DOI: https://doi.org/10.18370/2309-4117.2019.49.24-28

Pregnancy management in patients with acromegaly

L. B. Markin, K. L. Shatylovych

Abstract


Acromegaly is a rare, chronic, endocrine disorder, usually caused by hypersecretion of growth hormone (GH) for a prolonged period from a somatotroph adenoma. Hormonal evaluation becomes more complex in pregnant women due to physiological changes in the pituitary and target hormone levels, binding globulins, and placental hormones. Evaluation of pituitary functions in pregnant women is quite different from nonpregnant women because of physiological hormonal changes. Pregnancy in acromegaly continues to be an uncommon event and a challenge for clinicians despite the positive impact of current treatments on survival and quality of life. Diagnosis of acromegaly during pregnancy is difficult because of changes in GH and insulin like growth factor 1 (IGF 1) levels, GH production by placenta, and the inability of routine methods to distinguish the pituitary GH from placental GH.

In the majority of patients with acromegaly pregnancy does not have an adverse effect on mother or fetus and pituitary mass does not increase in size. Tumor enlargement may theoretically occur if pre-existing therapies such as somatostatin analogues are discontinued with the onset of pregnancy. Acromegalic symptoms may improve during pregnancy, possibly from the increased estrogen production inhibiting hepatic IGF 1 production. Pregnancy course is mostly uneventful but the literature indicates an increased risk of gestational diabetes and gravid hypertension in women with non-controlled GH/IGF 1 hypersecretion before gestation.

In case of tumor enlargement frequent monitoring is required, surgery can be considered in the second trimester. Dopamine agonists and somatostatin analogs can be used without any adverse consequences on mother or fetus. In pregnancy acromegaly medical therapy should be withheld and administered only for tumor growth and headache control during pregnancy. Breast feeding does not affect the course of acromegaly. Postpartum pituitary imaging demonstrates no increased tumor growth after pregnancy.


Keywords


acromegaly; pregnancy; growth hormone; insulin like growth factor-1; dopamine agonists; somatostatin analogs

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References


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Dias, M.L., Vieira, J.G., Abucham, J. “Detecting and solving the interference of pregnancy serum, in a GH immunometric assay.” Growth Hormone IGF Research 23 (2013): 13–8. DOI: 10.1016/j.ghir.2012.11.001

Feldt-Rasmussen, U., Mathiesen, E.R. “Endocrine disorders in pregnancy: physiological and hormonal aspects of pregnancy. Best Practice & Research.” Clinical Endocrinology & Metabolism 25 (2011): 875–84. DOI: 10.1016/j.beem.2011.07.004

Petersenn, S., Christ-Crain, M., Droste, M., et al. “Pituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?” Geburtshilfe Frauenheilkd Apr 79.4 (2019): 365–74. DOI: 10.1055/a-0794-7587

Cheng, V., Faiman, C., Kennedy, L., et al. “Pregnancy and acromegaly: a review.” Pituitary 15 (2012): 59–63. DOI: 10.1007/s11102-011-0330-3

Katznelson, L., Laws, E.R. Jr., Melmed, S., et al. “Acromegaly: an endocrine society clinical practice guideline.” J Clin Endocrinol Metab 99 (2014): 3933–51. DOI: 10.1210/jc.2014-2700

Al Dallal, S. “Acromegaly: a challenging condition to diagnose.” International Journal of General Medicine 11 (2018): 337–43. DOI: 10.2147/IJGM.S169611

Fleseriu, M. “Medical treatment of acromegaly in pregnancy, highlights on new reports.” Endocrine 49 (2015): 577–9. DOI: 10.1007/s12020-015-0603-0

Kaltsas, G., Androulakis, I., Tziveriotis, K., et al. “Polycystic ovaries and the polycystic ovary syndrome phenotype in women with active acromegaly.” Clin Endocrinol 67 (2007): 917–22. DOI: 10.1111/j.1365-2265.2007.02987

