Bankstown Hospital - Grand Rounds - Further Reading

​​​​​Welcome to the Grand Rounds Further Reading List, Obstetrics and Gynaecology edition, brought to you by the Clinical Library, on Level 4, next to the Auditorium.

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Topic of the Week:

"Acromegaly and Pregnancy"

Laway, B. A. (2015). "Pregnancy in acromegaly." Therapeutic Advances in Endocrinology and Metabolism 6(6): 267-272  https://journals.sagepub.com/doi/abs/10.1177/2042018815603927

                With advances in surgical and medical treatment and the availability of assisted reproductive techniques, pregnancy in women with acromegaly is more frequently encountered. Diagnosis of acromegaly during pregnancy is difficult because of changes in growth hormone and insulin like growth factor-1 (IGF-1) axis secondary to placental production of growth hormone. The difficulty is compounded by the inability of routine hormone assays to detect placental growth hormone. 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. The level of IGF-1 usually remains stable because of the effect of estrogen causing a growth hormone resistant state. In patients with pituitary macroadenoma, the possibility of an increase in size of the pituitary mass needs to be kept in mind and more frequent monitoring is required. In case of tumor enlargement, pituitary surgery can be considered in the mid trimester. Experience with the use of medical treatment for acromegaly during pregnancy is increasing. Dopamine agonists, somatostatin analogs or growth hormone receptor antagonists have been used without any adverse consequences on mother or fetus. At present, it is advisable to stop any medical treatment after confirmation of pregnancy till more data are available on the safety of these drugs.

Muhammad, A., et al. (2017). "Pregnancy and acromegaly." Pituitary 20(1): 179-184 MEDLINE https://access.ovid.com/custom/redirector/ciap.html?dest=https://acs.hcn.com.au/?acc=36422&url=https://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med14&DO=10.1007%2fs11102-016-0740-3

                INTRODUCTION: Acromegaly is a rare disorder in which, due to the high incidence of secondary hypogonadism, pregnancies are relatively rare. However, some women with acromegaly do get pregnant, which brings along questions about medication, complications and follow-up. This review tries to address these issues and provide the reader with practical information.

METHODS: This review summarizes published data.

CONCLUSIONS: Acromegaly is a disorder that is characterized by changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations and actions. All these hormones are important in pregnancy as well. In principle, the fetal-placental collaboration between mother and child more-or-less takes over the control over GH and IGF-1, not only in normal physiology but also to a certain extend in acromegaly. When medication for the high GH levels or actions is continued during pregnancy, both dopamine agonists, somatostatin analogs and GH receptor antagonists have been used and the available data suggest that there are no adverse consequences on mother or fetus to date. However, it is strongly advised to stop any medical intervention during pregnancy until more data are available on the safety of these compounds. Also, medical treatment is not needed as tumor size and disease activity are not reported to escape.

Neal, J. M. (2000). "Successful pregnancy in a woman with acromegaly treated with octreotide." Endocrine Practice 6(2): 148-150 MEDLINE https://access.ovid.com/custom/redirector/ciap.html?dest=https://acs.hcn.com.au/?acc=36422&url=https://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&DO=10.4158%2fEP.6.2.148     

                OBJECTIVE: To report a successful pregnancy in a 43-year-old woman with acromegaly and treatment during pregnancy with the somatostatin analogue octreotide, to review the physiologic aspects of acromegaly during pregnancy, and to discuss treatment options.

METHODS: A case report is presented, and the current literature is reviewed.

RESULTS: In a 40-year-old woman with acromegaly and secondary amenorrhea, menstrual periods resumed after treatment with octreotide. At age 43 years, she became pregnant and decided to continue octreotide therapy because of the relatively large size of the tumor and severe headaches when use of the medication was discontinued. Growth hormone and insulin-like growth factor I levels remained normal throughout pregnancy, and a normal full-term infant was born. Several months after delivery, severe cholecystitis developed, and the patient underwent laparoscopic cholecystectomy.

