Thyroid Gland PDF

# THYROID GLAND ## I. THYROGLOSSAL DUCT CYST - **A.** Cystic dilation of thyroglossal duct remnant - 1. Thyroid develops at the base of tongue and then travels along the thyroglossal duct to the anterior neck. - 2. Thyroglossal duct normally involutes; a persistent duct, however, may under...

# THYROID GLAND ## I. THYROGLOSSAL DUCT CYST - **A.** Cystic dilation of thyroglossal duct remnant - 1. Thyroid develops at the base of tongue and then travels along the thyroglossal duct to the anterior neck. - 2. Thyroglossal duct normally involutes; a persistent duct, however, may undergo cystic dilation. - **B.** Presents as an anterior neck mass ## II. LINGUAL THYROID - **A.** Persistence of thyroid tissue at the base of tongue - **B.** Presents as a base of tongue mass # HYPERTHYROIDISM ## I. BASIC PRINCIPLES - **A.** Increased level of circulating thyroid hormone - 1. Increases basal metabolic rate (due to increased synthesis of Na+-K+ ATPase) - 2. Increases sympathetic nervous system activity (due to increased expression of __β₁-adrenergic receptors__) - **B.** Clinical features include - 1. Weight loss despite increased appetite - 2. Heat intolerance and sweating - 3. Tachycardia with increased cardiac output - 4. Arrhythmia (e.g., atrial fibrillation), especially in the elderly - 5. Tremor, anxiety, insomnia, and heightened emotions - 6. Staring gaze with lid lag - 7. Diarrhea with malabsorption - 8. Oligomenorrhea - 9. Bone resorption with hypercalcemia (risk for osteoporosis) - 10. Decreased muscle mass with weakness - 11. Hypocholesterolemia - 12. Hyperglycemia (due to gluconeogenesis and glycogenolysis) ## II. GRAVES DISEASE - **A.** Autoantibody (IgG) that stimulates TSH receptor (type II hypersensitivity) - **B.** Leads to increased synthesis and release of thyroid hormone - 1. Most common cause of hyperthyroidism - 2. Classically occurs in women of childbearing age (20-40 years) - **C.** Clinical features include - 1. Hyperthyroidism - 2. Diffuse goiter - Constant TSH stimulation leads to thyroid hyperplasia and hypertrophy (Fig. 15.1A). - 3. Exophthalmos and pretibial myxedema - i. Fibroblasts behind the orbit and overlying the shin express the TSH receptor. - ii. TSH activation results in glycosaminoglycan (chondroitin sulfate and hyaluronic acid) buildup, inflammation, fibrosis, and edema leading to exophthalmos and pretibial myxedema. - 4. Irregular follicles with scalloped colloid and chronic inflammation are seen on histology (Fig. 15.18). - **D.** Laboratory findings include - 1. __↑__ total and free T₄; __↓__ TSH (free T₄ downregulates TRH receptors in the anterior pituitary to decrease TSH release) - 2. Hypocholesterolemia - 3. Increased serum glucose - **E.** Treatment involves β- blockers, thioamide, and radioiodine ablation. - **F.** Thyroid storm is a potentially fatal complication. - 1. Due to elevated catecholamines and massive hormone excess, usually in response to stress (e.g., surgery or childbirth) - 2. Presents as arrhythmia, hyperthermia, and vomiting with hypovolemic shock - 3. Treatment is propylthiouracil (PTU), β- blockers, and steroids. - i. PTU inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis, as well as peripheral conversion of T₄ to T₃. ## III. MULTINODULAR GOITER - **A.** Enlarged thyroid gland with multiple nodules (Fig. 15.2) - **B.** Due to relative iodine deficiency - **C.** Usually nontoxic (euthyroid) - **D.** Rarely, regions become TSH-independent leading to T₄ release and hyperthyroidism ('toxic goiter'). # HYPOTHYROIDISM ## I. CRETINISM - **A.** Hypothyroidism in neonates and infants - **B.** Characterized by mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, and umbilical hernia - 1. Thyroid hormone is required for normal brain and skeletal development. - **C.** Causes include maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter, and iodine deficiency. - 1. Dyshormonogenetic goiter is due to a congenital defect in thyroid hormone production; most commonly involves thyroid peroxidase ## II. MYXEDEMA - **A.** Hypothyroidism in older children or adults - **B.** Clinical features are based on decreased basal metabolic rate and decreased sympathetic nervous system activity. - 1. Myxedema - accumulation of glycosaminoglycans in the skin and soft tissue; results in a deepening of voice and large tongue - 2. Weight gain despite normal appetite - 3. Slowing of mental activity - 4. Muscle weakness - 5. Cold intolerance with decreased sweating - 6. Bradycardia with decreased cardiac output, leading to shortness of breath and fatigue - 7. Oligomenorrhea - 8. Hypercholesterolemia - 9. Constipation - **C.