Lebbe, M., Hubinont, C., Bernard, P., et al. “Outcome of 100 pregnancies initiated under treatment with cabergoline in hyperprolactinaemic women.” Clin Endocrinol 73 (2010): 236–42. DOI: 10.1111/j.1365-2265.2010

Grynberg, M., Salenave, S., Young, J., et al. “Female gonadal function before and after treatment of acromegaly.” Journal of Clinical Endocrinology and Metabolism 95 (2010): 4518–25. DOI: 10.1210/jc.2009-2815

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Frankenne, F., Closset, J., Gomez, F., et al. “The physiology of growth hormones (GHs) in pregnant women and partial characterization of the placental GH variant.” J Clin Endocrinol Metab 66 (1988): 1171–80. DOI: 10.1210/jcem-66-6-1171

Feldt-Rasmussen, U., Mathiesen, E.R. “Endocrine disorders in pregnancy: Physiological and hormonal aspects of pregnancy.” Best Pract Res Clin Endocrinol Metab 25 (2011): 875–84. DOI: 10.1016/j.beem.2011.07.004

Laway, B. “Pregnancy in acromegaly.” Therapeutic advances in endocrinology and metabolism 6.6 (2015): 1–6. DOI: 10.1177/2042018815603927

Velegrakis, A., Sfakiotaki, M., Sifakis, S. “Human placental growth hormone in normal and abnormal fetal growth.” Biomed Rep 7.2 (2017): 115–22. DOI: 10.3892/br.2017.930

Shimatsu, A., Usui, T., Tagami, T., et al. “Suppressed levels of growth hormone and insulin-like growth factor-1 during successful pregnancy in persistent acromegaly.” Endocrine Journal 57 (2010): 551–3. DOI: 10.1507/endocrj.K10E-069

Beckers, A., Stevenaert, A., Foidart, J.M., et al. “Placental and pituitary growth hormone secretion during pregnancy in acromegalic women.” Journal of Clinical Endocrinology and Metabolism 71 (1990): 725–31. DOI: 10.1210/jcem-71-3-725

Dias, M., Boguszewski, C., Gadelha, M., et al. “Acromegaly and pregnancy: a prospective study.” European Journal of Endocrinology 170 (2014): 301–10. DOI: 10.1530/EJE-13-046

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Caron, P., Broussaud, S., Bertherat, J., et al. “Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women.” Journal of Clinical Endocrinology and Metabolism 95 (2010): 4680–7. DOI: 10.1210/jc. 2009-2331

Laway, B.A. “Pregnancy in acromegaly.” Ther Adv Endocrinol Metab 6.6 (2015): 267–72. DOI: 10.1177/2042018815603927

Famini, P., Maya, M.M., Melmed, S. “Pituitary Magnetic Resonance Imaging for Sellar and Parasellar Masses: Ten-Year Experience in 2598 Patients.” J Clin Endocrinol Metab 96.6 (2011): 1633–41. DOI: 10.1210/jc.2011-0168

Tosaka, M., Higuchi, T., Horiguchi, K. “Preoperative Evaluation of Sellar and Parasellar Macrolesions by [18F] Fluorodeoxyglucose Positron Emission Tomography.” World Neurosurg 103 (2017): 591–9. DOI: 10.1016/j.wneu.2017.04.032

Lau, S.L., McGrath, S., Evain-Brion, D., et al. “Clinical and biochemical improvement in acromegaly during pregnancy.” J of Endocrin Invest 31 (2008): 255–61. DOI: 10.1007/BF03345599

Caron, C., Buscail, L., Beckers, A., et al. “Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy.” The Journal of Clinical Endocrinology & Metabolism 82.11 (1997): 3771–6. DOI: 10.1210/jcem.82.11.4350

Araujo, P.B., Neto, L.V., Gadelha, M.R. “Pituitary Tumor Management in Pregnancy.” Endocrinol Metab Clin North Am 44 (2015): 181–97. DOI: 10.1016/j.ecl.2014.10.015

Melmed, S., Casanueva, F.F., Klibanski, A., et al. “A consensus on the diagnosis and treatment of acromegaly complications.” Pituitary 16 (2012): 294–302. DOI: 10.1007/s11102-012-0420-x

