Thyroid gland diseases Dr.Isazadehfar Synthesis and Secretion Follicular cells arranged in clumps Clumps of cells contain colloid Colloid an iodine containing protein called thryoglobulin. This is the precursor and storage form of thyroid hormone Thyroxine (T4), Triiodothyronone (T3) Thyroid hormone action T4 and T3 circulate in the blood bound to plasma proteins. TBG(70%), TBPA(20%) and albumin(10%). T3 is the active form, 5 times more active than T4. T4 is converted to T3 outside the thyroid, mostly in liver and kidney. T3 binds to a nuclear receptor Regulation of the H-P-T axis TRH secreted from hypothalamus controls TSH production. TSH from anterior pituitary stimulates secretion of T4 and T3 from thyroid Regulated by a negative feedback loop Hypothyroidism Prevalence of Hypothyroidism Prevalence is 14/1000 females and 1/1000 males Other autoimmune diseases Family history of autoimmune diseases Primary hypothyroidism-Causes Autoimmune thyroiditis (Hashimotos)(most common in adults) Radioactive iodine Post thyroidectomy Anti-thyroid drugs (CMZ PTU) Lithium - Amioderone Iodine deficiency Subacute thyroiditis Infiltrative disease Agenesis Secondary hypothyroidism-causes Hypothalamic disease Pituitary disease Clinical features General and CVS Tiredness Weight gain Cold intolerance Goitre Constipation Hair loss Bradycardia Angina Cardiac Failure Pericardial effusion Hypothermia Clinical Features Neurological and Haematological Aches and Pains Carpal Tunnel Deafness Hoarseness Ataxia Depression Psychosis Iron deficiency A Pernicious Anemia Clinical Features Skin and Reproduction Dry skin Erythema Vitiligo Infertility Menorrhagia Galactorrhoea Amenorrhea Laboratory Diagnosis T4/FT4 reduced T3/FT3 reduced TSH elevated Thyroid Antibodies may indicate aetiology If TSH is reduced or normal in the presence of a low T4, pituitary function necessary Additional abnormal tests Fasting cholesterol and triglycerides may be raised AST and LDH may be raised CK , Chol , Triglyceride Normochromic or macrocytic anemia ECG: Bradycardia with small QRS complexes Treatment Levothyroxine If no residual thyroid function 1.5 g/kg/day Patients under age 60, without cardiac disease can be started on 50 100 g/day. Dose adjusted according to TSH levels In elderly especially those with CAD the starting dose should be much less 12.5 25 g/day Compliance and adequacy of dose checked by TSH measurements Try to maintain TSH in normal range Subclinical Hypothyroidism Primary thyroidal failure (Hashimotos) is a gradual process Non specific symptoms Reduced thyroid activity has been compensated by an increase TSH output to maintain a euthyroid state Normal T4/FT4 with elevated TSH Thyroid antibodies usually positive Treatment Repeat tests after an interval If TSH is continuing to rise in the presence of strongly positive antibodies, the risk of developing hypothyroidism in the future is high. Thus treatment with thyroxin at this early stage may be justified if symptomatic Beware: Thyroxine may not cure all symptoms Myxoedema Coma Requires prompt treatment. Mortality of 50%. Suspect in cases of hypothermia T3 20 g bid IM Steroids recommended Glucose to correct hypoglycaemia Rewarming Assisted ventilation Thyroid hormone deficiency in Pregnancy Goitre is common in pregnant women TBG increased, thus total T4 and T3 increased. FT4 and FT3 are normal and TSH remains unchanged. Hypothyroidism treated with thyroxin during pregnancy. Dose requirements increase. A change in dose usually needed each trimester. Post-partum thyroiditis Incidence is about 9%. Transitory or permanent Early hyperthyroidism,later hypothyroidism,euthyroid later. Increased microsomal antibodies. Thyroxine Elderly Non specific symptoms Osteoporosis Anemia Heart Failure Treatment with thyroxine Start with small doses and titrate slowly. (25 g). Summary Suspicion Women Previous thyroid disease or treatment Other autoimmune diseases Elderly- caution with treatment HYPERTHYROIDISM Prevalence Women 2% Men 0.2% 15% of cases occur in patients older than 60 years of age Mechanism of Clinical Symptoms 1. Catabolism 2. Enhancement of sensitivity to catecholamines Hyperthyroidism Symptoms Hyperactivity/ irritability/ dysphoria Heat intolerance and sweating Palpitations Fatigue and weakness Weight loss with increase of appetite Diarrhoea Polyuria Oligomenorrhoea, loss of libido Hyperthyroidism Signs Tachycardia (AF) Tremor Goiter Warm moist skin Proximal muscle weakness Lid