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- 1. Thyroid disorders Dr ArinolaEsan FMCP,FWACP,FACE Consultant Endocrinologist University College Hospital, Ibadan
- 2. Objectives • To givean overview of thyroid disorders • To discuss approach to management of some of them
- 3. Outline • Introduction • BriefAnatomy • Functions • Regulation of hormone production • Classification of disorders • Hyperthyroidism • Hypothyroidism • Goitres –non functional
- 4. Introduction • Thyroid disordersare common in endocrinology • These disorders affect most of the systems of the body • Complications are usually difficult to manage
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- 8. The thyroid gland •2 lobes connected in the middle by an isthmus • Produces thyroxine (T4) & triidothyronine (T3) • T4 secreted > than T3 ; T3 more biologically potent • Most T3 derived from extrathyroidal conversion of T4
- 9. Functions of thethyroid gland Thyroid hormones play critical role in: • Cell differentiation during development • maintaining thermogenesis • metabolic homeostasis
- 10. Regulation of thyroidhormone
- 11. Classification • With goitreor without goitre • Hyper or hypofunctioning • Benign or malignant
- 12.
- 13. Thyrotoxicosis • results fromexposure of body tissues to excess circulating levels of thyroid hormones • Several disorders cause Thyrotoxicosis • Hyperthyroidism: a subset of thyrotoxicosis • accounts for major aetiologies of thyrotoxicosis in which there is excess synthesis & secretion of thyroid hormone by the thyroid gland
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- 16. Thyrotoxicosis contd • Thyrotoxicosiswith high RAIU indicates de novo synthesis of hormone • Thyrotoxicosis with low RAIU indicates either: • Inflammation & destruction of thyroid tissue with release of preformed hormone into the circulation or • extrathyroidal source of thyroid hormone
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- 18. Graves disease • Mostcommon cause of thyrotoxicosis (50- 80%) • Autoimmune disorder resulting from TSH receptor antibodies (a.k.a. thyroid- stimulating immunoglobulins), which activate receptor & stimulate thyroid gland growth & thyroid hormone synthesis • Characterized by a variety of circulating antibodies to thyroid components including: • TSH-R-stimulating Ab – specific for Graves disease • anti-thyroid peroxidase (anti-TPO) • antithyroglobulin (anti-TG) antibodies
- 19. Graves disease • TSH-R-Abis directed toward epitopes of the TSH receptor & acts as a TSH-receptor agonist • Similar to TSH, TSH-R-Ab binds to the TSH receptor on the thyroid follicular cells to activate thyroid hormone synthesis, release & thyroid growth
- 20. Graves disease Consists of •Hyperthyroidism • Goiter • Ophthalmopathy • & occasionally a dermopathy (pretibial or localized myxedema)
- 21. Graves disease • Peakincidence: 20-40yrs • Prevalence varies among populations - areas of high iodine intake ass with ↑ prevalence of Graves’ • Female:Male ratio reported as ~ 5-10:1 • Combination of genetic & environmental factors → ↑ susceptibility to Graves’ disease
- 22. Graves disease: Precipitatingfactors • Genetic susceptibility • Abundant epidemiologic evidence in support • Stress: • Often hx of psychological stress before onset of dx. Suppression of stress followed by immunologic hyperactivity → disease in genetically susceptible • Pregnancy: a time of immune suppression, with rebound post partum
- 23. Precipitating & Predisposingfactors • Sex steroids • estrogen enhances immunologic activity • Smoking • Drugs: Iodine & iodine containing drugs may ppt disease in susceptible individual • may also damage thyroid cell directly & release thyroid antigens to immune system • Interferon α treatment of patients with hepatitis C infection • Infections: • Possible infections of the thyroid gland could initiate class II molecule expression
