Thyroid Disorders Quiz

Thyroid Gland

• The thyroid gland controls metabolism in the body.
• Hyperthyroidism is high thyroid hormone in the blood, increasing the speed of body processes.
• Treatment options for hyperthyroidism include radioactive iodine, surgery, and thioureylenes.
• Patients on antithyroid drugs should be counselled about agranulocytosis.
• Beta-blockers may be used to manage excess thyroid hormone.
• Hypothyroidism is low thyroid hormone, slowing down body processes.
• Treatment for hypothyroidism is levothyroxine (LT4).
• Increased speed in all body processes is caused by High thyroid hormone present in blood.
• Reduced thyroid hormone in blood leads to slower body processes.

Parathyroid Glands

• The parathyroid gland controls calcium levels in the body.
• Hyperparathyroidism is high parathyroid hormone, leading to brittle bones (osteoporosis).
• Hypoparathyroidism is low parathyroid hormone, leading to cardiac arrhythmias, neuromuscular irritability, and tetany.
• Treatment for hyperparathyroidism is typically surgery. If not a surgical candidate, calcimimetics and bisphosphonates are options.
• Treatment for hypoparathyroidism involves calcium and 1,25-dihydroxy vitamin D.

Diseases of the Thyroid

• Hyperthyroidism ("overactive thyroid gland"): Excess circulating free thyroxine (T4) or free triiodothyronine (T3), or both.
• Hypothyroidism ("underactive thyroid gland"): Insufficient production of thyroid hormone by the thyroid gland.
• Major causes of Hyperthyroidism: Graves' disease, Toxic thyroid adenoma, Toxic multinodular goitre.

Hyperthyroidism - Learning Outcomes

• LO1: Describe the mechanism of action of drugs used to treat hyperthyroidism or hypothyroidism.
• LO2: Recall the pharmacokinetics and side effects associated with hyperthyroidism or hypothyroidism treatments.
• LO3: Describe the mechanism of action of drugs used to treat hyperparathyroidism or hypoparathyroidism.
• LO4: Recall the pharmacokinetics and side effects associated with hyperparathyroidism or hypoparathyroidism treatments.

Hyperthyroidism - Signs and Symptoms

• Signs: Normal/Distorted nail beds angle, clubbed fingers, tremors, diarrhea, menstrual changes (amenorrhea), intolerance to heat, fine/straight hair, bulging eyes, facial flushing, enlarged thyroid, tachycardia, systolic BP increase, weight loss, localized edema.

Hyperthyroidism - Diagnosis

• Laboratory: Low serum TSH, High serum T3 and T4, Anti-TSH receptor antibodies.
• Imaging: Thyroid ultrasound, Radioactive iodine imaging (using Iodine 123) to determine the cause of hyperthyroidism.

Hyperthyroidism - Imaging

• Cold Nodule, Grave's Disease, Toxic Multinodular, Hot Nodule, Autonomous Nodule, Thyroiditis
• Imaging helps identify the cause through visual characteristics of the thyroid gland.

Synthesis of Thyroid Hormones

• Iodide trapping (1st step)
• Oxidation and iodination of tyrosine residues on Tg (2nd step)
• Coupling of iodotyrosine to form T3 & T4 (3rd step)
• Proteolysis of Tg, releasing T4, T3, and iodotyrosines (4th step)
• Deiodination (5th Step)

Thyroid Treatment Options

• Thioureylenes (e.g., carbimazole, methimazole, propylthiouracil)
• Radioactive iodine (131I)
• Surgery

 Thio(n)amides/Thioureylenes - Clinical Use

• Reduce the level of thyroid hormone
• Inhibits the enzyme thyroperoxidase.

 Thio(n)amides/Thioureylenes - Pharmacokinetics

• Carbimazole is rapidly converted to methimazole.
• PTU has a half-life of 1 hour, methimazole 4–6 hours.
• There is a latent period of 2-4 weeks before clinical improvement.
• PTU is protein-bound, while methimazole is not.

 Thio(n)amides/Thioureylenes - Adverse Effects

• Major: Agranulocytosis (0.1–0.5% risk), which can occur at any time and dosage, potentially fatal.
• Stop antithyroid medication and monitor CBC with differential if fever or sore throat.
• If granulocyte count <500, hospitalize and give broad-spectrum antibiotics.

Thyroid Drugs - When to Use Carbimazole

• Use carbimazole in all Graves' disease patients, except during the first trimester of pregnancy, thyroid storm, or adverse reactions.

Radioactive Iodine - Clinical use

• Reduce the level of thyroid hormone
• The isotope used is 131I.
• Incorporated into thyroglobulin.
• Emits gamma and beta rays (short-range emission).
• Exerts cytotoxic action (kills cells).
• Hypothyroidism often develops after treatment.

Radioactive Iodine - Pharmacokinetics

• 131 I oral administration (Single dose).
• Half-life 8 days, effects diminish to undetectable levels by 60 days.
• Action may take up to 2 weeks to have an effect.
• Potential adverse effect is nausea.
• Special precaution - not for pregnant or breastfeeding women or children.

Surgery

• Equally effective as other treatments for Graves' disease.
• Choice of therapy often involves patient-physician discussion.
• Reasons for choosing surgery include avoiding radioiodine, avoiding side effects of antithyroid drugs needing rapid reduction of hyperthyroidism and large goiters (obstructing the airway).
• Total thyroidectomy typically leads to hypothyroidism.

Adjunctive Therapy

• Iodine or glucocorticoids, used with antithyroid drugs in severe thyrotoxicosis (e.g., thyroid storm).
• Beta-adrenoceptor antagonists (e.g., propranolol) can inhibit peripheral conversion of T4 to T3, relieving adrenergic symptoms (tremor, palpitations, heat intolerance, nervousness), and are used while waiting for other drugs to take effect.
• Contraindications: asthma, heart failure, and vasoconstrictor conditions like Raynaud's syndrome.

Corticosteroids

• Can inhibit T4 to T3 conversion.
• Helpful for relieving thyroiditis inflammation/pain, and thyroid eye disease (Graves' disease).

NSAIDs

• Used in subacute thyroiditis

Hypothyroidism

• Hypothyroidism slows down bodily functions.
• Major causes include Hashimoto's thyroiditis (tissue destruction by circulating antibodies and lymphocytes), genetic factors, and iatrogenic causes (e.g., post-thyroidectomy or radiation therapy).

Hypothyroidism - Signs and Symptoms

• Symptoms: Hair loss, apathy, lethargy, dry (coarse/scaly) skin, muscle aches/weakness, constipation, intolerance to cold, receding hairline, facial edema, extreme fatigue, thick tongue, slow speech, anorexia, brittle nails/hair, menstrual disturbances, late manifestations (hypothermia, bradycardia, weight gain, LOC, thickened skin), cardiac complications.

Thyroxine & Liothyronine (LT3)

• Treatment by administering hormone directly.
• Synthetic thyroxine derivative (Hormone Replacement Therapy)
• T4 metabolically converts to T3; LT3 is rarely used except for myxedema coma or with combined T4 treatment.
• Potential side effect is iatrogenic hyperthyroidism (palpitations, nervousness, headache, difficulty sleeping, insomnia, swelling of legs/ankles, weight loss).

TSH Monitoring

• Monitoring frequency: every 6 weeks, until the results are normalized.
• Target TSH normal range: 0.5–4.5 mIU/L (0.5–2.5 mIU/L, or 1–6 mIU/L in older patients).
• Cannot rely on TSH results in secondary (pituitary) hypothyroidism.

Calcium Salts

• Replaces calcium, improves bone mineralisation, and regulates nervous/muscle tissue.
• Pharmacokinetics: Oral solution (calcium citrate/carbonate), NOT IM (causes necrosis).
• Side effects mainly include constipation and potentially chronic kidney disease/kidney stones.

Vitamin D

• Vitamin D (Calcifediol/calcitriol) binds to vitamin D-binding protein and goes throughout the body.
• Promotes calcium absorption.
• Maintains calcium & phosphate levels, important for bone mineralisation.
• Potential side effects include allergic skin reactions, calcium buildup in arteries, and cholesterol changes.
• Monitor serum and urinary Ca2+ levels.

Hyperparathyroidism

• Causes of primary hyperparathyroidism include benign growth (adenoma) on one or more glands.
• Enlargement of two or more glands also common.

Treatment Options for Hyperparathyroidism

• Treatment of choice is surgery: removal of one or more glands.
• Minimally Invasive Radioguided Parathyroidectomy (MIRP) also performed.

Calcimimetics

• Mimics calcium circulating in the blood, causing the parathyroid gland to release less parathyroid hormone.

Bisphosphonates

• Possible mechanism of action includes inhibiting osteoclast recruitment or inducing osteoclast apoptosis.
• Used for osteoporosis treatment, increasing bone density up to 10% in three years and decreasing fracture incidence.
• Systemic bioavailability is about 0.6–0.7% for women and men when under fasting conditions.

Hypoparathyroidism

• Caused by inadequate parathyroid hormone resulting in lower than normal calcium in body fluids (i.e., hypocalcemia).

Hypoparathyroidism - Causes

• Post-surgical: following total thyroidectomy or radical neck dissection.
• Infiltrative diseases: Hemochromatosis, Wilson's disease.
• Hypomagnesemia: Decreased functional activation of adenylate cyclase leads to decreased PTH activity.
• Congenital defects in DiGeorge syndrome (formation of branchial pouches 3, 4, and 5), Familial syndromes (e.g., autoimmune polyglandular syndrome type 1), and hereditary resistance to parathyroid hormone (pseudohypoparathyroidism).
• Renal tubule dysfunction where they fail to respond to the presence of parathyroid hormone.

Questions & Answers (Q&A)

• Q1: The most serious side effect of carbimazole in a patient with Graves' disease is agranulocytosis.
• Q2: Carbimazole blocks the synthesis of thyroid hormone.