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Pituitary and Adrenal Disorders of Pregnancy

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Pituitary and Adrenal Disorders of Pregnancy PITUITARY AND ADRENAL DISORDERS OF PREGNANCY Melanie Nana, Specialist Registrar in Diabetes and Endocrinology, School of Life Course Sciences, Guy’s site, King’s College London, London SE1 1UL, [email protected] Catherine Williamson, Professor of Women’s Health, School of Life Course Sciences, Guy’s site, King’s College London, London SE1 1UL. [email protected] Updated April 15, 2019 ABSTRACT enlargement, compressive symptoms are not typically seen during pregnancy. The pituitary and adrenal glands play an integral role in the endocrine and physiological changes of normal pregnancy. Pituitary gland enlargement is related to estrogen- This is associated with alterations in the normal ranges of stimulated hypertrophy and hyperplasia of the lactotrophs endocrine tests and in the appearance of the glands. It is (4). While lactotroph cells maKe up 20% of anterior pituitary important for the medical team to be aware of the altered cells in the nonpregnant state, they comprise up to 60% by normal ranges for clinical tests in pregnant women. Some the third trimester of pregnancy (5). Gonadotrophs decline disorders affect women more commonly during pregnancy in number during pregnancy whilst numbers of corticotrophs or the puerperium, e.g. lymphocytic hypophysitis, while and thyrotrophs remain constant (5). Somatotrophs are other pre-existing disorders such as macroprolactinomas generally suppressed (as a consequence of negative can have worse outcomes in pregnancy. Other conditions feedbacK secondary to high levels of insulin like growth may be incidental to pregnancy, but management strategies factor-1 which is stimulated by placental growth hormone) require modification to ensure safety of the pregnant woman and may function as lactotrophs (5, 6). After the initial or fetus. This chapter describes the normal physiological increase in size postpartum there is then a reduction in size alterations in the pituitary and adrenal glands and describes back to normal by 6 months postpartum (regardless of the impact of disorders of these endocrine glands on breastfeeding status) (2). pregnant women, the fetus and children of affected women. An understanding of these anatomical changes is important It also describes the existing data with regard to safety of when investigating suspected pituitary pathology during drugs used to treat pituitary and adrenal disease in pregnancy, and also when monitoring pre-existing tumors pregnancy. (1). Investigation should be reserved for those patients with symptoms or signs consistent with tumor or pituitary PITUITARY DISORDERS IN PREGNANCY enlargement, asymmetrical growth, deviation of the stalk, or when the height of the pituitary is larger than expected in Anterior Pituitary Gland Anatomy pregnancy (7). The pituitary gland enlarges in a three-dimensional fashion The mainstay of pituitary imaging in pregnancy is non- by approximately 136% throughout pregnancy (1). There is contrast MRI, which is considered safe due to the absence a progressive linear increase in pituitary height of of ionizing radiation. There is reassuring evidence for its use approximately 0.12mm for each gestational weeK (2), and in all trimesters with no evidence for adverse pregnancy the gland is thought to reach its peak size in the first 3 days outcomes (8-10). As a precaution, it has been suggested postpartum when it may reach a height of 12mm on that 1.5-Tesla scanners should be used rather than 3.0- magnetic resonance imaging (MRI) (1, 2). The superior Tesla scanners as the specific absorption rate quadruples aspect of the gland expands to adopt a dome-like contour when the magnetic field doubles, although the risK of this is moving closer to the optic chiasm (3). Despite this theoretical (8, 11) www.EndoText.org 1 Dopamine agonists remain the treatment of choice for the Prolactin majority of patients with a prolactinoma. Bromocriptine restores ovulatory menses in 70-80% of patients with 50- INTRODUCTION 75% of patients experiencing an over 50% reduction in size of the pituitary tumor (28, 29). Cabergoline is more effective, Prolactin (PRL) is secreted by the pituitary and a number of restoring ovulatory menses in >90% of women and extra pituitary sites including the hypothalamus, achieving >90% reduction in tumor size (28, 29). lymphocytes, uterus, placenta and lactating mammary Bromocriptine, however, has a larger volume of safety data gland (12, 13). Extra-pituitary secretion, however, is thought (although the data are reassuring for both), and this should to account for only a small proportion of the overall be discussed during the pre-conception counselling period. secretion, as supported by one study which reported that In