Our patient was a 26-year-old female with history of end-stage renal disease secondary to systemic lupus erythematosus. She received her first kidney transplant from a living donor in 1994 and the second transplant from a deceased donor in 2003 due to primary loss of the first graft. She had no history of acute rejection episodes of her graft. Other significant past medical history included hypertension, migraines, and GERD.
She presented at the transplant outpatient clinic for an urgent visit after she noticed continuous bilateral milky white discharge from her breast nipples for a couple of days prior to her presentation consistent with galactorrhea. The patient's kidney graft function had been stable until eighteen months prior to this visit with a glomerular filtration rate (GFR) of 40-50 mL/min/1.7m2 (by CKD-EPI equation) when it gradually started to drop to less than 15 mL/min/1.73m2.
At the time of presentation, her renal function had further worsened to GFR 11 mL/min/1.73 m2 (chronic kidney disease stage 4-5). She reported that about a week earlier, she had visited the emergency department due to migraine headaches and at that time, she was given metoclopramide by mouth as needed for nausea and naratriptan in place of sumatriptan. She had also reported that about three months ago, due to worsening gastroesophageal reflux disease symptoms, omeprazole dose had been increased from 20 mg twice a day to 40 mg twice a day. Other oral medications included tacrolimus (levels ranging from of 4 to 6 ng/mL) and prednisone 5 mg for immunosuppression, amlodipine 10 mg once daily and labetalol 100 mg every 8 hours for hypertension, lovastatin 20 mg daily for hypercholesterolemia, nortriptyline 10 mg at bedtime for anxiety, and pyridoxine 50 mg once a day. Other than the recent omeprazole dose change, no other changes were reported for any of the medications above.
At that time, we attributed galactorrhea to metoclopramide as the most probable causative agent and stopped it since to our knowledge and based on the literature, none of the other long-term medications have been linked to an effect on prolactin secretion.
However, four weeks later, the symptoms persisted. Further investigation was initiated to look for other possible causes. She had been on nortriptyline for years without any issues so that was ruled out as the cause. A urine pregnancy test was negative. Thyroid function tests were normal, with a thyroid-stimulating hormone of 1.69 muIU/mL (0.55-4.78 muIU/mL). She had no history of liver disease or alcohol misuse. Laboratory investigation showed that she had normal liver function tests with alanine aminotransferase 20 U/L (normal range: <53 U/L), aspartate aminotransferase 18 U/L (normal range: 15-46 U/L), total bilirubin 0.6 mg/dL (normal range: <1.4 mg/dL), total alkaline phosphatase 94 U/L (normal range: 38-126 U/L), serum albumin 3.9 g/dL (normal range: 3.4-4.9 g/dL, total protein 6.8 g/dL (normal range: 6.5-8.3 g/dL), platelet count of 395000, and prothrombin time of 12.4 (INR 1.1). Furthermore, abdominal ultrasound few months earlier did not show abnormal liver.
Magnetic resonance imaging (MRI) of the brain ruled out any pituitary lesions or other pathology. However, fasting serum prolactin level was elevated for a nonpregnant woman at 140 ng/mL (normal range: 2.8-29.2 ng/mL). At that point, based on few previous case reports suggesting a possible link between PPIs and hyperprolactinemia, we stopped omeprazole 40 mg twice daily and the patient was given calcium carbonate as needed for heartburn as an alternative treatment. Two weeks after stopping omeprazole, fasting serum prolactin level returned to normal (18.8 ng/mL) accompanied by resolution of galactorrhea. She remained heartburn-free for about 2 months. Unfortunately, her kidney graft function deteriorated further and she started in-center hemodialysis. Due to worsening heartburn, it was decided to restart omeprazole but this time, at a lower dose 20 mg once a day. Two months later, her fasting serum prolactin level had remained normal at 9.5 ng/mL and without galactorrhea.