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Assessment and management of thyroid disease
Acute Care
Assessment and management of thyroid disease
Relevance to the curriculum 1.0 Good clinical care 1.1 History, examination, diagnosis (recognising clinical features of hypothyroidism and hyperthyroidism, atypical presentations of thyroid disease, interpreting thyroid function tests) 1.2 Time management and decision-making (recognising acute presentations thyroid disease, pre-operative assessment of thyroid dysfunction) 2.0 Maintaining good medical practice 2.1 Learning 2.2 Research, evidence and guidelines 7.0 Recognition and management of the acutely ill 7.1 Core skill (basic resuscitation in thyroid storm, myxoedema coma and airways obstruction) 7.2 Resuscitation (as 7.1) 7.5 Selection and interpretation of investigations (interpretation of liver function tests, thyroid function tests, renal function, ECG in context of thyroid emergencies covered)
Miles Levy
Abstract Thyroid emergencies are rare but are important to recognise because of the high mortality associated with them. Thyroid storm is a clinical syndrome associated with fever, central nervous effects, gastrointestinalhepatic dysfunction, tachycardia and congestive cardiac failure. Myxoedema coma is typically associated with hypothermia, hypoventilation, hyponatraemia, hypoglycaemia and decreased mental function. Surgical and anaesthetic aspects of thyroid disease include the assessment of patients with thyroid dysfunction before non-thyroidal surgery, recognising post-thyroidectomy complications, and the management of acute upper airway obstruction due to goitre. Factors including systemic illness, medication and pregnancy may affect thyroid function, and it is important to consider these before deciding on the appropriate management strategy.
fever are present thyroid storm may initially be mistaken for sepsis. If there is a high index of clinical suspicion for a hyperthyroid crisis, modern assays will allow for a rapid turnaround of free thyroxine levels (fT4), free tri-iodothyronine levels (fT3), and thyroid stimulating hormone (TSH) levels. Particular clinical clues include a vascular goitre, thyroid eye disease, and vitiligo or other auto-immune disease, although these may be absent. Preliminary blood tests may reveal pre-renal failure, hypercalcaemia, abnormal liver function and signs of sepsis. ECG changes will reveal a narrow complex tachycardia, commonly fast atrial fibrillation, and there is usually radiological evidence of pulmonary oedema in frank thyroid storm. The management of thyroid storm involves basic resuscitation, control of tachycardia and cardiac failure, symptomatic treatment of agitation and fever, and specific anti-thyroid medication (Table 1). Because severe hyperthyroidism is associated with increased metabolic rate and renal clearance of drugs, high doses of β-blockers and digoxin may be required to control ventricular rate. In terms of anti-thyroid therapy, it probably does not matter whether carbimazole or propylthiouracil (PTU) is used, but it is important that either drug is administered via the appropriate route. This usually means a nasogastric tube if patients are too unwell to take oral medication. PTU is often preferred because it reduces the conversion of T4 to T3, although carbimazole has a longer duration of action, so both drugs have advantages. Many endocrine units advocate the use of Lugol’s iodine because it reduces the conversion of T4 to T3. It is important that Lugol’s iodine is given more than 4 hours after the administration of the first dose of carbimazole or PTU, as there may be a paradoxical rise in T4 in response to an acute iodine load. Corticosteroids are also known to reduce the peripheral conversion of T4 to T3, and are commonly given in thyroid storm. Prophylactic anticoagulation should be given in hyperthyroid crises, and if thrombo-embolic disease is suspected, therapeutic doses should be given. Hyperpyrexia is treated with anti-pyretics
Keywords myxoedema coma; sick euthyroid syndrome; thyroid emergencies, thyroid storm
Introduction Abnormal thyroid function can be the main reason for hospital admission or an incidental finding during an inpatient stay. It is important to measure thyroid function in all inpatients because both hyper- and hypothyroidism are common and have a wide range of clinical presentations. Thyroid emergencies are rare but important to recognise because they are associated with a high mortality.
Thyroid emergencies Thyroid storm Hyperthyroidism can lead to an extreme biochemical and clinical disturbance known as thyroid storm. Thyroid storm is characterized by a collection of clinical features, including fever, central nervous effects, gastrointestinal-hepatic dysfunction, tachycardia and congestive cardiac failure (Table 1).1 Usually there is an obvious trigger, such as thyroid surgery or radioiodine therapy in a patient with known thyroid disease, or non-thyroid surgery in a patient with undiagnosed hyperthyroidism. Any form of catecholamine excess can resemble thyroid storm, and if jaundice and
Miles Levy MBBS FRCP MD is a Consultant Endocrinologist at Leicester Royal Infirmary and Honorary Senior Lecturer at Leicester Medical School, UK. He has a particular interest in pituitary tumours and medical education. Conflicts of interest: none declared.
