NES Pharmacy CPD: Thyroid Developed and delivered by Dr James Boyle SpR in Endocrinology Glasgow Royal Infirmary February 2010 Amended by NES 2010

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 4

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 Multinodular Goitre 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 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