Fludrocortisone Treatment for Chronic Fatigue Syndrome

Introduction

Chronic fatigue syndrome (CFS) is characterized by persistent and unexplained fatigue resulting in severe impairment in daily living. The causes of CFS can be seen in Table 1.¹ There are many factors that may trigger CFS, one of which is autonomic dysfunction.² In this case report, we discuss the management of an electrophysiology patient who developed persistent hypotension and CFS. 

Case Description

A previously active 68-year-old male with a longstanding history of atrial fibrillation (AF) since 2005, cardiomyopathy, and gastroesophageal reflux disease (GERD), presents with a chief complaint of marked and persistent fatigue. He had a prior AF ablation (both percutaneously and surgically), but persisted in having atrial fibrillation. In June 2006, the patient received a dual-chamber pacemaker implant due to recurrent presyncope, and AF with greater than 3-second pauses. In December 2014, a tilt table test was performed due to symptoms of persistent fatigue as well as associated lightheadedness and dizziness (presyncope). The patient’s baseline blood pressure was 143/107 mmHg supine and 120/88 mmHg immediately upright at 70 degrees. The patient felt lightheaded and short of breath, but did not lose consciousness. Throughout the study, the patient’s heart rate remained steady at around 100 beats per minute, and his blood pressure at the end of the study was 76/54 mmHg. Office visits demonstrated persistent systolic blood pressure between 70 and 90 mmHg, which correlated with his symptoms of marked fatigue.   

At his 6-month follow-up in June 2015, the patient complained of persistent decreased energy, lack of endurance, and continuous hypotension. Workup failed to elicit any evidence of anemia, endocrinopathy (hypothyroidism), congestive heart failure, vitamin deficiency, or other known chronic illnesses. He was initially prescribed midodrine (10 mg/day orally); however, in less than a week, the patient stopped due to adverse side effects including headaches, dizziness, and nausea. He was subsequently placed on fludrocortisone at an initial dosage of 0.1 mg orally twice daily, without a significant improvement in symptoms or significant increase in his blood pressure (92/69 mmHg). The dosage was doubled to 0.2 mg orally twice daily, and his blood pressure increased to 135/62 mmHg. Within days the patient had increased endurance, felt drastically better, and became more active. At his last follow-up in September 2015, the patient continued feeling less fatigued and was normotensive (136/84 mmHg). 

Discussion 

This case emphasizes the difficulty in diagnosis and treatment of CFS in a patient with newly occurring persistent unexplained hypotension. Table 2 shows the potential causes of persistent hypotension.³ The patient’s medications and other causes from Table 2 were considered, with no evidence pointing to the root cause of the patient’s hypotension. Possible disease causes and hormonal changes all came back negative. Pacemaker syndrome was also considered and ruled out.⁴ The possibility of a change in the “set point” of the patient’s blood pressure was determined. Having initially presented as a normotensive patient, Dr. Cohen hypothesized that extensive atrial surgery and ablation might have affected the cardiac and/or ganglionic feedback system, changing this patient’s blood pressure set point. Midodrine, an alpha1-agonist, was initially prescribed. This medication affects the alpha-adrenergic receptors of the arterial and venous vasculature, which increases vascular tone and elevates blood pressure.⁵ However, the patient could not tolerate the medication. 

The next medication to be prescribed in this case, fludrocortisone, expands plasma volume and increases sensitivity of alpha-adrenoceptors. A study by Peterson and colleagues demonstrated that “low-dose fludrocortisone does not provide sufficient benefit to be evident in a preliminary blinded trial of unselected patients with chronic fatigue syndrome.”⁶ As observed in our patient, low-dose fludrocortisone had no effect on his hypotension or other symptoms. Once the dose was doubled to 0.2 mg orally twice a day, the patient’s symptoms improved and his blood pressure increased to a normal range.

References

1. Cornuz J, Guessous I, Favrat B. Fatigue: a practical approach to diagnosis in primary care. CMAJ. 2006;174(6):765-767.
2. Prins J, Van der Meer J, Bleijenberg G. Chronic fatigue syndrome. Lancet. 2006;367(9507):346-355.
3. NIH: National Heart, Lung, and Blood Institute. What causes hypotension? Available online at: https://www.nhlbi.nih.gov/health/health-topics/topics/hyp/causes#. Updated November 10, 2010. Assessed September 27, 2015. 
4. Link MS, Hellkamp AS, Estes N, et al. High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the mode selection trial (MOST). J Am Coll Cardiol. 2004;43(11):2066-2071.
5. Naschitz J. Midodrine treatment for chronic fatigue syndrome. Postgrad Med J. 2004;80(942):230-232.
6. Peterson PK, Pheley A, Schroeppel J, et al. A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome. Arch Intern Med. 1998;158(8):908-914.