Pituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?

Abstract

The diagnosis and treatment of pituitary disease in pregnancy represents a special clinical challenge. Not least because there is very little data on the treatment of pregnant patients with pituitary disorders. A selective search of the literature was carried out with the aim of compiling evidence about the diagnosis and treatment of pituitary disease in pregnancy. The search covered the databases PubMed/MEDLINE including PubMed Central and also used the Livivo (ZB MED) search engine. Recent studies were evaluated for recommendations about the care of pregnant patients with hormone-inactive and hormone-active pituitary adenomas (prolactinoma, acromegaly and Cushingʼs disease), pituitary insufficiency, pituitary apoplexy and hypophysitis. The most well-established forms of treatment are for prolactinoma, due to the incidence of this disease and its impact on fertility. When pregnancy has been confirmed, prolactinoma treatment with dopamine agonists should be paused. Although microprolactinomas rarely increase significantly in size after the administration of dopamine agonists is discontinued, symptomatic tumor growth of macroprolactinomas can occur. In such cases, treatment with dopamine agonists can be resumed. If the primary tumor is large and the risk that it will continue to grow is high, it may be necessary to continue medical treatment from the start of pregnancy. If one of the partners has a pituitary disorder, it is often still possible for many couples to achieve their wish of having children if they receive medical support to plan and the pregnancy is carefully monitored. Given the complexity of pituitary disease, pregnant patients with pituitary disorders should be cared for and treated by a multidisciplinary team in centers specializing in the diagnosis and treatment of pituitary disease.

Key words

pituitary disease - pituitary tumor - pregnancy - fertility - diabetes insipidus

• References/Literatur

• 1 Karaca Z, Tanriverdi F, Unluhizarci K. et al. Pregnancy and pituitary disorders. Eur J Endocrinol 2010; 162: 453-475
• 2 Muhammad A, Neggers SJ, van der Lely AJ. Pregnancy and acromegaly. Pituitary 2017; 20: 179-184
• 3 Glezer A, Jallad RS, Machado MC. et al. Pregnancy and pituitary adenomas. Minerva Endocrinol 2016; 41: 341-350
• 4 Alexander EK, Pearce EN, Brent GA. et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 2017; 27: 315-389
• 5 Melmed S, Casanueva FF, Hoffman AR. et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 273-288
• 6 Molitch ME. Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma. Eur J Endocrinol 2015; 172: R205-R213
• 7 Lebbe M, Hubinont C, Bernard P. et al. Outcome of 100 pregnancies initiated under treatment with cabergoline in hyperprolactinaemic women. Clin Endocrinol (Oxf) 2010; 73: 236-242
• 8 Molitch ME. Pituitary tumors and pregnancy. Growth Horm IGF Res 2003; 13 (Suppl. A) S38-S44
• 9 Almalki MH, Ur E, Johnson M. et al. Management of prolactinomas during pregnancy – a survey of four Canadian provinces. Clin Invest Med 2012; 35: E96-E104
• 10 Schock H, Zeleniuch-Jacquotte A, Lundin E. et al. Hormone concentrations throughout uncomplicated pregnancies: a longitudinal study. BMC Pregnancy Childbirth 2016; 16: 146
• 11 Almalki MH, Alzahrani S, Alshahrani F. et al. Managing Prolactinomas during Pregnancy. Front Endocrinol (Lausanne) 2015; 6: 85
• 12 Schlechte J, Dolan K, Sherman B. et al. The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab 1989; 68: 412-418
• 13 Lambert K, Rees K, Seed PT. et al. Macroprolactinomas and Nonfunctioning Pituitary Adenomas and Pregnancy Outcomes. Obstet Gynecol 2017; 129: 185-194
