Endocrine drugs
Thyroid, Corticosteroid, Sex Hormone and Bone Drugs: FCPS Part 1 Pharmacology
Antithyroid drugs, levothyroxine, corticosteroids, contraceptives, HRT, SERMs, fertility drugs and bone drugs for FCPS Part 1. Covers carbimazole agranulocytosis, PTU in pregnancy, thyroid storm, adrenal crisis, emergency contraception, clomifene, tamoxifen and bisphosphonates.
Thyroid hormone basics
- The gland releases mostly T4 (about 90%); most active T3 is made peripherally by deiodinase conversion of T4. Thyroid hormones act on nuclear receptors that alter gene transcription.
- Oestrogen (pregnancy, the pill) raises thyroxine-binding globulin: total T4 rises, free T4 stays normal.
Antithyroid drugs
| Drug | Mechanism | Key points |
|---|---|---|
| Carbimazole (to methimazole) | Inhibits thyroid peroxidase (iodine organification and coupling) | First line in Graves; agranulocytosis; rash; teratogenic (aplasia cutis), so avoided in the first trimester |
| Propylthiouracil | TPO inhibition plus blocks peripheral T4 to T3 conversion | First trimester and thyroid storm; severe hepatotoxicity |
| Lugol's iodine, potassium iodide | High iodide inhibits hormone release and synthesis (Wolff–Chaikoff) and reduces gland vascularity | 7–10 days before thyroidectomy; thyroid storm (after a thionamide) |
| Propranolol | Blocks adrenergic symptoms; reduces T4 to T3 conversion | Symptom control |
| Radioiodine (I-131) | Destroys thyroid tissue | Not in pregnancy or breastfeeding; may worsen eye disease |
- Carbimazole with sore throat or fever: stop it immediately and check the blood count, because agranulocytosis (usually in the first 3 months) can be fatal. Patients are warned in advance.
- Thyroid storm: propranolol, PTU, iodine at least 1 hour later, hydrocortisone, cooling (avoid aspirin, which displaces T4 from binding proteins), ICU.
- After thyroidectomy: hypocalcaemia (parathyroid injury), recurrent laryngeal nerve palsy, haematoma compressing the airway (open the wound at the bedside), hypothyroidism.
- Thyroid eye disease: swollen extraocular muscles in the orbital apex can cause optic nerve compression: falling colour vision first, then acuity and a relative afferent pupillary defect. It is an emergency treated with IV methylprednisolone or orbital decompression.
Levothyroxine
- Half-life about 7 days; recheck TSH 6–8 weeks after a change. Take on an empty stomach, away from iron, calcium and PPIs. Increase the dose by 25–50% as soon as pregnancy is confirmed.
- Elderly patients or those with angina: start low (25 micrograms) and increase slowly; a rapid rise in metabolic rate raises myocardial oxygen demand and worsens angina.
- Over-replacement (suppressed TSH, high free T4) causes atrial fibrillation and bone loss (osteoporotic fractures); reduce the dose. TSH suppression after thyroid cancer is a planned exception.
- Liothyronine (T3) acts quickly: myxoedema coma (with hydrocortisone).
- Amiodarone and lithium alter thyroid function.
Corticosteroids
| Steroid | Equivalent dose | Mineralocorticoid effect |
|---|---|---|
| Hydrocortisone | 20 mg | High |
| Prednisolone | 5 mg | Low |
| Dexamethasone | 0.75 mg | Almost none (less salt retention than hydrocortisone) |
| Fludrocortisone | Used for mineralocorticoid effect | Very high |
- Steroid hormones, including oestrogen, progesterone and testosterone, enter cells and act through intracellular receptors that regulate transcription.
- Uses: inflammation, autoimmunity, asthma, allergy, transplantation, cerebral oedema (dexamethasone), adrenal insufficiency (hydrocortisone plus fludrocortisone), CAH, intranasal steroids for allergic rhinitis.
- Intranasal corticosteroid spray daily is the most effective treatment for the congestion of perennial allergic rhinitis; topical decongestants cause rebound.
