Journal of Intensive Care Medicine http://jic.sagepub.com/
Hypertriglyceridemic Pancreatitis Caused by the Oral Contraceptive Agent Estrostep Mary Abraham, Jennifer Mitchell, Debra Simsovits and James Gasperino J Intensive Care Med published online 26 March 2014 DOI: 10.1177/0885066614528083 The online version of this article can be found at: http://jic.sagepub.com/content/early/2014/03/25/0885066614528083
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Article
Hypertriglyceridemic Pancreatitis Caused by the Oral Contraceptive Agent Estrostep
Journal of Intensive Care Medicine 1-5 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0885066614528083 jic.sagepub.com
Mary Abraham, MD, MBA1, Jennifer Mitchell, PharmD1, Debra Simsovits, DO1, and James Gasperino, MD, PhD, MPH1
Abstract Norethindrone acetate/ethinyl estradiol (Estrostep; Warner Chilcott, Rockaway, New Jersey) is an ‘‘estrophasic’’ type of oral contraceptive, which combines a continuous low progestin dose with a gradually increasing estrogen dose. In clinical trials, this medication failed to produce clinically significant changes in serum lipid levels. We report a case of severe hypertriglyceridemiainduced acute pancreatitis in a 24-year-old woman caused by Estrostep, occurring nearly 10 years after she began using the drug. The patient was admitted to the medical intensive care unit (ICU) for aggressive volume resuscitation and management of severe electrolyte abnormalities. Laboratory studies obtained on admission indicated severe hypertriglyceridemia (2,200 mg/dL), hyponatremia (120 mEq/L), and hypocalcemia (0.78 mmol/L). Amylase and lipase levels were also elevated (193 and 200 U/L, respectively). Ranson score calculated after 48 hours of admission was 4, and her Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 35. Treatment included an insulin infusion, o-3 fatty acid esters, and gemfibrozil. The insulin infusion reduced serum triglyceride levels by 50% after 1 day of treatment and to 355 mg/dL by day 7 of her ICU course. We believe that this is the first reported case of severe, acute hypertriglyceridemia-induced pancreatitis caused by this medication. Keywords estrophasic, estrostep, ethinyl estradiol, norethindrone
Introduction
Case Report
Although acute pancreatitis is a common clinical presentation, hypertriglyceridemia-induced pancreatitis occurs in only 7% of all cases of pancreatitis.1 Hypertriglyceridemia can be acquired or inherited. Familial hyperlipidemia syndromes such as lipoprotein lipase deficiency and familial hypertriglyceridemia are examples of the latter, whereas the use of estrogen-containing oral contraceptives (OCTs) is an example of the former. Often, OCTs unmask a familial hyperlipidemia syndrome that had not been discovered before the patient began taking the OCT.2-5 We present what appears to be the first reported case of severe hypertriglyceridemic acute pancreatitis in a young woman taking norethindrone acetate/ethinyl estradiol (Estrostep; Warner Chilcott, Rockaway, New Jersey), an estrophasic OCT agent. This relatively new OCT medication was not shown to significantly elevate serum triglyceride levels in clinical trials. It is noteworthy that severe acute pancreatitis was the first clinical presentation of this adverse drug event; our patient had been using the agent for several years without complications. Moreover, the patient was neither pregnant nor had a history of familial hyperlipidemia syndrome. We review the current pathogenesis and management of hypertriglyceridemia-induced acute pancreatitis and report an excellent clinical outcome using insulin infusion, o-3 fatty acid esters, and gemfibrozil to treat hypertriglyceridemia in the intensive care unit (ICU) setting.
A 24-year-old woman with a history of intermittent asthma presented to our emergency department reporting nausea, vomiting, and ‘‘crampy’’ pain in the right upper quadrant of the abdomen, radiating to the back, which she scored a 6 on a scale of 1 to 10. The patient reported that these symptoms started 1 day prior to her presentation to the emergency department. Three weeks earlier, she was notified by her primary care physician during a routine periodic examination that she had an abnormal lipid profile and she was scheduled to see a specialist. The patient was unable to recollect the exact characteristics of the dyslipidemia and we were unable to obtain the laboratory report. The patient’s outpatient medications included albuterol and Estrostep. She reported that she had used Estrostep for
1
Department of Medicine, Section of Critical Care Medicine, Drexel University College of Medicine, Philadelphia, PA, USA
Received November 15, 2013, and in revised form January 09, 2014. Accepted for publication January 13, 2014. Corresponding Author: James Gasperino, Department of Medicine, Section of Critical Care Medicine, Drexel University College of Medicine, 245 N. 15th Street, MS #487, Philadelphia, PA, USA. Email: [email protected]
Downloaded from jic.sagepub.com at DUQUESNE UNIV on June 8, 2014
2
Journal of Intensive Care Medicine
Table 1. Laboratory Studies Obtained for a Patient With Hypertriglyceridemic Pancreatitis During 7 Days in the Medical Intensive Care Unit.
