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Pituitary adenomas can show a tendency to grow, despite multimodal treatment. Temozolomide (TMZ) has been used in the last 15 years in patients with aggressive pituitary tumors. TMZ requires a careful balance of different expertise, especially for selection criteria. We conducted: (1) a systematic review of the published literature from 2006 to 2022, collecting only cases with a complete description of patient follow-up after TMZ discontinuation; (2) a description of all patients with aggressive pituitary adenoma or carcinoma treated in Padua (Italy). There is considerable heterogeneity in the literature: TMZ cycles duration ranged from 3 to 47 months; the follow-up time after TMZ discontinuation ranged from 4 to 91 months (mean 24 months, median 18 months), at least a stable disease has been reported in 75% of patients after a mean 13 months (range 3–47 months, median 10 months). The Padua (Italy) cohort reflects the literature. Future directions to explore are to understand the pathophysiological mechanism of TMZ resistance escape, to develop predicting factors to TMZ treatment (especially through the delineation of the underlying transformation processes), and to further expand the therapeutic applications of TMZ (as neoadjuvant, combined with radiotherapy). [ABSTRACT FROM AUTHOR]

Introduction: Pasireotide (PAS) is a novel somatostatin receptor ligands (SRL), used in controlling hormonal hypersecretion in both acromegaly and Cushing's Disease (CD). In previous studies and meta-analysis, first-generation SRLs were reported to be able to induce significant tumor shrinkage only in somatotroph adenomas. This systematic review and meta-analysis aim to summarize the effect of PAS on the shrinkage of the pituitary adenomas in patients with acromegaly or CD. Materials and methods: We searched the Medline database for original studies in patients with acromegaly or CD receiving PAS as monotherapy, that assessed the proportion of significant tumor shrinkage in their series. After data extraction and analysis, a random-effect model was used to estimate pooled effects. Quality assessment was performed with a modified Joanna Briggs's Institute tool and the risk of publication bias was addressed through Egger's regression and the three-parameter selection model. Results: The electronic search identified 179 and 122 articles respectively for acromegaly and CD. After study selection, six studies considering patients with acromegaly and three with CD fulfilled the eligibility criteria. Overall, 37.7% (95%CI: [18.7%; 61.5%]) of acromegalic patients and 41.2% (95%CI: [22.9%; 62.3%]) of CD patients achieved significant tumor shrinkage. We identified high heterogeneity, especially in acromegaly (I2 of 90% for acromegaly and 47% for CD), according to the low number of studies included. Discussion: PAS treatment is effective in reducing tumor size, especially in acromegalic patients. This result strengthens the role of PAS treatment in pituitary adenomas, particularly in those with an invasive behavior, with progressive growth and/or extrasellar extension, with a low likelihood of surgical gross-total removal, or with large postoperative residual tissue. [ABSTRACT FROM AUTHOR]

Adrenocorticotropic Hormone (ACTH)-secreting pituitary adenomas are rare tumors characterized by autonomous ACTH secretion with a consequent increase in circulating cortisol levels. The resulting clinical picture is called Cushing's disease (CD), a severe condition burdened with high morbidity and mortality. Apart from increased cortisol levels, CD patients exhibit a partial resistance to the negative glucocorticoid (GC) feedback, which is of paramount clinical utility, as the lack of suppression after dexamethasone administration is one of the mainstays for the differential diagnosis of CD. Since the glucocorticoid receptor (GR) is the main regulator of negative feedback of the hypothalamic–pituitary–adrenal axis in normal conditions, its implication in the pathophysiology of ACTH-secreting pituitary tumors is highly plausible. In this paper, we review GR function and structure and the mechanisms of GC resistance in ACTH-secreting pituitary tumors and assess the effects of the available medical therapies targeting GR on tumor growth. [ABSTRACT FROM AUTHOR]

