Letters to the Editor

Differential Diagnosis of Muscle Weakness in Adults


Am Fam Physician. 2020 Jul 15;102(2):73.

Original Article: Muscle Weakness in Adults: Evaluation and Differential Diagnosis

Issue Date: January 15, 2020

Available online at: https://www.aafp.org/afp/2020/0115/p95.html

To the Editor: We read this article with interest. The authors concluded that if the cause of muscle weakness remains elusive, a muscle biopsy or consultation with a specialist may be necessary to reach the correct diagnosis. However, other possible etiologies should be added to the differential diagnosis.

Because lactic acidosis can cause muscle weakness, we recommend obtaining serum or cerebrospinal fluid lactate levels. If resting lactate is normal but lactic acidosis is still suspected, a lactate stress test should be performed.1 In patients with a subclinical or mildly manifesting mitochondrial disorder, the lactate stress test may reveal lactate elevations with mild exercise that are below the normal lactate threshold.

Pituitary insufficiency is another cause of muscle weakness.2 Thus, it is important to determine hormone levels, particularly those produced in the pituitary gland. Reduced production of pituitary hormones may lead not only to short stature or hypothyroidism but also to hypogonadism or hypocorticism. Low levels of gonadotropic hormones, glucocorticoids, or mineralocorticoids may lead to severe muscle weakness with or without hypotonia.

Muscle weakness in adults may also be caused by reduced extraction of oxygen from the arterial blood.3 To assess if the muscle weakness is from hypooxygenation of the skeletal muscle, it is crucial to determine the oxygen concentration in the venous blood or measure the oxygen extraction fraction using magnetic resonance imaging. The muscle will be unable to use arterial oxygen properly if functions of respiratory chain complexes are impaired or if the oxidative phosphorylation is disrupted.

In patients with subclinical myopathy, general or local anesthetics or muscle relaxants may trigger muscle weakness postintervention.4 Obstructive or restrictive sleep apnea syndrome may be associated with severe daytime fatigue and muscle weakness. Thus, all patients with undiagnosed muscle weakness and fatigue should undergo testing for sleep apnea syndrome. Wilson disease is another rare cause of muscle weakness, which can be diagnosed with serum copper levels.5

Author disclosure: No relevant financial affiliations.


show all references

1. Finsterer J, Milvay E. Stress lactate in mitochondrial myopathy under constant, unadjusted workload. Eur J Neurol. 2004;11(12):811–816....

2. Paz Flores C, Rosales Carballa J, Blanco Loberías J. Muscle weakness as first manifestation of panhypopituitarism secondary to empty sella syndrome. Article in Spanish. An Med Interna. 2008;25(6):309–311.

3. Tarnopolsky M. Exercise testing as a diagnostic entity in mitochondrial myopathies. Mitochondrion. 2004;4(5–6):529–542.

4. Kini YK, Kharkar VR, Kini AY. Transient diplopia with ipsilateral abducent nerve palsy and ptosis following a maxillary local anesthetic injection: a case report and review of literature. Oral Maxillofac Surg. 2012;16(4):373–375.

5. Zhang QJ, Xu LQ, Wang C, et al. Four-year follow-up of a Wilson disease pedigree complicated with epilepsy and hypopituitarism: case report with a literature review. Medicine (Baltimore). 2016;95(49):e5331.

In Reply: We appreciate Dr. Finsterer's close reading of our manuscript and his attention to detail. Although we wish that we could have written an article on the diagnostic evaluation of muscle weakness that was all-inclusive, our perspective was that of the family physician and the typical office evaluation for this presentation. We certainly considered discussing invasive and specialized testing methods for the evaluation of weakness, but most family physicians would not have access to or familiarity with some of the tests Dr. Finsterer suggests. For this reason, we recommend specialty referral after completing a reasonably thorough primary care evaluation.

Author disclosure: No relevant financial affiliations.

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This series is coordinated by Kenny Lin, MD, MPH, Associate Deputy Editor for AFP Online.



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