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CONTEXT: Invasive and somatostatin receptor ligand (SRL)-resistant pituitary tumors represent a challenge in the clinical practice of endocrinologists. Efforts have been made to elucidate reliable makers for both. Survivin and eukaryotic translation initiation factor-binding protein 1 (4EBP1) are upregulated in several cancers and involved in apoptosis and cell proliferation. OBJECTIVE: We explored the role of these markers in somatotropinomas. METHODS: Immunostains for survivin and 4EBP1, and also for somatostatin receptor type 2 (SSTR2), Ki-67, and cytokeratin 18, were analyzed in tissue microarrays containing 52 somatotropinoma samples. Tumor invasiveness was evaluated in all samples while drug resistance was evaluated in 34 patients who received SRL treatment. All these parameters were correlated with first-generation SRL (fg-SRL) responsiveness and tumor invasiveness. RESULTS: Low survivin expression (P = 0.04), hyperintense signal on T2 weighted image (T2WI) (P = 0.01), younger age (P = 0.01), sparsely granular adenomas (SGA) (P = 0.04), high postoperative growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels (P = 0.049 and P < 0.001, respectively), and large postoperative tumor size (P = 0.02) were associated with resistance to fg-SRL. Low survivin and SSTR2 expression and high 4EBP1 expression were associated with SGA (P = 0.04, P = 0.01, and P = 0.001, respectively). Younger age (P = 0.03), large tumor pre- and postoperative (P = 0.04 and P = 0.006, respectively), low SSTR2 expression (P = 0.03), and high baseline GH and IGF-1 (P = 0.01 and P = 0.02, respectively) were associated with tumor invasiveness. However, survivin, 4EBP1, Ki-67, and granulation patterns were not associated with tumor invasion. CONCLUSION: This study suggests that low survivin expression is predictive of resistance to fg-SRL in somatotropinomas, but not of tumor invasiveness.
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Acromegalia , Adenoma , Hormona de Crecimiento Humana , Neoplasias Hipofisarias , Humanos , Receptores de Somatostatina/metabolismo , Somatostatina/uso terapéutico , Factor I del Crecimiento Similar a la Insulina , Acromegalia/tratamiento farmacológico , Survivin/uso terapéutico , Antígeno Ki-67 , Adenoma/metabolismo , Hormona de Crecimiento Humana/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Hormona del Crecimiento/uso terapéuticoRESUMEN
Hyperprolactinemia can be caused by several conditions and its effects on the hypothalamic-pituitary-gonadal axis are understood in more detail. Nevertheless, in recent decades, other metabolic effects have been studied and data pointed to a potential increased cardiovascular disease (CVD) risk. A recent study showed a decrease in total and LDL- cholesterol only in men with prolactinoma treated with dopamine agonists (DA) supporting the previous results of a population study with increased CVD risk in men harboring prolactinoma. However, other population studies did not find a correlation between prolactin (PRL) levels and CVD risk or mortality. There is also data pointing to an increase in high-density lipoprotein levels, and decreases in triglycerides, carotid-intima-media thickness, C-reactive protein, and homocysteine levels in patients with prolactinoma on DA treatment. PRL was also implicated in endothelial dysfunction in pre and postmenopausal women. Withdrawal of DA resulted in negative changes in vascular parameters and an increase in plasma fibrinogen. It has been shown that PRL levels were positively correlated with blood pressure and inversely correlated with dilatation of the brachial artery and insulin sensitivity, increased homocysteine levels, and elevated D-dimer levels. Regarding possible mechanisms for the association between hyperprolactinemia and CVD risk, they include a possible direct effect of PRL, hypogonadism, and even effects of DA treatment, independently of changes in PRL levels. In conclusion, hyperprolactinemia seems to be associated with impaired endothelial function and DA treatment could improve CVD risk. More studies evaluating CVD risk in hyperprolactinemic patients are important to define a potential indication of treatment beyond hypogonadism.
