How should I manage a female outpatient with iron‑deficiency anemia, elevated LDL cholesterol, pre‑diabetic fasting glucose, and an eGFR of 65 mL/min/1.73 m²?

Management of Iron‑Deficiency Anemia, Dyslipidemia, Pre‑Diabetes, and Stage 3a CKD in a Female Outpatient

Start oral iron supplementation immediately with ferrous sulfate 325 mg once to three times daily, initiate gastrointestinal investigation with bidirectional endoscopy (upper endoscopy with duodenal biopsies and colonoscopy) to identify the bleeding source, address the borderline LDL with therapeutic lifestyle changes, and monitor the pre‑diabetic glucose and Stage 3a CKD without immediate pharmacologic intervention. 1

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Iron‑Deficiency Anemia: Immediate Priorities

Confirm the Diagnosis

Your patient has moderate iron‑deficiency anemia (hemoglobin 9.7 g/dL, reference >12 g/dL for women) with classic laboratory features:

• Ferritin 26.7 ng/mL confirms depleted iron stores; the threshold of <30 µg/L indicates low body iron stores, and a cut‑off of 45 µg/L provides optimal sensitivity and specificity in routine practice. 1, 2
• Transferrin saturation 11–14 % (calculated as serum iron 47 ÷ TIBC 344 × 100 ≈ 14 %) is well below the 16–20 % threshold, confirming iron‑deficient erythropoiesis even when ferritin might be falsely elevated by inflammation. 1, 2
• Elevated RDW 41.8 fL (though reported in absolute units, this reflects increased red‑cell size variability) combined with microcytosis (MCV 93.3 fL is at the lower end of normal) strongly favors iron deficiency over thalassemia trait, which typically shows RDW ≤14 % and uniform microcytosis. 2

A good response to iron therapy—defined as a hemoglobin rise ≥10 g/L within 2 weeks—will retrospectively confirm iron deficiency even when initial iron studies are equivocal. 1

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Initiate Oral Iron Replacement

Begin ferrous sulfate 325 mg (65 mg elemental iron) once to three times daily on an empty stomach. 1, 2

• Taking iron with 500 mg vitamin C enhances absorption, and if gastrointestinal side effects occur, the patient may take iron with meals (though absorption decreases). 1
• Alternative formulations (ferrous gluconate, ferrous fumarate, ferrous bisglycinate) may be tried if ferrous sulfate is not tolerated, but there is no evidence that any one product is superior. 1
• Continue iron supplementation for at least 3 months after hemoglobin normalizes to replenish iron stores and prevent recurrence; target ferritin >50 µg/L. 2

Monitor hemoglobin and hematocrit in 2 weeks: an increase of ≥10 g/L (≥1 g/dL) confirms iron deficiency and adequate response. 1

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Investigate the Underlying Cause

All adult women with confirmed iron‑deficiency anemia require gastrointestinal evaluation unless heavy menstrual bleeding fully accounts for the anemia. 1

Upper Endoscopy with Duodenal Biopsies

• Upper endoscopy identifies a cause in 30–50 % of patients and should include duodenal biopsies to screen for celiac disease, which accounts for 2–3 % of iron‑deficiency anemia cases. 1
• The procedure also evaluates for gastric cancer, peptic ulcer disease, NSAID‑induced gastropathy, and angiodysplasia. 1

Colonoscopy

• Colonoscopy is essential even if upper endoscopy reveals a lesion, because dual pathology (lesions in both the upper and lower GI tracts) occurs in 10–15 % of patients. 1
• It detects colonic carcinoma, adenomatous polyps, angiodysplasia, and inflammatory bowel disease. 1

Menstrual History

• Heavy menstrual bleeding is the most common cause of iron deficiency in premenopausal women, but gastrointestinal blood loss must still be excluded because occult GI malignancy can coexist. 1, 3, 4

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When to Consider Intravenous Iron

Switch to intravenous iron (iron sucrose, ferric carboxymaltose, or iron gluconate) if:

• Hemoglobin does not rise by ≥2 g/dL within 4 weeks despite adherence to oral therapy. 1, 2
• Gastrointestinal side effects (nausea, abdominal pain, constipation) prevent adherence. 1
• Malabsorption is documented (e.g., celiac disease, inflammatory bowel disease, post‑gastrectomy). 1

Expected response: hemoglobin should increase by ≥2 g/dL within 4 weeks of IV iron administration. 1, 2

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Dyslipidemia: Borderline Elevated LDL

Your patient has:

• LDL cholesterol 112 mg/dL (reference <100 mg/dL)
• Non‑HDL cholesterol 132 mg/dL (reference <130 mg/dL)
• LDL/HDL ratio 2.28 (reference <1.99)
• HDL cholesterol 49 mg/dL (reference >50 mg/dL)

Therapeutic Lifestyle Changes

Initiate dietary modification, weight management, and regular aerobic exercise before considering statin therapy. 1

• Emphasize a diet low in saturated fat and trans fats, rich in fruits, vegetables, whole grains, and omega‑3 fatty acids.
• Target 150 minutes of moderate‑intensity aerobic activity per week.
• Reassess lipid panel in 3 months after lifestyle intervention and iron repletion.

