Neurogenic myocardial dysfunction post craniopharyngioma resection: A diagnostic dilemma.

Endoscopic transsphenoidal resection of craniopharyngioma is a commonly used technique. Cerebral vasospasm may occur in nearly 10% of cases leading to adverse neurological outcomes. Cardiopulmonary dysfunction may be seen in patients with severe vasospasm. The literature describing the occurrence of neurogenic stunned myocardium following craniopharyngioma resection in pediatric patients is very sparse. Here, we describe such a case managed with a combination of milrinone (to relieve vasospasm and improve cardiac pump function), noradrenaline (to obtain target blood pressure), and vasopressin (to control urine output). This case report proposes the treatment plan of neurogenic stunned myocardium following vasospasm in pediatric patients.

Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors.

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Investigating the results of neuroendoscopic surgery in the treatment of pituitary adenoma and leptin gene expression.

Neuroendoscopic surgery of pituitary adenoma has been one of the technologies with rapid progress in neurosurgery in this decade. This method has known advantages and limitations. This study aims to investigate the results of pituitary adenoma treatment using the neuroendoscopy technique in a group of patients. Also, the level of leptin gene expression (LEP), which is produced exclusively in the pituitary gland, was measured for further evaluation. For this purpose, 26 patients who were diagnosed with pituitary adenoma and underwent endoscopic surgery in the hospital between 2018-2022, in terms of age, gender, disease symptoms, functional and non-functional tumor, and neurological examination findings before and after the procedure, complications, and the length of stay in the hospital were investigated. Also, before and 6 months after the operation, blood samples were prepared from patients to evaluate LEP gene expression by real-time PCR technique. The results illustrated that of the 26 patients studied, 14 were men, and 12 were women. Most of the patients were in their third to sixth decades of life. The tumors were non-functioning adenoma in 11 cases, somatotroph adenoma in 9 patients, corticotroph adenoma in 3 cases, and prolactinoma in 3 cases. Seven patients suffered postoperative complications, including 6 cases of reversible complications and one case of patient death. In the 2-year follow-up, 6 cases of tumor recurrence were observed. Also, the evaluation of LEP gene expression showed no significant difference between pre-operative and post-operative expressions. In general, neuroendoscopic surgery in treating pituitary adenoma is a method worthy of attention, considering factors such as fewer complications and a shorter stay in the hospital increase the acceptability of this method.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). CONCLUSIONS: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Downregulation of miR-216a-5p and miR-652-3p is associated with growth and invasion by targeting JAK2 and PRRX1 in GH-producing pituitary tumours.

Expression of aberrant microRNA (miRNA) is associated with tumour formation, migration, and invasion. However, there is limited information about the epigenetics of pituitary tumorigenesis. This study investigated the role of miRNA expression during the tumorigenesis of growth hormone (GH)-secreting pituitary tumours. miRNA profiling and real-time PCR were used to analyse the mRNA expression profile in sequential pituitary tissues of a unique animal model with a GH-producing pituitary tumour. Selected miRNAs were further validated in GH-producing cell lines and human pituitary tumour samples. The expression of significantly altered miRNAs and their predicted targets, as detected by microarray, was evaluated by real-time PCR, Western blotting, and immunohistochemistry using samples from mouse models and human pituitary tumours. The effect of miRNAs on tumour proliferation and invasion was examined in GH3 cells using the MTS and Matrigel invasion assays. Among the 14 miRNAs whose expression was significantly changed, miR-216a-5p (fold change = -5.638, P -value = 0.014) and miR-652-3p (fold change = -3.482, P -value = 0.010) were constantly and significantly downregulated. Transfection with mimics of miR-216a-5p and miR-652-3p inhibited GH3 proliferation and invasion, whereas inhibitors promoted them. The direct target genes of miR-216a-5p and miR-652-3p were Jak2 and Prrx1, respectively, which were downregulated in GH3 cells transfected with mimics and in serial pituitary gland tissues, including hyperplasic tissues and tumours of acromegalic animal models and pituitary tumour tissues of acromegalic patients. Downregulated miR-216a-5p and miR-652-3p expression may contribute to tumour progression by targeting JAK2 and PRRX1 on GH-producing pituitary tumours.