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Enfermedades Cardiovasculares , Hiperprolactinemia , Hipogonadismo , Neoplasias Hipofisarias , Prolactinoma , Masculino , Humanos , Femenino , Prolactina/metabolismo , Hiperprolactinemia/complicaciones , Prolactinoma/complicaciones , Prolactinoma/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Grosor Intima-Media Carotídeo , Agonistas de Dopamina , LDL-Colesterol , Neoplasias Hipofisarias/metabolismo , HomocisteínaRESUMEN
BACKGROUND: The dopaminergic agonist cabergoline (CAB) has been used in the pharmacological treatment of Cushing's disease (CD). The effect is attributed to the frequent expression of the dopamine receptor subtype 2 in corticotroph tumors. However, in vivo studies have demonstrated the normalization of 24-h urinary cortisol (24-h UC) in approximately 30-40% of patients over the long term, mainly after surgical failure. OBJECTIVE: To evaluate the effect of CAB as monotherapy in the early preoperative period and on the recurrence of CD. METHODS: A single-center retrospective study was conducted in a tertiary referral center. Twenty-one patients with confirmed CD were included. The median age was 32 years (13-70), 86% were female, 10 had microadenomas, and 11 had macroadenomas. They were diagnosed from 1986 to 2016 and used CAB as monotherapy either in the preoperative period (n=7, CABi) or upon recurrence before any other treatment (n=14, CABr). A 'complete response' was considered 24-h UC normalization and a 'partial response' was considered a 24-h UC reduction of >50%. UC was obtained at the last follow-up evaluation. The normalization of late-night salivary cortisol (LNSC) after CAB use was evaluated in most patients, as well as the tumor diameter by pituitary MRI, before and after CAB treatment. RESULTS: Complete response was achieved in 29% (6/21) of subjects after 14.9±16.4 months of treatment, with an average dose of 2.2±1.0 mg/week. Partial response occurred in 9.5% (2/21). LNSC normalized in 35% (6/17) of patients, and no variation in tumor diameter before and after CAB use was observed (n=13): 6.8±6.8 vs. 7.2±7.1 mm. There was no normalization of 24-h-UC in the CABi subgroup at the end of the treatment, whereas 43% (6/14) of patients in the CABr subgroup reached complete response. The CABi subgroup was treated for 4.7±1.9 months, and the CABr subgroup was treated for 20.1±18.1 months. Both groups were administered similar doses of CAB (CABi 2.1±0.9 and CABr 2.3±1.1 mg/week). Interestingly, the difference between the subgroups' complete response was evident early on in the three months of treatment: no patients in the CABi subgroup vs. 6/10 (60%) in the CABr subgroup (p=0.035), despite a lower dose in the CABr subgroup (1.1 vs. 1.6; p=0.008). The normalization of LNSC occurred in 20% of the CABi subgroup and in 42% of the CABr subgroup. CONCLUSIONS: The normalization of 24-h UC and LNSC occurred in approximately 30% of all patients, mainly in those who used CAB for the recurrence of CD. Despite the small number of subjects in the CABi subgroup, the absence of hormone control in this subgroup discourages the use of this medication as primary therapy or as a preoperative treatment option.
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Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.
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Síndrome de Cushing , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Consenso , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Síndrome de Cushing/terapia , Humanos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/complicaciones , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/terapia , Hipófisis/cirugíaRESUMEN
Non-functioning pituitary adenomas (NFPA) usually present with symptoms of mass effect. Thus, the first-line treatment generally consists of transsphenoidal surgery. Since these tumors are usually large and invasive, post-surgical tumor remnants are common. Active surveillance is the follow-up strategy adopted by most pituitary centers, although the prevalence of residual tumor growth may reach 50% in 5-10 years, often leading to repeat surgery, radiation therapy, or both. NFPA remain the only pituitary tumor type for which no medical therapy has been approved. In this debate, we consider the evidence in favor and against using cabergoline to treat progressing NFPA.