THE FOUNDATION YEARS 4:6
237
© 2008 Elsevier Ltd. All rights reserved.
Acute Care
Clinical features, range of presentation and management of thyroid storm
Clinical features, investigation findings and management of myxoedema coma
Clinical feature
Range of presentation
Management
Clinical features
Investigations
Management
Cardiac failure
Mild ankle oedema Basal lung crepitations Frank pulmonary oedema
Oxygen ECG monitoring
Confusion Psychosis Coma Hypothermia
Hyponatraemia Hypoglycaemia Elevated CK Type 2 respiratory acidosis High TSH (often >100 iU/l)
Passive rewarming Mechanical ventilation Fluid balance Intravenous dextrose
Tachycardia
Fast AF SVT
Central nervous effects
Fever
Gastrointestinal effects
Degree of tachycardia related to disease severity Mild agitation Psychosis Delirium Seizure Coma Degree of hyperpyrexia related to disease severity Diarrhoea
Vomiting Jaundice
Frusemide as appropriate Digoxin as appropriate Propranolol 40–80 mg po 6-hourly Diltiazem 60–120 mg po 6-hourly if β-blocker contraindicated Prophylactic anticoagulation in fast AF Chlorpromazine 50 mg po 8-hourly (or 25 mg IM)
Bradycardia
Hypoventilation
Low fT4
Preceding hypothyroid symptoms
Low random cortisol ECG CXR Septic screen
Hydrocortisone 100 mg i.v. 6-hourly until random cortisol result known Treat sepsis as appropriate T3 (5–20 μg via NG tube then 2.5–10 μg 8-hourly po for 2–3 days) Change to T4 50-100 ug od po when clinical improvement
CK, creatinine kinase; CXR, chest radiograph; NG, nasogastric; TSH, thyroid stimulating hormone.
Tepid sponging Paracetamol Consider dantrolene in malignant hyperthermia (T > 40°C) Propylthiouracil 200 mg 4-hourly or carbimazole 20 mg 4-hourly Lugol’s iodine 6-hourly (first dose 4 hours after anti-thyroid drugs)
Table 2
is the skin thickening that occurs in profound hypothyroidism due to the accumulation of mucopolysaccharide in subcutaneous tissues. Patients often have preceding symptoms of classical hypothyroid features when asked in retrospect. The presence of frank psychotic symptoms may lead to acute psychiatric admission (‘myxoedema madness’), and the presence of a pericardial effusion may lead to cardio-respiratory collapse (Figure 1). In addition to hypoglycaemia and hyponatraemia, patients may have very elevated creatine kinase levels and evidence of sepsis.
AF, atrial fibrillation; IM, intramuscular; SVT, supraventricular tachycardia.
Table 1
and peripheral cooling techniques, and in significant hyperthermia dantrolene may be considered (as for neuroleptic malignant syndrome). Fluid balance usually requires central venous pressure monitoring because of the presence of cardiac failure, and this should ideally occur in a high dependency or ITU environment. In rare cases, patients who fail to improve after initial measures may require haemofiltration or haemodialyis. The mortality of thyroid storm is approximately 10%, underlying the importance of intensive monitoring and treatment in the early phase of this condition. Myxoedema coma Severe hypothyroidism, especially in the elderly, may present with confusion or even coma. The presence of hypothermia, hypoventilation, hyponatraemia and hypoglycaemia raises the possibility of a hypothyroid crisis (Table 2). When patients are unconscious, this is referred to as myxoedema coma. Myxoedema
THE FOUNDATION YEARS 4:6
Figure 1 CT thorax showing pericardial effusion in a patient with myxoedema coma (arrow shows pericardial fluid).
238
© 2008 Elsevier Ltd. All rights reserved.
