What are the differential diagnoses and management options for thyromegaly?

Thyromegaly: Differential Diagnoses and Management

Differential Diagnoses

Thyromegaly (goiter) has multiple etiologies that must be systematically evaluated, with the most common causes being autoimmune thyroiditis, multinodular goiter, Graves' disease, and malignancy.

Benign Causes

• Autoimmune (Hashimoto's) thyroiditis is the most common cause of nonendemic thyromegaly and acquired hypothyroidism in children and adolescents, presenting with palpable thyroid enlargement in 85% of cases 1
• Multinodular goiter presents as diffuse or nodular enlargement, often causing compressive symptoms including dyspnea, orthopnea, and dysphagia, particularly with substernal extension 2
• Graves' disease causes diffuse thyromegaly with hyperthyroidism and suppressed TSH 3
• Simple (colloid) goiter results from iodine deficiency or goitrogens in endemic areas 2

Malignant Causes

• Differentiated thyroid carcinoma (papillary or follicular) may present as thyromegaly with or without discrete nodules, requiring fine-needle aspiration for nodules ≥1 cm with suspicious ultrasound features 4
• Medullary thyroid cancer accounts for 5-7% of thyroid cancers and can be detected by elevated serum calcitonin, which should be measured as part of thyroid nodule evaluation 4
• Thyroid lymphoma and plasmacytoma are rare causes of diffuse thyromegaly that may present with compressive symptoms and require tissue diagnosis 5

Other Causes

• Thyroiditis (subacute, acute) presents with painful thyromegaly and transient thyroid dysfunction 1
• Infiltrative disorders including amyloidosis, sarcoidosis, and hemochromatosis are uncommon causes 5

Diagnostic Approach

Initial Laboratory Evaluation

• Measure serum TSH first as it is the single best initial test of thyroid function and significantly impacts management, with elevated TSH (>1.64 mU/L) substantially increasing malignancy risk in nodular disease 6, 7
• Free T4 measurement should follow if TSH is abnormal to classify the thyroid dysfunction as primary hypothyroidism (elevated TSH, low free T4), subclinical hypothyroidism (elevated TSH, normal free T4), hyperthyroidism (suppressed TSH, elevated free T4), or subclinical hyperthyroidism (suppressed TSH, normal free T4) 3, 7, 8
• Anti-TPO antibodies should be measured when autoimmune thyroiditis is suspected based on clinical presentation or ultrasound findings 7, 1
• Serum calcitonin should be measured as an integral part of thyroid nodule evaluation to screen for medullary thyroid cancer, as it has higher sensitivity than fine-needle aspiration for this malignancy 4

Imaging Studies

• Neck ultrasound is essential to assess thyroid size, echotexture, presence of nodules, and cervical lymphadenopathy 4, 3, 6
• Ultrasound findings in autoimmune thyroiditis show inhomogeneous and hypoechoic pattern in 94% of cases 1
• Thyroid scan with technetium-99m should be performed when TSH is suppressed with normal free T4 to determine if nodules are hyperfunctioning (hot) or non-functioning (cold) 3
• CT scan of neck and chest is indicated when substernal extension is suspected or to evaluate compressive symptoms, showing the extent of mediastinal involvement 2, 5

Tissue Diagnosis

• Fine-needle aspiration biopsy (FNAB) is recommended for solid hypoechoic nodules ≥1 cm or with suspicious ultrasound characteristics (hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, regional lymphadenopathy) 4, 3
• FNAB should be repeated if initial samples are inadequate; false negatives occur in 5-10% of cases, so maintain clinical suspicion if other worrisome features are present 3
• For follicular neoplasia with normal TSH and cold appearance on thyroid scan, surgery should be considered as FNAB cannot distinguish benign from malignant follicular lesions 4

Management Based on Etiology

Autoimmune Thyroiditis

• Levothyroxine therapy is indicated for patients with hypothyroidism (elevated TSH with low or normal free T4) 9, 1
• Starting dosage for adults with primary hypothyroidism is 1.6 mcg/kg/day, with dose adjustment based on serum TSH levels monitored at 6-8 week intervals 9
• In pediatric patients, monitor TSH and total or free-T4 at 2 and 4 weeks after initiation, 2 weeks after any dosage change, then every 3-12 months until growth is completed 9
• Thyromegaly decreases in approximately one-third of patients during follow-up with levothyroxine treatment 1