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Adenoma/tratamiento farmacológico , Cabergolina/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Adenoma/epidemiología , Adenoma/patología , Adenoma/cirugía , Quimioterapia Adyuvante , Progresión de la Enfermedad , Humanos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Neoplasia Residual , Procedimientos Neuroquirúrgicos , Selección de Paciente , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Carga Tumoral/efectos de los fármacosRESUMEN
CONTEXT: The SAGIT® instrument (SAGIT) has been developed to enable accurate characterization of acromegaly disease activity. OBJECTIVE: We evaluated the ability of SAGIT to discriminate acromegaly disease control status. METHODS: This multicenter, noninterventional, prospective and retrospective, longitudinal study, conducted at academic and private clinical practice sites, included patients agedâ ≥â 18 years with a diagnosis of controlled (nâ =â 109) or non-controlled (nâ =â 105) acromegaly, assessed by clinical global evaluation of disease control (CGE-DC) questionnaire, investigator therapeutic decision, and international guidelines. Control status was not determined at baseline for 13 patients. Since 9 patients were enrolled retrospectively, all presented analyses are based on the prospective population (Nâ =â 227). Patients were assessed over a 2-year follow-up period. Classification and regression tree (CART) analyses were performed to investigate how SAGIT components at baseline (signs/symptoms [S], associated comorbidities [A], growth hormone levels [G], insulin-like growth factor 1 levels [I], tumor features [T]) discriminate between controlled and non-controlled acromegaly. RESULTS: Baseline mean subscores S, G, I, and T were significantly lower in patients with CGE-DC controlled vs CGE-DC non-controlled acromegaly. SAGIT components I and G for CGE-DC and S, A, G, I, and T for the clinician's therapeutic decision were retained by CART analyses. For international guidelines, only SAGIT component I was retained. The risk for undergoing ≥ 1 treatment change during the study was 3.44 times greater for CGE-DC non-controlled acromegaly relative to CGE-DC controlled acromegaly. CONCLUSION: The SAGIT instrument is a valid and sensitive tool to comprehensively and accurately assess acromegaly severity.
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Acromegalia/diagnóstico , Biomarcadores/sangre , Pruebas Diagnósticas de Rutina/instrumentación , Hormona de Crecimiento Humana/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Acromegalia/sangre , Estudios de Casos y Controles , Pruebas Diagnósticas de Rutina/métodos , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Curva ROC , Estudios RetrospectivosRESUMEN
CONTEXT: Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VFs). OBJECTIVE: To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers, Wnt inhibitors, bone mineral density (BMD), microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared with healthy control group (HC). DESIGN, SETTING, AND PATIENTS: Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA), and 53 HC. Serum procollagen type 1 N-terminal propeptide, ß-carboxy-terminal crosslinked telopeptide of type 1 collagen, osteocalcin, sclerostin, and DKK1 were measured in blood samples. dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) and vertebral fractures evaluation were also assessed simultaneously. MAIN OUTCOME AND RESULTS: AcroA showed significantly lower sclerostin and higher DKK1 compared with HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity, and increased cortical area and cortical thickness compared with HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (Râ =â 0.45, Pâ =â 0.044). Mild VFs were present in approximately 30% of patients. CONCLUSIONS: Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure, and increased VF. Sclerostin was not correlated with any HR-pQCT parameters; however, DKK1 was correlated with cortical porosity in tibia (Pâ =â 0.027). Additional studies are needed to clarify the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.