retraction or lag Gynecomastia Causes of Hyperthyroidism Most common causes Graves disease Toxic multinodular goiter Autonomously functioning nodule Rarer causes Thyroiditis or other causes of destruction Thyrotoxicosis factitia Iodine excess (Jod- Basedow phenomenon) Struma ovarii Secondary causes (TSH or HCG) Graves Disease Autoimmune disorder Ab s directed against TSH receptor with intrinsic activity. Thyroid and fibroblasts Responsible for 60-80% of Thyrotoxicosis More common in women Graves Disease Eye Signs N- No signs or symptoms O Only signs (lid retraction or lag) no symptoms S Soft tissue involvement (peri- orbital oedema) P Proptosis (>22 mm)(Hertls test) E Extra ocular muscle involvement (diplopia) C Corneal involvement (keratitis) S Sight loss (compression of the optic nerve) Graves Disease Other Manifestations Pretibial mixoedema Thyroid acropachy Onycholysis Thyroid enlargement with a bruit frequently audible over the thyroid Onycholysis : softening of nails and loosening of nail beds Low total cholesterol Low HDL Low total cholesterol/HDL ratio Diagnosis of Graves Disease TSH , free T4 Thyroid auto antibodies Nuclear thyroid scintigraphy (I 123, Te 99 ) Treatment of Graves Disease Reduce thyroid hormone production or reduce the amount of thyroid tissue Antithyroid drugs: propyl-thiouracil, carbimazole Radioiodine Subtotal thyroidectomy relapse 4-6 W after antithyroid therapy(euthyroid), pregnancy, young people? Smptomatic treatment Propranolol Neoplastic Thyroid Disease Thyroid Nodules Goiter Multinodular Diffuse Endemic Thyroid Cancer Well differentiated and poorly differentiated Thyroid Nodular Disease Thyroid gland nodules are common in the general population Mainly in women Most thyroid nodules are benign Less than 5% are malignant Only 8% to 10% of patients with thyroid nodules have thyroid cancer Multinodular Goiter (MNG) MNG is an enlarged thyroid gland containing multiple nodules The thyroid gland becomes more nodular with increasing age In MNG, nodules typically vary in size Most MNGs are asymptomatic MNG may be toxic or nontoxic Toxic MNG occurs when multiple sites of autonomous nodule hyperfunction develop, resulting in thyrotoxicosis Toxic MNG is more common in the elderly Endemic Goiter No longer a problem in the developed world Still a serious health concern in parts of the world with iodine deficiency including mountainous areas or areas with high rainfall/flooding Kaplan, E. et al. Thyroid Disease Manager Surgery of the Thyroid Gland Chapter 21, May 99 Thyroid Carcinoma Incidence Thyroid carcinoma occurs relatively infrequently compared to the common occurrence of benign thyroid disease Thyroid carcinomas Papillary (70%) Follicular (15%) Medullary thyroid (5%) Anaplastic carcinoma (5%) Primary thyroid lymphomas (5%) Metastatic from other primary sites (rare) Risk factors for Malignancy Solitary thyroid nodules in patients >60 or 3 or 4 cm) Growth of nodule Evaluating Thyroid Nodules TSH measurement Ultrasound of the thyroid Fine needle aspiration Radioactive iodine imaging Thyroid Ultrasonography Excellent for characterizing size and other features of nodule Useful in localizing nodule for FNA Cannot distinguish between benign vs. malignant Thyroid FNA Now considered the most cost effective and sensitive/specific diagnostic test of thyroid nodules The use of US has expanded the role of FNA in evaluating nodules and improved the validity of the results Typical Presentation of Thyroid Cancer Painless lump Normal thyroid function tests Found on routine examination or by the patient Slow growth or no growth over several months Types of Thyroid Cancer Papillary :develops from thyroid follicle cells in 1 or both lobes; grows slowly but can spread Follicular :common in countries with insufficient iodine consumption; lymph node metastases are uncommon Medullary: develops from C-cells, can spread quickly; sporadic and familial types Anaplastic: develops from existing papillary or follicular cancers; aggressive, usually fatal Lymphoma: develops from lymphocytes; uncommon Papillary Thyroid Cancer Most common type Makes up about 70% of all thyroid carcinomas Females outnumber males 3:1 Highest incidence in women in midlife Papillary Thyroid Cancer Characteristics Unencapsulated tumor nodule with ill-defined margins Tumor typically firm and solid May present as nodal enlargement Commonly metastasizes to neck and mediastinal lymph nodes 40% to 60% in adults and 90% in children