Which hormone deficiency is the highest priority: Follicle Stimulating Hormone (FSH), Growth Hormone (GH), Thyroid Stimulating Hormone (TSH), or Luteinizing Hormone (LH)?

Thyroid Stimulating Hormone (TSH) Deficiency is the Highest Priority Hormone Deficiency

Among the hormone deficiencies of FSH, GH, TSH, and LH, thyroid stimulating hormone (TSH) deficiency is the highest priority to address due to its profound impact on morbidity, mortality, and quality of life.

Rationale for TSH Deficiency Priority

Critical Impact on Multiple Body Systems

• TSH deficiency leads to hypothyroidism, affecting virtually every organ system in the body 1
• Untreated central hypothyroidism (low TSH with low free T4) has significant cardiovascular consequences including:
  • Increased risk of cardiac events
  • Abnormal cardiac output
  • Ventricular hypertrophy 2, 1
• Neurological manifestations include confusion, cognitive dysfunction, and in severe cases, coma 1

Diagnostic Considerations

• Central hypothyroidism presents with low free T4 with low/normal TSH, requiring careful evaluation 2
• Diagnostic confirmation requires:
  • Morning thyroid function tests (TSH, free T4)
  • Assessment for other pituitary hormone deficiencies 2
  • MRI of the sella in cases of suspected hypophysitis 2

Comparison with Other Hormone Deficiencies

Growth Hormone (GH) Deficiency

• While GH deficiency affects growth in children and body composition in adults, it is less acutely life-threatening
• GH replacement is important but typically addressed after thyroid function is normalized 2
• GH therapy may actually unmask central hypothyroidism by altering thyroid hormone metabolism 3

Gonadotropin Deficiencies (FSH/LH)

• FSH/LH deficiencies primarily affect reproductive function and secondary sex characteristics
• While important for quality of life, these deficiencies don't pose the same immediate physiological risks as thyroid dysfunction 2
• Testosterone or estrogen therapy should only be initiated after addressing adrenal and thyroid deficiencies to avoid precipitating an adrenal crisis 2

Management Approach

Immediate Priorities

1. Assess thyroid function with TSH and free T4 measurements
2. In central hypothyroidism, target free T4 in the upper half of the reference range (TSH is not accurate for monitoring in central hypothyroidism) 2
3. Initiate levothyroxine replacement therapy with careful dose titration 4

Monitoring Requirements

• Regular monitoring of free T4 levels (not TSH) in central hypothyroidism
• Assess clinical response every 6-12 months and whenever there's a change in clinical status 4
• Avoid overtreatment which can lead to:
  • Increased risk of atrial fibrillation
  • Accelerated bone mineral density loss
  • Fractures 1, 5

Special Considerations

Concurrent Adrenal Insufficiency

• Critical safety note: When both adrenal insufficiency and hypothyroidism are present, always start steroid replacement before thyroid hormone to avoid precipitating an adrenal crisis 2
• All patients with adrenal insufficiency should obtain and carry a medical alert bracelet 2

Pregnancy

• Requires trimester-specific reference ranges and more frequent monitoring
• Increased levothyroxine requirements during pregnancy 4

Elderly Patients

• Require more careful dosing and monitoring due to increased cardiac risk
• Consider higher TSH targets and avoid suppression 1

Pitfalls to Avoid

• Relying solely on TSH for diagnosis can miss central hypothyroidism cases where TSH may be normal with low free T4 6
• Failure to recognize that TSH is not a reliable marker for monitoring treatment in central hypothyroidism 7
• Initiating sex hormone replacement before addressing thyroid deficiency 2
• Overlooking the interaction between GH replacement and thyroid function 3

By prioritizing TSH deficiency, clinicians can address the most immediately impactful hormone deficiency that affects multiple body systems and poses significant risks to morbidity and mortality if left untreated.