Thyroid Disorder PDF

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Summary

Thyroid Disorder- Hypothyroidism- Primary (~95%) - Failure of the thyroid gland to produce thyroid hormones. Iodine deficiency (less common in developed countries) Autoimmune thyroiditis e. Hashimoto’s Destruction of thyroid gland e. Surgery, radioactive iodine, radiotherapy Drugs e. amiodarone and ...

Description

Thyroid Disorder - Hypothyroidism • Primary (~95%) - Failure of the thyroid gland to produce thyroid hormones. Iodine deficiency (less common in developed countries) Autoimmune thyroiditis e.g. Hashimoto’s Destruction of thyroid gland e.g. Surgery, radioactive iodine, radiotherapy Drugs e.g. amiodarone and lithium Congenital hypothyroidism • Secondary (~5%) -> endocrine referral - Underproduction of TSH by pituitary gland. Pituitary or hypothalamic dysfunction Tumours, surgery, trauma, radiotherapy, etc. Overt or Subclinical Hypothyroidism Overt – May or may not be symptomatic – T4 ↓ TSH ↑ Aim: To improve symptoms and get TFTs back in range (or close to range) Subclinical – Usually, asymptomatic – Many people do not need treatment o Interval screening of TFTS – If symptoms-trial of levothyroxine – T4 ↔ (normal) TSH ↑ Symptoms may take a while to improve (for weeks-months)

Clinical Features Symptoms Fatigue Cold intolerance Weight gain Non-specific weakness Arthralgia Myalgia Constipation Menstrual irregularities Depression Impaired concentration, and memory Dry skin, and reduced body and scalp hair Thyroid pain

Signs Changes to appearance such as: coarse dry hair and skin and hair loss Oedema Vocal changes such as hoarseness or deepening of the voice Goitre Bradycardia Diastolic hypertension. Delayed relaxation of deep tendon reflexes. Paraesthesia —due to carpal tunnel syndrome

Complication of Hypothyroidism • CV complications – Dyslipidaemia, CHD, HF • Reproductive – Fertility, complications in pregnancy • Neurological – Deafness, concentration, memory, language, perception • Myxoedema coma...medical emergency

INVESTIGATION TFTs requested if: – clinical suspicion of thyroid disorder, due to presenting symptoms/signs – to rule this out as part of a screening process e.g. osteoporosis, AF, subfertility, amiodarone, lithium, diabetes, autoimmune diseases… – People with existing thyroid disorders for monitoring purposes (or at high risk of developing these) • Usually test TSH (and free T4) • Further testing e.g. T3, thyroid antibodies • Other types of investigation e.g. biopsy, scans

Management of Overt Hypothyroidism Often managed in primary care • Consider a referral to endocrinologist if – Goitre, suspected Addison’s disease, pregnant/planning pregnancy, cardiac disease, atypical thyroid tests, drug causes • Levothyroxine 1stline – Aim to resolve signs/symptoms, normalise TSH • Liothyronine (rarely used) – Endocrinologist Levothyroxine: Ideally should be taken at least 30 minutes before breakfast, caffeine containing liquids or other drugs Initiation: • 1.6 microgram/kg/day (rounded to nearest 25 micrograms) for adults 60-65yrs o 25-50 micrograms adjusted in 25 microgram increments Key Points: Monitor TSH and patient symptoms; adjust/titrate dose

NICE: TFTs [at least] 3 monthly until stable TSH reached (2 similar measurements in the ref range 3m apart), then annually Adverse effect of levothyroxine: (often with excessive dosing) • GI disturbances • CV –arrhythmias, tachycardia • Flushing, fever, heat intolerance • Weight loss • Hypersensitivity reactions –rash, oedema etc. • Muscle cramps, weakness • Anxiety, tremor, restlessness, insomnia • Mania • Menstrual irregularities • Headache

Drug Interactions: - Calcium/Antacids/Iron Salts – decreases the absorption of levothyroxine (at least 4 hours apart) - Amiodarone - predicted to increase the risk of thyroid dysfunction when given with Levothyroxine - Carbamazepine - increase the risk of hypothyroidism when given with Levothyroxine - HRT - decrease the effects of Levothyroxine - Phenytoin - increase the risk of hypothyroidism when given with Levothyroxine - Phenobarbital - decrease the effects of Levothyroxine

Hyperthyroidism: TSH (low), T4 (high) endocrine referral Primary hyperthyroidism - Most commonly Graves’ disease (autoimmune) – antibodies stimulate and increase secretion of thyroid hormones – Confirmed by testing for TSH receptor antibodies –secondary care - Other causes e.g. toxic multinodular goitre, toxic thyroid nodule, drugs e.g. amiodarone, lithium Secondary - Such as a TSH secreting pituitary tumour