Acute Care Arterial blood gas analysis often shows type 2 respiratory failure. In myxoedema coma, fT4 levels are very low and TSH is usually significantly elevated when due to primary hypothyroidism. Hypoadrenal crises often occur in conjunction with myxoedema coma because of the association between auto-immune hypothyroidism and Addison’s disease. Adrenal insufficiency is particularly likely in the presence of hypoglycaemia, hyponatraemia, hyperkalaemia and hypotension. The management of myxoedema coma includes passive rewarming, careful fluid balance, correction of hypoglycaemia with intravenous dextrose, treatment of any underlying infection, and the administration of thyroid hormones (Table 2). Intravenous hydrocortisone (100 mg) should be given empirically, and continued until hypoadrenalism has been excluded. A random cortisol of less than 100 nmol/l in an unwell patient is diagnostic of adrenal failure. The mortality of myxoedema coma is 30–40%, and patients usually require mechanical ventilation on ITU with central venous pressure monitoring.2 T3 is often preferred to T4 because of its faster onset of action. This is usually given via a nasogastric tube, although some endocrine units advocate the use of slow intravenous administration. A few days after recovery, the patient should be switched to T4 in standard replacement doses (Table 2).
after surgery and is temporary. The precise cause of transient hypocalcaemia is unknown but may be due to release of calcitonin during manipulation of the thyroid gland, devascularization of the parathyroid glands, or ‘hungry bone syndrome’ in hyperthyroid patients. The latter describes the rapid mobilization of calcium into bones, which may occur after correction of hyperthyroidism. The incidence of hypocalcaemia post-thyroidectomy may be as high as 46%, although less than half of patients are symptomatic.3 When symptoms of hypocalcaemia are present, the appropriate management is 10 ml of 10% intravenous calcium gluconate. If hypocalcaemia persists for more than 48 hours after surgery, hypoparathyroidism is likely to be due to inadvertent removal of the parathyroid glands. In this situation, patients should be started on 1 α-cholecalciferol and calcium supplementation, and long-term follow up is recommended. Upper airway obstruction due to goitre Rarely, patients with goitre may present with acute respiratory distress due to tracheal compression (Figure 2). If there is significant airway obstruction and hypoxia, a senior anaesthetist should be called immediately. Endotracheal intubation may be difficult and the use of a rigid ‘bougie’ or fibre-optic aid may be required. If the patient is significantly hypoxic and distressed while waiting for a secure airway, upper airway resistance may be reduced by administering a mixture of oxygen and helium (heliox), although this is only a temporary manoeuvre, and the patient will require permanent airway protection until a definitive thyroidectomy is performed.
Anaesthetic and surgical aspects of thyroid disease Thyroid dysfunction in non-thyroidal surgery Occasionally thyroid dysfunction is found incidentally in the pre-operative assessment of patients for non-thyroidal surgery. Whether this should delay routine surgery depends upon the degree of biochemical and clinical disturbance, the urgency of surgery, and the individual view of the responsible anaesthetist or surgeon. Although not subjected to randomized prospective trials, it is generally felt that mild to moderate hypothyroidism is not associated with a particular anaesthetic risk. In severe hypothyroidism, the risk of precipitating a myxoedema crisis is a consideration, and it is sensible to treat with thyroxine and defer the operation unless surgery is urgent. In hyperthyroidism, the risk of peri-operative atrial fibrillation should be taken into account, and it is advisable to delay surgery and treat with anti-thyroid medication and β-blockers until the biochemical and clinical thyroid status of the patient is satisfactory. In the urgent surgical situation it may be necessary to anaesthetise a patient with uncontrolled thyrotoxicosis, and such patients require early senior anaesthetic review. In this situation, long-acting β-blockade and anti-thyroid medication should be administered, with close peri- and intra-operative monitoring due to the risk of fast atrial fibrillation, cardiac failure and, in extreme circumstances, thyroid storm.
Non-thyroidal illness Sick euthyroid syndrome It may be difficult to interpret abnormal thyroid function in the acute care setting because systemic disease can lead to abnormal thyroid results. In any acute non-thyroidal illness, the normal dynamics of the hypothalamo-pituitary-thyroid axis are impaired, leading to reduced central TSH secretion and marginally low T4 and T3 levels. This situation is known as ‘sick euthyroid
Post-thyroidectomy complications Thyroidectomy is a common operation and it is important for junior doctors covering surgical wards to be aware of the potential complications. The most serious problem is bleeding into the wound, which may lead to respiratory distress and asphyxia, and this requires urgent senior surgical review for re-exploration of the neck. If a patient complains of post-operative peri-oral/ peripheral paraesthesia or tetany, it is important to consider hypocalcaemia. Typically, hypocalcaemia occurs 10–18 hours
THE FOUNDATION YEARS 4:6
Figure 2 CT scan thoracic inlet showing nodular goitre with tracheal compression (arrow shows narrow trachea).
