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<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Med.</abbrev-journal-title>
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<issn pub-type="epub">2296-858X</issn>
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<publisher-name>Frontiers Media S.A.</publisher-name>
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<article-meta>
<article-id pub-id-type="doi">10.3389/fmed.2025.1651834</article-id><article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading"><subject>Case Report</subject></subj-group>
</article-categories>
<title-group>
<article-title>Case Report: Management of a pregnancy complicated by a symptomatic macroprolactinoma</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Topis</surname>
<given-names>Spyridon</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Christodoulaki</surname>
<given-names>Kalliopi</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Riga</surname>
<given-names>Maria</given-names>
</name>
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<contrib contrib-type="author">
<name>
<surname>Arkoulis</surname>
<given-names>Ioannis</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Karampitsakos</surname>
<given-names>Theodoros</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Sidiropoulou</surname>
<given-names>Tatiana</given-names>
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<contrib contrib-type="author">
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<surname>Drakakis</surname>
<given-names>Peter</given-names>
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<name>
<surname>Potiris</surname>
<given-names>Anastasios</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<xref ref-type="author-notes" rid="fn0003"><sup>&#x2020;</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Stavros</surname>
<given-names>Sofoklis</given-names>
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<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn0003"><sup>&#x2020;</sup></xref>
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<aff id="aff1"><label>1</label><institution>Third Department of Obstetrics and Gynecology, University General Hospital &#x201C;ATTIKON&#x201D;, Medical School, National and Kapodistrian University of Athens</institution>, <city>Athens</city>, <country country="gr">Greece</country></aff>
<aff id="aff2"><label>2</label><institution>Second Department of Anesthesiology, University General Hospital &#x201C;ATTIKON&#x201D;, Medical School, National and Kapodistrian University of Athens</institution>, <city>Athens</city>, <country country="gr">Greece</country></aff>
<author-notes><corresp id="c001"><label>&#x002A;</label>Correspondence: Anastasios Potiris, <email xlink:href="mailto:apotiris@med.uoa.gr">apotiris@med.uoa.gr</email></corresp><fn fn-type="equal" id="fn0003"><label>&#x2020;</label><p>These authors have contributed equally to this work and share last authorship</p></fn></author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2025-11-11">
<day>11</day>
<month>11</month>
<year>2025</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>12</volume>
<elocation-id>1651834</elocation-id>
<history>
<date date-type="received">
<day>26</day>
<month>06</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>24</day>
<month>10</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2025 Topis, Christodoulaki, Riga, Arkoulis, Karampitsakos, Sidiropoulou, Drakakis, Potiris and Stavros.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Topis, Christodoulaki, Riga, Arkoulis, Karampitsakos, Sidiropoulou, Drakakis, Potiris and Stavros</copyright-holder>
<license><ali:license_ref start_date="2025-11-11">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Background</title>
<p>Prolactinomas are the most common functional pituitary adenomas and may lead to infertility, visual field defects, and neurological impairment. Pregnancy poses unique challenges to women with macroprolactinomas due to the potential for tumor enlargement under the influence of gestational hormonal changes.</p>
</sec>
<sec id="sec2">
<title>Case</title>
<p>We present the case of a 40-year-old woman who conceived through <italic>in vitro</italic> fertilization (IVF) and presented at 38&#x202F;+&#x202F;3&#x202F;weeks of gestation with new-onset diplopia. The magnetic resonance imaging (MRI) revealed a 29-mm hemorrhagic macroprolactinoma causing compression of the optic chiasm. The tumor had previously been asymptomatic and untreated. Management was undertaken by a multidisciplinary team including obstetricians, endocrinologists, neurosurgeons, and anesthesiologists. An elective cesarean section was performed under general anesthesia with careful attention to intracranial pressure control and hemodynamic stability.</p>
</sec>
<sec id="sec3">
<title>Outcome</title>
