Lesson 33: Thyroid and Parathyroid (PDF)

Lesson 33 Thyroid and Parathyroid 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  1. Introduction Thyroid hormones are synthesised in the thyroid follicle: T3 is more active Tri-iodothyronine (T3) Thyroxine (T4) Regulation TRH (Thyro...

Lesson 33 Thyroid and Parathyroid 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  1. Introduction Thyroid hormones are synthesised in the thyroid follicle: T3 is more active Tri-iodothyronine (T3) Thyroxine (T4) Regulation TRH (Thyrotropin-releasing hormone) hypothalamic TSH (Thyroid-stimulating hormone) pituitary T3 and T4 actions: 1. Increase in the metabolism of carbohydrates, fats and proteins: oxygen consumption and heat production→increase in the basal metabolic rate. Administration of thyroid hormone results in augmented cardiac rate and output, and increased tendency to dysrhythmias such as atrial fibrillation 2. Regulation of growth and development  Regulation of thyroid hormone release By hypothalamic-pituitary-thyroid (HPT) axis: Hypothalamus: releases TRH (thyrotropin- releasing hormone), which stimulates the pituitary gland. Pituitary Gland: releases TSH (thyroid- stimulating hormone) in response to TRH. Thyroid Gland: under TSH stimulation, produces and releases T3 and T4 into the bloodstream. Peripheral Conversion: in tissues like the liver and muscles, T4 is converted into T3, the more active form. Negative Feedback: adequate levels of T3 and T4 inhibit TRH and TSH release, maintaining hormonal balance. This system ensures stable thyroid hormoneReduction in plasma levels, regulating metabolism and growth. [I-] Regulation of thyroid hormone release CALCITONIN (disminuye ca) T3,T4 Reduction in plasma [I-]  1. Introduction Mechanism of action T4 accounts for about 80% of the hormones secreted by the thyroid, and T3 accounts for the remainder. T3 enters the target cell, it binds to thyroid hormone receptors (TR) that activate gene transcription, leading to increased synthesis of proteins necessary for growth, development, and calorigenesis (heat production)  2. Thyroid disorders Abnormally low or high T4 and T3 levels result in clinical manifestations 1. Hypothyroidism is characterized by low T4 levels and leads to impaired growth and development, decreased physiologic and metabolic activity, and decreased heat production (calorigenesis) TRH TSH 2. Hyperthyroidism is characterized by high T 4 levels, leading to hyperactivity of organ systems (particularly the nervous and cardiovascular systems) and an increased metabolic rate and calorigenesis. TSH 2. Simple non-toxic goitre: caused by dietary iodine deficiency with normal thyroid function 2. Thyroid disorders tiredness eyes: exoftalmos lethargy constipation protuding eye  2. Thyroid disorders 1. Hypothyroidism In children and infants: causes irreversible mental retardation and impairs growth and development. In adults, hypothyroidism is associated with impairment of physical and mental activity and slowing of cardiovascular, gastrointestinal, and neuromuscular functions. Symptoms: Lethargy, cold intolerance, weight gain, and constipation. The skin may become coarse, dry, and cold. Long-standing, untreated hypothyroidism: Myxedema, which is described as a dry, waxy swelling of the skin bwith non-pitting edema. *Non-pitting edema occurs when excess fluid builds up in the body causing swelling that does not indent when pressure is applied. 2. Thyroid disorders 1. Hypothyroidism Causes Autoimmune thyroiditis (Hashimoto disease). Dietary iodine deficiency Pituitary or hypothalamic dysfunction can cause secondary hypothyroidism Drugs can induce thyroid disorders: Lithium inhibits the release of thyroid hormones by the thyroid gland Amiodarone (iodine-containing antiarrhythmic) casues either hypothyroidism or hyperthyroidism. Most commonly, amiodarone causes hypothyroidism by inhibiting conversion of peripheral T4 to T3. The treatment for all forms of hypothyroidism is replacement therapy with a thyroid hormone preparation.  2. Thyroid disorders 2. Hyperthyroidism (Thyrotoxicosis) Excessive thyroid hormone production due to: Excessive TSH (TSH-secreting pituitary adenomas) Gland stimulation by thyroid antibodies, as occurs in patients with Graves disease. Graves disease is the most common cause of hyperthyroidism Production of Ab directed against the TSH receptor on the surface of thyroid cells. These antibodies stimulate the receptor in the same manner as TSH, resulting in overproduction of thyroid hormones. Characterized by hyperthyroidism, thyroid enlargement, and exophthalmos 2. Thyroid disorders 2. Hyperthyroidism (Thyrotoxicosis) Treatment Antithyroid agents, surgery, β-blockers to control the cardiovascular symptoms of hyperthyroidism until definitive treatment, and RAI Treatment (radioactive iodine treatment) 3. Treatment of thyroid disorders Hypothyroidism There are no drugs that specifically increase the synthesis or release of thyroid hormones. IODIDE (in case of iodine defficiency) Replacement therapy: levothyroxine (T4) and liothyronine (T3) LEVOTHYROXINE (orally, 50–100 μg/day) is the first-line drug of choice. Drug of choice for suppressive therapy in patients with thyroid nodules, diffuse goiters, or thyroid cancer. In these conditions, levothyroxine acts to suppress TSH production and reduce stimulation of abnormal thyroid tissue LIOTHYRONINE (IV) has a faster onset but a shorter duration of action, and is generally reserved for acute emergencies such as the rare condition of myxoedema coma.  3. Treatment of thyroid disorders Hypothyroidism LEVOTHYROXINE (orally, 50–100 μg/day) is the first-line drug of choice. - Different brands and generic formulations may vary in their bioavailability: formulations should not be substituted for one another without monitoring T4 and TSH levels. - Coffee, soy, and dietary fiber, can reduce absorption of levothyroxine→recommended administration on an empty stomach, either 1 hour before or 4 hours after meals, or at bedtime, to achieve consistent blood levels. - 35% of T 4 is converted to T 3 in peripheral tissues, levothyroxine administration produces physiologic levels of both T4 and T3. 