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THYROID GLAND MJ Noon 2014-57 Anatomy of the thyroid gland •Light brown, firm organ •15 – 20 gms in weight •Two lateral lobes connected by an isthmus •4 x 2 cm in dimension; 20 – 40 mm thickness •Pyramidal lobe present in 80% of normal persons; usually left of midline •Four parathyroid glands closely related •Recurrent laryngeal nerves on both sides Anatomy of the thyroid gland Biosynthesis of T4 and T3 The process includes • Dietary iodine (I) ingestion • Active transport and uptake of iodide (I-) by thyroid gland • Oxidation of I- and iodination of thyroglobulin (Tg) tyrosine residues • Coupling of iodotyrosine residues (MIT and DIT) to form T4 and T3 • Proteolysis of Tg with release of T4 and T3 into the circulation 4 Regulation of TH synthesis/secretion Normal circulatory concentrations – T4 4.5-11 g/dL – T3 60-180 ng/dL (~100-fold less than T4) 6 Carriers for Circulating Thyroid Hormones • More than 99% of circulating T4 and T3 is bound to plasma carrier proteins – Thyroxine-binding globulin (TBG), binds about 75% – Transthyretin (TTR), also called thyroxine-binding prealbumin (TBPA), binds about 10%-15% – Albumin binds about 7% – High-density lipoproteins (HDL), binds about 3% • Carrier proteins can be affected by physiologic changes, drugs, and disease 7 Thyroid Hormone Plays a Major Role in Growth and Development • Thyroid hormone initiates or sustains differentiation and growth – Stimulates formation of proteins – Is essential for normal brain development • Essential for childhood growth – Untreated congenital hypothyroidism or chronic hypothyroidism during childhood can result in incomplete development and mental retardation 8 Thyroid Hormones and the Central Nervous System (CNS) • Thyroid hormones are essential for neural development and maturation and function of the CNS • Decreased thyroid hormone concentrations may lead to alterations in cognitive function – Patients with hypothyroidism may develop impairment of attention, slowed motor function, and poor memory – Thyroid-replacement therapy may improve cognitive function when hypothyroidism is present 9 Thyroid Hormone Influences the Female Reproductive System • Normal thyroid hormone function is important for reproductive function – Hypothyroidism may be associated with menstrual disorders, infertility, risk of miscarriage, and other complications of pregnancy 10 Thyroid Hormone is Critical for Normal Bone Growth – T3 also may participate in osteoblast differentiation and proliferation, and chondrocyte maturation leading to bone ossification 11 Thyroid Hormone Regulates Mitochondrial Activity • T3 is considered the major regulator of mitochondrial activity – A potent T3-dependent transcription factor of the mitochondrial genome induces early stimulation of transcription and increases transcription factor (TFA) expression – T3 stimulates oxygen consumption by the mitochondria 12 Thyroid Hormones Stimulate Metabolic Activities in Most Tissues • Thyroid hormones (specifically T3) regulate rate of overall body metabolism – T3 increases basal metabolic rate • Calorigenic effects – T3 increases oxygen consumption by most peripheral tissues – Increases body heat production 13 Evaluation of patients with Thyroid gland disorder THREE MAIN CATEGORIES • HYPOFUNCTION • HYPERFUNCTION • ENLARGMENTS/GOITER – DIFFUSE ENLARGMENT – NODULAR ENLARGMENT Thyroid Disease Spectrum 15 Clinical evaluation • • • HISTORY AND PHYSICAL EXAMINATION Clinical manifestations: – HYPERFUNCTION • Weight loss, irritability, heat intolerance, thinning of hair, palpitations, tachycardia – HYPOFUNCTION • Weight gain, lethargy, coarse hair, cold intolerance, thick skin, slowed muscle reflex, constipation, slow mentation – GOITER • Anterior neck mass that moves on deglutition is thyroid gland in origin unless proven otherwise; enlarged thyroid gland Physical Examination: – Accurate description of the thyroid gland and mass – Appreciate presence or absence of associated cervical lymphadenopathy Thyroid Function Tests • T3 AND T4 LEVELS • Serum TSH and TRH • Free and bound ratio • Plain films; X-Rays(chest/thoracic inlet;clinical evidence of tracheal deviation,compression,retrosternal extension) • Ultrasonography(solid/cystic)or radioisotope scanning(99mTcsodium pertechnate) for differentiating between A. HOT nodules (actively functioning) B. COLD nodules (non-functioning) C. COOL (normaly functioning) MRI and CT (EXTENT OF GOITRE) FNAC(nature of thyroid nodules) Thyroid antibodies HYPERTHYROIDISM • Clinical syndrome of excess thyroid hormone in the circulation • Two dominant types or causes: – Grave’s disease – Toxic multinodular or solitary nodular goiter (Plummer’s disease) • Can be PRIMARY (increased Thyroid hormone independent of TSH) or SECONDARY (increased in hormone due to increased TSH) HYPERTHYROIDISM/THYROTOXICOSIS I. II. III. IV. V. VI. SIGNS sinus Tachycardia Hot,moist palms Exosphthalmos Lid lag Agitation Thyroid goitre SYMPTOMS I. Tiredness II. Emotional lability III. Heat intolerance IV. Wt.loss V. Excessive appetite VI. palpitations 19 Graves’ disease (diffuse toxic goiter) • Most common cause of primary hyperthyrodism • Female dominant autoimmune disease • Inciting events; infection, steroid withdrawal, postpartum, iodide excess • Anti-TSH receptor antibodies(IgG),type2 hypersensitivity • TSI can cross placenta so neonatal thyrotoxicosis can occur • LABS; A. Raised T3,T4 B. Low TSH C. TSH producing response to TRH is absent because of atrophy of pituitary TSH producing cells Graves’ Disease • CLINACAL FEATURES; INFILTRATIVE OPHTHALMOPATHY Proptosis of eye(volume of retro-orbital connective tissue is increased; inflamation,GAGS,fatty infiltration;orbital fibroblasts have TSH receptor and become targets of antibody attack) Pretibial myxedema( GAGS in dermis) Thyroid acropachy; a) Digital swelling b) Finger clubbing • • • Cardiac problems;CHF,AF Apathy,muscle weakness thyromegaly 21 Graves’ Disease 22 Graves’ Disease • Manage graves by 1)anti-thyroid drugs and,2)radioactive iodine ablation<CI in preg.> 3)surgery; subtotal-thyroidectomy 23 Multinodular Toxic Goiter (Plummer’s disease) • One or more thyroid nodules trapping and organifying more iodine and increase secretion of hormone independent of TSH control; autonomously functioning nodule/s • No exophthalmos or pretibial myxoedema (Milder with no extrathyroidal manifestations) • Demonstrate increased uptake or radioactive iodine I131 localized to the nodule/s • Hot nodules on scan • Poor response to radioactive iodine treatment; surgery is the choice of management Thyroid Storm • • • • Rare but life-threatening complication of hyperthyroidism Induced by thyroidal or non-thyroidal surgery; can be induced by infection or other forms of stress (eg. Labor & delivery, pulmonary infection, after RAI treatment) Signs and symptoms of severe thyrotoxicosis – Hyperpyrexia, severe tachycardia, irritability, vomiting, diarrhea, and proximal muscle weakness; cause of death due to high cardiac output Management: – Prevention