Growth hormone secreting pituitary carcinomas: Case report and review of literature.

OBJECTIVE: Pituitary carcinoma is a rare tumor, defined as a tumor of adenohypophyseal cells with systemic or craniospinal metastasis. We present a case of a growth hormone (GH)-secreting pituitary carcinoma with a review of literature to better characterize this disease. DESIGN: Case report and literature review of 25 cases of GH-secreting pituitary carcinomas RESULTS: The age of diagnosis of GH-secreting carcinomas ranged 24-69 years old with a mean age of 44.4 with 52% of cases present in females. Mean latency period between diagnosis of acromegaly and transition to pituitary carcinoma was 11.4 years with mean survival being 3.4 years. CONCLUSION: Growth hormone (GH)-secreting pituitary carcinomas are rare and hard to distinguish from aggressive pituitary adenomas. From review of literature, treatment options include debulking surgery, radiotherapy, or chemotherapy with dismal outcomes. There are no diagnostic markers or features which can predict metastatic progression of these tumors. Future studies with genomic landscapes and relevant tumor markers are needed to identify pituitary tumors most likely to metastasize.

Hormone-Dependent Tumors and Sexuality in the Neuro-Oncology of Women (N.O.W.): Women's Brain Tumors, Gaps in Sexuality Considerations, and a Need for Evidence-Based Guidelines.

PURPOSE OF REVIEW: While females make up almost 60% of all brain and spinal cord tumors in adults, guidelines that address women's issues in neuro-oncology are lacking. This review sheds light on two common women's issues in neuro-oncology. RECENT FINDINGS: Neuro-oncology providers are often faced with patient questions about fertility and pregnancy maintenance or prevention and typically respond with generic cancer chemotherapy recommendations, based on the paucity of evidence on the use of common neuro-oncology chemotherapies and pregnancy. While these remain important gap issues, there are several other poorly researched issues in the Neuro-Oncology of Women (N.O.W.) including recommendations around endogenous and iatrogenic hormone exposure and female sexuality in cancer. As a significant percentage of cancers are hormone-dependent, it is important to understand how changes in hormone levels impact tumor biology over the course of a woman's lifespan. Furthermore, greater attention should be given to the impact of tumors and tumor treatments on female sexuality. This article is intended to serve as an introduction to these two specific subjects within the vast expanse of N.O.W. subject matter.

Predictive and prognostic significance of tumour subtype, SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly.

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.

Clinical and Molecular Update on Genetic Causes of Pituitary Adenomas.

Pituitary adenomas are benign tumors with variable functional characteristics that can have a significant impact on patients. The majority arise sporadically, but an inherited genetic susceptibility is increasingly being recognized. Recent advances in genetics have widened the scope of our understanding of pituitary tumorigenesis. The clinical and genetic characteristics of pituitary adenomas that develop in the setting of germline-mosaic and somatic GNAS mutations (McCune-Albright syndrome and sporadic acromegaly), germline MEN1 mutations (multiple endocrine neoplasia type 1), and germline PRKAR1A mutations (Carney complex) have been well described. Non-syndromic familial cases of isolated pituitary tumors can occur as familial isolated pituitary adenomas (FIPA); mutations/deletions of the AIP gene have been found in a minority of these. Genetic alterations in GPR101 have been identified recently as causing X-linked acro-gigantism (X-LAG) leading to very early-onset pediatric gigantism. Associations of pituitary adenomas with other tumors have been described in syndromes like multiple endocrine neoplasia type 4, pheochromocytoma-paraganglioma with pituitary adenoma association (3PAs) syndrome and some of their genetic causes have been elucidated. The genetic etiologies of a significant proportions of sporadic corticotropinomas have recently been identified with the discovery of USP8 and USP48 mutations. The elucidation of genetic and molecular pathophysiology in pituitary adenomas is a key factor for better patient management and effective follow-up.

Pituitary macroadenoma secondary to Hashimoto's thyroiditis: inadvertent diagnosis in a pre-pubertal girl.

Pituitary hyperplasia as a result of autoimmune thyroiditis has been rarely reported in children. We report a prepubertal girl with Hashimoto's thyroiditis who was inadvertently diagnosed to have a pituitary macroadenoma based on neuroimaging.

