Management Of Pituitary Adenomas Research Articles

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases.

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing.

Management of pituitary adenoma: Preliminary experience with endoscopic endonasal transphenoidal surgery in a developing country. Example of Senegal about 180 cases

IntroductionEndoscopic endonasal transsphenoidal surgery is currently the gold-standard therapeutic approach for pituitary adenomas. Although being spread worldwide, the endoscopic endonasal approach for pituitary adenomas is recently implemented in Senegal.This study aimed to report our results and the complications observed in the context of an under-equipped facility. Materials and methodsWe conducted a retrospective study including all patients with a pituitary adenoma treated who underwent endonasal transsphenoidal resection under a single endoscopic approach from January 2014 to May 2022, in the Neurosurgery Department of Fann National Hospital Centre, Dakar. All patients were assessed according to clinical, radiological, and endocrinological criteria. They all were operated by the same team with an average follow-up of 24 months. ResultsIn this series of 180 patients, including 57.7 % women and 42.3% men with a mean age of 44.8 years (extremes of 18 and 76 years), the visual deficit was the most frequent onset symptom (69.4 %), followed by clinical forms of hormone hypersecretion (30.5 %). Twelve cases of pituitary apoplexy and 1 case of incidentaloma were reported. The most frequent tumors were non-functional tumors (61.6 %). Among the functional adenomas, the most frequent was prolactinoma (15.5 %). Regarding tumor size, 75 % were macroadenomas, 15.5 % were microadenomas, and 9.5 % were giants. Cavernous sinus invasion (Knosp grade ≥ 3) and suprasellar extension were noted in 14.4 % and 53.3 %, respectively. The resection was total in 80 % of cases, subtotal in 18.8 %, and partial in 1.2 %. Partial improvement of sight was observed in 91.1% and endocrine hypersecretion remission in 76.6 %. As for complications, the most frequent was transient diabetes insipidus (32.7 %). ConclusionDespite the scanty resources, our results are similar to the best-reported series and strengthen scientific evidence on the efficacy and safety of performing this technique in an under-equipped setting context.

CircDDX17 inhibits invasive progression of pituitary adenomas by sponging miR-1279 and regulating CADM2 expression.

Increasing evidence has revealed that circDDX17 plays significant regulatory roles in tumor progression. In the present study, we investigated the role of circDDX17 in pituitary adenomas (PAs). Reverse transcription-quantitative PCR was performed to detect the expression of Circular RNA DDX17 (circDDX17), microRNA-1279 (miR-1279), and cell adhesion molecule 2 (CADM2) in PA tissues. Cell abilities of migration and invasion were examined by wound healing and transwell assays. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were applied to confirm the associations among circDDX17, miR-1279, and CADM2. Xenograft tumor experiments were performed to investigate the roles of circDDX17 in vivo. In the present study, we found that circDDX17 was downregulated in PA tissues correlated with invasion, tumor size, and progression-free survival of patients with PA. Enforced expression of circDDX17 significantly inhibited migration and invasion through miR-1279. Notably, CADM2 was verified as the direct binding target of miR-1279, and silencing the expression of CADM2 reverses the tumor suppressing effects induced by circDDX17 overexpression. We demonstrated that circDDX17 upregulated the expression of CADM2 by sponging miR-1279, which suppressed the invasive biological behaviors of PA. CircDDX17 may serve as a tumor suppressor and potential promising biomarker and effectively therapeutic target for the management of PA.

In Reply: A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

In Reply: A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

Endoscopic Transsphenoidal Surgery of Pituitary Adenomas: Preliminary Results of the Neurosurgery Service of Hospital Cristo Redentor