Ramirez, C., Vargas, G., Gonzalez, B. “Discontinuation of octreotide LAR after long term, successful treatment of patients with acromegaly: is it worth trying?” European Journal of Endocrinology 166 (2012): 21–6. DOI: 10.1530/EJE-11-0738

Kasuki, L., Neto, L.V., Takiya, C.M., et al. “Growth of an aggressive tumor during pregnancy in an acromegalic patient.” Endocrine Journal 59 (2012): 313–9. DOI: 10.1507/endocrj.EJ11-0306

Adelman, D.T., Liebert, K.J., Nachtigall, L.B., et al. “Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment.” Int J Gen Med 6 (2013): 31–8. DOI: 10.2147/IJGM.S38594

Abreu, A, Tovar, A.P., Castellanos, R., et al. “Challenges in the diagnosis and management of acromegaly: a focus on comorbidities.” Pituitary 19.4 (2016): 448–57. DOI: 10.1007/s11102-016-0725-2

Leung, K.C., Johannsson, G., Leong, G.M., et al. “Estrogen regulation of growth hormone action.” Endocrine Reviews 25.5 (2004): 693–721. DOI: 10.1210/er.2003-0035

Shimon, I., Barkan, A. “Estrogen treatment for acromegaly.” Pituitary 15 (2012): 601–7. DOI: 10.1007/s11102-012-0426-4

Clemmons, D.R. “Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays.” Clin Chem 57.4 (2011): 555–9. DOI: 10.1373/clinchem.2010.150631

Rosario, P.W., Calsolari, M.R. “Laboratory investigation of acromegaly: Is basal or random GH > 0.4 µg/L in the presence of normal serum IGF1 an important result?” Arch Endocrinol Metab 59.1 (2015): 54–8. DOI: 10.1590/2359-3997000000010

Van der Lely, A.J., Gomez, R., Heissler, J.F., et al. “Pregnancy in acromegaly patients treated with pegvisomant.” Endocrine 49.3 (2014): 769–73. DOI: 10.1007/s12020-014-0508-3

Paragliola, R.M., Salvatori, R. “Novel Somatostatin Receptor Ligands Therapies for Acromegaly.” Front Endocrinol (Lausanne) 7.9 (2018): 78. DOI: 10.3389/fendo.2018.00078

Colao, A., Abs, R., Barcena, D.G., et al. “Pregnancy outcomes following cabergoline treatment: extended results from a 12-year observational study.” Clinical Endocrinology 68 (2008): 66–71. DOI: 10.1111/j.1365-2265.2007.03000.x

Colao, A., Auriemma, R.S., Pivonello, R. “The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly.” Pituitary 19.2 (2016): 210–21. DOI: 10.1007/s11102-015-0677-y

Paragliola, R.M., Corsello, S.M., Salvatori, R. “Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance.” Pituitary 20.1 (2017): 109–15. DOI: 10.1007/s11102-016-0768-4

Anthony, L., Freda, P.U. “From somatostatin to octreotide LAR: evolution of a somatostatin analogue.” Curr Med Res Opin 25.12 (2009): 2989–99. DOI: 10.1185/03007990903328959

Cuevas-Ramos, D., Fleseriu, M. “Somatostatin receptor ligands and resistance to treatment in pituitary adenomas.” J Mol Endocrinol 52.3 (2014): 223–40. DOI: 10.1530/JME-14-0011

Starke, R.M., Raper, D.M., Payne, S.C., et al. “Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission.” J Clin Endocrinol Metab 98.8 (2013): 3190–8. DOI: 10.1210/jc.2013-1036


GOST Style Citations


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2.         Dias, M.L., Vieira, J.G., Abucham, J. “Detecting and solving the interference of pregnancy serum, in a GH immunometric assay.” Growth Hormone IGF Research 23 (2013): 13–8. DOI: 10.1016/j.ghir.2012.11.001

