A cohort study of CNS tumors in Multiple Endocrine Neoplasia Type 1.

PURPOSE: Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). EXPERIMENTAL DESIGN: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed-up in the French MEN1 national cohort. Standardized incidence rate (SIR) was calculated based on the French Gironde CNS tumors registry. Genomic analyses were performed on somatic DNA from 7 CNS tumors including meningiomas and ependymomas from MEN1 patients, then in 50 sporadic meningiomas and ependymomas. RESULTS: Twenty-nine CNS tumors were found among the 1498 symptomatic patients (2%) (incidence=47.4/100'000 person-years; SIR=4.5), including 12 meningiomas (0.8%) (incidence=16.2/100'000; SIR=2.5), 8 ependymomas (0.5%) (incidence=10.8/100'000; SIR=17.6), 5 astrocytomas (0.3%) (incidence=6.7/100'000; SIR=5.8), and 4 schwannomas (0.3%) (incidence=5.4/100'000; SIR=12.7). Meningiomas in MEN1 patients were benign, mostly meningothelial, with 11 years earlier onset compared to the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified WHO grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from the MEN1 patients, whereas MEN1 deletion in one allele was present in respectively 3/41 and 0/9 sporadic meningiomas and ependymomas. CONCLUSIONS: Incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.

Impact of exenatide on weight loss and eating behavior in adults with craniopharyngioma-related obesity: the CRANIOEXE randomized placebo-controlled trial.

IMPORTANCE: A major issue in the management of craniopharyngioma-related obesity (CRO) is the ineffectiveness of the current therapeutic approaches. OBJECTIVE: To study the efficacy of glucagon-like peptide-1 analogs compared with placebo in adults with obesity CRO. DESIGN: A double-blind multicenter superiority randomized clinical in trial in two parallel arms. SETTING: Eleven French University Hospital Centers. PARTICIPANTS: Adults with CRO (body mass index > 30 kg/m²) without the sign of recurrence of craniopharyngioma in the past year. INTERVENTIONS: Exenatide or placebo injected subcutaneously twice a day during 26 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change in body weight at week 26 in the intention-to-treat population. Secondary outcomes were eating behavior, calories intake, energy expenditure, cardiovascular, metabolic risk factor, quality of life, and the tolerance profile. RESULTS: At week 26, weight decreased from baseline by a mean of -3.8 (SD 4.3) kg for exenatide and -1.6 (3.8) kg for placebo. The adjusted mean treatment difference was -3.1 kg (95% confidence interval [CI] -7.0 to 0.7, P = 0.11). Results were compatible with a higher reduction of hunger score with exenatide compared with placebo (estimated treatment difference in change from baseline to week 26: -2.3, 95% CI -4.5 to -0.2), while all other outcomes did not significantly differ between groups. Adverse events were more common with exenatide versus placebo, and occurred in, respectively, 19 (95%) participants (108 events) and 14 (70%) participants (54 events). CONCLUSIONS AND RELEVANCE: Combined with intensive lifestyle interventions, a 26-week treatment with exenatide was not demonstrated superior to placebo to treat craniopharyngioma-related obesity.

Position statement on the diagnosis and management of congenital pituitary deficiency in adults: The French National Diagnosis and Treatment Protocol (NDTP).

Pituitary deficiency, or hypopituitarism, is a rare chronic disease. It is defined by insufficient synthesis of one or more pituitary hormones (growth hormone, TSH, ACTH, LH-FSH, prolactin), whether or not associated with arginine vasopressin deficiency (formerly known as diabetes insipidus). In adult patients, it is usually acquired (notably during childhood), but can also be congenital, due to abnormal pituitary development. The present study focuses on congenital pituitary deficiency in adults, from diagnosis to follow-up, including special situations such as pregnancy or the elderly. The clinical presentation is highly variable, ranging from isolated deficit to multiple deficits, which may be part of a syndromic form or not. Diagnosis is based on a combination of clinical, biological (assessment of all hormonal axes), radiological (brain and hypothalamic-pituitary MRI) and genetic factors. Treatment consists in hormonal replacement therapy, adapted according to the period of life and the deficits, which may be progressive. Comorbidities, risk of complications and acute decompensation, and the impact on fertility and quality of life all require adaptative multidisciplinary care and long-term monitoring.

Beyond MEN1, when to think about MEN4? Retrospective study on 5600 patients in the French population & literature review.