239
© 2008 Elsevier Ltd. All rights reserved.
Acute Care s yndrome’ and is not necessarily indicative of thyroid pathology. In this situation, specific thyroid treatment may not be indicated,4 and it is more appropriate to treat the underlying illness and repeat the thyroid function after recovery.
(PTU) are the most commonly prescribed anti-thyroid drugs, and it is important to warn the patient of potential side effects of rash, sore throat or fever. Agranulocytosis is a rare but recognised complication of anti-thyroid therapy and if symptoms occur, the drug should be stopped and a full blood count performed. In young women planning pregnancy, PTU is preferred to carbimazole because of the potential association of choanal atresia and aplasia cutis with carbimazole. When starting anti- thyroid medication, the dose and treatment regime should be discussed with a local endocrinologist and appropriate follow up arranged. It is helpful to measure anti-thyroid peroxidise antibodies at diagnosis, and a repeat thyroid function test should be organised 4–6 weeks after starting treatment.
Drugs Many drugs interfere with thyroid function, although the measurement of fT4 means that clinicians no longer have to consider the effect of enzyme-inducers/inhibitors on total thyroxine levels. Medications which interfere with thyroxine absorption include proton pump inhibitors and ferrous sulphate, which may lead to under-replacement in patients on thyroxine. Lithium therapy may lead to hypothyroidism due to its direct inhibitory effect on thyroid hormone secretion. Amiodarone warrants special mention because it is commonly prescribed for patients with arrhythmias. Due to its high iodine content, amiodarone can lead to either hypothyroidism or hyperthyroidism via two different idiosyncratic responses. Patients on amiodarone without underlying thyroid disease may have marginally elevated fT4 levels due to reduced conversion of T4 to T3, although TSH usually normalizes after the first 6 months of treatment in this situation. Patients with frank hypoor hyperthyroidism usually have an underlying predisposition to thyroid disease, which requires treatment. Amiodarone-induced hyperthyroidism may be difficult to treat and often requires a joint approach between an endocrinologist and cardiologist.5
Summary There are numerous clinical situations where hospital physicians might need to consider thyroid disease. Thyroid emergencies are rare but a high index of clinical suspicion is required for early diagnosis and treatment. Incidental hyper- and hypothyroidism is commonly found in the hospital setting, and an accurate assessment of the clinical context is important before deciding on subsequent management. ◆
Pregnancy Normal pregnancy can lead to thyroid function abnormalities, so it is important to consider this in any young woman with abnormal thyroid function results. In the first trimester, it is not unusual to see a modest elevation in fT4 and fT3, with a suppressed TSH, because β-HCG is a partial agonist to the TSH receptor. Occasionally, β-HCG has a significant effect, causing severe nausea and vomiting (hyperemesis gravidarum) requiring hospital admission, and in this situation patients may be frankly thyrotoxic. The appropriate treatment is supportive management with fluids and anti-emetics rather than specific anti-thyroid medication, because the biochemical abnormalities will resolve as the pregnancy progresses if there is no underlying thyroid disorder. Anti-thyroid treatment should only be considered in pregnancy when there is frank thyrotoxicosis or other clinical features of thyroid disease, such as goitre, thyroid ophthalmopathy or a strong family history of thyroid disease.
References 1 Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am 2006; 35: 663. 2 Kwaku MP, Burman KD. Myxedema Coma. J Intensive Care Med 2007; 22(4): 224–31. 3 See AC, Soo KC. Hypocalcaemia following thyroidectomy for thyrotoxicosis. British Journal of Surgery 1997; 84: 95–7. 4 Utiger RD. Altered thyroid function in nonthyroidal illness and surgery. To treat or not to treat? N Engl J Med 1995; 333: 1562. 5 Franklyn JA, Gammage MD. Treatment of amiodarone-associated thyrotoxicosis. Nat Clin Pract Endocrinol Metab 2007; 3(9): 662–6.
Questions for reflection What is the presentation and optimal management of thyroid storm? What is the presentation and optimal management of myxoedema coma? What are the potential complications of thyroidectomy? What non-thyroidal conditions may lead to thyroid dysfunction?
Starting patients on anti-thyroid therapy If patients are found to have newly diagnosed hyperthyroidism during their inpatient stay, and it is felt the clinical features are directly due to thyroid pathology rather than non-thyroidal illness, it is appropriate for a hospital physician to start anti-thyroid treatment before discharge. Carbimazole and propylthiouracil
THE FOUNDATION YEARS 4:6
240
© 2008 Elsevier Ltd. All rights reserved.
