Genetic diagnosis in acromegaly and gigantism: From research to clinical practice.

It is usually considered that only 5% of all pituitary neuroendocrine tumours are due to inheritable causes. Since this estimate was reported, however, multiple genetic defects driving syndromic and nonsyndromic somatotrophinomas have been unveiled. This heterogeneous genetic background results in overlapping phenotypes of GH excess. Genetic tests should be part of the approach to patients with acromegaly and gigantism because they can refine the clinical diagnoses, opening the possibility to tailor the clinical conduct to each patient. Even more, genetic testing and clinical screening of at-risk individuals have a positive impact on disease outcomes, by allowing for the timely detection and treatment of somatotrophinomas at early stages. Future research should focus on determining the actual frequency of novel genetic drivers of somatotrophinomas in the general population, developing up-to-date disease-specific multi-gene panels for clinical use, and finding strategies to improve access to modern genetic testing worldwide.

[Acromegaly in the differential diagnosis of hearing loss].

Acromegaly is a multifactorial neuroendocrine disease caused by hyperproduction of growth hormone (GH). In more than 95% of cases the reason of acromegaly the GH-secreting pituitary adenoma. In patients with this neuroendocrine disease, a slowly developing complex of symptom can manifest with concomitant pathological conditions, including auditory function disordersDiagnostic difficulties of acromegaly at the ambulatory stage determine the importance of doctor`s awareness in different medical specialties.Here we demonstrate a clinical case of the improvement of the auditory function due to combined surgical and medical treatment of a patient with the pituitary macroadenoma, acromegaly and hearing loss.Anamnesis features: a patient with an active stage of acromegaly and a pituitary macroadenoma measuring 57x35x32 mm with ante-, supra-, infra-, parasellar spread, (Knosp III(D), Knosp IV(S) noted a violation of auditory function. She was consulted by an otolaryngologist, sensorineural hearing loss on the right of the 3rd degree was diagnosed, on the left of the 1st degree. The patient underwent surgical treatment of pituitary adenoma, noted a significant improvement in auditory function in the early postoperative period. Six months later, repeated audiometry was performed, marked regression of hearing damage was noted.The case described by us indicates the reversibility of a rare complication of acromegaly - hearing loss and the importance of an interdisciplinary approach in the management of patients with this pathology.

Caloric restriction as a possible pitfall for persistent acromegaly follow-up - case report.

BACKGROUND: Acromegaly diagnosis is established when plasma levels of IGF-1 are increased and the Oral Glucose Tolerance Test (OGTT) with 75gr of glucose can't suppress Growth Hormone (GH) levels. These two parameters are also useful during follow-up, after surgical/radiologic therapy and/or during medical therapy. CASE PRESENTATION: A 29-year-old woman was diagnosed with acromegaly after a severe headache. Previous amenorrhea and facial and acral changes were noticed. A pituitary macroadenoma was found, biochemical evaluation was in agreement with the suspected acromegaly and a transsphenoidal adenectomy was performed. As the disease recurred, a surgical reintervention and radiosurgery (Gamma Knife, 22 Gy) were necessary. No normalization of IGF-1 was achieved during three years after radiosurgery. Surprisingly, then, and although clinical features seemed getting worse, IGF-1 levels became consistently controlled to 0.3-0.8 times the upper limit of the reference range. Questioned, the patient referred that she was following an intermittent fasting dietary plan. However, based on the dietary questionnaire, she was found to be under severe caloric restriction. First OGTT (under caloric restriction) showed absence of GH suppression and an IGF-1 value of 234 ng/dL (Reference Range 76-286 ng/mL). A second OGTT, one month after an eucaloric diet was instituted, showed an increased IGF-1 of 294 ng/dL, maintaining an unsuppressed, yet less elevated, GH. CONCLUSIONS: GHRH/GH/IGF-1 axis controls somatic growth. Regulation is complex, and nutrition status and feeding pattern have a recognized role. Like systemic inflammation or chronic liver disease, fasting and malnutrition decrease the expression of hepatic GH receptors, with consequent reduction of IGF-1 levels, through resistance to GH. This clinical report shows that caloric restriction may represent a pitfall in acromegaly follow-up.

Growth Hormone Excess: Implications and Management.