3. Treatment of thyroid disorders Hypothyroidism ADRs: OVERDOSE: there is a risk of precipitating angina pectoris, cardiac dysrhythmias or even cardiac failure Interactions Aluminum hydroxide, calcium supplements, cholestyramine, ferrous sulfate reduce absorption 3. Treatment of thyroid disorders Hyperthyroidism Hyperthyroidism may be treated pharmacologically or surgically (thyroidectomy) Although the condition of hyperthyroidism can be controlled with antithyroid drugs, these drugs do not alter the underlying autoimmune mechanisms (genetically induced)  3. Treatment of thyroid disorders Hyperthyroidism: Thioureylenes CARBIMAZOLE, PROPYLTHIOURACIL Group thiocarbamide (S–C–N) group is essential for antithyroid activity. Mechanism of action Reduce the iodination of tyrosyl residues in thyroglobulin Decrease the output of thyroid hormones from the gland: gradual Reduction in the signs and symptoms of thyrotoxicosis Oral administration Both drugs may be used during pregnancy but both can cross the placenta and may affect the fetal thyroid gland. 3. Treatment of thyroid disorders Hyperthyroidism: Thioureylenes CARBIMAZOLE, PROPYLTHIOURACIL Indication: Graves disease: thioureylenes can either aim to resolve the disease entirely (remission) or prepare the patient for more permanent treatment options like surgery or RAI therapy. ADRs: Many patients experience benign and transient leukopenia Rashes (2%–25%) and other symptoms, including headaches, nausea, jaundice and arthralgia, are common Rare: neutropenia and agranulocytosis (usually during the first 3 months) 3. Treatment of thyroid disorders Hyperthyroidism: IODINE/IODIDE Mechanism of action Iodine is converted in vivo to iodide (I − ), which temporarily inhibits the release of thyroid hormones. Effect is limited to several weeks Often given orally in a solution with potassium iodide Indications Preparation of hyperthyroid subjects for surgical resection Severe thyrotoxic crisis (thyroid storm) In the event of a nuclear reactor leak, administering potassium iodide helps block the thyroid's absorption of radioactive iodine, significantly reducing the risk of thyroid cancer and other radiation-induced thyroid conditions. 3. Treatment of thyroid disorders Hyperthyroidism: IODINE/IODIDE Thyroid storm is a rare, life-threatening condition caused by a sudden and severe exacerbation of hyperthyroidism. It results in dangerously high levels of thyroid hormones, leading to a hypermetabolic state that can affect multiple organs. In the past, thyroid storm was commonly observed during thyroid surgery, but improved preoperative management (potassium iodide) has markedly decreased the incidence of this complication. Symptoms: Hypermetabolism state. (Hypertension, tachycardia, heart failure…) 3. Treatment of thyroid disorders Hyperthyroidism: IODINE/IODIDE Following a nuclear reactor accident or nuclear bomb explosion: The thyroid gland naturally concentrates iodine from the bloodstream, including radioactive iodine isotopes like iodine- 131 (¹³¹I). When absorbed, this "hot" isotope can destroy thyroid tissue by emitting harmful radiation. To prevent this, iodide salts (such as potassium iodide) can be administered. These salts act by competitively blocking the uptake of radioactive iodine by the thyroid gland, reducing its harmful effects in cases of accidental exposure to radioactive iodine (RAI). https://www.youtube.com/watch?time_continue=38&v=s9APLXM9Ei8&feat ure=emb_logo  3. Treatment of thyroid disorders Hyperthyroidism: RADIOIODINE Indications First-line treatment for HYPERTHYROIDISM. Thyroid cancer in combination with surgery, radiotherapy and/or tyrosine kinase inhibitor chemotherapeutics Dose generally 5–15 mCi. Given orally. Mechanism of action The isotope emits β radiation: β particles exert a powerful cytotoxic action that is restricted to the cells of the thyroid follicles. 3. Treatment of thyroid disorders Hyperthyroidism RADIOIODINE ADRs: Hypothyroidism will eventually occur after treatment with radioiodine, particularly in patients with Graves’ disease (autoimmune disease that affects the thyroid) Easily managed by replacement therapy with T4. Absolutely contraindicated in pregnant women because it destroys fetal thyroid tissue! 4. Other drugs used β-BLOCKERS decrease many of the signs and symptoms of hyperthyroidism (tachycardia, dysrrhythmias, tremor and agitation) They are used during the preparation for surgery During the initial treatment period while the thioureylenes or radioiodine take effect Treatment of acute hyperthyroid crisis. Eye drops containing GUANETHIDINE A noradrenergic blocking agent , are used to mitigate the exophthalmos of hyperthyroidism (inhibiting sympathetic activation) GLUCOCORTICOIDS or surgical decompression may be needed to mitigate severe exophthalmia in Graves’ disease. exoftalmos