Thyroid disorders
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  • 1. Thyroid Gland Disorders
  • 2. Thyroid Gland: Introduction  The largest pure endocrine gland (15-25 gm), located in the anterior neck  Consists of two lateral lobes connected by a median tissue mass called the isthmus. 2
  • 3. Thyroid Gland: introduction  Blood supply  Arterial blood supply  Superior thyroid artery from external carotid  Inferior thyroid artery from subclavians  Blood flow 4-6 ml/min/gm  Venous blood supply  Three pairs of veins supply blood to the gland
  • 4.  The thyroid gland is made up of closely packed sacs called thyroid follicles.  The structural and functional unit of thyroid gland.  Cyst-like structure  0.2 – 0.9 mm in diameter  Simple cuboidal epithelial (follicular cells) surrounding a lumen filled with colloid.  T4 and T3 present in colloid bound to a large protein called thyroglobulin. Thyroid Gland: introduction
  • 5. Thyroid follicles
  • 6. Development  from the floor of the primitive pharynx during the third week of gestation  developing gland migrates along the thyroglossal duct to reach its final location in the neck  rare ectopic location of thyroid tissue at the base of the tongue (lingual thyroid)  occurrence of thyroglossal duct cysts along this developmental tract
  • 7.  Thyroid gland secret 3 hormones  Thyroxin or (T4)  Tri-iodotyronine or (T3)  Main hormones secreted by thyroid gland  Secreted by follicular cells  Amino acid derivatives (tyrosine)  Calcitonin  Produced by parafollicular cells – C cells Thyroid Gland: Introduction
  • 8. Regulation of Thyroid Axis  TSH –  Thyrotrope cells of ant. Pituitary  31 kDa hormone α and β subunits  α subunit similar to LH, FSH and hCG  Stimulated by TRH  TSH, TRH supressed by Thyroxine
  • 9. Actions of Thyroid Hormones  Increase the body’s overall basal metabolic rate  Increase oxygen consumption  Essential for normal growth  Mental development  Sexual maturation  Increase the sensitivity of CVS and CNS to catecholamines (↑COP and HR)
  • 10. Thyroid disorders  Hypothyroidism  Underactive thyroid  Hyperthyroidism  Overactive thyroid  Goiter  Thyroid enlargement
  • 11. 12 Hypothyroidism Definition  A clinical and biochemical syndrome that results from a deficiency in thyroid hormone secretion from thyroid gland or in the action
  • 12. 13 Hypothyroidism Prevalence  It is a common disorder with prevalence ranges from 2-15% population  ♀ > ♂  Female to male ratio = 10:1  ↑ with age; ♀ = ♂  Mean age at diagnosis is 60 years
  • 13.  Iodine deficiency remains the most common cause of hypothyroidism worldwide  areas of iodine sufficiency, autoimmune disease (Hashimoto's thyroiditis) and iatrogenic causes (treatment of hyperthyroidism) are most common
  • 14.  Primary Hypothyroidism  Disease of the thyroid gland  Secondary Hypothyroidism  Hypothalamic-pituitary diseases (reduced TSH) Hypothyroidism
  • 15. Causes of Hypothyroidism PRIMARY  Congenital  Agenesis  Ectopic thyroid remnants  Defects of hormone synthesis  Iodine deficiency  Dyshormonogenesis  Antithyroid drugs  Other drugs (e.g. lithium, amiodarone, interferon)
  • 16. Causes of Hypothyroidism  Autoimmune  Atrophic thyroiditis  Hashimoto's thyroiditis  Postpartum thyroiditis  Infective  Post-subacute thyroiditis
