Hyperthyroidism Flashcards
What is the epidemiology of hyperthyroidism?
2-5% females, 0.2-.03% men; 5:1 ratio
99% cases due to intrinsic thyroid disease:
Graves disease = 60-80%; nodular thyroid disease = 20-40%
Graves onset age 20-40
What is Graves disease?
TSH receptor antibody production
Genetics:
20-50% concordance in MZ twins – so some link
No exact cause known:
Links to E.coli and other g-ve bacteria who also have TSH binding sites
Triggers:
High iodine intake
Stress
Smoking
Related disorders:
Autoimmune diseases – myasthenia gravis and pernicious anaemia
What are some other causes of hyperthyroidism?
Rarer causes:
Iodine excess
Thyroid carcinoma
TSH receptor mutation
Secondary causes:
TSH secreting pituitary tumour
Thyroid hormone resistance
Gonadotrophin-secreting tumour
What is the pathophysiology of hyperthyroidism?
T4 serves to increase BMR, Gluconeogenesis, Glycogenolysis, Protein synthesis, Lipogenesis, Thermogenesis
- Does this by increasing: the number of mitochondria in cells, the activity of Na/K/ATPase, the number of B-adrenergic receptors in some tissues (e.g. myocytes) - this then helps explain all the symptoms
Disease follows relapse and remission pattern - though up to 40% might only have a single episode
Many patients become hypothyroid
Thyroid hypertrophy and hyperplasia:
But have reduced colloid (as components of colloid all being used up more quickly)
Lymphocytic infiltrate
Lymph node hyperplasia in spleen (splenomegaly) + thymus
Changes reversible with antithyroid drugs
How does hyperthyroidism present?
Hyperactivity, irritability
Heat intolerance, sweating
Oligomenorrhoea, menorrhagia
Weight loss with increased appetite (though can have weight gain if appetite exceeds increased metabolism)
Diarrhoea, polyuria
Loss of libido
Fatigue, weakness, wasting
Sinus tachycardia, atrial fibrillation
Fine tremor
Goitre, eyelid retraction, pretibial myxoedema (swollen + brown shins)
Rarely:
Psychosis
Periodic paralysis (Asian males)
Impaired consciousness
SWEATING: Sweating Weight loss Emotional lability Appetite increased Tremor/ tachycardia Intolerance of heat/ Irregular menstruation/ Irritability Nervousness Goitre and GI problems (diarrhoea)
What is a thyrotoxic crisis/storm?
Acute presentation of hyperthyroidism - often in the undiagnosed
Fever - >38.5 degrees Seizures
Diarrhoea, vomiting
Jaundice (possibly due to some hepatocyte hypoxia -> failures of conjugation -> accumulation)
Death – arrhythmias, heart failure, hyperthermia
20-30% mortality
Management:
IV propranolol
Corticosteroids
Carbimazole PO
How might hyperthyroidism present in children? and in the elderly?
Children:
Excessive growth rate
Behavioural problems – hyperactivity
Elderly:
Atrial fibrillation and sinus tachycardia tend to be the only symptoms
Apathetic thyrotoxicosis
Few signs, and might even mimic hypothyroidism
How do you investigate hyperthyroidism?
TSH test:
Will be low - <0.05U/L
To confirm, T4 or T3 levels need to be high
T3 is more sensitive than T4 in this instance
TPO and thyroglobulin and TSH receptor antibodies:
Likely to be present
How do you manage hyperthyroidism?
Antithyroid drugs:
Carbimazole, methimazole, propylthyrouracil
Prevent the output of thyroid hormones by reducing the action of peroxidise enzyme involved in the production of thyroglobulin
Reduce hormone production quickly but takes a long time for clinical effects to be seen (3-4 weeks) due to the long half life of T4 in the blood and the excess T4 stored in the thyroid itself
Dose titration:
Use T3/4 levels to establish effects
Supplement any low T4 levels with thyroxine (known as the block and replace method)
Continue to reduce drugs until patient is euthyroid on 5mg carbimazole then stop treatment
Side effects:
Agranulocytosis
(low levels of WBCs esp neutrophils)
Pregnancy:
Thyroid stimulating immunoglobulin can cross the placenta and stimulate the foetuses thyroid
Carbimazole can easily cross placenta too so mother prescribed small amount of it (as T4 cannot cross so cannot be replaced – infant still needs some so mothers carbimazole dose can’t be too high)
What other drugs can be used in hyperthyroidism?
Beta-blockers – propanalol:
Symptom reduction of tachycardia, dysrhythmias, tremor etc
Also decreases peripheral T4→T3 conversion
Radioiodine:
Radioactive iodine taken up by thyroid which then irradiates and destroys local cells
Given as single dose
Cytotoxic effect seen within 1-2 months
Radiation eliminated after 2 months
Many patients become hypothyroid after
Not prescribed in the UK, those with thyroid eye disease, children and pregnant women
What surgery is indicated in hyperthyroidism?
Subtotal thyroidectomy
Should only be performed in patients who are euthyroid (having undergone drug treatment)
Indications: Patient choice Persistent drug side effects Poor compliance Recurrent hyperthyroidism after drug treatment Large goitre that affects swallowing
What is toxic multinodular goitre?
A type of hyperthyroidism mainly occuring in older women
Associated with increased iodine intake:
Dietary
Drugs – amiodarone
Iodinated contrast media
Develops from a simple sporadic goitre
Genetic mutation in the TSH receptor
Mixture of normal tissue and areas of hyperplasia with colloid filled nodules
Fibrosis, calcification and haemorrhage
What is the breakdown for different thyroid carcinomas?
Papillary:
70% - mostly young people, local spread, good prognosis
Follicular:
20% - mostly females, spreads to lungs/bone, good prognosis if completely resected
Both are still rare in the UK
- Near total or total thyroidectomy are treatment +/- radioiodine +/- post surgery thyroxine to suppress TSH
- Yearly thyroglobulin levels to detect early recurrent disease
Also:
- Medullary - often secrete calcitonin and monitoring the serum levels is useful in detecting recurrence
- Anaplastic
