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University of Toronto St. George
Laboratory Medicine and Pathobiology

LECTURE EIGHT: THYROID DISEASES GOITER  It can be associated with both hyperthyroidism and hypothyroidism  The patient may also have normal thyroid function THYROID GLAND AND THYROID HORMONES  Thyroid gland secreted mostly T4 and some T3. The peripheral tissues (e.g. the liver and kidney) deiodinate (convert) T4 to produce 2/3 of the circulating T3  Thyroid hormones bind to receptors and trigger the hormonal effects. T3 is more biologically active than T4, but at a lower concentration in plasma (2 nmol/L for T3 vs 100 nmol/L for T4)  Reverse T3 (rT3) is an inactive form metabolized from T4. Local thyroid status can be modulated by the relative production of T3 and rT3.  Thyroid hormones are essential for the normal maturation and metabolism of all the tissues in the body.  Reverse T3 and is the inactive form – this is how the peripheral issue can fine tune the levels of T3 in the body This is how they are synthesized – they start with the tyrosine and then there are a couple of the iodonization reactions It is called T4 since there are 4 iodines on the molecule - get rid of a DIFFERENT iodine and we get this form - remember that rT3 is made by the tissues Can get rid of one of the iodines and form T3 TOTAL VS. FREE  Reversibly bound to carrier proteins e.g. T4-binding globulin (TBG)  Only very small fraction is unbound and free for biological activity Total nmol/L Free pmol/L Free T4 0.03% of total T4 Free T3 0.3% of total T3  Alterations in the concentration or affinity of binding proteins may change the concentration of thyroid hormones (i.e. we can modify the levels of the thyroid hormones using the levels of the binding proteins)  Question: FT4 and FT3 vs. total T4 and total T3, which are the better markers in routine assessment of thyroid function (Why?) (we use the free levels of the T3 and the T4 since the total is changed by the levels of the binding proteins – THE FREE IS NOT AFFECTED BY THE LEVELS OF BINDING PROTEINS) CHANGES OF TBG BINDING AFFECTS THYROID FUNCTION TESTS CAUSE COMPOUND EFFECTS Increase TBG - Estrogen ↑T ,4T 3(the total T4 and T3 will - Oral Contraceptive be increased/ ↔ FT 4 TSH (the free TSH and free T4 will stay normal) Decrease TBG (there is decreased - Androgen ↓ T 4 T 3 (there is less of it being concentration of the thyroid binding - Glucocorticoids bound hence the total levels of the globulin) T4 and T3 decreas/)↔ FT ,4 TSH (does not change it is the free T4 and TSH) Inhibit binding of T4/T3 to TBG - Salicylates ↓ T 4 ↔ FT 4 of thyroid hormones to their binding globulins – the free T4 will be maintained while the bound T4 will be decreased (and hence total t4) is decreased) MYXEDEMA (this is a symptom of severe hypothyroidism)  Dry, waxy swelling of the skin, with abnormal deposits of glycosaminoglycan’s (unbranched polysaccharides) (there is a gradual changes in the facial features) SYMPTOMS AND SIGNS OF HYPOTHYROIDISM – HYPOMETABOLIC SYNDROME  SYMPTOMS: - Weight gain - Growth retardation in children (the child is not growing as fast as the peers are) - Depression - Deep, hoarse voice - Easy fatigue - Dry, coarse skin - Lethargy (feel tired) - Cold intolerance - Myxedema (dry skin) - Hair loss - High Cholesterol (there is decreased synthesis of the LDH receptor) - Constipation - Bradycardia (slow heart rate)  These symptoms are not specific for hypothyroidism – e.g. people that have anemia or diabetes can also have fatigue (lethargy), and weight gain and depression CAUSES OF HYPOTHYROIDISM 1. Primary Hypothyroidism (this is the most common) - Autoimmune destruction of the thyroid gland (it gradually loses its function) (Hashimoto’s disease) - Radioiodine or surgical treatment of hyperthyroidism (this may cause it) - Iodine deficiency (in certain regions of the world such as in central Africa this is common cause of the hypothyroidism (not enough iodine to make T3 and T4) - Congenital defects in hormone biosynthesis and action - Transient hypothyroidism due to drug therapy (anti-thyroid drugs) (may revert to normal if the drug is stopped; they are initially give a drug to reduce their HYPERthyroidism BUT it is too effective and hence leads to hypothyroidism if the drug is stopped the they may revert to normal (transient)) 2. Secondary Hypothyroidism - Pituitary disease 3. Tertiary Hypothyroidism - Hypothalamic disease (cannot produce TRH) DIAGNOSTIC STRATEGY FOR SUSPECTED HYPOTHYROIDISM (this is how we diagnose it) TSH is the normal hormone that stimulates the thyroid gland and it there is low TSH then the feedback should increase the levels of the TSH. This is the specific thyroid test The thyroid gland is not making the T4 Excludes the possibility This is due to the destruction or They are not This is due to the of the hypothyroidism- the loss of the function of the diagnosed with the pituitary disease. This is thyroid gland – it is called primary they are fine from this true version yet – we due to the pituitary not point of view since it is in the thyroid gland itself need to monitor them making the TSH and (secondary is one level up (this and they may hence there is no release would be the pituitary) eventually get it of the T4 COMPLICATIONS OF HYPOTHYROIDISM Depending on when during life a patient is hypothyroid, clinical outcomes vary.  Pregnancy: irreversible fetal malformation, growth retardation and neurological deficits (this is permanent – even after birth)  Infancy & early childhood: decreased linear growth, inadequate brain maturation, low IQ and psychomotor development; severe condition (this is treatable if its discovered early enough) – Cretinism  Adult: severe condition – death from myxedema coma - Longstanding severe hypothyroidism facing a precipitating factor, e.g. infection, a cardiovascular event, sedating medication - Features: severe hypothermia (<80°F) and loss of consciousness
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