  • 17. Causes of Hypothyroidism  Iatrogenic  Radioactive iodine therapy  External neck irradiation  post-surgery  Infiltration  amyloidosis, sarcoidosis, hemochromatosis, scleroderma
  • 18. SECONDARY  Hypopituitarism: tumors, pituitary surgery or irradiation, infiltrative disorders, Sheehan's syndrome, trauma, genetic forms of combined pituitary hormone deficiencies  Isolated TSH deficiency or inactivity  Hypothalamic disease: tumors, trauma, infiltrative disorders, idiopathic
  • 19. HASHIMOTO THYROIDITIS  Most common cause of hypothyroidism  Autoimmune, non-Mendelian inheritance  45-65 years, F:M = 10-20:1  Painless symmetrical enlargement  Risk of developing  B-cell non-Hodgkin’s lymphoma  Other concomitant autoimmune diseases  Endocrine and non-endocrine
  • 20. Hashimoto Thyroiditis Pathogenesis  Immune systems reacts against a variety of thyroid antigens  Progressive depletion of thyroid epithelial cells which are gradually replaced by mononuclear cells → fibrosis  Immune mechanisms may includes:  CD8+ cytotoxic T cell-mediated cell death  Cytokine-mediated cell death  Binding of antithyroid antibodies → antibody dependent cell-mediated cytotoxicity
  • 21. Symptoms and Signs
  • 22. Investigation of primary hypothyroidism  Serum TSH  The investigation of choice.  A high TSH level confirms primary hypothyroidism.  Serum T4  low free T4 level confirms the hypothyroid state.  Thyroid and other organ-specific antibodies TPO antibodies
  • 23. Investigations of other abnormalities:  Anaemia.  Increased serum aspartate transferase levels, from muscle and/or liver  Increased serum creatine kinase levels, with associated myopathy  Hypercholesterolaemia  Hyponatraemia due to an increase in ADH and impaired free water clearance.
  • 24. Treatment  Replacement therapy with levothyroxine (thyroxine, i.e. T4) is given for life.  In the young and fit, 100 - 150 μg daily is suitable.  thyroid function tests after at least 2 months on a steady dose  the aim is to restore T4 and TSH to well within the normal range  An annual thyroid function test is recommended .
  • 25. Subclinical Hypothyroidism  biochemical evidence of thyroid hormone deficiency in patients who have few or no apparent clinical features of hypothyroidism  guidelines do not recommend routine treatment when TSH levels are below 10 mU/L  low dose of levothyroxine (25–50 g/d) with the goal of normalizing TSH
  • 26. Myxoedema coma  Severe hypothyroidism, associated with: - confusion or even coma. - hypothermia. - severe cardiac failure. - Hypoventilation. - Hypoglycaemia. - hyponatraemia.  patients require full intensive care.
  • 27.  occurs in the elderly  usually precipitated by factors that impair respiration  drugs (especially sedatives, anesthetics, antidepressants)  pneumonia, congestive heart failure, myocardial infarction  gastrointestinal bleeding  cerebrovascular accidents  Sepsis
  • 28. Myxoedema coma  Treatment:  Levothyroxine as a single IV bolus of 500 g, which serves as a loading dose-50–100 ug/d  oxygen (by ventilation if necessary)  monitoring of cardiac output and pressures  gradual rewarming  hydrocortisone 100 mg i.v. 8-hourly  glucose infusion to prevent hypoglycaemia.
