Diseases of the Thyroid Gland

1. Classification of Thyroid Diseases

• Hyperthyroidism (thyrotoxicosis) — excess thyroid hormone
• Hypothyroidism — deficient thyroid hormone
• Euthyroid goiter — enlarged gland with normal function

• Hashimoto (chronic autoimmune) thyroiditis
• Subacute granulomatous thyroiditis (de Quervain)
• Subacute lymphocytic (painless/postpartum) thyroiditis
• Riedel thyroiditis (fibrous)

• Benign: follicular adenoma
• Malignant: papillary carcinoma, follicular carcinoma, medullary carcinoma, anaplastic carcinoma

• Diffuse goiter
• Multinodular goiter (simple or toxic/Plummer syndrome)

2. Methods of Examining Patients

History & Physical Examination

• Symptoms of hyper- or hypothyroidism; neck mass, pain, dysphagia, hoarseness, dyspnea
• Palpation: size, consistency, nodularity, tenderness of the gland; regional lymph nodes
• Signs of systemic effects: exophthalmos, pretibial myxedema, tremor, bradycardia/tachycardia

Laboratory Tests

• TSH — the single most sensitive screening test; suppressed in hyperthyroidism, elevated in primary hypothyroidism
• Free T4 and free T3 — confirm the functional state; T3 toxicosis may show elevated T3 with normal/low T4
• Thyroid autoantibodies: anti-TPO (anti-thyroid peroxidase) and anti-thyroglobulin in Hashimoto; TSI (thyroid-stimulating immunoglobulins) / TRAb (TSH receptor antibodies) in Graves disease
• Calcitonin + CEA — elevated in medullary thyroid carcinoma; useful pre- and postoperatively
• Thyroglobulin — tumor marker for differentiated thyroid carcinoma post-thyroidectomy

Imaging

• Ultrasound — first-line imaging; assesses size, echotexture, nodule morphology (suspicious features: hypoechoic, irregular borders, microcalcifications, taller-than-wide shape, absent halo)
• Radionuclide scanning (⁹⁹ᵐTc or ¹²³I) — "hot" (functional) nodules are almost always benign; "cold" nodules carry higher malignancy risk; diffusely increased uptake in Graves; decreased uptake in thyroiditis
• CT/MRI — assess substernal extension, tracheal deviation, lymphadenopathy, surgical planning

Fine-Needle Aspiration Biopsy (FNA)

• The most definitive pre-operative tool for thyroid nodules
• Indications based on ultrasound risk stratification (size + suspicious features)
• Reported by Bethesda System (I–VI: non-diagnostic → malignant)
• Molecular analysis (BRAF, RAS, RET/PTC fusions) aids cases with indeterminate cytology (Bethesda III/IV)

3. Clinical Presentation

Hyperthyroidism

Hypothyroidism

Hashimoto Thyroiditis

• Most common cause of goitrous hypothyroidism in the developed world
• Autoimmune; anti-TPO and anti-thyroglobulin antibodies destroy follicles via cytotoxic T cells and antibody-dependent cytotoxicity
• Gland enlarged, rubbery; histology: lymphocytic infiltrate with germinal centers, Hürthle (oxyphilic) cell metaplasia of follicular epithelium, follicular atrophy
• Associated with increased risk of thyroid lymphoma (marginal zone B-cell type)
• Patients may pass through a transient thyrotoxic phase ("Hashitoxicosis") before becoming hypothyroid

Goiter

• Diffuse goiter: compensatory TSH-driven hypertrophy from iodine deficiency; follicles crowded with columnar cells; usually euthyroid
• Multinodular goiter: long-standing diffuse goiters develop asymmetric nodularity from recurrent cycles of hyperplasia and involution; degenerative changes (fibrosis, hemorrhage, calcification, cysts)
• Toxic multinodular goiter (Plummer syndrome): ~10% of long-standing MNG develop autonomous nodules → thyrotoxicosis without ophthalmopathy or dermopathy
• Mass effects: airway obstruction, dysphagia, superior vena cava syndrome (substernal extension)