CONTEXT: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically-negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear. OBJECTIVE: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients. DESIGN: Retrospective observational nationwide study. Narrative review of literature and variant class reassessment. PATIENTS: We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French TENGEN network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants, i.e. with genetically-confirmed MEN4 diagnosis, in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database. RESULTS: From 5600 MEN1-suspected patients analyzed, four patients with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, PHPT and adrenal nodule, isolated PHPT, PHPT and pNET. We listed 29 patients with CDKN1B class 4/5 variants from literature. Compared to matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis. CONCLUSION: The prevalence of MEN4 is low. PHPT and PA represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families.

Performance of [18F]fluorocholine PET/CT in MEN1-related primary hyperparathyroidism before initial surgery or for persistent/recurrent disease.

PURPOSE: The aims of the study were to evaluate the performance and robustness of [18F]fluorocholine PET/CT in detecting hyperfunctioning parathyroid glands in MEN1-related primary hyperparathyroidism (pHPT) at different stages of their disease. METHODS: Retrospective French multicenter study including patients with MEN1 pHPT who underwent [18F]fluorocholine PET/CT at initial diagnosis or for evaluation of persistent/recurrent disease. PET/CT were independently reviewed by two readers in a blinded manner. The assessment of PET/CT on a per-patient basis was assessed using a comprehensive set of criteria that considered pathological findings or agreement with alternative diagnostic methods in non-operated patients. The secondary objectives included the analysis of the performance of PET/CT at a per-lesion level, with reference to a pathological Gold Standard, and examining its interobserver reproducibility. RESULTS: A total of 71 MEN1 patients were included (73 PET/CT) in the study. At the per-patient level (entire cohort), [18F]fluorocholine PET/CT sensitivity ranged from 98.5 to 100% among the different readers. An average of 1.77 glands per PET was described, with 2.35 glands at the initial diagnosis (n = 23) and 1.5 in previously operated cases (n = 50). PET/CT detected more lesions than conventional imaging work-up (neck ultrasound and/or scintigraphy). At the per-lesion level (41 operated patients), sensitivity ranged across different readers from 84.4 to 87%, and specificity ranged from 94.7 to 98.8%. At initial diagnosis, all patients that exhibited 3 or more abnormal glands on PET underwent subtotal parathyroidectomy while 7 out of 13 patients with 1 or 2 gland abnormalities on PET underwent less than subtotal parathyroidectomy. Finally, the degree of inter-observer agreement was high. CONCLUSION: [18F]fluorocholine PET/CT is a reliable and robust imaging modality for the evaluation of MEN1-related pHPT and could guide surgeons in achieving the optimal benefit-risk ratio. This study gives a great impetus for its adoption as a primary diagnostic tool in this context.

Cinacalcet Reverses Short QT Interval in Familial Hypocalciuric Hypercalcemia Type 1.

CONTEXT: Familial hypocalciuric hypercalcemia type 1 (FHH-1) defines an autosomal dominant disease, related to mutations in the CASR gene, with mild hypercalcemia in most cases. Cases of FHH-1 with a short QT interval have not been reported to date. OBJECTIVE: Three family members presented with FHH-1 and short QT interval (<360 ms), a condition that could lead to cardiac arrhythmias, and the effects of cinacalcet, an allosteric modulator of the CaSR, in rectifying the abnormal sensitivity of the mutant CaSR and in correcting the short QT interval were determined. METHODS: CASR mutational analysis was performed by next-generation sequencing and functional consequences of the identified CaSR variant (p.Ile555Thr), and effects of cinacalcet were assessed in HEK293 cells expressing wild-type and variant CaSRs. A cinacalcet test consisting of administration of 30 mg cinacalcet (8 Am) followed by hourly measurement of serum calcium, phosphate, and parathyroid hormone during 8 hours and an electrocardiogram was performed. RESULTS: The CaSR variant (p.Ile555Thr) was confirmed in all 3 FHH-1 patients and was shown to be associated with a loss of function that was ameliorated by cinacalcet. Cinacalcet decreased parathyroid hormone by >50% within two hours, and decreases in serum calcium and increases in serum phosphate occurred within 8 hours, with rectification of the QT interval, which remained normal after 3 months of cinacalcet treatment. CONCLUSION: Our results indicate that FHH-1 patients should be assessed for a short QT interval and a cinacalcet test used to select patients who are likely to benefit from this treatment.

Genetic testing in prolactinomas: a cohort study.