Acromegaly is described as the oversecretion of growth hormone (GH) and, subsequently, insulin-like growth factor 1 (IGF-1), ascribed in most cases to a pituitary adenoma. This disease presents a progressive disfigurement, along with other systemic manifestations, which altogether diminishes the quality of life in the patients. Prolonged exposure to abnormally high levels of GH and IGF-1 levels results in cardiovascular, cerebrovascular, and pulmonary dysfunction which overall produces a fall in life expectancy. Timely diagnosis and further treatment decreased the mortality rate of the patients and showed an improvement in the quality of life. Surgical procedures, advanced radiation therapy tools, and the availability of pharmacological compounds that act on pituitary growth hormone-producing cells have enabled an improved approach to treating the disease. Pharmacological treatment is currently an important management option, and it may also be the first-line treatment in patients with acromegaly who do not benefit from or are ineligible for first-line surgical procedures. From its inception until 2021, we used a comprehensive search strategy on Medline/PubMed, Scopus, Embase, Web of Science, and the Cochrane Library electronic databases. All human research articles and review articles published in English were considered for the review. In this review, we describe the clinical implications and management of patients with acromegaly, consisting of scientific improvements underlying the developing understanding of pathogenesis and diagnosis, associated comorbidities and mortality rate with the disease, and major improvements in the treatment of the disease, along with novel strategies including quality of life and patient-reported outcomes.

Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas.

PURPOSE: Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated. METHODS: In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored. RESULTS: Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein-protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected. CONCLUSION: Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.

Predictors for Remission after Transsphenoidal Surgery in Acromegaly: A Dutch Multicenter Study.

CONTEXT: Transsphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. It is important to identify patients in whom surgical cure is not attainable at an early stage, both to inform patients on expected treatment outcome and to select those who are more likely to need additional therapy. OBJECTIVE: To identify predictors for remission after TSS in acromegaly. METHODS: Large multicenter study with retrospective data collection from 3 tertiary neurosurgical referral centers in The Netherlands. We analyzed clinical data since 2000 from 3 cohorts (Groningen, Nijmegen, and Rotterdam, total n = 282). Multivariate regression models were used to identify predictors of early biochemical remission (12 weeks to 1 year postoperatively) according to the 2010 consensus criteria, long-term remission (age- and sex-normalized insulin-like growth factor 1 [IGF-1] and the absence of postoperative treatment until last follow-up), and relative IGF-1 and growth hormone [GH] reduction. RESULTS: A larger maximum tumor diameter (odds ratio [OR] 0.91, 95% CI 0.87-0.96, P ≤ .0001) was associated with a lower chance of early biochemical remission. A larger maximum tumor diameter (OR 0.93, 95% CI 0.89-0.97, P = .0022) and a higher random GH concentration at diagnosis (OR 0.98, 95% CI 0.96-0.99, P = .0053) were associated with a lower chance of long-term remission. CONCLUSION: Maximum tumor diameter and random GH concentration at diagnosis are the best predictors for remission after TSS in acromegaly.

Two Cases of Double Pituitary Adenomas in a Surgical Series Over 16 Years in a Single Centre.

BACKGROUND: Double pituitary adenomas (DA) are two morphologically and immunohystochemically different tumours in the same gland. They are rare, generally small adenomas and divided in: separated, when clearly recognizable before or during surgery, and contiguous, when diagnosed only in the following histopathological examination. Acromegaly and Cushing's disease are the main prevalent clinical presentation. OBJECTIVE: We described two cases of DA in a surgical series over 16 years in a single center. METHODS: In September 2018, we diagnosed a DA in a man with acromegaly (case 1). In order to assess the presence of other cases of DA, we performed a retrospective analysis of the endonasal endoscopically operated sellar adenomas from January 2004 to December 2019. RESULTS: 468 pituitary adenomas were found. A DA with a Pit-1 positive macroadenoma (GH-TSH- PRL positive) and an ACTH microadenoma clinically silent in an acromegalic woman was retrospectively found (case 2). CONCLUSION: Our analysis confirms that DA are rare (0.4% of the pituitary adenomas) and often associated with acromegaly. Their pre-operatively diagnosis is difficult but clinician's awareness of DA can improve the diagnosis. The use of pituitary transcription factors could be useful in detecting DA.

Acromegaly accompanied by diabetes mellitus and polycystic kidney disease.