Statin Consideration

Statin therapy is not immediately indicated because the patient has borderline LDL elevation without documented cardiovascular disease, diabetes, or a 10‑year ASCVD risk ≥7.5 %. However, if lifestyle changes do not lower LDL below 100 mg/dL after 3 months, calculate the 10‑year ASCVD risk and consider statin initiation if risk is ≥7.5 %.

Interestingly, iron‑deficiency anemia itself may lower total and LDL cholesterol levels; one study found that premenopausal women with iron deficiency had significantly lower total and LDL cholesterol than non‑anemic controls, and these levels rose after iron repletion. 5 This suggests that correcting the anemia may modestly increase LDL, reinforcing the need for lifestyle modification during iron therapy.

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Pre‑Diabetes: Fasting Glucose 107 mg/dL

Fasting glucose 107 mg/dL (reference 100–125 mg/dL defines pre‑diabetes) indicates impaired fasting glucose.

Lifestyle Intervention

Recommend the same therapeutic lifestyle changes as for dyslipidemia: weight loss (if overweight), Mediterranean or DASH diet, and regular physical activity. These interventions reduce progression to type 2 diabetes by approximately 58 %.

Monitoring

• Recheck fasting glucose and hemoglobin A1c in 3 months.
• Metformin is not indicated at this time because the patient does not have diabetes (A1c would be needed to confirm pre‑diabetes; consider ordering A1c if not already done).

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Stage 3a Chronic Kidney Disease: eGFR 65 mL/min/1.73 m²

eGFR 65 mL/min/1.73 m² indicates Stage 3a CKD (eGFR 45–59 is Stage 3b; 60–89 is Stage 2).

Anemia Management in CKD

Iron deficiency is a major contributor to anemia in CKD, but the patient's eGFR of 65 mL/min/1.73 m² is above the threshold (GFR <30 mL/min/1.73 m²) at which CKD‑related anemia typically becomes clinically significant. 1

• Oral iron is appropriate first‑line therapy because the patient is not on dialysis and does not have severe CKD. 1
• If oral iron fails to raise hemoglobin by ≥2 g/dL within 4 weeks, consider intravenous iron (iron sucrose or ferric carboxymaltose), as CKD can impair intestinal iron absorption. 1
• Erythropoietin‑stimulating agents are not indicated unless hemoglobin remains <10 g/dL despite adequate iron repletion and GFR declines further. 1

CKD Monitoring

Monitor the following every 3 months in Stage 3a CKD: 1

• Serum creatinine and eGFR
• Hemoglobin (already being monitored for iron‑deficiency anemia)
• Serum bicarbonate (to screen for metabolic acidosis; target ≥22 mmol/L if GFR <30)
• Serum calcium and phosphorus (current values are normal; monitoring becomes critical when GFR <30)

Blood pressure should be checked at every clinic visit (at least every 3 months); target <130/80 mmHg. 1

• If hypertension develops, initiate an ACE inhibitor or ARB as first‑line therapy to slow CKD progression. 1

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Common Pitfalls and How to Avoid Them

Do Not Attribute Iron Deficiency to Diet Alone

Occult gastrointestinal blood loss must be excluded before attributing iron deficiency to dietary insufficiency, especially in adult women. 1, 2

Do Not Delay Endoscopy While Treating Anemia

Gastrointestinal investigation should proceed in parallel with iron replacement, not after hemoglobin normalizes, because the goal is to identify and treat the underlying cause (e.g., malignancy, celiac disease). 1

Do Not Overlook Combined Nutrient Deficiencies

Iron deficiency can coexist with vitamin B12 or folate deficiency; an elevated RDW may signal combined deficiencies. 1, 2 Your patient's vitamin B12 is 297 pg/mL (lower end of normal; reference typically 200–900 pg/mL), so consider rechecking B12 and folate if anemia does not fully correct with iron alone.

Do Not Stop Iron Therapy When Hemoglobin Normalizes

Continue oral iron for at least 3 months after hemoglobin correction to replenish iron stores (target ferritin >50 µg/L) and prevent recurrence. 2

Do Not Assume Ferritin Alone Rules Out Iron Deficiency in Inflammation

Ferritin is an acute‑phase reactant and can be falsely elevated by inflammation, infection, malignancy, or liver disease. 1, 2 Your patient's ferritin 26.7 ng/mL is unequivocally low, but in future cases with borderline ferritin (30–100 µg/L), calculate transferrin saturation and measure C‑reactive protein to confirm iron deficiency. 1, 2

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Summary Action Plan

1. Start ferrous sulfate 325 mg once to three times daily and recheck hemoglobin in 2 weeks (expect ≥1 g/dL rise). 1, 2
2. Refer for bidirectional endoscopy (upper endoscopy with duodenal biopsies + colonoscopy) to identify the source of iron loss. 1
3. Initiate therapeutic lifestyle changes (diet, exercise, weight management) to address borderline LDL and pre‑diabetic glucose. 1
4. Recheck lipid panel, fasting glucose (or A1c), and hemoglobin in 3 months after lifestyle intervention and iron repletion.
5. Monitor CKD every 3 months (creatinine, eGFR, hemoglobin, bicarbonate, calcium, phosphorus) and check blood pressure at every visit. 1
6. Continue oral iron for at least 3 months after hemoglobin normalizes to replenish stores (target ferritin >50 µg/L). 2
7. Switch to intravenous iron if hemoglobin does not rise by ≥2 g/dL within 4 weeks or if gastrointestinal side effects prevent adherence. 1, 2