Thyroid Neoplasms

4. Conservative (Medical) Treatment

Hyperthyroidism

• Thionamides: Propylthiouracil (PTU) and methimazole inhibit oxidation of iodide, blocking thyroid hormone synthesis; PTU additionally inhibits peripheral T4→T3 deiodination (preferred in thyroid storm and first trimester pregnancy); methimazole preferred otherwise (once-daily dosing, fewer side effects)
• Beta-blockers (propranolol, atenolol): rapid symptomatic relief of adrenergic symptoms (tachycardia, tremor, anxiety); does not reduce hormone levels
• Radioactive iodine (¹³¹I): definitive treatment for Graves disease and toxic nodular goiter in most adults; destroys thyroid tissue; majority become hypothyroid requiring lifelong levothyroxine; contraindicated in pregnancy and in patients with active/severe thyroid eye disease (may worsen ophthalmopathy)
• Lugol's iodine / potassium iodide: large doses block thyroid hormone release (Wolff-Chaikoff effect); used pre-operatively to reduce vascularity, or in thyroid storm
• Thyroid storm management: PTU + beta-blockers + high-dose iodine + corticosteroids (inhibit T4→T3 conversion and autoimmunity) + supportive ICU care
• Graves ophthalmopathy: selenium (mild-moderate); glucocorticoids + orbital radiation (moderate-severe); orbital decompression surgery (sight-threatening)

Hypothyroidism

• Levothyroxine (L-T4): mainstay of treatment; synthetic T4 converted to active T3 in peripheral tissues; dose titrated to normalize TSH (target: 0.5–2.5 mU/L); taken fasting, 30–60 min before breakfast
• Myxedema coma: IV levothyroxine (300–500 mcg loading dose) ± IV liothyronine (T3), hydrocortisone (relative adrenal insufficiency), warming, ventilatory support
• Congenital hypothyroidism: immediate thyroid hormone replacement after newborn screening to prevent irreversible neurological damage

Thyroiditis

• Hashimoto: levothyroxine if hypothyroid; no specific treatment if euthyroid
• Subacute granulomatous (de Quervain): self-limiting; NSAIDs/aspirin for pain; corticosteroids (prednisone) for severe cases; beta-blockers for thyrotoxic phase; usually resolves in 6–8 weeks
• Postpartum/painless thyroiditis: beta-blockers for thyrotoxic phase; levothyroxine if hypothyroid phase prolonged

5. Surgical Treatment

Indications for Surgery

• Large or compressive goiter (airway/dysphagia symptoms)
• Substernal goiter
• Suspicious or malignant thyroid nodule
• Thyroid carcinoma
• Toxic goiter refractory to or unsuitable for medical/radioiodine therapy
• Cosmetically unacceptable goiter
• Prophylactic thyroidectomy in RET mutation carriers (MEN2)

Types of Operations

Post-Thyroidectomy Management

• Levothyroxine replacement (all total thyroidectomy patients)
• TSH suppression therapy (in differentiated carcinoma — high-risk patients)
• Radioiodine (¹³¹I) ablation post-thyroidectomy for differentiated carcinoma to destroy remnant tissue and facilitate surveillance via thyroglobulin
• Calcium/vitamin D supplementation if permanent hypoparathyroidism develops (inadvertent parathyroid removal)
• Thyroglobulin monitoring as tumor marker for recurrence in differentiated carcinoma
• Calcitonin/CEA monitoring in medullary carcinoma

Surgical Complications

• Recurrent laryngeal nerve injury → hoarseness (unilateral) or respiratory compromise (bilateral)
• Hypoparathyroidism → hypocalcemia, tetany (paresthesias, Chvostek/Trousseau signs)
• Hemorrhage → potentially life-threatening airway compression
• Wound infection, seroma

Summary of Key Diagnostic Lab Values