The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas.

Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA.

The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.

Background: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood.

Methods: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors.

Clinical Heterogeneity of Ectopic ACTH Syndrome: A Long-Term Follow-Up Study.

Objective: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a heterogeneous condition caused by neuroendocrine neoplasms (NENs) located in the lungs, thymus, or pancreas. Our purpose was to evaluate the long-term outcome of these patients.

Methods: Retrospective study at a referral center.

Proteomic and Transcriptomic Analysis Identify Spliceosome as a Significant Component of the Molecular Machinery in the Pituitary Tumors Derived from - and -Cell Lineages.

Background: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA.

Erratum to "From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells".

[This corrects the article DOI: 10.1155/2020/4768281.].

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.

From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells.

Objective: To report the immunohistochemical and molecular evaluation of a patient with ectopic ACTH syndrome (EAS) from a MCAT which has single cells with features of both 96 medullary and cortical differentiation. . A 16-year-old woman presented with severe EAS and a large right MCAT composed of ACTH-secreting cells resembling pheochromocytoma and another lineage similar to adrenal carcinoma.

Prevalence, Clinical and Biochemical Spectrum, and Treatment Outcome of Acromegaly With Normal Basal GH at Diagnosis.

Context: The term micromegaly has been used to describe a subset of patients who have elevated IGF-1 levels but apparently normal basal GH (bGH) concentrations and often a glucose-suppressed GH of <1 ng/mL.

Objective: To evaluate the prevalence, clinical spectrum, and therapeutic outcome of acromegaly with normal bGH at diagnosis.

Design And Methods: Retrospective analysis of a cohort of patients with acromegaly diagnosed and treated at a tertiary care center.

Persistence of Diabetes and Hypertension After Multimodal Treatment of Acromegaly.

Context: Diabetes and hypertension are frequent comorbidities of acromegaly.

Objective: To analyze the course of diabetes and hypertension at diagnosis and after multimodal therapy in a large cohort of patients with acromegaly.

Design And Setting: Retrospective study at a tertiary care center.

LONG-TERM OUTCOME OF THE DIFFERENT TREATMENT ALTERNATIVES FOR RECURRENT AND PERSISTENT CUSHING DISEASE.

Objective: Treatment alternatives for persistent and recurrent Cushing disease (CD) include pituitary surgical re-intervention, radiation therapy (RT), pharmacotherapy, and bilateral adrenalectomy (BA). The decision of which of these alternatives is better suited for the individual patient rests on clinical judgment and the availability of resources. This retrospective cohort study was performed at a referral center to evaluate the long-term efficacy of different secondary interventions for persistent and recurrent CD.

AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience.

Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset <30 years was analysed (median age of disease onset of 23 years) and correlated with clinical, biochemical and imaging characteristics.

Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic.

Context: Acromegaly is usually due to the excessive secretion of GH by a pituitary adenoma. It is frequently accompanied by comorbidities that compromise quality of life and results in elevated mortality rates.

Objective: To evaluate mortality and morbidity in patients with acromegaly receiving multimodal care.

Octreotide LAR treatment of acromegaly in "real life": long-term outcome at a tertiary care center.

Objective: To report our day-to day experience with the long-term use of octreotide LAR in the treatment of acromegaly.

Patients And Methods: Patients with acromegaly managed between 2003 and 2012 with octreotide LAR for a median of 27 months (interquartile ranges 12-60) and who had not received radiation therapy or concomitant treatment with cabergoline were retrospectively evaluated. Both primarily treated patients (n = 33) and patients who received octreotide after failed pituitary surgery (adjunctive treatment, n = 124) were included.

The role of primary pharmacological therapy in acromegaly.

Background And Objectives: Primary pharmacological therapy may be the only viable treatment option for many patients with acromegaly, especially those presenting with advanced disease with large inoperable tumors. Long-acting somatostatin analogs are currently the first-line treatment of choice in this setting, where they provide biochemical control and reduce tumor size in a significant proportion of patients. We herein present a brief overview of the role of primary pharmacological therapy in the treatment of acromegaly within the context of Latin America and support this with a representative case study.

Ectopic acromegaly due to a GH-secreting pituitary adenoma in the sphenoid sinus: a case report and review of the literature.

