A Child With Severe Hearing Loss Associated With Maternal Cisplatin Treatment During Pregnancy
the diagnosis of severe perceptive hearing loss after cisplatin administration during the late second and third trimesters of pregnancy.
Eric C.T. Geijteman, MD, Celesta W.M. Wensveen, MD, PhD, Johannes J. Duvekot, MD, PhD, and Lia van Zuylen, MD, PhD
A 34-year-old Caucasian woman (gravida 2, para 1) presented at 24 2/7 weeks of gestation with profuse vaginal bleeding. Her medical history included a loop excision of the transformation zone of the uterine cervix 4 years previously because of cervical intraepithelial neoplasia grade 3. She had no other symptoms. At gynecologic examination, an exophytic growing tumor was seen on the cervix and a solid mass was palpated continuous with the anterior vaginal wall. Biopsy results showed moderately differentiated squamous cell carcinoma. Because of her pregnancy, abdominal magnetic resonance imaging was performed instead of computed tomography. This demonstrated a large cervical tumor (6.434.536 cm) with parametrial invasion and enlargement of pelvine and para-aortic lymph nodes. Thoracic computed tomography without contrast revealed no signs of metastases. The decision was made to initiate cisplatin (70 mg/m2) and paclitaxel (90 mg/m2) administered weekly for 6 weeks. The first dose was administered at 26 5/7 weeks of gestation. After three cycles of chemotherapy, pelvic examination showed a decrease in the tumor volume. Because of neutropenia and thrombopenia and because of a decrease the creatinine clearance (less than 50 mL/ min) after the fifth cycle, it was decided to stop the chemotherapy. The magnetic resonance imaging scan demonstrated a further decrease of the tumor to 3.931.732.8 cm. Also, lymphadenopathy was no longer evident. Three weeks after the last dose of cisplatin and paclitaxel, at 34 4/7 weeks of gestation, an elective cesarean delivery was performed to make it possible to start as soon as possible with local radiation therapy and hyperthermia. A male neonate with a birth weight of 2,085 g was delivered (Apgar scores 8 at 1 minute and 9 at 5 minutes). Neonatal adaption was normal, and laboratory evaluation did not reveal any abnormalities. The neonate was discharged soon after delivery and was not treated with any medication during the admission. The mother decided not to breastfeed. Because of a strong suspicion for hearing impairment of the newborn during the routine screening several days after birth, he was referred to an audiology center. Otoscopic examination revealed normal tympanic membranes and air-holding middle ears, which made a conductive hearing problem less likely. Brainstem-evoked response audiometry showed a hearing loss on the right of 30 dB and on the left of 60 dB. Approximately 6 months after birth, audiometry revealed a bilateral hearing loss of 50 dB at 3 kHz, with normal values for peak latencies (ie, severe bilateral hearing loss). Tympanometry showed no abnormalities. Because of the diagnosis of severe bilateral perceptive hearing loss, bilateral hearing aids were fitted.