Pituitary adenoma secondary to primary hypothyroidism: Two case reports.

RATIONALE: Primary hypothyroidism is characterized by loss of thyroxine feedback inhibition and overproduction of thyrotropin-releasing hormone, which might result in reactive pituitary hyperplasia. However, pituitary adenoma secondary to primary hypothyroidism is extremely rare and usually underdiagnosed, and the pathogenic mechanism remains unclear. Herein, we reported two cases with pituitary adenoma secondary to primary hypothyroidism. PATIENT CONCERNS: Case 1: A 35-year-old man presented to the local clinic with a 2-year history of fatigue, puffiness in the bilateral lower extremities and facial region, and coarseness of facial features. Additionally, his relatives also supplemented that he suffered from hypomnesis and hypophrenia.Case 2: A 56-year-old, postmenopausal woman presented to the local clinic with fatigue, dry skin, and sluggishness. DIAGNOSES: The pathological diagnosis of two patients was plurihormonal pituitary adenoma. INTERVENTIONS: A microscopical tumorectomy was performed when the two patients were admitted to our hospital. Thyroid hormone replacement therapy (thyroxine 50 µg/day) was prescribed after microsurgery. OUTCOMES: After 32 months (Case 1) or 43 months (Case 2) follow-up respectively, there was no recurrence, and the symptoms were completely relieved. LESSONS: Pituitary hyperplasia caused by primary hypothyroidism responds well to thyroid hormone replacement therapy. It is worth noting that repeated detection of serum T3, T4, and thyroid-stimulating hormone (TSH) should be performed 3 months after replacement therapy. If the results showed that TSH level decreased partly, while thyroid function did not improve significantly, long-term increased secretion of pituitary TSH adenoma should be considered. And microsurgical resection via a transsphenoidal approach could be ordered. If the optic nerve or optic chiasm were pressed by the adenoma, microsurgery should be performed to relieve the pressure immediately. And then, thyroxine tablet substitute therapy should be performed after surgery.

Concurrent Pituicytoma, Meningioma, and Cavernomas After Cranial Irradiation for Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: The majority of patients with acute lymphoblastic leukaemia develop disease relapse in the central nervous system in the absence of central nervous system-directed prophylactic therapy. In the past, prophylactic cranial irradiation was commonly used in the form of whole-brain radiotherapy in patients with acute lymphoblastic leukemia to prevent the development of intracranial diseases. However, in addition to the inherent risk of toxicity, this type of therapy has several delayed side effects including the development of secondary intracranial tumors. CASE DESCRIPTION: We report a rare case of a patient with concurrent pituicytoma, meningioma, and cavernomas 44 years after prophylactic cranial irradiation for childhood acute lymphoblastic leukemia. The patient presented with visual disturbance, headache, and features of hypopituitarism. Endoscopic transsphenoidal resection of the pituicytoma and meningioma was performed. Subsequent regrowth of the residual meningioma necessitated further surgery and adjuvant treatment with radiotherapy. CONCLUSIONS: This case report highlights the unusual case of a patient with 3 concurrent intracranial lesions of distinct pathologies after prophylactic cranial irradiation therapy for childhood acute lymphoblastic leukemia.

Biochemical Control in Acromegaly With Multimodality Therapies: Outcomes From a Pituitary Center and Changes Over Time.

