What is the initial treatment for a newborn with a midline face deformity and panhypopituitarism, characterized by low thyroid hormone, cortisol, and growth hormone levels?

Initial Management of Neonatal Panhypopituitarism

Start hydrocortisone immediately, followed by levothyroxine at least 1 week later, and defer growth hormone therapy until after 2-3 months of age once cortisol and thyroid replacement are optimized. 1

Critical First Step: Hydrocortisone Must Be Given First

• Hydrocortisone is the absolute priority and must be initiated immediately upon diagnosis to prevent life-threatening adrenal crisis, which is the primary cause of excess mortality in hypopituitarism. 1
• The recommended dose is 8-10 mg/m²/day divided into 2-3 doses for neonates. 1
• Starting thyroxine before hydrocortisone can trigger fatal adrenal crisis—this is the most critical pitfall to avoid. 1
• Monitor closely for signs of adrenal crisis including hypotension, hypoglycemia, and hyponatremia in the first 2-4 weeks after diagnosis. 1

Second Step: Levothyroxine After Adequate Cortisol Replacement

• Wait at least 1 week after starting hydrocortisone before initiating levothyroxine. 1
• The goal is to achieve free T4 in the upper half of the reference range. 1
• In neonates with congenital hypothyroidism, the recommended starting dose is 10-15 mcg/kg/day. 2
• Caution must be exercised when administering levothyroxine to patients with concomitant adrenal insufficiency, which is why cortisol replacement must be established first. 2
• Check free T4 at 2 and 4 weeks after starting levothyroxine, and assess feeding tolerance and weight gain. 1

Important Monitoring Caveat for Central Hypothyroidism

• Do not rely on TSH to guide thyroid replacement in central hypothyroidism (panhypopituitarism)—use free T4 levels instead. 1
• In secondary (pituitary) hypothyroidism, levothyroxine dose should be titrated until the patient is clinically euthyroid and serum free-T4 is restored to the upper half of the normal range. 2
• TSH will not be a reliable marker because the pituitary dysfunction prevents appropriate TSH elevation. 1

Third Step: Growth Hormone Is NOT an Emergency

• Growth hormone replacement should be deferred until the acute phase is stabilized, with consideration for initiation after 2-3 months of age once cortisol and thyroid replacement are optimized. 1
• Growth hormone deficiency, while universal in panhypopituitarism, does not require emergency treatment in the neonatal period. 1
• Adequate glucocorticoid and thyroid hormone replacement must be established first before starting GH therapy to prevent complications. 3
• Starting GH without proper cortisol replacement can precipitate adrenal crisis. 3

Why "Wait 1 Month and Repeat" Is Incorrect

• Waiting without initiating treatment would be dangerous—cortisol deficiency is life-threatening and requires immediate replacement. 1, 4
• The midline face deformity in this case suggests septo-optic dysplasia or similar congenital hypopituitarism, where the diagnosis is structural and will not change with repeat testing. 1
• Delays in treatment can lead to severe hypoglycemia, adrenal crisis, and adverse effects on neurocognitive development. 5

Sequential Treatment Algorithm

1. Day 1: Start hydrocortisone 8-10 mg/m²/day in 2-3 divided doses 1
2. Week 1-2: Monitor for adrenal crisis signs, hypoglycemia, feeding tolerance 1
3. After 1 week minimum: Start levothyroxine 10-15 mcg/kg/day 1, 2
4. Weeks 2-4: Check free T4 levels (not TSH) to guide levothyroxine dosing 1
5. After 2-3 months: Consider initiating growth hormone therapy once acute phase stabilized 1

Additional Clinical Considerations

• Neonatal hypoglycemia is common in panhypopituitarism and may be the presenting feature, requiring both cortisol replacement and glucose management. 6
• Hyperbilirubinemia (both direct and indirect) can occur with neonatal hypopituitarism and typically resolves over 5-8 months with appropriate hormone replacement. 6
• The newborn may require stress-dose hydrocortisone (2-3 times maintenance) during intercurrent illness or surgical procedures. 4