BACKGROUND: Cisplatin is considered safe to use during the second and third trimesters of pregnancy in patients with cancer. CASE: A 34-year-old pregnant woman was diagnosed with cervical cancer. She received five weekly dosages of cisplatin and paclitaxel, starting at 26 5/7 weeks of gestation. An elective cesarean delivery was performed at 34 4/7 weeks of gestation. After birth, the neonate was diagnosed with severe bilateral perceptive hearing loss. CONCLUSION: Cisplatin during the second and third trimesters of pregnancy may lead to fetal ototoxicity. (Obstet Gynecol 2014;124:454–6) DOI: 10.1097/AOG.0000000000000389
C
ancer occurs in approximately 1 in 1,000 to 2,000 pregnancies.1 Because maternal age at birth in most western countries has increased, it can be expected that cancer will be diagnosed more often during pregnancy.1 One of the most common solid tumors during pregnancy is cervical cancer.2 For patients with cervical cancer treated with chemotherapy, first-line chemotherapy treatments are platinum derivates, particularly cisplatin, in combination with paclitaxel.3,4 Usual side effects of cisplatin and paclitaxel are decrease in bone marrow and peripheral neuropathy. In addition, cisplatin can be nephrotoxic and ototoxic. However, it is generally assumed that cisplatin may be used safely for the treatment of cancer during the second and third trimesters of pregnancy.2–4 We report a case of a newborn with From the Department of Medical Oncology, Erasmus MC Cancer Institute, and the Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands. Corresponding author: Eric C.T. Geijteman, MD, Department of Medical Oncology, P.O. Box 2040, 3000 CA, Rotterdam, the Netherlands; e-mail: e.geijteman@ erasmusmc.nl. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
454
Geijteman et al
CASE
Ototoxicity After Intrauterine Cisplatin
OBSTETRICS & GYNECOLOGY
COMMENT In this case, cisplatin administration during pregnancy was associated with severe fetal ototoxicity. Hearing loss at a young age has a significant effect on speech and language development.5 Moreover, it may influence educational achievement and social-emotional development.5 Although we cannot absolutely prove that cisplatin was the cause of this neonatal hearing loss, the relationship makes it most likely. Cisplatin causes, as in this neonate, an irreversible, bilateral, perceptive hearing loss, which typically affects the high frequencies.5 Basic mechanisms of platinum-induced ototoxicity are in line with cytotoxicity in tumor cells through binding to nuclear DNA and subsequent interference with DNA replication mechanisms.6 In addition, cisplatin is trafficked across the blood–endolymph barrier and preferentially enters inner ear hair cells.6 The reported incidence of ototoxicity in children who were treated directly with cisplatin ranges from 26% to 90%.5 Another argument that cisplatin was most likely the cause of the hearing loss is that other causes of hearing loss in children— such as a positive family history for hearing loss, recurrent ear infections, or antibiotic use—could be excluded. Our finding contrasts with the general opinion that cisplatin may be used safely as a treatment for cancer patients during the second and third trimesters of pregnancy.4 This opinion is based on the fact that, until now, no increased risks of spontaneous abortion or congenital anomalies were shown, as described in two systematic reviews on this subject.2,4 These reviews included 70 pregnant women with cancer who were treated with cisplatin during the second and third trimesters of pregnancy. Severe toxicity was reported in only two children.2,4 In these two children, the role of cisplatin as a toxic agent was highly speculative. In one fetus, a ventriculomegaly was diagnosed during the second trimester, 7 days after the first dose of cisplatin.2 The other child had perceptive bilateral hearing loss diagnosed at 1 year of age, but cisplatin had been administered for only 3 consecutive days at 26 weeks of gestation.2 This child received aminoglycosides soon after birth, which also can result in irreversible ototoxicity. Despite previous publications, there may be underrecognition and under-reporting of the side effects of cisplatin use during pregnancy. Many of the previously described cases lack long-term follow-up of the children. In young patients who were treated with platinum-based chemotherapy, delayed-onset or progressive hearing loss sometimes occurs.5 This is even seen in patients who had normal audiometry at the end of their chemotherapy.5
VOL. 124, NO. 2, PART 2, AUGUST 2014
Previously, a significant level of cisplatin, 40 micrograms/mL, was identified in the blood of a neonate on the day of birth after cisplatin (100 mg/m2) was administered 3 days before delivery.2 In comparison, in adult patients a platinum concentration of 1.8 micrograms/mL or higher is a strong predictor of development of cisplatin side effects.7 In another report, cisplatin was administered 16 days before delivery, after which at-birth cisplatin levels in the cord blood were only slightly less than in the maternal blood (0.82 micromoles/L compared with 1.10 micromoles/L).2 These findings of substantial transplacental transfer of cisplatin are supported by the characteristics of the drug. Although cisplatin is highly protein-bound, the drug has a low molecular weight (300.1 g/mol) and can easily cross the placenta.8 These findings are in contrast with the results of an in vitro study. In this study, it was shown that the transport of cisplatin from the maternal to the fetal circulation is only approximately 9% of the injected maternal drug load.9 However, the placental perfusion model the researchers used does not always correlate well with in vivo data.10 In addition to this, the perfusion model is based on placentas of uncomplicated term pregnancies and extrapolation of the results to earlier gestational periods may not be accurate.10 Our case calls into question the opinion that cisplatin-based chemotherapy during the second and third trimesters of pregnancy does not lead to ototoxicity. Further studies and reports are warranted to answer the question of whether cisplatin during second and third trimesters of pregnancy is safe for the fetus. One of these studies is an ongoing European study that aims to record systematically the short-term and long-term safety and efficacy of chemotherapy and radiotherapy during pregnancy.11 If cisplatin indeed leads to ototoxicity, it is also important to examine whether the dosing schedule per course affects the toxicity profile. It is known that in patients treated with the same overall cumulative dose of cisplatin, toxicity is less when the dosing schedule is more frequent.12 Until robust information from this large study and other (case) studies arises, potential risks and benefits of the cisplatin treatment have to be carefully weighed. REFERENCES 1. Amant F, Han SN, Gziri MM, Dekrem J, Van Calsteren K. Chemotherapy during pregnancy. Curr Opin Oncol 2012;24:580–6. 2. Mir O, Berveiller P, Ropert S, Goffinet F, Goldwasser F. Use of platinum derivatives during pregnancy. Cancer 2008;113:3069–74.