- 24. Graves disease continued •Usually thyroid gland palpable with diffusely enlarged smooth goitre, initially soft • May become progressively firmer • Nodular Graves (Marine-Lenart syndrome) • Graves disease in association with thyroid nodules reportedly increases risk of thyroid carcinoma
- 25. Symptoms in thyrotoxicosis •Tremors • Heat intolerance • Hyperkinesis • Irritability, nervousness • Jitteriness • increased sweating • Increased appetite • Palpitations • Eye symptoms (staring gaze, increased protrusion, pain, redness) • Diarrhea / Hyperdefaecation • Weight loss despite good or appetite • Dyspnoea on exertion • Itching • Muscle weakness/wasting •may manifest as exercise intolerance or difficulty climbing stairs • Menstrual irregularities • Reduced libido/ED
- 26. Signs may include: General/skin • Fine tremor • Evidence of weight loss • Warm, moist skin • Fine silky hair ± alopecia • Hyperhidrosis • Sweaty palms • Palmar erythema • Onycholysis
- 27. Signs in thyrotoxicosis Eyesigns • Lid lag, Lid retraction • Exophthalmos (Graves disease) • Cranial nerve palsy • Goitre • Thyroid bruit
- 28. Signs in thyrotoxicosis Cardiovascular •Tachycardia • Atrial fibrillation • High output heart failure • Systolic hypertension • Pretibial myxedema (Graves disease)
- 29. Signs Neurological • Restlessness • Othermental state changes • Irritability, anxiety, emotional lability, depression, other psychiatric reactions • Proximal myopathy • Hyperreflexia
- 30. Other findings inthyrotoxicosis • Skin - hyperpigmentation, acropachy, urticaria, vitiligo • CVS-premature atrial contractions • GIT - hepatomegaly, LFT abnormalities, jaundice • Metabolic-serum calcium & alkaline phosphatase, hypercalciuria, glucose intolerance • Neuromuscular-periodic paralysis(Asian males, sudden flaccid paralysis of muscles, occ hypo K+), muscle atrophy
- 31. Other findings inthyrotoxicosis • Osseous-osteoporosis • Reproductive - gynecomastia, sub-fertility • Hematopoietic- normochromic, normocytic anemia, lymphocytosis, lymphadenopathy, thymus enlargement, splenomegaly • Neurologic: Choreoathetosis • Others: Syncope, Delirium, stupor, coma, vomiting, (in severe cases)
- 32. Thyroid eye disease •Clinically evident in 20-25 % • More may have evidence on USS, CT, MRI (enlarged retro-ocular muscles) • appears before, concurrently or after treatment in Graves • most patients with ophthalmopathy have evidence of thyroid disease, but absent in ~ 10% of patients •“Euthyroid graves” • Ophthalmopathy may occur in chronic autoimmune thyroiditis (Hashimoto's) & may have TSHR receptor Ab (blocking )
- 33.
- 34. Thyroid eye disease •Look out for: redness, congestion, periorbital oedema conjunctival injection & oedema, proptosis, ophthalmoplegia • Failure of lid apposition promotes drying & ulceration of cornea • Objective measurement of degree of proptosis using an hertel’s exophthalmometer • measurement of distance b/w lateral angle of bony orbit & imaginary line tangent to most anterior part of cornea • upper limit of normal: 20 mm in whites; 22 mm in blacks • Visual acuity, visual fields & color vision
- 36. Thyroid eye disease •N –No signs or symptoms 0 • O – only symptoms 1 • S – soft tissue involvement 2 • P – proptosis 3 • E – Extraocular muscle involvement 4 • C- corneal involvement 5 • S – sight loss 6
- 37. Pretibial myxoedema • Accumulationof fluid & mucopolysaccharides in pretibial region • Mild • Severe • Incapacitating May appear as: • Non pitting oedema • Nodular • Plaques
- 38.
- 39. Graves disease –some associations • Addisons disease • DM • Vitiligo • Myasthenia gravis • SLE • RA • Scleroderma • Thymic hyperplasia • ITP • Dermatitis herepetiformis • Pernicious anaemia • Albright syndrome • Cutaneous pigmentation • Precocious puberty • Polyostotic fibrous dysplasia
- 40. Toxic multinodular goitre •Orbitopathy, pretibial myxedema, acropachy not observed • TSH-R antibodies absent • Size of thyroid gland variable with a dominant nodule or multiple irregular, variably sized nodules typically present • Neck USS should help delineate discrete unpalpable nodules
- 41. Thyroiditis Causes include: • Directchemical toxicity with inflammation (amiodarone) • Radiation thyroiditis, from external radiation or after radioiodine therapy • Palpation thyroiditis e.g occurring during parathyroid surgery
- 42. Diff diagnosis ofthyrotoxicosis • Single nodule raises possibility of an autonomously functioning thyroid adenoma • Painful, tender thyroid in subacute granulomatous thyroiditis • Subacute lymphocytic (usually painless) thyroiditis may have no, minimal, or modest thyroid enlargement • Absence of any thyroid enlargement: consider exogenous thyroid hormone ingestion or ectopic thyroid tissue
- 43. Investigation of thyroidfunction • Sensitive TSH assay • 3rd gen assays:10 fold greater functional sensitivity than 2nd gen • Assay of circulating thyroid hormones • Total (protein bound) • Free T4/T3
- 44. Assessment of thyroidfunction • Thyroid autoantibody tests • Thyroid imaging - of value in assessment of thyroid size & differential diagnosis – Ultrasound scan; CT; MRI • Nuclear scintigraphy: Radionuclide imaging • evaluate functional activity of thyroid -hot or cold • determine location & size of functional thyroid tissue (& to localize ectopic thyroid tissue) • Fine needle aspiration cytology • differentiating benign from malignant disease
- 45. Biochemical diagnosis ofHyperthyroidism • Overt: except for lab error, all patients with low/undetectable serum TSH & high free T4 & T3 concentrations have hyperthyroidism • In some pts, only serum T3 or serum T4 is elevated • T3 toxicosis – Low serum TSH; high free T3; normal free T4 • Tends to occur early in course of hyperthyroidism • T4 toxicosis – Low serum TSH, high free T4, normal T3 • Pattern in pts with hyperthyroidism & non thyroidal illness • May occur in persons with amiodarone induced thyrotoxicosis
- 46. Biochemical diagnosis ofHyperthyroidism • TSH-induced hyperthyroidism: Very rare cause of hyperthyroidism, due to: TSH-secreting pituitary adenoma or partial resistance to feedback effect of thyroid hormones on TSH secretion defects in the T3-nuclear receptor Normal or high serum TSH despite high free T4 & T3 concn
- 47. Radioactive I uptake& thyroid scanning Radionuclide scans provide information • shape, size of thyroid gland, distribution of tracer activity within gland • limited role in differentiating benign from malignant nodule • Thyroid gland selectively transports radioisotopes allowing for thyroid imaging & quantification of radioactive tracer uptake • useful to differentiate causes of thyrotoxicosis particularly when used in conjunction with imaging • Graves: usually diffuse uptake • Toxic nodular goiter usually patchy uptake, with areas of increased & decreased uptake
- 49. Nuclear scintigraphy Cold nodule:nonfunctioning thyroid nodule/lump • doesn't concentrate radioactive isotopes in thyroid scan • Higher incidence of malignancy Hot nodule: nodular region of thyroid gland • takes up large amounts of radioactive iodine relative to rest of thyroid gland, visualized as "hot spot" • majority of hot nodules function autonomously • Much lower malignancy potential
- 51. Treatment of hyperthyroidism B-blockers •relieves many of the symptoms (particularly palpitations, tremor, anxiety) • Atenolol – advantage of single daily dose & -1 selectivity • Propanolol also reduces T4 to T3 conversion • Contraindicated in asthma; caution in patients with heart failure Antithyroid drugs: Carbimazole, Methimazole, Propyl thiouracil inhibit thyroid hormone biosynthesis & secretion
- 52. Thionamide therapy inHyperthyroidism • Aim: to restore euthyroid state as soon as possible, so as to achieve lasting remission in patients with Grave's disease or to prepare patients treatment with radioactive iodine or surgery • Duration of treatment with drugs:– 12 to 24 months if ablation not intended • Reports of permanent remission after discontinuing drugs is achieved - 15-80%
