In a 6‑month postpartum woman who stopped breastfeeding 2 weeks ago, with month‑long fatigue, low mood, low motivation, difficulty losing weight, occasional missed levothyroxine (25 µg daily) doses, restarted fluoxetine (Prozac) 2 weeks ago, and new snoring, what are the likely differential diagnoses and which laboratory tests and screenings should be ordered?

Differential Diagnoses and Laboratory Workup

Most Likely Diagnosis: Inadequately Treated Hypothyroidism

The primary concern is inadequately treated hypothyroidism given the low levothyroxine dose (25 mcg), poor medication adherence, and classic symptoms of fatigue, difficulty losing weight, and new-onset snoring. 1

Key Clinical Reasoning:

• Levothyroxine 25 mcg is a subtherapeutic dose for most adults with hypothyroidism (typical replacement doses range 75-150 mcg daily), and she admits to frequently missing doses 1
• New snoring suggests possible myxedema-related upper airway changes or weight gain from undertreated hypothyroidism 1
• Difficulty losing weight postpartum is a hallmark of hypothyroidism, particularly when thyroid replacement is inadequate 1
• The timing (symptoms worsening over the last month, 2 weeks after stopping breastfeeding) suggests hormonal shifts may have unmasked inadequate thyroid replacement 1

Secondary Diagnosis: Postpartum Depression

While she restarted Prozac only 2 weeks ago (insufficient time for full therapeutic effect), postpartum depression remains a strong consideration given:

• Low mood and motivation are cardinal features of postpartum depression, which affects 10-15% of mothers 2
• Fatigue is a shared symptom between hypothyroidism and depression, making differentiation challenging 1, 3
• Stopping breastfeeding 2 weeks ago may have triggered mood changes through hormonal shifts, though research shows breastfeeding cessation itself doesn't directly cause increased fatigue 4

Tertiary Considerations:

Sleep-Disordered Breathing

• New-onset snoring warrants evaluation for obstructive sleep apnea, which can cause fatigue, mood disturbances, and difficulty with weight loss 1
• Postpartum weight retention combined with possible hypothyroid-related upper airway changes increases risk 1

Anemia

• Postpartum anemia is a common, treatable cause of fatigue that often goes unrecognized in "healthy" postpartum women 1
• Six months postpartum with possible inadequate iron repletion from pregnancy/breastfeeding 1

---

Essential Laboratory Tests and Screenings

Tier 1: Immediate Priority Labs

1. Thyroid Function Panel (TSH, Free T4)

• TSH is the single most important test to assess adequacy of levothyroxine replacement 1
• Given poor adherence and subtherapeutic dosing, expect elevated TSH 1
• Target TSH for reproductive-age women: 0.5-2.5 mIU/L 1

2. Complete Blood Count (CBC)

• Screen for anemia, a frequently overlooked cause of postpartum fatigue 1
• Assess hemoglobin, hematocrit, and MCV to differentiate iron deficiency from other causes 1

3. Comprehensive Metabolic Panel (CMP)

• Rule out electrolyte abnormalities and renal dysfunction that can contribute to fatigue 1
• Assess glucose to exclude diabetes-related fatigue 1

4. Ferritin and Iron Studies

• Ferritin <30 ng/mL can cause fatigue even without anemia 1
• Iron deficiency is extremely common postpartum and often persists months after delivery 1

Tier 2: Secondary Screening

5. Vitamin D Level (25-OH Vitamin D)

• Deficiency is prevalent postpartum and contributes to fatigue and mood symptoms 1

6. Vitamin B12 Level

• Screen for deficiency, particularly if dietary intake is limited 1

7. C-Reactive Protein (CRP)

• Consider if infection/inflammation is suspected, though evidence for routine screening in postpartum depression is mixed 5

Tier 3: If Initial Workup Normal

8. Sleep Study Referral

• Polysomnography if snoring persists and other causes excluded, as sleep-disordered breathing can mimic and exacerbate both hypothyroidism and depression 1

---

Critical Clinical Pitfalls to Avoid

Pitfall #1: Assuming Prozac Will Address All Symptoms

• Fluoxetine requires 6-8 weeks for full therapeutic effect 2
• Untreated hypothyroidism will prevent adequate antidepressant response 1
• Do not wait to optimize thyroid function—address both simultaneously 1

Pitfall #2: Overlooking Medication Non-Adherence

• "Sometimes forgets" levothyroxine is a red flag for inadequate treatment 1
• Counsel on taking levothyroxine on empty stomach, 30-60 minutes before food, and consider strategies to improve adherence 1
• Recheck TSH 6-8 weeks after dose adjustment and adherence improvement 1

Pitfall #3: Dismissing Snoring as Trivial

• New-onset snoring in a postpartum woman with fatigue warrants investigation 1
• Sleep-disordered breathing is underdiagnosed in women and can profoundly impact quality of life 1

Pitfall #4: Delaying Treatment While Awaiting Lab Results

• If TSH is significantly elevated (>10 mIU/L), increase levothyroxine immediately rather than waiting for follow-up 1
• Target dose is typically 1.6 mcg/kg ideal body weight (usually 100-150 mcg daily for most women) 1

---

Algorithmic Approach to Management

Step 1: Order Labs Immediately

• TSH, Free T4, CBC, CMP, Ferritin, Vitamin D, B12 1

Step 2: While Awaiting Results

• Continue Prozac (only 2 weeks in, needs 6-8 weeks for full effect) 2
• Counsel on levothyroxine adherence and proper administration 1
• Screen for postpartum depression severity using Edinburgh Postnatal Depression Scale 2

Step 3: Based on Lab Results

If TSH >10 mIU/L:

• Increase levothyroxine to 75-100 mcg daily immediately 1
• Recheck TSH in 6-8 weeks 1

If TSH 2.5-10 mIU/L:

• Increase levothyroxine by 25-50 mcg 1
• Recheck TSH in 6-8 weeks 1

If Hemoglobin <12 g/dL or Ferritin <30 ng/mL:

• Start iron supplementation (ferrous sulfate 325 mg daily or equivalent elemental iron 65 mg) 1
• Recheck CBC and ferritin in 8-12 weeks 1

If Vitamin D <30 ng/mL:

• Supplement with 1000-2000 IU daily 1

Step 4: Reassess in 2-4 Weeks

• Monitor mood symptoms (should begin improving if depression is primary) 2
• Monitor energy levels (should improve with thyroid/iron optimization) 1
• If snoring persists and fatigue continues despite treatment, refer for sleep study 1

Step 5: At 6-8 Weeks

• Recheck TSH and adjust levothyroxine to achieve TSH 0.5-2.5 mIU/L 1
• Assess antidepressant response (should see significant improvement by now) 2
• If depression persists despite optimized thyroid function, consider increasing Prozac or adding psychotherapy 2

---

Additional Considerations

Breastfeeding Cessation and Hormonal Shifts

• Stopping breastfeeding causes prolactin withdrawal, which has been inconsistently linked to mood changes 5
• The timing (2 weeks post-cessation) coincides with Prozac initiation, making it difficult to attribute symptoms solely to hormonal changes 5
• Hormonal fluctuations may unmask underlying hypothyroidism that was partially compensated during breastfeeding 1

Psychotherapy Consideration

• Cognitive behavioral therapy (CBT) is first-line for postpartum depression and should be offered alongside medication for moderate-to-severe symptoms 2
• Interpersonal therapy (IPT) focusing on role transitions is also effective 2
• Combined treatment (medication + psychotherapy) provides optimal outcomes 2