Search

Background: Patients with non-functioning pituitary adenoma (NFPA) often present with a variety of clinical manifestations and comorbidities, mainly determined by the local mass effect of the tumor and by hypopituitarism. Whether this has an impact on overall mortality, however, is still unclear., Methods: PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until May 2023 for studies reporting data either about standardized mortality ratios (SMRs) or about predictors of mortality in patients with NFPA. Effect sizes were pooled through a random-effect model. This systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, #CRD42023417782)., Results: Eleven studies were eligible for inclusion in the systematic review; among these, five studies reported data on SMRs, with a total follow-up time of approximately 130,000 person-years. Patients with NFPA showed an increased mortality risk compared to the general population (SMR = 1.57 [95%CI: 1.20-1.99], p < 0.01). Age and sex appeared to act as effect modifiers, with a trend towards higher SMRs in females (SMR = 1.57 [95%CI: 0.91-2.41], p = 0.10) than in males (SMR = 1.00 [95%CI: 0.89-1.11], p = 0.97), and in patients diagnosed at age 40 years or younger (SMR = 3.19 [95%CI: 2.50-3.97], p < 0.01) compared to those with later onset of the disease (SMR = 1.26 [95%CI: 0.93-1.65], p = 0.13). The trend towards excess mortality was similar in patients with normal (SMR = 1.22 [95%CI: 0.94-1.53], p = 0.13) or deficient (SMR = 1.26 [95%CI: 0.82-1.79], p = 0.27) pituitary function., Conclusions: Excess mortality is observed in patients with NFPA, regardless of pituitary function, especially in women and in patients with a younger age at diagnosis., (© 2024. The Author(s).)

Background: Most patients treated for hypothalamic-pituitary tumours develop GH deficiency. Long-term GH replacement treatment in adults with a previous history of hypothalamic-pituitary tumour could represent a concern about increasing the risk of tumour enlargement or recurrence., Purpose: To assess the progression risk of hypothalamic-pituitary tumours according to the GH secretory status (normal GH secretion, non-treated and treated GH deficiency). and determine the predictors of neoplasm recurrence., Methods: We retrospectively reviewed 309 patients with tumours of the hypothalamic-pituitary region (294 subjects underwent neurosurgery while 81 radiotherapy) who were followed for 9.9 ± 8.3 years., Results: Out of 309 patients, 200 were affected by severe GH deficiency; 90 of these underwent GH therapy. The tumour progression rate did not differ among GH-sufficient, not-treated and treated GH-deficient patients (16.5%, 16.4%. and 10.0%, respectively). In a multivariate analysis, previous radiotherapy (HR 0.12, CI 0.03-0.52, p < 0.005) and residual tumour (HR 8.20, CI 2.38-28.29, p < 0.001) were independent predictors of recurrence. After controlling for multiple covariates, the tumour recurrence risk in GH-sufficient and GH-treated patients was similar to that observed in not-treated GH-deficient patients., Conclusions: With limitations of retrospective analysis, GH therapy is not associated with an increased progression rate of tumours of the hypotalamic-pituitary region during long follow-up, thus supporting the long-term safety of GH treatment. The only predictors of tumour recurrence appear to be the presence of residual disease and the lack of radiotherapy.

Purpose: To determine the validity of a self-administered questionnaire (Acro-CQ) developed to systematically assess the presence, type and time of onset of acromegaly comorbidities., Methods: This is a cross-sectional study; 105 acromegaly patients and 147 controls with other types of pituitary adenoma, referred to a specialized Italian Center, autonomously compiled Acro-CQ in an outpatient clinical setting. To test its reliability in a different setting, Acro-CQ was administered via mail to 78 patients with acromegaly and 100 with other pituitary adenomas, referred to a specialized US Center. Data obtained from questionnaires in both settings were compared with medical records (gold standard)., Results: Demographics of patients and controls from both countries were similar. In both settings, >95 % of the questionnaires were completely filled; only one item was missed in the others. Concordance with medical record was excellent (k > 0.85) for most of the items, independently from the way of administration, patient age, gender and nationality, pituitary adenoma type and disease activity., Conclusions: Acro-CQ is an inexpensive, highly accepted from patients and reliable tool recommended to expedite systematic collection of relevant clinical data in acromegaly at diagnosis, to be replicated at follow-ups. This tool may guide a targeted, cost-effective management of complications. Moreover, it could be applied to retrieve data for survey studies in both acromegaly and other pituitary adenomas, as information is easily and rapidly accessible for statistical analysis.

