Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
The study aims to update current knowledge about the epidemiology of pituitary tumours (PiT),
 based on the wide body of scientific literature on new familial and/or syndromic forms.
 Although inherited predisposition is increasingly recognized, its clinical relevance in
 unselected series of PiT patients has not been specifically addressed. In addition, it is
 likely that further recognition of peculiar associations between PiT and other endocrine
 and/or non-endocrine neoplasia will further increase the spectrum of syndromic forms. Since
 the identification of inherited forms of PiT may have significant clinical implications in
 terms of patients management and familial screening, we aim to collect any relevant
 information in order to estimate their prevalence in a large unselected series of PiT
 patients and provide new clues for a modern clinical approach to these patients.
Recent epidemiological studies indicate that clinically relevant PiT have a prevalence around
 1%. The Neuromed Scientific Institute for Research and Cure (IRCCS) is a third referral
 center for the diagnosis and treatment of patients with hypothalamic-pituitary disorders, and
 PiT represent the most frequent condition.

 The best known syndromic of PiT is Multiple Endocrine Neoplasia type 1 (MEN1), others are
 rare conditions, such as MEN1-like syndromes, Carney complex, Mc Cune Albright syndrome, the
 pheochromocytoma/paraganglioma/Pit syndrome. Apparently isolated familial forms of PiT (FIPA)
 have also been well characterized in the last decade.The genetics of inherited PiT is
 involving a growing number of genes.At the moment, the most frequently reported gene
 abnormalities consist of inactivating mutations of the MEN1 and Aryl hydrocarbon receptor
 Interacting Protein (AIP) genes, which are mainly observed in syndromic and isolated familial
 forms of PiT, respectively.

 On the other hand, patients affected by growth-hormone (GH)-secreting PiT
 (acromegaly/gigantism) have an increased risk of associated neoplasia, which has been mainly
 attributed to the growth-promoting effects of GH and/or Insulin-like Growth Factor 1(IGF1).
 However, a variety of neoplasia have been recently observed in patients with non-functioning
 PiT, whereas patients affected by prolactinoma - the most common PiT phenotype - have been
 poorly studied. Associations between PiT and a variety of neoplasia may represent new forms
 of systemic forms of PiT.

 The aim of the study is to evaluate the prevalence of endocrine and non-endocrine neoplasia
 in a large series of PiTpatients and to identify potential familial and syndromic forms,
 including new forms of tumor associations, in order to provide new insights in the
 epidemiology and genetics of PiT and evaluate their clinical relevance in daily practice.

 Eligible patients will receive a detailed informative form about the aim, methods and
 potential implications of the study. They will be included upon written informed consent and
 be re-assured that they may refuse to participate or withdraw from the study at any time,
 without any prejudice in their clinical management.

 Data will be collected retrospectively in patients followed-up in the last 5 years, when an
 increased awareness of systemic conditions has lead, in the respect of good clinical
 practice, to a systematic registration of familiarity for PiT and/or for associated
 neoplasia. As clinically recommended, most patients have been screened at least once for
 primary hyperparathyroidism (pHPT), which is the most prevalent endocrine tumor in MEN1, and
 thyroid ultrasound, which is generally proposed as an extension of any endocrinological
 visit. Therefore, parathyroid and/or thyroid tumours should have been correctly identified in
 a large majority of patients. In contrast, except for systemic search for colonic polyps or
 tumours by coloscopy in acromegalic patients, and screening for breast and colon cancer
 performed by the patients in the setting of the Italian National Health System (NHS)
 programme since the age of 50 yr-old, no systematic search for additional tumours was
 performed and diagnoses were typically made by the general practitioner and other
 specialists.

 Any relevant clinical, biological or imaging data about PiT and extrapituitary tumours will
 be collected for each patients.

 All data will be collected anonymously in a dedicated Excel file.

 Statistical analysis will be performed with using a commercially available software - JMP
 version 11.0 distributed by Statistical Analysis Systems (SAS) (USA). The first part of the
 report will be descriptive, report all endocrine and non-endocrine neoplasia and potential
 familiarity for PiT and/or any other associated neoplasia. Then, a comparison will be made
 between groups and subgroups of PiT patients defined according to the PiT phenotype
 (functioning and nonfunctioning PiT subgroups, tumour volume and invasiveness), as well as
 gender, age and the presence of a familial setting. Based on public reports of the Italian
 registry of cancer (AIRTUM), an attempt will be made to compare the prevalence of the most
 frequent neoplasia in PiT patients with the general population. Attention will be paid to
 recognize syndromic forms of PiT, including known syndromes and new forms of associations
 between PiT and any endocrine or non-endocrine neoplasia.

 Genetic evaluation and counselling will be proposed in selected cases, based on evaluation of
 the clinical picture with the specialist in clinical genetics present in the study team. A
 specific additional consent will be necessary to proceed to the genetic step and DNA
 conservation for further studies where appropriate. Leukocyte DNA will be collected by blood
 sampling. Diagnostic genetic testing will be appropriately performed according to the
 clinical presentation. For unknown associations, this study is intended to be preliminary to
 further genetic studies aiming to identify new candidate genes.
Inclusion Criteria:

 -  Any patient affected by a documented endocrine pituitary tumour (PiT)

 -  At least one evaluation during the study period (2014-2018)

 Exclusion Criteria:

 -  Uncertain diagnosis of endocrine pituitary tumour

 -  Any adult patient declining to enter the study

 -  For the (few) patients aged less than 18 years, parents or legal tutors declining to
 include the patient in the study