Hyperthyroidism, Thyrotoxicosis and Thyroid Storm Flashcards
Symptoms of hyperthyroidism
- Heat intolerance, profuse sweating
- Weight loss
- Fatigue
- Palpitations and abnormal rhythm
- Exertional dyspnoea
- Diarrhoea and hyperdefecation
- Amenorrhoea / oligomenorrhoea with anovulation (infertility)
- Rarely polyphagia and resultant weight gain
- Hair loss and hair thinning
- Anxiety, restlessness, insomnia
- Impaired concentration/memory
- Irritability and emotional liability
Signs of thyrotoxicosis
Inspection
1. Resting tremors
2. Warm and moist skin
3. Tachycardia or irregular rhythm
4. Hypertension
Upper and lower limbs
5. Pretibial myxedema
6. Acropachy
7. Proximal myopathy
8. Hyperreflexia with rapid relaxation phase
Face and head
8. Thin and fine hair
10. Lid lag or retraction
11. Orbitopathy
Head and neck
12. Goitre (useful but may or may not be present)
13. Thyroid bruit
Cardiovascular
14. Flow murmur
15. Cardiomegaly, heaves
Thyrotoxicosis is the general term for the presence of increased __, __ or both due to any cause.
Subclinical hyperthyroidism is __ and __
Clinical signs and symptoms are __ or __
Thyrotoxicosis
Increased T4 - thyroxine
Increased T3 - tri-iodothyronine
Subclinical hyperthyroidism
Low TSH
High-normal T4 or T3
Absent or non-specific
Apathetic hyperthyroidism
In elderly individuals with lack of signs indicating hyperthyroidism
Non-specific features: weight loss, AF, congestive heart failure
What are the causes of hyperthyroidism?
A. Increased hormonal synthesis
1. Graves disease (60-80%)
2. Toxic adenoma or toxic multinodular goitre
3. Iodine induced hyperthyroidism (contrast agent, amiodarone)
4. Trophoblastic disease and germ cell tumours (hCG stimulates TSH receptor)
5. TSH secreting pituitary tumour
B. Gland inflammation and release of preformed hormone - which may turn hypothyroidism
1. Hashimoto’s thyroiditis (thyrotoxicosis to hypothyroidism)
2. de Quervain’s thyroiditis (coxsackie virus)
3. Infective thyroiditis (bacterial, TB, fungal)
4. Radiation thyroiditis
5. Postpartum thyroiditis
6. Drug-induced thyroiditis (interferon-alpha, amiodarone, lithium)
What are the drugs that could potentially induce thyroiditis and hypothyroidism?
- Amiodarone
- Lithium
- Interferon-alpha
- Propylthiouracil
- Sunitinib (for RCC and GIST)
- Phenytoin, rifampicin, carbamazepine - increases thyroxine requirement
Effects of iodine on thyroid gland
- Iodine deficiency
- Wolff-Chaikoff effect and Jod-Basedow phenomenon
Iodine deficiency < 100mcg/day causes hypothyroidism
Iodine excess can either cause:
A. Wolff-Chaikoff effect
- Iodine excess prevents organification of iodine and inhibits hormone synthesis
- Undiagnosed autoimmune thyroid disease are at risk when taking iodine-containing drugs (amiodarone, contrast)
B. Jod-Basedow phenomenon
- Exposure to large quantities of iodine causes thyrotoxicosis
Confirmatory investigations of hyperthyroidism/thyrotoxicosis
Confirmatory tests
1. Thyroid function test
- TSH - suppressed / low
- fT4 and fT3 - elevated - biochemical degree of thyrotoxicosis
2. Thyroid autoantibodies - TRAb, anti-TPO, anti-TG
3. Radioactive iodine uptake (RAIU)
4. Thyroid scan (thyroid scintigraphy)
5. US thyroid
6. FNA or biopsy
Other labs
1. FBC - leukopenia, NCNC anaemia
2. LFT - hepatic transaminitis, high ALP (bone turnover), low albumin
3. BMP - hypercalcaemia, hyperphosphataemia
4. Lipid panel - low cholesterol
Autoantibodies
- Graves disease
- Hashimoto’s thyroiditis
Graves disease
Thyroxine receptor antibody (TRAb)
Hashimoto’s thyroiditis
Anti-thyroglobulin (anti-TG)
Anti-thyroid peroxidase (anti-TPO)
Role of US thyroid
- Assess size and consistency of nodule(s)
- Vascularity and flow pattern
Principles of management of hyperthyroidism
- Anti-thyroid drugs (ATDs)
- Methimazole, carbimazole, PTU - Beta blockers
- Radioiodine I-131 ablation
- Surgery in selected patients (see other card)
What are the considerations to think of for anti-thyroid drugs (ATDs)?