Acromegaly is characterized by autonomous excessive growth hormone (GH) secretion, generally due to GH-producing pituitary adenoma, and is associated with various systemic comorbidities including diabetes mellitus. Polycystic kidney disease (PKD) is characterized by the growth of numerous cysts in the kidneys that deteriorate renal function. While possible renal effects of excessive GH exposure have been a current issue in experimental medicine, only five cases of coexisting acromegaly and PKD have been reported previously, and little is known regarding the influence of acromegaly on renal disease. We treated a 50-year-old male with diabetes mellitus who showed a sudden and rapid decline of renal function along with increasing proteinuria, which led to diagnoses of PKD and acromegaly. His urinary protein levels were increased together with excessive GH secretion and worsening glycemic control. An increase of total kidney volume was also noted. Transsphenoidal surgery for the pituitary adenoma was successfully performed. Marked improvement of hyperglycemia and proteinuria were observed after the surgery, but renal function was unchanged. The patient's clinical course suggested common aspects of excessive GH secretion as an accelerating factor of the progression of diabetic nephropathy and PKD via direct and indirect pathways. Although coexisting acromegaly and PKD is clinically rare, vigilance for early diagnosis of acromegaly is appropriate in patients with diabetes and/or PKD, especially in those showing unexpected exacerbation of renal dysfunction.

Intensity-modulated Radiotherapy for Pituitary Somatotroph Adenomas.

OBJECTIVE: To summarize our experience in the treatment of pituitary somatotroph adenomas by fractionated intensity-modulated radiotherapy (IMRT), describe the treatment outcomes, and determine predictors. METHODS AND MATERIALS: Patients with pituitary somatotroph adenoma treated by IMRT in our institution from August 2009 to January 2019 were reviewed. A total of 113 patients (37 male) were included in this study. The median age was 33 years (range 12-67 years). A total of 112 patients had not achieved complete remission after surgery, and 1 patient was treated by radiotherapy (RT) alone because she refused to surgery. The median growth hormone level was 8.6 ng/mL (range 2-186 ng/mL) and the median insulin-like growth factor (IGF)-1 level was 732 ng/mL (range 314-1485 ng/mL) pre-RT. The radiation doses to clinical target volume were usually 50-56 Gy in 25 to 30 fractions and to gross tumor volume were 60.2 Gy in 28 fractions while simultaneous integrated boost-IMRT used. After RT, the patients were followed up with endocrine testing every 6 to 12 months and magnetic resonance imaging annually. Endocrine complete remission was defined as a normal sex- and age-adjusted IGF-1 level without any pituitary suppressive medications. The outcomes including endocrine remission and new hypopituitarism after RT were recorded. The median follow-up time was 36 months (range 6-105.5 months). RESULTS: The endocrine complete remission rates of IGF-1 at 1, 2, 3, and 5 years were 6%, 22.8%, 48.6%, and 74.3%, respectively. The median time to complete remission was 36.2 ±â€…3.8 months. The tumor control rate was 99% during the follow-up. The overall incidence of RT-induced hypopituitarism was 28.3% at the last follow-up. Univariate and multivariate analysis demonstrated that tumor sizes before RT, pre-RT IGF-1 level, and age significant predicted the endocrine remission. CONCLUSIONS: IMRT is a highly effective treatment for pituitary somatotroph adenoma. Endocrine remission rate, tumor control rate, the median time to remission and hypopituitarism incidence are similar to stereotactic radiosurgery. Age and IGF-1 level before RT were significant predictive factors in endocrine remission.

Surgical and Pharmacological Outcomes in Acromegaly: Real-Life Data From the Mexican Acromegaly Registry.

CONTEXT: Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life. OBJECTIVE: The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR). DESIGN AND METHODS: Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN. RESULTS: A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity. CONCLUSION: Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.

Updates in Feline Diabetes Mellitus and Hypersomatotropism.

Flash glucose monitoring is a novel, noninvasive monitoring technique that is increasingly used in the management of small animal diabetes. This article provides guidance on the use of flash glucose monitoring in cats and demonstrates how this technique can be used in a range of feline diabetic cases, including those where management is proving challenging. Other aspects of complicated feline diabetic care are also discussed, including management of the sick diabetic cat, potassium depletion myopathy, and treatment options for cats with hypersomatotropism-associated diabetes mellitus. The use of insulin glargine 300 U/ml as a promising new long-acting insulin for diabetic cats is also discussed.

Thyroid and colorectal cancer screening in acromegaly patients: should it be different from that in the general population?

The literature on an association between acromegaly and cancer is particularly abundant on either colorectal cancer or thyroid cancer, and an endless debate is ongoing whether patients with acromegaly should be submitted to specific oncology screening and surveillance protocols. The aim of the present work is to review the most recent data on the risk of either colorectal cancer or thyroid cancer in acromegaly and discuss the opportunity for specific screening in relation to the accepted procedures in the general population.

Ectopic GH-secreting pituitary adenoma of the clivus: systematic literature review of a challenging tumour.