- Antenatal betamethasone or dexamethasone before 34 weeks accelerates fetal lung maturity (surfactant production by type II pneumocytes), reducing respiratory distress syndrome, intraventricular haemorrhage and neonatal death. These fluorinated steroids cross the placenta because 11β-HSD2 does not inactivate them.
- Adverse effects: Cushingoid features, hyperglycaemia, hypertension, osteoporosis, avascular necrosis, proximal myopathy, skin thinning, poor healing, peptic ulcer (with NSAIDs), infection and TB reactivation, posterior subcapsular cataract, glaucoma, psychosis, growth suppression, hypokalaemia, adrenal suppression.
- Abrupt withdrawal: long-term prednisolone suppresses CRH and ACTH, so the adrenal cortex atrophies. When the drug stops, the atrophic glands cannot make cortisol: adrenal crisis with hypotension, vomiting, hyponatraemia and hypoglycaemia. Taper after more than 3 weeks; give IV hydrocortisone 100 mg and saline in a crisis; double the dose on sick days; hydrocortisone cover for surgery.
- Steroids are for induction, not maintenance, in IBD: Crohn remission is maintained with azathioprine or mercaptopurine (or methotrexate).
Contraception
| Method | Mechanism | Notes |
|---|---|---|
| Combined pill | Oestrogen and progestogen suppress GnRH, FSH and the LH surge, so ovulation is inhibited; progestogen thickens cervical mucus | VTE, stroke; contraindicated in migraine with aura, smokers over 35, past VTE, breast cancer |
| Progestogen-only pill, implant, injection, LNG-IUS | Cervical mucus, ovulation inhibition (implant, injection) | Implant and IUS are the most effective (failure under 1%) |
| Copper IUD | Toxic to sperm and ovum; prevents implantation | Failure under 1%; most effective emergency contraception up to 5 days |
| Levonorgestrel | Delays ovulation | Emergency use within 72 hours |
| Ulipristal | Progesterone receptor modulator | Emergency use within 120 hours |
- Enzyme inducers (carbamazepine, phenytoin, rifampicin) speed oestrogen and progestogen metabolism, so the pill may fail: advise a copper IUD, LNG-IUS or depot injection. The combined pill lowers lamotrigine levels.
- Long-term combined pill use is linked to hepatocellular adenoma, which can rupture and bleed (sudden RUQ pain, hypotension, normal AFP). Do not biopsy; stop the pill.
- Benefits: lower ovarian and endometrial cancer risk.
Other sex hormone drugs
- HRT: oestrogen for vasomotor symptoms; add progestogen if the uterus is present; transdermal has lower VTE risk.
- Tamoxifen: SERM, antagonist in breast, agonist in endometrium (endometrial hyperplasia and cancer, bleeding) and bone; VTE and hot flushes. Raloxifene: bone agonist, breast and uterine antagonist.
- Aromatase inhibitors (anastrozole, letrozole): postmenopausal ER-positive breast cancer; osteoporosis, arthralgia; letrozole for ovulation induction.
- Clomifene: blocks oestrogen receptors in the hypothalamus, removing oestrogen negative feedback; GnRH, FSH and LH rise and drive follicle growth and ovulation in PCOS. Risks: multiple pregnancy, ovarian hyperstimulation.
- GnRH agonists (goserelin): initial flare, then pituitary desensitisation; prostate cancer (cover the flare), endometriosis. Degarelix (antagonist) has no flare.
- Finasteride (5α-reductase), cyproterone, bicalutamide, spironolactone for androgen effects. Mifepristone with misoprostol for medical abortion.
- Natural oestrogens: estradiol is the most potent; estriol is the main pregnancy oestrogen. The corpus luteum makes progesterone and oestrogen until the placenta takes over at about 8–10 weeks.
Magnesium sulphate in eclampsia
- IV magnesium sulphate is the drug of choice to stop and prevent eclamptic seizures (better than diazepam or phenytoin). Toxicity: loss of patellar reflexes first, then respiratory depression; antidote IV calcium gluconate.