addition, bromocriptine is cheaper, and some clinicians hypophysectomized female rats had 10-20% lactogenic may elect to use it as its use has not been reported to have activity in their serum compared to control (14). In an association with heart valve disease. However, it should combination with other hormones, PRL mediates be noted that there are no published reports of cardiac valve mammogenesis, lactogenesis and galactopoiesis, and abnormalities in cabergoline-treated pregnant women or plays a role in the regulation of humoral and cellular immune their fetuses. The disadvantages with bromocriptine include responses. Placental estrogen stimulates lactotroph PRL twice-daily dosing (vs twice weeKly with cabergoline), synthesis in the first trimester (15, 16) while progesterone although this may not be strictly necessary, a greater side also stimulates prolactin secretion (17, 18). Prolactin levels effect profile, and inferior effectiveness at normalizing progressively increase throughout gestation (approximately prolactin concentrations (30, 31). For women who cannot 10-fold) (19), and then decline postpartum in non-lactating tolerate bromocriptine, cabergoline should be women. Despite increased PRL levels, the normal recommended as 70% of patients who have not responded lactotroph continues to respond to TRH and anti- to bromocriptine respond to cabergoline (32). In those who dopaminergic stimulation. Postpartum, the circadian rhythm do not achieve restoration of menses, clomiphene citrate or of PRL release is enhanced by the effects of suckling. recombinant gonadotrophin may be considered for ovulation induction (33). FERTILITY Surgical therapy is curative in approximately 70-80% of Hyperprolactinemia has been reported to account for patients with microadenomas and rarely causes between 7% and 20% of female infertility (20). It reduces hypopituitarism in expert hands. The cure rate is lower luteinizing hormone (LH) pulse amplitude and frequency (30%) in patients with macroadenomas, and the risK of through suppression of gonadotrophin-releasing hormone hypopituitarism and subsequent infertility is marKedly (GnRH) (21), and is associated with diminished positive increased (28). estrogen feedbacK on gonadotrophin secretion at mid-cycle (22). Prolactin also has a direct effect on the ovarian EFFECTS OF DOPAMINE AGONISTS ON THE granulosa cells and suppresses progesterone and estrogen DEVELOPING FETUS secretion from the ovaries (23). It can decrease estrogen levels through a direct effect on ovarian aromatase activity Bromocriptine has been shown to cross the placenta in and by blocking the stimulatory effects of follicle-stimulating human studies (34); cabergoline lacKs human data but has hormone (FSH) (24, 25). At high levels PRL also inhibits been found to do so in animal studies. Current progesterone production (26). As a consequence, most recommendations, therefore, advise that women with hyperprolactinemic women become anovulatory with prolactinomas discontinue dopamine agonist therapy when resultant amenorrhea and infertility (27). they discover that they are pregnant (29). There is a subset of patients in whom this may not apply, e.g. women with PRECONCEPTION MANAGEMENT AND RESTORATION macroadenomas, in particular those with an invasive tumor OF MENSES or where it is abutting the optic chiasm. In such cases, the management must be considered on a case by case basis. www.EndoText.org 2 In the majority of cases, in order to limit the exposure time Such short-term exposure to both bromocriptine and to the developing fetus it is beneficial to know the timing of cabergoline is unavoidable but reassuringly pregnancy the normal menstrual cycle. Use of mechanical outcomes with respect to spontaneous abortions, contraception may facilitate this if used for the first two to terminations, ectopic pregnancies, pre-term births, multiple three cycles after starting treatment. As a consequence, pregnancies, and malformations do not differ from the women will know when they have missed a period, a normal population Table 1 summarizes outcome data from pregnancy test can be performed in a timely manner and 6239 pregnancies following bromocriptine treatment and the dopamine agonist can be stopped in cases where a 968 where the mother tooK cabergoline (21). There was no pregnancy is confirmed. This approach aims to limit the time increased risK demonstrated by either drug but due to the that the fetus is exposed to bromocriptine to 3-4 weeKs and greater wealth of experience with bromocriptine it is the cabergoline to around 5 weeKs (as a consequence of its preferred drug of choice for those wishing to become longer half-life (21). pregnant according to the European guideline (29). Table 1. Pregnancy Outcomes While Taking Bromocriptine or Cabergoline Compared to the Normal Population Bromocriptine
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