MON-657 - Worsening Postural Orthostatic Tachycardia Syndrome Associated with Compounded Tirzepatide Use

Gastrointestinal and cardiovascular effects of GLP-1 receptor agonists (GLP-1RAs) are well recognized, but autonomic complications remain poorly characterized. We report a case of severe worsening of postural orthostatic tachycardia syndrome (POTS) temporally associated with compounded tirzepatide use.
A 47-year-old female with a history of dyslipidemia and obstructive sleep apnea presented with progressive episodes of palpitations, dizziness, diaphoresis, nausea, and near-syncope. She reported rare, milder, similar symptoms in the prior year. Seven months prior to presentation, the patient began using compounded tirzepatide which contained methylcobalamin obtained from a medical spa, losing 20 pounds. Over the following five months, her symptoms worsened significantly, leading to one emergency department visit and two hospital admissions.
On evaluation, she was noted to have recurrent sinus tachycardia. On repeated orthostatic testing, her heart rate increased by 30–50 beats per minute with standing, rising from 98 to 136 bpm, from 102 to 148 bpm, and from 68 to 130 bpm, without associated orthostatic hypotension. Cardiac evaluation, including echocardiography, stress testing, and rhythm monitoring, was unremarkable. Neurologic evaluation, along with CT head and MRI of the brain and cervical spine, showed no acute abnormalities. Laboratory evaluation demonstrated normal electrolytes with a creatinine of 0.78 mg/dl and they remained within normal limits throughout her multiple hospitalizations. Thyroid function, plasma and urine catecholamines, metanephrines, and serotonin levels were within normal limits. Morning cortisol was normal at 17.4 µg/dL. Gynecology consultation felt that her presentation was not compatible with perimenopausal symptoms.
The compounded tirzepatide was discontinued; intravenous fluid boluses and maintenance were given without heart rate improvement, and beta-blocker therapy was initiated for the possible diagnosis of POTS. However, beta-blockers were poorly tolerated, causing hypotension and relative bradycardia, and were discontinued. Her symptoms subsequently slightly improved with supportive management, including compression stockings and positional precautions, with continued adequate oral hydration, and neurology suggested low-dose benzodiazepines to help with her anxiety, and she was discharged with outpatient follow-up in an autonomic disorder clinic.
Given the close temporal relationship between tirzepatide initiation and symptom progression, the absence of alternative etiologies, and improvement following discontinuation, drug-induced worsening of POTS was suspected. This case suggests a potential association between compounded tirzepatide and autonomic dysfunction, highlighting the need for clinical awareness as GLP-1RA use expands.

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