Multinodular Goiter with Compressive Symptoms

• Surgical management (total or near-total thyroidectomy) is recommended for goiters causing compressive symptoms including dyspnea, orthopnea, and dysphagia 2
• Several studies demonstrate improved breathing and swallowing outcomes after thyroidectomy for symptomatic goiters 2
• Preoperative planning must include careful assessment of airway anatomy, consideration of anesthesia type and intubation method, and close collaboration between experienced surgical and anesthesia teams 2
• Potential complications include bleeding, airway distress, recurrent laryngeal nerve injury (<1-2% in expert hands), and transient hypoparathyroidism 4, 2

Hyperfunctioning Nodules (Suppressed TSH)

• For hyperfunctioning (hot) nodules identified on thyroid scan, therapy options include radioactive iodine (I-131) ablation or surgical removal 3
• Ablative therapy guided by ultrasound is an option for benign nodules ≥2 cm causing compressive symptoms or aesthetic concerns 3
• Propylthiouracil may be used for hyperthyroidism management, particularly in the first trimester of pregnancy, though patients must be counseled about rare but severe hepatotoxicity risk and monitored for symptoms of liver dysfunction 10

Differentiated Thyroid Cancer

• Total or near-total thyroidectomy is the initial treatment for differentiated thyroid carcinoma ≥1 cm, or regardless of size if metastatic, multifocal, or familial 4
• Neck ultrasound should always precede surgery to assess lymph node status; compartment-oriented lymph node dissection should be performed when lymph node metastases are suspected or proven 4
• Radioiodine ablation (131-I) is recommended post-operatively in high-risk and low-risk patients to ablate remnant thyroid tissue and potential microscopic residual tumor, but not in very low-risk patients (unifocal T1 tumors <1 cm with favorable histology, no extrathyroidal extension or lymph node metastases) 4
• Preparation for radioiodine ablation is based on recombinant human TSH (rhTSH) administration while continuing levothyroxine therapy, which is highly effective and safe with similar ablation rates to levothyroxine withdrawal 4

Post-Treatment Surveillance for Thyroid Cancer

• At 2-3 months post-treatment, check thyroid function tests (FT3, FT4, TSH) to verify adequate levothyroxine suppressive therapy 11
• At 6-12 months, perform physical examination, neck ultrasound, and rhTSH-stimulated serum thyroglobulin (Tg) measurement with or without diagnostic whole body scan 11
• Low-risk patients with undetectable stimulated Tg (<1.0 ng/ml) and normal neck ultrasound are considered in complete remission with recurrence risk <1% at 10 years and may shift from suppressive to replacement levothyroxine therapy (TSH within normal range) 11
• High-risk patients in remission should maintain suppressive levothyroxine doses (TSH 0.1 mIU/L) for 3-5 additional years 11
• Annual surveillance for disease-free patients includes physical examination, basal serum Tg measurement, and neck ultrasound 11

Critical Management Pitfalls

• Never rely on Tg measurements in the presence of Tg antibodies, as they invalidate the results 11
• Do not omit neck ultrasound evaluation, as it detects structural disease that may not correlate with Tg levels and can identify suspicious lymphadenopathy 11, 6
• Avoid routine suppressive levothyroxine therapy for benign nodules, as it may cause or worsen osteoporosis, especially in postmenopausal women 3
• Recognize delayed diagnosis of autoimmune thyroiditis: the high proportion of hypothyroid patients at diagnosis (44% in one series) reflects diagnostic delay, with symptoms present for median 9 months in hypothyroid patients 1
• Monitor for severe complications with propylthiouracil: cases of vasculitis resulting in severe complications and death have occurred; patients must promptly report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 10
• Maintain clinical suspicion despite negative FNAB: false negatives occur in 5-10% of cases, so consider surgery if other worrisome clinical or ultrasound features persist 3