Assessment and management of thyroid disease
Relevance to the curriculum 1.0 Good clinical care 1.1 History, examination, diagnosis (recognising clinical features of hypothyroidism and hyperthyroidism, atypical presentations of thyroid disease, interpreting thyroid function tests) 1.2 Time management and decision-making (recognising acute presentations thyroid disease, pre-operative assessment of thyroid dysfunction) 2.0 Maintaining good medical practice 2.1 Learning 2.2 Research, evidence and guidelines 7.0 Recognition and management of the acutely ill 7.1 Core skill (basic resuscitation in thyroid storm, myxoedema coma and airways obstruction) 7.2 Resuscitation (as 7.1) 7.5 Selection and interpretation of investigations (interpretation of liver function tests, thyroid function tests, renal function, ECG in context of thyroid emergencies covered)
Miles Levy
Abstract Thyroid emergencies are rare but are important to recognise because of the high mortality associated with them. Thyroid storm is a clinical syndrome associated with fever, central nervous effects, gastrointestinalhepatic dysfunction, tachycardia and congestive cardiac failure. Myxoedema coma is typically associated with hypothermia, hypoventilation, hyponatraemia, hypoglycaemia and decreased mental function. Surgical and anaesthetic aspects of thyroid disease include the assessment of patients with thyroid dysfunction before non-thyroidal surgery, recognising post-thyroidectomy complications, and the management of acute upper airway obstruction due to goitre. Factors including systemic illness, medication and pregnancy may affect thyroid function, and it is important to consider these before deciding on the appropriate management strategy.
fever are present thyroid storm may initially be mistaken for sepsis. If there is a high index of clinical suspicion for a hyperthyroid crisis, modern assays will allow for a rapid turnaround of free thyroxine levels (fT4), free tri-iodothyronine levels (fT3), and thyroid stimulating hormone (TSH) levels. Particular clinical clues include a vascular goitre, thyroid eye disease, and vitiligo or other auto-immune disease, although these may be absent. Preliminary blood tests may reveal pre-renal failure, hypercalcaemia, abnormal liver function and signs of sepsis. ECG changes will reveal a narrow complex tachycardia, commonly fast atrial fibrillation, and there is usually radiological evidence of pulmonary oedema in frank thyroid storm. The management of thyroid storm involves basic resuscitation, control of tachycardia and cardiac failure, symptomatic treatment of agitation and fever, and specific anti-thyroid medication (Table 1). Because severe hyperthyroidism is associated with increased metabolic rate and renal clearance of drugs, high doses of β-blockers and digoxin may be required to control ventricular rate. In terms of anti-thyroid therapy, it probably does not matter whether carbimazole or propylthiouracil (PTU) is used, but it is important that either drug is administered via the appropriate route. This usually means a nasogastric tube if patients are too unwell to take oral medication. PTU is often preferred because it reduces the conversion of T4 to T3, although carbimazole has a longer duration of action, so both drugs have advantages. Many endocrine units advocate the use of Lugol’s iodine because it reduces the conversion of T4 to T3. It is important that Lugol’s iodine is given more than 4 hours after the administration of the first dose of carbimazole or PTU, as there may be a paradoxical rise in T4 in response to an acute iodine load. Corticosteroids are also known to reduce the peripheral conversion of T4 to T3, and are commonly given in thyroid storm. Prophylactic anticoagulation should be given in hyperthyroid crises, and if thrombo-embolic disease is suspected, therapeutic doses should be given. Hyperpyrexia is treated with anti-pyretics
Keywords myxoedema coma; sick euthyroid syndrome; thyroid emergencies, thyroid storm
Introduction Abnormal thyroid function can be the main reason for hospital admission or an incidental finding during an inpatient stay. It is important to measure thyroid function in all inpatients because both hyper- and hypothyroidism are common and have a wide range of clinical presentations. Thyroid emergencies are rare but important to recognise because they are associated with a high mortality.
Thyroid emergencies Thyroid storm Hyperthyroidism can lead to an extreme biochemical and clinical disturbance known as thyroid storm. Thyroid storm is characterized by a collection of clinical features, including fever, central nervous effects, gastrointestinal-hepatic dysfunction, tachycardia and congestive cardiac failure (Table 1).1 Usually there is an obvious trigger, such as thyroid surgery or radioiodine therapy in a patient with known thyroid disease, or non-thyroid surgery in a patient with undiagnosed hyperthyroidism. Any form of catecholamine excess can resemble thyroid storm, and if jaundice and
Miles Levy MBBS FRCP MD is a Consultant Endocrinologist at Leicester Royal Infirmary and Honorary Senior Lecturer at Leicester Medical School, UK. He has a particular interest in pituitary tumours and medical education. Conflicts of interest: none declared.
