100_Cases_in_Clinical_Medicine

CASE 20: FEVERS AND FATIGUE

History

A 33-year-old woman is admitted to hospital because of general fatigue, fever and weight loss. She has lost 5 kg in weight over the last 3 months. She has felt increasingly fatigued and has a poor appetite. Over the past few weeks she has felt as if she was feverish and has developed night sweats. She has no chest pain or shortness of breath. She and her two children, aged 4 and 6 years, have come from Nigeria to visit her husband who has been in this country for 2 years. She has visited the UK twice before. She has had occasional fevers over the last 10 years and these have been treated presumptively as malaria with a good response. She has been otherwise well, although her periods have been irregular over the last 3 months. She has had no other serious medical illnesses. She is a non-smoker and drinks no alcohol. The ward receptionist has suggested that she is not entitled to NHS treatment.

Examination

She is thin and looks unwell. Her temperature is 38.2°C. There are no abnormalities in the cardiovascular or respiratory systems and there are no lymph nodes palpable. Her conjunctivae look pale. Physical examination is otherwise normal.

INVESTIGATIONS

Blood film: immature red cells/nucleated red cells present

Serum electrophoresis: normal

Urinalysis: no protein; no blood

Blood and urine cultures: negative

A chest X-ray is shown in Fig. 20.1.

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Figure 20.1 Chest X-ray.

Questions

•What is the diagnosis?

•How would you investigate and manage this patient?

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ANSWER 20

This patient has fever, marked weight loss and a leucoerythroblastic anaemia. The length of the symptoms makes infections such as malaria unlikely, although this should be checked since she arrived from Nigeria and combined infections are possible. A very important finding is that immature red and white cells are seen in the peripheral blood. This leucoerythroblastic anaemia indicates bone-marrow replacement by tumour or infection forcing immature cells out into the blood. This woman has miliary tuberculosis. Miliary tuberculosis is characterized by tuberculous granulomata throughout the body due to widespread dissemination of tubercle bacilli. It is now usually seen in elderly persons and the diagnosis is often only made at autopsy. The chest X-ray shows miliary lesions (multiple small nodules 2–5 mm in diameter). These are often subtle or not visible at presentation. There may be choroidal tubercles in the eyes on funduscopy and hepatosplenomegaly.

!Differential diagnoses of fevers !3 weeks

•Other infections: visceral abscesses, infective endocarditis, specific organisms (e.g. brucellosis, actinomycosis or toxoplasmosis) and tropical diseases (e.g. malaria or trypanosomiasis).

•Neoplastic diseases: lymphomas, renal cell carcinomas, pancreatic tumours.

•Collagen vascular diseases, e.g. systemic vasculitis, rheumatoid arthritis, systemic lupus erythematosus, temporal arteritis.

•Miscellaneous: recurrent pulmonary emboli, drug fever, sarcoidosis.

This patient needs an urgent diagnosis. Bronchoscopy with lavage may reveal acid-fast bacilli. Biopsy of her liver and bone marrow may show tubercle bacilli or caseating granulomas. The tissue should also be sent for culture. The tuberculin test may be negative because of immunoincompetence induced by the disease. Antituberculous treatment with four agents must be started immediately once biopsy material has been obtained. In a woman of child-bearing age a pregnancy test should be done, particularly in the face of menstrual irregularities. In severely ill patients corticosteroids are of benefit. The total lymphocyte count is low and, in a patient from Africa, HIV infection is a distinct possibility. Informed consent should be sought for an HIV test. Tuberculosis is a notifiable disease and the diagnosis should be notified and arrangements made to screen her children and any other close contacts.

Although eligibility for treatment needs to be assessed by appropriate managers, this woman has an acute life-threatening illness and is a potential infective risk to others. Investigation and treatment should be undertaken in the normal way.

KEY POINTS

•Miliary tuberculosis is often missed as a cause of weight loss and fever in the elderly.

•Miliary tuberculosis may present with a leucoerythroblastic anaemia.

•Always culture biopsy material in patients with pyrexias of unknown origin.

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CASE 21: TIREDNESS

History

A 55-year-old man presents to his general practitioner (GP), complaining of lack of energy. He has become increasingly tired over the past 18 months. He works as a solicitor and describes episodes where he has fallen asleep in his office. He is unable to stay awake after 9.30 pm, and sleeps through until 7.30 am. He finds it difficult to concentrate at work, and has stopped playing his weekly game of tennis. He had an episode of depression 10 years ago related to the break-up of his first marriage. He has no current personal problems. He has had no other major illnesses. His brother developed type 1 diabetes mellitus at the age of 13. On direct questioning, he has noticed that he has become more constipated but denies any abdominal pain or rectal bleeding. He has put on 8 kg in weight over the past year.

