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History & Pituitary Adenoma Epidemiology
Pituitary adenomas are typically prolactinomas, which are the most frequent cause of elevated prolactin levels. Pituitary adenomas comprise over 85% of pituitary tumors, and 25% to 30% of these are hormonally inactive.1 The incidence of prolactinomas is four times greater in women than in men.2
They are the most frequent pituitary tumors among individuals of childbearing age, yet few studies have addressed what effects pituitary tumors during pregnancy or after have on the patient.3 Additionally, prolactinomas occur in both males and females with the same frequency after age 50, and a prevalence of about 10%, according to recorded autopsy studies.2,1
Pituitary Adenoma Diagnosis & Presentation
The pituitary gland undergoes morphological and physiological changes during pregnancy.
The size of the gland increases during late pregnancy and the first few days after delivery, peaking at up to 12 mm, before gradually regressing to a normal size six months later. This growth is linked to lactotroph hyperplasia, which begins in the first month of pregnancy and is brought on by elevated levels of estradiol (E2), the form of estrogen produced by the ovaries.4
Women with prolactinomas frequently experience infertility due to impairment of the hypothalamic-pituitary-gonadal axis (HPG axis).5 This is due to the direct association between pregnancy and the activation of the maternal HPA axis, which increases adrenocorticotropic hormone (ACTH) and cortisol levels.4
When using formal testing, visual deficits can be found in 5% to 15% of cases and up to 50% of cases. Up to 15% to 30% of people experience some sort of pituitary dysfunction. More than one-third of them are macroadenomas, and of those, about 30% will enlarge noticeably over time. The likelihood of clinically significant growth in small, asymptomatic incidental microadenomas is lower, and they are frequently able to be monitored over time with repeated MRIs.6
In some cases of macroprolactinomas, which are characterized by persistent and accelerated growth or regrowth despite repeated attempts at treatment, medications and sometimes surgery may be necessary to lower the risk of growing pituitary tumors during pregnancy.
Surgery after the second trimester should only be considered if the tumor significantly increases in size despite the use of DA therapy while a person is pregnant.7 The main benefits of surgery are mainly seen in cases of critical visual impairment and/or life-threatening endocrine complications. Surgery can also enable the patient to go through with a pregnancy after pituitary tumor removal.8
Diagnostic Workup
Prolactinoma diagnosis is based on clinical and laboratory imaging. The pituitary region is now better visible thanks to advancements in neuroimaging, particularly CT, CT angiography, and particularly magnetic resonance imaging (MRI). Adenomas are being discovered more frequently by chance while evaluating conditions like sinus problems (15%), trauma (19%), and stroke (15%), among others.5
The majority of patients have microprolactinomas, which are <10 mm in diameter, and present with symptoms including galactorrhea and hypogonadism. On the other hand, patients with macroprolactinomas, which are >10 mm in diameter, often present with headaches, visual disturbances, and additional hypopituitarism.9
Surgical indications for a pituitary tumor in pregnancy are uncommon and determined by weighing the expected benefits, particularly for the mother, with the risks associated with anesthesia and surgery. These indications, in the case of prolactinomas, are mainly macroadenomas with a symptomatic tumor volume increase and severe visual defects when dopamine agonists fail or are not tolerated.8 The two most efficient treatment options for prolactinomas that can be used in conjunction are dopamine agonist (DA) medication and transsphenoidal surgery.6
Transsphenoidal surgery is performed via minimally invasive microscopic or endoscopic techniques.6 Based on the literature, surgery is being looked at as a possible better option than medications, but at this point, current guidelines support DAs as a primary therapy.10
In DA-resistant cases, transsphenoidal pituitary surgery is recommended. However, fetal exposure and symptomatic tumor growth are possible risks of DA-induced pregnancies.6 About 5% to 17% of prolactinomas are resistant to DA therapy.7
Differential Diagnosis
Pituitary apoplexy within pituitary tumors during pregnancy and after delivery is difficult to diagnose because its symptoms can also be caused by other conditions. Pituitary apoplexy during pregnancy is a potentially life-threatening emergency that requires a high index of suspicion during diagnosis.11
Since headaches can be signs and symptoms of multiple serious conditions, high index of suspicion and low threshold for a neuroimaging investigation of pituitary apoplexy are required. Although pituitary adenomas are rarely part of the differential diagnosis in pregnancies and postpartum headaches, they are when in conjunction with vision loss.11
Pituitary apoplexy is commonly caused by bleeding inside a benign pituitary adenoma. It is an uncommon endocrinological emergency that can happen randomly. However, there are known risk factors in the majority of cases of pituitary apoplexy. These include major surgery, hypertension, coagulopathies, and postpartum hemorrhage.11
Management of Pituitary Adenoma in Pregnancy (Nonpharmacotherapy and pharmacotherapy)
The most frequent functioning pituitary tumor, prolactinoma, is responsible for 30% to 40% of hyperprolactinemic infertility in young individuals of childbearing age.7 It is necessary to manage a pituitary tumor pregnancy because it frequently presents with difficult and morbid symptoms, such as headaches and seizures.12
Despite the prevalence of pituitary tumors, there is a lack of standardization in diagnostic and therapeutic approaches.1 The care team decides on each patient’s course of treatment and management of the pituitary tumor pregnancy based on experiential evidence, guidelines for nonpregnant patients, and the patient’s values and preferences.