THE FOUNDATION YEARS 4:6
237
© 2008 Elsevier Ltd. All rights reserved.
Acute Care
Clinical features, range of presentation and management of thyroid storm
Clinical features, investigation findings and management of myxoedema coma
Clinical feature
Range of presentation
Management
Clinical features
Investigations
Management
Cardiac failure
Mild ankle oedema Basal lung crepitations Frank pulmonary oedema
Oxygen ECG monitoring
Confusion Psychosis Coma Hypothermia
Hyponatraemia Hypoglycaemia Elevated CK Type 2 respiratory acidosis High TSH (often >100 iU/l)
Passive rewarming Mechanical ventilation Fluid balance Intravenous dextrose
Tachycardia
Fast AF SVT
Central nervous effects
Fever
Gastrointestinal effects
Degree of tachycardia related to disease severity Mild agitation Psychosis Delirium Seizure Coma Degree of hyperpyrexia related to disease severity Diarrhoea
Vomiting Jaundice
Frusemide as appropriate Digoxin as appropriate Propranolol 40–80 mg po 6-hourly Diltiazem 60–120 mg po 6-hourly if β-blocker contraindicated Prophylactic anticoagulation in fast AF Chlorpromazine 50 mg po 8-hourly (or 25 mg IM)
Bradycardia
Hypoventilation
Low fT4
Preceding hypothyroid symptoms
Low random cortisol ECG CXR Septic screen
Hydrocortisone 100 mg i.v. 6-hourly until random cortisol result known Treat sepsis as appropriate T3 (5–20 μg via NG tube then 2.5–10 μg 8-hourly po for 2–3 days) Change to T4 50-100 ug od po when clinical improvement
CK, creatinine kinase; CXR, chest radiograph; NG, nasogastric; TSH, thyroid stimulating hormone.
Tepid sponging Paracetamol Consider dantrolene in malignant hyperthermia (T > 40°C) Propylthiouracil 200 mg 4-hourly or carbimazole 20 mg 4-hourly Lugol’s iodine 6-hourly (first dose 4 hours after anti-thyroid drugs)
Table 2
is the skin thickening that occurs in profound hypothyroidism due to the accumulation of mucopolysaccharide in subcutaneous tissues. Patients often have preceding symptoms of classical hypothyroid features when asked in retrospect. The presence of frank psychotic symptoms may lead to acute psychiatric admission (‘myxoedema madness’), and the presence of a pericardial effusion may lead to cardio-respiratory collapse (Figure 1). In addition to hypoglycaemia and hyponatraemia, patients may have very elevated creatine kinase levels and evidence of sepsis.
AF, atrial fibrillation; IM, intramuscular; SVT, supraventricular tachycardia.
Table 1
and peripheral cooling techniques, and in significant hyperthermia dantrolene may be considered (as for neuroleptic malignant syndrome). Fluid balance usually requires central venous pressure monitoring because of the presence of cardiac failure, and this should ideally occur in a high dependency or ITU environment. In rare cases, patients who fail to improve after initial measures may require haemofiltration or haemodialyis. The mortality of thyroid storm is approximately 10%, underlying the importance of intensive monitoring and treatment in the early phase of this condition. Myxoedema coma Severe hypothyroidism, especially in the elderly, may present with confusion or even coma. The presence of hypothermia, hypoventilation, hyponatraemia and hypoglycaemia raises the possibility of a hypothyroid crisis (Table 2). When patients are unconscious, this is referred to as myxoedema coma. Myxoedema
THE FOUNDATION YEARS 4:6
Figure 1 CT thorax showing pericardial effusion in a patient with myxoedema coma (arrow shows pericardial fluid).
238
© 2008 Elsevier Ltd. All rights reserved.
