Hereditary Hemochromatosis as a Cause of Hypogonadism

Once the diagnosis of hemochromatosis has been confirmed, CT or MRI can be used to assess for increased density of the liver.¹ Liver biopsy can determine the degree of fibrosis and is often considered in patients with more extreme elevations of serum ferritin levels and/or hepatomegaly. Liver biopsy is the only reliable method for determining whether hepatic cirrhosis, which increases risk for hepatocellular carcinoma, is present.¹

TREATMENT

All patients with homozygous HH and evidence of iron overload require treatment, regardless of symptoms. Phlebotomy is the standard of care, due to its low cost and relative safety. Chelating agents are a second-line option when contraindications to phlebotomy (eg, anemia) exist.^1,2

Alcohol consumption, espe­cially in the presence of iron overload or liver disease, should be avoided, as it can increase risk for cirrhosis by nearly tenfold.¹ Dietary modification is typically unnecessary, aside from the avoidance of iron and vitamin C supplementation.² Patients should also eliminate raw shellfish from their diet, as they may carry bac­teria that can cause ­potentially ­fatal infection (since high iron levels impair hepcidin bactericidal activity).²

The management of hepatic failure, cardiac failure, and diabetes in patients with HH is similar to conventional management of these conditions.¹ With phlebotomy, the liver and spleen often decrease in size, liver function improves, skin pigmentation lightens, cardiac failure may be reversed, and diabetes control often improves.^1,2 Testosterone levels may normalize after phlebotomy, especially if HH is diagnosed in the early stages. In more advanced cases, testosterone replacement therapy in combination with aggressive phlebotomy may be necessary.⁴

CONCLUSION

A high index of suspicion is required to diagnose hemochromatosis early. HH should be considered in the differential diagnosis for patients with hypogonadotropic hypogonadism, abnormal iron studies, elevated transaminase levels, and a family history of hemochromatosis.

Once the diagnosis is established, all first-degree relatives should be screened.¹ Early therapy is crucial to prevent complications from iron overload.

REFERENCES

1. Powell LW. Hemochromatosis. In: Fauci AS, Braunwald E, Kasper DL, et al (eds). Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008:2429-2433.

2. Crownover BK, Carlton JC. Hereditary hemochromatosis. Am Fam Phys. 2013;87(3):183-190.

3. Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood. 2005;106(12):3710-3717.

4. McDermott JH, Walsh CH. Hypogonadism in hereditary hemochromatosis. J Clin Endocrinol Metab. 2005;90(4):2451-2455.

5. Hudec M, Grigerova M, Walsh CH. Secondary hypothyroidism in hereditary hemochromatosis: recovery after iron depletion. Thyroid. 2008;18(2):255-257.