<p>Delivery was uneventful, with no perioperative neurological or anesthetic complications. The patient was discharged in good general condition and commenced long-term dopamine agonist therapy, with planned close endocrinological and neurosurgical follow-up.</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>This case highlights the importance of early diagnosis, individualized management, and multidisciplinary coordination in pregnant women with macroprolactinomas. Dopamine agonists remain the cornerstone of therapy and are generally safe during early pregnancy. Meticulous anesthetic planning is essential to optimize maternal and fetal outcomes.</p>
</sec>
</abstract>
<kwd-group>
<kwd>prolactinoma</kwd>
<kwd>macroprolactinoma</kwd>
<kwd>dopamine agonists</kwd>
<kwd>cabergoline</kwd>
<kwd>diplopia</kwd>
<kwd>pituitary adenoma</kwd>
<kwd>pregnancy</kwd>
</kwd-group><funding-group><funding-statement>The author(s) declare that no financial support was received for the research and/or publication of this article.</funding-statement></funding-group>
<counts>
<fig-count count="2"/>
<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="17"/>
<page-count count="5"/>
<word-count count="3044"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Obstetrics and Gynecology</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<label>1</label>
<title>Introduction</title>
<p>Prolactinomas (PRLs) are the most common type of benign pituitary adenomas associated with hyperprolactinemia, leading to a wide range of clinical manifestations that primarily affect the reproductive and neurological systems. They represent the most frequent hormone-secreting pituitary tumors, accounting for approximately 40% of all pituitary adenomas (<xref ref-type="bibr" rid="ref1">1</xref>). Microprolactinomas, defined as lesions measuring less than 10&#x202F;mm in diameter, are often asymptomatic and typically managed conservatively. In contrast, macroprolactinomas, which exceed 10&#x202F;mm in diameter, are more likely to cause clinically significant complications&#x2014;particularly during pregnancy, when physiological hormonal changes may promote tumor growth (<xref ref-type="bibr" rid="ref2">2</xref>). The clinical manifestations of prolactinomas include menstrual irregularities, galactorrhea, infertility, headaches, and visual field defects, especially when the tumor compresses the optic chiasm (<xref ref-type="bibr" rid="ref3">3</xref>). Diagnosis is based on elevated serum prolactin levels&#x2014;confirmed by immunoassays such as the Ima2 multimeric assay&#x2014;and neuroimaging, most commonly magnetic resonance imaging (MRI). The mainstay of treatment remains dopamine agonists (DAs), particularly bromocriptine and cabergoline, which effectively suppress prolactin secretion and reduce tumor size with variable degrees of success (<xref ref-type="bibr" rid="ref1">1</xref>).</p>
<p>The coexistence of prolactinoma and pregnancy presents a clinical challenge. During gestation, elevated estrogen concentrations induce lactotroph hyperplasia within the pituitary gland, potentially leading to tumor enlargement and compressive symptoms (<xref ref-type="bibr" rid="ref4">4</xref>). While microprolactinomas rarely cause complications during pregnancy, macroprolactinomas&#x2014;especially those involving critical structures such as the optic chiasm&#x2014;require close monitoring and individualized management strategies. Dopamine agonists are recommended as the first-line therapy for women seeking fertility and during early pregnancy. Among them, bromocriptine remains the traditional choice, although cabergoline is increasingly preferred owing to its superior tolerability and efficacy (<xref ref-type="bibr" rid="ref5">5</xref>). Anesthetic considerations in pregnant patients with intracranial masses are of paramount importance. Pituitary macroadenomas necessitate meticulous anesthetic planning to prevent hemodynamic instability and elevations in intracranial pressure (ICP). General anesthesia is often preferred over neuraxial techniques because of the potential risk of brain herniation or neurological deterioration in the setting of increased ICP (<xref ref-type="bibr" rid="ref6">6</xref>, <xref ref-type="bibr" rid="ref7">7</xref>).</p>
<p>The aim of the present report is to describe the management of a challenging case of macroprolactinoma in a pregnant woman presenting with new-onset diplopia who underwent cesarean section under general anesthesia. This case underscores the importance of early recognition, multidisciplinary collaboration, and individualized therapeutic planning to optimize maternal and fetal outcomes. The report follows CARE guidelines for clinical case reporting.</p>
</sec>
<sec id="sec6">
<label>2</label>
<title>Case presentation</title>
<p>A 40-year-old woman, gravida 2 para 1, at 38&#x202F;+&#x202F;3&#x202F;weeks of gestation, presented to the emergency department of &#x201C;ATTIKON&#x201D; University General Hospital with new-onset diplopia for further evaluation and delivery planning. Her past medical history was notable for an untreated prolactinoma diagnosed after her first pregnancy, when elevated serum prolactin levels (220&#x202F;ng/mL) prompted further investigation. At that time, neuroimaging had demonstrated a 15-mm pituitary adenoma. The patient remained asymptomatic thereafter, and no follow-up assessments were performed. The current pregnancy was achieved via assisted reproductive techniques (ARTs) and was complicated by diet-controlled gestational diabetes mellitus. It is noteworthy that neither a complete hormonal profile nor repeat neuroimaging was conducted prior to the initiation of IVF treatment.</p>
