Hemochromatosis

Background

• Accumulation of iron in the body
• Most commonly due to hereditary hemochromatosis (HHC) or iron overload from transfusion
  • Hereditary hemochromatosis most common in people of Celtic ancestry
• AKA "bronze diabetes"

Clinical Features

Abdomen enlargement caused by giant hepatomegaly occupying the entire abdomen in a patient with secondary hemochromatosis.

• Cirrhosis
• Diabetes due to iron deposition in pancreatic beta cells
• Cardiomyopathy
• Arthritis: knuckles of the second and third fingers most common
• Bronzing of the skin

Differential Diagnosis

Hepatic Dysfunction

Infectious

• Hepatitis
  • Viral hepatitis
• Malaria
• HIV (present in 50% of AIDS patients)
• EBV
• Babesiosis, leptospirosis
• Typhoid
• Hepatic abscess, amebiasis

Neoplastic

• Metastases
• Hepatocellular carcinoma
• Multiple myeloma
• Leukemia
• Lymphoma
• Myeloproliferative disorders

Metabolic

• Hemochromatosis
• Wilson's disease
• Non-alcoholic steatohepatitis
• Inborn errors of metabolism

Biliary

• Biliary cirrhosis

Drugs

• Alcoholic cirrhosis
• Alcoholic hepatitis
• Hepatotoxic drugs

Miscellaneous

• Other causes of cirrhosis
• Autoimmune hepatitis
• Veno-occlusive disease
• CHF (right heart failure)

Hyperglycemia

Diabetic Emergencies

• Diabetic ketoacidosis (DKA)
• Diabetic ketoacidosis (peds)
• Hyperosmolar hyperglycemic state (HHS)
• Nonketotic hyperglycemia
• Euglycemic DKA (SGLT-2 inhibitors, pregnancy, fasting)

Diabetes Mellitus (New or Known)

• Type 1 diabetes mellitus (new-onset or uncontrolled)
• Type 2 diabetes mellitus (new-onset or uncontrolled)
• Medication noncompliance or insulin pump malfunction
• Gestational diabetes
• Latent autoimmune diabetes of adults (LADA)

Medication/Drug-Induced

• Corticosteroids (most common drug-induced cause)
• Thiazide diuretics
• Atypical antipsychotics (olanzapine, clozapine, quetiapine)
• Beta-blockers (especially non-selective)
• Phenytoin
• Tacrolimus, cyclosporine (transplant patients)
• Protease inhibitors (HIV antiretrovirals)
• Catecholamines (epinephrine, norepinephrine infusions)
• SGLT-2 inhibitors (paradoxical DKA with euglycemia)
• Total parenteral nutrition (TPN)
• Dextrose-containing IV fluids (iatrogenic)
• Niacin
• Pentamidine (initially hyperglycemia, then hypoglycemia from beta-cell destruction)

Physiologic Stress Response

• Sepsis / critical illness (stress hyperglycemia — very common in the ED)
• Trauma / major surgery / burns
• Acute coronary syndrome / myocardial infarction
• Stroke (especially hemorrhagic)
• Pancreatitis (both a cause and consequence)
• Shock (any etiology)
• Pain (catecholamine surge)
• Seizure (postictal)
• Physiologic stress alone rarely causes glucose >200 mg/dL in non-diabetics; glucose >200 in a "stress response" should prompt evaluation for undiagnosed diabetes or prediabetes

Endocrine

• Cushing syndrome / Cushing disease (cortisol excess)
• Pheochromocytoma (catecholamine excess)
• Hyperthyroidism / thyroid storm
• Acromegaly (growth hormone excess)
• Glucagonoma (rare)
• Somatostatinoma (rare)

Pancreatic

• Pancreatitis (acute or chronic — destruction of islet cells)
• Pancreatic malignancy (adenocarcinoma, neuroendocrine tumors)
• Post-pancreatectomy
• Cystic fibrosis-related diabetes
• Hemochromatosis (iron deposition in pancreas — "bronze diabetes")

Toxic/Overdose

• Iron toxicity (hepatic injury → impaired glucose regulation)
• Salicylate toxicity (can cause both hyper- and hypoglycemia)
• Sympathomimetic toxicity (cocaine, methamphetamine)
• Calcium channel blocker toxicity (impairs insulin secretion)
• Carbon monoxide toxicity (stress response)

Other

• Renal failure (chronic kidney disease, acute kidney injury — impaired insulin clearance AND insulin resistance)
• Cirrhosis / hepatic failure (impaired glycogenolysis regulation)
• Pregnancy (gestational diabetes, steroid administration for fetal lung maturity)
• Parenteral nutrition (TPN, dextrose-containing fluids)
• Post-transplant diabetes (immunosuppressants)

Complications of Diabetes (Not Causes of Hyperglycemia)

These are associated conditions that may be present alongside hyperglycemia but do not themselves cause elevated glucose:

• Diabetic foot infection
• Diabetic peripheral neuropathy
• Cerebral edema in DKA
• Diabetic retinopathy
• Diabetic nephropathy

Evaluation

• Serum ferritin:
  • >300 ng/mL in males and postmenopausal women
  • >150 - 200 ng/mL in premenopausal women
• Transferrin saturation: >45-50% is suggestive of iron overload
• Outpatient HFE genetic test to confirm diagnosis

Management

• Phlebotomy
• Chelation with deferoxamine

See Also

• Iron toxicity