What is the appropriate workup for a 46-year-old female presenting with significant fatigue, insomnia (sleep disorder), and currently on hormone replacement therapy (HRT) for insomnia?

From the Guidelines

To work up a 46-year-old female with significant fatigue, I recommend starting with a comprehensive history, physical examination, and targeted laboratory testing, prioritizing her insomnia and potential underlying medical conditions that may impact her morbidity, mortality, and quality of life. Begin with complete blood count, comprehensive metabolic panel, thyroid function tests (TSH, free T4), ferritin, vitamin B12, vitamin D, and hemoglobin A1c, as these tests can help identify potential underlying causes of fatigue, such as anemia, thyroid disorders, or diabetes, which can significantly impact her quality of life and mortality risk 1. Consider screening for sleep apnea with a validated questionnaire like the STOP-BANG or refer for a sleep study if her insomnia symptoms suggest this possibility, as untreated sleep apnea can lead to increased morbidity and mortality 1. Evaluate for depression and anxiety using PHQ-9 and GAD-7 screening tools, as these conditions can significantly impact her quality of life and are often comorbid with insomnia. Since she's already on hormone replacement therapy (HRT) for insomnia with some benefit, review her current regimen and consider adjustments if needed, taking into account the potential risks and benefits of HRT on her morbidity and mortality. Address lifestyle factors by recommending regular physical activity (30 minutes most days), consistent sleep-wake schedule, and stress management techniques like mindfulness or cognitive behavioral therapy for insomnia (CBT-I), which can help improve her sleep quality and overall quality of life. Her fatigue likely has multiple contributing factors including poor sleep quality, possible perimenopause, work-life balance challenges with two children, and potential underlying medical conditions, and a comprehensive approach that prioritizes her morbidity, mortality, and quality of life is essential. If initial testing is unrevealing but symptoms persist, consider referrals to sleep medicine, endocrinology, or psychiatry depending on predominant symptoms, to ensure that any underlying conditions are properly diagnosed and managed to minimize their impact on her morbidity, mortality, and quality of life. Key considerations in her workup include:

• Identifying and managing underlying medical conditions that may be contributing to her fatigue, such as sleep apnea or thyroid disorders
• Optimizing her sleep quality through lifestyle modifications and potentially adjusting her HRT regimen
• Addressing potential mental health conditions, such as depression and anxiety, that may be comorbid with her insomnia
• Prioritizing her morbidity, mortality, and quality of life in all treatment decisions, and considering the potential risks and benefits of any interventions on these outcomes.

From the Research

Approach to Fatigue Workup

To work up a 46-year-old female with significant fatigue, it's essential to consider a comprehensive approach that includes a thorough history, physical examination, and targeted laboratory tests.

• The patient's history of insomnia, use of hormone replacement therapy (HRT), and full-time work with two kids should be taken into account when evaluating her fatigue 2.
• A comprehensive history and physical examination, including cardiopulmonary, neurologic, and skin examinations, can help guide the workup and diagnosis of fatigue 2.

Laboratory Tests

Laboratory tests may be useful in identifying underlying conditions that could be contributing to the patient's fatigue.

• A complete blood count (CBC) can be used to assess for cardiovascular and metabolic diseases, which may be related to fatigue 3.
• Thyroid function tests, such as thyroid-stimulating hormone (TSH) and free thyroid hormone tests, can help diagnose thyroid disorders, which are common and can cause fatigue 4.

Classification of Fatigue

Fatigue can be classified as physiologic, secondary, or chronic.

• Physiologic fatigue can be addressed by proper sleep hygiene, a healthy diet, and balancing energy expenditure 2.
• Secondary fatigue is improved by treating the underlying condition 2, 5.
• Chronic fatigue, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a chronic, severe, and potentially debilitating disorder with demonstrated inflammatory, neurologic, immunologic, and metabolic abnormalities 2.

Management of Fatigue

Management of fatigue depends on the underlying cause.

• For secondary fatigue, treatment of the underlying condition is essential 2, 5.
• For chronic fatigue, cognitive behavior therapy, exercise therapy, and acupuncture may be helpful 2.
• Individualized exercise therapy and cognitive behavioral therapy are also recommended for primary fatigue, now known as system exertion intolerance disease 5.