PURPOSE: Acromegaly is usually due to growth hormone (GH)-secreting pituitary adenomas, but it may be exceptionally caused by GH-secreting ectopic pituitary adenomas (EPA). EPA are defined as extra-sellar pituitary tumours, extra- or intra-cranially sited, entirely separated from the pituitary stalk and gland. The aim of the study is to address the challenges in the management of clival GHEPA. METHODS: We reported a case of a 53-year-old acromegalic patient with a primary clival GHEPA and reviewed systematically the relevant English literature between 1975 and 2019, in keeping with the PRISMA guidelines. RESULTS: Four cases of primary clival GHEPA have been described in literature apart from ours. All patients presented with acromegalic features, elevated circulating GH and/or insulin-like growth factor-1 levels. Hyperprolactinemia and empty sella were described in two cases, respectively. These tumours show the typical imaging characteristics of pituitary adenomas, but their neuroradiological diagnosis may be challenging due to their sizes and the difficulty in defining the absence of connections with the pituitary fossa. CONCLUSION: Although primary clival GHEPA are exceedingly rare, even if likely under-reported in literature, they should be considered in the differential diagnosis of clival tumours because of their specific management. Surgery represents the first-line treatment option, while medical and radiation therapies can be adopted as neo-adjuvant, adjuvant or primary treatments according to tumour and patient characteristics.

Fluctuation analysis of postoperative secretory status in patients operated for acromegaly.

OBJECTIVE: The aim of this study was to describe endocrinological outcome in patients operated on for acromegaly. METHODS: A retrospective study included 167 patients. Patients were assessed in the early postoperative period (EPP), at 3 months (M3), at 1 year (Y1), and then annually. They were classified as grade I (IGF-1 level normal-for-age and positive GH response on oral glucose tolerance test [nadir <0.4ng/L]); grade II (discordant); or grade III or IV (acromegaly, controlled or uncontrolled under medical therapy, respectively). RESULTS: Taking all patients with all grades, 35% changed grades between EPP and M3, 26% between M3 and Y1 and 9% after Y1. In grade I, respectively 22%, 15% and 2% of patients changed grades between EPP and M3, between M3 and Y1, and after Y1, compared to 31%, 6% and 6% in grade IV. Respectively 57%, 67%, and 47% of grade II patients changed grades between EPP and M3, between M3 and Y1, and after Y1; between EPP or M3 and last follow-up (>1 year), respectively 74% and 75% of grade II patients changed grades. Knosp category, resection quality and abnormal GH response (vs. abnormal IGF-1) significantly impacted grade II patients' outcome. CONCLUSIONS: Whereas outcome in grades I and III-IV seems to be determined by 1 year, grade II discordant patients' outcome remains uncertain even after 1 year.

Significant Benefits of AIP Testing and Clinical Screening in Familial Isolated and Young-onset Pituitary Tumors.

CONTEXT: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). OBJECTIVE: To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. DESIGN: 12-year prospective, observational study. PARTICIPANTS & SETTING: We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. INTERVENTIONS & OUTCOME: AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). RESULTS: Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). CONCLUSIONS: Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

Simultaneous diagnosis of glioblastoma, cervical schwannoma, adrenal masses and growth hormone-secreting adenoma in a previously healthy patient.

A constellation of newly diagnosed benign tumours and glioblastoma is an uncommon occurrence in a single individual. We present a case of a patient with a history of skin lipomas who presented with seizures and was found to have a left frontotemporal multifocal enhancing mass on MRI. Work-up for metastatic disease revealed a benign lung carcinoid tumour, a cervical schwannoma, adrenal masses, a growth hormone-secreting pituitary adenoma, and lastly a glioblastoma following brain biopsy.

[Acromegaly due to a pituitary tumor in a dog - diagnosis, therapy and long-term follow-up]. / Akromegalie aufgrund eines Hypophysentumors bei einem Hund ­ Diagnose, Therapie und Verlauf.

INTRODUCTION: Acromegaly due to a pituitary tumor has so far only been described in 3 dogs. The present case report describes a 7-year-old male-castrated Labrador Retriever which was referred because of difficult-to-control diabetes. Physical examination revealed markedly enlarged head, tongue and paws, widened interdental spaces and thickening of the skin in the head and neck area. IGF-1 and GH were increased and the latter continued to be abnormal after somatostatin application. Computed tomography demonstrated a space-occupying lesion in the pituitary gland and the diagnosis of acromegaly due to a GH-producing tumor of the pituitary was made. The dog underwent radiation therapy with a 6MV linear accelerator (3×8Gy) and improved substantially. Two and a half years after radiation therapy the dog developed lethargy and anorexia and was euthanized. Necropsy was not permitted. This case report represents the description of a dog suffering from pituitary-dependent acromegaly which was successfully treated and had a long-term survival.

