NES Pharmacy CPD: Thyroid

SpR in Endocrinology

Glasgow Royal Infirmary

February 2010

Amended by NES 2010

Developed and delivered by Dr James Boyle

Glands and Hormones

Endocrine Glands: Glands that secrete their products (hormones) directly into the bloodstream rather than through a duct

Hormone: Chemical substance formed in the body that is carried in the bloodstream to affect another part of the body.

Thyroid gland

Secrets two iodinated hormones T3 and T4. Responsible for optimal growth, development

and function of body tissues. The synthesis of T3 and T4 requires iodine. Release of T3 and T4 controlled by negative

feedback.

TRH/TSH Feedback Loop

TRH

Thyrotrophin releasing hormone. Tripeptide produced by hypothalamus. Release is pulsatile. Downregulated by T3.

Travels through portal venous system to adenohypophysis.

Stimulates TSH synthesis and release.

TSH

Thyroid stimulating hormone. Produced by the pituitary gland Upregulated by TRH Downregulated by T4, T3

Travels through portal venous system to cavernous sinus and body.

Stimulates several processes synthesis and release of hormones from the gland as well as gland growth

Thyroid hormones (T4, T3)

T3/T4 enter circulation transported to plasma proteins (99%).

Thyroid only contributes 20% of the free circulating T3 with the rest produced by peripheral conversion of T4 to T3. T4 may be deiodinated to inactive reverse T3.

Regulation is based on the free component of thyroid hormone.

Action not understood but thought to involve high affinity binding sites in plasma membrane, mitochondria and nucleus resulting in protein synthesis and increased energy metabolism.

Common diagnostic tools

TSH Free T3, Free T4

Thyroid autoantiboides Thyroid ultrasound Radio-isotope uptake and scan Fine need aspiration of thyroid

Hypothyroidism

Clinical syndrome that results in deficiency of the thyroid hormones T4 and T3.

Common, prevalence 1-2% F:M preponderance of 10:1 Congenital hypothyroidism is 1:4000 live

births in the UK.

Types of hypothyroidism

Primary – Thyroid gland failure

Secondary – Pituitary failure

Tertiary – Hypothalamic failure

Sub-clinical

Aetiology of hypothyroidism

Agenesis Thyroid destruction

– Hashimoto’s thyroiditis– Surgery– Radio-iodine ablation– Infiltration (tumour, sarcoidosis)

Inhibition of function– Iodine deficiency– Anti-thyroid medications (Carbimazole, PTU, lithium, amiodarone)– Inherited defects

Transient– Postpartum– Sub-acute thyroiditis

Secondary/Tertiary (pituitary, hypothalamic)

Subclinical hypothyroidism

Estimated to affect 10% of females > 50yrs Normal FT4/FT3, mildly elevated TSH Few report symptoms High risk of developing primary hypothyroidism Can be associated with dyslipidaemia and

subtle cardiac abnormalities. Management a matter of clinical judgement

Clinical Presentation

Symptoms – Tiredness, cold intolerance, weight gain, constipation, aches and pains, depression, psychosis, angina and menorrhagia.

Signs – Hair loss, hoarseness, goitre, bradycardia, dry skin, slow relaxing reflexes, anaemia, heart failure, effusions, carpal tunnel syndrome, mxyoedema coma.

Diagnosis of hypothyroidism

Primary – Low FT4/FT3 and high TSH

Secondary – Low FT4/FT3 and low TSH

Tertiary – Low FT4/FT3 and low TSH

Sub-clinical – Normal FT4/FT3 and slightly high TSH

Management

Apart from subacute and postpartum thyroiditis most require long term replacement in form of Levothyroxine.

Starting dose usually 50 -100mcg/daily. Increased in steps of 25-50mcg every 4-6 weeks

until FT4 is above middle of normal range and TSH normal/low normal.

Usual maintenance is 100mcg-200mcg/daily. Suppressed TSH acceptable in certain cases

Management

In cardiac disease cautious replacement is required to decompensation ie. Thyroxine 25mcg with steps of 25mcg only.

In secondary/tertiary cases ensure good adrenal reserve before commencing thyroxine replacement and dont use TSH to assess response.

In pregnancy requirements go up 50-100% and more monitoring is required. Use TSH to monitor at least every trimester.

Management of subclinical cases

If TSH>10 – treat with thyroxine

If TSH 4-10 and asymptomatic – rpt TFT 6/12

If TSH 4-10 and symptomatic or antibodies +ve or dyslipidaemia or history or radioiodine or surgery – treat with thyroxine

Nurse Led Management

Patients often managed in nurse led clinics using questionnaire/algorithms.