<p>Five days before admission, magnetic resonance imaging (MRI) revealed a hemorrhagic macroprolactinoma measuring 28.7&#x202F;&#x00D7;&#x202F;21.2&#x202F;mm (<xref ref-type="fig" rid="fig1">Figure 1a</xref>), compressing the optic chiasm and displacing the right internal carotid artery toward the left (<xref ref-type="fig" rid="fig1">Figure 1b</xref>). Baseline endocrine evaluation on admission demonstrated normal thyroid function tests (TSH and free T4). Morning cortisol was 12&#x202F;&#x03BC;g/dL, indicating an intact hypothalamic&#x2013;pituitary&#x2013;adrenal axis. Serum prolactin levels were elevated at 310&#x202F;ng/mL. Ophthalmologic examination confirmed diplopia and mild right-sided ptosis. The pupils were equal and reactive to light. Ocular motility assessment revealed restricted abduction and elevation of the right eye, consistent with partial involvement of the oculomotor (III) and abducens (VI) cranial nerves, while left eye movements were normal. A multidisciplinary evaluation by the neurosurgery and endocrinology teams was undertaken. Neurosurgical consultation recommended expectant management of the tumor, with delivery followed by postpartum reassessment. Initiation of cabergoline therapy was planned after birth.</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption><p><bold>(a)</bold> Brain magnetic resonance imaging (MRI) reveals a hemorrhagic macroprolactinoma with dimensions of 28.7&#x202F;&#x00D7;&#x202F;21.2&#x202F;mm (marked with red lines) and <bold>(b)</bold> coronal T1 post-contrast MRI shows macroprolactinoma impinging on the right cavernous sinus (marked with red arrow).</p></caption>
<graphic xlink:href="fmed-12-1651834-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">MRI images of the brain. The left panel (a) shows a sagittal view with measurements labeled 2.87 centimeters and 2.12 centimeters. The right panel (b) displays a coronal view with a red arrow indicating a specific area in the brain.</alt-text>
</graphic>
</fig>
<p>Given the tumor&#x2019;s size and suprasellar extension, a comprehensive anesthetic strategy was formulated. A cesarean section was performed under general anesthesia, following established principles for patients with intracranial mass lesions, with an emphasis on maintaining hemodynamic stability and minimizing intracranial pressure fluctuations. Although some literature supports the cautious use of neuraxial techniques in selected cases, general anesthesia was deemed safer in this instance due to the risk of neurological compromise (<xref ref-type="bibr" rid="ref6">6</xref>, <xref ref-type="bibr" rid="ref7">7</xref>). An indwelling arterial line was placed prior to induction for continuous invasive blood pressure monitoring, alongside standard anesthetic surveillance. Lidocaine and remifentanil were administered to attenuate the hypertensive response to laryngoscopy, while esmolol was used for immediate blood pressure control owing to its rapid onset and short duration of action (<xref ref-type="bibr" rid="ref8">8</xref>). The surgical procedure proceeded uneventfully. The neonate&#x2019;s Apgar scores were 8 and 9 at 1&#x202F;min and 5&#x202F;min, respectively. The patient experienced no intraoperative or postoperative complications. Postpartum diplopia and other visual disturbances resolved completely. The patient was monitored in a standard ward setting and discharged 3&#x202F;days later in good general condition. She was advised to commence cabergoline therapy, undergo a follow-up MRI at 4&#x202F;months, and maintain regular endocrinological and neurosurgical surveillance, including serial serum prolactin and macroprolactin measurements.</p>
<p>At the 6-week postpartum review, the patient remained asymptomatic, and serum prolactin levels had decreased to 180&#x202F;ng/mL. Follow-up MRI at 4&#x202F;months demonstrated a slight reduction in tumor size, measuring 24.4&#x202F;&#x00D7;&#x202F;20.7&#x202F;mm (<xref ref-type="fig" rid="fig2">Figure 2</xref>). Under ongoing multidisciplinary follow-up, she remained stable, with no recurrence of diplopia. A chronological summary of the case is presented in <xref ref-type="table" rid="tab1">Table 1</xref>.</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption><p>Follow-up brain magnetic resonance imaging (MRI) after 4&#x202F;months of delivery. The figure shows a slight decrease in the hemorrhagic macroprolactinoma with dimensions of 24.4&#x202F;&#x00D7;&#x202F;20.7&#x202F;mm (marked with red lines).</p></caption>
<graphic xlink:href="fmed-12-1651834-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">MRI scan of a human brain in sagittal view, showing part of the brainstem and an haemorrhagic macroprolactinoma. Two measurement lines indicate distances: one is 2.44 centimeters, and the other is 2.07 centimet.</alt-text>
