Endocrinology
Question 161 of 180
A 47 year old woman presents to the Emergency Department complaining of palpitations. On examination you note exophthalmos. You suspect hyperthyroidism. Which of the following signs is NOT typical of hyperthyroidism?
Answer:
Suspect a diagnosis of hyperthyroidism if there are one or more signs of:- Agitation, fine tremor, warm moist skin, palmar erythema
- Sinus tachycardia, atrial fibrillation, heart failure, peripheral oedema
- Thyroid enlargement (a goitre)
- Pruritus, urticaria, vitiligo, diffuse alopecia
- Muscle wasting, proximal myopathy, hyperreflexia
- Splenomegaly, lymphadenopathy
- Gynaecomastia in men
- Extrathyroidal manifestations of Graves' disease (rare):
- Thyroid acropachy (clubbing and swelling of the distal fingers and toes)
- Thyroid dermopathy (slightly pigmented thickened skin and swelling of both legs, usually in the pretibial area)
- Graves' orbitopathy
Hyperthyroidism
Endocrinology
Last Updated: 12th February 2021
Hyperthyroidism is a biochemical diagnosis which occurs when there is pathologically increased thyroid hormone production and secretion by the thyroid gland. Thyrotoxicosis is the clinical manifestation of excess circulating thyroid hormones due to any cause, including hyperthyroidism.
Causes
- Graves disease
- Most common cause of hyperthyroidism in iodine-sufficient areas, accounting for about 80% of cases. It is a systemic autoimmune disorder mediated by thyroid-stimulating hormone (TSH)-receptor antibodies (TRAbs) that stimulate the TSH receptor, leading to thyroid hyperplasia and unregulated excessive production and secretion of thyroid hormone. Peak incidence is at 30–50 years of age, and it is 10 times more common in women than men.
- Toxic multinodular goitre
- This is the second most common cause of hyperthyroidism in the UK, and is more common in older adults. It occurs in a thyroid gland with at least two autonomously functioning thyroid nodules that secrete excess thyroid hormone. Histologically the nodules are benign follicular adenomas.
- Toxic thyroid nodule (adenoma)
- This accounts for up to 5% of cases of hyperthyroidism, and is more common in older adults. The nodule produces enough hormone to suppress secretion of TSH from the pituitary, with consequent suppression of the contralateral thyroid lobe.
- TSH-secreting pituitary adenoma
- This is a rare tumour secreting large quantities of TSH, leading to inappropriately normal or elevated TSH levels, with elevated free thyroxine (FT4), and total triiodothyronine (T3) levels. The pituitary does not respond to normal T4 and T3 feedback mechanisms.
- Pituitary thyroid hormone resistance syndrome
- This is a rare condition caused by genetic mutations in the thyroid hormone receptor-beta gene. A positive family history supports the diagnosis. Usually the person is euthyroid, but thyrotoxic symptoms may occur.
- High concentrations of human chorionic gonadotrophin (hCG)
- Can stimulate TSH receptors and suppress TSH e.g. gestational thyrotoxicosis, hyperemesis gravidarum and chorionic gonadotrophin-secreting tumours
- Drugs e.g. iodine, amiodarone, lithium, excess intake of levothyroxine
- Functional thyroid cancer metastases
- These can result in extrathyroidal foci of thyroid hormone production
- Thyroiditis
- Causes a usually transient release of preformed thyroid hormones into the circulation due to inflammatory destruction of the thyroid follicles e.g. postpartum thyroiditis, subacute (de Quervain's) thyroiditis and drug-induced thyroiditis
Clinical features
The symptoms and signs of hyperthyroidism may be mild and non-specific, especially in the elderly.
Suspect a diagnosis of hyperthyroidism if there are one or more symptoms of:
- Rapid-onset malaise, fever, and thyroid pain
- Compression symptoms of breathlessness, hoarse voice, dysphagia, neck pressure
- Agitation, emotional lability, insomnia, irritability, anxiety, palpitations
- Exercise intolerance, fatigue, muscle weakness
- Heat intolerance, increased sweating
- Increased appetite with unintentional weight loss, diarrhoea
- Subfertility, oligomenorrhoea, amenorrhoea
- Polyuria, thirst, generalised itch
- Reduced libido, gynaecomastia in men.