  • 29.  Thyrotoxicosis - as the state of thyroid hormone excess  Hyperthyroidism - result of excessive thyroid function  major etiologies of thyrotoxicosis are hyperthyroidism caused by Graves' disease, toxic MNG, and toxic adenomas
  • 30. Causes of hyperthyroidism Common  Graves' disease (autoimmune)  Toxic multinodular goitre  Solitary toxic nodule/adenoma
  • 31. Causes of Thyrotoxicosis Primary hyperthyroidism  Graves' disease  Toxic multinodular goiter  Toxic adenoma  Functioning thyroid carcinoma metastases  Struma ovarii  Drugs: iodine excess (Jod-Basedow phenomenon)
  • 32. Thyrotoxicosis without hyperthyroidism  Subacute thyroiditis  Silent thyroiditis  Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma  Ingestion of excess thyroid hormone (thyrotoxicosis factitia) or thyroid tissue
  • 33. Secondary hyperthyroidism  TSH-secreting pituitary adenoma  Chorionic gonadotropin-secreting tumorsa  Gestational thyrotoxicosisa
  • 34. Graves' disease  The most common cause of hyperthyrodism  It is an autoimmune disorder. where the thyroid is overactive, producing an excessive amount of thyroid hormones  More common in adults -between 20 and 50 years  Can be familial and associated with other autoimmune diseases  Characterized by hyperthyroidism, ophthalmopathy with exophthalmos and dermopathy (pretibial myxedema)
  • 35. Graves’ Disease Autoimmune disease with breakdown of helper-T-cell tolerance Excessive production of thyroid autoantibodies: Thyroid-stimulating antibody (TSI) Antibodies bind to the TSH receptor of the follicular cell Stimulation of the cell resulting in: Increased levels of thyroid hormones & Hyperplasia of the thyroid gland Hyperthyroidism and Thyroid gland enlargement
  • 36. Hyperthyrodism  Clinical features: due to  Hypermetabolic state  Overactivity of sympathetic nervous system
  • 37. Symptoms  Weight loss  Increased appetite  Irritability  Tremor  Goiter  Restlessness  Stiffness  Muscle weakness  Breathlessness  Palpitation  Heat intolerance  Excessive sweating  Itching  Thirst  Vomiting  Diarrhoea  Oligomenorrhoea  Loss of libido
  • 38. Signs  Tremor  Irritability  Psychosis  Tachycardia or atrial fibrillation  Warm peripheries  Systolic hypertension  Cardiac failure
  • 39. Signs  Lid lag  Proximal myopathy  Proximal muscle wasting  Onycholysis  Palmar erythema
  • 40. Eye disease
  • 41. Graves' Ophthalmopathy  earliest manifestations - sensation of grittiness, eye discomfort, and excess tearing  most serious manifestation is compression of the optic nerve at the apex of the orbit, leading to papilledema; peripheral field defects; and, if left untreated, permanent loss of vision
  • 42.  0 = No signs or symptoms  1 = Only signs (lid retraction or lag), no symptoms  2 = Soft-tissue involvement (periorbital edema)  3 = Proptosis (>22 mm)  4 = Extraocular-muscle involvement (diplopia)  5 = Corneal involvement  6 = Sight loss
  • 43.  Thyroid dermopathy/pretibial myxedema - most frequent over the anterior and lateral aspects of the lower leg  Thyroid acropachy - clubbing found in <1% of patients with Graves' disease
  • 44. Investigation  Thyroid function test:  Serum TSH is suppressed in hyperthyroidism .  Diagnosis is confirmed with a raised free T4 or T3  . Measurement of TPO antibodies or TBII may be useful if the diagnosis is unclear clinically
  • 45. Treatment Antithyroid drugs: 1. Carbimazole. 2. Propylthiouracil.  These drugs inhibit the formation of thyroid hormones  common side effects - rash, urticaria, fever, and arthralgia  Rare but major side effects include hepatitis; an SLE-like syndrome; and, most important, agranulocytosis
  • 46. Treatment  Radioactive iodine  RAI accumulates in the thyroid and destroys the gland by local radiation.  It takes several months to be fully effective.
  • 47. Treatment  Surgery:  subtotal thyroidectomy  Only in patient who have previously been rendered euthyroid.
  • 48. Goiter  Goiter refers to an enlarged thyroid gland  Biosynthetic defects, iodine deficiency, autoimmune disease, and nodular diseases can each lead to goiter  diffuse nontoxic goiter - diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism  Worldwide, diffuse goiter is most commonly caused by iodine deficiency and is termed endemic goiter
  • 49. Congenital Thyroid Diseases  Agenesis /Aplasia  Hypoplasia  Accessory or aberrant thyroid glands  Thyroglossal duct cyst
  • 50. Thyroglossal Duct Cyst  A thyroglossal duct cyst is a neck mass or lump that develops from cells and tissues remaining after the formation of the thyroid gland during embryonic development.  Children  Failure of regression  Neck, medial  Squamous or columnar lining  often appears after an upper respiratory infection when it enlarges and becomes painful.  Complications: inflammation, sinus tracts
  • 51.  Thank you