What hormonal changes occur in patients entering the end of life?

Hormonal Changes in End-of-Life Patients

Key Hormonal Alterations During End-of-Life Phase

Patients approaching the end of life experience significant hormonal dysregulation characterized by decreasing thyroid hormone levels, rising stress hormones, and disruption of the hypothalamic-pituitary axis. These changes reflect the body's response to severe physiological stress and contribute to the clinical manifestations observed in terminal patients.

Thyroid Hormone Changes

• Initial development of "low T3 syndrome" with decreased triiodothyronine (T3) and normal to low-normal thyroxine (T4) levels, while TSH remains within normal range 1
• Progressive decline in T4 and T3 levels as death approaches, with T4 dropping to approximately 2.6 μg/dL and T3 to 30.6 ng/dL in non-survivors 1
• Diminished TSH response to thyroid-releasing hormone (TRH) stimulation, indicating hypothalamic-pituitary dysregulation 1

Adrenal and Stress Hormone Changes

• Initial elevation of catecholamines (epinephrine and norepinephrine) in critically ill patients 1, 2
• Dramatic increase in epinephrine levels before death, with the norepinephrine-to-epinephrine ratio decreasing from 5.7:1 to 2:1 1
• Cortisol levels may remain elevated or normal throughout the end-of-life period 1, 2
• Possible development of centrally mediated adrenal insufficiency in some patients 3

Reproductive and Growth Hormones

• Development of hypogonadotropic hypogonadism with decreased sex hormone production 2
• Growth hormone and prolactin levels may remain normal or show variable changes 1
• Disruption of normal hormonal rhythms and pulsatile secretion patterns 2

Clinical Implications of Hormonal Changes

Volume Status and Electrolyte Management

• Altered renin-aldosterone axis may lead to fluid retention and hyponatremia in some patients 2
• Some patients may develop hyperreninemic hypoaldosteronism, though its clinical significance remains unclear 2
• Vasopressin dysregulation can contribute to fluid and electrolyte abnormalities 2

Metabolic Effects

• Hyperglycemia and hypercatabolism are common due to elevations in stress hormones 2
• Insulin resistance increases, potentially requiring adjustment of diabetes management 2
• Protein catabolism accelerates, contributing to muscle wasting and frailty 2, 4

Symptom Management Considerations

• Hormonal changes may contribute to fatigue, weakness, and decreased appetite common in end-of-life care 3
• Treatment should focus on symptom control rather than attempting to normalize hormone levels 3
• Opioids can be effective for managing dyspnea and pain in advanced illness 3

Management Approach

• Focus on palliative care with emphasis on symptom control rather than hormone replacement 3
• Maintain volume status close to euvolemia to improve function and comfort 3
• Continue medications that address neurohormonal alterations (such as ACEIs and β-blockers in heart failure) as they may palliate symptoms until limited by decreased oral intake, inability to swallow, or hypotension 3
• Regular assessment of symptoms including pain, anxiety, depressive symptoms, and fatigue is essential 3
• Consider early morning serum adrenocorticotropic hormone and cortisol evaluations when patients are well, and repeat during severe illness 3
• Consider prophylactic hydrocortisone during critical illness episodes in patients with suspected adrenal insufficiency 3

Important Caveats

• Hormone replacement therapy is generally not recommended in end-of-life care as potential adverse events often outweigh benefits 4
• Interpretation of hormone levels in critically ill patients is challenging and may not reflect true endocrine dysfunction 2
• Indiscriminate hormone testing may lead to uninterpretable results or inappropriate interventions 2
• Hormonal changes should be viewed as part of the body's complex response to severe physiological stress rather than isolated endocrine disorders 2

Understanding these hormonal changes can help clinicians anticipate and manage symptoms in end-of-life care, focusing on comfort and quality of life rather than attempting to normalize laboratory values.