Geijteman et al
Ototoxicity After Intrauterine Cisplatin
455
3. Amant F, Van Calsteren K, Halaska MJ, Beijnen J, Lagae L, Hanssens M, et al. Gynecologic cancers in pregnancy: guidelines of an international consensus meeting. Int J Gynecol Cancer 2009;19(suppl 1):S1–12. 4. Zagouri F, Sergentanis TN, Chrysikos D, Bartsch R. Platinum derivatives during pregnancy in cervical cancer: a systematic review and meta-analysis. Obstet Gynecol 2013;121:337–43. 5. Knight KR, Kraemer DF, Neuwelt EA. Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol 2005;23:8588–96. 6. Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O. Understanding platinum-induced ototoxicity. Trends Pharmacol Sci 2013;34:458–69. 7. Mayo Medical Laboratories. Interpretive handbook. Available at: http://www.mayomedicallaboratories.com/interpretive-guide/. Retrieved April 21, 2014.
Factitious Hypoglycemia in Pregnancy in a Patient With Type 2 Diabetes Begoña Vega Guedes, MD, Concepción Santana Acosta, MD, Francisco Cabrera, MD, and Ana M. Wägner, MD, PhD BACKGROUND: Glycemic control in pregnancy complicated by diabetes is important. Spontaneous symptomatic hypoglycemia, in the absence of glucose-lowering treatment, is rare and requires evaluation to prevent harm. CASE: As a result of hypoglycemia, a pregnant woman with type 2 diabetes mellitus had progressive reduction of her insulin requirements until treatment was discontinued at 27 weeks. Despite this, she reported persistent From the Obstetrics and Gynecology Department and the Endocrinology and Nutrition Department, Complejo Hospitalario Universitario Insular MaternoInfantil, the Endocrinology and Nutrition Department, Hospital Dr Negrín, and the Departamento de Ciencias Médicas y Quirúrgicas, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. Drs. Vega Guedes and Wägner are being supported by a grant from the Spanish National Research Plan (Instituto de Salud Carlos III; PI 11/02441). The authors thank Aquilina López Alonso and Alejandra Nimptsch for their cooperation in the diagnosis and follow-up of the reported patient. Corresponding author: Ana M. Wägner, Endocrinology and Nutrition Department, Complejo Hospitalario Universitario Insular Materno-Infantil, Av Marítima s/n, 35016 Las Palmas de Gran Canaria, Spain; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
456
Vega Guedes et al
8. Gedeon C, Koren G. Designing pregnancy centered medications: drugs which do not cross the human placenta. Placenta 2006;27:861–8. 9. Al-Saleh E, Al-Harmi J, Nandakumaran M, Al-Shammari M. Transport kinetics of cisplatin in the perfused human placental lobule in vitro. J Matern Fetal Neonatal Med 2008;21:726–31. 10. Van Calsteren K, Verbesselt R, Van Bree R, Heyns L, de Bruijn E, de Hoon J, et al. Substantial variation in transplacental transfer of chemotherapeutic agents in a mouse model. Reprod Sci 2011;18:57–63. 11. Cancer in Pregnancy. Prospective study on chemotherapy during pregnancy. Available at: http://www.cancerinpregnancy. org/. Retrieved April 21, 2014. 12. Yancey A, Harris MS, Egbelakin A, Gilbert J, Pisoni DB, Renbarger J. Risk factors for cisplatin-associated ototoxicity in pediatric oncology patients. Pediatr Blood Cancer 2012;59: 144–8.