Abstract Objective The transsphenoidal surgery is a safe and effective technique to manage different skull base pathologies, such as pituitary adenomas. The purpose of the present study is to describe the initial experience with endoscopic transsphenoidal surgery in the treatment of pituitary adenoma patients at a tertiary hospital that is a reference in neurosurgery in Southern Brazil. Materials and Methods We retrospectively analyzed data from 60 patients with pituitary adenoma who underwent endoscopic transsphenoidal surgery between 2012 and 2019. Demographic characteristics, type of tumor, baseline hormonal changes, and clinical presentation were reported, as well as postoperative outcomes, tumor resection rate, and complications. Results The male/female ratio was of 0.53:1, and the mean age of the sample was of 54 (range: 26 to 79) years. In total, 34 patients (57%) presented the non-functioning adenoma subtype, and 26 (43%), the functioning adenoma subtype. In the non-functioning and functioning subtype groups, the average tumor diameter was of 32 mm and 18 mm, and the mean follow-up was of 27 months and 32 months respectively. Regarding visual symptoms, 79% of the patients showed improvement after surgery. Hormonal remission was achieved in 71% of the patients with prolactinoma, 85% of those with cushing, and 57% of patients with acromegaly. Overall, gross total resection (GTR) was achieved in 50% of patients but with a significantly lower rate among patients with tumors with parasellar growth (high grade on the Knosp classification). The most prevalent surgical complications observed were postoperative cerebrospinal fluid (CSF) leak and meningitis in 11% and 6% of the cases respectively. Conclusion We have shown that transsphenoidal endoscopic surgery can produce good results in the management of pituitary adenomas, with acceptable peri- and postoperative morbidity and mortality. Regardless of the technique used, the presence of large and giant pituitary adenomas with a high Knosp grade represents an enormous challenge for contemporary neurosurgery.

A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery. To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed. Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (β = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach. Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices.

Pituitary adenomas in children and adolescents: Diagnostic challenge

Pituitary adenomas have a low incidence in pediatric and adolescent patients, ant they are usually benign and relatively common intracranial tumors, with under- and overexpression of pituitary hormones and local mass effects causing considerable morbidity and increased mortality We report the observations of three patients who presented visual disorders, an MRI was done objectifying a sellar tumoral process with suspicion of a craniopharyngioma for the 3 cases, a surgical treatment was indicated with rectification of the diagnosis after the anatomopatho-immunohistochemical study, which concluded to a prolactinoma for 1st end 2nd cases which were put under dopamine agonists, and to a somatotropic adenoma for 3rd case which was addressed for revision surgery. Immunohistochemistry remains the key element in diagnosing pituitary tumors and orientating their management. The management of pituitary adenomas in pediatric patient’s mimic’s patterns of management in the adult population end requires a multidisciplinary management.

Complications in Endoscopic Endonasal Pituitary Adenoma Surgery: An Institution Experience in 310 Patients.

Objective  Endoscopic endonasal approaches (EEAs) have shown excellent results for majority of hypophyseal tumors. The aim of this study was to evaluate and report the complications of EEA in patients with pituitary adenoma (PA) who underwent surgery between 2013 and 2018. Methods  We performed a retrospective review of 310 consecutive patients/325 procedures with PA treated with an EEA from May 2013 to January 2018. Minor complications including transient diabetes insipidus (DI) or new anterior pituitary hormone insufficiency in one axis and major complications including CSF leakage, hematoma needing reoperation, vascular damage, brain infection, new pan-hypopituitarism permanent DI, new visual impairment, neurological deficits, and mortality were recorded. Results  We encountered 58 complications in 310 patients (18.7%) and 325 procedures (17.7%). Minor complications were 43 (13.9 and 13.2%) in 310 patients and in 325 procedures, respectively; whereas, major complications were 28 (9 and 8.6%, respectively). Total complications were associated with diameter group 2 (>30 mm), diaphragm sella violation, suprasellar extension, parasellar involvement, nonfunctional secretory type, and intraoperative arachnoid tearing. Conclusion  EEA can be considered as a safe surgical treatment which has acceptable complications in the management of PAs.