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Acromegalia/patología , Huesos/ultraestructura , Vía de Señalización Wnt/fisiología , Adulto , Densidad Ósea , Huesos/metabolismo , Estudios Transversales , Femenino , Análisis de Elementos Finitos , Humanos , Péptidos y Proteínas de Señalización Intercelular/sangre , Persona de Mediana Edad , Premenopausia , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiologíaRESUMEN
CONTEXT: Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. OBJECTIVE: To develop a prediction model of therapeutic response of acromegaly to fg-SRL. METHODS: Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). RESULTS: A total of 153 patients were analyzed. Controlled patients were older (Pâ =â .002), had lower GH at diagnosis (Pâ =â .01), had lower pretreatment GH and IGF-I (Pâ <â .001), and more frequently harbored tumors that were densely granulated (Pâ =â .014) or highly expressed SST2 (Pâ <â .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. CONCLUSION: We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.
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Acromegalia/tratamiento farmacológico , Reglas de Decisión Clínica , Monitoreo de Drogas/métodos , Aprendizaje Automático , Receptores de Somatostatina/administración & dosificación , Acromegalia/sangre , Adulto , Anciano , Biomarcadores/sangre , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Queratinas , Ligandos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Receptores de Somatostatina/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
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PURPOSE: Non-syndromic pituitary gigantism (PG) is a very rare disease. Aryl hydrocarbon receptor-interacting protein (AIP) and G protein-coupled receptor 101 (GPR101) genetic abnormalities represent important etiologic causes of PG and may account for up to 40% of these cases. Here, we aimed to characterize the clinical and molecular findings and long-term outcomes in 18 patients (15 males, three females) with PG followed at a single tertiary center in Sao Paulo, Brazil. METHODS: Genetic testing for AIP and GPR101 were performed by DNA sequencing, droplet digital PCR and array comparative genomic hybridization (aCGH). RESULTS: Pathogenic variants in the AIP gene were detected in 25% of patients, including a novel variant in splicing regulatory sequences which was present in a sporadic male case. X-LAG due to GPR101 microduplication was diagnosed in two female patients (12.5%). Of interest, these patients had symptoms onset by age 5 and 9 years old and diagnosis at 5 and 15 years, respectively. X-LAG, but not AIP, patients had a significantly lower age of symptoms onset and diagnosis and a higher height Z-score when compared to non-X-LAG. No other differences in clinical features and/or treatment outcomes were observed among PG based on their genetic background. CONCLUSION: We characterize the clinical and molecular findings and long-term outcome of the largest single-center PG cohort described so far.
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Gigantismo/genética , Gigantismo/patología , Adolescente , Adulto , Brasil , Niño , Hibridación Genómica Comparativa , Femenino , Pruebas Genéticas , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Imagen por Resonancia Magnética , Masculino , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Receptores Acoplados a Proteínas G/genética , Adulto JovenRESUMEN
The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
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Acromegalia/terapia , Consenso , Agonistas de Dopamina/uso terapéutico , Procedimientos Neuroquirúrgicos , Grupo de Atención al Paciente , Guías de Práctica Clínica como Asunto , Radioterapia , Receptores de Somatotropina/antagonistas & inhibidores , Somatostatina/análisis , Acromegalia/diagnóstico , Humanos , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/normas , Radioterapia/métodos , Radioterapia/normasRESUMEN
OBJECTIVE: In the Phase III PAOLA study (clinicaltrials.gov: NCT01137682), enrolled patients had uncontrolled acromegaly despite ≥6 months of octreotide/lanreotide treatment before study start. More patients achieved biochemical control with long-acting pasireotide versus continued treatment with octreotide/lanreotide (active control) at month 6. The current work assessed the extent of comorbidities at baseline and outcomes during a long-term extension. DESIGN/METHODS: Patients receiving pasireotide 40 or 60 mg at core study end could continue on the same dose in an extension phase if biochemically controlled or receive pasireotide 60 mg if uncontrolled. Uncontrolled patients on active control were switched to pasireotide 40 mg, with the dose increased at week 16 of the extension if still uncontrolled (crossover group). Efficacy and safety are reported to 304 weeks (~5.8 years) for patients randomized to pasireotide (core + extension), and 268 weeks for patients in the crossover group (extension only). RESULTS: Almost half (49.5%; 98/198) of patients had ≥3 comorbidities at core baseline. During the extension, 173 patients received pasireotide. Pasireotide effectively and consistently reduced GH and IGF-I levels for up to 5.8 years' treatment; 37.0% of patients achieved GH <1.0 µg/L and normal IGF-I at some point during the core or extension. Improvements were observed in key symptoms. The long-term safety profile was similar to that in the core study; 23/173 patients discontinued treatment because of adverse events. CONCLUSIONS: In this patient population with a high burden of comorbid illness, pasireotide was well tolerated and efficacious, providing prolonged maintenance of biochemical control and improving symptoms.