Cushing's syndrome (CS) is a rare disease caused by chronic and excessive cortisol secretion. When adrenocorticotropin hormone (ACTH) is measurable, autonomous adrenal cortisol secretion could be reasonably ruled out in a differential diagnosis of CS. ACTH-dependent CS accounts for 80%-85% of cases and involves cortisol production stimulated by uncontrolled pituitary or ectopic ACTH secretion. Pituitary adenoma is not detected in up to one-third of cases with pituitary ACTH secretion, whereas cases of CS due to ectopic ACTH secretion may be associated with either malignant neoplasia (such as small cell lung carcinoma) or less aggressive neuroendocrine tumors, exhibiting only the typical symptoms and signs of CS. Since the differential diagnosis of ACTH-dependent CS may be a challenge, many strategies have been proposed. Since none of the available tests show 100% diagnostic accuracy, a step-by-step approach combining several diagnostic tools and a multidisciplinary evaluation in a referral center is suggested. In this review, we present a clinical case to demonstrate the diagnostic work-up of ACTH-dependent CS. We describe the most commonly used dynamic tests, as well as the applications of conventional or nuclear imaging and invasive procedures. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenomas are usually considered benign tumours, although some of them can exhibit an aggressive behaviour. Patients with clinically aggressive pituitary adenomas are frequently diagnosed with larger masses, and may present an earlier recurrence (or persistence) after surgery. Our aim was to characterise the clinical, histopathological and radiological features of patients with aggressive pituitary adenoma, in order to correlate their clinical behaviour with the response to treatment plan. Method: We considered an aggressive pituitary adenoma on the basis of radiological features (size, local invasion), pathological reports (atypical adenoma: MIB-1 >3%, p53 immunoreactivity, increased mitotic activity) and clinical aspects (response to surgery, radiotherapy and medical treatment). Results: Among our cohort of 582 patients, we considered 102 subjects with aggressive pituitary adenomas (18%, 56 male and 46 female): 14 adrenocorticotrophic hormone (ACTH)-secreting, 18 growth hormone (GH)-secreting, 23 prolactin (PRL)-secreting and 47 non-secreting, with a median follow-up of 5 years. In the whole cohort, 75% of patients with aggressive pituitary adenomas presented invasion of surrounding structure, especially GH-secreting, PRL-secreting and non-secreting. Besides invasion, their remission rate after surgery, radiotherapy or medical treatment was similar, irrespective of hormonal secretion. Surgery was the most performed treatment (overall remission rate of 24%), especially in those patients with ACTH- or GH-secreting adenoma, and 22% of patients were submitted to radiotherapy, with a remission rate of 45% after a median of 3 years. Two consecutive years of medical treatment, in patients with secreting pituitary adenoma, achieved disease control in 41% of them. Considering pathological reports, 24% of cases were defined as atypical adenomas; radiological characteristics, responses to medical treatment and remission rates were similar among patients with typical and atypical adenoma. Conclusions: We proposed a new and comprehensive definition of aggressive pituitary adenoma, based upon radiological, clinical and pathological features. In a selected cohort of patients, radiological invasion resulted in the most common marker to describe the aggressive behaviour of pituitary adenoma. Surgery, radiotherapy and medical treatment (the latter only in secreting adenoma) achieved disease control in half of the patients with aggressive adenoma, especially surgery in those with ACTH-oma and medical treatment in those with GH- and PRL-secreting adenoma. Nevertheless, radiological, clinical or atypical features did not affect the outcome. [ABSTRACT FROM AUTHOR]

Objective Cushing's disease ( CD) presents a remarkable preponderance in female gender, with a female-to-male ratio of 3-8:1. The aim of this study was to evaluate gender-related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease. Methods We retrospectively studied 84 adult patients with CD, 67 women and 17 men, evaluated at diagnosis. We compared the features of the disease between the sexes and analysed the effect of gender on CD complications, adjusted for potential confounders (age, gonadal status, BMI, urinary free cortisol values). Results We observed no differences between males and females as regards age at diagnosis, disease duration and BMI. Men, compared with women, presented higher urinary free cortisol values ( P < 0·001) and ACTH values ( P < 0·05). As regards diagnostic tests, men presented a lower ACTH response to DDAVP stimulation ( P < 0·05). The pituitary tumour itself was less easily visualized by pituitary MRI in males compared with females ( P < 0·05). Furthermore, some complications of disease were more frequent or more severe in men, in particular hypokalaemia ( P < 0·05), hypercoagulable state and osteoporosis at lumbar spine ( P < 0·01), with consequent higher risk of vertebral fractures. Male gender was found to be an independent risk factor for dyslipidaemia, severity of hypertension, lumbar osteoporosis and fractures. Conclusions Although CD is less frequent in male patients, in this gender, it presents with more florid clinical manifestations and may imply more diagnostic difficulties. [ABSTRACT FROM AUTHOR]