INTRODUCTION: L'acromégalie due à une tumeur hypophysaire n'a jusqu'à présent été décrite que chez 3 chiens. Le présent rapport de cas décrit un Labrador Retriever de 7 ans mâle castré, qui a été référé en raison d'un diabète difficile à contrôler. L'examen physique a révélé une tête, une langue et des pattes de taille nettement augmentée, des espaces interdentaires élargis et un épaississement de la peau dans la région de la tête et du cou. L'IGF-1 et la GH étaient augmentées et la seconde restait anormale après l'application de somatostatine. La tomodensitométrie a mis en évidence une masse dans la région de l'hypophyse et le diagnostic d'acromégalie due à une tumeur de l'hypophyse productrice de GH a été posé. Le chien a subi une radiothérapie avec un accélérateur linéaire de 6MV (3×8Gy) et son état s'est considérablement amélioré. Deux ans et demi après la radiothérapie, le chien développa une léthargie et une anorexie et fut euthanasié. L'autopsie n'a pas été autorisée. Ce rapport de cas représente la description d'un chien souffrant d'acromégalie dépendant de l'hypophyse, traité avec succès et ayant une survie à long terme.

Silent pituitary plurihormonal adenoma: clinical relevance of immunohistochemical analysis / Adenoma hipofisario silente plurihormonal: relevancia clínica de la inmunohistoquímica

Background: Non-functional pituitary adenomas (NFPAs) present low growth rates; however, some are aggressive and invasive. In 2017 the World Health Organization recognized clinically aggressive adenomas as "high-risk pituitary adenomas". These include the sparsely granulated somatotroph adenoma, the Crooke's cell adenoma, the silent corticotroph adenoma and the plurihormonal Pit-1-positive adenoma (subtype 3). Clinical case: 25-year-old woman who presented oligomenorrhea, increased weight, decreased visual acuity and chronic headache. Biochemical and imaging evaluation showed a NFPA. Transsphenoidal surgery was performed with complete resection of lesion, and during short-term follow-up it was observed recurrence, which is why the patient needed two more interventions. The immunohistochemistry reported: ACTH ++ 90%, prolactin ++ 20%, GH ++ 5%, CKAE1-AE3 +++ 90%, Ki-67 10%. The final diagnosis was plurihormonal adenoma, since the immunohistochemical analysis was positive for more than one pituitary hormone and suggested two distinct cell lineages: Pit-1 and Tpit, both recognized as aggressive adenomas. Conclusions: This case report highlights the significance of a comprehensive immunohistochemical study, which includes transcriptional factors to classify cell lineage, in order to predict aggressiveness and provide personalized treatment.

Introducción: los adenomas hipofisarios no funcionantes (AHNF) presentan una baja tasa de crecimiento; sin embargo, algunos son agresivos e invasivos. En 2017 la Organización Mundial de la Salud denominó los adenomas de comportamiento clínico agresivo como "tumores hipofisarios de alto riesgo", incluyendo los adenomas del somatotropo escasamente granulados, los adenomas de células de Crooke, los silentes de corticotropo y los adenomas plurihormonal Pit-1 positivo (subtipo 3). Caso clínico: mujer de 25 años de edad con oligoamenorrea, aumento de peso, disminución del campo visual y cefalea crónica. La evaluación bioquímica y de imagen correspondió a un AHNF. Se realizó cirugía transesfenoidal con resección completa de la lesión y durante el seguimiento a corto plazo se observó recurrencia tumoral, por lo que ameritó dos intervenciones más. La inmunohistoquímica reportó: ACTH ++ 90%, prolactina ++ 20%, GH ++ 5%, CKAE1-AE3 +++ 90%, Ki-67 10%. El diagnóstico definitivo correspondió a un adenoma plurihormonal, debido a que la inmunohistoquímica fue positiva para la expresión de más de una hormona hipofisaria, con sugerencia de contenido celular con dos linajes distintos, tanto de Pit-1 como de Tpit, ambos reportados como adenomas agresivos. Conclusiones: este caso resalta la importancia de una inmunohistoquímica completa que incluya factores de transcripción que permitan clasificar el linaje celular para predecir agresividad y proporcionar un tratamiento individualizado.

Genetic Testing in Pituitary Adenomas: What, How, and In Whom? / Genética en adenomas hipofisarias: ¿qué, cómo y a quién?

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