Setting: office
CC: “My joints hurt and my skin is turning dark.”
VS: BP: 104/74 mm Hg; P: 76 beats/minute
HPI: A 54-year-old man with progressive arthralgia of the lower extremities, tiredness, and fatigue comes to the office because his wife says his skin is darkening. She also brought him for his erectile dysfunction.
PMHX:
Type 2 diabetes
ROS:
Dyspnea on exertion
Medications:
Metformin, repaglinide
What is the mechanism of the repaglinide?
a. Increased insulin release from the pancreas
b. Peripheral insulin sensitization
c. Decreased gluconeogenesis
d. Increased levels of incretins (glucose-dependent insulinotropic peptide [GIP], glucagonlike peptide [GLP])
Answer a. Increased insulin release from the pancreas
Repaglinide and nateglinide are insulin secretagogues that function in the same way as sulfonylureas. They increase insulin release from the pancreas. They can, therefore, cause hypoglycemia and weight gain.
PE:
General: tired, dark skin clearly obvious
Extremities: no joint swelling, no deformity
Abdomen: enlarged spleen
Genitals: testicles small
Initial Orders:
CBC
Liver function tests
CHEM-20
Glycated hemoglobin (HbA1c)
Testosterone level
Abnormal Reports:
Albumin 2.5 mg/dL (low)
Aspartate aminotransferase (AST) 123 units/L, alanine aminotransferase (ALT) 145 units/L (both three times the upper limit of normal)
HbA1c 7.2%
Free and total testosterone decreased
Which is the best initial test for to give a specific diagnosis?
a. Liver biopsy
b. Iron, total iron-binding capacity (TIBC), ferritin
c. Hemochromatosis (HFE) gene test
d. MRI
Answer b. Iron, TIBC, ferritin
Iron and ferritin levels are elevated. TIBC is decreased. Hemochromatosis is a collection of information that can be difficult to put together. There is no single physical finding that is specific for the disorder. It is a collection of abnormalities that only in a pattern suggest iron overload.
• Liver disease
• Joint pain
• Hypogonadism
• Hypopituitarism
• Diabetes
The patient’s diabetes may be from undiagnosed hemochromatosis.
Joint pain in hemochromatosis is from the calcium pyrophosphate deposition of pseudogout.
The patient’s iron and ferritin levels are elevated and the transferring saturation is over 80%. The patient refuses liver biopsy.
Patients can refuse procedures on CCS. A spontaneous note will pop up as you move the clock forward saying “Patient declines procedure.”
Orders:
HFE gene
Liver MRI
The HFE gene test is abnormal and the liver MRI shows markedly increased iron.
What is the best initial therapy?
a. Phlebotomy
b. Deferoxamine
c. Deferasirox
d. Deferiprone
Answer a. Phlebotomy
Phlebotomy is able to remove far more iron than a chelating agent. The chelating agents are used when someone receives frequent transfusions and you cannot treat with phlebotomy. Deferoxamine is much harder to use than deferasirox or deferiprone because it must be given by subcutaneous injection. Deferasirox and deferiprone are administered orally.
What is the site of the fundamental defect that causes hemochromatosis?
a. Duodenum
b. Liver
c. Heart
d. Pituitary
Answer a. Duodenum
The genetic defect that leads to hemochromatosis causes the overabsorption of iron in the duodenum. Normally, hepcidin is made by the liver and stops iron absorption when the body has what is required. In hemochromatosis, there is persistent iron absorption. This leads to accumulation in the liver, heart, pituitary, pancreas, joints, and skin.
Iron accumulation in the pituitary gland decreases levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
The patient is not enthusiastic about repeated episodes of phlebotomy.
What do you tell him the most common cause of death is without phlebotomy?
a. Cirrhosis
b. Liver cancer
c. Cardiac failure
d. Diabetes
Answer a. Cirrhosis
Liver disease kills more people than heart failure in hemochromatosis. The causes of death in patients with hemochromatosis are as follows:
• Cirrhosis: 60%
• Hepatoma: 20%
• Cardiac failure: 15%
Restrictive cardiomyopathy is the most common heart disease associated with hemochromatosis.
After telling the patient he will have progressive cirrhotic death or liver cancer without phlebotomy, he agrees to the phlebotomy.