Case study - Tinnitus with an unexpected outcome

A chance consultation led Dr David Morris to uncover an uncommon underlying syndrome in his patient.

The patient had disturbed LFTs but low alcohol intake and no symptoms
The patient had disturbed LFTs but low alcohol intake and no symptoms

In the 11 years James had been registered with the practice he had never sought a doctor's appointment, until now. So when he arrived at afternoon surgery complaining of a high-pitched buzzing in his ears, I took notice.

James was a 45-year-old site foreman, married with two children, with no significant past medical history. His tinnitus was principally left-sided and had persisted for around two months.

James reported a sensation of dizziness on suddenly looking upward, but this did not amount to vertigo, and there had been no associated loss of hearing or balance disturbance.

Examination of his ENT system was unremarkable, with no suggestion of nystagmus or cranial nerve deficit, and fundal appearances were normal. His BP was elevated at 156/107mmHg but the remainder of his cardiovascular system was normal on examination.

Investigations
James's BP remained elevated on repeat measurement, and routine investigations for hypertension were arranged.

The unexpected finding was disturbed LFTs with an ALT of 150U/l and a gamma GT of 214U/l. FBC, U&Es, TFTs and fasting blood glucose were normal, together with a reasonable lipid profile and a satisfactory resting ECG.

James denied any right upper quadrant pain, episodic fever or jaundice, and was adamant that his alcohol consumption was no more than moderate (less than 20 units per week).

He had not been on any foreign travel, was not taking any medication and could not recall any family history of liver problems. Examination of his abdomen did not reveal any tenderness or hepatomegaly.

Repetition of LFTs confirmed the persistence of raised ALT and gamma GT levels, although these values appeared to be stable. An ultrasound scan of his abdomen was requested.

It is not always my practice to check serum ferritin levels in response to disturbed LFTs, but on this occasion I did.

The serum ferritin came back markedly elevated at 1,326ng/ml, which raised the possibility of haemochromatosis. While serum ferritin is an acute phase protein, James was not systemically unwell, and in any case the magnitude of the elevation seemed to genuinely indicate iron overload.

Other than showing a little fatty change, the ultrasound scan did not reveal any significant abnormality. James was referred to the gastroenterologist with a presumptive diagnosis of haemochromatosis.

The outcome
I received a fax back from the gastroenterologist explaining that James had been found to be homozygous for the C282Y mutation, which is the most common genetically inherited form of haemochromatosis.

Transferrin saturation indicated significant iron overload and James was referred to the haematologists for consideration of venesection.

I remain unaware of any connection between haemochromatosis and tinnitus or hypertension, the initial findings.

James was referred to the ENT consultant and subsequently an MRI brain scan was all clear.

After intolerance to ramipril James's hypertension was well controlled with candesartan.

The condition
Hereditary haemochromatosis is an autosomal recessive gene disorder with a carrier rate of around one in 10 and a prevalence of one in 400 of the condition (the homozygous state has incomplete penetrance).

The responsible gene lies on the short arm of chromosome 6 and is denoted HFE, the most common mutation being C282Y. Bearing in mind the inheritance pattern, consideration should be given to screening siblings, partner or children for the condition.

The metabolic disorder is characterised by excessive intestinal iron absorption, leading to iron deposition in multiple organs, notably the liver, heart, pancreas, pituitary, adrenal glands and skin.

Men tend to be affected around the age of 50, typically 10 years earlier than their female counterparts who are relatively protected by loss of iron from menstruation.

Haemochromatosis may be suspected from disturbed LFTs or a raised serum ferritin. Organ specific damage may be apparent from the occurrence of diabetes mellitus, hepatomegaly, cardiac failure or hypogonadism (from pituitary failure).

The skin may take on a bronze pigmentation and arthralgia may arise secondary to chondrocalinosis (calcium pyrophosphate deposition). Ultimately, signs of chronic liver disease can appear, such as gynaecomastia, spider naevi, palmar erythema and loss of body hair.

Regular venesection is undertaken to restrict organ damage and prolong life. While there is no clinical reason why a patient with genetic haemochromatosis should not donate blood, there are ethical concerns about patients doing so, and the permitted frequency may not be sufficient to control the condition.

Haematocrit, serum ferritin and transferrin saturation should be monitored, aiming to keep them within the normal range. Hepatic damage can progress to cirrhosis, from which there is a risk of developing hepatocellular carcinoma.

In cases of hepatic failure, transplantation may be offered. When endocrine organ damage is significant, hormone replacement may be offered, such as testosterone replacement in hypogonadism or insulin therapy in diabetes.

  • Dr Morris is a GP in Shrewsbury, Shropshire

CAUSES OF DISTURBED LFTS

  • Alcohol
  • Gallstone pathology, e.g. cholecystitis, cholangitis
  • Drugs, e.g. statins, paracetamol overdose
  • Infection, e.g. viral hepatitis
  • Autoimmune disease, e.g. biliary cirrhosis, autoimmune hepatitis
  • Tumours
  • Vascular, e.g. right heart failure
  • Haemochromatosis
  • Alpha-1 antitrypsin deficiency
  • Wilson's disease

LEARNING POINTS

  • Haemochromatosis is a condition of iron overload.
  • Consider the diagnosis in the patient with disturbed LFTs without any other explanation.
  • Serum ferritin levels are significantly raised in haemochromatosis.
  • Iron deposition can lead to damage of liver, heart and endocrine organs.
  • Venesection is the mainstay of treatment.

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