BACKGROUND: Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on hereditary predisposition to prolactinoma. OBJECTIVE: We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinomas. MATERIALS AND METHODS: A retrospective study was performed combining genetic and clinical data from patients referred for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. SF3B1 was Sanger sequenced in genetically negative patients. RESULTS: About 506 patients with a prolactinoma were included: 80 with microprolactinoma (15.9%), 378 with macroprolactinoma (74.7%), 48 unknown; 49/506 in a familial context (9.7%). Among these, 14 (2.8%) had a (likely) pathogenic variant (LPV) in MEN1 or AIP, and none in CDKN1B. All positive patients had developed a macroprolactinoma before age 30. The prevalence of germline mutations in patients with isolated macroprolactinoma under 30 was 4% (11/258) in a sporadic context and 15% (3/20) in a familial context. Prevalence in sporadic cases younger than 18 was 15% in men (5/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 264 patients with macroprolactinomas. CONCLUSIONS: We did not identify any LPVs in patients over 30 years of age, either in a familial or in a sporadic context, and in a sporadic context in our series or the literature. Special attention should be paid to young patients and to familial context.

The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) gene.

Introduction: Prolactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar). Methods: We compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas ("unselected", n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39). Results: AIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p<0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p<0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p<0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p<0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA-induced macroadenoma shrinkage (>50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p<0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p<0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups. Discussion: AIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically-negative tumors.

The socioeconomic burden of acromegaly.

Acromegaly is a rare and insidious disease characterized by chronic excess growth hormone, leading to various morphological changes and systemic complications. Despite its low prevalence, acromegaly poses a significant socioeconomic burden on patients and healthcare systems. This review synthesizes the current state of knowledge on the psychosocial burden, disability, impact on daily life, and cost of acromegaly disease, focusing on the quality of life, partnership, medical care and treatment afflictions, participation in daily activities, professional and leisure impairment, and cost of treatment for acromegaly and its comorbidities. It also examines management strategies, coping mechanisms, and interventions aimed at alleviating this burden. A comprehensive understanding of the extent of the socioeconomic burden in acromegaly is crucial to develop effective strategies to improve treatment and care. Further research is warranted to explore the myriad factors contributing to this burden, as well as the efficacy of interventions to alleviate it, ultimately enhancing the quality of life for patients with acromegaly.

Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in adult cancers: data mining of 1385 electronic patient records.

BACKGROUND: Dysthyroidism (DT) is a common toxicity of immune checkpoint inhibitors (ICIs) and prior work suggests that dysthyroidism (DT) might be associated with ICI efficacy. PATIENTS AND METHODS: ConSoRe, a new generation data mining solution, was used in this retrospective study, to extract data from electronic patient records of adult cancer patients treated with ICI at Institut Paoli-Calmettes (Marseille, France). Every DT was verified and only ICI-induced DT was retained. Survival analyses were performed by Kaplan-Meier method (log-rank test) and Cox model. To account for immortal time bias, a conditional landmark analysis was performed (2 months and 6 months), together with a time-varying Cox model. RESULTS: Data extraction identified 1385 patients treated with ICI between 2011 and 2021. DT was associated with improved overall survival (OS) (HR 0.46, (95% CI 0.33 to 0.65), p<0.001), with a median OS of 35.3 months in DT group vs 15.4 months in non-DT group (NDT). Survival impact of DT was consistent using a 6-month landmark analysis with a median OS of 36.7 months (95% CI 29.4 to not reported) in the DT group vs 25.5 months (95% CI 22.8 to 27.8) in the NDT group. In multivariate analysis, DT was independently associated with improved OS (HR 0.49, 95% CI 0.35 to 0.69, p=0.001). After adjustment in time-varying Cox model, this association remained significant (adjusted HR 0.64, 95% CI 0.45 to 0.90, p=0.010). Moreover, patients with DT and additional immune-related adverse event had increased OS compared with patients with isolated DT, with median OS of 38.8 months vs 21.4 months, respectively. CONCLUSION: Data mining identified a large number of patients with ICI-induced DT, which was associated with improved OS accounting for immortal time bias.

The pre-thyroidectomy surgeon's checklist. Recommendations of the AFC>E (Association francophone de chirurgie endocrinienne), with the SFE (Société française d'endocrinologie) and the SFMN (Société française de médecine nucléaire).