- 53. Side effects ofThionamides • Rash • Nausea • Epigastric distress • Agranulocytosis* • Hepatitis • Lupus like syndrome • Vasculitis • Polyarthritis
- 54. Other Medications Iodides, Ipodate(iodinated radio contrast agent) • Inhibit thyroid hormone synthesis and secretion • Useful in lowering T3 & T4 • Can be used to quickly prepare patients for surgery, when there is insufficient time to give thionamides • Useful in combination treatment of thyroid storm
- 55. Radioactive iodine (I131) • Treatment of choice in patients with toxic nodular goitre • 1st line for patients with Graves’ disease in US • Increasingly used as first-line therapy for adults • Contraindicated in children, during pregnancy & breast feeding • Pregnancy contraindicated for 6-12 months after therapy • Fixed or individualized doses
- 56. Radioactive iodine (I131) • Stop thionamides 3-5 days before RAI, to avoid impairing uptake; restart few days later • May aggravate uncontrolled hyperthyroidism • Small but definite risk of development or worsening of ophthalmopathy, esp if smoker or high T3 before therapy • (Tx with prednisolone reported to prevent worsening) • Toxic nodules require higher doses • side effect – hypothyroidism, radiation thyroiditis • life-long follow-up of thyroid function required
- 57. Thyroidectomy • Those withvery large goiters • Where there is possibility of malignancy • Severe or advancing ophthalmopathy • Patient who relapses after medical therapy • Pregnant patient on drugs whose disease is hard to control • Those with severe reactions to antithyroid drugs • Patients who have refused I 131 therapy • Woman wishing to achieve a pregnancy in near future
- 58. Treatment of othercauses Self-limiting causes of thyrotoxicosis: subacute thyroiditis, iodine- induced, exogenous administration of T4 • Treat symptomatically • Therapy: beta-blockers for symptomatic control and antiinflammatory drugs such as aspirin, or nonsteroidal antiinflammatory drugs, or, in severe cases, prednisone • Ipodate also useful: blocks conversion of T4 to T3 & reduces the tissue effects of thyroid hormones • Thionamides have no role in treatment, since new hormone is not being synthesized
- 59.
- 60. Hypothyroidism Clinical syndrome resultingfrom a deficiency of thyroid hormone → to generalised slowing of metabolic process
- 61. Hypothyroidism • Diagnosis reliesheavily on lab tests •many of the clinical manifestations non-specific • Clinical presentation highly variable •depends on age of onset and duration & severity of disease •Presentation in adults varies from asymptomatic elevation in TSH concentration to myxedema coma
- 62. Hypothyroidism Classified as: • Primary •Secondary • Tertiary • Peripheral resistance to action of thyroid hormone OR • Goitrous • Non- Goitrous
- 63. Primary Hypothyroidism: Causes •Chronic autoimmune thyroiditis • Iodine deficiency & iodine excess • Post irradiation (I131, external irradiation) • Post ablative • Drug induced: Thionamides, lithium, amiodarone, IF- • Infiltrative diseases: Sarcoidosis, haemochromatosis, amyloidosis, • Congenital thyroid agenesis, dysgenesis or biosynthetic defects
- 64. Transient hypothyroidism • Subacute lymphocytic thyroiditis • Sub acute granulomatous • Postpartum thyroiditis • After 131I treatment or subtotal thyroidectomy for Graves’ disease
- 65. Chronic Autoimmune thyroiditis •Commonest cause of hypothyroidism in iodine-sufficient areas of the world • Commoner in older women • cellular & antibody-mediated destruction of thyroid tissue • Goitrous • Atrophic • differ in extent of lymphocytic infiltration, fibrosis, & follicular cell hyperplasia of thyroid, but not in pathophysiology
- 66. Chronic Autoimmune thyroiditis Hashimoto’s •Marked lymphocytic infiltration CD4+, CD8+ & B cells Atrophic • More fibrosis, less lymphocytic infiltration • Represents end stage of Hashimoto thyroiditis
- 67. Chronic autoimmune (Hashimoto's)thyroiditis Role for genetic susceptibility • more likely to have personal or family history of autoimmune diseases • Association with Turners syndrome No well-defined environmental risk factors for chronic autoimmune thyroiditis • evidence linking a high iodine intake with this disorder • serum antithyroid antibody concentrations increase after dietary iodine intake is increased in endemic goiter regions • Reports of association between cigarette smoking & risk of hypothyroidism in pts with autoimmune thyroid disease
- 68. Hypothyroidism Symptoms in adultsoften non-specific: • Fatigue • Cold intolerance • Weight gain • Constipation • Myalgia • Menstrual irregularities • Slow movement and speech