PURPOSE: To determine the prevalence of insulin-like growth factor-1 (IGF-1) normalization with long-term multimodality therapy in a pituitary center and to assess changes over time. METHODS: Patients with acromegaly (N = 409), with ≥1 year of data after surgery and at least 2 subsequent clinic visits were included in long-term analysis (N = 266). Biochemical data, clinical characteristics, and therapeutic interventions were reviewed retrospectively. RESULTS: At diagnosis, mean [standard deviation] age was 43.4 [14.3] years, body mass index was 28.5 (24.9-32.1) kg/m2 (median, interquartile range), serum IGF-1 index (IGF-1 level/upper limit of normal) was 2.3 [1.7-3.1], and 80.5% had macroadenomas. Patients with transsphenoidal surgery after 2006 were older [46.6 ± 14.3 vs 40.0 ± 13.4 years; P < 0.001]. Age and tumor size correlated inversely. Overall (N = 266), 93.2% achieved a normal IGF-1 level during 9.9 [5.0-15.0] years with multimodality therapy. The interval to first normal IGF-1 level following failed surgical remission was shorter after 2006: 14.0 (95% confidence interval, 10.0-20.0) versus 27.5 (22.0-36.0) months (P = 0.002). Radiation therapy and second surgery were rarer after 2006: 28 (22%) versus 62 (47.0%); P < 0.001 and 12 (9.4%) versus 28 (21.2%); P = 0.010, respectively. Age at diagnosis increased over time periods, possibly reflecting increased detection of acromegaly in older patients with milder disease. Male gender, older age, smaller tumor and lower IGF-1 index at diagnosis predicted long-term sustained IGF-1 control after surgery without adjuvant therapies. CONCLUSION: The vast majority of patients with acromegaly can be biochemically controlled with multimodality therapy in the current era. Radiotherapy and repeat pituitary surgery became less frequently utilized over time. Long-term postoperative IGF-1 control without use of adjuvant therapies has improved.

Outcomes of surgical and/or medical treatment in patients with prolactinomas during long-term follow-up: a retrospective single-centre study.

OBJECTIVES: Prolactinoma is the most common cause of pituitary tumours. Current medical guidelines recommend dopamine agonists (cabergoline or bromocriptine) as the initial therapy for prolactinoma. However, surgical removal can also be considered in selected cases, such as patients with macroadenomas with local complications (bleeding or optic chiasm pressure) or those not responding to medical treatment. METHODS: The present retrospective study included patients with prolactinomas (n=43; female, 24; male, 19) who were primarily managed with medical (n=32) or surgical (n=11) treatment. RESULTS: Macroadenoma (n=29.67%) was commonly detected in both genders (female, 54%; male, 84%). Moreover, the mean pre-treatment prolactin levels were similar in both genders (female, 683.3 ± 1347 ng/mL; male, 685.4 ± 805 ng/mL; p=0.226). Surgically treated patients had a greater reduction in tumour size (27.7 ± 17.9 mm pre-treatment vs. 8.72 ± 14.2 mm post-treatment) than non-surgically treated ones (12.5 ± 7.5 mm pre-treatment vs. 4.1 ± 4.2 mm post-treatment; p=0.00). However, the decrease in prolactin levels was similar between the two patient groups (p=0.108). During the follow-up period (10.6 ± 7.0 years), the average cabergoline dose of the patients was 1.42 ± 1.47 mcg/week. CONCLUSIONS: Although a surgical approach was considered for selected cases of prolactinoma, the average dose used for medical treatment was highly inadequate for the patients in the present study.

Genetic and Epigenetic Causes of Pituitary Adenomas.

Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel-Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein (AIP) mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha (GNAS) and G protein-coupled receptor 101 (GPR101) mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene USP8, USP48, and BRAF mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.

Pituitary Adenomas in Transgender Individuals?

Transgender individuals may receive long-term hormonal treatment as part of their sexual transition; limited literature has suggested that they consequently may be predisposed to development of prolactinomas. We questioned whether we had encountered such cases. Pathology databases were searched for the years 2000-2019 for tissue specimens from transgender individuals; Sixty surgical specimens from 58 individuals and 8 cytology specimens were identified. Two of these 60 were pituitary adenomas, neither of which were lactotroph adenomas (prolactinomas).The first occurred in a 71-year-old transgender male-to-female who had undergone high-dose hormone therapy, followed by orchiectomy 30 years prior. Chronic hypertension, dizziness, and vertigo prompted an endocrine workup which revealed elevated IGF-1 and prolactin; The pituitary mass proved to be a mixed somatotroph/lactotroph adenoma. The second occurred in a 53-year-old transgender male-to-female who was being evaluated by an endocrinologist prior to initiating hormone therapy for transition when a slightly elevated prolactin level was discovered. This pituitary macroadenoma proved to be a gonadotroph adenoma. The most common surgical specimens were 33 bilateral mastectomies, 13 hysterectomies, and 4 orchiectomies, almost all for gender transition purposes rather than medical conditions. Pathologists may wish to be aware of the occurrence of pituitary adenomas in transgender individuals, although the incidence is quite low.