Acute Care Arterial blood gas analysis often shows type 2 respiratory failure. In myxoedema coma, fT4 levels are very low and TSH is usually significantly elevated when due to primary hypothyroidism. Hypoadrenal crises often occur in conjunction with myxoedema coma because of the association between auto-immune hypothyroidism and Addison’s disease. Adrenal insufficiency is particularly likely in the presence of hypoglycaemia, hyponatraemia, hyperkalaemia and hypotension. The management of myxoedema coma includes passive rewarming, careful fluid balance, correction of hypoglycaemia with intravenous dextrose, treatment of any underlying infection, and the administration of thyroid hormones (Table 2). Intravenous hydrocortisone (100 mg) should be given empirically, and continued until hypoadrenalism has been excluded. A random cortisol of less than 100 nmol/l in an unwell patient is diagnostic of adrenal failure. The mortality of myxoedema coma is 30–40%, and patients usually require mechanical ventilation on ITU with central venous pressure monitoring.2 T3 is often preferred to T4 because of its faster onset of action. This is usually given via a nasogastric tube, although some endocrine units advocate the use of slow intravenous administration. A few days after recovery, the patient should be switched to T4 in standard replacement doses (Table 2).
after surgery and is temporary. The precise cause of transient hypocalcaemia is unknown but may be due to release of calcitonin during manipulation of the thyroid gland, devascularization of the parathyroid glands, or ‘hungry bone syndrome’ in hyperthyroid patients. The latter describes the rapid mobilization of calcium into bones, which may occur after correction of hyperthyroidism. The incidence of hypocalcaemia post-thyroidectomy may be as high as 46%, although less than half of patients are symptomatic.3 When symptoms of hypocalcaemia are present, the appropriate management is 10 ml of 10% intravenous calcium gluconate. If hypocalcaemia persists for more than 48 hours after surgery, hypoparathyroidism is likely to be due to inadvertent removal of the parathyroid glands. In this situation, patients should be started on 1 α-cholecalciferol and calcium supplementation, and long-term follow up is recommended. Upper airway obstruction due to goitre Rarely, patients with goitre may present with acute respiratory distress due to tracheal compression (Figure 2). If there is significant airway obstruction and hypoxia, a senior anaesthetist should be called immediately. Endotracheal intubation may be difficult and the use of a rigid ‘bougie’ or fibre-optic aid may be required. If the patient is significantly hypoxic and distressed while waiting for a secure airway, upper airway resistance may be reduced by administering a mixture of oxygen and helium (heliox), although this is only a temporary manoeuvre, and the patient will require permanent airway protection until a definitive thyroidectomy is performed.
Anaesthetic and surgical aspects of thyroid disease Thyroid dysfunction in non-thyroidal surgery Occasionally thyroid dysfunction is found incidentally in the pre-operative assessment of patients for non-thyroidal surgery. Whether this should delay routine surgery depends upon the degree of biochemical and clinical disturbance, the urgency of surgery, and the individual view of the responsible anaesthetist or surgeon. Although not subjected to randomized prospective trials, it is generally felt that mild to moderate hypothyroidism is not associated with a particular anaesthetic risk. In severe hypothyroidism, the risk of precipitating a myxoedema crisis is a consideration, and it is sensible to treat with thyroxine and defer the operation unless surgery is urgent. In hyperthyroidism, the risk of peri-operative atrial fibrillation should be taken into account, and it is advisable to delay surgery and treat with anti-thyroid medication and β-blockers until the biochemical and clinical thyroid status of the patient is satisfactory. In the urgent surgical situation it may be necessary to anaesthetise a patient with uncontrolled thyrotoxicosis, and such patients require early senior anaesthetic review. In this situation, long-acting β-blockade and anti-thyroid medication should be administered, with close peri- and intra-operative monitoring due to the risk of fast atrial fibrillation, cardiac failure and, in extreme circumstances, thyroid storm.
Non-thyroidal illness Sick euthyroid syndrome It may be difficult to interpret abnormal thyroid function in the acute care setting because systemic disease can lead to abnormal thyroid results. In any acute non-thyroidal illness, the normal dynamics of the hypothalamo-pituitary-thyroid axis are impaired, leading to reduced central TSH secretion and marginally low T4 and T3 levels. This situation is known as ‘sick euthyroid
Post-thyroidectomy complications Thyroidectomy is a common operation and it is important for junior doctors covering surgical wards to be aware of the potential complications. The most serious problem is bleeding into the wound, which may lead to respiratory distress and asphyxia, and this requires urgent senior surgical review for re-exploration of the neck. If a patient complains of post-operative peri-oral/ peripheral paraesthesia or tetany, it is important to consider hypocalcaemia. Typically, hypocalcaemia occurs 10–18 hours
THE FOUNDATION YEARS 4:6
Figure 2 CT scan thoracic inlet showing nodular goitre with tracheal compression (arrow shows narrow trachea).
