EpidemioPIT: Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia

Sponsor

Neuromed IRCCS (Other)

Overall Status

Recruiting

CT.gov ID

NCT03973450

Collaborator

(none)

400

Enrollment

Location

32.5

Anticipated Duration (Months)

12.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pituitary Tumor Endocrine Neoplasia Hyperparathyroidism Solid Tumor Familial Tumor Syndrome	Other: Registration of familial forms and associated neoplasia

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Epidemiology of Pituitary Tumours: Prevalence of Associated Endocrine and Non-endocrine Tumours and Potential Implications in the Management and Follow-up of Patients"

Actual Study Start Date :

Jun 15, 2019

Anticipated Primary Completion Date :

Nov 30, 2021

Anticipated Study Completion Date :

Feb 28, 2022

Arms and Interventions

Arm	Intervention/Treatment
Pituitary tumours Patients affected by pituitary tumours and followed-up at the Neuroendocrinology Unit over a 5 yrs period (2014-2018)	Other: Registration of familial forms and associated neoplasia Retrospective registration of associated endocrine and non-endocrine neoplasia and potential familial setting Other Names: Genetic counselling where appropriate

Arm

Intervention/Treatment

Pituitary tumours

Patients affected by pituitary tumours and followed-up at the Neuroendocrinology Unit over a 5 yrs period (2014-2018)

Other: Registration of familial forms and associated neoplasia

Retrospective registration of associated endocrine and non-endocrine neoplasia and potential familial setting

Other Names:

Genetic counselling where appropriate

Outcome Measures

Primary Outcome Measures

Prevalence of hyperparathyroidism (HPT) [Up to 6 months]
measurement of plasma Parathormone (PTH) in % of upper limit of normal values (ULN)
Prevalence of hypercalcemia (hypercalcemic hyperparathyroidism) [Up to 6 months]
measurement of calcemia (mg/dl)
Search for secondary cause of hyperparathyroidism (1): vit D deficiency [Up to 6 months (where indicated)]
measurement of plasma 25(OH)D (ng/ml)
Search for secondary cause of hyperparathyroidism (2): renal failure [Up to 6 months]
measurement of plasma creatinine (mg/dl)
Prevalence of thyroid nodules [Up to 6 months]
Thyroid ultrasound
Prevalence of other endocrine and non-endocrine neoplasia (1) [Up to 6 months]
Report of any neoplasia before the diagnosis of PiT
Prevalence of other endocrine and non-endocrine neoplasia (2) [Up to 6 months]
Report of any neoplasia diagnosed during the follow-up of PiT
Familial setting (1) [Up to 6 months]
Report of any available information concerning familiarity for PiT
Familial setting (2) [up to 6 months]
Familiarity for any associated neoplasia

Secondary Outcome Measures

Genetics (1) familial forms of PiT [up to 15 months]
AIP gene sequencing upon genetic counselling
Genetics (2) familial PiT and/or association with HPT [up to 15 months]
MEN1 sequencing upon genetic counselling
Genetics (3) any other clinical suspicion for MEN1 [up to 15 months]
MEN1 gene sequencing upon genetic counselling
Genetics (4) any other clinical suspicion of inherited neoplasia syndrome [up to 15 months]
genetic counselling for appropriate gene sequencing

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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