A 43-year-old man is being evaluated for erectile dysfunction, which has been progressive over the past year. He has no other symptoms except some fatigue that he attributes to his intense work schedule. The patient drinks 1-2 beers every day after work and has a 20-pack-year smoking history. He does not use recreational drugs or take over-the-counter medications. Vital signs are normal. BMI is 29 kg/m². Skin examination shows brownish skin pigmentation, most pronounced over the face and both arms. The abdomen is soft and nontender without organomegaly. Cardiopulmonary examination shows no abnormalities, and there is no peripheral edema. Laboratory results are as follows: If untreated, this patient is at increased risk for developing which of the following complications?

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11ec25c8_d417_8209_bc81_7325d507771b_MD0003_00 This patient's presentation is most consistent with hereditary hemochromatosis (HH). The increased total body iron leads to deposits in various organs (eg, liver, pancreas), resulting in multisystem organ damage. Disease progression typically requires decades of increased iron deposition. Consequently, patients tend to present in their 30s to 50s, with women presenting later due to therapeutic iron loss through menstruation. Most patients with HH are diagnosed early in the disease due to elevated liver enzymes on routine laboratory studies. However, continued iron deposition can cause hepatic fibrosis and cirrhosis, skin pigmentation (sun-exposed areas, scars, genitalia), diabetes mellitus ("bronze diabetes"), arthropathy, and hypogonadism (diminished libido, erectile dysfunction [ED]). Patients with HH have an approximate 20-fold increased risk for hepatocellular cancer (HCC), accounting for 45% of deaths in HH patients. The initial evaluation of HH commonly shows elevated iron studies. Diagnosis can be confirmed by genetic analysis of HFE mutations. Serial phlebotomy to deplete excess iron stores can significantly reduce the risk for cirrhosis and HCC. (Choice A) Gastric adenocarcinoma is rarely associated with Leser-Trélat sign (sudden development of seborrheic keratoses) or acanthosis nigricans (thickened, hyperpigmented, velvety skin patches over the neck and folds). In this patient, the distribution of hyperpigmentation and lack of skin thickening are not consistent with acanthosis nigricans. In addition, the combination of ED, skin pigmentation, hyperglycemia, and liver function test abnormalities makes HH more likely. (Choice C) Hypotensive crisis can complicate Addison disease (primary adrenal insufficiency). Hyperpigmentation (due to increased ACTH leading to increased melanocyte-stimulating hormone) is common; however, Addison disease is associated with hypoglycemia, not hyperglycemia. (Choice D) Primary systemic amyloidosis, which commonly presents with fatigue, hepatomegaly, and petechiae/ecchymosis on the face, can be complicated by nephrotic syndrome. However, it is usually not associated with ED or hyperglycemia. (Choice E) Pancreatic cancer can be associated with chronic pancreatitis and certain genetic syndromes (eg, Peutz-Jeghers syndrome), but not HH. (Choice F) Patients with genetic disorders such as xeroderma pigmentosum and albinism are at increased risk for skin cancer. HH does not confer increased risk. Educational objective: Hereditary hemochromatosis should be considered in patients who have elevated liver enzymes, diabetes mellitus, and skin hyperpigmentation. It can progress to cirrhosis and is associated with a significantly increased risk for hepatocellular carcinoma. References: Hepatic iron overload and hepatocellular carcinoma. (http://www.ncbi.nlm.nih.gov/pubmed/24804175) Hereditary hemochromatosis. (http://www.ncbi.nlm.nih.gov/pubmed/23418762) Non-viral causes of hepatocellular carcinoma. (http://www.ncbi.nlm.nih.gov/pubmed/20677332)

A 43-Year-Old Man Is Being Evaluated for Erectile Dysfunction, Which