is the best management – Immediate control of tachycardia, mechanical cooling, oxygen and volume resuscitation – Steroids – Intravenous beta-blockers (propranolol) – Anti-thyroid drugs and Iodine solution – Peritoneal dialysis in extreme cases Hyperthyroidism DIFFUSE GLAND ENLARGMENT PRETIBIAL MYXEDEMA GRAVE’S OPHTHALMOPATHY Hyperthyroidism DIAGNOSIS • History and Physical Examination • Thyroid Function tests • Radioactive iodine thyroid scan • Ultrasonography MANAGEMENT • MEDICAL MANAGEMENT – Anti-thyroid drugs (methimazole, PTU) – Beta-blockers (propranolol) – Radioactive Iodine • SURGERY – Subtotal thyroidectomy; Lobectomy • RADIOACTIVE IODINE TREATMENT – Diffuse = 7 – 9 mCi – Nodular = 12 – 15 mCi RADIOACTIVE IODINE SCAN (Iodine 131) HYPOTHYROIDISM • Syndrome of deficient circulating levels of thyroid hormone • Cretinism in neonates – neurological impairment and mental retardation • Clinical manifestations: – Myxedema (severe form) – Bradycardia & cardiomegaly • Laboratory: – Decreased T3 and T4; Elevated TSH • Management: – Thyroxine replacement THYROID CANCER • The most common endocrine malignancy that requires surgery • Included in the top 10 sites of malignancy for both sexes in the Philippines • Generally slow-growing and indolent malignancy • AGE – considered the most important prognostic factor • Certain types are also aggressive malignancy and potentially fatal disease THYROID CANCER • MAJOR HISTOLOGIC TYPES • PAPILLARY THYROID CANCER – Most common (70%); well-differentiated – Slow-growing; lymphatic spread – Good prognosis • FOLLICULAR THYROID CANCER – Well-differentiated; 2nd most common (10%) – More aggressive; vascular invasion and spread • MIXED PAPILLARY-FOLLICULAR THYROID CANCER – Behaves and managed as papillary carcinoma • HURTHLE-CELL TUMOR – 5% incidence; intermediate differentiation – Behaves like follicular carcinoma but spread by lymphatics THYROID CANCER • MAJOR HISTOLOGIC TYPES • LYMPHOMA (5%) – Usually in females; history of previous hashimoto’s – Surgery for compressive symptoms – Chemo and radiation sensitive • MEDULLARY THYROID CANCER – Aggressive; calcitonin producing tumor – 90% sporadic; 10% part of the MEN II syndrome – Does not uptake I131 – Poor prognosis; undifferentiated carcinoma • ANAPLASTIC THYROID CANCER – Worst prognosis; very aggressive – 30% developed from well-differentiated cancer (degeneration) – Chemo and radiation treatment – Palliatve surgery THYROID CANCER • MANAGEMENT • SURGERY • LOBECTOMY + ISTHMUSECTOMY • TOTAL THYROIDECTOMY • INDICATED NECK DISSECTION • ADJUVANT TREATMENT • POSTOPERAIVE RADIOACTIVE IODINE TREATMENT • EXTERNAL BEAM RADIATION • CHEMOTHERAPY (emerging) INDICATIONS FOR THE PERFORMANCE OF THYROID SURGERY • Thyroid enlargement (Goiter) causing compression symptoms (dysphagia, dyspnea) • Certain types of Hyperthyroidism • Thyroid Nodule/s or Thyroid Cancer • Cosmetic indication Types of thyroid surgeries • • • • SUBTOTAL-THYROIDECTOMY TOTAL-THYROIDECTOMY(bilateral lobectomy) ISTHMUSECTOMY NEAR-TOTAL THYROIDECTOMY(total thyroid lobectomy on affected side with conservation of 12grm of thyroid on contralateral side to preserve blood flow to parathyroids 34 Complications of thyroid surgery HAEMORRHAGE NERVE DAMAGE HYPOTHYROIDISM HYPOPARATHYROIDISM Wound infection(abscess must be drained) Respiratory obstruction(kinking of trachea,laryngeal oedema,trauma during intubation) Technique of thyroidectomy Technique of thyroidectomy Technique of thyroidectomy Technique of thyroidectomy Technique of thyroidectomy THANK YOU