Endocrinology
Question 191 of 300
A 56 year old woman presents to the Emergency Department due to fatigue and worsening confusion. Her blood tests show an elevated TSH and you consider if her symptoms are the result of hypothyroidism. Which of the following clinical features is NOT typical of hypothyroidism?
Answer:
The symptoms and signs of hypothyroidism may be mild and non-specific, especially in the elderly. Suspect a diagnosis of hypothyroidism if there are more than one of the following clinical features:- Fatigue/lethargy, cold intolerance; weight gain, constipation.
- Non-specific weakness, arthralgia, and myalgia.
- Menstrual irregularities; infertility or subfertility.
- Depression, impaired concentration and memory.
- Dry skin and hair loss (such as loss of lateral eyebrows).
- Thyroid pain, for example in subacute thyroiditis.
- Thyroid enlargement (a goitre) and/or thyroid nodules.
- Changes to appearance such as coarse dry hair and skin, and hair loss.
- Oedema, including swelling of the eyelids.
- Hoarseness or deepening of the voice; goitre.
- Bradycardia and diastolic hypertension; pericardial effusion.
- Delayed relaxation of deep tendon reflexes.
- Paraesthesia (due to carpal tunnel syndrome) or peripheral neuropathy.
- A diagnosis or signs of other autoimmune disease.
Hypothyroidism
Endocrinology
Last Updated: 15th December 2022
Hypothyroidism is a common condition of thyroid hormone (thyroxine [T4] and tri-iodothyronine [T3]) deficiency, which are essential for normal growth, development, and metabolism.
- Primary hypothyroidism (95% of cases) occurs when there is thyroid hormone deficiency due to the thyroid gland being unable to produce thyroid hormones because of iodine deficiency or an abnormality within the gland itself.
- Secondary hypothyroidism is the result of insufficient thyroid stimulation due to a pituitary or hypothalamic disorder.
Causes
- Primary:
- Iodine deficiency (commonest cause worldwide)
- Autoimmune thyroiditis e.g. Hashimoto’s thyroiditis, atrophic thyroiditis (commonest cause in iodine-sufficient areas such as the UK)
- Post-ablative therapy or surgery or post-radiotherapy
- Drugs e.g. antithyroid drugs, iodine, amiodarone, lithium, sodium valproate, interferon-alpha, thalidomide, and rifampicin
- Transient thyroiditis e.g. subacute (de Quervain's) thyroiditis, postpartum thyroiditis
- Thyroid infiltrative disease e.g. sarcoidosis, amyloidosis, tuberculosis, malignant infiltration
- Congenital hypothyroidism
- Secondary:
- Pituitary or hypothalamic dysfunction, due to:
- Tumours — most commonly pituitary adenomas or gliomas
- Surgery, radiotherapy, or trauma
- Pituitary infarction
- Sheehan's syndrome — postpartum pituitary necrosis due to postpartum haemorrhage
- Infiltrative disorders — such as amyloidosis, sarcoidosis, haemochromatosis, and tuberculosis
- Isolated thyroid-stimulating hormone (TSH) deficiency or inactivity
- Idiopathic hypothalamic disease
- Drugs — such as cocaine, dopamine, glucocorticosteroids, and metformin
- Pituitary or hypothalamic dysfunction, due to:
Clinical features
The symptoms and signs of hypothyroidism may be mild and non-specific, especially in the elderly. Suspect a diagnosis of hypothyroidism if there are more than one of the following clinical features:
- Fatigue/lethargy, cold intolerance; weight gain, constipation.
- Non-specific weakness, arthralgia, and myalgia.
- Menstrual irregularities; infertility or subfertility.
- Depression, impaired concentration and memory.
- Dry skin and hair loss (such as loss of lateral eyebrows).
- Thyroid pain, for example in subacute thyroiditis.
- Thyroid enlargement (a goitre) and/or thyroid nodules.
- Changes to appearance such as coarse dry hair and skin, and hair loss.
- Oedema, including swelling of the eyelids.
- Hoarseness or deepening of the voice; goitre.
- Bradycardia and diastolic hypertension; pericardial effusion.
- Delayed relaxation of deep tendon reflexes.
- Paraesthesia (due to carpal tunnel syndrome) or peripheral neuropathy.
- A diagnosis or signs of other autoimmune disease.
In secondary hypothyroidism there may be clinical features of primary hypothyroidism together with clinical features of possible hypothalamic-pituitary disease such as recurrent headache, diplopia, and/or visual field defects. In addition, abnormal pituitary hormone production may cause skin depigmentation, atrophic breasts, galactorrhoea, amenorrhoea, erectile dysfunction, loss of body hair, Cushing’s syndrome, or acromegaly.