episodes of hypoglycemia. Investigation of possible causes resulted in the discovery that she was covertly treating herself with insulin. CONCLUSION: Factitious hypoglycemia should be considered as part of the differential diagnosis of unexplained hypoglycemia. Blood sampling during an episode of hypoglycemia is pivotal in this assessment. (Obstet Gynecol 2014;124:456–8) DOI: 10.1097/AOG.0000000000000138
A
fter the first trimester of pregnancy, glycemic control for diabetic women primarily involves controlling hyperglycemia caused by the increasing insulin resistance, changes in diet and exercise patterns, patient compliance with prescribed regimens, and body weight. Hypoglycemic episodes raise concerns regarding placental dysfunction or sporadic incorrect medication dosing or missed meals. The differential diagnosis of frequent symptomatic hypoglycemic episodes in pregnancy includes placental dysfunction, insulinoma, incorrect prescription fulfillment, patient error, and intentional patient overdosing of medications. We present the course of a patient that illustrates the importance of considering the full differential diagnosis.
CASE A 29-year-old woman, gravida 1, initiated care at 9 weeks of gestation. She had type 2 diabetes mellitus, diagnosed 9 years earlier, and was being treated before pregnancy with glybenclamide (glyburide) 5 mg daily, metformin 850 mg three times per day, and simvastatin 40 mg daily. She had no vascular complications of her diabetes, although her glycemic control was poor (previous hemoglobin A1C was 9.1%). She had worked as a shop assistant but was unemployed at the time of presentation. Her history was
Factitious Hypoglycemia in Pregnancy
OBSTETRICS & GYNECOLOGY
the diagnosis of severe perceptive hearing loss after cisplatin administration during the late second and third trimesters of pregnancy.
Eric C.T. Geijteman, MD, Celesta W.M. Wensveen, MD, PhD, Johannes J. Duvekot, MD, PhD, and Lia van Zuylen, MD, PhD
A 34-year-old Caucasian woman (gravida 2, para 1) presented at 24 2/7 weeks of gestation with profuse vaginal bleeding. Her medical history included a loop excision of the transformation zone of the uterine cervix 4 years previously because of cervical intraepithelial neoplasia grade 3. She had no other symptoms. At gynecologic examination, an exophytic growing tumor was seen on the cervix and a solid mass was palpated continuous with the anterior vaginal wall. Biopsy results showed moderately differentiated squamous cell carcinoma. Because of her pregnancy, abdominal magnetic resonance imaging was performed instead of computed tomography. This demonstrated a large cervical tumor (6.434.536 cm) with parametrial invasion and enlargement of pelvine and para-aortic lymph nodes. Thoracic computed tomography without contrast revealed no signs of metastases. The decision was made to initiate cisplatin (70 mg/m2) and paclitaxel (90 mg/m2) administered weekly for 6 weeks. The first dose was administered at 26 5/7 weeks of gestation. After three cycles of chemotherapy, pelvic examination showed a decrease in the tumor volume. Because of neutropenia and thrombopenia and because of a decrease the creatinine clearance (less than 50 mL/ min) after the fifth cycle, it was decided to stop the chemotherapy. The magnetic resonance imaging scan demonstrated a further decrease of the tumor to 3.931.732.8 cm. Also, lymphadenopathy was no longer evident. Three weeks after the last dose of cisplatin and paclitaxel, at 34 4/7 weeks of gestation, an elective cesarean delivery was performed to make it possible to start as soon as possible with local radiation therapy and hyperthermia. A male neonate with a birth weight of 2,085 g was delivered (Apgar scores 8 at 1 minute and 9 at 5 minutes). Neonatal adaption was normal, and laboratory evaluation did not reveal any abnormalities. The neonate was discharged soon after delivery and was not treated with any medication during the admission. The mother decided not to breastfeed. Because of a strong suspicion for hearing impairment of the newborn during the routine screening several days after birth, he was referred to an audiology center. Otoscopic examination revealed normal tympanic membranes and air-holding middle ears, which made a conductive hearing problem less likely. Brainstem-evoked response audiometry showed a hearing loss on the right of 30 dB and on the left of 60 dB. Approximately 6 months after birth, audiometry revealed a bilateral hearing loss of 50 dB at 3 kHz, with normal values for peak latencies (ie, severe bilateral hearing loss). Tympanometry showed no abnormalities. Because of the diagnosis of severe bilateral perceptive hearing loss, bilateral hearing aids were fitted.
