissue → often subclinical hyperthyroidism (isolated low TSH) for years before frank hyperthyroidism → Jod-Basedow phenomenon: exposure to iodine (contrast PCI + amiodarone) → thyrotoxic decompensation in a pre-existing GMNT → inform radiologists and emergency physicians before any examination with iodinated contrast in a patient with known GMN | Treatment of toxic goiter - three options: synthetic antithyroid drugs (STDs): methimazole (Tapazole) 10-30 mg/d PO (1st line in North America except 1st trimester pregnancy) + propylthiouracil (PTU) 100-150 mg × 3/d (1st line in 1st trimester pregnancy - risk of methimazole embryopathy: choanal atresia + aplasia cutis) → mechanism: inhibition of thyroperoxidase (TPO) → blockade of T3/T4 synthesis + PTU also inhibits peripheral T4→T3 conversion → time to efficacy: 4-8 weeks + goal: normalization of free T4 then TSH → NFS monitoring (risk of agranulocytosis 0.3-0.5 % → patient warning: «consult ER if fever or oral ulcerations») + liver workup (PTU: risk of fulminant hepatitis - rare but serious) → remission of Graves' disease: 30-50 % after 12-18 months of TSA → favorable remission criteria: small goiter + low TRAb at end of treatment + HLADR3 and HLA-B8 genetic variants associated with low remission; radioactive iodine (¹³¹I): definitive treatment - single-dose oral administration → selective irradiation of hypercaptant thyroid tissue → destruction of the thyroid → almost-certain long-term hypothyroidism → indications: relapsed Graves' disease or 1st line if no desire for pregnancy within 6 months + GMNT (very effective) + solitary toxic adenoma → relative ICs: pregnancy + breastfeeding + compressive bulky goiter + active moderate to severe Graves' ophthalmopathy (risk of worsening - pretreatment with corticoids) → available in Quebec in nuclear medicine (CHU + CISSS with nuclear medicine) + thyroid surgery: total (or near-total) thyroidectomy: preferred indication if: very large goiter + compressive symptoms + severe ophthalmopathy (rapid euthyroidism improves ophthalmopathy) + desire for pregnancy within 6 months + associated suspicious nodule → surgery in euthyroidism (prepare with ATS + βblockers + Lugol's 5 days before) → lifelong hypothyroidism after total thyroidectomy → L-T4 started D1 post-op. |
| Goiter and pregnancy Iodine requirements - TSH in pregnancy - Fetal Graves' disease - post-partum |
Pregnancy induces significant changes in thyroid physiology that may aggravate a pre-existing goiter or reveal a new one; physiological thyroid changes in pregnancy: increased iodine requirement (150 → 250 µg/d) → relative deficiency in Quebec possible → slight increase in thyroid volume (10-15 %) → no true goiter if iodine intake is sufficient + increase in TBG (thyroxine-binding globulin) → increase in total T4 and total T3 → free T4 and free T3 remain normal (reference parameters in pregnancy) + hCG stimulates TSH receptor (homologous structure) → TSH physiologically low in 1st trimester (0,1-2.5 mIU/L) → peak free T4 → sometimes picture of transient gestational thyrotoxicosis (TGT): intense nausea + vomiting (hyperemesis gravidarum) → negative TRAb + transiently low TSH → spontaneous resolution 2nd trimester → no ATS; reference values for TSH in pregnancy (ATA 2017): 1st trimester: 0.1-2.5 mUI/L + 2nd trimester: 0.2-3.0 mUI/L + 3rd trimester: 0.3-3.5 mUI/L → laboratory-specific values if available → screening for hypothyroidism in pregnancy: TSH in early pregnancy if: thyroid history + symptoms + known positive anti-TPO + infertility + repeated miscarriage + living in an iodine-deficient area; Graves' disease and pregnancy: ATS necessary to protect fetus from thyrotoxicosis → PTU in 1st trimester (methimazole teratogenic in 1st trimester) → switch to methimazole in 2nd trimester (PTU risk of hepatitis) → lowest possible dose + TRAb crosses placenta → fetal or neonatal thyrotoxicosis