Purpose: The management of choice of non-functioning pituitary adenomas (NFPAs) remains debulking surgery when symptomatic. However, patient series systematically reporting the NFPAs outcome that were not treated either surgically, medically or with radiotherapy during long follow-up thereby giving an indication of their natural history are limited. Aim of the present study was to evaluate the natural course of presumed NFPAs, the outcome of confirmed NFPAs during a long follow-up period., Methods: Between 1993 and 2013, 84 patients with presumed NFPA were studied retrospectively. Patients were enrolled based on the following criteria: imaging suggestive of pituitary adenoma, absence of any biochemical/clinical evidence of hormonal excess, exclusion of prolactinomas and at least one sequential imaging during the follow-up. Repeated assessment of the pituitary function, visual fields and imaging was performed at regular intervals. The follow-up duration was evaluated from the first and last imaging dates., Results: In group F (follow-up without surgery, 33 patients), the macroadenomas showed a 15% probability of tumor growth and reduction. Similar tumor size alterations were observed also for the microadenomas. In group S (surgery, 51 patients), both residual tumors (>1 and <1 cm) following initial surgical resection remain mainly stable until the last imaging., Conclusions: Based on the given lack of approved medical treatment and the possible risks of surgical intervention in presence of significant comorbidities, our study proposes a conservative approach with a careful follow-up in patients with NFPAs without visual or neurological abnormalities.

Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with < or =3 mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.

Context: Impaired glucose tolerance and diabetes mellitus are frequently present in acromegalic patients in whom the degree of impaired glucose metabolism seems directly correlated with GH levels. Microalbuminuria is reported to be directly correlated with insulin resistance, and both conditions predict cardiovascular disease mortality., Objective: Our objective was to investigate the microalbuminuria levels as a marker of endothelial dysfunction in acromegalic patients., Design: We conducted an observational, multicenter, open prospective study., Subjects: Subjects included 74 patients with active acromegaly (52 with normal glucose tolerance, 16 with impaired glucose tolerance, and six with diabetes), and 50 healthy subjects matched for age, gender, and body mass index were studied as controls., Results: In the whole group, mean GH and IGF-I levels were 24.2+/-3.9 ng/ml and 700.1+/-23.0 microg/liter, respectively. The insulin sensitivity index (ISI) in the patients was lower than in the controls (P<0.0005). In impaired glucose tolerance and diabetic patients, microalbuminuria was higher than in normal glucose tolerance patients (P<0.05 and P<0.0005 respectively). Hypertensive patients had higher levels of microalbuminuria than normotensive ones (P<0.005). The levels of microalbuminuria related to creatinine were directly correlated with fasting glucose levels (r=0.27; P=0.0019), fasting insulin levels (r=0.28; P=0.017), and insulin after 90 (r=0.26; P=0.027) and 120 min after glucose load (r=0.26; P=0.023) and indirectly correlated with ISI composite (P<0.0001; r=-0.48). By a multivariate analysis, the log-ISI composite was the strongest predictor of microalbuminuria (t=-3.19; P=0.0021)., Conclusions: Impairment of glucose tolerance in acromegaly is associated with high levels of microalbuminuria. For this reason, microalbuminuria should be part of cardiovascular risk assessment in these patients.

Context: Cortistatin binds all somatostatin receptor subtypes but also has particular central actions; moreover, a specific cortistatin receptor has also been discovered., Objective: We compared the endocrine effects of cortistatin-17 with those of somatostatin-14 in patients with acromegaly (ACRO) or prolactinoma (PRLOMA). Normal subjects (NS) were studied as control group., Design: All subjects underwent the following tests: 1) saline, 2) somatostatin-14 (2.0 microg/kg.h iv, 0-120 min) and 3) cortistatin-17 (2.0 microg/kg.h iv, 0-120 min) infusion., Results: Cortistatin-17 and somatostatin-14 inhibited GH secretion to the same extent in ACRO (P < 0.05) and NS (P < 0.01). Cortistatin-17 and somatostatin-14 inhibited PRL secretion in PRLOMA (P < 0.05), to some extent in ACRO (P value not significant), but not in NS. Insulin secretion was inhibited by both cortistatin-17 and somatostatin-14 to the same extent in all groups (P < 0.05)., Conclusions: Cortistatin-17 and somatostatin-14 display the same effects on GH, PRL, and insulin secretion in patients with ACRO or PRLOMA.