Second brain tumours after pituitary irradiation: lower risk than once thought

Since its first proposal in the treatment of pituitary tumours more than a century ago, indications for cranial radiotherapy have notably evolved. In rare pituitary carcinomas, indication of radiotherapy remains undisputable after surgical treatment in case of remnant tumour or recurrence. Until the availability of effective medical treatment, radiotherapy was the second-line treatment for many secreting pituitary adenomas after surgery. Thanks to the use of cabergoline, which controls prolactin secretion and is able to shrink even giant macroprolactinomas, nowadays, radiotherapy is hardly ever proposed. 1 Chanson P Maiter D Prolactinoma. in: Melmed S The pituitary. 5th ed. Academic Press, London2022: 495-543 Google Scholar In patients with acromegaly, with the availability of somatostatin receptor ligands and growth hormone receptor antagonists, the indication of radiotherapy in patients in whom surgery was unable to achieve cure of the disease, has also clearly decreased over time. 2 Maione L Chanson P National acromegaly registries. Best Pract Res Clin Endocrinol Metab. 2019; 33101264 Crossref PubMed Scopus (37) Google Scholar In patients with non-functioning pituitary adenomas, indications for radiotherapy have also evolved—while it was routinely administered after surgery some decades ago, it is now reserved to patients with a postoperative remnant, with its timing, immediately after, or only in case of remnant regrowth, being a matter of debate. 3 Chanson P Dormoy A Dekkers OM Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas. Eur J Endocrinol. 2019; 181: 1-13 Crossref PubMed Scopus (15) Google Scholar Indeed, even if the efficacy of radiotherapy is remarkable for achieving local control of pituitary tumours (roughly 90% of cases), 4 Loeffler JS Shih HA Radiation therapy in the management of pituitary adenomas. J Clin Endocrinol Metab. 2011; 96: 1992-2003 Crossref PubMed Scopus (151) Google Scholar the issue of side effects and particularly late toxicities long after radiation exposure has somewhat dampened the enthusiasm for this technique. The main adverse effect of radiotherapy is the occurrence of anterior pituitary hormone deficiency in about 30% of individuals at 5 years and 50% at 10 years after fractionated radiotherapy, respectively. 3 Chanson P Dormoy A Dekkers OM Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas. Eur J Endocrinol. 2019; 181: 1-13 Crossref PubMed Scopus (15) Google Scholar , 5 Fernandez A Brada M Zabuliene L Karavitaki N Wass JA Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009; 16: 733-772 Crossref PubMed Scopus (68) Google Scholar Whether or not radiotherapy technical refinement (eg, use of fractionated stereotactic radiotherapy or radiosurgery) will decrease this rate remains to be determined. Optic neuropathy, another side effect of radiotherapy, is nowadays quite rare, thanks to the limited radiation dose administered to the optic chiasm, as a result of improvements in radiotherapy techniques. But one of the main concerns with radiotherapy was the potential occurrence of secondary brain tumours, 6 Yamanaka R Abe E Sato T Hayano A Takashima Y Secondary intracranial tumors following radiotherapy for pituitary adenomas: a systematic review. Cancers (Basel). 2017; 9: 103 Crossref Scopus (27) Google Scholar some being devastating (eg, glioblastomas) when radiotherapy had been used in these patients for treating a benign condition. However, in clinical practice, this adverse effect seemed to be much more exceptional than previously reported. Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillanceIrradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. Full-Text PDF Open Access

Transsphenoidal Surgery of Giant Pituitary Adenoma: Results and Experience of 239 Cases in A Single Center.