- Deterioration in blood glucose control and hyperglycaemia in people with diabetes mellitus
- Deterioration of comorbid heart disease, for example in the elderly
Suspect a diagnosis of hyperthyroidism if there are one or more signs of:
- Agitation, fine tremor, warm moist skin, palmar erythema
- Sinus tachycardia, atrial fibrillation, heart failure, peripheral oedema
- Thyroid enlargement (a goitre)
- Pruritus, urticaria, vitiligo, diffuse alopecia
- Muscle wasting, proximal myopathy, hyperreflexia
- Splenomegaly, lymphadenopathy
- Gynaecomastia in men
- Extrathyroidal manifestations of Graves' disease (rare):
- Thyroid acropachy (clubbing and swelling of the distal fingers and toes)
- Thyroid dermopathy (slightly pigmented thickened skin and swelling of both legs, usually in the pretibial area)
- Graves' orbitopathy:
- Eye irritation, photophobia, or excessive watering of the eyes
- Redness of the eyes or eyelids and/or lid swelling
- Change in the appearance of the eye or eyelids:
- Eyelid retraction (sclera is visible above the superior corneal limbus)
- Lid lag (delay in moving the eyelid as the eye moves downward)
- Proptosis (exophthalmos, eyeball protrusion, an inability to fully close the eyes as the upper and lower lids do not fully oppose)
- Persistent double vision in any direction of gaze (typically when looking upwards and outwards)
- Unexplained deterioration in visual acuity; change in the intensity or quality of colour vision in one or both eyes; orbital aching or restricted eye movements — suggests dysthyroid optic neuropathy
- History of globe subluxation — one or both eyes suddenly 'popping out'; typically lasts more than a few seconds, is painful, and the lids could not be closed
Complications
- Graves orbitopathy
- About 25% of people with Graves' disease have Graves' orbitopathy. Sight-threatening complications include dysthyroid optic neuropathy, severe corneal exposure and ulceration, or corneal breakdown leading to frank perforation
- Thyrotoxic crisis (thyroid storm)
- This is a rare and potentially life-threatening complication, which may occur after a trigger such as acute infection, trauma, pregnancy, surgery including thyroidectomy, or stroke. It may occur in people with previously undiagnosed hyperthyroidism or those who have abruptly stopped antithyroid medication. Clinical features reflect systemic decompensation and include fever, tachycardia, agitation, hyperthermia, hypertension, atrial fibrillation, heart failure, jaundice, delirium, and coma. The mortality rate is estimated at about 10% due to hyperthermia, cardiac arrhythmias, multi-organ failure, and sepsis.
- Compression symptoms
- A large goitre may cause dysphagia or breathlessness due to oesophageal or tracheal compression
- Musculoskeletal
- Thyrotoxic periodic paralysis — this is a rare complication characterised by muscle paralysis and hypokalaemia, which is more prevalent in Asian people with hyperthyroidism
- Reduced bone mineral density and osteoporosis
- Cardiovascular
- Atrial fibrillation
- Coronary heart disease
- Heart failure
- Mood disorders
- Psychosis (rare) has been noted to complicate some cases of severe hyperthyroidism
- Pregnancy
- Increased risk of pregnancy and fetal complications
Investigations
- Thyroid function tests:
- Suspect a diagnosis of overt hyperthyroidism if the TSH level is low and FT4 and/or FT3 levels are raised above the normal reference ranges.
- Suspect a diagnosis of subclinical hyperthyroidism if the TSH level is below the normal reference range and FT3 and FT4 levels are within the normal reference range.
- If the TSH is within the reference range, further investigations are not usually needed, as hyperthyroidism is very unlikely.
- Additional blood tests:
- TSH-receptor antibodies (TRAbs) if a diagnosis of Graves' disease is suspected or the person is pregnant
- Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) if a diagnosis of thyroiditis is suspected
- Thyroid peroxidase antibodies (TPOAbs) if a woman is postpartum and a diagnosis of postpartum thyroiditis is suspected.
- Baseline full blood count (FBC) and liver function tests (LFTs) if antithyroid drugs are to be started.
