9 Agents for Thyroid Parathyroid Disorders 2025 (1) PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pharmacological Control of the Thyroid and Parathyroid Gland Developed by Prof. Steve Kerrigan (Professor Personalised Therapeutics) Delivered in Bahrain by Prof Will Ford  LEARNING OUTCOMES...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Pharmacological Control of the Thyroid and Parathyroid Gland Developed by Prof. Steve Kerrigan (Professor Personalised Therapeutics) Delivered in Bahrain by Prof Will Ford  LEARNING OUTCOMES Thyroid Gland: Treatment Parathyroid Gland: Treatment Describe the mechanism of action of the LO1 Describe the mechanism of action of the drugs LO3 drugs used to treat either used to treat either hyperparathyroidism or hyperthyroidism or hypothyroidism hypoparathyroidism Recall the pharmacokinetics and side LO2 Recall the pharmacokinetics and side effects LO4 effects associated with each treatment associated with each treatment for either hyperthyroidism or hyperparathyroidism or hypothyroidism hypothyroidism  DISEASES OF THE THYROID Hyperthyroidism (or "overactive thyroid gland") – is caused by an excess of circulating free thyroxine (T4) or free triiodothyronine (T3), or both. Hypothyroidism (or “underactive thyroid gland”) – is caused by insufficient production of thyroid hormone by the thyroid gland.  HYPERTHYROIDISM Hyperthyroidism is a condition with excess thyroid hormone this causes an overactive metabolism and increased speed of all the body's processes. Major causes in humans are: – Graves' disease (Autoimmune disease affecting TSH receptor) – Toxic thyroid adenoma (Benign tumor, can’t metastasize) – Toxic multinodular goitre (Overgrowth of gland) SIGNS AND SYMPTOMS OF HYPERTHYROIDISM * * *  DIAGNOSIS OF HYPERTHYROIDISM Laboratory Imaging Serum TSH: low Thyroid ultrasound Serum T3 and T4: high Radioactive imaging using Iodine Anti-TSH receptor antibodies (I123): – Radioisotope most often used in nuclear imaging of the thyroid and for thyroid uptake scans (used to determine cause of hyperthyroidism-  IMAGING IN HYPERTHYROIDISM Laboratory Imaging  BIOSYNTHESIS OF THYROID HORMONES (RECAP PHYSIOLOGY) 1. Iodide trapping 14x more T4 than T3 5. Deiodination 4. Proteolysis of Tg, releasing T4, T3, and iodotyrosines 2. Oxidation and iodination of tyrosine residues on Tg 3. Coupling of iodotyrosine to form T3 & T4  LO1 Treatment options Thioureylenes Short range emission radioactive iodine Surgery Adjunctive therapy - symptoms  LO1 Thio(n)amides / Thioureylenes T4 Examples: carbimazole, methimazole, propylthiouracil (PTU) I I I Clinical use I Reduce the level of thyroid hormone TPO T3 Mechanism of action I Inhibits the enzyme thyroperoxidase (TPO), – adds iodide to the hormone precursor thyroglobulin, I forming thyroxine (all) Active hormone I Also acts by inhibiting the enzyme 5'-deiodinase, which converts T4 to the active form T3 (propylthiouracil only)  LO2 Thio(n)amides / Thioureylenes Pharmacokinetics Carbimazole is rapidly converted to methimazole ½ life PTU is 1 hour, methimazole 4-6 hours Causes 90% inhibition of iodine within 12 hrs Latent period before clinical improvement (2-4 wks) -> this is due to T4 having a long t½ and due to large storage of the hormone PTU protein-bound, methimazole not PTU also decreases T4 to T3 conversion  LO1 When do you use which drug? Use carbimazole in all Graves’ disease patients Except: First trimester of pregnancy Thyroid storm Adverse reaction to carbimazole  LO2 Thio(n)amides / Thioureylenes Adverse Effects Major - Agranulocytosis 0.1 – 0.5 % o Can occur at any time, any dose Can be fatal - Stop antithyroid medication - Check WBC with differential if fever or sore throat - If granulocyte count