BackgroundTranssphenoidal surgery (TSS) is first-line treatment for giant pituitary adenomas (PAs). Although PA is a benign neuroendocrine tumor that originates from adenohypophysial cells, the surgical outcomes and prognosis of giant PAs differ significantly due to multiple factors such as tumor morphology, invasion site, pathological characteristics and so on. The aim of this study was to evaluate surgical outcomes of giant PAs in a single-center cohort.MethodsThe clinical features and outcomes of 239 patients with giant PA who underwent sphenoidal surgery at the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2021 were collected from medical records. The basic clinical information (age, gender, function etc.), surgical procedure, imaging features (maximum diameter, invasion characteristics, tumor shape etc.) and histopathological characteristics (pathological results, Ki-67, P53 etc.) were retrospectively reviewed. SPSS 25.0 and Stata 12.0 software were used for statistical analysis.ResultsA total of 239 patients with giant PAs underwent TSS, of which 168 surgeries (70.29%) were endoscopic endonasal transsphenoidal (EETS) and 71 (29.71%) were microscopic transsphenoidal (MTS). The mean preoperative maximum diameter in the cohort was 45.64 mm. Gross-total resection was achieved in 46 patients (19.25%), near-total in 56 (23.43%), subtotal in 68 (28.45%), and partial in 69 (28.87%) patients. The maximum tumor diameter and Knosp grade were the significant factors that limited the extent of the resection of giant PAs. A total of 193 patients (80.75%) experienced surgical complications, and the most common complications were postoperative diabetes insipidus (DI) (91, 38.08%), intracranial infection (36, 15.06%) and cerebrospinal fluid (CSF) leaks (37, 15.48%). In addition, there was a significant difference in the incidence of CSF leaks between the neuroendoscopy group and the microscopic group (P < 0.05).ConclusionThe management of giant PAs remains a therapeutic challenge due to their large size and postoperative complications. The maximum diameter and Knosp grade of giant PAs significantly limited the extent of resection, which warrants a reasonable surgical plan.

Nonsurgical Management of a Patient with Hypopituitarism Secondary to Nonfunctioning Pituitary Macroadenoma: A Case Report

Pituitary adenoma is a benign neoplasm of pituitary gland. Pituitary adenoma, particularly a macroadenoma,may produce mass effect symptoms by compressing surrounding tissues. Due to pituitary function as aneuroendocrine organ, pituitary adenoma may also cause multiple endocrine disturbances. The authors reportthe case of a 39-year-old male patient presenting with chronic headache and history of seizure. MRI imagingrevealed pituitary macroadenoma with optic chiasm compression. Further diagnostic workup indicatedsecondary hypogonadism and adrenal insufficiency. The patient was given hormone replacement therapyand was then advised for surgery, but the patient refused any surgical procedure. Subsequent follow-upswere somewhat difficult due to poor patient adherence. Nevertheless, appropriate management of pituitaryadenoma is needed to achieve optimal result.

Using Molecular Imaging to Enhance Decision Making in the Management of Pituitary Adenomas.

In most patients with suspected or confirmed pituitary adenomas (PAs), MRI, performed using T1- (with or without gadolinium enhancement) and T2-weighted sequences, provides sufficient information to guide effective clinical decision making. In other patients, additional MR sequences (e.g., gradient recalled echo, fluid-attenuation inversion recovery, MR elastography, or MR angiography) may be deployed to improve adenoma detection, assess tumoral consistency, or aid distinction from other sellar/parasellar lesions (e.g., aneurysm, meningioma). However, there remains a small but important subgroup of patients in whom primary or secondary intervention (e.g., first or redo transsphenoidal surgery, stereotactic radiosurgery) is limited by the inability of MRI to accurately localize the site(s) of de novo, persistent, or recurrent PA. Emerging evidence indicates that hybrid imaging, which combines molecular (e.g. 11C-methionine PET) and cross-sectional (MRI) modalities, can enable the detection and precise localization of sites of active tumor to guide targeted intervention. This not only increases the likelihood of achieving complete remission with preservation of remaining normal pituitary function but may mitigate the need for long-term (even lifelong) high-cost medical therapies. Here, we review published evidence supporting the use of molecular imaging in the management of PAs, including our own 10-y experience with 11C-methionine PET.

The use of mass spectrometry in a proteome-centered multiomics study of human pituitary adenomas.