Clinical Features Symptoms Breathlessness, dysphagia, neck pressure (may be caused by a toxic multinodular goitre). Hyperactivity Emotional lability Insomnia, irritability, anxiety Palpitations Exercise intolerance Fatigue, muscle weakness Heat intolerance Increased appetite with weight loss Diarrhoea Infertility, oligomenorrhoea, amenorrhoea. Polyuria Generalized itch Reduced libido, gynaecomastia in men. Deterioration in blood glucose control and hyperglycaemia in people with diabetes mellitus

Sign Agitation, fine tremor, warm moist skin, palmar erythema. Sinus tachycardia, atrial fibrillation, heart failure, dependent oedema. Eye signs. Goitre Gynaecomastia in men Splenomegaly Muscle wasting

Hyperthyroid Complications: • Cardiovascular-including atrial fibrillation and associated increased stroke risk • Osteoporosis • Eye disease, which can lead to vision loss • Thyroid storm: release of large amounts of thyroid hormone and sudden worsening of symptoms-medical emergency that can lead to loss of consciousness

Management: • Refer to specialist and consider following options: • Surgery • Radioiodine treatment • Antithyroid drugs –carbimazole, propylthiouracil – Short-term while waiting for specialist review – Short-term in prep for radioiodine treatment or surgery – Medium-term in inducing remission of Grave’s disease – Long-term where radioiodine treatment or surgery is contraindicated or declined

Management for adrenergic symptoms: Consider prescribing a beta-blocker and titrating the dose depending on clinical response, to provide relief of adrenergic symptoms (tachycardia, sob, HTN) • The beta-blockers propranolol (used most commonly), metoprolol, and nadolol are licensed for the treatment of thyrotoxicosis as an adjunct to anti-thyroid drug treatment • e.g. – Propranolol 10–40 mg three to four times a day. Modified-release 80 mg and 160 mg capsules are available which can be administered once daily. (Diltiazem could be used as alternative in asthma)

Radioiodine treatment: Induces damage of DNA leading to death of thyroid cells. •Radioprotection measures after treatment – e.g. close and prolonged contact with children and pregnant women should be avoided for ~ three weeks after standard-dose radioiodine treatment. • Not recommended for people with active thyroid eye disease as it may worsen this • Contraindicated in pregnancy and in women who are breastfeeding. – Women should be advised to avoid becoming pregnant for at least six months after radioiodine treatment. – Men should be advised not to father children for at least four months after radioiodine treatment.

• Most people with Graves' disease become euthyroid and then hypothyroid within six weeks to six months after completing radioiodine treatment.

Anti-thyroid drugs: High dose (usually) carbimazole is given initially, then following repeat TFT, if things are improving, adjustment of medication by either: – Titration-block regime (40%) –Dose adjustment every 4-6weeks, dose reduced if T4 falls to low or low-normal levels indicating hypothyroidism (aiming to use lowest dose of drug that achieves euthyroidism) – Block and replace regime (60%) —the anti-thyroid drug is used to block the synthesis of thyroid hormone. T4 is monitored and levothyroxine is added. Adjustments to the levothyroxine dose are made to maintain T4 levels in the reference range. • For both regimes, the remission rate is about 50% if treatment is continued for 6–18 months and then stopped. Carbimazole: - Check FBC and LFT first Dose: - 15 to 40mg daily - Reduced to maintenance dose of 5 to 15mg - Usually for 12-18 months - Or if using as part of a block and replace regimen 40-60mg daily - Many people with Graves' disease become euthyroid after 4–8 weeks of treatment with carbimazole Adverse effects: Nausea, taste disturbance, headache, fever, malaise, and arthralgia. • Itch and rash (common) —can usually be treated with antihistamines without the need to stop drug treatment. Usually goes away within a week or so. • Bone marrow suppression (including pancytopenia and life-threatening agranulocytosis)

– If occurs STOP (don’t re-start) and consider referral for alternative management options. • Hepatobiliary disorders, most commonly jaundice (stop)

Neutropenia and agranulocytosis (BNF): (always ask for easy bruising or bleeding) - Patient should be asked to report symptoms and signs suggestive of infection, especially sore throat and fever. - A white blood cell count should be performed if there is any clinical evidence of infection (same day). - Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia.