Once patients with primary hypothyroidism are stable for 6 months (12 months for post radioiodine) they are discharged to GP for annual check.

Majority of patients unlikely to need to change dose of levothyroxine in the community.

Hyperthyroidism

Clinical syndrome associated with raised levels of the thyroid hormones T4 and/or T3.

Can be increased production, release from damaged gland or exogenous T4.

Prevalence 1-2% Incidence 3 per 1000 per year Secondary hyperthyroidism due to increased TSH

secretion is very rare (>1% of all cases) Common, prevalence 1-2%

Aetiology of hyperthyroidism

Grave’s disease Toxic multinodular goitre Toxic adenoma Thyroiditis (sub-acute, postpartum) Drug induced (amiodarone) Over treatment of T4 TSH secreting adenoma

Clinical Presentation

Symptoms – Heat intolerance, weight loss, loose motions, tremor, increased appetite, amenorrhoea, fatigue, anxiety, itch, angina.

Signs – Goitre, tachycardia, AF, tremor, warm hands, proximal myopathy, lid lag/retraction, Grave’s opthalmopathy, cardiac failure, hypertension, onycholysis, acropachy, pretibial myxoedema, thyroid storm .

Diagnosis of thyrotoxicosis

Primary – High FT4 and/or FT3 and low TSH

Secondary – High FT4 and/or FT3 and high TSH

Sub-clinical – Normal FT4/FT3 and low TSH

Grave’s disease versus Toxic MNG

Grave’s Disease

Female>male Peak age 20-40 years Diffuse and smooth Lid lag and retraction,

Grave’s eye signs, pretibial mxyoedma

Acropachy, onycholysis Autoantibodies usually

present RAU scan uniform increased

uptake

Multinodular Goitre

Female>male Peak age >50 years Multinodular goitre Lid lag and retraction No skin, nail or finger

changes Autoantibodies usually

absent RAU patchy, irregular

appearance

Management

Carbimazole 20-40mg daily to render euthyroid (alternatively PTU).

Propanolol 40mg bd/tds to control symptoms in the short term.

Dose titration or “block and replace” regimen depending on individual practice.

Decision of definitive therapy needs to be made.

Drugs

Carbimazole: Inhibits hormone production, side effects include rash and agranulocytosis (0.1%).

Propythiouracil: Inhibits hormone production as well as blocking T4 to T3 conversion, side effects include rash and agranulocytosis (0.4%).

Pregnancy and lactation

Increased risk of fetal and neonatal thyrotoxicosis. PTU preferred to Carbimazole due to less found in

breast milk and less crossing placenta. Carbimazole has been associated with aplasia cutis. Requirements fall in Grave’s. Lowest dose possible should be used. Radio-iodine contra-indicated during pregnancy TSH receptor titres should be determined early in third

trimester to assess risk of neonatal thyroid dysfunction.

Management

In Grave’s disease option to treat with drugs for 18 months and stop (50% chance of remission). Can also opt for radioiodine or surgery.

In toxic multinodular goitre/toxic adenoma need to use radioiodine or surgery to cure. Small number opt for long term drug therapy.

Radio-iodine therapy

131I is a safe and effective means of treatment. Emits locally destructive beta particles to lead to cell

damage and death over months. Render euthyroid with drugs first and stop before to

allow uptake of isotope. In Glasgow, antithyroid drugs are not restarted

afterwards unless thyrotoxicosis confirmed. High risk of subsequent hypothyroidism.

Nurse Led Management

Patients often managed in nurse led clinics using questionnaire/algorithms.

Very few if any patients discharged to GP on anti-thyroid drugs

Nurse led management appropriate if diagnosis made, decision of definitive therapy made and no complications.

Majority of patients unlikely to need to change dose of anti-thyroid drug in the long term.

Pharmaceutical Care Issues – Hypothyroidism (examples)

Monitoring for signs & symptoms for dosage– Compliance can be a problem

Advise on treatment increments Slow dose increments in heart disease Anaemia can be associated with hypothyroid

– Macrocytic mild anaemia (responds to thyroxine)– Pernicious anaemia common (treatment)

Pharmaceutical Care Issues – Hyperthyroidism (examples)

Explain dosage regime for carbimazole Monitor for side-effects of carbimazole

– skin rashes, sore throat or mouth ulcers

Monitor for side-effects of beta blockers Block & replace – also on thyroxine Eye grittiness ->hypromellose eyedrops