A pituitary adenoma (PA) is a common intracranial neoplasm, and is a complex, chronic, and whole-body disease with multicausing factors, multiprocesses, and multiconsequences. It is very difficult to clarify molecular mechanism and treat PAs from the single-factor strategy model. The rapid development of multiomics and systems biology changed the paradigms from a traditional single-factor strategy to a multiparameter systematic strategy for effective management of PAs. A series of molecular alterations at the genome, transcriptome, proteome, peptidome, metabolome, and radiome levels are involved in pituitary tumorigenesis, and mutually associate into a complex molecular network system. Also, the center of multiomics is moving from structural genomics to phenomics, including proteomics and metabolomics in the medical sciences. Mass spectrometry (MS) has been extensively used in phenomics studies of human PAs to clarify molecular mechanisms, and to discover biomarkers and therapeutic targets/drugs. MS-based proteomics and proteoform studies play central roles in the multiomics strategy of PAs. This article reviews the status of multiomics, multiomics-based molecular pathway networks, molecular pathway network-based pattern biomarkers and therapeutic targets/drugs, and future perspectives for personalized, predeictive, and preventive (3P) medicine in PAs.

Long-term cardiometabolic outcome in patients with pituitary adenoma diagnosed in chilhood and adolescence

Pituitary adenomas (PAs) rarely occur in childhood and adolescence. Management of PAs in this critical age can be particularly challenging considering the auxological sequelae and potential long-term cardiometabolic consequences. We aimed to describe the clinical characteristics of patients with PA aged < 18years at diagnosis and during long-term follow-up, focusing on the prevalence of cardio-metabolic comorbidities and the impact of different therapeutic strategies. Clinical data at diagnosis and at last follow-up visit (mean 10.3 ± 9.2years) of 101 patients aged < 18years with PA, referred to our University Hospital from 1990 to 2017, were retrospectively evaluated. At diagnosis, 11.9% of patients presented with pituitary hormone deficiencies, whose number was positively correlated with pituitary tumor diameter (p < 0.001). At diagnosis, 26.7% of patients were overweight and 15.8% were obese. In patients with hypercortisolism or GH excess the prevalence of obesity was more than 2-fold greater than in general population. No correlation was found between pituitary tumor size and BMI. At baseline, the greater the number of pituitary hormone deficits, the higher BMI (p = 0.039). In prolactinoma patients still on medical therapy at last visit, BMI was higher than at baseline. We found an increased prevalence of overweight/obesity only in pediatric and adolescent patients with GH- or ACTH-secreting PA. Regarding cardio-metabolic comorbidities other than obesity/overweight, we have not found anything worth of mention. The remission of hypercortisolism positively impacted on BMI, while medical therapy in patients with prolactinoma seemed unable to avoid weight gain, suggesting a careful metabolic management of these patients.

Impact of age on postsurgical outcomes of nonfunctioning pituitary adenomas.

The management of pituitary adenomas in the elderly has become a relevant clinical issue, in relationship with improved life expectancy and spreading use of imaging techniques. In this single-center and retrospective study, we investigated the impact of age on peri- and postsurgical outcomes in patients undergoing transnasal sphenoidal (TNS) surgery for pituitary adenomas. One-hundred-sixty-nine patients (62% males) undergoing endoscopic transphenoidal (TNS) surgery for nonfunctioning pituitary adenomas (NFPAs) were enrolled. Patients were subdivided into three groups according to age tertiles: ≤56 (group 1), 57-69 (group 2), and ≥70 (group 3) years. Postsurgical and endocrinological outcomes were evaluated and compared among the three age groups. 37/169 patients (21.9%) developed at least one perisurgical complication, without significant association with the patients' age (P = 0.838), Charlson co-morbidity score (P = 0.326), and American Society of Anesthesiologist score (P = 0.616). In the multivariate regression analysis, the adenoma size resulted the only determinant of perisurgical complication (odds ratio [OR] 1.07, 95% confidence interval [C.I.] 1.00-1.13; P = 0.044). The development and the recovery of at least one pituitary hormone deficiency were observed in 12.2% and 14.2% of patients, respectively. The risk of developing new pituitary hormone deficiencies was correlated with cavernous sinus invasion as evaluated by magnetic resonance imaging (hazard ratio [HR] 4.19, 95% C.I. 1.39-12.66; P = 0.010), whereas the probability to normalize at least one pituitary hormone deficiency was significantly correlated with younger age of patients (HR 0.27, 95% CI 0.12-0.61; P = 0.002). The results of this study reinforce the concept that endoscopic TNS surgery is a safe therapeutic option in the elderly patients with NFPA, even in presence of comorbidities and high anesthetic risk.

