Thyroid Disease Dr J. Bennett FY2

Objectives To understand basic thyroid axis physiology To know the common causes of hypo and hyperthyroidism To recognise the signs and symptoms associated with hypo and hyperthyroidism To understand TFT interpretation To know the management for hypo and hyperthyroidism, and the more important complications associated with these

Hypothalamus-Pituitary-Thyroid Axis Hypothalamus secretes thyrotropin-releasing hormone (TRH) TRH stimulates thyroid stimulating hormone (TSH) from anterior pituitary. TSH stimulates T3 & T4 production from the thyroid T3 & T4 exert –ve feedback on the pituitary and hypothalamus.

Hypothyroidism - Aetiology Primary hypothyroidism Autoimmune mediated Primary atrophic hypothyroidism Hashimoto’s thyroiditis Acquired Iatrogenic – Post-thyroidectomy or radio-iodine treatment Drug-induced – Anti-thyroid, lithium, amiodarone Iodine deficiency – Most common cause worldwide Sub-acute thyroiditis – May result in thyroroxicosis for first 4-6 weeks Post partum thyroiditis Sick euthyroidism - Secondary hypothyroidism – hypopituitarism (rare)

Hypothyroidism – Signs and Symptoms Weight gain Fatigue, lethargy Dislike of cold Constipation Menorrhagia Hoarse voice Myalgia Carpal tunnel syndrome Psychiatric symptoms Depression Dementia Signs General Dry skin and hair Goitre Non-pitting oedema Facial features – purple lips, malar flush, periorbital oedema, lateral eyebrow loss CVS Bradycardia Neuro Cerebellar ataxia Slow relaxing reflexes Peripheral neuropathy

Hyperthyroidism – Aetiology Hyperthyroidism (thyrotoxicosis) Graves Disease (76%) IgG antibodies directed against TSH receptors on thyroid – stimulates T3 & T4 production and proliferation of thyroid follicular cells Long term can result in hypothyroidism Toxic adenoma and toxic multinodular goitre Autonomously secretes thyroid hormones, inhibits endogenous TSH Thyroiditis Iodide induced TSH induced – eg TSH secreting pituitary adenoma (rare)

Hyperthyroidism – Signs and Symptoms Weight loss Increased appetite Heat intolerance Palpitations Fatigue Sweating Diarrhoea Oligomenorrhoea Psychiatric symptoms Irritability Emotional lability Psychosis Signs General Hair thinning Goitre Lid lag, lid retraction Pre-tibial myxoedema Eye signs Palmar erythema CVS Tachycardia AF Neuro Fine tremor

Hyperthyroidism – Eye Disease Associated with Graves’ disease Inflammation of retro-orbital tissues Symptoms Eye discomfort, grittiness Excess tear production Photophobia Diplopia Decreased acuity Signs Exopthalmos Proptosis Opthalmoplegia

Investigations – TFTs T3, T4 + TSH TSH + T3, T4 Hypothyroidism - TSH TSH TSH + - T3, T4 T3, T4 T3, T4 Hypothyroidism Hyperthyroidism Hypopituitarism TSH secreting tumour ↑TSH; ↓T4,T3 ↓TSH; ↑T4,T3 ↓TSH; ↓T4,T3 ↑TSH; ↑T4,T3

Investigations – Other tests Bloods Thyroid auto-antibodies TSH receptor antibodies – Graves’ disease USS Thyroid + FNAC Isotope scan

Hypothyroidism - Management Conservative Lifestyle - smoking cessation, weight loss Medical Levothyroxine (T4) – adjust dose according to clinical response and normalisation of TSH levels. Caution required in patients with IHD as exacerbation of myocardial ischaemia and infarction are known complications Surgical Symptomatic – carpal tunnel decompression, thyroidectomy if compression of local structures

Hyperthyroidism - Management Conservative Smoking cessation – especially with Graves’s ophthalmology, associated with worse prognosis Medical Symptomatic – β-blockers Carbimazole, propylthiouracil Risk of agranulocytosis Radio-iodine treatment – caution in patients of childbearing age; must avoid contact with pregnant women and small children Long term likely to become hypothyroid Usually avoided in Graves’ disease

Hyperthyroidism - Management Surgical Subtotal/total thyroidectomy Orbital decompression if thyroid eye disease causing compression of optic nerve Complications of thyroid surgery Immediate Haemorrhage (haematoma can cause airway obstruction) Short term Infection Long term Damage to laryngeal nerve – hoarse voice Hypothryoidism Transient hypocalcaemia Hypoparathyroidism

Thyroid Storm Medical emergency (rare) – 10% mortality even with early recognition and management Aetiology - Infection in a patient with unrecognised or inadequately treated thyrotoxicosis Post 131I treatment or post sub-total thyroidectomy Signs Fever Agitation and confusion Tachycardia +/- AF Management IV fluids Broad spectrum antibiotics Propanolol, digoxin Antithyroid drugs – sodium ipodate, Lugol’s solution, carbimozole

Thyroid Cancers Type of tumour Frequency (%) Age at presentation (years) 20 year survival (%) Papillary 70 20-40 95 Follicular 10 40-60 60 Anaplastic 5 >60 <1 Medullary 5-10 >40 50 Lymphoma

Clinical Scenario 39 year old lady presents with 3 months history of weight loss and diarrhoea. She has been suffering from excessive sweating and a recent family holiday to Tunisia was ruined as she was unable to tolerate the weather. Her eyes also feel gritty a lot of the time and she has had friends ask her why she is staring at them. She is otherwise well and her only medication is St John’s Wort. She has no known allergies. She does not smoke and drinks alcohol socially. On exam she is slight with sweaty palms and a fine tremor when her arms are out stretched. Her pulse is 100bpm and irregularly irregular. She has exophthalmos and lid lag. She also has a diffuse non tender swelling on the front of her neck which moves with swallowing. What are your differentials for this lady? How would you investigate her? How would you manage her? What are the cardinal features of Grave’s disease? What drug is used in pregnant hyperthyroid patients? What are complications of thyroid surgery?

Further topics to cover Thyroid Anatomy Cellular structure and function Blood supply Thyroid physiology Production of T3 and T4 in thyroid follicles Transport of T3 and T4 (protein binding) Peripheral conversion of T4 to T3 Further TFT results and their significance Impact of amiodarone on the thyroid – complex, can cause both hypo and hyperthyrodism Details of thyroid malignancy Management of thyroid disease in pregnancy