- Carbimazole - embryopathy in 1st trimester
- Propylthiouracil
- Hepatotoxicity
- Used only in 1st trimester (P convert to C)
- Thyroid storm - PTU blocks T4 to T3 conversion
- Reactions to carbimazole
What are the considerations and advice to women going for RAI?
- Avoid pregnancy for 4-6 months
- Oral contraceptives LESS effective in hyperthyroid state
- Increased sex hormone binding globulin
- Increased contraceptive clearance
What are the indications for surgery in hyperthyroidism?
Pre-operative planning for thyroid surgery
indications
1. Symptomatic compression or large goitres (>80g) less likely to respond to ATDs
2. Large non-functioning, photopenic or hypofunctioning nodules
3. Low RAIU less likely to respond to I-131
4. Suspected or confirmed thyroid acncer
5. Pregnant patients allergic or intolerance to ATDs and contraindicated for I-131
6. Co-existing hyperparathyroidism requiring surgery
7. Planned pregnancy in < 6 months with normal TFT
8. Patients declining long term ATDs and I-131
9. Mod to severe Graves - I-131 may worsen orbitopathy
Pre-operative planning
1. Euthyroid - ATD pretreatment, beta blockers
- Reduces arrhythmias and post-operative storm
2. Potassium iodide (KI) pre-surgery - reduces thyroid blood flow, vascularity and blood loss
Graves’ disease is an __ disease in which __ are directed against __
- Results in continuous stimulation of __ and __ (goitre)
- There is extrathyroidal manifestations such as (3)
Autoimmune disease - autoantibodies directed against TSH receptor (TSHRAb)
- Stimulation of thyroid hormone production and secretion, thyroid growth (goitre)
Extrathyroidal manifestations
1. Orbitopathy - proptosis, periorbital oedema, EOM dysfunction, optic neuropathy
2. Dermopathy - pretibial myxedema
3. Thyroid acropachy - digital clubbing/oedema
Physical examination of Graves’ disease
A. Graves ophthalmopathy
1. Periorbital oedema
2. Conjunctival chemosis, eye irritation, excessive tearing
3. Exophthalmos and proptosis
- Look from the side or from above whilst standing behind patient
4. Diplopia
4. Lid retraction
5. Ophthalmoplegia - simple or complex
- Upward gaze diplopia - inferior rectus involvement
- Complex ophthalmoplegia
6. Exposure keratitis and corneal ulceration, lateral tarsorrhaphy
7. Optic nerve compression - BOV, visual acuity loss, colour loss, RAPD
8. Glaucoma
B. Goitre
1. Thyroidectomy scar (if any)
2. Diffuse enlarged thyroid gland +/- nodular
3. Thyroid bruit
C. Graves dermopathy
1. Pretibial myxedema (5% of patients)
- Bilateral asymmetrical firm, non-pitting plaques or nodules with pink, purple or brown appearance
- Tender and pruritic
- Usually over anterolateral aspect of lower legs
(Other sites: thighs, shoulders, hands, forehands, areas of recent or prior trauma or skin graft donor site)
- Thyroid acropachy - digital clubbing (1% patients)
- Subperiosteal new bone formation, may be disabling and lead to complete loss of hand function
D. Thyroid state - euthyroid, hypothyroid or hyper thyroid state
Pathophysiology of Graves’ disease
Autoantibodies - TSH receptor antibody
- Binds to TSH receptors, causing thyroid gland enlargement, increased thyroid follicle synthesis of thyroid hormones
Explain the pathogenesis of Graves ophthalmopathy
- Oedema - deposition of GAGs and water influx into EOM increases orbital pressure and compresses superior ophthalmic vein
- Visual/colour loss and RAPD - increased orbital pressure compresses on optic nerve
- Exophthalmos is the protrusion of eyeball such that sclera is visible above lower eyelid when eyes in neutral position
- Ophthalmoplegia is due to infiltration, oedema and fibrosis of EOM
- Exposure keratitis and corneal ulceration due to exophthalmos and corneal exposure
- Glaucoma is due to decreased episcleral venous flow
What are the eponymous signs of Graves ophthalmopathy?
