A rare case of idiopathic haemochromatosis with Addison’s disease

INTRODUCTION

Addison’s disease is a rare endocrinal disorder that affects 1 in 100,000 people. It is seen in all age groups and affects male and female sexes equally. This disease is named after Thomas Addison, who first described patients affected by this disorder in 1855.^1,2 The common causes of Addison’s disease are autoimmune and tuberculosis. Tuberculosis is the most common cause of Addison’s disease in developing countries. Fungal infection, hemochromatosis, metastatic neoplasm, and X-linked adrenoleukodystrophy are other causes of Addison’s disease.^7,9

Hemochromatosis is a disorder, associated with an abnormal accumulation of iron leading to toxic organ damage. HFE-associated hemochromatosis mutations are among the most common inherited disease alleles. It is most common in populations of northern European extraction in whom approximately 1 in 10 persons are heterozygous carriers and 0.3–0.5% are homozygotes. Initial symptoms are often nonspecific and include lethargy, arthralgia, change in skin color, loss of libido, and features of diabetes mellitus. Hepatomegaly, increased pigmentation, spider angiomas, splenomegaly, arthropathy, ascites, cardiac arrhythmias, congestive heart failure, loss of body hair, testicular atrophy, and jaundice are prominent in advanced disease. Clinical symptoms develop during a long period of time, thus, determining accidental or late diagnosis, usually when complications are evident.

CASE REPORT

A 46-years old female presented to the medical OPD with a history of hyperpigmentation of the body involving face, palms, tongue and buccal mucosa, and chronic constipation since 2 years and repeated attacks of giddiness and generalized weakness with lethargy since 2 months along with menstrual irregularities. There was no history of syncopal attacks or seizures

There was no history of chronic intake of drugs or any previous blood transfusions. The family history revealed no similar abnormalities in any of the family members, either dead or alive.

On clinical examination, there was generalized hyperpigmentation of skin with palmar and oral pigmentation being quite evident (Fig 1, 2, and 3) . There were no signs of pallor, clubbing or pedal edema. Her vitals revealed persistent or (Fig.1, and 2). thostatic hypotension with a BP in supine position of 90/70mmHg and that in standing position was 76/60mmHg with a pulse rate of 86beats/pm. The systemic examination revealed no abnormalities.

Her investigations showed a haemoglobin level of 13.8g/dL, hyponatraemia (Na-130mEq/L), hyperkalaemia (K-5.49mEq/L). The levels of serum iron (191.4mcg), serum ferritin (794.7ng/L), transferrin saturation (66.1%) were all elevated. The 8am serum cortisol levels were reduced at 3.34nmol/L with a raised serum ACTH levels of 102.8pg/mL. The cosynotropin test was positive. Serum TSH level was normal with the Random blood sugar levels of 136 mg/dL.

The chest Xray and ultrasound of the abdomen showed no abnormalities. The 2D Echo showed a normal study with a LVEF of 62%. The MRI abdomen showed moderate atrophic changes in both the adrenal glands with a homogenous low signal intensity in both liver and spleen with paradoxical increase in signal intensity on ‘Out of phase’ imaging, suggesting iron deposition and left sided adrenal atrophy (Fig.4 and 5).

She was put on tapering dose of steroids, oral prednisolone (1mg/kg body weight) and referred to a haematological center for treatment of haemochromatosis.

DISCUSSION

A variety of pathological processes may cause Addison’s disease, which was first described by Thomas Addison.^1,2,3 The commonest causes of Addison’s disease are autoimmune conditions and tuberculosis. Several autoimmune processes can lead to adrenal insufficiency affecting exclusively the adrenal glands or be part of a more complex inherited autoimmune polyglandular syndrome.^5,7 Tuberculosis is the most common cause of Addison’s disease in developing countries. Fungal infection, hemochromatosis, metastatic neoplasm, and X-linked adrenoleukodystrophy are other causes of Addison’s disease.^7,9

One of the hallmark signs of Addison’s disease is cutaneous and mucosal hyperpigmentations related to ACTH melanogenesis action.^3,4 Soule reported that the presenting features among 50 patients seen over a 17-year period, as including hyperpigmentation (86%), weight loss (67%), abdominal pain (20%), and diarrhea (16%).⁶ Pigmentation can be homogeneous or blotchy. The pigmentation may involve skin, oral cavity, conjunctiva, and genitalia.^3,4 Brown patches of gingival, vermillion border of the lips, buccal mucosa, palate, and tongue may represent the first signs of Addison’s disease.⁴

During our evaluation, multiple abnormalities suggested iron overload or an underlying hematologic disorder. Adult and juvenile forms of hemochromatosis can cause adrenal gland dysfunction via an infiltrative mechanism, a factor that initially supported a unifying diagnosis for this case.^9,10

Attributable to hemochromatosis, our patient has derangements in her hematologic parameters, including elevations in ferritin, iron, and transferrin saturation. Systemic inflammation could account for these findings, as it is well known that ferritin and hepcidin can be upregulated in inflammatory states, with subsequent sequestration of iron within macrophages and hepatocytes.¹¹ An alternative theory is that adrenal gland insufficiency has an impact on iron metabolism. In our case, we were unable to prove that haemochromatosis had led to Addison’s disease or adrenal insufficiency has impacted the iron metabolism.

CONCLUSION

When differentiating the possible causes of Addison’s disease, it is important to test for the most common etiologies (autoimmune) as well as rare etiologies such as Haemochromatosis. In patients presenting with both Addison’s disease and Haemochromatosis, treatment should be focused first on management of adrenal insufficiency and then on close follow up for secondary complications from Haemochromatosis and subsequent treatment when indicated.

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