Radiation therapy in the management of pituitary adenomas

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: The roles of AIP and GPR101 in familial isolated pituitary adenomas (FIPA).

Familial isolated pituitary adenoma (FIPA) is one of the most frequent conditions associated with an inherited presentation of pituitary tumors. FIPA can present with pituitary adenomas of any secretory/non-secretory type. Mutations in the gene for the aryl-hydrocarbon receptor interacting protein (AIP) have been identified in approximately 20% of FIPA families and are the most frequent cause (29%) of pituitary gigantism. Pituitary tumors in FIPA are larger, occur at a younger age and display more aggressive characteristics and evolution than sporadic adenomas. This aggressiveness is especially marked in FIPA kindreds with AIP mutations. Special attention should be paid to young patients with pituitary gigantism and/or macroadenomas, as AIP mutations are prevalent in these groups. Duplications on chromosome Xq26.3 involving the gene GPR101 lead to X-linked acrogigantism (X-LAG), a syndrome of pituitary gigantism beginning in early childhood; three kindreds with X-LAG have presented in the setting of FIPA. Management of pituitary adenomas in the setting of FIPA, AIP mutations and GPR101 duplications is often more complex than in sporadic disease due to early onset disease, aggressive tumor growth and resistance to medical therapy.

Current Status of Diagnosis and Management for Functioning Pituitary Tumors: Part I.

Pituitary adenomas (PA) account for approximately 15% of all intracranial neoplasms. Pituitary adenomas can be of different subtypes based on the cell of origin or associated hormone hypersecretion (non-functioning pituitary adenoma, prolactinoma, somatotropinoma, corticotropinoma, thyrotropinoma, and gonadotropinoma). Functioning PAs are associated with relatively higher morbidity and mortality because of associated hormone hypersecretion syndromes. Diagnosis of functioning PA is established by biochemical confirmation of hormone hypersecretion and demonstration of a pituitary lesion on imaging. Trans-sphenoidal surgical resection of tumor represents the first-line treatment for most tumor types, except for prolactinomas where medical therapy with dopamine agonists is preferred. Radiotherapy (RT) and medical therapy are the other options for the management of PA. It is important to individualize treatment options based on tumor type, patient's clinical condition, expertise of surgeon, affordability and patient preferences. In the first part of this series, we review the presentation and management of adrenocorticotropic hormone secreting, gonadotropin secreting and aggressive PA. Despite several recent advances, the diagnosis and management of Cushing's disease is still a challenge. Modifications in magnetic resonance imaging techniques like volume interpolated 3D spoiled gradient echo sequence have improved the sensitivity to detect microcorticotropinomas. Pituitary RT, preferably conventional RT, is a useful second-line therapy for the management of CD. Besides the conventional drugs, few drugs such as pasireotide and osilodrostat have been approved by US FDA recently, whereas several others are in pipeline which provide hope for a better outcome in CD patients. Temozolomide is a useful drug for the management of aggressive PA.

Role of Stereotactic Radiosurgery in Pituitary Adenomas.

Pituitary adenomas are one of the common indications for gamma knife radiosurgery. Gamma knife enables one to deliver a very high radiation dose to the target in a single fraction. Due to steep radiation fall out of Gamma Knife, the adjacent visual apparatus gets minimal radiation. The aim of stereotactic radiosurgery for pituitary adenomas is to stop tumor growth, normalize hormonal hypersecretion, preserve pituitary function, and protect important surrounding structures. Surgery is the treatment modality of choice in the management of pituitary adenomas and gamma knife radiosurgery is restricted for residual or recurrent lesions only. The acceptable marginal dose for non-functional adenomas is 12 Gy. Control rates varies from 76-87% at 10 years are described in non-functional pituitary adenomas. In functional adenomas, to achieve hormonal remission a higher marginal dose up to 25 Gy is needed. However, primary gamma knife radiosurgery is needed in some situations - for instance, when the patient is unfit for surgery due to various reasons or surgical difficulties like the presence of kissing carotids.