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Review Article Hypopituitarism and Successful Pregnancy

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Review Article Hypopituitarism and Successful Pregnancy Int J Clin Exp Med 2014;7(12):4660-4665 www.ijcem.com /ISSN:1940-5901/IJCEM0002633 Review Article Hypopituitarism and successful pregnancy Xue Du*, Qing Yuan*, Yanni Yao, Zengyan Li, Huiying Zhang Department of Obstetrics and Gynecology, General Hospital, Tianjin Medical University, Tianjin, China Received September 19, 2014; Accepted November 24, 2014; Epub December 15, 2014; Published December 30, 2014 Abstract: Hypopituitarism is a disorder characterized by the deficiency of one or more of the hormones secreted by the pituitary gland. Hypopituitarism patients may present the symptoms of amenorrhea, poor pregnancy potential, infertility, and no production of milk after delivery. Successful pregnancy in hypopituitarism patient is rare because hypopituitarism is associated with an increased risk of pregnancy complications, such as abortion, anemia, preg- nancy-induced hypertension, placental abruption, premature birth, and postpartum hemorrhage. Hypopituitarism during pregnancy and perinatal period should be managed carefully. The hormone levels should be restored to normal before pregnancy. GH and HMG-hCG are combined to improve follicular growth and the success rate of preg- nancy. Hypopituitary patients must be closely monitored as changes may need to be made to their medications, and serial ultrasound measurements are also necessary for fetal growth assessment. Keywords: Hypopituitarism, assisted reproductive techniques, pregnancy, hormone replacement Introduction pregnancy. Hypopituitarism is associated with an increased risk of pregnancy complications, Pituitary gland is the most important endocrine such as abortion, anemia, pregnancy-induced gland in the body, and composed of adenohy- hypertension, placental abruption, premature pophysis (anterior pituitary) that secretes birth, and postpartum hemorrhage [3-5]. The gonadotropins (FSH and LH), TSH, ACTH, GH, advance of assisted reproductive techniques and prolactin (PRL), and neurohypophysis (pos- makes it possible to improve the pregnancy terior pituitary) that stores antidiuretic hormone rate in hypopituitary patients. This highlights (ADH) and oxytocin released in the hypothala- the need for an accurate assessment and treat- mus. These hormones play important roles in a ment of this disease during pregnancy and peri- wide variety of physiological processes, includ- natal period. The common types of hypopituita- ing metabolism, growth and development, and rism include Simmonds’ syndrome, also refer- reproduction. Hypopituitarism is a disorder red to as Sheehan’s syndrome that occurs as a characterized by the deficiency of one or more result of ischemic pituitary necrosis due to of the hormones secreted by the pituitary severe postpartum hemorrhage, and pituitary gland. It has been suggested that damage to > dwarfism which is characterized by small stat- 50% of pituitary gland may inhibit the secretion ure but normal body proportions due to growth of anterior pituitary hormones, which in turn hormone deficiency in childhood. may affect a variety of target organs, including ovary, thyroid gland, and adrenal gland. The Dökmetaş et al. [6] investigated the clinical deficiencies of growth hormone (GH), follicle- characteristics of Sheehan’s syndrome in 20 stimulating hormone (FSH) and luteinizing hor- patients, and found that hypopituitarism due to mone (LH) are the most commonly encountered Sheehan’s syndrome could be of different [1], whereas the deficiencies of adrenocortico- degrees of severity, ranging from partial failure trophic hormone (ACTH) and/or thyroid-stimu- to panhypopituitarism. Panhypopituitarism has lating hormone (TSH) are the least [2]. been reported to occur in between 55% and Therefore, it is still possible for patients with 86% of patients with Sheehan’s syndrome, and partial necrosis of anterior pituitary to have a almost all of these patients have GH deficiency. normal ovulatory function, and even to achieve The most common causes of hypopituitarism Hypopituitarism and pregnancy are pituitary adenomas and postpartum hem- [4] found that only one patient could breastfeed orrhage, the clinical manifestations of which her baby. vary considerably, depending on the severity of hormone deficiency and the atrophy of target gla- Maternal thyroid deficiency may be detrimental nds. Patients may have isolated or combined to fetal brain development [9], and the infants pituitary hormone deficiencies, and impairment could develop respiratory distress syndrome of hormone secretion usually occurs in the and have a high risk of cognitive disorders. order of gonadotropin, thyroid hormone, and Lazarus et al. [10] showed that perinatal thyroid adrenocorticotropic hormone. Patients