Coexistence of Orthostatic Hypotension and Refractory Hypertension in Diabetic Cardiovascular Autonomic Neuropathy

Coexistence of Orthostatic Hypotension and Refractory Hypertension in Diabetic Cardiovascular Autonomic Neuropathy: A Therapeutic Dilemma

Background:
Diabetic cardiovascular autonomic neuropathy (DCAN) is an under-recognised complication of diabetes that can cause profound cardiovascular dysregulation. The coexistence of severe orthostatic hypotension (OH) and supine hypertension (SH) presents a major therapeutic challenge, as treatment of one condition may exacerbate the other. We present a case illustrating the severe functional and end-organ consequences of this autonomic disorder.

Case Presentation:
A 57-year-old woman with previously undiagnosed, poorly controlled type 2 diabetes mellitus (HbA1c 117 mmol/mol) developed recurrent syncope and falls associated with severe OH. She subsequently developed diabetic retinopathy, chronic kidney disease (CKD) stage 3, gastroparesis and progressive cardiovascular autonomic dysfunction. Autonomic testing demonstrated marked BP instability, with supine BP of 209/111 mmHg falling to 82/58 mmHg after seven minutes of head-up tilt, with minimal compensatory increase in heart rate. Deep breathing demonstrated absent respiratory sinus arrhythmia, and autonomic olfactory testing was abnormal, supporting a diagnosis of cardiovascular autonomic failure consistent with DCAN. Extensive investigations excluded significant arrhythmia, adrenal insufficiency, structural cardiac disease and autoimmune or malignant causes.

Management was complicated by progressive SH and refractory hypertension, with subsequent target-organ damage including moderate concentric left ventricular hypertrophy, hypertensive crisis, pulmonary oedema and acute kidney injury on CKD. Multiple agents for OH, including fludrocortisone, midodrine and pyridostigmine, were trialled alongside compression therapy and abdominal binders, but recurrent symptomatic hypotension persisted. Conversely, multiple antihypertensive regimens were required, including irbesartan, hydralazine, clonidine, indapamide and bisoprolol. Treatment was repeatedly adjusted according to haemodynamic response and comorbidities. Ultimately, pressor therapy was discontinued because of worsening hypertension, while BP remained labile despite five antihypertensive agents. Prolonged hospitalisation and recurrent haemodynamic instability resulted in severe deconditioning and wheelchair dependence.

Conclusion:
This case demonstrates the profound clinical burden associated with advanced DCAN and the difficulty of managing coexisting OH and refractory hypertension. Conventional therapies may provide conflicting effects and can be limited by renal, cardiac and gastrointestinal comorbidities. Management requires individualised, iterative treatment and close multidisciplinary collaboration involving autonomic, cardiology, renal, endocrinology, neurology, physiotherapy and occupational therapy teams. Earlier recognition of DCAN in patients with poorly controlled diabetes and labile BP may facilitate intervention before irreversible functional and end-organ complications develop. There remains an important unmet need for therapies that selectively improve upright BP without worsening supine hypertension.