Sodium, mmol/L Potassium, mmol/L Chloride, mmol/L Calcium (uncorrected), mg/dL Calcium (corrected), mg/dL Ionized calcium, mmol/L Blood urea nitrogen, mg/dL Creatinine, mg/dL CO2, mmol/L Lactate, mmol/L White blood cells/10 3, K/UL Platelet, K/UL Neutrophil, % Lymphocyte, % Bands, % Monocyte, % Absolute neutrophils, K/UL Hemoglobin, g/dL Hematocrit, % Total bilirubin, mg/dL Conjugated bilirubin, mg/dL Glucose, mg/dL Alkaline phosphatase, U/L Total protein, g/dL Albumin, g/dL Prothrombin time, seconds International normalized ratio Partial thromboplastin time, seconds Phosphorus, mg/dL Magnesium, mEq/L Cholesterol, mg/dL Triglycerides, mg/dL High-density lipoprotein, mg/dL Low-density lipoprotein, mg/dL Amylase, U/L Lipase, U/L
Day 1
Day 2
Day 7
120 3.4 88 6.1 7.5 0.78 10 0.53 17 2.1 14.7 285 66 6 22 3.9 13.3 13.4 40.2 1.31 0.39 169 31 8 2.3 13.1 1.18 26.3 1.6 1.2 409 2230 25 51 193 200
126 3.3 102 5.2 6.9 0.89 6 0.53 17 2 11.3 210 90.3 5.8 0 3.8 10.2 13 36.7 0.57 0.12 141 36 N/A 1.9 13.6 1.22 27.9 1.5 N/A 261 1101 N/A N/A 184 178
134 3.8 100 8.6 10.2 N/A 4 0.46 26 N/A 10.1 220 78.3 10.6 0 8.3 7.9 8.9 25.9 0.59
Hypertriglyceridemic Pancreatitis Caused by the Oral Contraceptive Agent Estrostep Mary Abraham, Jennifer Mitchell, Debra Simsovits and James Gasperino J Intensive Care Med published online 26 March 2014 DOI: 10.1177/0885066614528083 The online version of this article can be found at: http://jic.sagepub.com/content/early/2014/03/25/0885066614528083
Published by: http://www.sagepublications.com
Additional services and information for Journal of Intensive Care Medicine can be found at: Email Alerts: http://jic.sagepub.com/cgi/alerts Subscriptions: http://jic.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Mar 26, 2014 What is This?
Downloaded from jic.sagepub.com at DUQUESNE UNIV on June 8, 2014
Article
Hypertriglyceridemic Pancreatitis Caused by the Oral Contraceptive Agent Estrostep
Journal of Intensive Care Medicine 1-5 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0885066614528083 jic.sagepub.com
Mary Abraham, MD, MBA1, Jennifer Mitchell, PharmD1, Debra Simsovits, DO1, and James Gasperino, MD, PhD, MPH1
Abstract Norethindrone acetate/ethinyl estradiol (Estrostep; Warner Chilcott, Rockaway, New Jersey) is an ‘‘estrophasic’’ type of oral contraceptive, which combines a continuous low progestin dose with a gradually increasing estrogen dose. In clinical trials, this medication failed to produce clinically significant changes in serum lipid levels. We report a case of severe hypertriglyceridemiainduced acute pancreatitis in a 24-year-old woman caused by Estrostep, occurring nearly 10 years after she began using the drug. The patient was admitted to the medical intensive care unit (ICU) for aggressive volume resuscitation and management of severe electrolyte abnormalities. Laboratory studies obtained on admission indicated severe hypertriglyceridemia (2,200 mg/dL), hyponatremia (120 mEq/L), and hypocalcemia (0.78 mmol/L). Amylase and lipase levels were also elevated (193 and 200 U/L, respectively). Ranson score calculated after 48 hours of admission was 4, and her Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 35. Treatment included an insulin infusion, o-3 fatty acid esters, and gemfibrozil. The insulin infusion reduced serum triglyceride levels by 50% after 1 day of treatment and to 355 mg/dL by day 7 of her ICU course. We believe that this is the first reported case of severe, acute hypertriglyceridemia-induced pancreatitis caused by this medication. Keywords estrophasic, estrostep, ethinyl estradiol, norethindrone
Introduction
Case Report
Although acute pancreatitis is a common clinical presentation, hypertriglyceridemia-induced pancreatitis occurs in only 7% of all cases of pancreatitis.1 Hypertriglyceridemia can be acquired or inherited. Familial hyperlipidemia syndromes such as lipoprotein lipase deficiency and familial hypertriglyceridemia are examples of the latter, whereas the use of estrogen-containing oral contraceptives (OCTs) is an example of the former. Often, OCTs unmask a familial hyperlipidemia syndrome that had not been discovered before the patient began taking the OCT.2-5 We present what appears to be the first reported case of severe hypertriglyceridemic acute pancreatitis in a young woman taking norethindrone acetate/ethinyl estradiol (Estrostep; Warner Chilcott, Rockaway, New Jersey), an estrophasic OCT agent. This relatively new OCT medication was not shown to significantly elevate serum triglyceride levels in clinical trials. It is noteworthy that severe acute pancreatitis was the first clinical presentation of this adverse drug event; our patient had been using the agent for several years without complications. Moreover, the patient was neither pregnant nor had a history of familial hyperlipidemia syndrome. We review the current pathogenesis and management of hypertriglyceridemia-induced acute pancreatitis and report an excellent clinical outcome using insulin infusion, o-3 fatty acid esters, and gemfibrozil to treat hypertriglyceridemia in the intensive care unit (ICU) setting.