</graphic>
</fig>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption><p>Timeline of events.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Time point</th>
<th align="left" valign="top">Event/Intervention</th>
<th align="left" valign="top">Comments</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">5&#x202F;days before admission</td>
<td align="left" valign="top">Brain MRI examination</td>
<td align="left" valign="top">Hemorrhagic macroprolactinoma of 28.7&#x202F;&#x00D7;&#x202F;21.2&#x202F;mm</td>
</tr>
<tr>
<td align="left" valign="top">Admission</td>
<td align="left" valign="top">Onset of diplopia</td>
<td align="left" valign="top">Neurosurgical consultation, decision to deliver (38&#x202F;+&#x202F;3&#x202F;weeks of gestation)</td>
</tr>
<tr>
<td align="left" valign="top">Admission&#x202F;+&#x202F;1&#x202F;day</td>
<td align="left" valign="top">Cesarean section</td>
<td align="left" valign="top">Total anesthetic plan with general anesthesia, according to the principles of intracranial&#x2002;mass patients, based on hemodynamic stability and the reduction of elevated intracranial pressure</td>
</tr>
<tr>
<td align="left" valign="top">Admission&#x202F;+ 4&#x202F;days</td>
<td align="left" valign="top">Patient&#x2019;s discharge</td>
<td align="left" valign="top">Stable in good condition</td>
</tr>
<tr>
<td align="left" valign="top">4&#x202F;months after admission</td>
<td align="left" valign="top">Follow-up brain MRI</td>
<td align="left" valign="top">Slight reduction of the macroprolactinoma with dimensions 24.4&#x202F;&#x00D7;&#x202F;20.7&#x202F;mm</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec sec-type="discussion" id="sec7">
<label>3</label>
<title>Discussion</title>
<p>The management of macroprolactinomas during pregnancy remains particularly challenging, requiring careful consideration of maternal and fetal wellbeing as well as tumor control. Prolactinomas, including macroprolactinomas, may enlarge during gestation due to estrogen-mediated stimulation. Elevated estrogen concentrations lead to lactotroph hyperplasia, which can promote tumor expansion and precipitate clinical symptoms such as headaches and visual disturbances (<xref ref-type="bibr" rid="ref4">4</xref>, <xref ref-type="bibr" rid="ref9">9</xref>). Symptomatic tumor growth has been reported in approximately 20&#x2013;30% of pregnant women with macroprolactinomas, particularly when dopamine agonist therapy is discontinued (<xref ref-type="bibr" rid="ref2">2</xref>). The risk is further increased when the lesion is in proximity to vital structures such as the optic chiasm, as observed in the present case (<xref ref-type="bibr" rid="ref1">1</xref>).</p>
<p>Dopamine agonists remain the cornerstone of prolactinoma management. Bromocriptine, with its well-established safety profile during pregnancy, is generally regarded as the first-line treatment (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref3">3</xref>). Cabergoline, a longer-acting agent with better tolerability and efficacy, is increasingly used; however, data regarding its safety in pregnancy remain comparatively limited (<xref ref-type="bibr" rid="ref5">5</xref>, <xref ref-type="bibr" rid="ref10">10</xref>). Current recommendations suggest that, in women with invasive macroprolactinomas or tumors exhibiting suprasellar extension, continuation of dopamine agonist therapy during pregnancy may be necessary to prevent the development of a symptomatic mass effect (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref11">11</xref>). A recent systematic review encompassing 2,544 pregnancies in women with pituitary adenomas reported miscarriage in 10% of cases, tumor growth in 4%, and congenital anomalies in 2% of those exposed to dopamine agonists (<xref ref-type="bibr" rid="ref4">4</xref>).</p>
<p>More recent evidence further refines the safety profile of cabergoline in pregnancy. In a 2025 meta-analysis, incorporating 12 studies and 1,387 pregnancies with prolactinoma, fetal loss occurred in 16.1% of cases and congenital malformations in 4.7%. While live birth rates were slightly lower among cabergoline users than among non-users [RR 0.81 (95% CI 0.67&#x2013;0.98); <italic>p</italic>&#x202F;=&#x202F;0.03], no significant differences were observed for congenital malformations, preterm birth, or low birth weight (RRs close to 1.0) (<xref ref-type="bibr" rid="ref12">12</xref>). Similarly, another 2025 systematic review analyzing 1,662 pregnancies exposed to cabergoline during the first trimester found no increased risk of congenital malformations or spontaneous abortion compared with other treatments or untreated controls (<xref ref-type="bibr" rid="ref13">13</xref>). Collectively, these findings reinforce the relative safety of dopamine agonist use during gestation when the anticipated benefits outweigh potential risks (<xref ref-type="bibr" rid="ref14">14</xref>).</p>
