What is the appropriate management for a patient with hyperferritinemia, normal thyroid function, impaired renal function, and diabetes mellitus?

Management of Elevated Ferritin, Normal TSH, Elevated ACR, and HbA1c 7.4

Your patient requires immediate focus on diabetes control and kidney protection with an ACE inhibitor or ARB, while the ferritin elevation at 442 ng/mL is most likely secondary to metabolic syndrome and does NOT require phlebotomy or iron-specific treatment. 1

Immediate Priority: Address Diabetes and Kidney Disease

Diabetes Management

• Target HbA1c between 6.5-7.5% given the presence of diabetic nephropathy (ACR 41.08 mg/mmol indicates microalbuminuria). 2
• The elevated ACR (>30 mg/g) with diabetes confirms diabetic nephropathy requiring aggressive intervention. 3
• Initiate or intensify glucose-lowering therapy, prioritizing SGLT2 inhibitors or GLP-1 receptor agonists as they provide kidney protection independent of glucose lowering. 2

Kidney Protection (Critical)

• Start an ACE inhibitor or ARB immediately (such as losartan) for diabetic nephropathy with proteinuria, as this reduces progression to end-stage renal disease. 3
• Losartan is specifically indicated for diabetic nephropathy with elevated serum creatinine and proteinuria (ACR ≥300 mg/g) in type 2 diabetes with hypertension history. 3
• Target blood pressure <130/80 mmHg with sodium restriction to <2g/day. 2

Lifestyle Modifications

• Dietary protein intake: 0.8 g/kg/day (do not restrict further as this does not improve kidney outcomes). 2
• Physical activity: 150 minutes/week moderate-intensity exercise to improve insulin sensitivity and metabolic parameters. 2
• Adopt a diet high in vegetables, fruits, whole grains, fiber, plant-based proteins, and unsaturated fats while limiting processed meats and refined carbohydrates. 2

Ferritin Interpretation: NOT Iron Overload

Why This Ferritin is Metabolic, Not Hemochromatosis

• Ferritin 442 ng/mL with diabetes and kidney disease is characteristic of dysmetabolic hyperferritinemia, not true iron overload. 1, 4
• Ferritin is an acute phase reactant that commonly elevates with metabolic syndrome, NAFLD, inflammation, and diabetes—independent of iron stores. 2, 1
• The critical test is transferrin saturation: if <45%, this confirms the ferritin elevation is NOT from iron overload. 2, 1, 4

Required Testing to Confirm

• Measure fasting transferrin saturation immediately. If <45% in women or <50% in men, iron overload is excluded. 2, 1
• Check ALT, AST, and GGT to assess for NAFLD, which commonly causes ferritin elevation with metabolic syndrome. 1
• Screen for other causes of hyperferritinemia: check CRP (inflammation), consider malignancy screening if clinically indicated. 2, 5

When to Consider HFE Genetic Testing

• Only pursue HFE testing if transferrin saturation is elevated (>45%) along with the elevated ferritin. 2
• Do NOT test for hemochromatosis genes based on ferritin alone with normal transferrin saturation. 2, 1

Monitoring Strategy

Short-term (3 months)

• Recheck HbA1c to assess diabetes control response to intensified therapy. 1
• Recheck ACR to monitor kidney disease progression. 2
• Measure transferrin saturation and ferritin together to confirm metabolic etiology. 1
• Monitor serum creatinine and eGFR for kidney function. 2

Long-term (6-12 months)

• Continue monitoring HbA1c every 3-6 months until stable at target. 2
• Monitor ACR every 6 months to assess nephropathy progression. 2
• Recheck ferritin and transferrin saturation every 6-12 months if initial transferrin saturation was normal. 1
• Annual screening for diabetes complications including retinopathy and neuropathy. 2

Critical Pitfalls to Avoid

Do NOT Initiate Phlebotomy

• Never start phlebotomy based on ferritin alone without confirming elevated transferrin saturation—this is the most common error. 2, 1
• Phlebotomy is only indicated for confirmed iron overload (transferrin saturation >45% AND elevated ferritin). 2

Do NOT Delay Diabetes/Kidney Management

• Do not delay ACE inhibitor/ARB initiation or diabetes intensification while investigating ferritin—cardiovascular and kidney protection is the immediate priority. 1, 3
• The ferritin elevation will likely normalize with improved metabolic control. 6, 7

Recognize Transient Hyperferritinemia

• Ferritin commonly elevates transiently at diabetes diagnosis and decreases with metabolic control improvement. 7
• In newly diagnosed or poorly controlled diabetes, hyperferritinemia often resolves within 7 months of achieving better glucose control. 7

Avoid Unnecessary Iron Restriction

• Do NOT restrict dietary iron or recommend phlebotomy for ferritin <500 ng/mL with normal transferrin saturation. 2, 1
• Iron supplementation should be avoided, but normal dietary iron intake is appropriate. 2