Cairo University Faculty of Pharmacy Department of Pharmacology & Toxicology

1. Thyroid hormones Cairo University Faculty of Pharmacy Department of Pharmacology & Toxicology Pharmacology III Practical Sessions

2. Hormones Pharma-III Practical Thyroid gland Thyroid gland secretes 3 main hormones • Thyroxine (T4) • Triiodothyronine (T3) • Calcitonin Energy & Growth Control of calcium

3. - - Hormones Pharma-III Practical - Regulation of TH secretion: Hypothalamus TRH AnteriorPituitary TSH Thyroid Gland TH

4. Hormones Pharma-III Practical Actions of thyroid hormone • Calorigenic actions BMR (stimulation of oxygen consumption by tissues) • Adipose tissues (catabolic lipolysis ) and cholesterol • Muscle (catabolic protein breakdown) • Body temperature ( heat production 2ry to energy production) • Bone, skeletal muscle and nervous system (normal development).

5. Hormones Pharma-III Practical Actions of thyroid hormone • Heart (upregulation of β receptor and sensitivity to circulating catecholamines). • CNS stimulation resulting in anxiety, restlessness, insomnia and tremors. All these actions are remarkable in patients with abnormally hyperthyroidism

6. Hormones Pharma-III Practical Thyroid hormone blood tests 1-Total thyroxine (T4) T4 in the blood is attached to a protein called the thyroxine-binding globulin.. A total T4 blood test measures both bound and free thyroxine..(Normal values: T4 = 4.5–12.0 µg/dL 2- Free Thyroxine (FT4) Measures only free thyroxine, as free thyroxine affects tissue function in the body.(Normal values: FT4 8–2.4 ng/dL)

7. Hormones Pharma-III Practical 3-Total T3 (triiodo-L-thyronine): A total T3 blood test measures both bound and free T3.(Normal values: T3 = 80–200 ng/dL) 4- Free T3 (FT3): Measures only free T3 (Normal values: FT3 0.2–0.6 ng/dL) NB:T3 is quicker in action (reaches its peak activity faster) and is of shorter t ½ life than T4. Generally, T3 is about five times as potent as T4why ?. T3 is loosely bound to TBG than T4, more available in free active form T3 binds to TH receptor with more affinity than T4

8. Hormones Pharma-III Practical 5- Thyroid stimulating hormone (TSH): TSH levels is the most sensitive and specific test for thyroid dysfunction (why?). Any small changes in free TH levelproduces exponential or logarithmic changes in TSH (Normal level in body is 0.2 – 6 mU/L) NB:a raised level of TSH means 1ry hypothyroidism while a lowered level means 1ry hyperthyroidism

9. Hormones Pharma-III Practical 6- Other blood tests a- Thyroid antibodies test: This test measures the presence of Abs against thyroid tissue. Antibodies may mean that you have an autoimmune disease such as Hashimoto’s thyroiditis (hypothyroidism) or Graves' disease (hyperthyroidism) ! b- Thyroxine-binding globulin (TBG) test. TBG is an important protein in the blood that carries the thyroid hormones T3 and T4. TBG testing is not done very often.

10. Hormones Pharma-III Practical Thyroid hormones and lab. values

11. Hormones Pharma-III Practical Hyperthyroidism The thyroid gland excessively Overproducing thyroid hormone Toxic goiter (Graves’ disease) TSH Receptor on Thyroid Gland Autoantibodies (TSI) Excessive TH production

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13. Hormones Pharma-III Practical Symptoms • Protrusion of the eye ball (exophthamlus), goiter and  HR • Heat intolerance, weight loss, excessive sweating and GIT motility • Nervousness, irritability, restlessness and muscle weakness

14. Hormones Pharma-III Practical Treatment • Antithyroid drugs: thioureylenes propylthiouracil, methimazole & carbimazole • Surgery ( may cause hypothyroidism or hypoparathyrodism) • Radioactive I131 (may cause delayed hypothyroidism).