The aim of the present multicentric, open-label, non-comparative study was to evaluate the role of octreotide long-acting repeatable (LAR) as primary therapy for the treatment of GH-secreting pituitary macroadenomas. The patients received octreotide LAR 20 mg every 4 weeks for 12 weeks; afterwards the dose was confirmed or adjusted at 30 mg every 4 weeks, for the remaining 12 weeks, for responder or non-responder patients, respectively. Responder patients continued the study until 48 weeks. Twenty-one naive active acromegalic patients were enrolled. In all patients, GH profile, IGF-I levels and magnetic resonance imaging (MRI) were evaluated at baseline and during treatment. The ability of octreotide LAR to decrease mean GH < 2.5 microg/I and/or normalize IGF-I levels, adjusted for age and gender, was defined respectively as total or partial success. Total success was achieved in 5/21 (23.8%), 6/20 (30%) and 4/14 (28.6%) patients after 12, 24 and 48 weeks; partial success in 7/21 (33.3%), 9/20 (45%) and 9/14 (64%) patients at 12, 24 and 48 weeks according to GH levels, while according to IGF-I levels in 7/21 (33.3%), 7/20 (35%) and 5/14 (35.7%) patients at 12, 24 and 48 week. Tumor size was notably decreased after treatment with octreotide LAR: in 16 macroadenoma patients completing the study, the tumor sizes were 1609 +/- 1288, 818 +/- 616 (49.1 +/- 23.7%) and 688 +/- 567 mm3 (54.6 +/- 24.4%) at baseline, 24 and 48 weeks. This study shows that octreotide LAR is effective in suppressing GH/IGF-I secretion and inducing tumor shrinkage in GH-secreting macroadenomas in a 48-week treatment. Octreotide LAR could be used as primary therapy in patients harbouring large pituitary tumors, who are less likely to be cured by neurosurgery.

Hypothalamus-pituitary tumours and their treatments (neurosurgery and/or radiotherapy) are major causes of acquired hypopituitarism. Scientific and clinical evidences show the positive effect of GH replacement therapy in severe adult GH deficiency (GHD) pointed toward the need of diagnostic screening of conditions at high risk for GHD. We screened 152 adults (82 males, 70 females; age: 52.3+/-1.2 years, age-range: 20-80 years, BMI: 26.4+/-0.8 kg/m(2)) in order to disclose the presence of GHD after neurosurgery for hypothalamus-pituitary tumours. The whole group (studied at least 3 months after neurosurgery) included: 111 non-functioning pituitary adenomas and 41 peri-pituitary tumours (24 craniopharyngiomas, 7 meningiomas, 5 cysts, 2 chondrosarcomas, 1 colesteatoma, 1 germinoma and 1 hemangiopericitoma). In 14 patients who underwent both neurosurgery and radiotherapy due to a tumour remnant, the somatotroph function was evaluated again 6 months after the end of radiotherapy. GHD was assumed to be shown by GH peak <5 microg/L (severe <3 microg/L) after Insulin Tolerance Test (ITT) or <16.5 microg/L (severe <9 microg/L) after GH-releasing hormone+arginine test (GHRH+ARG) (3rd and 1st centile limits of normality, respectively), two widely accepted provocative tests. Before neurosurgery GHD was present in 97/152 (63.8%) and resulted severe in 66/152 (43.4%) patients. After neurosurgery GHD was present in 122/152 (80.2%) and severe in 106/152 (69.7%). While 26 patients developed severe GHD (GHD) as consequence of neurosurgery, only one patient who had been classified as GHD before neurosurgery showed normal GH response after surgery. After neurosurgery, 91.0% (81/89) of the pan-hypopituitaric patients showed severe GHD. Considering the 14 patients who underwent also radiotherapy after neurosurgery, 7/14 had GHD before neurosurgery while 12/14 became severe GHD after radiotherapy in a context of pan-hypopituitarism. IGF-I levels below the 3rd age-related normal limits were present in 39.0% of patients in whom severe GHD was showed by provocative tests. In conclusion, this study shows that the occurrence of acquired severe GHD is extremely common in adult patients bearing non-functioning tumour masses in the hypothalamus-pituitary area and further increases after neurosurgery. All patients bearing non-functioning hypothalamus-pituitary tumours should undergo evaluation of their somatotroph function before and after neurosurgery that represents a condition at obvious more than high risk for hypopituitarism.