A 24-year-old woman with a history of intermittent asthma presented to our emergency department reporting nausea, vomiting, and ‘‘crampy’’ pain in the right upper quadrant of the abdomen, radiating to the back, which she scored a 6 on a scale of 1 to 10. The patient reported that these symptoms started 1 day prior to her presentation to the emergency department. Three weeks earlier, she was notified by her primary care physician during a routine periodic examination that she had an abnormal lipid profile and she was scheduled to see a specialist. The patient was unable to recollect the exact characteristics of the dyslipidemia and we were unable to obtain the laboratory report. The patient’s outpatient medications included albuterol and Estrostep. She reported that she had used Estrostep for
1
Department of Medicine, Section of Critical Care Medicine, Drexel University College of Medicine, Philadelphia, PA, USA
Received November 15, 2013, and in revised form January 09, 2014. Accepted for publication January 13, 2014. Corresponding Author: James Gasperino, Department of Medicine, Section of Critical Care Medicine, Drexel University College of Medicine, 245 N. 15th Street, MS #487, Philadelphia, PA, USA. Email: [email protected]
Downloaded from jic.sagepub.com at DUQUESNE UNIV on June 8, 2014
2
Journal of Intensive Care Medicine
Table 1. Laboratory Studies Obtained for a Patient With Hypertriglyceridemic Pancreatitis During 7 Days in the Medical Intensive Care Unit.
Sodium, mmol/L Potassium, mmol/L Chloride, mmol/L Calcium (uncorrected), mg/dL Calcium (corrected), mg/dL Ionized calcium, mmol/L Blood urea nitrogen, mg/dL Creatinine, mg/dL CO2, mmol/L Lactate, mmol/L White blood cells/10 3, K/UL Platelet, K/UL Neutrophil, % Lymphocyte, % Bands, % Monocyte, % Absolute neutrophils, K/UL Hemoglobin, g/dL Hematocrit, % Total bilirubin, mg/dL Conjugated bilirubin, mg/dL Glucose, mg/dL Alkaline phosphatase, U/L Total protein, g/dL Albumin, g/dL Prothrombin time, seconds International normalized ratio Partial thromboplastin time, seconds Phosphorus, mg/dL Magnesium, mEq/L Cholesterol, mg/dL Triglycerides, mg/dL High-density lipoprotein, mg/dL Low-density lipoprotein, mg/dL Amylase, U/L Lipase, U/L
Day 1
Day 2
Day 7
120 3.4 88 6.1 7.5 0.78 10 0.53 17 2.1 14.7 285 66 6 22 3.9 13.3 13.4 40.2 1.31 0.39 169 31 8 2.3 13.1 1.18 26.3 1.6 1.2 409 2230 25 51 193 200
126 3.3 102 5.2 6.9 0.89 6 0.53 17 2 11.3 210 90.3 5.8 0 3.8 10.2 13 36.7 0.57 0.12 141 36 N/A 1.9 13.6 1.22 27.9 1.5 N/A 261 1101 N/A N/A 184 178
134 3.8 100 8.6 10.2 N/A 4 0.46 26 N/A 10.1 220 78.3 10.6 0 8.3 7.9 8.9 25.9 0.59
![[Plasmapheresis in hypertriglyceridemic acute pancreatitis].](/assets/img/hold.png)
