Endocrine Abstracts

Heat shock protein 90 (HSP90) plays a pivotal role in maturation and stabilization of proteins in conditions of stress. Many HSP90 client proteins are involved in oncogenic signaling and cancer progression, therefore HSP90 inhibitors have a potential as pharmaceutical agents. We reported a strong HSP90 overexpression in corticotroph adenomas and the treatment with C-terminal HSP90 inhibitors has potent anti-tumorigenic and anti-secretory effects in these tumors in vitro</e...

Glucose-dependent insulinotropic polypeptide (GIP) receptor is a member of the G protein-coupled receptors family. According to its incretin properties, GIPR is expressed in tissues such as pancreas, stomach and adipose tissue. However GIPR expression pattern appears to be broader, as it was detected in other tissues such as heart, lung and the central nervous system, thus suggesting either novel ligands for GIPR or novel actions for GIP. Moreover, in some patients with food-d...

Adrenocortical carcinoma (AC) is a rare neoplasm with poor prognosis. Medical treatment of AC is actually based on the use of op’DDD (mitotane) with or without traditional chemotherapeutic agents. Only very few information are available about the effectiveness of somatostatin analogs in AC. In human adrenal gland the expression of all five somatostatin receptor (SSTR) subtypes was previously demonstrated. A differential expression was shown in adrenal adenomas and carcino...

Ectopic Cushing syndrome (EAS) is a rare condition characterized by ACTH-dependent hypercortisolism resistant to normal physiologic suppression by glucocorticoids. EAS is due to an extra-pituitary tumor producing bioactive molecules generated by post-translational cleavage of the proopiomelanocortin gene (POMC). EAS is associated with significant morbidity and mortality and although surgical resection of the primary ACTH-producing tumor remains the mainstay of therapy, not all...

Background: Familial isolated pituitary adenomas (FIPA) is a rare inherited disorder accounting for about 2% of pituitary adenomas. Mutations in the Aryl hydrocarbon receptor Interacting Protein (AIP) gene have been described in about 15% of FIPA families and rarely in early onset sporadic pituitary adenomas. Among the AIP mutations reported so far, the R304X represents, after the Finnish founder mutation Q14X, the second most common one.Me...

The glucose-dependent insulinotropic polypeptide receptor (GIPR) is a 7-transmembrane class B G-protein coupled receptor that mediates the incretin response after nutrient stimulation. Although mostly involved in metabolic disorders, in the last years an improper activation of the GIP/GIPR axis has been increasingly recognized in endocrine tumors, with a potential diagnostic and prognostic value. In Medullary Thyroid Cancer (MTC), a neuroendocrine tumor of the parafollicular C...

Introduction: Paradoxical increase of GH following oral glucose load has been described in ~30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing’s syndrome. Patients...

Introduction: Heterozygous mutations in the AIP gene are associated with young-onset pituitary adenomas while homozygous loss of AIP in animal models is lethal. As early diagnosis could lead to better outcomes, family members of AIP mutation-positive patients need follow up. The R304Q variant is commonly described as pathogenic based on clinical assessment. However, it is also present in the general population (minor-allele-frequency (MAF) 0.0007&#15...