Bone drugs
| Drug | Mechanism | Notes |
|---|---|---|
| Bisphosphonates (alendronate, zoledronic acid) | Inhibit osteoclasts (farnesyl pyrophosphate synthase) | Osteoporosis first line, Paget, hypercalcaemia; take fasting, upright, with water; jaw osteonecrosis, atypical femoral fractures |
| Denosumab | Anti-RANKL antibody | Rebound fractures if stopped; hypocalcaemia |
| Teriparatide | Intermittent PTH (1–34): anabolic | Severe osteoporosis |
| Romosozumab | Anti-sclerostin | Cardiovascular risk |
| Calcitonin | Inhibits osteoclasts | Short-term hypercalcaemia |
| Cinacalcet | Calcium-sensing receptor agonist | Secondary hyperparathyroidism |
- Patients on long-term steroids (7.5 mg prednisolone or more for 3 months) get a bisphosphonate with calcium and vitamin D.
- Hypercalcaemia of malignancy: IV saline, then IV bisphosphonate.
Remember Continuous GnRH shuts the pituitary down; pulsatile GnRH switches it on.
Exam trap Carbimazole with a sore throat: stop the drug and check neutrophils the same day.
How FCPS asks about this
- Carbimazole with sore throat and fever: stop it and check the blood count.
- Antithyroid drug in the first trimester or thyroid storm: propylthiouracil.
- Hypotension and hyponatraemia after stopping long-term prednisolone: ACTH suppression with adrenal atrophy.
- Most effective emergency contraception up to 5 days: copper IUD.
- Clomifene mechanism: blocks hypothalamic oestrogen feedback, raising FSH and LH.
- Antenatal steroids: accelerate fetal lung maturity.
- Levothyroxine in angina: start 25 micrograms, increase slowly; over-replacement causes AF and bone loss.
Test yourself on this topic
5 of the 111 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A student has had sneezing, a blocked nose and pale, boggy nasal mucosa for 3 months (perennial allergic rhinitis). Which treatment is most effective for nasal congestion?
Answer: Intranasal corticosteroid spray daily
Intranasal corticosteroids (for example fluticasone, mometasone) are the most effective treatment for allergic rhinitis, especially congestion, with regular daily use for several days before full effect. Non-sedating oral antihistamines help sneezing and itch. Topical decongestants should be limited to a few days because of rebound congestion (rhinitis medicamentosa). Allergen avoidance and, in selected cases, immunotherapy are used.
Allergic rhinitis
- Best: intranasal steroid daily
- Add non-sedating antihistamine
- Topical decongestant: max ~7 days
- Rebound: rhinitis medicamentosa
Remember Spray steroid daily for a blocked allergic nose.
Exam trap Long-term topical decongestants cause rebound congestion.
Why the other options are wrong
- Oral decongestant for months Hypertension, insomnia; not for long term.
- Topical decongestant spray for months Rebound congestion after about a week.
- Oral antibiotics Not an infection.
- Oral steroids long term Side effects outweigh benefit.
A 78-year-old with stable angina is diagnosed with hypothyroidism (TSH 28 mU/L). How should levothyroxine be started?
Answer: Low dose, 25 micrograms, increased slowly
Thyroid hormone increases heart rate, contractility and myocardial oxygen demand. In older people and those with ischaemic heart disease, starting at full replacement can provoke angina, arrhythmia or MI. Levothyroxine is started low (12.5–25 micrograms daily) and increased slowly every few weeks guided by TSH and symptoms. Younger healthy adults can start near full dose.
Starting levothyroxine
- Elderly or heart disease: start low
- 12.5–25 micrograms daily
- Increase slowly
- Young and well: near full dose
Remember Start low and go slow in the old heart.
Exam trap Worsening angina on starting thyroxine means the increase is too fast.
Why the other options are wrong
- Full dose of 1.6 micrograms/kg at once Risky in angina.
- Loading dose of 500 micrograms Only in myxoedema coma, with care.
- Liothyronine IV Not for routine replacement.
- Delay until angina is cured Hypothyroidism should still be treated.
A 27-year-old woman taking carbimazole for Graves disease finds she is 6 weeks pregnant. She is switched to propylthiouracil until the end of the first trimester. Which fetal abnormality linked to carbimazole is this switch meant to avoid?
