GH receptor polymorphisms guide second-line therapies to prevent acromegaly skeletal fragility: preliminary results of a pilot study.

Background: Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies.

Vitamin D in pituitary driven osteopathies.

The evidence that pituitary hormones may bypass peripheral endocrine glands to exert remarkable effects on the skeleton is gaining ground. Both hormonal excess and deficit may determine impairment in bone structure, and they commonly result in bone loss in patients affected by pituitary and neuroendocrine disorders. Vertebral fractures are the most common skeletal alterations and may occur independently of bone mass.

The Differential Diagnosis between Cushing's Disease and Pseudocushing Syndrome in a Pre-agonic Patient.

Background: The pseudo-Cushing's encompass several disorders that can occur in high-stress situations and that show biochemical features like those of Cushing's syndrome. We present a case with difficult differential diagnosis for overlapping laboratory findings.

Case Report: A 74-year-old man was admitted to our hospital for worsening dyspnoea for a month, 15 kilograms of weight loss in the previous months, asthenia, hypotonia, and muscle hypotrophy.

Pregnancy in Autoimmune Hypophysitis: Management of a Rare Condition.

Introduction: Hypophysitis is an inflammatory disorder of the pituitary gland. It can manifest variously, with endocrinological and neuro-ophthalmologic symptoms and signs, due to the compression of sellar and parasellar structures.

Case Representation: Although hypophysitis is rare, this pituitary disease can occur during pregnancy or in the postpartum period.

A Toluene-induced Infundibulo-neurohypophysitis: A New Cause of Hypophysitis Secondary to Toxic Exposure.

Background: Hypophysitis is a rare inflammatory disorder of the pituitary gland. Symptoms and signs of hypophysitis can be various, and its recognition may be challenging. Arginine vasopressin deficiency (AVP-D) due to exposure to a variety of drugs and toxic substances is rare, but some cases have been reported.

The Role of the GH Receptor Polymorphisms as a Prognostic Factor of Vertebral Fractures in Acromegalic Patients Resistant to First-generation SSAs and Treated with Pegvisomant or Pasireotide LAR.

Background: Acromegaly is associated with skeletal fragility and increased prevalence of vertebral fractures (VF). Two isoforms of GH receptor (GHR) have been described, which differ in the presence or absence of a transcript of exon 3 of the GHR gene. Both isoforms produce a functional receptor, but the exon 3-deleted isoforms (d3-GHR) have greater sensitivity to endogenous and recombinant GH than the full-length isoform (fl-GHR).

Clinical implications of the 2022 WHO classification on the multidisciplinary management of PitNETS patients.

The review explores the 2022 update to the World Health Organization (WHO) classification of pituitary adenomas, now referred to as pituitary neuroendocrine tumors (PitNETs), and his possible impact on the clinical management of PitNET patients. The review highlights the differences and the evolution from the 2017 to 2022 version, with the current classification considering the lineage of the tumor cells, cell type, hormones produced, and other auxiliary characteristics for a comprehensive histological classification. The revision in terminology reflects a broader perspective on neuroendocrine neoplasia.

Long-term pasireotide-LAR treatment in the personalized therapy of patients with complex acromegaly: a collection of clinical experiences.

Pasireotide-LAR is recommended as a second-line treatment for patients with acromegaly. Although the effects of pasireotide-LAR have been well characterized in clinical studies, real-practice evidence is scant, especially in the long term and within the individualization of therapy in patients with comorbidities. To provide additional insight on the individualized approach to acromegaly management, six clinical cases of complex acromegaly treated with pasireotide-LAR for more than 5 years were reported.

Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot single center experience.

Introduction: Skeletal fragility is a clinically relevant and not-reversible complication of acromegaly, involving around 30-40% of patients since the disease diagnosis. Few studies have investigated the effects on skeletal health of medical therapies for acromegaly. In this retrospective longitudinal monocentre study, we investigated the outcome of skeletal fragility in patients treated with Pasireotide Lar in combination with Pegvisomant (Pasi-Lar + Peg-V), also comparing those observed in patients treated with conventional therapies.

The Pathogenic RET Val804Met Variant in Acromegaly: A New Clinical Phenotype?

Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a pathogenic variant: c.2410G>A (rs79658334), p.