Background: In more than 98% of cases, acromegaly is due to a GH-secreting pituitary adenoma. The term "ectopic acromegaly" includes neuroendocrine tumors secreting GH releasing hormone (GHRH), usually located in the lungs, thymus and endocrine pancreas. Considerably less frequent are cases of ectopic acromegaly due to GH-secreting tumors located out of the pituitary fossa; except for one isolated case of a well-documented GH-secreting lymphoma, the majority of these lesions are located in the sphenoid sinus.

Patient-focussed outcomes in acromegaly.

Background: Health-related quality of life (QoL) is severely impaired in acromegaly due to the physical and psychological consequences of the disease. Pharmacological and surgical treatments, when available, can improve QoL and life expectancy.

Case Description: A 34-year-old male with uncontrolled acromegaly due to a large and invasive macroadenoma, which could not be resected by transsphenoidal surgery.

Persistence of Cushing's disease symptoms and comorbidities after surgical cure: a long-term, integral evaluation.

Objectives: Successful surgery does not always resolve all the clinical consequences of hypercortisolism in patients with Cushing's disease (CD). Our purpose was to integrally evaluate a group of CD patients cured by pituitary surgery and look for the persistence of CD symptoms, signs, and comorbidities.

Methods: We performed clinical and biochemical evaluations of 29 CD patients (2 males) cured by pituitary surgery.

Discontinuation of octreotide LAR after long term, successful treatment of patients with acromegaly: is it worth trying?

Background: Somatostatin analogs (SA) have been used for over 25 years in the treatment of acromegaly. A major disadvantage is the need to continue therapy indefinitely.

Objective: To evaluate the feasibility of discontinuing therapy in well-controlled patients with acromegaly treated chronically with SA.

Efficacy and safety of radiotherapy in acromegaly.

Background And Aims: Transsphenoidal surgery remains the treatment of choice in acromegaly, yet 40-50% of patients require secondary forms of therapy such as radiation therapy (RT) and somatostatin analogues (SA). We undertook this study to evaluate the efficacy and safety of RT in acromegaly.

Methods: Forty patients with acromegaly treated with RT (mean dose, 52 Gy) after failed pituitary surgery between 1993 and 2007 were analyzed; all were clinically and biochemically active.

Clinical and biochemical characteristics of acromegalic patients with different abnormalities in glucose metabolism.

To determine the prevalence of diabetes, glucose intolerance and impaired fasting glucose in Mexican patients with acromegaly and establish associations with clinical, anthropometric and biochemical variables. 257 patients with acromegaly were evaluated by a 75 g-oral glucose tolerance test with measurements of both GH and glucose (0, 30, 60, 90 120 min) as well as baseline IGF-1. Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes (DM) were defined based on the 2003 ADA criteria.

Management of acromegaly in Latin America: expert panel recommendations.

Although there are international guidelines orienting physicians on how to manage patients with acromegaly, such guidelines should be adapted for use in distinct regions of the world. A panel of neuroendocrinologists convened in Mexico City in August of 2007 to discuss specific considerations in Latin America. Of major discussion was the laboratory evaluation of acromegaly, which requires the use of appropriate tests and the adoption of local institutional standards.

[Case report of mucormycosis in a patient with secondary methimazole-induced agranulocytosis].

Agranulocytosis is a rare side effect of antithyroid drugs, it occurs in less than 0.5% of patients, usually during the first few months of treatment. It is considered to be the most serious adverse effect of these medications since it may be complicated by serious, life-threatening infections.

Surgical reintervention in acromegaly: is it still worth trying?

Background And Objective: There has not been a formal evaluation of how frequently and to what extent surgical reintervention in patients with persistently active acromegaly may achieve significant, albeit incomplete, reductions in growth hormone (GH) and insulinlike growth factor-I (IGF-I) levels. Of importance, recent studies suggest that the response to radiotherapy and pharmacotherapy is better with lower degrees of hypersomatotropism. The objective of this study was to evaluate the outcome of surgical reintervention in patients with active acromegaly at our institution between 1995 and 2005.

[Treatment of acromegaly with octreotide LAR].

Background: Treatment of acromegaly with somastostatin analogues, albeit highly effective, is not curative and its elevated cost represents a major disadvantage. Hereby we describe our Center's experience using a fixed, 20 mg q.4 weeks- dose of octreotide LAR.

Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly.

Context: Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture.

Objective: Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment.