Differential Diagnosis for a Middle-Aged Patient with Worsening Fatigue

Based on the provided Initial Patient History (HPI) and other relevant information, the following differential diagnoses are considered:

• Single Most Likely Diagnosis
  • Obstructive Sleep Apnea (OSA): The patient's report of loud snoring, waking up 2-3 times to urinate, and daytime fatigue despite sleeping 7-8 hours a night are classic symptoms of OSA. According to the American Academy of Sleep Medicine, OSA is a common cause of excessive daytime sleepiness 1. The patient's history of hypertension and hyperlipidemia also increases the risk for OSA.
• Other Likely Diagnoses
  • Chronic Kidney Disease (CKD): The patient's history of variably controlled hypertension, intermittent ankle swelling, and nocturia (waking up to urinate) suggest possible CKD. The National Kidney Foundation recommends evaluating patients with hypertension for CKD 2.
  • Heart Failure with Preserved Ejection Fraction (HFpEF): The patient's symptoms of shortness of breath, especially when climbing stairs, and intermittent ankle swelling are consistent with HFpEF. The American Heart Association notes that HFpEF is a common cause of heart failure in patients with hypertension and hyperlipidemia 3.
  • Anemia: The patient's fatigue, shortness of breath, and history of smoking (which increases the risk of chronic diseases) suggest possible anemia. The Centers for Disease Control and Prevention recommend evaluating patients with fatigue and shortness of breath for anemia 4.
  • Hypothyroidism: The patient's fatigue, weight gain, and history of hypothyroidism in a half-sister increase the suspicion for hypothyroidism. The American Thyroid Association recommends evaluating patients with fatigue and weight gain for hypothyroidism 5.
• Do Not Miss Diagnoses
  • Pulmonary Embolism: Although the patient denies chest pain, the history of smoking and intermittent cough increase the risk of pulmonary embolism. The American College of Chest Physicians recommends evaluating patients with shortness of breath and cough for pulmonary embolism 6.
  • Coronary Artery Disease: The patient's history of hypertension, hyperlipidemia, and family history of myocardial infarction increase the risk of coronary artery disease. The American Heart Association recommends evaluating patients with chest pain or shortness of breath for coronary artery disease 7.
  • Sleep-Disordered Breathing due to Other Causes (e.g., Central Sleep Apnea): The patient's symptoms of fatigue and shortness of breath could be due to other sleep-disordered breathing causes. The American Academy of Sleep Medicine recommends evaluating patients with excessive daytime sleepiness for other sleep disorders 1.
• Rare Diagnoses
  • Addison's Disease: The patient's fatigue, weight gain, and history of intermittent ankle swelling could be due to Addison's disease, although it is a rare condition. The Endocrine Society recommends evaluating patients with fatigue and weight gain for Addison's disease 8.
  • Pernicious Anemia: The patient's fatigue, shortness of breath, and history of smoking increase the risk of pernicious anemia, although it is a rare condition. The National Institutes of Health recommend evaluating patients with fatigue and shortness of breath for pernicious anemia 9.

References: 1 American Academy of Sleep Medicine. (2014). International Classification of Sleep Disorders. 3rd ed. 2 National Kidney Foundation. (2012). KDOQI Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 3 American Heart Association. (2017). Heart Failure: A Scientific Statement From the American Heart Association. 4 Centers for Disease Control and Prevention. (2020). Anemia. 5 American Thyroid Association. (2014). Hypothyroidism. 6 American College of Chest Physicians. (2016). Antithrombotic Therapy for VTE Disease. 7 American Heart Association. (2019). Coronary Artery Disease. 8 Endocrine Society. (2016). Evaluation and Treatment of Adult Growth Hormone Deficiency. 9 National Institutes of Health. (2020). Pernicious Anemia.