3.         Feldt-Rasmussen, U., Mathiesen, E.R. “Endocrine disorders in pregnancy: physiological and hormonal aspects of pregnancy. Best Practice & Research.” Clinical Endocrinology & Metabolism 25 (2011): 875–84. DOI: 10.1016/j.beem.2011.07.004

4.         Petersenn, S., Christ-Crain, M., Droste, M., et al. “Pituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?” Geburtshilfe Frauenheilkd Apr 79.4 (2019): 365–74. DOI: 10.1055/a-0794-7587

5.         Cheng, V., Faiman, C., Kennedy, L., et al. “Pregnancy and acromegaly: a review.” Pituitary 15 (2012): 59–63. DOI: 10.1007/s11102-011-0330-3

6.         Katznelson, L., Laws, E.R. Jr., Melmed, S., et al. “Acromegaly: an endocrine society clinical practice guideline.” J Clin Endocrinol Metab 99 (2014): 3933–51. DOI: 10.1210/jc.2014-2700

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11.       Grynberg, M., Salenave, S., Young, J., et al. “Female gonadal function before and after treatment of acromegaly.” Journal of Clinical Endocrinology and Metabolism 95 (2010): 4518–25. DOI: 10.1210/jc.2009-2815

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16.       Laway, B. “Pregnancy in acromegaly.” Therapeutic advances in endocrinology and metabolism 6.6 (2015): 1–6. DOI: 10.1177/2042018815603927

17.       Velegrakis, A., Sfakiotaki, M., Sifakis, S. “Human placental growth hormone in normal and abnormal fetal growth.” Biomed Rep 7.2 (2017): 115–22. DOI: 10.3892/br.2017.930

18.       Shimatsu, A., Usui, T., Tagami, T., et al. “Suppressed levels of growth hormone and insulin-like growth factor-1 during successful pregnancy in persistent acromegaly.” Endocrine Journal 57 (2010): 551–3. DOI: 10.1507/endocrj.K10E-069

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20.       Dias, M., Boguszewski, C., Gadelha, M., et al. “Acromegaly and pregnancy: a prospective study.” European Journal of Endocrinology 170 (2014): 301–10. DOI: 10.1530/EJE-13-046

21.       Cheng, S., Grasso, L., Martinez-Orozco, J.A., et al. “Pregnancy in acromegaly: experience from two referral centers and systematic review of the literature.” Clinical Endocrinology 76 (2012): 264–71. DOI: 10.1111/j.1365-2265.2011.04180

22.       Caron, P., Broussaud, S., Bertherat, J., et al. “Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women.” Journal of Clinical Endocrinology and Metabolism 95 (2010): 4680–7. DOI: 10.1210/jc. 2009-2331

23.       Laway, B.A. “Pregnancy in acromegaly.” Ther Adv Endocrinol Metab 6.6 (2015): 267–72. DOI: 10.1177/2042018815603927

24.       Famini, P., Maya, M.M., Melmed, S. “Pituitary Magnetic Resonance Imaging for Sellar and Parasellar Masses: Ten-Year Experience in 2598 Patients.” J Clin Endocrinol Metab 96.6 (2011): 1633–41. DOI: 10.1210/jc.2011-0168

25.       Tosaka, M., Higuchi, T., Horiguchi, K. “Preoperative Evaluation of Sellar and Parasellar Macrolesions by [18F] Fluorodeoxyglucose Positron Emission Tomography.” World Neurosurg 103 (2017): 591–9. DOI: 10.1016/j.wneu.2017.04.032

26.       Lau, S.L., McGrath, S., Evain-Brion, D., et al. “Clinical and biochemical improvement in acromegaly during pregnancy.” J of Endocrin Invest 31 (2008): 255–61. DOI: 10.1007/BF03345599

27.       Caron, C., Buscail, L., Beckers, A., et al. “Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy.” The Journal of Clinical Endocrinology & Metabolism 82.11 (1997): 3771–6. DOI: 10.1210/jcem.82.11.4350

28.       Araujo, P.B., Neto, L.V., Gadelha, M.R. “Pituitary Tumor Management in Pregnancy.” Endocrinol Metab Clin North Am 44 (2015): 181–97. DOI: 10.1016/j.ecl.2014.10.015