BACKGROUND: Cisplatin is considered safe to use during the second and third trimesters of pregnancy in patients with cancer. CASE: A 34-year-old pregnant woman was diagnosed with cervical cancer. She received five weekly dosages of cisplatin and paclitaxel, starting at 26 5/7 weeks of gestation. An elective cesarean delivery was performed at 34 4/7 weeks of gestation. After birth, the neonate was diagnosed with severe bilateral perceptive hearing loss. CONCLUSION: Cisplatin during the second and third trimesters of pregnancy may lead to fetal ototoxicity. (Obstet Gynecol 2014;124:454–6) DOI: 10.1097/AOG.0000000000000389
C
ancer occurs in approximately 1 in 1,000 to 2,000 pregnancies.1 Because maternal age at birth in most western countries has increased, it can be expected that cancer will be diagnosed more often during pregnancy.1 One of the most common solid tumors during pregnancy is cervical cancer.2 For patients with cervical cancer treated with chemotherapy, first-line chemotherapy treatments are platinum derivates, particularly cisplatin, in combination with paclitaxel.3,4 Usual side effects of cisplatin and paclitaxel are decrease in bone marrow and peripheral neuropathy. In addition, cisplatin can be nephrotoxic and ototoxic. However, it is generally assumed that cisplatin may be used safely for the treatment of cancer during the second and third trimesters of pregnancy.2–4 We report a case of a newborn with From the Department of Medical Oncology, Erasmus MC Cancer Institute, and the Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands. Corresponding author: Eric C.T. Geijteman, MD, Department of Medical Oncology, P.O. Box 2040, 3000 CA, Rotterdam, the Netherlands; e-mail: e.geijteman@ erasmusmc.nl. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
454
Geijteman et al
CASE
Ototoxicity After Intrauterine Cisplatin
OBSTETRICS & GYNECOLOGY
COMMENT In this case, cisplatin administration during pregnancy was associated with severe fetal ototoxicity. Hearing loss at a young age has a significant effect on speech and language development.5 Moreover, it may influence educational achievement and social-emotional development.5 Although we cannot absolutely prove that cisplatin was the cause of this neonatal hearing loss, the relationship makes it most likely. Cisplatin causes, as in this neonate, an irreversible, bilateral, perceptive hearing loss, which typically affects the high frequencies.5 Basic mechanisms of platinum-induced ototoxicity are in line with cytotoxicity in tumor cells through binding to nuclear DNA and subsequent interference with DNA replication mechanisms.6 In addition, cisplatin is trafficked across the blood–endolymph barrier and preferentially enters inner ear hair cells.6 The reported incidence of ototoxicity in children who were treated directly with cisplatin ranges from 26% to 90%.5 Another argument that cisplatin was most likely the cause of the hearing loss is that other causes of hearing loss in children— such as a positive family history for hearing loss, recurrent ear infections, or antibiotic use—could be excluded. Our finding contrasts with the general opinion that cisplatin may be used safely as a treatment for cancer patients during the second and third trimesters of pregnancy.4 This opinion is based on the fact that, until now, no increased risks of spontaneous abortion or congenital anomalies were shown, as described in two systematic reviews on this subject.2,4 These reviews included 70 pregnant women with cancer who were treated with cisplatin during the second and third trimesters of pregnancy. Severe toxicity was reported in only two children.2,4 In these two children, the role of cisplatin as a toxic agent was highly speculative. In one fetus, a ventriculomegaly was diagnosed during the second trimester, 7 days after the first dose of cisplatin.2 The other child had perceptive bilateral hearing loss diagnosed at 1 year of age, but cisplatin had been administered for only 3 consecutive days at 26 weeks of gestation.2 This child received aminoglycosides soon after birth, which also can result in irreversible ototoxicity. Despite previous publications, there may be underrecognition and under-reporting of the side effects of cisplatin use during pregnancy. Many of the previously described cases lack long-term follow-up of the children. In young patients who were treated with platinum-based chemotherapy, delayed-onset or progressive hearing loss sometimes occurs.5 This is even seen in patients who had normal audiometry at the end of their chemotherapy.5