• 14 Galland F, Vantyghem MC, Cazabat L. et al. Management of nonfunctioning pituitary incidentaloma. Ann Endocrinol (Paris) 2015; 76: 191-200
• 15 Araujo PB, Vieira Neto L, Gadelha MR. Pituitary tumor management in pregnancy. Endocrinol Metab Clin North Am 2015; 44: 181-197
• 16 Greenman Y, Cooper O, Yaish I. et al. Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists. Eur J Endocrinol 2016; 175: 63-72
• 17 Chanson P, Raverot G, Castinetti F. et al. Management of clinically non-functioning pituitary adenoma. Ann Endocrinol (Paris) 2015; 76: 239-247
• 18 Lusis EA, Scheithauer BW, Yachnis AT. et al. Meningiomas in pregnancy: a clinicopathologic study of 17 cases. Neurosurgery 2012; 71: 951-961
• 19 Moscovici S, Fraifeld S, Cohen JE. et al. Parasellar meningiomas in pregnancy: surgical results and visual outcomes. World Neurosurg 2014; 82: e503-e512
• 20 Laviv Y, Bayoumi A, Mahadevan A. et al. Meningiomas in pregnancy: timing of surgery and clinical outcomes as observed in 104 cases and establishment of a best management strategy. Acta Neurochir (Wien) 2018; 160: 1521-1529
• 21 Melmed S. Acromegaly. N Engl J Med 1990; 322: 966-977
• 22 Thorner MO, Frohman LA, Leong DA. et al. Extrahypothalamic growth-hormone-releasing factor (GRF) secretion is a rare cause of acromegaly: plasma GRF levels in 177 acromegalic patients. J Clin Endocrinol Metab 1984; 59: 846-849
• 23 Fleseriu M. Medical treatment of acromegaly in pregnancy, highlights on new reports. Endocrine 2015; 49: 577-579
• 24 Caron P, Broussaud S, Bertherat J. et al. Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women. J Clin Endocrinol Metab 2010; 95: 4680-4687
• 25 Katznelson L, Laws jr. ER, Melmed S. et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99: 3933-3951
• 26 Caron P. Acromegaly and pregnancy. Ann Endocrinol (Paris) 2011; 72: 282-286
• 27 Jallad RS, Shimon I, Fraenkel M. et al. Outcome of pregnancies in a large cohort of women with acromegaly. Clin Endocrinol (Oxf) 2018; 88: 896-907
• 28 Brian SR, Bidlingmaier M, Wajnrajch MP. et al. Treatment of acromegaly with pegvisomant during pregnancy: maternal and fetal effects. J Clin Endocrinol Metab 2007; 92: 3374-3377
• 29 van der Lely AJ, Gomez R, Heissler JF. et al. Pregnancy in acromegaly patients treated with pegvisomant. Endocrine 2015; 49: 769-773
• 30 Novartis Pharma GmbH. Sandostatin^® LAR^®-Fachinformation. Stand: Februar 2018.
• 31 Pfizer Pharma GmbH. Somavert^® Fachinformation. Stand August 2018.
• 32 Ipsen Pharma GmbH. Somatuline^® Fachinformation. Stand Februar 2015.
• 33 Caimari F, Valassi E, Garbayo P. et al. Cushingʼs syndrome and pregnancy outcomes: a systematic review of published cases. Endocrine 2017; 55: 555-563
• 34 Caimari F, Corcoy R, Webb SM. Cushingʼs disease: major difficulties in diagnosis and management during pregnancy. Minerva Endocrinol 2018; 43: 435-445 doi:10.23736/S0391-1977.18.02803-1
• 35 Carr BR, Parker jr. CR, Madden JD. et al. Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am J Obstet Gynecol 1981; 139: 416-422
• 36 Odagiri E, Ishiwatari N, Abe Y. et al. Hypercortisolism and the resistance to dexamethasone suppression during gestation. Endocrinol Jpn 1988; 35: 685-690
• 37 Viardot A, Huber P, Puder JJ. et al. Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test. J Clin Endocrinol Metab 2005; 90: 5730-5736
• 38 Lindsay JR, Jonklaas J, Oldfield EH. et al. Cushingʼs syndrome during pregnancy: personal experience and review of the literature. J Clin Endocrinol Metab 2005; 90: 3077-3083
• 39 Bronstein MD, Machado MC, Fragoso MC. Management of endocrine disease: management of pregnant patients with Cushingʼs syndrome. Eur J Endocrinol 2015; 173: R85-R91
• 40 Burman P, Eden-Engstrom B, Ekman B. et al. Limited value of cabergoline in Cushingʼs disease: a prospective study of a 6-week treatment in 20 patients. Eur J Endocrinol 2016; 174: 17-24
