findings were consistent with endogenous hyperinsulinism. (Table 1). Results from abdominal computed tomographic. (CT) scan and mesenteric arteriography ...
CASE REPORT Insulinoma associated with pregnancy Adriana G. Diaz, M.D.,a Javier Herrera, M.D.,a Mariana L opez, M.D.,a F elix M. Puchulu, M.D.,b c a Pedro Ferraina, M.D., and Oscar D. Bruno, M.D. Divisions of a Endocrinology and b Diabetes and c Department of Surgery, Hospital de Clınicas, University of Buenos Aires, Buenos Aires, Argentina
Objective: To report three cases of insulinoma associated with pregnancy. Design: Case report. Setting: Divisions of Endocrinology and Gastroenterologic Surgery, Hospital de Clınicas, University of Buenos Aires, Argentina. Patient(s): Three patients with hypoglycemic signs due to insulinoma appearing during pregnancy or shortly after delivery. Intervention(s): Laparoscopic excision of insulinoma in two and laparotomy in one of the patients were performed after the end of their pregnancies. Main Outcome Measure(s): Disappearance of hypoglycemic crises and histologic proof of insulinomas. Result(s): In two of the three patients, hypoglycemia occurred within 2–12 weeks after delivery, suggesting that signs could have been masked because of metabolic changes during gestation; in the third patient, hypoglycemia appeared in the first trimester but was misinterpreted. Conclusion(s): Insulinoma is often not suspected during the first trimester of pregnancy because signs resemble episodes of hypotension or emesis. Later, with the increase in insulin resistance, symptoms subside. (Fertil Steril 2008;90:199.e1–e4. 2008 by American Society for Reproductive Medicine.) Key Words: Insulinoma, hypoglycemia, pregnancy
Insulinomas are rare insulin-secreting tumors that occur with an incidence of 1 per 250,000 people per year. Characteristically, patients with insulinoma present profound and symptomatic hypoglycemia. Hypoglycemic episodes are diagnosed in the presence of the Whipple’s triad, consisting of neuroglycopenic or autonomic manifestations, simultaneous low plasma glucose, and the relief of all symptoms through correction of hypoglycemia (1). Confirmation of diagnosis is usually obtained by showing the association of hypoglycemia with nonsuppressed insulin secretion, during normal or prolonged fasting (2). Typically, insulinomas are small benign tumors; malignancy or association with multiple endocrine neoplasia (MEN 1) is seen in less than 10%–15% of all cases (1). Insulinoma associated with pregnancy is a very rare event. Until recently, approximately 20 cases had been reported. Most of the reported cases appeared during the first trimester with hypoglycemic episodes (3). We report here three new clinical cases of insulinoma associated with pregnancy and/ or the postpartum period. Received April 22, 2007; revised June 21, 2007; accepted June 25, 2007. Request reprints: Oscar D. Bruno, M.D., Division of Endocrinology, Hospi rdoba 2351, 1120 tal de Clınicas, University of Buenos Aires, Avenida Co Buenos Aires, Argentina (FAX: 54-11-48050631; E-mail: bodomingo@ intramed.net).
0015-0282/08/$34.00 doi:10.1016/j.fertnstert.2007.06.092
CASE REPORTS Case 1 A 35-year-old obese (BMI 43 kg/m2) woman presented 3 months after the delivery of twins with episodes of confusion, dizziness, and loss of consciousness that progressed in frequency and duration. The babies, a girl and a boy, were born at 36 weeks’ gestation and weighed 1800 g and 1900 g, respectively. Seizure disorder was diagnosed and treated with phenytoin, showing no clinical response. Episodes improved with frequent carbohydrate ingestion. During the next 4 years, the patient gained 45 kg. At this stage she was admitted to our institution for further evaluation. Prolonged fasting test results were positive after 8 hours; biochemical findings were consistent with endogenous hyperinsulinism (Table 1). Results from abdominal computed tomographic (CT) scan and mesenteric arteriography were negative. A 15-mm mass in the junction of the head and body of the pancreas was removed through exploratory laparotomy. Immediately after surgery the patient showed hyperglycemia that resolved spontaneously. Pathology and immunostaining confirmed the diagnosis of insulinoma. Case 2 A 35-year-old woman was admitted to our institution on the 26th postpartum day with confusion, dysarthria, and
Fertility and Sterility Vol. 90, No. 1, July 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
199.e1
TABLE 1 Laboratory test results in three patients with insulinoma associated with pregnancy. Test Glycemia (mg/dL) Serum insulin (mU/mL) (MEIA) Serum C-peptide (nmol/L) Positive PFT results at: (h)
Normal values
Case 1
Case 2
Case 3
70–110 5–25 0.2–1.2
27 25.7 0.90 8
34 6.8 0.29 17
42 68.7 nd 3
Note: MEIA ¼ microparticle enzyme immunoassay; nd ¼ not done; PFT ¼ prolonged fasting test. Diaz. Insulinoma and pregnancy. Fertil Steril 2008.
quadriplegia. She related a history of frequent episodes of dizziness starting within the first trimester of pregnancy that mitigated with frequent meals. Subsequently she did not have any other hypoglycemic signs. Pregnancy developed without complications, ending in normal delivery at 40 weeks’ gestation of a normal baby girl weighing 3170 g. At admission, laboratory study results were normal except for a capillary blood glucose value of 43 mg/dL. Symptoms subsided after administration of an intravenous glucose infusion. Additional studies were performed. Prolonged fasting test results were positive after 17 hours (Table 1). Results on abdominal CT and endoscopic ultrasound were unrewarding. An intra-arterial calcium stimulation test (4) induced selective insulin rise in the splenic artery region. Laparoscopy with intraoperative ultrasound showed a mass in the tail of the pancreas. Enucleation of an 8-mm tumor was performed. Pathological analysis was consistent with insulinoma. Postoperatively the patient had hyperglycemia (180 mg/dL) and developed pancreatic cysts and hyperamylasemia that resolved spontaneously with no complications. She remains asymptomatic and normoglycemic after a 2.5-year follow-up.
Case 3 A 22-year-old primigravid woman developed headache, tremor, tachycardia, confusion, and loss of consciousness during the second month of pregnancy. Hypoglycemia (