with dysfunction caused a significant reduction in hypogonadism may present symptoms of atro- body weight and height, delayed neurodevelop- phic breast, amenorrhea, infertility, and no pro- ment, and depression-like behaviors of the duction of milk after delivery. In recent years, infants. This is because that approximately one the rapid development of endocrinology and third of maternal thyroid hormone is delivered imaging techniques contributes significantly to to the fetus, and it plays an important role in the detection and treatment of pituitary tumors. fetal neurodevelopment in the first half of preg- However, due to the increasing incidence of nancy prior to fetal pituitary-thyroid axis devel- hypopituitarism in young adults who wants chil- opment [1]. Alexander et al. [11] showed an dren, the preparation and perinatal treatment association between gestational hypopituita- of hypopituitarism have become a topic of rism and impaired intellectual and cognitive interest. development in offspring, and Wada et al. [12] also showed irreversible damage to the audito- Effects of hypopituitarism during pregesta- ry system functions caused by perinatal hypo- tional, gestational, and postnatal period thyroidism in rats. Hypopituitary patients may present the symp- Treatment of hypopituitarism toms of amenorrhea, poor pregnancy potential, and infertility. In addition, hypopituitarism has General treatment been reported to be associated with an increa- sed risk of pregnancy complications, including Replacement of deficient hormones remains high rate of abortion during early gestation and the main treatment modality for hypopituita- postpartum uterine inertia, thus leading to rism, and the order of treatment is glucocorti- postpartum hemorrhage and poor pregnancy coid, thyroid hormone, sex hormone, and outcomes. Idris et al. [7] retrospectively studied growth hormone. In general, thyroid hormone 167 pregnancies managed in the antenatal replacement should be initiated two weeks endocrine clinic, and showed that the cesarean after glucocorticoid replacement, and it is section rate was significantly higher in hypopi- advisable to begin with low dosage to prevent tuitary patients (28.7%) than in normal local addisonian crisis. women (18%). Preparation before pregnancy Breastfeeding in the postpartum period depe- nds to a great extent on the PRL level of the Adult hypopituitary patients with hypogonad- mother. Although failure of milk production is a ism should also receive hormones to maintain typical symptom of Sheehan’s syndrome, hyper- the secondary sex characteristics and uterine prolactinemia has also been reported in pati- reproductive function. Artificial cycle treatment ents with Sheehan’s syndrome [1]. PRL defi- could stimulate the proliferation of endometri- ciency is common in panhypopituitary patients um and vaginal epithelium. It also allows the [8]. Hyposecretion of PRL can lead to failure of vaginal superficial cells to be epithelialized, and milk production in the postpartum period; on leads to increase in intracellular glycogen. The the other hand, hypersecretion of PRL can lead breakdown of glycogen to lactic acid is expect- to galactorrhea and nipple tenderness, neither ed to be beneficial for vaginal self-cleaning and of which is suitable for breastfeeding. Thus, maintenance of secondary sex characteristics. hypopituitary patients generally do not have Thus, sequential replacement of estrogen and sufficient milk production to breastfeed their progesterone is a viable method to promote babies. In a retrospective study of 18 pregnan- uterine development and prepare for pregnan- cies in 9 hypopituitary patients, Overton et al. cy. The hormone levels should be restored to 4661 Int J Clin Exp Med 2014;7(12):4660-4665 Hypopituitarism and pregnancy normal before pregnancy. High-dose estrogen The mechanisms of GH responsible for the and GH could improve the prognosis of hypopi- improved pregnancy outcomes may be that: (1) tuitarism, and GH is helpful for the preparation GH can stimulate follicular growth and matura- of uterus and conception [1]. However, in hypo- tion, and it may also facilitate ovulation by pituitary patients with hyperprolactinemia, it is increasing the sensitivity of ovarian response desirable to reduce the prolactin level to nor- to gonadotropins, such as LH and FSH, and by mal prior to the artificial cycle treatment to reducing the rate of apoptosis in preovulatory induce ovulation. Patients can be treated with ovarian follicles, which is thought to be IGF-I human menopausal gonadotropin (HMG) and mediated, while GH has no such effect in preg- human chorionic gonadotropin (hCG) during nant women with normal pituitary function [17]; preparation for pregnancy. Thomas et al. [8] (2) GH/IGF-1 has a role in fertility disorders showed that the combination of GH and HMG-
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