3 185 A Luger and others ESE CPG on pituitary adenomas 185:3 G1–G33 Clinical Practice in pregnancy Guideline ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy A Luger1, L H A Broersen2, N R Biermasz3, B M K Biller4, M Buchfelder5, P Chanson 6, J O L Jorgensen 7, F Kelestimur8, S Llahana9, D Maiter10, G Mintziori11, F Petraglia12, R Verkauskiene13, S M Webb 14 and O M Dekkers 15,16,17 1Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria, 2Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands, 3Division of Endocrinology, Department of Medicine, Pituitary Center and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands, 4Neuroendocrine & Pituitary Tumor Clinical Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA, 5Department of Neurosurgery, University Hospital Erlangen, Erlangen, Germany, 6Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction et Centre de Réference des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France, 7Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark, 8Department of Endocrinology, Yeditepe University, Istanbul, Turkey, 9School of Health Sciences, City, University of London, London, UK, 10Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium, 11Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki Medical School, Thessaloniki, Greece, 12Department of Obstetrics and Gynecology, University of Florence, Florence, Italy, 13Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania, 14IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, Universitat Autónoma de Barcelona, and Centro de Correspondence Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unit 747), ISCIII, Barcelona, Spain, 15Department should be addressed of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands, 16Department of Clinical to A Luger Endocrinology, Leiden University Medical Center, Leiden, The Netherlands, and 17Department of Clinical Email Epidemiology, Aarhus University, Aarhus, Denmark anton.luger@meduniwien. ac.at Abstract European Journal of Endocrinology Pregnancies are rare in women with pituitary adenomas, which may relate to hormone excess from secretory subtypes such as prolactinomas or corticotroph adenomas. Decreased fertility may also result from pituitary hormone deficiencies due to compression of the gland by large tumours and/or surgical or radiation treatment of the lesion. Counselling premenopausal women with pituitary adenomas about their chance of conceiving spontaneously or with assisted reproductive technology, and the optimal pre-conception treatment, should start at the time of initial diagnosis. The normal physiological changes during pregnancy need to be considered when interpreting endocrine tests in women with pituitary adenomas. Dose adjustments in hormone substitution therapies may be needed across the trimesters. When medical therapy is used for pituitary hormone excess, consideration should be given to the known efficacy and safety data specific to pregnant women for each therapeutic option. In healthy women, pituitary gland size increases during pregnancy. Since some pituitary adenomas also enlarge during pregnancy, there is a risk of visual impairment, especially in women with macroadenomas or tumours near the optic chiasm. Pituitary apoplexy represents a rare acute complication of adenomas requiring surveillance, with surgical intervention needed in some cases. This guideline describes the choice and timing of diagnostic tests and treatments from the pre-conception stage until after delivery, taking into account adenoma size, location and endocrine activity. In most cases, pregnant women with pituitary adenomas should be managed by a multidisciplinary team in a centre specialised in the treatment of such tumours. European Journal of Endocrinology (2021) 185, G1–G33 https://eje.bioscientifica.com © 2021 European Society of Endocrinology Published by Bioscientifica Ltd. https://doi.org/10.1530/EJE-21-0462 Printed in Great Britain Downloaded from Bioscientifica.com at 09/28/2021 03:15:02AM via free access -21-0462 Clinical Practice Guideline A Luger and others ESE CPG on pituitary adenomas 185:3 G2 in pregnancy 1. Overview of recommendations if medical tumour treatment is unfeasible or ineffective (⊕⊕◯◯). General recommendations: Pre-conception stage R.2.7. If surgery is indicated, we suggest to perform R.1.1. We recommend that women of reproductive age transsphenoidal surgery in the second trimester if the with a diagnosis of