Have you had other tests done, such as thyroid function tests or autoimmune tests? Sometimes muscle biopsies can also be telling.
A full pulmonology/cardiology workup often does not include CPET (cardiopulmonary exercise test to VO2max). I would encourage you to get one, but they can be expensive. See if your insurance might cover it.
I'm very biased since this is my field, but your story reminds me of an usual case I read about a man with ongoing trouble with rhabdomyolysis who experienced symptoms at submaximal exercise intensities. CPET was used to help diagnose him.
***Clinical Findings***
This 53 year-old man was referred for exercise testing to characterize his impairment due to an unspecified myopathy. He was normally active as a child and young adult. In his early 30s, he had consulted a rheumatologist for vague muscle symptoms, but no specific diagnosis was made. At age 47, he had an episode of rhabdomyolysis complicated by acute renal failure after a day of river rafting and over the next 5 years had several more documented episodes of rhabdomyolysis. Laboratory evaluation, including electrolytes, thyroid function tests, and autoimmune studies, had been normal, and electromyography showed non-specific abnormalities. At the time of testing, he reported easy fatigability and delayed muscle soreness after modest levels of exertion. He worked part time as a nurse and did minimal exercise. Medical history included hypertension and prior back surgeries with residual chronic pain. He had undergone general anesthesia without adverse reactions. His family history was not contributory. His medications included metoprolol, lisinopril, and methadone. Examination demonstrated a normal body habitus without obvious skeletal muscle hypertrophy or wasting. The resting electrocardiogram was normal.
A muscle biopsy had been performed several years prior to this test, and the patient was screened for the most commonly recognized enzyme deficiencies associated with rhabdomyolysis. The report indicated no specific structural abnormalities and normal straining for phosphorylase a and b, myoadenylate deaminase, phosphoglycerate kinase, phosphoglycerate mutase, lactate dehydrogenase, and carnitine palmitoyltransferase. The basis of his myopathy, therefore, was not defined.
***Exercise Findings***
The patient performed exercise on a cycle ergometer. After 3 minutes of rest, he pedaled at 60 rpm as work rate was increased by 20 watts/min. He stopped exercise due to shortness of breath and "burning" in his leg muscles. There were no significant ECG changes.
***Analysis***
The test appears to reflect good effort based on the high peak heart rate and end-exercise respiratory exchange ratio value of close to 1.4, indicating substantial carbon dioxide from buffering of lactic acid. Oxygen uptake (VO2) increased appropriately with work rate, but peak VO2 and anaerobic threshold were both low. The increase in heart rate was steep relative to VO2. The oxygen pulse increased during the first few minutes of exercise but failed to increase further and remained lower than the predicted maximum for the remainder of the test. These findings are consistent with either impairment in oxygen delivery (low stroke volume) or impaired oxygen extraction at the muscle level (low a-v O2 difference). The latter explanation is most consistent with the clinical history. Reduction in the capacity for oxidation of substrate in the muscle with early lactic acidosis, as occurred in this patient, would be associated with an abnormally low a-v O2 difference, reflecting failure to utilize and extract oxygen normally in the muscle. This would be consistent with impaired mitochondrial oxidative metabolism. A hyperdynamic circulatory response, suggested by the heart rate pattern, is characteristic of defects in skeletal muscle oxidation. The test showed typical gas exchange changes associated with lactic acidosis, making McArdle disease (myophosphorylase deficiency) unlikely.
***Conclusion***
Although a specific metabolic defect was not identified on this patient's muscle biopsy, the exercise findings are suggestive of a deficiency in mitochondrial oxidative metabolism.