ANSWER 21
Fatigue is a very common symptom of both physical and mental illness. The differential diag-
nosis is extensive and includes cancer, depression, anaemia, renal failure and endocrine dis-
eases. 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. Obstruct-
ive 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 neuro-
logical syndromes which may occur in association with hypothyroidism include carpal
tunnel syndrome, a cerebellar sydrome or polyneuritis. Patients may present with psychi-
atric 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 B 12 defi-
ciency. 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 bradycar-
dia, 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: !6mU/L); free thyroxine (T 4 ) 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.
- 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
! Causes of hypothyroidism