CONCLUSIONS: This case report describes the oldest documented woman with acromegaly who has completed a pregnancy and only the second patient treated with octreotide for the entire pregnancy. During a normal pregnancy, placental growth hormone suppresses pituitary growth hormone secretion; in patients with acromegaly, pituitary growth hormone secretion remains autonomous. Treatment of acromegaly with octreotide, bromocriptine, irradiation, or surgical intervention may restore menses and fertility to women of reproductive age. Bromocriptine has been used throughout pregnancy without teratogenic effects in many patients. Octreotide has been used during the first trimester of pregnancy in seven other women with acromegaly (throughout pregnancy in one of those patients) and for the entire pregnancy in one woman with a thyrotropin-secreting pituitary tumor; no adverse effects were noted. Lanreotide was also used in one patient briefly during the first trimester without adverse consequences. Although the outcomes of the current and previous pregnancies have been favorable, insufficient data are available to recommend the routine use of octreotide in all pregnant women with acromegaly.

Popescu, A. D., et al. (2022). "Approach of Acromegaly during Pregnancy." Diagnostics 12(11): 2669  https://www.mdpi.com/2075-4418/12/11/2669

Takano, T., et al. (2006). "Normal delivery following an uneventful pregnancy in a Japanese acromegalic patient after discontinuation of octreotide long acting release formulation at an early phase of pregnancy." Endocrine Journal 53(2): 209-212 MEDLINE https://access.ovid.com/custom/redirector/ciap.html?dest=https://acs.hcn.com.au/?acc=36422&url=https://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&DO=10.1507%2fendocrj.53.209

                We report a 35-year-old woman with active acromegaly despite pituitary surgery and irradiation who received continuous octreotide LAR treatment for the control of GH excess until discovery of her pregnancy. The patient delivered a healthy boy following an uneventful pregnancy after discontinuing octreotide LAR as soon as possible at the early phase of pregnancy. Despite a substantial maternal-fetal transfer of octreotide, postnatal development was normal at 3 years of age. In almost all previously described cases, octreotide was discontinued after pregnancy was confirmed. No side-effects of mother or fetus have been reported. Octreotide treatment in pregnancy seems to be feasible and safe. Due to the still-limited number of reported cases treated with octreotide LAR, the potential benefits of octreotide LAR treatment should be weighed carefully against its possible risks.

Teltayev, D., et al. (2017). "Pregnancy in women after successful acromegaly treatment, including surgical removal of pituitary adenoma and postoperative therapy using lanreotide acetate." Gynecological Endocrinology 33(sup1): 50-51 MEDLINE https://access.ovid.com/custom/redirector/ciap.html?dest=https://acs.hcn.com.au/?acc=36422&url=https://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med14&DO=10.1080%2f09513590.2017.1404240

                Acromegaly is one of the most common syndromes in pituitary adenomas. Naturally, women with this condition have trouble with their reproductive function. The difficulty in diagnosing acromegaly progression in pregnancy is that there is also production of placental growth hormone observed, making it impossible to differentiate from neoplastic growth hormone production using conventional methods of investigation. This article is about a clinical case of acromegaly in a 22 years old woman who was operated on using transnasal transsphenoidal approach and received postoperative treatment with somatostatin analog - lanreotide acetate autogel - for six months. The woman became pregnant in the course of the treatment. During pregnancy, the GH and IGF-I levels in serum remained within normal limits. Lanreotide acetate therapy was discontinued. The woman successfully gave birth to a healthy baby. There was a remission of the disease after pregnancy.

Tomczyk, K., et al. (2017). "Pregnancy in a woman with acromegaly after transsphenoidal partial resection of pituitary macroadenoma - a case report." Polski Merkuriusz Lekarski 43(258): 268-271 MEDLINE https://access.ovid.com/custom/redirector/ciap.html?dest=https://acs.hcn.com.au/?acc=36422&url=https://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med14&AN=29298966

                Acromegaly is a systemic disease caused by an excessive release of growth hormone and the hypopituitarism, which is induced by macroadenoma local mass effect. The gynecological and obstetric disorders include irregular menstrual cycles, anovulatory cycles and infertility. Therefore, pregnancy in patients affected by the disease is rare.

A CASE REPORT: Patient described in this study became pregnant after pharmacological, surgical and infertility treatment. Hence, the following paper presents the course of pregnancy and the discussion of the impact of acromegaly on female fertility, pregnancy, and concerns related to the diagnosis and treatment.