Propylthiouracil: (risk of severe liver injury) Indication: - Useful if carbimazole not tolerated - In pregnancy or trying to conceive

- History of pancreatitis Dose: - 200 to 400mg daily in divided doses in adults - Maintained until the patient becomes euthyroid; the dose may then be gradually reduced to a maintenance dose of 50 to 150mg daily in divided doses. - Dose adjustments in renal impairment Adverse effect: - Leucopenia (reversible) - Rarely, cutaneous vasculitis, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis, hypoprothrombinaemia, nephritis, lupus erythematous-like syndromes. - Hepatic disorders including hepatitis, hepatic failure, encephalopathy, hepatic necrosis (usually develop within 6 months of starting the drug)

Amiodarone and Lithium Induced Thyroid Disorder: Hypothyroidism: continue amiodarone/lithium just increase levothyroxine after checking TFT. TFT monitoring before (TSH,T3,T4,thyroidantibodies) and during treatment (TSH,T3, T4) and for a year after stopping (long t1/2)

Osteoporosis: Causes: -

aging postmenopausal women men >50 long term oral glucocorticoids IBD, Hyperthyroidism, Cushing’s syndrome, celiac disease

Risk Factors: •Fragility # •Excess alcohol (>14 women, >21men) •Smoking •Immobility •Falls Drugs: - Corticosteroids - PPIs - Anti-epileptics - SSRIs - Aromatase inhibitors - Parental hip fracture Secondary causes: - amenorrhoea - eating disorders - inflammatory bowel disease - Rheumatoid Arthritis - COPD - early menopause/hypogonadism - low BMI (65 female >75 male) – Other patients with specified risk factors • Fracture risk assessment tools available include FRAX® and QFracture® • Following risk assessment: – Lifestyle advice (smoking, alcohol, vitD, calcium, exercise) – refer for DXA (specialist review) – start treatment (red)

FRAX is an online tool that can be used to assess fracture risk (40-90 yrs) Gives a result as: 10 year risk of osteoporotic fracture and 10 yr risk of hip fracture (%) Links to NOGG (National Osteoporosis Guideline Group) guidance which classifies patients as red (start treatment) amber (DXA scan) or green (lifestyle advice) www.shef.ac.uk/FRAX QFracture: shows a 10 year probability of fracture of at least 1% Secondary prevention: pick up over 50s with fragility fracture and offer DXA scan Hip Fracture Interventions: If already on treatment check adherence and administration • Lifestyle advice • Falls assessment • Including medication review • Prevention of venous thromboembolism with LMWH • Appropriate pain management Vertebral Fracture Intervention: • Lifestyle advice • Pain control and analgesia review • Physiotherapy • Surgical management

Pharmacological Treatment: • Oral Bisphosphonates - alendronic acid (for women 70 mg/week, for men 10mg OD) *first line* - risedronate (35mg/week) - ibandronic acid (150mg/monthly) Main drug interactions (absorption)

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Avoid any other medicines for at least 30 mins Avoid calcium supplements for at least 2 hours (preferably 4hrs) iron supplement antacids

Main cautions & contraindications - eGFR35) - CALCIUM and - VITAMIN D before each infusion (correct first) - Regular dental check-ups + ONJ reminder card - ibandronic acid (3mg/3monthly IV)

• Denosumab (subcutaneous injection)

- 60mg/ 6monthly - First dose in hospital; after that via GP - Check bloods before each injection (renal, calcium, vitamin D); hypocalcaemia risk - Correct calcium deficiency, vitamin D loading if D low. - Not renally excreted but caution in renal impairment due to increased risk of hypocalcaemia(deaths and hospital admissions reported) - ?Increased risk of UTI/chest infection, rash/cellulitis - No drug interactions known - Rare atypical fracture/osteonecrosis of jaw (good dental hygiene, report hip/thigh/groin pain) - NOT suitable for drug holiday o Risk of new + worsening vertebral # quickly increases to levels similar to risk in untreated pts o Missing one dose or delaying by a few months may increase # risk o Half of patients sustained >1 vertebral # o Higher risk if hxvertebral # o ?Consider alternative treatment on denosumabcessation e.g. bisphosphonate • Calcium (500-1000mg OD) • VitD (400-800 IU OD) • Less commonly used: –HRT (early menopause 7.5mg/day, all doses increase # risk significantly at the spine - Increased risk of vertebral and non-vertebral (including hip) #, Spine # more common than hip # - # risk declines after d/c and on continued therapy - In UK, FRAX links to NOGG Guidance - 2 points on graph relate to lower (2.5mg) and higher doses of steroids (7.5mg). - If much higher than 7.5mg may need to adjust risk further upwards - Generally if higher risk, E.g. 70 yrs+ female , high dose pred+ other CRF, BMD...