From the Guidelines
When evaluating fatigue and malaise potentially related to endocrine disorders, I recommend a comprehensive panel of laboratory tests including thyroid function tests (TSH, free T4, free T3), morning cortisol levels, ACTH, comprehensive metabolic panel, complete blood count, hemoglobin A1c, and vitamin D levels, as suggested by the most recent guidelines 1.
Key Laboratory Tests
- Thyroid function tests: TSH, free T4, free T3
- Morning cortisol levels and ACTH
- Comprehensive metabolic panel
- Complete blood count
- Hemoglobin A1c
- Vitamin D levels
Additional Tests to Consider
- Sex hormones: estradiol, testosterone, FSH, LH
- Prolactin
- Growth hormone/IGF-1
Important Considerations
- Collect blood samples in the morning when possible, particularly for cortisol which follows a diurnal pattern
- Patients should fast for at least 8 hours before testing for accurate glucose and lipid measurements
- Endocrine causes of fatigue commonly include hypothyroidism, adrenal insufficiency, diabetes mellitus, and vitamin D deficiency
- The pattern of abnormal results will guide further testing and treatment, such as elevated TSH with low free T4 indicating primary hypothyroidism requiring thyroid hormone replacement, or low morning cortisol with elevated ACTH suggesting primary adrenal insufficiency requiring corticosteroid replacement 1
Referral to Specialist
If initial testing is normal but symptoms persist, consider referral to an endocrinologist for more specialized testing or evaluation for non-endocrine causes of fatigue, as recommended by the guidelines 1
From the FDA Drug Label
• General:fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating The answer to the question about fatigue and malaise in relation to endocrine labs is that fatigue is listed as a potential adverse reaction associated with levothyroxine sodium therapy, which is primarily those of hyperthyroidism due to therapeutic overdosage. There is no direct information in the label about malaise. 2
From the Research
Fatigue and Malaise Endocrine Labs
- Fatigue is a common complaint in primary care, with a broad differential diagnosis, making the approach complex and often ineffective 3
- The most important symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is postexertional malaise, and exercise can be harmful to patients with ME/CFS because it can trigger postexertional malaise 4
- Fatigue can be due to any of a broad spectrum of diseases, including decompensation of already known conditions, sleep disorders, depression, and excessive psychosocial stress 5
- Investigations beyond the history, physical examination, and simple laboratory tests are needed only in the presence of additional symptoms or findings, and watchful waiting and regularly scheduled follow-up can help prevent an excessive focus on somatic causes, leading to overdiagnosis 5
- Complete blood count (CBC) components, such as white blood cell count, neutrophil-to-lymphocyte ratio, and red cell distribution width, can be useful markers to predict cardiovascular and metabolic diseases 6
- The diagnostic value of history, neurological examination, and ancillary investigations in patients with myalgia, exercise intolerance, or fatigue is unknown, but CK levels, EMG, ultrasound, and muscle biopsy can independently contribute to predicting a myopathy 7
Laboratory Tests
- Laboratory tests, such as CBC, may not be contributory to the diagnosis or management of fatigue in most cases 3
- The yield of diagnostic work-up of patients presenting with myalgia, exercise intolerance, or fatigue is low, and a diagnostic algorithm can facilitate a more efficient work-up in future patients 7
- Positive predictive values for myopathy were calculated for CK, EMG, ultrasound, and muscle biopsy, and all contributed significantly in predicting myopathy 7
Diagnosis and Management
- Fatigue can be classified as physiologic, secondary, or chronic, and the diagnosis and management of fatigue should be guided by investigating common and/or potentially dangerous disorders 4, 5
- Cognitive behavior therapy, exercise therapy, and acupuncture may help with some of the fatigue associated with chronic conditions, but exercise can be harmful to patients with ME/CFS 4
- Treatment should prioritize comorbidities and symptoms based on severity, and patients should be educated about pacing their activity not to exceed their limited energy capacity 4