Pancreas as an Unusual Metastatic Site of Medullary Thyroid Carcinoma: A Case of Very Long-term Follow-up Under Prolonged Treatment with Somatostatin Analogues.

Background: Pancreatic metastases from medullary thyroid carcinoma (MTC) are exceptional. Imaging and treatment based on somatostatin receptors may play a role, though the evidence is unconvincing.

Case Presentation: We have, herein, documented a unique case of metastatic MTC, where pancreatic metastasis was identified by 68Ga-PET/CT, with the disease showing very slow progression during treatment with lanreotide autogel.

The Multibiomarker Acro-TIME Score Predicts fg-SRLs Response: Preliminary Results of a Retrospective Acromegaly Cohort.

Context: The prompt control of acromegaly is a primary treatment aim for reducing related disease morbidity and mortality. First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of medical therapies. A non-negligible number of patients do not respond to this treatment.

Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways.

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series.

Unveiling the Etiopathogenic Spectrum of Hypophysitis: A Narrative Review.

Hypophysitis, a rare inflammatory disorder of the pituitary gland, has seen an uptick in reported cases in recent years. Our objective is to summarize the most recent research on the etiopathogenesis, molecular mechanisms, and genetics of both primary and secondary hypophysitis. Primary autoimmune hypophysitis (PAH): During the acute phase of the disease, the pituitary gland in enlarged due to the infiltration of T and B lymphocytes.

Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly.

Context: Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis.

Objective: We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly.

Multidisciplinary management of difficult/aggressive growth-hormone pituitary neuro-endocrine tumors.

Growth Hormone-secreting adenomas exhibits variable biological behavior and heterogeneous natural history, ranging from small adenomas and mild disease, to invasive and aggressive neoplasms with more severe clinical picture. Patients not cured or controlled after neurosurgical and first-generation somatostatin receptor ligands (SRL) therapy could require multiple surgical, medical and/or radiation treatments to achieve disease control. To date, no clinical, laboratory, histopathological, or neuroradiological markers are able to define the aggressiveness or predict the disease prognosis in patients with acromegaly.

CD68+ and CD8+ immune cells are associated with the growth pattern of somatotroph tumors and response to first generation somatostatin analogs.

Somatotropinomas are pituitary tumors with a heterogenous clinical behavior. The tumor microenvironment regulates the interaction between tumor cells and the host immune system, potentially modulating tumor behavior. Here, we aimed to investigate the tumor immune infiltration in a cohort of medically naïve acromegaly patients.

Pituitary Enlargement and Hypopituitarism in Patients Treated with Immune Checkpoint Inhibitors: Two Sides of the Same Coin?

Background: Immune checkpoint inhibitor hypophysitis (IIHs) is an emerging problem in cancer patients treated with immune checkpoint inhibitors (ICIs). We aimed to describe the clinical and molecular features of a multicenter series of IIHs.

Methods: Demographic and clinical features were retrospectively collected for all cases.

De-escalation treatment with pasireotide for acromegaly: a long-term experience.

Introduction: Pasireotide long-acting release (LAR) is approved for second-line treatment of acromegaly. Starting pasireotide LAR 40 mg every 4 weeks is recommended and then up-titrate to 60 mg monthly in case of IGF-I uncontrolled levels. We present three patients treated with a de-escalation approach with pasireotide LAR.

The immune microenviroment in somatotropinomas: from biology to personalized and target therapy.

Pituitary tumors are rare neoplasms, with a heterogeneous biological and clinical behavior, due to their clinical course, local invasive growth, resistance to conventional therapies and the risk of disease progression. Recent studies on tumor microenvironment (TME) provided new knowledge on the biology of these neoplasia, that may explain the different phenotypes of these tumors and suggest new biomarkers able to predict the prognosis and the treatment outcome. The identification of molecular markers that act as targets for biological therapies may open new perspectives in the medical treatments of aggressive pituitary tumors.

Systemic comorbidities of acromegaly in real-life experience: which difference among young and elderly patients?

Introduction: Acromegaly is a rare but potentially life-threatening disease, if not promptly managed, for the systemic complications due to the GH/IGF-I hypersecretion. According to the increased population life span, the number of older acromegaly patients is growing. We aim to investigate clinical features of elderly acromegaly (elderly-ACRO) and to identify the risk factors for the occurrence of comorbidities in elderly-ACRO.