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Acromegalia/tratamiento farmacológico , Hormonas/administración & dosificación , Somatostatina/análogos & derivados , Factores de Tiempo , Acromegalia/sangre , Adulto , Estudios Cruzados , Esquema de Medicación , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/efectos de los fármacos , Masculino , Persona de Mediana Edad , Octreótido/uso terapéutico , Péptidos Cíclicos/uso terapéutico , Estudios Prospectivos , Somatostatina/administración & dosificación , Somatostatina/uso terapéutico , Resultado del TratamientoRESUMEN
Pasireotide, a multireceptor-targeted somatostatin analog with highest affinity for somatostatin receptor subtype (SST) 5, has demonstrated superior efficacy over the SST2-preferential somatostatin analogs octreotide and lanreotide. The safety profile is similar to those of octreotide and lanreotide, except for a higher frequency and degree of hyperglycemia. This analysis investigated baseline characteristics and occurrence and management of hyperglycemia during pasireotide treatment in patients with acromegaly treated in two prospective clinical studies, SOM230C2305 (C2305) and SOM230C2402 (C2402; PAOLA). One hundred and seventy-eight patients naïve to medical therapy at baseline (C2305) and 125 uncontrolled on first-generation somatostatin analogs at baseline (C2402) received long-acting pasireotide in these studies. Of patients treated with pasireotide in studies C2305 and C2402, respectively, 75.3 (134/178) and 65.6% (82/125) developed hyperglycemia or experienced worsening of existing hyperglycemia. Occurrence of hyperglycemia during pasireotide treatment was less frequent in patients with lower age (<40 years, C2402; <30 years, C2305), normal glucose tolerance, and no history of hypertension or dyslipidemia at baseline. Thirteen (4%) patients discontinued pasireotide because of hyperglycemia-related adverse events. Metformin alone or in combination with other oral antidiabetic medications controlled elevations in glucose levels in most pasireotide-treated patients; 78% of C2305 patients and 73 (pasireotide 40 mg) and 60% (pasireotide 60 mg) of C2402 patients achieved the ADA/EASD goal of HbA1c <7% (<53 mmol/mol) at the end of the core phase. Not all patients develop hyperglycemia, and it is reversible upon pasireotide withdrawal. Close monitoring, patient education and prompt action remain key elements in addressing hyperglycemia during pasireotide treatment.
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Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to the gonadal axis impairment. The gold-standard treatment is dopamine agonist (DA) which can reverse hyperprolactinemia and hypogonadism, and promote tumor shrinkage in the majority of cases. Therefore, reports of pregnancy in such cohort become more common. In this scenario, bromocriptine is still the DA of choice due to its shorter half-life and larger experience as compared to cabergoline. In DA resistant cases, transsphenoidal pituitary surgery is indicated. However, potential risks of DA-induced pregnancies include fetal exposition and symptomatic tumor growth. Dopamine agonist should be discontinued as soon as pregnancy is confirmed in microprolactinomas and intrasellar macroprolactinomas (MAC). Concerning expansive/invasive MAC, DA maintenance should be considered. Periodically clinical evaluation should be performed during pregnancy, being sellar imaging indicated if tumor symptomatic growth is suspected. In such cases, if DA treatment fails, neurosurgery is indicated.