VOL. 124, NO. 2, PART 2, AUGUST 2014
Previously, a significant level of cisplatin, 40 micrograms/mL, was identified in the blood of a neonate on the day of birth after cisplatin (100 mg/m2) was administered 3 days before delivery.2 In comparison, in adult patients a platinum concentration of 1.8 micrograms/mL or higher is a strong predictor of development of cisplatin side effects.7 In another report, cisplatin was administered 16 days before delivery, after which at-birth cisplatin levels in the cord blood were only slightly less than in the maternal blood (0.82 micromoles/L compared with 1.10 micromoles/L).2 These findings of substantial transplacental transfer of cisplatin are supported by the characteristics of the drug. Although cisplatin is highly protein-bound, the drug has a low molecular weight (300.1 g/mol) and can easily cross the placenta.8 These findings are in contrast with the results of an in vitro study. In this study, it was shown that the transport of cisplatin from the maternal to the fetal circulation is only approximately 9% of the injected maternal drug load.9 However, the placental perfusion model the researchers used does not always correlate well with in vivo data.10 In addition to this, the perfusion model is based on placentas of uncomplicated term pregnancies and extrapolation of the results to earlier gestational periods may not be accurate.10 Our case calls into question the opinion that cisplatin-based chemotherapy during the second and third trimesters of pregnancy does not lead to ototoxicity. Further studies and reports are warranted to answer the question of whether cisplatin during second and third trimesters of pregnancy is safe for the fetus. One of these studies is an ongoing European study that aims to record systematically the short-term and long-term safety and efficacy of chemotherapy and radiotherapy during pregnancy.11 If cisplatin indeed leads to ototoxicity, it is also important to examine whether the dosing schedule per course affects the toxicity profile. It is known that in patients treated with the same overall cumulative dose of cisplatin, toxicity is less when the dosing schedule is more frequent.12 Until robust information from this large study and other (case) studies arises, potential risks and benefits of the cisplatin treatment have to be carefully weighed. REFERENCES 1. Amant F, Han SN, Gziri MM, Dekrem J, Van Calsteren K. Chemotherapy during pregnancy. Curr Opin Oncol 2012;24:580–6. 2. Mir O, Berveiller P, Ropert S, Goffinet F, Goldwasser F. Use of platinum derivatives during pregnancy. Cancer 2008;113:3069–74.
Geijteman et al
Ototoxicity After Intrauterine Cisplatin
455
3. Amant F, Van Calsteren K, Halaska MJ, Beijnen J, Lagae L, Hanssens M, et al. Gynecologic cancers in pregnancy: guidelines of an international consensus meeting. Int J Gynecol Cancer 2009;19(suppl 1):S1–12. 4. Zagouri F, Sergentanis TN, Chrysikos D, Bartsch R. Platinum derivatives during pregnancy in cervical cancer: a systematic review and meta-analysis. Obstet Gynecol 2013;121:337–43. 5. Knight KR, Kraemer DF, Neuwelt EA. Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. J Clin Oncol 2005;23:8588–96. 6. Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O. Understanding platinum-induced ototoxicity. Trends Pharmacol Sci 2013;34:458–69. 7. Mayo Medical Laboratories. Interpretive handbook. Available at: http://www.mayomedicallaboratories.com/interpretive-guide/. Retrieved April 21, 2014.
