Lecture 83: Pharmaceutical care of hypo- and hyper- thyroidism

What are the 2 main jobs of the thyroid gland?

1. Make thyroid hormones (T3 and T4) which control metabolism and regulate heart rate, energy use and development

2. Makes calcitonin which lowers blood calcium

What is the role of the parathyroid gland?

Sit behind the thyroid, makes parathyroid hormone and increases blood calcium (opposite to calcitonin)

What is the process from the hypothalamus as to how thyroid hormones are produced?

1. Hypothalamus produces thyrotropin-releasing hormone (TRH) which stimulates pituitary gland to produce thyroid stimulating hormone (TSH)

2. TSH binds and activates the thyroid gland to produce thyroid hormones (T4 and T3)

3. T4/T3 go back to pituitary gland and hypothalamus to promote negative feedback, to stop producing TRH/TSH

What is primary hypothyroidism?

Characterized by dysfunction of the thyroid gland itself, leading to insufficient hormone production

What are the causes of primary hypothyroidism?

Autoimmune thyroiditis, iodine deficiency, post-thyroidectomy, drug-induced factors, and congenital diseases like thyroid agenesis

What are some symptoms of hypothyroidism?

• Fatigue

• Weight gain

• Cold intolerance

• Constipation

• Bradycardia

• Dry skin / coarse hair

How is hypothyroidism diagnosed?

Clinical symptoms + thyroid function tests (TSH and FT4 (free thyroxine))

Can also use thyroid antibodies (TPOAb, TgAb, TRAb)

What thyroid function test results indicates overt and subclinical primary hypothyroidism, and secondary hypothyroidism?

Overt: High TSH + low FT4

Subclinical: Slightly raised TSH + normal FT4

Secondary: Low TSH + low FT4

What is the purpose of a short synacthen test in hypothyroidism?

To assess for glucocorticoid deficiency (low cortisol)

Why must adrenal (glucocorticoid specifically) insufficiency be ruled out before starting thyroid hormone?

Thyroid hormone increases metabolism and cortisol breakdown, which can cause adrenal crisis if cortisol levels are low

What is the first-line treatment for hypothyroidism and the usual starting dose?

Levothyroxine

1.6 micrograms/kg, rounded to the nearest 25 micrograms

What must be treated before starting levothyroxine if present?

Glucocorticoid deficiency

How often are thyroid function tests (TFTs) monitored in hypothyroidism?

Every 3 months until stable, then annually

What should be checked if TSH is normal but symptoms persist?

FT4 to assess for secondary hypothyroidism

When might once-weekly levothyroxine dosing be used?

In poor adherence or patients unable to self-medicate (rare)

What are some counselling points for patients taking levothyroxine?

Take 30-60 minutes before food/other medications so usually immediately after waking up

Interactions: foods/milk, calcium/iron supplements, PPIs, comorbidities like IBD or coeliac

How does uncontrolled hypothyroidism affect pregnancy and how often should TSH be monitored during?

Impairs fertility and can cause teratogenic effects

Measure TSH every 4-6 weeks

What change is made to levothyroxine dose in pregnancy?

Increase by 25–50 micrograms immediately

Safe for breastfeeding

What is hyperthyroidism?

Excess production of thyroid hormones from the thyroid or pituitary

What is thyrotoxicosis?

A condition caused by excessive thyroid hormone levels in the body

What are the core symptoms of hyperthyroidism?

Weight loss, increased appetite, anxiety, tremor, heat intolerance, and palpitations

What is Graves’ disease?

An autoimmune cause of hyperthyroidism involving thyroid-stimulating antibodies

What is thyroiditis?

Inflammation of the thyroid causing pain and fluctuating thyroid hormone levels

What thyroid function test (TFT) results indicate hyperthyroidism of thyroidal origin and how is a definitive diagnosis made?

Low TSH + raised FT4 and FT3 (TRABs confirm thyroiditis)

Diagnosis requires 2 sets of TFTs taken at least 6 weeks apart

What is the first-line pharmacological treatment for hyperthyroidism and give information about dosing?

Carbimazole 20-60mg daily

Works within 4-8 weeks

When at normal level, can either titrate dose down or block with carbimazole and add levothyroxine to ensure controlled levels

What are key side effects and contraindications of carbimazole?

Side effects: macropapular rash (treat with antihistamine), bone marrow suppression

Contraindications: pregnancy, pre-existing blood disorders, severe hepatic impairment

What are the main counselling points for carbimazole?

• Explain may need other medications for the plan, e.g. B-blockers for symptom management

• Advise on urgency to report signs/symptoms of blood dyscrasias

• Start contraception as is teratogenic

• May influence warfarin doses

What is the mechanism of action of carbimazole?

Prodrug converted to methimazole that inhibits thyroid peroxidase, reducing synthesis of T3 and T4

What is the second line pharmacological treatment for hyperthyroidism?

Propylthiouracil

What is the mechanism of action of propylthiouracil?

Inhibits thyroid peroxidase to reduce T3 and T4 synthesis and also inhibits peripheral conversion of T4 to T3

What are the side effects and contraindications of propylthiouracil?

Side effects: macropapular rash, acute liver injury, bone marrow suppression, thrombocytopenia, risk of agranulocytosis

Contraindications: hepatic impairment, pre-existing blood disorders

What is involved in the monitoring for antithyroid drugs (e.g. carbimazole and propylthiouracil)?

TFTs every 6 weeks until stable, then TSH every 3 months

After stopping → check at 8 weeks, then every 3 months for 1 year

What is the aim and effect of radioactive iodine treatment?

Resolve hyperthyroidism while limiting hypothyroidism; takes 2–3 months to work

What is the key safety advice after radioactive iodine treatment?

Avoid close contact (especially pregnant women/children) as patient is radioactive for up to 6 weeks

How is radioactive iodine treatment monitored?

Check TSH every 6 weeks until within range

When is thyroidectomy indicated?

Large goitre (enlargement of thyroid gland) causing compression symptoms (e.g. airway/windpipe)

What is given after total thyroidectomy?

Levothyroxine at ~1.6 micrograms/kg

What is thyroid crisis (thyrotoxic storm)?

A severe, life-threatening form of hyperthyroidism causing multiorgan failure

What can trigger thyroid crisis?

Infection, trauma, surgery, radioiodine, medications, or stopping antithyroid drugs

What are the key symptoms of thyroid crisis?

Hyperthermia, tachycardia, hypotension, dehydration, confusion/agitation

What are the 4 treatment principles of thyroid crisis and drug example for each?

1. Inhibit hormone synthesis - carbimazole

2. Inhibit hormone release - iodine (Lugol’s solution)

3. Inhibit peripheral action - propranolol

4. Supportive care - help underlying e.g. use antipyretics

Which drugs inhibit thyroid hormone synthesis in thyroid crisis?

Carbimazole and propylthiouracil