29.       Melmed, S., Casanueva, F.F., Klibanski, A., et al. “A consensus on the diagnosis and treatment of acromegaly complications.” Pituitary 16 (2012): 294–302. DOI: 10.1007/s11102-012-0420-x

30.       Ramirez, C., Vargas, G., Gonzalez, B. “Discontinuation of octreotide LAR after long term, successful treatment of patients with acromegaly: is it worth trying?” European Journal of Endocrinology 166 (2012): 21–6. DOI: 10.1530/EJE-11-0738

31.       Kasuki, L., Neto, L.V., Takiya, C.M., et al. “Growth of an aggressive tumor during pregnancy in an acromegalic patient.” Endocrine Journal 59 (2012): 313–9. DOI: 10.1507/endocrj.EJ11-0306

32.       Adelman, D.T., Liebert, K.J., Nachtigall, L.B., et al. “Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment.” Int J Gen Med 6 (2013): 31–8. DOI: 10.2147/IJGM.S38594

33.       Abreu, A, Tovar, A.P., Castellanos, R., et al. “Challenges in the diagnosis and management of acromegaly: a focus on comorbidities.” Pituitary 19.4 (2016): 448–57. DOI: 10.1007/s11102-016-0725-2

34.       Leung, K.C., Johannsson, G., Leong, G.M., et al. “Estrogen regulation of growth hormone action.” Endocrine Reviews 25.5 (2004): 693–721. DOI: 10.1210/er.2003-0035

35.       Shimon, I., Barkan, A. “Estrogen treatment for acromegaly.” Pituitary 15 (2012): 601–7. DOI: 10.1007/s11102-012-0426-4

36.       Clemmons, D.R. “Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays.” Clin Chem 57.4 (2011): 555–9. DOI: 10.1373/clinchem.2010.150631

37.       Rosario, P.W., Calsolari, M.R. “Laboratory investigation of acromegaly: Is basal or random GH > 0.4 µg/L in the presence of normal serum IGF1 an important result?” Arch Endocrinol Metab 59.1 (2015): 54–8. DOI: 10.1590/2359-3997000000010

38.       Van der Lely, A.J., Gomez, R., Heissler, J.F., et al. “Pregnancy in acromegaly patients treated with pegvisomant.” Endocrine 49.3 (2014): 769–73. DOI: 10.1007/s12020-014-0508-3

39.       Paragliola, R.M., Salvatori, R. “Novel Somatostatin Receptor Ligands Therapies for Acromegaly.” Front Endocrinol (Lausanne) 7.9 (2018): 78. DOI: 10.3389/fendo.2018.00078

40.       Colao, A., Abs, R., Barcena, D.G., et al. “Pregnancy outcomes following cabergoline treatment: extended results from a 12-year observational study.” Clinical Endocrinology 68 (2008): 66–71. DOI: 10.1111/j.1365-2265.2007.03000.x

41.       Colao, A., Auriemma, R.S., Pivonello, R. “The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly.” Pituitary 19.2 (2016): 210–21. DOI: 10.1007/s11102-015-0677-y

42.       Paragliola, R.M., Corsello, S.M., Salvatori, R. “Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance.” Pituitary 20.1 (2017): 109–15. DOI: 10.1007/s11102-016-0768-4

43.       Anthony, L., Freda, P.U. “From somatostatin to octreotide LAR: evolution of a somatostatin analogue.” Curr Med Res Opin 25.12 (2009): 2989–99. DOI: 10.1185/03007990903328959

44.       Cuevas-Ramos, D., Fleseriu, M. “Somatostatin receptor ligands and resistance to treatment in pituitary adenomas.” J Mol Endocrinol 52.3 (2014): 223–40. DOI: 10.1530/JME-14-0011

45.       Starke, R.M., Raper, D.M., Payne, S.C., et al. “Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission.” J Clin Endocrinol Metab 98.8 (2013): 3190–8. DOI: 10.1210/jc.2013-1036





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