During the patient interview, signs of compression or invasion are sought out: dyspnea, dysphagia, dysphonia. The circumstances of discovery of the thyroid pathology are indicated. The surgeon must be closely acquainted with the EU-TIRADS and Bethesda classifications so as to be able to evaluate and explain to the patient the risk of malignancy. He must also be able to interpret a cervical ultrasound in view of proposing a procedure adapted to the pathology. Cervicothoracic CT-scan (or MRI) must be prescribed in the event of suspected plunging nodule or clinical/echography signs: non-palpable lower pole of the thyroid behind the clavicle, dyspnea, dysphagia, collateral circulation. The surgeon goes on to investigate possible relationships with adjacent organs, to evaluate extension toward the aortic arch and the positions (anterior, posterior or mixed) of the goiter, the objective being to determine the most adapted approach: classical cervicotomy, manubriotomy or sternotomy. Even in the event of a tumoral pathology, PET-FDG is not one of the imagery exams carried out systematically. Only in case of TSH < 0.5µU/mL should thyroid scintigraphy be proposed. Prior to any thyroid surgery, serum TSH levels, calcitoninemia and calcemia must be measured.

Real-life clinical impact of a five-tiered classification of pituitary tumors.

Introduction: Usually benign, pituitary tumors (PT) can be invasive and aggressive with a propensity to progress and/or recur. Trouillas's clinicopathological classification attempts to predict the evolutionary risk of a PT. In this study, we assessed the prognostic value of this classification in an independent patient cohort and analyzed its impact on treatment strategies. Patients and methods: In this study, 607 patients operated on between 2008 and 2018 for a PT were included. Grading was established based on invasion, proliferative activity (Ki-67, mitotic index) and p53 positivity. The therapeutic management following surgery was analyzed. Progression-free survival (PFS) of the graded tumors was estimated (Kaplan-Meier method and log-rank test) and a multivariate analysis was performed (Cox regression model). Results: Grading identified non-invasive PT without (grade 1a: 303 cases) or with proliferative activity (grade 1b: 53 cases) and invasive PT without (grade 2a: 202 cases) or with proliferative activity (grade 2b: 49 cases). The mean follow-up was 47 ± 30 months (median: 38 months). Progression/recurrence occurred in 127 cases. Grades were significant and independent predictors of PFS (P < 0.001) with a 4.8-fold higher risk of progression/recurrence in grade 2b as compared to grade 1a. As second-line therapy, gamma knife or conventional radiotherapy controlled tumor growth in 91.6 and 100% of cases, respectively, irrespective of the grade. Proliferative tumors exposed the patient to a 9.5-fold higher risk of having ≥3 adjuvant therapeutic lines as compared to non-proliferative tumors. Discussion: Grading of a PT according to Trouillas's classification predicts its risk of progression and should advocate for a personalized therapeutic approach in invasive and proliferative tumors. Significance statement: This is the first study to assess, on a cohort of 607 well-characterized patients, the real-life therapeutic impact of the five-tiered clinicopathological classification of pituitary tumors. First, we validate that pituitary tumor grades predict the evolutionary risk of the tumor, with a significant higher risk of progression/recurrence in invasive and/or proliferative tumors (mean follow-up: 47 ± 30 months, median: 38 months). Moreover, our study provides evidence that patients with proliferative tumors have a higher risk to be retreated after primary surgery and point toward the fact that radiotherapy can successfully control tumor growth in case of progression or recurrence. Our findings advocate for a personalized therapeutic approach in clinically aggressive pituitary tumors.

Real-life efficacy and predictors of response to immunotherapy in pituitary tumors: a cohort study.

Objective: After temozolomide failure, no evidence-based treatment is available for pituitary carcinomas (PCs) and aggressive pituitary tumors (APTs). To date, only 12 cases treated with immune-checkpoint inhibitors (ICIs) have been published, showing encouraging efficacy. Predictive factors of response are lacking. Here, we aimed to assess the real-life efficacy and predictors of response to ICIs in PCs and APTs. Design and methods: This study is a multicentric, retrospective, observational cohort study, including all PCs and APTs treated with ICIs in France up to March 2022. PD-L1 immunohistochemistry and CD8+ T cell infiltration were evaluated centrally. Results: Six PCs (four corticotroph and two lactotroph) and nine APTs (five corticotroph and four lactotroph) were included. The real-life efficacy of ICIs was lower than previously published data. Three corticotroph tumors (33.3%) showed partial response, one (11.1%) stable disease, while five (55.6%) progressed. One lactotroph tumor (16.7%) showed partial response, one (16.7%) stable disease, while four (66.7%) progressed. PCs responded far better than APTs, with 4/6 PCs showing partial response compared to 0/9 APTs. Corticotroph tumors responded slightly better than lactotroph tumors. In the four responsive corticotroph tumors, PD-L1 staining was negative and CD8+ T cell infiltration attained a maximum of 1% in the tumor center. Conclusions: Confirmation of the presence or absence of metastases is necessary before starting ICIs. After temozolomide failure, ICIs appear as a good therapeutic option for PCs, especially for corticotroph carcinomas. Negative PD-L1 staining and very low CD8+ T cell infiltration in the tumor center should not preclude ICI administration in corticotroph carcinomas. Significance statement: This is the first study to assess the real-life efficacy of ICIs in pituitary carcinomas (PCs) and aggressive pituitary tumors. We also assessed potential predictors of response and are the first to assess the predictive value of CD8+ cell infiltration. We identified the tumor type as a major predictor, ICIs proving far more effective in treating PCs. Our study provides evidence that ICIs are a good option after temozolomide failure for PCs (four of six responded), especially for corticotroph carcinomas (three of four responded). We also provide evidence that negative PD-L1 staining and very low CD8+ cell infiltration in the tumor center should not preclude ICI administration in corticotroph carcinomas. Moreover, our findings point toward the need to systematically perform extension workup before starting ICIs.