- Stellwag sign - incomplete, infrequent blinking
- Kocher sign - fixed staring look
- Dalrympole sign - lid retraction
- Goffroy sign - absent creases in forehead on upward gaze
- Mobius sign - poor convergence
- Von Graeffe sign - lid lag
- Ballet sign - restriction of 1 ore more EOM
- Grove sign - resistance to pulling down retracted eyelid
Graves’ malignant exophthalmos
Management of Graves’ malignant exophthalmos
Critical inflammation and congestion causing severe pain and optic nerve compression
High risk of blindness
Management
1. Systemic steroids
2. Orbital decompression
3. Radiotherapy
What are the mechanisms of lid retraction in Graves ophthalmopathy?
- Increased sympathetic tone of Muller muscle in thyrotoxicosis
- Proptosis
- Fibrosis of levator muscle
- Cogan lid twitch sign (also in MG, or Graves + MG)
What are the causes of proptosis?
- Graves’ disease
- Cavernous sinus thrombosis
- Carotico-cavernous fistula
- Orbital cellulitis
- Retro-orbital tumour (lymphoma, leukaemia, meningioma, metastasis)
- Retro-orbital granuloma (GPA, histiocytosis X, sarcoidosis)
- Trauma
What are the autoimmune conditions associated with autoimmune thyroid disease (Graves, Hashimoto)
- Type 1 diabetes mellitus - finger prick test, fundoscopy
- Addison’s disease - pigmentation, postural hypotension
- Pernicious anaemia - pallor, splenomegaly, polyneuropathy
- Hypoparathyroidism - Chvostek and Trousseau sign, cataracts
- Alopecia areata - hair loss in scalp, white short tapering exclamation mark hairs
- Vitiligo - skin depigmentation
- Rheumatoid arthritis - small joint arthropathy
- SLE - butterfly rash, arthropathy
- Sjogren’s syndrome - dry mouth and eyes
Management of Graves disease
A. Symptomatic management
1. Non-selective beta blockers (propranolol) - manages palpitation, tachycardia, tremor, anxiety, heat intolereance
(Cardioselective beta blockers for cardioprotection)
2. Eyedrops and lubricants
3. Tape eyelids closed, or lateral tarsorrhaphy
B. Definitive management
2. Carbimazole or propylthiouracil
- Carbimazole - greater efficacy
- PTU - early pregnancy (eventually convert P -> C)
(Side effects: agranulocytosis, ANCA vasculitis)
C. Radioiodine ablation
- Oral ingestion sodium iodide -> rapidly concentrated in thyroid tissue, causing destruction and ablation over 6-18 weeks
(Ophthalmopathy may worsen with RAI)
- Concomitant steroid therapy to reduce worsening
- Stop smoking
- Avoid contact with children, avoid pregnancy
D. Thyroidectomy
- Indication: large goitre, co-existing thyroid nodule
