Hyperthyroidism Pathophysiology, differentials, investigations and management. Quiz Cases Dr Azeem Alam, MBBS BSc (Hons) Surgical AFP Guy’s and St. Thomas’ Hospital Endocrinology series Content reviewed on the 26/04/2020.
Case 1 History A 45-year-old lady presents to the GP with a 1-month history of ‘hot flushes’. She is very anxious and on occasion feels her chest thumping. Her clothes no longer fit, and she wonders if her symptoms could be due to menopause. On examination, she has a 2 cm diffuse neck swelling. Observations HR 101, BP 138/98, RR 18, SpO 2 99%, Temp 37.8°C. 2
Case 1 History A 45-year-old lady presents to the GP with a 1-month history of ‘hot flushes’. She is very anxious and on occasion feels her chest thumping. Her clothes no longer fit, and she wonders if her symptoms could be due to menopause. On examination, she has a 2 cm diffuse neck swelling. Observations HR 101, BP 138/98, RR 18, SpO 2 99%, Temp 37.8°C. 4 4
Pathophysiology Definition: hyperthyroidism reflects an increased level of circulating thyroid hormones, Pathophysiology leading to raised metabolic rate and sympathetic nervous system activation. (1) 5
Pathophysiology Pathophysiology 6
Pathophysiology Primary hyperthyroidism Pathophysiology • Excessive production of T3/T4 by the thyroid gland • Thyroid gland pathology • Most common subtype Secondary hyperthyroidism • Stimulation of the thyroid gland by excessive TSH • Originates due to pathology of the pituitary or hypothalamus • May also be secondary to a TSH-secreting tumour (1) 7
Primary hyperthyroidism Pathophysiology Graves’ disease • Anti-TSH receptor antibodies • Most common cause of hyperthyroidism (75%) • Diffuse goitre and thyroid eye signs Toxic multinodular goitre • Iodine deficiency • Compensatory TSH secretion • Nodular goitre formation • Nodules become TSH-independent and thyroid hormones (2) 8
Primary hyperthyroidism Toxic adenoma Thyroiditis Pathophysiology • Single autonomous functional • Initial stage will include transient nodule hyperthyroidism • Hypothyroidism is the final stage • Hashimoto’s and De Quervain’s thyroiditis Subclinical hyperthyroidism Drugs • • Amiodarone: causes both Normal T3/T4, low TSH • May be due to any of the above hyperthyroidism and hypothyroidism causes • Typically due to toxic multinodular goitre or Graves’ disease 9
Secondary hyperthyroidism Pathophysiology Pituitary adenoma Ectopic tumour Hypothalamic tumour • • • TSH-secreting pituitary hCG-secreting tumours (e.g. Excessive TRH secretion • adenoma choriocarcinoma) Rare cause of hyperthyroidism Choriocarcinoma (3) 10
Risk factors • Female gender : particularly for Graves’ disease • Family history • Other autoimmune conditions • Smoking : increases risk of Graves’ eye disease • Trauma to the thyroid : including surgery • Drugs : e.g. amiodarone 11
Clinical features THYROIDISM Mnemonic Pathophysiology Symptoms Signs Weight loss Postural tremor T remor Heat intolerance and Palmar erythema H eart rate increase sweating Y awning Palpitations Graves’ disease R estless • Thyroid acropachy O ligomenorrhoea • Pretibial myxedema I rritability • Eye signs D iarrhoea • E xophthalmos I ntolerance to heat • O phthalmoplegia S weating Menstrual irregularity Lid lag and retraction M uscle wasting Anxiety Goitre (weight loss) Hyperreflexia 12
Clinical features: general Pathophysiology Goitre (4) 13
Clinical features: Graves’ disease (5) Thyroid acropachy N o signs O nly signs no symptoms Exophthalmos S oft tissue involvement P roptosis E xtraocular muscle Pretibial involvement myxedema (5) (ophthalmoplegia) (6) C orneal involvement S ight loss 14
Investigations: stable patient Thyroid autoantibodies Autoantibody Condition Prevalence Anti-TSH receptor Graves’ disease 90-100% Hashimoto’s thyroiditis 0-5% Anti-TPO Graves’ disease 70-80% Hashimoto’s thyroiditis 90-95% Anti-thyroglobulin Graves’ disease 20-40% Hashimoto’s thyroiditis 30-50% 16