15. Hormones Pharma-III Practical Other causes of hyperthyroidism • Hyperfunctioning follicular adenoma in thyroid gland (TH TSH) (1ry Hyperthyroidism) • 2ry hyperthyroidism (pituitary gland) ( TSH TH) • 3ry hyperthyroidism (hypothalamus) ( TRH  TSH TH) Note the difference in lab values

16. Hormones Pharma-III Practical Hypothyroidism A clinical syndrome in which the deficiency or absence of thyroid hormone slows body metabolic processes.

17. Hormones Pharma-III Practical 1- Cretinism Hypothyroidism in children If untreated, it results in mild to severe impairment of both physical and mental growth and development. Symptoms • Dwarf and obese • Infertile and mentally retarded

18. Hormones Pharma-III Practical Causes • Maternal iodine deficiency • Maternal antithyroid antibodies • Congenital abnormalities • If the pregnant woman hasabnormal hypothyroid function, this should be corrected during pregnancy or baby will havesevere mental deficiency at birth(difficult to be treated) • If the pregnant woman hasnormal thyroid function, baby will be normal. However, diagnosis should be done early at birth and rapid ttt byTH replacementtherapy should be startedif hypothyroidism is diagnosed

19. Hormones Pharma-III Practical 2- Hypothyroidism in adult (myxedema): Symptoms : • Weight gain, lethargy and sluggishness • Puffiness of skin (myxedema) • Bradycardia, cold intolerance and constipation

20. Hypothyroid Myopathy With high serum creatine kinase values Anemia in hypothyroidism • Normocytic Lack of erythropoietin production arising from the reduction in need of O2. • Microcytic Iron deficiency anemia is related with menorrhagia and iron malabsorption. • Macrocytic Failure of vitamin B12 absorption occurs in pernicious anemia. Impaired intestinal absorption of folic acid.

21. Hormones Pharma-III Practical Causes • Mainly Hashimoto’s(1ry hypothyroidism) Autoantibodies are directed to thyroglobulin or thyroid peroxidase inhibiting TH synthesis in thyroid gland • Rarely pituitary or hypothalamic hypofunction(2ry or 3ry hypothyroidism) Treatment:TH replacement therapy

22. Hormones Pharma-III Practical 3- Simple Goiter: • Hypothyroidism due to iodine deficiency •  synthesis of thyroid hormone TSH level  thyroid gland hypertrophy. • Causes • Mainly diminished intake of food containing iodine • Increased intake of food containing goitrogens (cabbage) • Drugs (lithium)

23. Hormones Pharma-III Practical Simple Goiter: Treatment Initially Levothyroxin normalization of TSH and gland size. Surgery may be needed to normalize gland size. Then Iodine supplementation in diet as preventive treatment. N.B. Iodine supplementation as initial therapy thyrotoxicosis due to TH production

24. Drug-induced thyroid disorder

25. Iodine-containing drugs (amiodarone)-induced hyperthyrodism • Incidence • In areas with high iodine intake - 1.7% • In areas with low iodine intake - 12% • Pathogenesis • Type 1 (AIT): occurs particularly in patients with underlying thyroid disease; iodine induced excessive synthesis of thyroid hormone. • Type 2 (AIT): destructive thyroiditis (amiodarone-induced); occurs in patients with no previous underlying thyroid disease; thyroiditis results in release of thyroid hormones into the circulation. Serum IL-6 and color flow doppler ultrasound assessment (thyroidal blood flow) are important diagnostic tools in the differentiation between T1AIT and T2AIT.

26. Treatment • If possible withdrawal of amiodarone. • T1AIT: treatment by Large doses of antithyroid drugs including methimazole or propylthiouracil. • T2AIT: steroid treatment. Amidarone-induced hypothyrodism Such as in iodine-sufficient parts of the world, such as the united states. High amount of iodine released during the metabolism Wollf-Chaikoff effect

27. Hormones Pharma-III Practical Drugs inhibit TH synthesis through : - Competition with iodide for transport to the gland. -Inhibition of thyroperoxidase. Drugs decrease peripheral deiodination (T4 to T3). Levothyroxine is sometimes used with antithyroid drugs in the treatment of hyperthrodism. Acetaminophen but not aspirin is used to alleviate hyperthermia in hyperthyrodism. Wolf Chaikoff effect. Patient on proylthiouracil cannot receive radioactive therapy.

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