Answer: Aplasia cutis of the scalp
Carbimazole and its active form methimazole cross the placenta, and exposure in weeks 6–10 is linked to an embryopathy: aplasia cutis (punched-out defects of scalp skin), choanal atresia, oesophageal atresia and abdominal wall defects. Propylthiouracil carries a lower risk of these defects, so it is preferred in the first trimester. Because propylthiouracil can cause severe liver failure, many guidelines advise switching back to carbimazole in the second trimester. The lowest dose that keeps free T4 at the upper end of normal is used.
Thionamides in pregnancy
- Carbimazole embryopathy: aplasia cutis
- Also choanal and oesophageal atresia
- First trimester: propylthiouracil
- Later: back to carbimazole (PTU liver risk)
Remember Scalp skin gap: think carbimazole in early pregnancy.
Exam trap Both thionamides cross the placenta and can cause fetal hypothyroidism and goitre if the dose is too high.
Why the other options are wrong
- Lumbosacral neural tube defect That is valproate and carbamazepine, or folate deficiency.
- Ebstein anomaly of the tricuspid That is lithium.
- Nasal hypoplasia, stippled epiphyses That is warfarin embryopathy.
- Phocomelia of the upper limbs That is thalidomide.
A woman on the combined oral contraceptive pill starts carbamazepine for epilepsy. What advice is needed?
Answer: Carbamazepine may make the pill fail
Carbamazepine, phenytoin, phenobarbital, topiramate and rifampicin induce hepatic enzymes, speeding metabolism of oestrogen and progestogen and causing contraceptive failure. A copper or levonorgestrel IUD, or medroxyprogesterone injection, is recommended instead. Valproate does not induce enzymes but is highly teratogenic.
Enzyme inducers and the pill
- Inducers: carbamazepine, phenytoin, rifampicin
- Faster breakdown of hormones
- Risk: contraceptive failure
- Use IUD or depot injection
Remember Inducers wash the pill out.
Exam trap Lamotrigine levels fall with the combined pill; the interaction runs both ways.
Why the other options are wrong
- No interaction exists Enzyme induction is well known.
- The pill will raise carbamazepine to toxic levels Not the main interaction.
- Carbamazepine increases the pill's clotting risk Not the main issue.
- She should take the pill twice daily Not an appropriate solution.
A woman with primary hypothyroidism on levothyroxine asks how her dose will be adjusted. Which test is used, and how soon after a dose change should it be repeated?
Answer: TSH, after 6–8 weeks
Levothyroxine (T4) has a half-life of about 7 days, so a steady state takes about 5–6 weeks; TSH is therefore rechecked 6–8 weeks after starting or changing the dose, aiming for TSH within the reference range. It is taken on an empty stomach, separate from iron, calcium and PPIs, which reduce absorption. In elderly patients or those with ischaemic heart disease, it is started at a low dose and increased slowly to avoid angina or arrhythmias. Requirements rise in pregnancy (often by 25–50%), and enzyme inducers increase clearance. In secondary (pituitary) hypothyroidism, TSH is unreliable and free T4 is monitored.
Levothyroxine
- Half-life ~7 days; steady state ~6 weeks
- Monitor TSH at 6–8 weeks after change
- Take on empty stomach; avoid with iron, calcium, PPI
- Elderly/IHD: start low, go slow
- Pregnancy: dose ↑ 25–50%
- Pituitary cause: monitor free T4
Remember Change the dose, wait six weeks, check TSH.
Why the other options are wrong
- T3, after 3 days Too soon; T3 is not the main guide.
- Thyroid antibodies, monthly Not used for dosing.
- Isotope uptake, yearly Not used for replacement monitoring.
- Serum calcitonin Medullary carcinoma marker.
Where this sits in the CPSP syllabus
- Paper 1: GI, respiratory and endocrine drugs, Thyroid, corticosteroid, sex hormone and bone drugs
- Surgery & Allied, Paper 2: Drugs in surgical practice, Antithyroid drugs and perioperative thyroid care
- Medicine & Allied, Paper 2: Systemic drugs, Thyroid and antithyroid drugs
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