Complications
- Cardiovascular
- Dyslipidaemia
- Metabolic syndrome
- Coronary heart disease and stroke
- Heart failure
- Reproductive
- Infertility and subfertility
- Increased risk of complications in pregnancy e.g. miscarriage, pre-eclampsia, placental abruption, anaemia, postpartum haemorrhage, stillbirth
- Adverse neonatal outcomes e.g. preterm delivery, low birthweight, congenital abnormalities
- Neurological and cognitive
- Decreased taste, vision, or hearing
- Impaired attention, concentration, memory, language, executive function, and psychomotor speed
- Myxoedema coma
- The hallmarks of myxoedema coma are decreased mental status and hypothermia, but hypotension, bradycardia, hyponatremia, hypoglycemia, and hypoventilation are often present as well.
- Affected people are typically older and have previously undiagnosed hypothyroidism or are poorly compliant with thyroid hormone medication. The precipitant is usually onset of another condition such as heart failure, sepsis, or stroke.
- The diagnosis of myxedema coma should be considered in any patient with coma or depressed mental status who also has hypothermia, hyponatremia, and/or hypercapnia. Important clues to the possible presence of myxoedema coma in a poorly responsive patient are the presence of a thyroidectomy scar or a history of radioiodine therapy or hypothyroidism. A history obtained from family members often reveals antecedent symptoms of thyroid dysfunction followed by progressive lethargy, stupor, and coma.
Investigations
- Thyroid function tests
- Suspect a diagnosis of primary hypothyroidism if TSH levels are above the normal reference range (usually above 10 mU/L) and FT4 is below the normal reference range.
- Suspect a diagnosis of subclinical hypothyroidism if TSH levels are above the normal reference range and FT4 is within the normal reference range.
- Suspect a diagnosis of secondary hypothyroidism if clinical features are suggestive and TSH levels are inappropriately low (may be normal), but FT4 is below the normal reference range.
- Suspect an alternative diagnosis if TFTs are within the normal euthyroid range.
- Additional blood tests
- Full blood count (FBC) and serum B12 level — to assess for possible associated pernicious anaemia
- Glycated haemoglobin (HbA1c) — to assess for associated type 1 diabetes mellitus
- Coeliac serology — to assess for coeliac disease if a diagnosis of autoimmune thyroid disease is suspected
- Serum lipids — to assess for associated dyslipidaemia
- Serum thyroid peroxidase antibodies (TPOAb) - if autoimmune thyroid disease is suspected
- Ultrasound of neck
- Arrange an ultrasound of the neck to image palpable thyroid enlargement or focal nodularity in adults with normal thyroid function if malignancy is suspected
Management
All patients with primary hypothyroidism should be treated. The goal of treatment is reduction of symptoms and prevention of long-term complications. Treatment is given upon establishing the diagnosis and is lifelong. Treatment is with levothyroxine monotherapy.
Management of myxoedema coma
If myxoedema coma is suspected, treatment should be instituted without waiting for laboratory confirmation. Myxedema coma is an endocrine emergency that should be managed aggressively as the mortality rate remains high, even with treatment.
Treatment consists of:
- Thyroid hormone
- The optimal mode of thyroid hormone therapy in patients with myxoedema coma is controversial, largely because the condition is so rare that there are no clinical trials comparing the efficacy of different treatment regimens. T4 and T3 should be given intravenously as a slow bolus, when available, because gastrointestinal absorption may be impaired.
- Glucocorticoids
- Until the possibility of coexisting adrenal insufficiency has been excluded, the patient must be treated with glucocorticoids in stress doses (e.g. hydrocortisone given intravenously, 100 mg every eight hours).
- Supportive measures
- Supportive measures are extremely important, including mechanical ventilation, appropriate fluid replacement, and correction of hyponatremia and hypothermia.
- Dilute fluids should be avoided in hyponatraemic patients to prevent a further reduction in the plasma sodium concentration.
- Hypotension, if present and not caused by volume depletion, will be corrected by thyroid hormone therapy over a period of hours to days. Severe hypotension that does not respond to fluids should be treated with a vasopressor drug until the T4 has had time to act.
- Passive rewarming with a blanket is preferred for correction of hypothermia. Active rewarming carries a risk of vasodilatation and worsening hypotension.
- Mechanical ventilation will be required if there is significant hypercapnia or hypoxia. Non-invasive ventilation such as continuous positive airway pressure (CPAP) may used.
- Appropriate management of coexisting problems (e.g. infection)
- As with any critically ill, comatose patient, empiric administration of antibiotics should be considered until appropriate cultures are proven negative.
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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 |
