THYROID DISEASEDr 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

• 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

• 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

TSH

T3, T4

--

TSH

T3, T4

++

T3, T4

++

TSH

Hypothyroidism Hyperthyroidism Hypopituitarism TSH secreting tumour

↑TSH; ↓T4,T3 ↓TSH; ↑T4,T3 ↓TSH; ↓T4,T3 ↑TSH; ↑T4,T3

--

TSH

T3, T4

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 CancersType 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 5-10 >60 10

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