- 70. Hypothyroidism Older children maypresent on account of: • Short stature due to linear growth retardation • Retarded secondary sexual characteristics • Delayed onset of puberty • Poor school performance
- 71. Hypothyroidism • Delayed relaxationof deep tendon reflexes • Bradycardia • Coarse hair and skin, puffy facies, loss of eyebrows, enlargement of the tongue, voice hoarseness • Overt muscle weakness
- 72. Other clinical features •Entrapment neuropathy of median nerve • producing paresthesia & weakness of hands • Obstructive sleep apnoea • Cardiomegaly: dilation of the heart; pericardial effusion • Neuropsychiatric manifestations • Adynamic ileus leading to mega colon & functional intestinal obstruction
- 73. Investigations • Primary hypothyroidsm– low or normal serum FT4 with elevated TSH • Secondary hypothyroidsm – low serum FT4 with low or inappropriately normal TSH • Subclinical hypothyroidsm – normal serum T4 & elevated serum TSH (no symptoms or signs usually)
- 74. Investigation • Raised TSH,normal free T4 or T3 • Recovery phase of non thyroidal illness • Intermittent thyroxine therapy in hypothyroidism • Interfering antibodies • Drugs-cholestyramine, sertraline • Congenital • TSH receptor defects • TSH resistance syndromes
- 75. Investigations • Hyperlipidaemia –occurs with increased frequency in hypothyroidism • Hyponatraemia – often resulting from inappropriate ADH secretion • Elevated muscle enzymes (CPK, AST. LDH) • Anaemia normochronic, normocytic • E.C.G. changes- bradycardia, low amplitude QRS complexes, evidence of ischaemic heart disease • Thyroid autoantibodies (antithyroglobulin antibody, thyroid peroxidase antibody)
- 76. Investigations contd • Imagingstudies of sellar and suprasellar region • Evaluate for other hormone deficiencies
- 77. Treatment • If noresidual thyroid function, daily replacement of levothyroxine @~1.6µg/kg( 1-2 µg/kg per day) • Elderly (> 50-60) years & no evidence of heart disease, stat 50 µg daily • Those who have history of CHD initiate at 25 µg /day • dose can be increased by 25 mcg/day every 3 to 6 wks until replacement is complete • Gradual increase, as rapid increase in dose may tax coronary or cardiac reserve
- 78. Treatment • Therapeutic goal:alleviation of clinical syndrome & normalization of TSH in primary hypothyroidism • After initiation of T4 therapy, reevaluate • Serum T4 & TSH measured in 3 to 6 wks (depending upon patient's symptoms) & dose adjusted accordingly • process of increasing dose of Levothyroxine should continue, based upon periodic measurements of serum TSH (& free T4 if therapeutic goals have not been achieved)
- 79. Treatment • Once desiredT4 dose is established, annual evaluation • Changing requirements • Altered absorption • Compliance issues • Monitor for signs of overtreatment • Life long therapy in majority • Surgical therapy for huge goiters with compressive symptoms •Subclinical hypothyroidism: Treat if there is goitre, suggestive symptoms, low T3, drugs which may potentiate, uncertain follow up, cholesterol
- 80. Thyroid cancer • 95%of thyroid cancer presents as nodule or lump in thyroid gland • Thyroid cancer may coexist with thyrotoxicosis • Graves disease in association with thyroid nodules reportedly ↑ risk of thyroid carcinoma •
- 81. • Cold nodulesfrequent in hyperthyroid patients in endemic iodine-deficient regions • 3.8% in GD; 6.4% Toxic multinodular goitre; 12% in thyroid adenoma • Older patients (>/=50 years) & cold nodules:- significant risk factors for malignancy in patients with hyperthyroidism Giles SY et al: Surgery 2008;144: 1028-36
- 82. Thyroid cancer • Differentiated •Papillary carcinomas • Follicular carcinomas • Undifferentiated • Anaplastic • Others • Medullary thyroid cancer • Lymphomas • Sarcomas • Metastases Pathogenesis • Radiation • TSH & growth factors • Oncogenes & tumour suppression genes • Approach to patients with thyroid nodules
- 83. Thyroid cancer Surgery isprimary mode of therapy for patients with differentiated thyroid cancer • For most patients with papillary or follicular carcinoma: • Total thyroidectomy followed by I131 ablation Levothyroxine TSH suppression • Diff thyroid cancers contain TSH receptors &TSH stimulates their growth • Reduced recurrence & cancer specific mortality rates
- 84. Thyroid cancer Follow-up • long-termwith physical examinations, biochemical testing (including serum thyroglobulin measurements), radioiodine imaging, ultrasound
- 85. Thank you foryour attention