if high titre (>3× normal in late pregnancy) → fetal ultrasound monitoring (tachycardia + fetal goiter) + TRAb assay in 3rd trimester (ACOG 2020) | Thyroid management in pregnancy and postpartum: pre-existing hypothyroidism and pregnancy: increase L-T4 dose by 20-30 % as soon as pregnancy is confirmed (needs increase in 1st trimester) → target TSH: 4.0 mUI/L + anti-TPO positive or symptoms → target TSH <2.5 mUI/L; postpartum thyroiditis: occurs within 12 months of delivery + prevalence: 5-10 % of women + risk factors: anti-TPO positive before pregnancy (risk ×30) → classic biphasic course: thyrotoxic phase (1-4 months postpartum - destructive - release of stored hormones - low TSH + high T4 + collapsed uptake scintigraphy) → hypothyroid phase (4-8 months postpartum) → recovery in 80 % of cases in 12 months → 20 % → permanent hypothyroidism → treatment: thyrotoxic phase: βblockers if symptomatic (no ATS - destructive thyrotoxicosis - no excessive hormone synthesis) + hypothyroid phase: L-T4 if symptomatic or desire for pregnancy → gradual weaning at 12 months; iodine supplementation in pregnancy: 250 µg/d recommended → iodized salt + prenatal supplements with iodine → caution: especially women with GMN → excess iodine can trigger hypothyroidism (Wolff-Chaikoff effect) or hyperthyroidism (Jod-Basedow) in multinodular goiters → supplement with caution + TSH monitoring |
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A «cold» thyroid nodule on scintigraphy is not necessarily suspicious of malignancy if the TSH is normal: thyroid scintigraphy is only indicated if TSH is low or collapsed. When TSH is normal, almost all nodules are «cold» on scintigraphy, making it impossible to distinguish benign from malignant nodules. In this context, ultrasound with TI-RADS classification and fine needle aspiration (FNA) guide management - not scintigraphy.
Situations requiring urgent medical assessment
Goiter + progressive dyspnea + inspiratory stridor + positive Pemberton sign (venous congestion on raising the arms) → compressive goiter with tracheal stenosis or superior cave syndrome → urgent cervico-thoracic CT scan + endocrine surgery opinion → urgent surgical indication if tracheal stenosis <9 mm.
Sudden and rapid increase in Hashimoto's goiter + hard cervical adenopathy + general condition deterioration → primary thyroid lymphoma (MALT type) to be excluded → urgent CAF ± surgical biopsy → oncology-haematology opinion.
Fever + tachycardia + agitation + confusion + vomiting in a known hyperthyroid patient → thyrotoxic crisis (thyroid storm - Burch-Wartofsky score) → life-threatening emergency → PTU 500-1,000 mg by nasogastric tube + Lugol's iodine (1h after PTU) + dexamethasone 2 mg × 4/d + propranolol + intensive care → mortality 10-30 % even treated.
Firm or stony thyroid nodule + rapid growth in weeks + persistent hoarseness + ipsilateral cervical adenopathy + history of cervical irradiation or MEN2 syndrome → thyroid cancer to be ruled out urgently → CAF guided by ultrasound + serum calcitonin + endocrinology opinion + endocrine surgery.
Consult at Clinique Omicron
Clinique Omicron's physicians carry out the initial evaluation of the goiter - thyroid biology workup (TSH, antibodies, calcitonin), prescription of thyroid ultrasound, TI-RADS interpretation and referral to cytopuncture or endocrinology depending on the results. Medical follow-up for benign stable goiters, Hashimoto's thyroiditis and levothyroxine substitutions can be provided at one of our points of service in Quebec, or via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for information purposes only and does not replace the advice of a physician or endocrinologist. Any newly diagnosed or evolving goiter should be evaluated by a healthcare professional to identify its nature and guide appropriate management.
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