Factitious Hypoglycemia in Pregnancy in a Patient With Type 2 Diabetes Begoña Vega Guedes, MD, Concepción Santana Acosta, MD, Francisco Cabrera, MD, and Ana M. Wägner, MD, PhD BACKGROUND: Glycemic control in pregnancy complicated by diabetes is important. Spontaneous symptomatic hypoglycemia, in the absence of glucose-lowering treatment, is rare and requires evaluation to prevent harm. CASE: As a result of hypoglycemia, a pregnant woman with type 2 diabetes mellitus had progressive reduction of her insulin requirements until treatment was discontinued at 27 weeks. Despite this, she reported persistent From the Obstetrics and Gynecology Department and the Endocrinology and Nutrition Department, Complejo Hospitalario Universitario Insular MaternoInfantil, the Endocrinology and Nutrition Department, Hospital Dr Negrín, and the Departamento de Ciencias Médicas y Quirúrgicas, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. Drs. Vega Guedes and Wägner are being supported by a grant from the Spanish National Research Plan (Instituto de Salud Carlos III; PI 11/02441). The authors thank Aquilina López Alonso and Alejandra Nimptsch for their cooperation in the diagnosis and follow-up of the reported patient. Corresponding author: Ana M. Wägner, Endocrinology and Nutrition Department, Complejo Hospitalario Universitario Insular Materno-Infantil, Av Marítima s/n, 35016 Las Palmas de Gran Canaria, Spain; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14
456
Vega Guedes et al
8. Gedeon C, Koren G. Designing pregnancy centered medications: drugs which do not cross the human placenta. Placenta 2006;27:861–8. 9. Al-Saleh E, Al-Harmi J, Nandakumaran M, Al-Shammari M. Transport kinetics of cisplatin in the perfused human placental lobule in vitro. J Matern Fetal Neonatal Med 2008;21:726–31. 10. Van Calsteren K, Verbesselt R, Van Bree R, Heyns L, de Bruijn E, de Hoon J, et al. Substantial variation in transplacental transfer of chemotherapeutic agents in a mouse model. Reprod Sci 2011;18:57–63. 11. Cancer in Pregnancy. Prospective study on chemotherapy during pregnancy. Available at: http://www.cancerinpregnancy. org/. Retrieved April 21, 2014. 12. Yancey A, Harris MS, Egbelakin A, Gilbert J, Pisoni DB, Renbarger J. Risk factors for cisplatin-associated ototoxicity in pediatric oncology patients. Pediatr Blood Cancer 2012;59: 144–8.
episodes of hypoglycemia. Investigation of possible causes resulted in the discovery that she was covertly treating herself with insulin. CONCLUSION: Factitious hypoglycemia should be considered as part of the differential diagnosis of unexplained hypoglycemia. Blood sampling during an episode of hypoglycemia is pivotal in this assessment. (Obstet Gynecol 2014;124:456–8) DOI: 10.1097/AOG.0000000000000138
A
fter the first trimester of pregnancy, glycemic control for diabetic women primarily involves controlling hyperglycemia caused by the increasing insulin resistance, changes in diet and exercise patterns, patient compliance with prescribed regimens, and body weight. Hypoglycemic episodes raise concerns regarding placental dysfunction or sporadic incorrect medication dosing or missed meals. The differential diagnosis of frequent symptomatic hypoglycemic episodes in pregnancy includes placental dysfunction, insulinoma, incorrect prescription fulfillment, patient error, and intentional patient overdosing of medications. We present the course of a patient that illustrates the importance of considering the full differential diagnosis.
CASE A 29-year-old woman, gravida 1, initiated care at 9 weeks of gestation. She had type 2 diabetes mellitus, diagnosed 9 years earlier, and was being treated before pregnancy with glybenclamide (glyburide) 5 mg daily, metformin 850 mg three times per day, and simvastatin 40 mg daily. She had no vascular complications of her diabetes, although her glycemic control was poor (previous hemoglobin A1C was 9.1%). She had worked as a shop assistant but was unemployed at the time of presentation. Her history was
Factitious Hypoglycemia in Pregnancy
OBSTETRICS & GYNECOLOGY
