THYROID DYSFUNCTION Graves disease 10 Autoimmune activating ABs

THYROID DYSFUNCTION

Grave’s disease (10) • Autoimmune - activating AB’s to TSH • • receptor High concentrations of circulating thyroid hormones Weight loss, tachycardia, tiredness Diffuse goitre - TSH stimulating growth Opthalmopathy and dermopathy

Hyperthyroidism • Level of the defect (1 , 2 , 3 ) • Thyrotoxicosis • Graves’ disease • Toxic Adenoma • Toxic Multinodular Goiter • Chronic Thyroiditis

Exophthalmos bilateral exophthalmos (bulging eyes) is typical marker of autoimmune Graves' disease (hypethyreoidismus) Thyroid-stimulating autoantibodies mimic the action of TSH; they are directed against the thyrotropin receptor autoantigen (TSHR) on the thyroid follicular cell and similar receptors throughout the body and they may also react with these autoantibodies Subset of orbital fibroblasts is rich in this membrane receptor After stimulation the orbital fibroblasts are capable of differentiating into adipocytes and thus increase orbital adipose tissue

Symptoms and signs of hyperthyroidism

Hypothyroidism • 1 , 2 , 3 • Newborn – Cretinism – Lack of myelination • Children – Retarded Growth – Disproportionate

Symptoms and signs of hypothyroidism

Myxedema (myxoedema) • Hypothyroid myxedema is specific form of skin edema • Increased activity of connective tissues leads to increased deposition of components of extracellular matrix (mainly glycosaminoglycans, proteoglycans) which retains large amounts of sodium ions and water • Stimulation of fibroblasts is caused by increased amount of TSH which is able to bind to some membrane receptors and by this way it activates biosynthesis of extracellular matrix

Thyroid hormone resistance • Mutation of the receptor. • Characterized by high blood levels of both TSH and Thyroid hormones

Non-toxic goiter • Iodine deficiency

Thyroiditis

Hashimoto’s (1 o) Autoimmune - AB’s destruction of thyroid gland Low concentrations of thyroid hormones Lethargy, intolerance to cold Lack of growth and development Diffuse goitre - lymphocytic infiltration of gland + TSH stimulated growth

Euthyroid Syndrome • Patient presents and complains of hypothyroid type symptoms • Levels of Thyroid hormones (free & total), & TSH in low normal range. • May be due to a 5’-deiodinase deficiency

Euthyroid Sick Syndrome • Occurs in acute and chronic illness. • Derangements of thyroid hormone levels are due to alterations in peripheral metabolism of T 4 and binding of T 4 to TBG. Fasting or illness also decrease the magnitude of TSH pulsations. • Low T 4 belays poor prognosis.

Euthyroid Sick Syndrome Severity of Illness Free T 4 Free T 3 Reverse T 3 TSH Mild Normal Reduced up to 50% Increased up to twofold Normal Moderate Increased Reduced up to 90% Increased up to several fold Normal Severe Reduced Almost undetectable Variable Reduced

Evaluating thyroid function The serum TSH is the best initial test of thyroid function. The latest generation of this assay has high sensitivity and is an excellent screening tool for those patients with a low pretest probability of thyroid disease.

• TSH of 0. 5 -4. 0 m. U/L is highly diagnostic for normal thyroid function. • A high TSH (>5. 0 m. U/L is an indication for further testing, such as a free T 4 (FT 4) determination or a free thyroxine index (FTI) • A patient who has a TSH in the gray zone (4. 1– 5. 0 m. U/L) is very likely to develop hypothyroidism and should be screened regularly

Thyroid hormones in various disorders condition TSH Free T 4 Free T 3 Primary hyperthyroid Undetectable V. high High T 3 thyrotoxicosis Undetectable Normal v. High Secondary hyperthyroidism Increased High Subclinical hyperthyroidism Low N N

Thyroid hormones conc. In various Disorders Condition TSH Thyroid H Resistance Primary hypothyroidism or N Secondary hypothyroidism or N Free T 4 Free T 3 or N