• 41 Pivonello R, De Martino MC, Cappabianca P. et al. The medical treatment of Cushingʼs disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab 2009; 94: 223-230
• 42 Nakhleh A, Saiegh L, Reut M. et al. Cabergoline treatment for recurrent Cushingʼs disease during pregnancy. Hormones (Athens) 2016; 15: 453-458
• 43 Woo I, Ehsanipoor RM. Cabergoline therapy for Cushing disease throughout pregnancy. Obstet Gynecol 2013; 122: 485-487
• 44 Reincke M, Ritzel K, Osswald A. et al. A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushingʼs syndrome. Eur J Endocrinol 2015; 173: M23-M32
• 45 Chrisoulidou A, Boudina M, Karavitaki N. et al. Pituitary disorders in pregnancy. Hormones (Athens) 2015; 14: 70-80
• 46 Honegger J, Giese S. Acute pituitary disease in pregnancy: how to handle hypophysitis and Sheehanʼs syndrome?. Minerva Endocrinol 2018; 43: 465-475
• 47 Faje A, Tritos NA, Swearingen B, Klibanski A. Neuroendocrine Disorders: pituitary Imaging. In: Masdeu JC, González RG. eds. Handbook of clinical Neurology, Neuroimaging, Part II. Amsterdam, Niederlande: Elsevier; 2016: 873-885
• 48 Broekman M, Goedee SH, Nieuwlaat WA. et al. Corticosteroid treatment buys time in case of a newly diagnosed hypophysitis with visual deterioration. BMJ Case Rep 2013;
• 49 Honegger J, Buchfelder M, Schlaffer S. et al. Treatment of Primary Hypophysitis in Germany. J Clin Endocrinol Metab 2015; 100: 3460-3469
• 50 Oldfield EH, Merrill MJ. Apoplexy of pituitary adenomas: the perfect storm. J Neurosurg 2015; 122: 1444-1449
• 51 Grzywotz A, Kleist B, Moller LC. et al. Pituitary apoplexy – A single center retrospective study from the neurosurgical perspective and review of the literature. Clin Neurol Neurosurg 2017; 163: 39-45
• 52 GrandʼMaison S, Weber F, Bedard MJ. et al. Pituitary apoplexy in pregnancy: A case series and literature review. Obstet Med 2015; 8: 177-183
• 53 Karaca Z, Laway BA, Dokmetas HS. et al. Sheehan syndrome. Nat Rev Dis Primers 2016; 2: 16092
• 54 Prabhakar VK, Shalet SM. Aetiology, diagnosis, and management of hypopituitarism in adult life. Postgrad Med J 2006; 82: 259-266
• 55 Kubler K, Klingmuller D, Gembruch U. et al. High-risk pregnancy management in women with hypopituitarism. J Perinatol 2009; 29: 89-95
• 56 Overton CE, Davis CJ, West C. et al. High risk pregnancies in hypopituitary women. Hum Reprod 2002; 17: 1464-1467
• 57 Davis LE, Leveno KJ, Cunningham FG. Hypothyroidism complicating pregnancy. Obstet Gynecol 1988; 72: 108-112
• 58 Stagnaro-Green A, Abalovich M, Alexander E. et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21: 1081-1125
• 59 McNeil AR, Stanford PE. Reporting Thyroid Function Tests in Pregnancy. Clin Biochem Rev 2015; 36: 109-126
• 60 Alexander EK, Marqusee E, Lawrence J. et al. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med 2004; 351: 241-249
• 61 Stagnaro-Green A, Abalovich M, Alexander E. et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21: 1081-1125
• 62 Henrichs J, Bongers-Schokking JJ, Schenk JJ. et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metab 2010; 95: 4227-4234
• 63 Lindsay JR, Nieman LK. The hypothalamic-pituitary-adrenal axis in pregnancy: challenges in disease detection and treatment. Endocr Rev 2005; 26: 775-799
• 64 Ambroziak U, Kondracka A, Bartoszewicz Z. et al. The morning and late-night salivary cortisol ranges for healthy women may be used in pregnancy. Clin Endocrinol (Oxf) 2015; 83: 774-778
• 65 Yuen KC, Chong LE, Koch CA. Adrenal insufficiency in pregnancy: challenging issues in diagnosis and management. Endocrine 2013; 44: 283-292
• 66 Langlois F, Lim DST, Fleseriu M. Update on adrenal insufficiency: diagnosis and management in pregnancy. Curr Opin Endocrinol Diabetes Obes 2017; 24: 184-192