239
© 2008 Elsevier Ltd. All rights reserved.
Acute Care s yndrome’ and is not necessarily indicative of thyroid pathology. In this situation, specific thyroid treatment may not be indicated,4 and it is more appropriate to treat the underlying illness and repeat the thyroid function after recovery.
(PTU) are the most commonly prescribed anti-thyroid drugs, and it is important to warn the patient of potential side effects of rash, sore throat or fever. Agranulocytosis is a rare but recognised complication of anti-thyroid therapy and if symptoms occur, the drug should be stopped and a full blood count performed. In young women planning pregnancy, PTU is preferred to carbimazole because of the potential association of choanal atresia and aplasia cutis with carbimazole. When starting anti- thyroid medication, the dose and treatment regime should be discussed with a local endocrinologist and appropriate follow up arranged. It is helpful to measure anti-thyroid peroxidise antibodies at diagnosis, and a repeat thyroid function test should be organised 4–6 weeks after starting treatment.
Drugs Many drugs interfere with thyroid function, although the measurement of fT4 means that clinicians no longer have to consider the effect of enzyme-inducers/inhibitors on total thyroxine levels. Medications which interfere with thyroxine absorption include proton pump inhibitors and ferrous sulphate, which may lead to under-replacement in patients on thyroxine. Lithium therapy may lead to hypothyroidism due to its direct inhibitory effect on thyroid hormone secretion. Amiodarone warrants special mention because it is commonly prescribed for patients with arrhythmias. Due to its high iodine content, amiodarone can lead to either hypothyroidism or hyperthyroidism via two different idiosyncratic responses. Patients on amiodarone without underlying thyroid disease may have marginally elevated fT4 levels due to reduced conversion of T4 to T3, although TSH usually normalizes after the first 6 months of treatment in this situation. Patients with frank hypoor hyperthyroidism usually have an underlying predisposition to thyroid disease, which requires treatment. Amiodarone-induced hyperthyroidism may be difficult to treat and often requires a joint approach between an endocrinologist and cardiologist.5
Summary There are numerous clinical situations where hospital physicians might need to consider thyroid disease. Thyroid emergencies are rare but a high index of clinical suspicion is required for early diagnosis and treatment. Incidental hyper- and hypothyroidism is commonly found in the hospital setting, and an accurate assessment of the clinical context is important before deciding on subsequent management. ◆
Pregnancy Normal pregnancy can lead to thyroid function abnormalities, so it is important to consider this in any young woman with abnormal thyroid function results. In the first trimester, it is not unusual to see a modest elevation in fT4 and fT3, with a suppressed TSH, because β-HCG is a partial agonist to the TSH receptor. Occasionally, β-HCG has a significant effect, causing severe nausea and vomiting (hyperemesis gravidarum) requiring hospital admission, and in this situation patients may be frankly thyrotoxic. The appropriate treatment is supportive management with fluids and anti-emetics rather than specific anti-thyroid medication, because the biochemical abnormalities will resolve as the pregnancy progresses if there is no underlying thyroid disorder. Anti-thyroid treatment should only be considered in pregnancy when there is frank thyrotoxicosis or other clinical features of thyroid disease, such as goitre, thyroid ophthalmopathy or a strong family history of thyroid disease.
References 1 Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am 2006; 35: 663. 2 Kwaku MP, Burman KD. Myxedema Coma. J Intensive Care Med 2007; 22(4): 224–31. 3 See AC, Soo KC. Hypocalcaemia following thyroidectomy for thyrotoxicosis. British Journal of Surgery 1997; 84: 95–7. 4 Utiger RD. Altered thyroid function in nonthyroidal illness and surgery. To treat or not to treat? N Engl J Med 1995; 333: 1562. 5 Franklyn JA, Gammage MD. Treatment of amiodarone-associated thyrotoxicosis. Nat Clin Pract Endocrinol Metab 2007; 3(9): 662–6.
Questions for reflection What is the presentation and optimal management of thyroid storm? What is the presentation and optimal management of myxoedema coma? What are the potential complications of thyroidectomy? What non-thyroidal conditions may lead to thyroid dysfunction?
Starting patients on anti-thyroid therapy If patients are found to have newly diagnosed hyperthyroidism during their inpatient stay, and it is felt the clinical features are directly due to thyroid pathology rather than non-thyroidal illness, it is appropriate for a hospital physician to start anti-thyroid treatment before discharge. Carbimazole and propylthiouracil
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