Investigations: stable patient Primary investigations: • Thyroid function tests (TFTs): first-line investigation • Antibodies : anti-TSH receptor antibodies (95%) and anti-TPO most often raised in Graves’ disease Investigations to consider: • Ultrasound: if thyrotoxic with have a palpable thyroid nodule • Technetium radionuclide scan: performed if anti-TSH antibodies are negative • Glucose: hyperthyroidism is associated with hyperglycaemia • ECG : hyperthyroidism is associated with atrial fibrillation TSH T4 Cause ↓ ↑ Primary hyperthyroidism: e.g. Graves’ disease ↓ Subclinical hyperthyroidism ↔ ↑ ↑ Secondary hyperthyroidism: e.g. TSH-secreting pituitary adenoma ↑ ↔ 17
Investigations: stable patient 18 (7)
Management Antithyroid medication: • Carbimazole: usually first-line • Propylthiouracil : first-line pre-pregnancy or in the first trimester • Titration regime : titrate down to lowest effective dose • Please note that there was a discrepancy previously regarding the titration regimen. This has now been rectified. • Block and replace regimen : levothyroxine is added as needed Radioiodine: • First-line definitive management in Graves' and toxic multinodular goitre • Contraindicated in pregnancy and breastfeeding • Offer patient advice Surgery : total or hemithyroidectomy • Requires pre-operative optimisation • Be aware of the risks Other : consider propranolol for symptomatic relief 21
Thyroid storm Aetiology Pathophysiology Untreated hyperthyroidism • Often provoked by infection • Clinical features Tachycardia: often > 140 BPM, with or without AF • High temperature: often > 40°C • Diarrhoea and vomiting • Jaundice • Confusion or mental agitation • Mortality rate With treatment, 20-40% • Untreated, up to 75% • 22
Investigations: thyroid storm Primary investigations TFTs: elevated T3 and T4, suppressed TSH • Screen for the cause: e.g. an infection screen • Full set of bloods: FBC, U&Es, LFTs, bone profile, blood glucose • CXR • Arterial blood gases • TSH T4 Cause ↓ ↑ Primary hyperthyroidism: e.g. Graves’ disease ↓ Subclinical hyperthyroidism ↔ ↑ ↑ Secondary hyperthyroidism: e.g. TSH-secreting pituitary adenoma ↑ ↔ 23
Management: thyroid storm Emergency • IV fluids : replace losses • NG tube insertion : if vomiting • Cooling : sponging and paracetamol • Antithyroid drugs : propylthiouracil is often preferred • Corticosteroid : IV hydrocortisone • Beta-blocker : propranolol PO or IV over 10 minutes • Oral iodine : Lugol’s iodine offered >1 hour after propylthiouracil • Sedation : if required, use chlorpromazine • Plasma exchange or thyroidectomy : in refractory patients 24
Recap • Graves’ disease is the most common cause of hyperthyroidism Pathophysiology • Graves’ disease occurs due to anti-TSH receptor antibodies • Patients often present with palpitations, weight loss and height intolerance • Graves’ may present with eye disease • Initial investigations are TFTs and autoantibodies • Additional investigations include ultrasound and Technetium radionuclide scanning • Thyroid storm is a life-threatening manifestation of thyrotoxicosis 26
Case 2 History A 55-year-old lady is currently on chemotherapy for ovarian cancer. She presents to the GP with an ongoing history of palpitations that are particularly worse at night. Her friends have told her she has lost weight and her clothes are loose. The GP checks her TFTs: low TSH and raised T3/T4. Observations HR 99, BP 148/98, RR 18, SpO 2 99%, Temp 37.5 ° C. 27
Case 2 History A 55-year-old lady is currently on chemotherapy for ovarian cancer. She presents to the GP with an ongoing history of palpitations that are particularly worse at night. Her friends have told her she has lost weight and her clothes are loose. The GP checks her TFTs: low TSH and raised T3/T4. Observations HR 99, BP 148/98, RR 18, SpO 2 99%, Temp 37.5 ° C. 29
Top decile question 30
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