<p>Transsphenoidal surgery is reserved for cases where medical therapy is ineffective, contraindicated, or poorly tolerated. In pregnant patients with significant visual compromise due to optic chiasm compression, surgical decompression is generally considered safe during the second trimester to minimize fetal risk (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref2">2</xref>). Furthermore, tumor debulking prior to conception has been associated with a lower incidence of symptomatic enlargement during pregnancy (<xref ref-type="bibr" rid="ref15">15</xref>).</p>
<p>Anesthetic management in pregnant women with intracranial mass lesions presents additional complexity. General anesthesia is typically preferred over neuraxial techniques due to concerns about elevated intracranial pressure and the risk of neurological deterioration (<xref ref-type="bibr" rid="ref6">6</xref>, <xref ref-type="bibr" rid="ref7">7</xref>). The use of short-acting agents such as remifentanil and esmolol can effectively attenuate hemodynamic fluctuations and the stress response during induction and emergence from anesthesia (<xref ref-type="bibr" rid="ref8">8</xref>). Nonetheless, isolated reports suggest that regional anesthesia may be safely used in selected patients without evidence of increased intracranial pressure, provided that meticulous monitoring and multidisciplinary coordination are ensured (<xref ref-type="bibr" rid="ref16">16</xref>). Ultimately, the choice of anesthetic technique should be individualized based on tumor characteristics, neurological status, and anesthesiology team expertise (<xref ref-type="bibr" rid="ref17">17</xref>).</p>
<p>Postpartum management involves the reinitiation of dopamine agonist therapy, particularly for women who do not intend to breastfeed. Long-term follow-up with periodic MRI imaging is essential to monitor changes in tumor size and guide ongoing care. Serial measurement of serum prolactin and macroprolactin levels facilitates the evaluation of therapeutic efficacy and the early detection of recurrence or progression (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref3">3</xref>).</p>
</sec>
<sec sec-type="conclusions" id="sec8">
<label>4</label>
<title>Conclusion</title>
<p>This case underscores the complex management challenges posed by macroprolactinomas during pregnancy and highlights the necessity of a personalized, multidisciplinary approach involving endocrinologists, obstetricians, neurosurgeons, and anesthesiologists. Early recognition, timely initiation of medical therapy, meticulous anesthetic planning, and structured postpartum follow-up are essential to ensure optimal maternal and fetal outcomes. Moreover, this report emphasizes that comprehensive neuroendocrine assessment and appropriate management prior to assisted reproduction could potentially prevent or mitigate such complications. Therefore, heightened clinical vigilance and preconception evaluation should be integral components of care for women with known pituitary adenomas seeking fertility treatment.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec9">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="ethics-statement" id="sec10">
<title>Ethics statement</title>
<p>Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.</p>
</sec>
<sec sec-type="author-contributions" id="sec11">
<title>Author contributions</title>
<p>ST: Conceptualization, Writing &#x2013; original draft. KC: Writing &#x2013; original draft, Data curation. MR: Investigation, Writing &#x2013; review &#x0026; editing. IA: Investigation, Writing &#x2013; review &#x0026; editing. TK: Visualization, Writing &#x2013; review &#x0026; editing. TS: Supervision, Validation, Writing &#x2013; review &#x0026; editing. PD: Supervision, Validation, Writing &#x2013; review &#x0026; editing. AP: Conceptualization, Project administration, Writing &#x2013; review &#x0026; editing. SS: Conceptualization, Project administration, Writing &#x2013; review &#x0026; editing.</p>
</sec>

<sec sec-type="COI-statement" id="sec13">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec14">
<title>Generative AI statement</title>
<p>The authors declare that no Gen AI was used in the creation of this manuscript.</p>
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<title>Publisher&#x2019;s note</title>
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</sec>
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</ref-list><fn-group><fn id="fn0001" fn-type="custom" custom-type="edited-by"><p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/692431/overview">Liza Das</ext-link>, Post Graduate Institute of Medical Education and Research (PGIMER), India</p></fn>
<fn id="fn0002" fn-type="custom" custom-type="reviewed-by"><p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1909119/overview">Hayri Bostan</ext-link>, &#x00C7;anakkale Mehmet Akif Ersoy State Hospital, T&#x00FC;rkiye; <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3162072/overview">H. S. Asha</ext-link>, Christian Medical College and Hospital, India</p></fn></fn-group></back>
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