Examination

On examination he is overweight. His facial skin is dry and scaly. His pulse is 56/min, regular and blood pressure 146/88 mmHg. Examination of his cardiovascular, respiratory and abdominal systems is unremarkable. Neurological examination was not performed.

INVESTIGATIONS

Urinalysis: nothing abnormal detected (NAD)

Questions

•What is the likely diagnosis?

•How would you further examine, investigate and manage this patient?

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ANSWER 21

Fatigue is a very common symptom of both physical and mental illness. The differential diagnosis is extensive and includes cancer, depression, anaemia, renal failure and endocrine diseases. In this case the main differential diagnoses are depression and hypothyroidism. He has a past history of depression, but currently has no obvious triggers for a further episode of depression. He is not waking early in the morning or having difficulty getting to sleep, which are common biological symptoms of severe depression. There are a number of clues in this case to the diagnosis of hypothyroidism. Insidious onset of fatigue, difficulty concentrating, increased somnolence, constipation and weight gain are features of hypothyroidism. As in this case there may be a family or past medical history of other autoimmune diseases such as type 1 diabetes mellitus, vitiligo or Addison’s disease. Hypothyroidism typically presents in the fifth or sixth decade, and is about five times more common in women than men. Obstructive sleep apnoea is associated with hypothyroidism and may contribute to daytime sleepiness and fatigue.

On examination the facial appearances and bradycardia are consistent with the diagnosis. Characteristically patients with overt hypothyroidism have dry, scaly, cold and thickened skin. There may be a malar flush against the background of the pale facial appearance (‘strawberries and cream appearance’). Scalp hair is usually brittle and sparse, and there may be thinning of the lateral third of the eyebrows. Bradycardia may occur and the apex beat may be difficult to locate because of the presence of a pericardial effusion. A classic sign of hypothyroidism is the delayed relaxation phase of the ankle jerk. Other neurological syndromes which may occur in association with hypothyroidism include carpal tunnel syndrome, a cerebellar sydrome or polyneuritis. Patients may present with psychiatric illnesses including psychoses (‘myxoedema madness’).

Clues to the diagnosis in the investigations are the normochromic, normocytic anaemia, marginally raised creatinine, and hypercholesterolaemia. The anaemia of hypothyroidism is typically normochromic, normocytic or macrocytic; microcytic anaemia may occur if there is menorrhagia. A macrocytic anaemia may represent undiagnosed vitamin B12 deficiency. Renal blood flow is reduced in hypothyroidism, and this can cause the creatinine to be slightly above the normal range.

The most severe cases of hypothyroidism present with myxoedema coma, with bradycardia, reduced respiratory rate and severe hypothermia. Typically, shivering is absent.

In this case the thyroid function tests were as follows: thyroid-stimulating hormone (TSH) 73 mU/L (normal range: !6 mU/L); free thyroxine (T4) 3 pmol/L (normal range 9–22 pmol/L). The high TSH indicates primary hypothyroidism rather than hypopituitarism. The most common cause of hypothyroidism is autoimmune thyroiditis and the patient should have thyroid autoantibodies assayed.

!Causes of hypothyroidism

•Panhypopituitarism

•Autoimmune thyroiditis

•Post-thyroidectomy

•Post-radio-iodine treatment for thyrotoxicosis

•Drugs for treatment of hyperthyroidism: carbimazole, propylthiouracil

•Amiodarone, lithium

•Dietary iodine deficiency

•Inherited enzyme defects

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Treatment is with T4 at a maintenance dose of 75–200 &g/day. Response is measured clinically and biochemically by the return of TSH to the normal range. Elderly patients or those with coronary heart disease should be started cautiously on T4 because of the risk of precipitating myocardial ischaemia.

KEY POINTS

•Hypothyroidism should be considered in the differential diagnosis of any patient presenting with fatigue.

•A neurological examination should be part of the routine assessment of such patients.

•Clinical symptoms of hypothyroidism are usually non-specific.

•Hypothyroidism may present in unusual ways such as psychoses or decreased conscious level.

•Autoimmune thyroiditis is the commonest cause of hypothyroidism.

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