Chief Concern

Persistent fatigue. Requesting chart update on newly identified genetic finding, review of two lab flags, and discussion of likely fatigue contributors given the full clinical picture.

1. New Genetic Finding: HFE C282Y Homozygous

Source: 23andMe v5 raw genome export, interpreted 2026-06-21.

Current iron status (05/15/2026), no active overload:

Female penetrance for clinical hemochromatosis with C282Y homozygosity is approximately 1%. Decades of menstrual blood loss are likely protective; patient is post-menopausal and iron accumulation risk increases going forward. No current overload. Iron supplementation is contraindicated regardless of ferritin level.

• Document C282Y homozygous status in chart
• Order iron panel + ferritin every 6 months (not annual)
• Discuss phlebotomy trigger: suggest ferritin >150 ng/mL or saturation >45% on repeat testing
• Patient's APOE4 status (below) makes tighter ferritin target appropriate: goal 50–100 ng/mL rather than broad lab normal of 232

2. Lab Flags from 05/15/2026

2a. Testosterone: Supraphysiologic with Hgb/Hct Elevation

Patient is on HRT. Testosterone total: 626 ng/dL (supraphysiologic for female). Hemoglobin and hematocrit are elevated on same draw. Secondary erythrocytosis from exogenous testosterone is a known adverse effect and is a plausible primary contributor to her fatigue via increased blood viscosity and impaired oxygen delivery.

• Review current testosterone dose and route
• Recheck CBC and testosterone; consider dose reduction if Hgb/Hct remain elevated

2b. TSH: Low

TSH: 0.27 mIU/L (below lower limit ~0.4). Free T4 and free T3 within normal limits on same draw. Patient is not on thyroid medication. May reflect pituitary suppression from exogenous sex hormones, subclinical hyperthyroidism, or early dysfunction.

• Recheck TSH in 3 months
• If persistently low: consider free T3/T4 and thyroid antibodies

3. Fatigue: Most Likely Contributors

In priority order based on current labs:

1. Secondary erythrocytosis from supraphysiologic testosterone, thicker blood, impaired oxygen delivery
2. Low-normal ferritin (34 ng/mL)- suboptimal for energy even within reference range; functional target 50–100 ng/mL. Cannot supplement iron given C282Y homozygous status
3. Low TSH- subclinical or medication-related; can cause fatigue
4. APOE4 e4/e4 brain energy metabolism- brain insulin resistance is intrinsic to this genotype and not captured in standard labs

4. Background: APOE4 e4/e4

Patient is homozygous APOE4 (e4/e4), highest-risk genotype for late-onset Alzheimer's disease. Actively engaged in evidence-based prevention. Relevant for prescribing decisions:

• ApoB target: 60 mg/dL (current 126 mg/dL as of 05/15/2026). Pursuing statin-free reduction via ezetimibe.
• Iron: As above, tighter ferritin targets appropriate for APOE4 carriers; excess iron is neurotoxic. Target 50–100 ng/mL.
• HRT: Estradiol 181 pg/mL (transdermal). Consistent with published data supporting early post-menopausal HRT initiation for APOE4 carrier women.