What is the appropriate evaluation and management for a 35‑year‑old woman with microcytic, hypochromic anemia (hemoglobin 9 g/dL, hematocrit 29.6 %, mean corpuscular volume 67.8 fL, mean corpuscular hemoglobin 20.6 pg, mean corpuscular hemoglobin concentration 30.5 g/dL) and low ferritin (12 µg/L), low vitamin D (27.5 ng/mL), low‑normal morning cortisol (6 µg/dL) and normal fasting glucose?

Immediate Management of Severe Iron‑Deficiency Anemia in a Young Woman

This 35‑year‑old woman has severe iron‑deficiency anemia (hemoglobin 9 g/dL, ferritin 12 µg/L, MCV 67.8 fL) that requires immediate oral iron supplementation while simultaneously investigating the underlying cause—most commonly heavy menstrual bleeding or gastrointestinal blood loss in this demographic. 1

Diagnostic Confirmation

Your patient's laboratory profile definitively confirms iron‑deficiency anemia:

• Ferritin 12 µg/L is below the 15 µg/L threshold, providing 99% specificity for absent iron stores and eliminating the need for bone marrow examination 1
• Severe microcytosis (MCV 67.8 fL) combined with elevated RDW (17%) is the pathognomonic pattern for iron deficiency, distinguishing it from thalassemia trait (which typically shows RDW ≤14%) 1, 2
• Low MCH (20.6 pg) and low MCHC (30.5 g/dL) confirm hypochromic, iron‑deficient erythropoiesis 1

The ferritin of 12 µg/L is unequivocally diagnostic; transferrin saturation measurement is unnecessary when ferritin is this low. 1

Immediate Treatment Protocol

Oral Iron Supplementation

Start ferrous sulfate 325 mg (65 mg elemental iron) once daily on an empty stomach. 1 Although traditional dosing recommends three times daily, once‑daily dosing improves adherence and is often sufficient for this degree of anemia. 1

• Expected response: hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks, confirming the diagnosis even if initial iron studies were equivocal 1, 2
• If gastrointestinal side effects occur, switch to ferrous gluconate or ferrous fumarate 1
• Adding 250 mg ascorbic acid (vitamin C) enhances absorption 2
• Continue iron for at least 3 months after hemoglobin normalizes to replenish iron stores and prevent recurrence 1, 3

Concurrent Vitamin D Replacement

Treat the severe vitamin D deficiency (27.5 ng/mL) with cholecalciferol 50,000 IU weekly for 8 weeks, then maintenance dosing. 1

Mandatory Investigation of Underlying Cause

Do not attribute iron deficiency in a 35‑year‑old woman solely to dietary insufficiency; occult blood loss must be excluded. 1

First‑Line Evaluation

1. Detailed menstrual history – Heavy menstrual bleeding is the most common cause in premenopausal women 1

   • Quantify duration, frequency, and number of pads/tampons per day
   • Consider gynecology referral if menorrhagia is confirmed

2. Gastrointestinal assessment – The second most common etiology 1

   • Stool guaiac testing immediately to screen for occult GI bleeding 1
   • Review for symptoms of celiac disease (diarrhea, bloating, weight loss)
   • Celiac serologies (tissue transglutaminase IgA with total IgA) – celiac disease accounts for 2–3% of iron‑deficiency cases 1

3. Dietary assessment – Evaluate for vegetarian/vegan diet or inadequate iron intake 1

Indications for Endoscopy

Upper endoscopy with duodenal biopsies and colonoscopy are indicated if: 1

• Stool guaiac is positive
• Celiac serologies are positive (duodenal biopsies confirm diagnosis)
• Gastrointestinal symptoms are present (dyspepsia, reflux, change in bowel habits)
• Anemia fails to respond to oral iron within 4 weeks despite good compliance
• Menstrual blood loss does not fully account for the severity of anemia

Upper endoscopy screens for gastric cancer, peptic ulcer disease, and NSAID‑induced gastropathy; colonoscopy detects colonic carcinoma, polyps, and angiodysplasia. 1

Monitoring Protocol

• Repeat CBC in 2 weeks – Hemoglobin should rise ≥1 g/dL, confirming iron deficiency 1, 2
• Repeat CBC and ferritin at 3 months – Hemoglobin should normalize; continue iron until ferritin >50 µg/L 1
• Monitor hemoglobin and MCV every 3 months for 1 year, then annually 1, 2

When to Consider Intravenous Iron

Switch to IV iron (iron sucrose or ferric carboxymaltose) if: 1, 2

• Hemoglobin fails to rise ≥2 g/dL within 4 weeks despite documented compliance
• Malabsorption is confirmed (e.g., celiac disease, inflammatory bowel disease, gastric bypass)
• Gastrointestinal side effects prevent adherence to oral therapy
• Ongoing blood loss exceeds oral replacement capacity

Expected response to IV iron: hemoglobin increase ≥2 g/dL within 4 weeks. 1

Addressing the Low‑Normal Morning Cortisol

The morning cortisol of 6 µg/dL is at the lower limit of normal and does not require immediate intervention in an otherwise asymptomatic patient. 1 Severe anemia itself can suppress the hypothalamic‑pituitary‑adrenal axis. Reassess cortisol after correcting the anemia; if symptoms of adrenal insufficiency develop (fatigue, hypotension, hyponatremia), perform an ACTH stimulation test. 1

Critical Pitfalls to Avoid

• Do not delay iron supplementation while awaiting endoscopy results; treat immediately while investigating 1
• Do not assume dietary insufficiency is the sole cause without excluding GI blood loss 1
• Do not stop iron therapy when hemoglobin normalizes; continue for 3 months to replenish stores 1, 3
• Do not overlook celiac disease—it is present in 2–3% of iron‑deficiency cases and requires duodenal biopsies for diagnosis 1
• Do not attribute all symptoms to anemia alone—severe vitamin D deficiency (27.5 ng/mL) contributes to fatigue and requires concurrent treatment 1
• Do not order hemoglobin electrophoresis at this stage; ferritin 12 µg/L confirms iron deficiency, and thalassemia screening is unnecessary 1, 2