Systematic detection of mosaicism by using digital NGS reveals three new MEN1 mosaicisms.

Purpose: Mosaicism is a feature of several inherited tumor syndromes. Only a few cases of mosaicism have been described in multiple endocrine neoplasia type 1 (MEN1). Next-generation sequencing (NGS) offers new possibilities for detecting mosaicism. Here, we report the first study to systematically look for MEN1 mosaicism, using blood DNA, in MEN1-suspected patients but without MEN1 pathogenic variants (PV) in a heterozygous state. Methods: Digital targeted NGS, including unique molecular identifiers (UMIs), was performed in routine practice, and the analytic performance of this method was verified. Results: Among a cohort of 119 patients harboring from 2 to 5 MEN1 lesions, we identified 3 patients with MEN1 mosaic PVs. The allele frequencies ranged from 2.3 to 9.5%. The detection rate of MEN1 mosaicism in patients bearing at least 3 MEN1 lesions was 17% (3/18). No cases were detected in patients with two lesions. Conclusion: We report here three new cases with MEN1 mosaicism. This study examined the performance of UMI in the diagnosis of MEN1 mosaicism in routine practice, and our results underline that the frequency of mosaicism is probably underestimated in patients with suspected MEN1.

The Challenging Management of Craniopharyngiomas in Adults: Time for a Reappraisal?

Craniopharyngiomas (CPs) are rare tumors of the skull base, developing near the pituitary gland and hypothalamus and responsible for severe hormonal deficiencies and an overall increase in mortality rate. While surgery and radiotherapy represent the recommended first-line therapies for CPs, a new paradigm for treatment is currently emerging, as a consequence of accumulated knowledge concerning the molecular mechanisms involved in tumor growth, paving the way for anticipated use of targeted therapies. Significant clinical and basic research conducted in the field of CPs will undoubtedly constitute a real step forward for a better understanding of the behavior of these tumors and prevent associated complications. In this review, our aim is to summarize the multiple steps in the management of CPs in adults and emphasize the most recent studies that will contribute to advancing the diagnostic and therapeutic algorithms.

Preoperative Medical Treatment for Patients With Acromegaly: Yes or No?

Transsphenoidal surgery is the first-line treatment for acromegaly. However, several factors can modify surgical remission rates, such as the initial hormone levels, the size and invasiveness of the tumor, and the degree of experience of the surgeon. Physicians treating patients with acromegaly should thus consider how to improve surgical remission rates. As stated in recent guidelines, the major point is to consider that any patient with acromegaly should be referred to an expert neurosurgeon to maximize the chances of surgical sure. The benefits of presurgical medical treatment, mainly using somatostatin receptor ligands (SRLs), given 3 to 6 months before surgery, remain controversial. By normalizing growth hormone and insulin-like growth factor 1 levels, SRLs may improve the overall condition of the patient, thus decreasing anesthetic and surgical complications. By decreasing the tumor size and modifying the consistency of the tumor, SRLs might also make surgical excision easier. This is however theoretical as published data are contradictory on both points, and only limited data support the use of a systematical presurgical medical treatment. The aim of this review is to analyze the potential benefits and pitfalls of using presurgical medical treatment in acromegaly in view of the contradictory literature data. We also attempt to determine the profile of patients who might most benefit from this presurgical medical treatment approach as an individualized therapeutic management of acromegaly.