a pituitary adenoma be counselled clinical course allows this (⊕⊕◯◯). about their potential fertility and pregnancy outcomes R.2.8. We recommend not to perform radiotherapy as early as possible. during pregnancy. R.1.2. We recommend that women of reproductive age with a diagnosis of pituitary adenoma, functioning or General recommendations: Delivery nonfunctioning, who consider pregnancy, be managed by and breastfeeding an endocrinologist. R.1.3. We recommend that management of women of R.3.1. We suggest that pregnant women with pituitary reproductive age with a large pituitary adenoma (>1 cm), adenomas should receive standard obstetrical care but Cushing’s disease or acromegaly, who consider pregnancy, recommend close maternal and foetal surveillance. be discussed in a multidisciplinary team. R.3.2. In general, breastfeeding is feasible and not R.1.4. We recommend that in women with a diagnosis contraindicated. of pituitary adenoma and hypopituitarism, hormone replacement therapy should be initiated or optimised prior to becoming pregnant. Nonfunctioning adenomas (NFAs) R.4.1. In women with an NFA near the optic chiasm who are planning a pregnancy, surgery may be considered to General recommendations: Pregnancy reduce the risk of chiasmal compression and to enhance R.2.1. We recommend that pregnant women with a fertility. known pituitary adenoma, in particular those with a R.4.2. We suggest that for women with intrasellar large pituitary adenoma (>1 cm), Cushing’s disease or nonfunctioning microadenomas and an uneventful acromegaly, and those with pituitary deficiencies, should pregnancy, there is no need for routine endocrinological be followed by an endocrinologist and an advanced nurse follow-up during pregnancy. practitioner where relevant. The frequency depends on the R.4.3. We recommend that for macroadenomas and/or European Journal of Endocrinology underlying condition and individualised needs. extrasellar NFAs, neuro-ophthalmologic and, if indicated, R.2.2. We recommend that pregnant women with MRI examination should be performed only in case of diagnosed hypopituitarism should have regular clinical symptoms of tumour progression or pituitary apoplexy and hormonal follow-up by an endocrinologist and an during pregnancy. advanced nurse practitioner where relevant. R.4.4. We recommend that in case of a clinical need to R.2.3. We recommend that women and their partners reduce adenoma volume during pregnancy, surgery is the be provided with education for glucocorticoid stress dose preferred option (⊕◯◯◯). adjustment and measures on how to prevent or manage R.4.5. We recommend awaiting reassessment of pituitary adrenal crisis during pregnancy. imaging and function until after delivery and breastfeeding. R.2.4. We recommend performing an MRI without contrast in pregnancy in case of symptoms of tumour Prolactinomas progression or apoplexy. R.2.5. We recommend that neuro-ophthalmologic R.5.1. We recommend treating women with a examination in pregnancy be performed for adenomas prolactinoma, who are actively seeking pregnancy, impinging visual pathways or in case of suspected tumour with a dopamine agonist and strive for normalisation of progression or pituitary apoplexy. prolactin concentrations and restoration of regular R.2.6. We recommend considering surgery in pregnant ovulatory cycles (⊕⊕⊕◯). women with deterioration of vision, ophthalmoplegia R.5.2. We recommend medical treatment as first-choice or severe headache attributable to tumour enlargement therapy for women with a prolactinoma and actively https://eje.bioscientifica.com Downloaded from Bioscientifica.com at 09/28/2021 03:15:02AM via free access Clinical Practice Guideline A Luger and others ESE CPG on pituitary adenomas 185:3 G3 in pregnancy seeking pregnancy; transsphenoidal surgery can be treatment, somatostatin analogues or cabergoline can considered in individual cases (⊕⊕⊕◯). be used until confirmation of pregnancy if surgery is not R.5.3. We recommend cabergoline as medical treatment an option. Pegvisomant should be reserved for selected at the lowest possible effective dose until pregnancy is uncontrolled cases (⊕◯◯◯). confirmed ⊕( ⊕◯◯). R.6.5. We recommend to consider stopping drugs for R.5.4. We recommend stopping the dopamine agonist acromegaly once pregnancy is established (⊕◯◯◯). once pregnancy is established. However, dopamine R.6.6. We recommend not to measure GH and IGF-I agonists may be given for a longer gestational