• 67 Nolten WE, Lindheimer MD, Oparil S. et al. Desoxycorticosterone in normal pregnancy. I. Sequential studies of the secretory patterns of desoxycorticosterone, aldosterone, and cortisol. Am J Obstet Gynecol 1978; 132: 414-420
• 68 McKenna DS, Wittber GM, Nagaraja HN. et al. The effects of repeat doses of antenatal corticosteroids on maternal adrenal function. Am J Obstet Gynecol 2000; 183: 669-673
• 69 Schulte HM, Weisner D, Allolio B. The corticotrophin releasing hormone test in late pregnancy: lack of adrenocorticotrophin and cortisol response. Clin Endocrinol (Oxf) 1990; 33: 99-106
• 70 Vila G, Akerblad AC, Mattsson AF. et al. Pregnancy outcomes in women with growth hormone deficiency. Fertil Steril 2015; 104: 1210-1217.e1
• 71 Curran AJ, Peacey SR, Shalet SM. Is maternal growth hormone essential for a normal pregnancy?. Eur J Endocrinol 1998; 139: 54-58
• 72 Davison JM, Sheills EA, Philips PR. et al. Metabolic clearance of vasopressin and an analogue resistant to vasopressinase in human pregnancy. Am J Physiol 1993; 264: F348-F353
• 73 Katz VL, Bowes jr. WA. Transient diabetes insipidus and preeclampsia. South Med J 1987; 80: 524-525
• 74 Bellastella A, Bizzarro A, Colella C. et al. Subclinical diabetes insipidus. Best Pract Res Clin Endocrinol Metab 2012; 26: 471-483
• 75 Sende P, Pantelakis N, Suzuki K. et al. Plasma oxytocin determinations in pregnancy with diabetes insipidus. Obstet Gynecol 1976; 48: 38S-41S
• 76 Cobo E, De Bernal M, Gaitan E. Low oxytocin secretion in diabetes insipidus associated with normal labor. Am J Obstet Gynecol 1972; 114: 861-866
• 77 Quigley J, Shelton C, Issa B. et al. Diabetes insipidus in pregnancy. Obstet Gynaecol 2018; 20: 41-48
• 78 Ray JG. DDAVP use during pregnancy: an analysis of its safety for mother and child. Obstet Gynecol Surv 1998; 53: 450-455
• 79 Daughters K, Manstead ASR, Rees DA. Hypopituitarism is associated with lower oxytocin concentrations and reduced empathic ability. Endocrine 2017; 57: 166-174
• 80 Nishimori K, Young LJ, Guo Q. et al. Oxytocin is required for nursing but is not essential for parturition or reproductive behavior. Proc Natl Acad Sci U S A 1996; 93: 11699-11704
• 81 Shinar S, Many A, Maslovitz S. Questioning the role of pituitary oxytocin in parturition: spontaneous onset of labor in women with panhypopituitarism–a case series. Eur J Obstet Gynecol Reprod Biol 2016; 197: 83-85
• 82 Rohayem J, Sinthofen N, Nieschlag E. et al. Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults. Andrology 2016; 4: 87-94
• 83 Liu PY, Baker HW, Jayadev V. et al. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab 2009; 94: 801-808
• 84 Carone D, Caropreso C, Vitti A. et al. Efficacy of different gonadotropin combinations to support ovulation induction in WHO type I anovulation infertility: clinical evidences of human recombinant FSH/human recombinant LH in a 2:1 ratio and highly purified human menopausal gonadotropin stimulation protocols. J Endocrinol Invest 2012; 35: 996-1002
• 85 [Anonym] Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. The European Recombinant Human LH Study Group. J Clin Endocrinol Metab 1998; 83: 1507-1514
• 86 Milardi D, Giampietro A, Baldelli R. et al. Fertility and hypopituitarism. J Endocrinol Invest 2008; 31: 71-74
• 87 Drakopoulos P, Pluchino N, Bischof P. et al. Effect of Growth Hormone on Endometrial Thickness and Fertility Outcome in the Treatment of Women with Panhypopituitarism: A Case Report. J Reprod Med 2016; 61: 78-82
• 88 Zitzmann M, Behre HM, Kliesch S. Gonadotropin treatment in male infertility. J Reproduktionsmed Endokrinol 2013; 10 (Sonderheft 1): 23-28
• 89 Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol 2000; 161: 73-88