Características clínicas, analíticas, radiológicas y manejo terapéutico de los adenomas hipofisarios clínicamente no funcionantes en el área sanitaria de A Coruña

Abstract

Pituitary adenomas (PA) are usually benign tumours, located in the anterior part of the pituitary gland. They are the most common cause of sellar masses from the third decade onwards, being considered the third most common cause of intracranial neoplasms, after meningioma and glioma (1). A proportion of them are asymptomatic and remain undetectable (2). Despite their benign nature, these tumours can cause considerable morbidity as they may be associated with hormone hypersecretion, mass effect and hypopituitarism and be a major burden on health care resources (3,4). Depending on the presence or absence of hormone secretion PAs can be functioning and non-functioning. The majority of PAs are Clinically Non- Functioning Pituitary Adenomas (CNFPA) and constitute about one third of all PAs, their incidence has been estimated at 1.79/100,000 inhabitants/year (4). Its prevalence is around 26-90 cases per million and constitutes 50 % of pituitary tumours in large surgical series (5). In clinical series its prevalence is much higher at around 400 per million (2). Tumours larger than or equal to 1 cm (macroadenomas) are the most frequent, depending on their size they can become symptomatic, usually causing mass effect, causing neuro-ophthalmological symptoms and hypopituitarism. In contrast, microadenomas (less than 1 cm) are asymptomatic and most are found incidentally on imaging studies (6-8). If we perform an anatomopathological analysis, CNFPA are mostly gonadotropinomas, which produce in most cases gonadotropin alpha subunit, or less frequently gonadotropins, followed by null cell adenomas and finally other silent PA such as corticotropinomas, somatotropinomas, and prolactinoma (9). Transsphenoidal resection is the treatment of choice for CNFPA, allowing decompression and rapid relief of symptoms in many cases (10). A high percentage of patients have residual tumour tissue after surgery, which if left untreated is associated with progression in 40 % in 5-10 years (11). Radiotherapy can be effective in preventing residual tumour growth, but is associated with a high rate of complications. Reoperation for tumour recurrence is sometimes necessary, particularly when there is a risk of compromised optic nerve function (10). