3.2 Thyroid, Bone & Calcium Agents

3.2 Thyroid, Bone & Calcium Agents

Thyroid replacement, antithyroid drugs and bone-protection therapy are high-yield areas because they combine classic counseling points with narrow safety margins.

Levothyroxine

Levothyroxine (LT4), synthetic thyroxine (T4), is the standard treatment for primary hypothyroidism. Because it has a narrow therapeutic index (NTI), small dose or formulation changes matter — keep patients on the same brand where possible. Key points:

• Administration: take on an empty stomach with water, 30-60 minutes before breakfast (or at bedtime at least 3 hours after the last meal), at a consistent time each day.
• Monitoring: check thyroid-stimulating hormone (TSH) 6-8 weeks after starting or changing a dose — the pituitary-thyroid axis needs that long to reach steady state — then every 6-12 months once stable.
• Interactions: calcium carbonate and ferrous sulfate chelate levothyroxine (separate by at least 4 hours); proton pump inhibitors (PPIs) and cholestyramine reduce absorption; enzyme inducers such as rifampicin, phenytoin and carbamazepine increase its metabolism.
• Pregnancy raises levothyroxine requirements by roughly 20-30%; monitor TSH each trimester.
• Over-replacement causes atrial fibrillation and accelerates bone loss — aim for a TSH within the reference range, not suppression.

Treatment is usually lifelong. In older patients and those with ischemic heart disease, start low (12.5-25 micrograms) and increase gradually to avoid provoking angina or arrhythmia. In secondary (central) hypothyroidism TSH is unreliable, so the dose is titrated against free T4 instead.

Antithyroid Drugs and Radioactive Iodine

The thionamides — carbimazole (a prodrug converted to methimazole), methimazole itself, and propylthiouracil (PTU) — inhibit thyroid peroxidase, blocking synthesis of T3 and T4. PTU additionally inhibits peripheral conversion of T4 to T3, making it useful in thyroid storm.

• Agranulocytosis is the hallmark serious adverse effect of all thionamides: counsel every patient that a sore throat, fever or mouth ulcer means stop the drug and obtain an urgent full blood count (FBC).
• PTU carries a hepatotoxicity risk, including rare liver failure; monitor for jaundice, dark urine and pruritus.
• Pregnancy: PTU is preferred in the first trimester because methimazole/carbimazole is associated with embryopathy; patients are then usually switched to methimazole for the second and third trimesters to limit PTU liver exposure.
• Radioactive iodine (iodine-131) is taken up by thyroid tissue and destroys it, providing definitive treatment for Graves' disease and toxic nodular goiter. It is contraindicated in pregnancy and breastfeeding, and most patients eventually become hypothyroid and need lifelong levothyroxine.

Thionamides are given either as a titration regimen (dose adjusted against thyroid function tests) or a block-and-replace regimen (high-dose thionamide plus levothyroxine replacement). Treatment for Graves' disease typically continues for 12-18 months. A baseline FBC is taken before starting, but routine monitoring does not reliably predict agranulocytosis — symptom-based counseling remains essential.

Osteoporosis Pharmacology

Treatment choices balance fracture reduction against class-specific harms:

Alendronate (70 mg once weekly) has strict administration rules: swallow whole with a full glass of plain water on arising, fasting, then remain upright and take nothing by mouth for at least 30 minutes. These steps prevent esophagitis and esophageal ulceration — bisphosphonates are contraindicated in esophageal motility disorders or in patients unable to sit upright. Long-term use is associated with osteonecrosis of the jaw (ONJ), so complete invasive dental work before starting, and with atypical femoral fractures, prompting consideration of a drug holiday after 3-5 years in lower-risk patients. Avoid when eGFR is below about 30-35 mL/min.

Denosumab is a RANKL inhibitor given subcutaneously every 6 months and is useful in renal impairment. It causes hypocalcemia, so correct vitamin D and calcium first. Critically, there is no drug holiday: stopping or delaying denosumab triggers rebound bone turnover and a rapid rise in multiple vertebral fracture risk — patients transitioning off it should be switched to a bisphosphonate.

Calcium and vitamin D underpin all regimens: target about 1000-1200 mg of elemental calcium daily (dietary sources preferred, supplementing the shortfall) plus 800-1000 IU of vitamin D.

Teriparatide, recombinant parathyroid hormone (PTH 1-34), is the main anabolic agent: daily subcutaneous dosing stimulates new bone formation in severe osteoporosis. Treatment is limited to about 2 years lifetime because of an osteosarcoma signal in rat studies, and an antiresorptive should follow to preserve gains.

Raloxifene, a selective estrogen receptor modulator (SERM), acts as an estrogen agonist in bone but an antagonist in breast and endometrium. It reduces vertebral fractures and invasive breast cancer risk but increases venous thromboembolism (VTE) risk and is weaker than bisphosphonates for non-vertebral sites — reserve it for selected postmenopausal women without VTE history.

Zoledronic acid, an intravenous bisphosphonate infused once yearly, suits patients who cannot tolerate or comply with oral therapy; it commonly causes a transient flu-like acute-phase reaction after infusion and carries the same ONJ caution. Treatment decisions are guided by fracture-risk assessment (for example FRAX), which combines bone mineral density with clinical risk factors such as age, prior fragility fracture, glucocorticoid use, smoking and parental history of hip fracture.