How should I interpret the labs of a 31‑year‑old woman who progressed from subclinical to overt primary hypothyroidism (elevated TSH, low free thyroxine) with persistent iron‑deficiency anemia, and what follow‑up, treatment, and specialist referrals are indicated?

Interpretation and Management of Progressive Hypothyroidism with Iron Deficiency

Laboratory Interpretation

This patient has progressed from subclinical to overt primary hypothyroidism due to Hashimoto thyroiditis, with concurrent persistent iron-deficiency anemia.

The initial labs showed subclinical hypothyroidism (TSH 5.77 with normal free T4 0.73) and microcytic anemia (MCV 76.5, hemoglobin 11.3). Seven months later, the patient developed overt hypothyroidism with TSH 27.3, critically low free T4 0.19, and strongly positive thyroid peroxidase antibodies (376), confirming autoimmune thyroiditis 1. The anemia persists with ferritin 27 ng/mL (below the threshold of <100 μg/L that may reflect iron deficiency in inflammatory states) and transferrin saturation 27% 1.

The presence of anti-TPO antibodies confers a 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative individuals 2. This patient's rapid progression over 7 months exemplifies this accelerated trajectory.

Immediate Treatment Required

Levothyroxine Initiation

Start levothyroxine immediately at 1.6 mcg/kg/day (approximately 100-125 mcg daily for a 31-year-old woman without cardiac disease). 2

• For patients under 70 years without cardiac disease or multiple comorbidities, full replacement dosing is appropriate 2
• Before initiating levothyroxine, rule out concurrent adrenal insufficiency by checking morning cortisol and ACTH, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 2, 3
• Recheck TSH and free T4 in 6-8 weeks after starting therapy, then adjust dose by 12.5-25 mcg increments every 6-8 weeks until TSH normalizes to 0.5-4.5 mIU/L 2
• Once stable, monitor TSH every 6-12 months 2

Iron Replacement Strategy

Treat both conditions simultaneously—levothyroxine therapy significantly enhances response to oral iron in patients with coexisting hypothyroidism and iron-deficiency anemia. 4

• A randomized controlled trial demonstrated that patients receiving both levothyroxine and oral iron had hemoglobin increases of 1.9 g/dL versus only 0.4 g/dL with iron alone 4
• Start oral iron 240 mg elemental iron daily (e.g., ferrous sulfate 325 mg three times daily) 4
• The increase in serum iron was 47.6 μg/dL greater in patients receiving combination therapy 4
• Recheck complete blood count, iron panel, and ferritin in 8-12 weeks 1

Investigation for Blood Loss

Evaluate for gastrointestinal blood loss, as iron deficiency in a non-menstruating woman (or one without excessive menstrual losses) warrants careful GI assessment. 1

• In non-dialysis CKD patients not on erythropoietic agents and without significant menstrual losses, iron deficiency should prompt assessment for GI bleeding 1
• All adult women with iron-deficiency anemia and men should have upper GI endoscopy with small bowel biopsy and colonoscopy to exclude malignancy 1
• Celiac disease screening (tissue transglutaminase antibodies) is essential, as it commonly coexists with autoimmune thyroiditis 1

Follow-Up Protocol

Thyroid Monitoring

• TSH and free T4 at 6-8 weeks after each dose adjustment 2
• Target TSH 0.5-4.5 mIU/L with normal free T4 2
• Once stable, annual TSH monitoring 2

Anemia Monitoring

• Complete blood count, serum iron, TIBC, ferritin, and transferrin saturation at 8-12 weeks 1
• Continue iron supplementation until ferritin >100 ng/mL and transferrin saturation >20% 1
• If anemia persists despite adequate thyroid replacement and iron therapy, consider bone marrow evaluation for other causes 1

Autoimmune Surveillance

• Screen for other autoimmune conditions annually, including type 1 diabetes (fasting glucose or HbA1c), celiac disease (if not already done), and vitamin B12 deficiency 1
• Monitor for development of adrenal insufficiency with annual assessment for unexplained fatigue, weight loss, hypotension, or salt craving 2

Specialist Referrals

Endocrinology Referral (Recommended)

Refer to endocrinology for management of severe overt hypothyroidism with positive anti-TPO antibodies and rapid progression. 2

• Severe hypothyroidism (TSH >20 mIU/L, free T4 <0.3 ng/dL) benefits from specialist oversight 5
• Autoimmune thyroiditis requires long-term monitoring for progression and associated autoimmune conditions 2
• Endocrinology can coordinate screening for polyglandular autoimmune syndrome 2

Gastroenterology Referral (Mandatory)

Refer to gastroenterology for bidirectional endoscopy to exclude GI malignancy and celiac disease. 1

• Upper endoscopy with duodenal biopsies to evaluate for celiac disease 1
• Colonoscopy to exclude colonic cancer, polyps, or angiodysplasia 1
• Iron deficiency in a 31-year-old woman without obvious blood loss mandates complete GI evaluation 1

Hematology Referral (If Anemia Persists)

• If anemia fails to respond to combined levothyroxine and iron therapy after 12 weeks, refer to hematology 1
• Abnormalities in two or more cell lines warrant hematology consultation 1
• Persistent iron deficiency despite adequate replacement suggests ongoing blood loss or malabsorption requiring specialist evaluation 1

Critical Pitfalls to Avoid

• Never start levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or multiple pituitary hormone deficiencies, as this can precipitate adrenal crisis 2, 3
• Do not attribute iron deficiency solely to hypothyroidism without investigating for GI blood loss—coexisting GI malignancy must be excluded 1
• Avoid treating iron deficiency alone without addressing hypothyroidism, as anemia will not adequately respond to oral iron therapy when both conditions coexist 4
• Do not delay treatment waiting for repeat testing—this patient has overt hypothyroidism requiring immediate intervention 2, 5
• Avoid overtreatment by monitoring TSH closely; approximately 25% of patients on levothyroxine are unintentionally overtreated, increasing risks for atrial fibrillation, osteoporosis, and fractures 2