Pituitary tumours in MEN1 syndrome - the new insight into the diagnosis and treatment.

Pituitary tumours are a common pathology affecting 15-20% of the population. Only about 1‰ of adenomas are clinically manifested; among them, about two/thirds are hormonally active, most often secreting prolactin or growth hormone. Pituitary tumours are mainly an isolated pathology, without any genetic background. However, the latest studies pay special attention to the possibility of developing an adenoma as a result of genetic mutation. Among pituitary adenomas, the leading group of genetically determined lesions is related to a mutation in AIP or MEN1, followed by PRKAR1A, GRP101, DICER, and SDHx. The genetic basis of these pituitary tumours is related to positive family history, young age of the patient, aggressive clinical process, and resistance to treatment. Pituitary tumours occur in over 40% of patients with MEN1 syndrome - often in women, they are more than 1 cm in diameter, and secrete prolactin. They are usually diagnosed in the fourth decade of life and show a worse response to pharmacotherapy than sporadic ones. Confirmation of the genetic background of the pituitary tumour implies measurable implications; it might help to direct the diagnosis in patients' family members, partially predict the development of the disease, and, above all, extend patients' life expectancy.

SCP2-mediated cholesterol membrane trafficking promotes the growth of pituitary adenomas via Hedgehog signaling activation.

BACKGROUND: Metabolic reprogramming is an important characteristic of tumors. In the progression of pituitary adenomas (PA), abnormal glucose metabolism has been confirmed by us before. However, whether cholesterol metabolism is involved in the process of PA remains unclear. This study aimed to investigate whether abnormal cholesterol metabolism could affect the progression of PA. METHODS: We analyzed the expression of sterol carrier protein 2 (SCP2) in 40 surgical PA samples. In vitro experiments and xenograft models were used to assess the effects of SCP2 and cholesterol on proliferation of PA. The incidence of hypercholesterolemia between 140 PA patients and 100 heathy controls were compared. RESULTS: We found an upregulation of SCP2 in PA samples, especially in tumors with high proliferation index. Forced expression of SCP2 promoted PA cell lines proliferation in vitro. Furthermore, SCP2 regulated cholesterol trafficking from cytoplasm to membrane in GH3 cells, and extracellularly treating GH3 cells and primary PA cells with methyl-ß-cyclodextrin/cholesterol complex to mimic membrane cholesterol concentration enhanced cell proliferation, which suggested a proliferative effect of cholesterol. Mechanistically, cholesterol induced activation of PKA/SUFU/GLI1 signaling via smoothened receptor, which was well-known as Hedgehog signaling, resulting in inhibiting apoptosis and promoting cell cycle. Accordingly, activation of Hedgehog signaling was also confirmed in primary PA cells and surgical PA samples. In vivo, SCP2 overexpression and high cholesterol diet could promote tumor growth. Intriguingly, the incidence of hypercholesterolemia was significantly higher in PA patients than healthy controls. CONCLUSIONS: Our data indicated that dysregulated cholesterol metabolism could promote PA growth by activating Hedgehog signaling, supporting a potential tumorigenic role of cholesterol metabolism in PA progression.

Biological and Biochemical Basis of the Differential Efficacy of First and Second Generation Somatostatin Receptor Ligands in Neuroendocrine Neoplasms.

Endogenous somatostatin shows anti-secretory effects in both physiological and pathological settings, as well as inhibitory activity on cell growth. Since somatostatin is not suitable for clinical practice, researchers developed synthetic somatostatin receptor ligands (SRLs) to overcome this limitation. Currently, SRLs represent pivotal tools in the treatment algorithm of neuroendocrine tumors (NETs). Octreotide and lanreotide are the first-generation SRLs developed and show a preferential binding affinity to somatostatin receptor (SST) subtype 2, while pasireotide, which is a second-generation SRL, has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). A number of studies demonstrated that first-generation and second-generation SRLs show distinct functional properties, besides the mere receptor affinity. Therefore, the aim of the present review is to critically review the current evidence on the biological effects of SRLs in pituitary adenomas and neuroendocrine tumors, by mainly focusing on the differences between first-generation and second-generation ligands.