Abstract: PUB111
Severe Hyponatremia After a Single Dose of Tirzepatide
Session Information
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Prajapati, Vishal, USF Health, Tampa, Florida, United States
- Seol, Jaehoon, USF Health, Tampa, Florida, United States
- Persaud, Steven H., USF Health, Tampa, Florida, United States
- Durr, Jacques A., USF Health, Tampa, Florida, United States
Introduction
While GLP-1 agonists target the brain to reduce appetite and the stomach to slow digestion, Tirzepatide (T) is a dual GLP-1/GIP agonist with broader metabolic effects. Currently, 6% of US adults (16M) use these therapies, with twice as many lifetime users [JAMA, PMID:38848082]. Although nausea, a potent trigger for ADH release, is the leading side effect, hyponatremia is rarely reported. We explore this paradox and compare T vs. GLP-1 effects through a case of severe hyponatremia after a single dose of T.
Case Description
A 55-year-old female presented with malaise and leg cramps 7 days after a single 10 mg dose of Tirzepatide (T). She experienced 4 days of nausea/vomiting, which subsided 3 days prior to admission. Medications included Synthroid 75 μg, HCTZ 12.5 mg, and Lisinopril 10 mg. Exam and vitals were normal. Labs: Serum Na 109 (repeat 111) mmol/L, glucose normal, POsm 239, UOsm 510 mOsm/kg. UA: SG 1.020, ketones >79 mg/dL, UNa 23, and UK 45 mmol/L. Normal cortisol, TSH, FT4, and Mg. HCTZ was held; ketosis and hyponatremia resolved with D5W and oral salt. Correction was carefully managed with D5W to avoid overcorrection.
Discussion
A 2026 case report [PMID:42051284] described severe T-induced hyponatremia in an AVP-deficient (AVP-D) patient on dDAVP, echoing a series where GLP-1 therapy required dDAVP dose reduction [PMID:39240512]. GLP-1 agonists could increase oral dDAVP absorption. A selective GLP-1 agonist was shown to minimally reduce copeptin in euvolemic patients [PMID:41525326]. Drug-induced hypodipsia likely protects against water intoxication; however, the rarity of severe hyponatremia with pure GLP-1 agonists suggests a GIP-specific effect. While hypothalamic nuclei show GLP-1 activity on CRH/oxytocinergic neurons, they show minimal activity on vasopressinergic neurons [PMID:18773953]. Conversely, GIP increases AVP mRNA by 47%, while GIPR knockout models show a 27% downregulation. This suggests GIPR is functionally integrated into the biosynthetic machinery of vasopressin neurons, potentially predisposing to hyponatremia via AVP stimulation.
Seum Sodium