Pharmacology: Thyroid Disorders PDF

PHARMACOLOGY: THYROID DISORDERS Dr. Adam NMT200 Gratton MSc ND October 9, 2023 LECTURE COMPETENCIES 1. Compare and contrast the mechanisms of action, indications, and adverse effects of drugs used to modulate thyroid function 1.Thyroid hormones – levothyroxine 2.Desiccat...

PHARMACOLOGY: THYROID DISORDERS Dr. Adam NMT200 Gratton MSc ND October 9, 2023 LECTURE COMPETENCIES 1. Compare and contrast the mechanisms of action, indications, and adverse effects of drugs used to modulate thyroid function 1.Thyroid hormones – levothyroxine 2.Desiccated thyroid 3.Antithyroid agents – methimazole, propylthiouracil 4.Radioactive iodine – I131 5.Beta blockers - propranolol 2. Recall commonly used medications that are known to interfere with thyroid function 3. Prescribe appropriate initial dosages of levothyroxine based on patient history 4. Prescribe appropriate initial dosages of desiccated thyroid based on patient history GOALS OF THERAPY Achieve a euthyroid state and manage symptoms in patients with hypothyroidism, thyrotoxicosis, or hyperthyroidism Recognize which patients with thyroid nodules require fine needle biopsy for cytologic diagnosis versus observation Ensure appropriate management of hypo- and hyperthyroidism during pregnancy HYPERTHYROIDISM INTRODUCTION Thyrotoxicosis is any condition of excessive thyroid hormone and its effects Hyperthyroidism is specifically due to excess thyroid hormone production Thyroid storm if a life-threatening medical emergency caused by severe thyrotoxicosis INTRODUCTION There are many causes of thyrotoxicosis including Graves disease, toxic nodules, iodine excess, and TSH-producing pituitary adenomas, among others Focus on hyperthyroidism as it is the more common presentation to typical naturopathic practice NONPHARMACOLOGIC CHOICES Important to consider surgery as an option given the limitations of medication and the potential for the formation of goitre Hypothyroidism is a common and likely adverse effect thyroid surgery RADIOACTIVE IODINE Iodine 131 Used to ablate thyroid tissue in patients with Graves disease and toxic nodules The thyroid rapidly concentrates iodine, so an oral dose has minimal effect on the rest of the body Beta wave emission destroys surrounding tissue within a range of 0.6 – 2 mm ADVERSE EFFECTS High risk of hypothyroidism Possible worsening of Graves orbitopathy Risk of radiation thyroiditis METHIMAZOLE Decreases the production of thyroid hormone Interferes with iodination of tyrosine as well as with coupling Does not affect stored thyroid hormone of thyroid hormone in circulation ADVERSE EFFECTS Risk of skin rash, allergic reaction, and agranulocytosis Can cause hepatotoxicity in rare instances Contraindicated during the first trimester of pregnancy due to causing aplasia cutis PROPYLTHIOURACIL Similar mechanism of action to methimazole Has the additional action of inhibiting the conversion of T4 to T3 in the periphery Affects production of thyroid hormone and existing thyroid hormone ADVERSE EFFECTS Similar adverse effects to methimazole Risk of skin rash, allergic reaction, and agranulocytosis Can cause severe hepatotoxicity that may be fatal in rare instances Does not cause aplasia cutis METHIMAZOLE VS PROPYLTHIOURACIL Methimazole is the preferred drug in most instances due to the lower risk of causing hepatotoxicity Methimazole is the preferred drug while patients are breastfeeding and in children Propylthiouracil is the preferred drug during the first trimester of pregnancy Propylthiouracil can be used to treat thyroid storm as it affects thyroid conversion in the periphery BETA BLOCKERS Do not affect thyroid hormone production Used to ameliorate the symptoms of adrenergic excess caused by excess thyroid hormone (elevated heart rate, hypertension, etc.) Propranolol can decrease the conversion of T4 to T3 in the periphery ADVERSE EFFECTS Bradycardia, dizziness, fatigue, headache, hypotension. Avoid in patients with asthma or conditions associated with bradycardia; taper once thyrotoxicosis improves. HYPOTHYROIDISM INTRODUCTION Very common Rarely caused by iodine deficiency in North America Most commonly caused by Hashimoto’s thyroiditis LEVOTHYROXINE The standard therapy for treating hypothyroidism Replacement therapy – essentially treatment using orally administered T4 Takes 6 weeks to attain a new steady state after dosage adjustments DOSING Average adult replacement: 1.6 mcg/kg/day PO Generally based on lean body mass Elderly patients may need less For those at risk of angina start with 12.5 – 25 mcg/day PO DOSING Initial doses vary depending on endogenous thyroid function In patients with an intact thyroid or with mild or subclinical disease much smaller initial dosages may be needed (25 – 50 mcg) In patients with negligible thyroid function full replacement dosages may be needed DOSING ADJUSTMENTS Wait at least 6 weeks after initial dosing or last dose adjustment TSH values slightly out of range can be increased or decreased slightly by 12.5 to 25 mcg INTERACTIONS Absorption may be reduced by antacids and mineral supplementation Proton pump inhibitors and estrogens may interfere with absorption Variable effects with anticoagulant drugs Separate administration by 6 hours Levothyroxine is typically taken first thing in the morning before any other medications ADVERSE EFFECTS Symptoms of hyperthyroidism if overtreated Possible exacerbation of angina Glycemic control may decline with initiation of levothyroxine, potentially necessitating dosage adjustment of antihyperglycemic agents DESICCATED THYROID Can be used based on patient preference Tablets contain T4 and T3 in fixed amounts Comes in 30 mg, 60 mg, or 125 mg tablets DESICCATED THYROID Levothyroxine Dose (mcg) Desiccated Thyroid Dose (mg) 50 32 100 65 200 130 300 200 400 260 500 325 ADVERSE EFFECTS Similar to levothyroxine Risk of cardiovascular and neurological adverse effects increases with larger doses (due to T3) - palpitation, tachycardia, cardiac arrhythmias, angina pectoris - nervousness, tremors, headache, insomnia - sweating, heat intolerance, fever, weight loss DOSING CASE #1 48-year-old patient assigned female at birth Chief concerns of constipation, feeling cold, weight gain and fatigue. No history of cardiovascular issues or thyroidectomy. Height: 160 cm (5 ft 3 in) Weight: 62 kg (137 lbs) BMI: 24.2 Serum TSH: 8.3 U/mL CONSIDERATIONS BMI under 25 Mild symptoms and mildly elevated TSH Patient has an intact thyroid Not elderly What dose should we give? DOSING Full replacement dose based on weight 1.6 x weight in kg = 1.6 x 62 = 99.2 Conservative initial dosing is 25 – 50 mcg Dose of desiccated thyroid? Take levothyroxine dose and multiply by 0.65 DOSING CASE #2 56-year-old patient assigned female at birth Chief concerns of hair loss and dry skin. Feels tired all the time despite sleeping 8 hours a night or more. Significant weight gain over the last 6 months. No history of cardiovascular concerns or thyroidectomy Height: 172 cm (5 ft 8 in) Weight: 102 kg (225 lbs) BMI: 34.5 Serum TSH: 21.3 U/mL CONSIDERATIONS Significant symptoms Serum TSH level is fairly high Not elderly Intact thyroid BMI above 25 What initial dose do we give? DOSING If we go by unadjusted weight 1.6 x 102 = 163.2 If we use an online calculator to determine the ideal body weight for a patient of that height, we get a value of 58.8 kg 1.6 x 58.8 = 94 We could use TSH, as well with an equation of 107 + 0.69(TSH) 107 + 0.69(21.3) = 121 SAMPLE QUESTION A patient returns for follow-up 6 weeks after receiving their first prescription for levothyroxine and their TSH value remains unchanged. The patient reports taking it every morning with the iron supplement they were also prescribed. Which of the following is the best course of action? A. Increase the dose of levothyroxine by 12.5 mcg B. Reduce the dose of levothyroxine by 12.5 mcg C. Switch the patient to an equivalent dose of desiccated thyroid D. Change the time the patient takes their iron supplement