Each of the treatments for pituitary adenomas may involve multimodal therapy, including medications — such as dopamine agonists, surgery, radiation, and chemotherapy — and carry risk to both the parent and the developing fetus.12
Although radiotherapy may also control tumor growth, its efficacy in normalizing levels of prolactin is limited. Only 20% of biochemical remission has been observed after radiosurgery. Alternative treatments, such as clomiphene citrate, gonadotropins, and pulsed GnRH, can induce ovulation and pregnancy without changing prolactin levels. Cabergoline and bromocriptine are both alternative options. Cabergoline is better tolerated and more effective in lowering prolactin levels.7
Pituitary Adenoma Monitoring for Changes or Improvement
Endocrine tests used to determine the appropriate treatment method in women with pituitary adenomas need to be interpreted, taking into account the normal physiological changes that occur during pregnancy.
Throughout the trimesters, hormone replacement therapies may require dose adjustments. The known efficacy and safety data specific to pregnant individuals for each therapeutic option should be considered when using medical therapy for excess pituitary hormone.4
The negative effects and potential risks associated with drug use during pregnancy depend on the gestational age of the fetus and the parent. Pregnancy-related clinical trials are rarely approved because they are risky, expensive, and necessitate strict ethical guidelines and long-term follow-up.13
References
1. Deutschbein T, Jaursch-Hancke C, Knappe UJ, Saeger W, Flitsch J, Bojunga J, Buchfelder M, Ditzen B, Gerlach R, Gertzen E, Honegger J. First German guideline on diagnostics and therapy of clinically non-functioning pituitary tumors. Experimental and Clinical Endocrinology & Diabetes. 2021 Mar;129(03):250-64. DOI: 10.1055/a-1373-4087
2. Cocks Eschler D, Javanmard P, Cox K, Geer EB. Prolactinoma through the female life cycle. Endocrine. 2018 Jan;59(1):16-29. https://doi.org/10.1007/s12020-017-1438-7
3. Laway BA, Baba MS, Bansiwal SK, Choh NA. Prolactinoma Outcome After Pregnancy and Lactation: A Cohort Study. Indian Journal of Endocrinology and Metabolism. 2021 Nov;25(6):559. 10.4103/ijem.ijem_372_21
4. Luger A, Broersen LH, Biermasz NR, Biller BM, Buchfelder M, Chanson P, Jorgensen JO, Kelestimur F, Llahana S, Maiter D, Mintziori G. ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. European journal of endocrinology. 2021 Sep 1;185(3):G1-33. https://doi.org/10.1530/EJE-21-0462
5. Jane JA Jr, Catalino MP, Laws ER Jr. Surgical Treatment of Pituitary Adenomas. South Dartmouth (MA): MDText.com, Inc.; 2022.
6. Glezer A, Bronstein MD. Prolactinomas in pregnancy: considerations before conception and during pregnancy. Pituitary. 2020 Feb;23(1):65-9. https://doi.org/10.1007/s11102-019-01010-5
7. Marques JV, Boguszewski CL. Fertility issues in aggressive pituitary tumors. Reviews in Endocrine and Metabolic Disorders. 2020 Jun;21(2):225-33. https://doi.org/10.1007/s11154-019-09530-y
8. Graillon T, Cuny T, Castinetti F, Courbiere B, Cousin M, Albarel F, Morange I, Bruder N, Brue T, Dufour H. Surgical indications for pituitary tumors during pregnancy: a literature review. Pituitary. 2020 Apr;23(2):189-99. https://doi.org/10.1007/s11102-019-01004-3
9. Glezer A, Jallad RS, Machado MC, Fragoso MC, Bronstein MD. Management of pituitary tumors during pregnancy and lactation. Current Opinion in Endocrine and Metabolic Research. 2018 Aug 1;1:42-50. https://doi.org/10.1016/j.coemr.2018.02.002
10. Chanson P, Maiter D. The epidemiology, diagnosis and treatment of Prolactinomas: The old and the new. Best practice & research Clinical endocrinology & metabolism. 2019;33(2):101290.
11. Pop LG, Ilian A, Georgescu T, Bacalbasa N, Balescu I, Toader OD. Pituitary adenoma apoplexy in pregnancy: Case report and literature review. Experimental and Therapeutic Medicine. 2022 Mar 1;23(3):1-7. https://doi.org/10.3892/etm.2022.11143
12. Eckenstein M, Thomas AA. Benign and malignant tumors of the central nervous system and pregnancy. Handbook of Clinical Neurology. 2020 Jan 1;172:241-58. https://doi.org/10.1016/B978-0-444-64240-0.00014-3
13. Calina D, Docea AO, Golokhvast KS, Sifakis S, Tsatsakis A, Makrigiannakis A. Management of endocrinopathies in pregnancy: a review of current evidence. International Journal of Environmental Research and Public Health. 2019 Mar;16(5):781. https://doi.org/10.3390/ijerph16050781
Sydney Murphy is the Associate Editor of HealthDay Physicians Briefing and a freelance science writer based in New York City. You can follow her on Twitter @SydneyLiz_Murph.
