The clinical course and pathophysiological investigation of adolescent gestational diabetes insipidus: a case report

Kondo et al. BMC Endocrine Disorders (2018):4 DOI 10.1186/s12902-018-0234-6 CASE REPORT Open Access The clinical course and pathophysiological investigation of adolescent gestational diabetes insipidus: a case report Tatsuya Kondo1*, Miwa Nakamura2, Sayaka Kitano1, Junji Kawashima1, Takeshi Matsumura1, Takashi Ohba2, Munekage Yamaguchi2, Hidetaka Katabuchi2 and Eiichi Araki1 Abstract Background: Gestational diabetes insipidus (GDI) is a rare endocrine complication during pregnancy that is associated with vasopressinase overproduction from the placenta. Although increased vasopressinase is associated with placental volume, the regulation of placental growth in the later stage of pregnancy is not well known. Case presentation: A 16-year-old pregnant woman was urgently transferred to our hospital because of threatened premature labor when the Kumamoto earthquakes hit the area where she lived. During her hospitalization, she complained of gradually increasing symptoms of polyuria and polydipsia. The serum level of arginine vasopressin (AVP) was 1.7 pg/mL, which is inconsistent with central DI. The challenge of diagnostic treatment using oral 1-deamino-8-D-AVP (DDAVP) successfully controlled her urine and allowed for normal delivery. DDAVP tablets were not necessary to control her polyuria thereafter. Based on these observations, clinical diagnosis of GDI was confirmed. Pathophysiological analyses revealed that vasopressinase expression was more abundant in the GDI patient’s syncytiotrophoblast in placenta compared with that in a control subject. Serum vasopressinase was also observed during gestation and disappeared soon after delivery. Vasopressinase is reportedly identical to oxytocinase or insulin regulated aminopeptidase (IRAP), which is an abundant cargo protein associated with the glucose transporter 4 (GLUT4) storage vesicle. Interestingly, the expression and subcellular localization of GLUT4 appeared to occur in a vasopressinase (IRAP)-dependent manner. Conclusion: Because placental volume may be associated with vasopressinase overproduction in GDI, vasopressinase (IRAP)/GLUT4 association appears to contribute to the growth of placenta in this case. Keywords: Gestational diabetes insipidus, Vasopressinase (=insulin regulated aminopeptidase: IRAP), Glucose transporter 4 Background Diabetes insipidus (DI) during pregnancy is characterized into three categories, 1) masked central DI that has become obvious, 2) nephrogenic DI and 3) transient DI of pregnancy (gestational diabetes insipidus or GDI) due to increased production and release of vasopressinase from growing placental tissue [1]. Among these, the prevalence of GDI is approximately 1 in 30,000 pregnancies, and patients with GDI are characterized in pregnancy by polyuria and polydipsia due to placental overproduction of * Correspondence: 1 Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Chuo-Ward, Honjo, Kumamoto 860-8556, Japan Full list of author information is available at the end of the article vasopressinase, which is expressed in placental trophoblasts and degrades arginine vasopressin (AVP) [2, 3]. Although there is an increase in endogenous AVP production during pregnancy to maintain sufficient antidiuretic activity, increased degradation of AVP by placental vasopressinase may result in GDI. Because vasopressinase is metabolized in liver, hepatic dysfunction could increase the amount of circulating vasopressinase. We present here a case of GDI having threatened premature labor in a 16-year-old woman with intact hepatic function who was successfully treated with oral DDAVP tablets. We also performed pathophysiological investigation using serum and placental tissue from the patient. © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kondo et al. BMC Endocrine Disorders (2018):4 Case presentation A 16-year-old Japanese primipara was urgently transported from a regional maternity clinic to our hospital because of threatened premature labor in the 25th week of pregnancy. There was no medical or family history of note. At that time, there had been extremely powerful earthquakes occurring in the Kumamoto area where she lived, and as a result, she had been forced to stay in an emergency shelter. When she arrived at our hospital, treatment with ritodrine hydrochloride, magnesium sulfate, betamethasone and hydroxyprogesterone was initiated, and her premature uterine contractions were successfully controlled. Soon after her admission, considerable polyuria (3000– 6000 mL/day), nocturia (5–6 times a night) and polydipsia gradually became obvious (Fig. 1a). Because she was restricted to bedrest to prevent premature labor, precise diagnosis and treatment of polyuria was necessary. From the 27th to the 28th week of gestation, the amount of urine increased from 4000 to 6000 mL/day (Fig. 1a). Fasting plasma glucose levels during hospitalization were around 78–88 mg/dL and the results from a 75-g oral glucose tolerance test indicated that she was not diabetic (Table. 1). Although she developed polyuria, serum sodium levels were constant at around 137–140 mEq/L during the clinical course (Table. 1a). Serum osmolality was maintained at around 260–265 mOsm/L, while urine osmolality (191–293 mOsm/L) showed below the levels of serum osmolality, indicating that her urine concentration ability had deteriorated (Fig. 1b). The serum level of AVP was 1.7 pg/mL (0.3–3.5; Table 1), which is inconsistent with central DI. At the time of admission, hepatic dysfunction was not observed (Table 1). A water deprivation test would have been unsuitable for diagnosis in this case because dehydration can deteriorate the maternal-fetus environment. Although a precise diagnosis of GDI was not made at that time, we decided to use oral 1-deamino-8-DAVP (DDAVP) tablets for diagnostic treatment to determine whether her urine would respond to DDAVP and treat DI, as well as to rule out nephrogenic DI. Thus, the patient was first given 120 μg of oral DDAVP tablets, and then the dose of DDAVP was gradually increased to 360 μg until the amount of urine was less than 2000 mL/ day (Fig. 1a) with a urine osmolality of 305–365 mOsm/L (Fig. 1b). At the 32nd week of gestation, fetal maturation was confirmed and medical support to prevent premature contractions was ceased. Soon after this decision, a male fetus weighing 1660 g and 45 cm was delivered with a one-min (...truncated)