What is the next step in management for a postpartum woman with fatigue, weight loss, cold intolerance, loss of appetite, inability to breastfeed, amenorrhea, croaky voice, and delayed relaxation phase of ankle jerks?

Sheehan Syndrome: Immediate Corticosteroid Replacement Before Thyroid Hormone

The next step is to administer corticosteroids BEFORE initiating thyroid hormone replacement, as this patient's presentation is highly suggestive of Sheehan syndrome (postpartum pituitary necrosis), and starting levothyroxine without first replacing cortisol can precipitate life-threatening adrenal crisis. 1, 2

Clinical Presentation Indicates Panhypopituitarism

This patient presents with a classic constellation of findings pointing to Sheehan syndrome:

• Failure to lactate postpartum - indicates prolactin deficiency 1
• Persistent amenorrhea after delivery - suggests gonadotropin deficiency 1
• Hypothyroid symptoms (fatigue, weight loss, cold intolerance, croaky voice, delayed ankle reflex relaxation) - indicates TSH deficiency 3, 4
• Loss of appetite and weight loss (rather than weight gain) - atypical for primary hypothyroidism but characteristic of adrenal insufficiency 5, 6

The combination of inability to breastfeed with failure of menses to return postpartum is pathognomonic for Sheehan syndrome, which causes deficiency of multiple pituitary hormones including ACTH, TSH, prolactin, and gonadotropins. 1

Why Corticosteroids Must Come First

In patients with suspected central hypothyroidism or hypopituitarism, always start physiologic dose steroids at least 1 week prior to thyroid hormone replacement. 1, 2 Starting levothyroxine before corticosteroids can precipitate life-threatening adrenal crisis because:

• Thyroid hormone increases cortisol metabolism 1
• In the setting of adrenal insufficiency, this accelerated cortisol breakdown depletes already inadequate cortisol stores 1
• This can trigger acute adrenal crisis with hypotension, shock, and death 1, 2

The FDA label for levothyroxine explicitly warns about this risk in patients with adrenal insufficiency. 2

Why Other Options Are Incorrect

Option A (Conjugated estrogen): While this patient has gonadotropin deficiency, sex hormone replacement is not the priority when life-threatening adrenal and thyroid deficiencies are present. 1

Option B (Request TSH level): While TSH testing would be appropriate, in suspected Sheehan syndrome the TSH will be inappropriately low or normal despite clinical hypothyroidism (central hypothyroidism). More importantly, obtaining TSH before addressing the adrenal crisis risk delays critical treatment. 1, 6

Option C (Correct hyponatremia with hypertonic saline): Hyponatremia in this context is likely due to adrenal insufficiency and SIADH from cortisol deficiency. Treating with hypertonic saline without addressing the underlying adrenal insufficiency is dangerous and ineffective. 1

Option D (Treat with levothyroxine 50 mcg per day): This is the most dangerous option. Starting thyroid hormone without first replacing cortisol can precipitate adrenal crisis and death in patients with panhypopituitarism. 1, 2

Correct Management Algorithm

1. Immediately start hydrocortisone (physiologic replacement dose, typically 15-25 mg daily in divided doses) 1
2. Wait at least 1 week before initiating thyroid hormone 1, 2
3. Then start levothyroxine at low dose (25-50 mcg daily), as elderly patients or those with cardiac disease require conservative initiation 1, 7
4. Monitor for adrenal crisis symptoms during the first 2 weeks of treatment 2
5. Titrate levothyroxine slowly by 12.5-25 mcg increments every 6-8 weeks based on free T4 levels (not TSH, which will remain low in central hypothyroidism) 1, 6

Critical Diagnostic Confirmation

After stabilizing with corticosteroids, confirm the diagnosis with:

• Morning cortisol and ACTH levels (both will be low in secondary adrenal insufficiency) 1
• Free T4 level (will be low with inappropriately normal or low TSH in central hypothyroidism) 1, 6
• Prolactin, LH, FSH, estradiol (all will be low) 1
• MRI of pituitary to assess for empty sella or pituitary necrosis 1

Common Pitfalls to Avoid

• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism - this can be fatal 1, 2
• Do not rely on TSH levels in suspected pituitary disease, as TSH will be inappropriately low or normal despite hypothyroidism 1, 6
• Do not assume primary hypothyroidism when the clinical picture suggests panhypopituitarism (failure to lactate + amenorrhea + hypothyroid symptoms) 1, 4
• Do not use full replacement doses of levothyroxine initially - start low (25-50 mcg) and titrate slowly 1, 7

The patient's presentation of postpartum failure to lactate, persistent amenorrhea, and hypothyroid symptoms with weight loss (not gain) strongly suggests Sheehan syndrome requiring immediate corticosteroid replacement before any thyroid hormone therapy. 1, 3, 4