** Most common causes are iodine deficiency and Hashimoto thyroiditis; other causes include drugs (e.g., lithium) and surgical removal or radioablation of the thyroid. # THYROIDITIS ## I. HASHIMOTO THYROIDITIS - **A.** Autoimmune destruction of the thyroid gland; associated with HLA-DR5 - 1. Most common cause of hypothyroidism in regions where iodine levels are adequate - **B.** Clinical features - 1. Initially may present as hyperthyroidism (due to follicle damage) - 2. Progresses to hypothyroidism; ↑ T₄ and ↑ TSH - 3. Antithyroglobulin and antithyroid peroxidase antibodies are often present (sign of thyroid damage). - **C.** Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles) is seen on histology (Fig. 15.3). - **D.** Increased risk for B-cell (marginal zone) lymphoma; presents as an enlarging thyroid gland late in disease course ## II. SUBACUTE GRANULOMATOUS (DE QUERVAIN) THYROIDITIS - **A.** Granulomatous thyroiditis that follows a viral infection - **B.** Presents as a tender thyroid with transient hyperthyroidism - **C.** Self- limited; rarely (15% of cases) may progress to hypothyroidism ## III. RIEDEL FIBROSING THYROIDITIS - **A.** Chronic inflammation with extensive fibrosis of the thyroid gland - **B.** Presents as hypothyroidism with a 'hard as wood, nontender thyroid gland - **C.** Fibrosis may extend to involve local structures (e.g., airway). - 1. Clinically mimics anaplastic carcinoma, but patients are younger (40s) and malignant cells are absent # THYROID NEOPLASIA ## I. BASIC PRINCIPLES - **A.** Usually presents as a distinct, solitary nodule - **B.** - 1. Thyroid nodules are more likely to be benign than malignant. - 2. ¹³¹I radioactive uptake studies are useful to further characterize nodules. - 1. Increased uptake ('hot' nodule) is seen in Graves disease or nodular goiter. - 2. Decreased uptake ('cold' nodule) is seen in adenoma and carcinoma; often warrants biopsy - **C.** Biopsy is performed by fine needle aspiration (FNA). ## II. FOLLICULAR ADENOMA - **A.** Benign proliferation of follicles surrounded by a fibrous capsule (Fig. 15.4) - **B.** Usually nonfunctional; less commonly, may secrete thyroid hormone ## III. PAPILLARY CARCINOMA - **A.** Most common type of thyroid carcinoma (80% of cases) - **B.** Exposure to ionizing radiation in childhood is a major risk factor. - **C.** Comprised of papillae lined by cells with clear, 'Orphan Annie eye' nuclei and nuclear grooves (Fig. 15.5A); papillae are often associated with psammoma bodies (Fig. 15.5B). - **D.** Often spreads to cervical (neck) lymph nodes, but prognosis is excellent (10-year survival > 95%) ## IV. FOLLICULAR CARCINOMA - **A.** Malignant proliferation of follicles surrounded by a fibrous capsule with invasion through the capsule (Fig. 15.6) - 1. Invasion through the capsule helps distinguish follicular carcinoma from follicular adenoma. - 2. Entire capsule must be examined microscopically. - 3. FNA only examines cells and not the capsule; hence, a distinction between follicular adenoma and follicular carcinoma cannot be made by FNA. - **B.** Metastasis generally occurs hematogenously. ## V. MEDULLARY CARCINOMA - **A.** Malignant proliferation of parafollicular C cells; comprises 5% of thyroid carcinomas - 1. C cells are neuroendocrine cells that secrete calcitonin. - 2. Calcitonin lowers serum calcium by increasing renal calcium excretion but is inactive at normal physiologic levels. - 3. High levels of calcitonin produced by tumor may lead to hypocalcemia. - 4. Calcitonin often deposits within the tumor as amyloid. - **B.** Biopsy reveals sheets of malignant cells in an amyloid stroma (Fig. 15.7). - **C.** Familial cases are often due to multiple endocrine neoplasia (MEN) 2A and 2B, which are associated with mutations in the RET oncogene. - 1. MEN 2 results in medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral mucosa (2B). - 2. Detection of the RET mutation warrants prophylactic thyroidectomy. ## VI. ANAPLASTIC CARCINOMA - **A.** Undifferentiated malignant tumor of the thyroid (Fig. 15.8); usually seen in elderly - **B.** Often invades local structures, leading to dysphagia or respiratory compromise - **C.** Poor prognosis