- Thyroid ultrasound scan with doppler
- Doppler provides relevant information on thyroid size, echogenicity, presence/absence of nodules, and vascularisation.
- Radionuclide thyroid uptake scan
- If thyroid-stimulating hormone (TSH)-receptor antibodies (TRAbs) are not present, a scan of radionuclide thyroid uptake (with radioiodine or technetium) can help distinguish different causes of hyperthyroidism. This typically shows a diffuse pattern of uptake in Graves' disease, compared with one or more 'hot' nodules in toxic nodular hyperthyroidism. All types of thyroiditis are associated with reduced or absent uptake of radioisotope into the thyroid.
Management
- Symptomatic therapy
- Beta-adrenergic blockers such as propranolol are used to provide symptomatic relief of adrenergic symptoms (such as palpitations, tremor, tachycardia, or anxiety) until specific therapy normalises peripheral thyroid hormone levels. Calcium-channel blockers are an alternative if beta-blockers cannot be used.
- Antithyroid drugs
- Antithyroid drug treatments (carbimazole and propylthiouracil) are used to decrease thyroid hormone synthesis, by acting as a preferred substrate for iodination by thyroid peroxidase, the key enzyme in thyroid hormone production.
- Antithyroid drugs should only be initiated on specialist advice, and are typically used:
- Short-term to restore euthyroidism in preparation for definitive treatment with radioactive iodine treatment or thyroid surgery.
- Medium-term with the aim of inducing remission of Graves' disease.
- Long-term if radioactive iodine treatment or surgery is contraindicated or declined.
- Two different treatment regimes may be used by the specialist, which require regular thyroid function monitoring:
- Titration-block regime — the dose is adjusted regularly depending on free thyroxine (FT4) measurements. A dose reduction may be needed if the FT4 level falls to low-normal or below the reference range, or the TSH level increases, indicating the development of hypothyroidism. The aim is to titrate to the lowest dose needed to maintain a euthyroid state.
- Block and replace regime — the antithyroid drug blocks the synthesis of thyroid hormone. The FT4 level is monitored and levothyroxine (LT4) is added in when the FT4 is in the reference range. Adjustments to the LT4 dose are made to maintain FT4 levels in the reference range.
- Radioactive iodine treatment
- Radioactive iodine treatment induces damage of DNA leading to death of thyroid cells, causing a decrease in thyroid function and/or reduction in thyroid size. It is a first-line definitive treatment for adults with Graves' disease and those with toxic multinodular goitre. It is contraindicated in people with Graves’ disease with active or severe orbitopathy as it may cause an exacerbation of orbitopathy or de novo development.
- Thyroid surgery
- Options include total thyroidectomy, or hemithyroidectomy for a single thyroid nodule, in people:
- To prevent the recurrence of hyperthyroidism
- With compression symptoms from a large toxic multinodular goitre
- With a coexisting potentially malignant thyroid nodule
- Who have not tolerated antithyroid drug treatment or it is ineffective, especially in pregnancy or active Graves' orbitopathy, or if radioactive iodine treatment is unsuitable
- Pre-operative treatment with antithyroid drugs aiming for euthyroidism reduces the risk of thyrotoxic crisis which may be precipitated by surgery
- Post-operative complications include hypothyroidism, hypocalcaemia due to hypoparathyroidism (often transient), and vocal cord paresis due to damage to the recurrent laryngeal nerve
- Options include total thyroidectomy, or hemithyroidectomy for a single thyroid nodule, in people:
- Thyroid storm
- Management of thyroid storm includes supportive treatment, such as cooling, correction of volume status, respiratory support if indicated, and treatment of underlying sepsis if appropriate, all of which should be managed in an intensive care environment with input from endocrine specialists.
- Treatment directed at thyroid hormone synthesis and secretion by the thyroid gland.
- Antithyroid medications (carbimazole or propylthiouracil orally)
- Lugol's solution (aqueous iodine oral solution) should typically be administered after thionamide therapy has been started to prevent stimulation of new hormone synthesis
- Beta-blockers (initially IV propranolol 5 mg, then orally)
- Hydrocortisone administration is also recommended. It treats possible relative adrenal insufficiency while also decreasing T4 to T3 conversion.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
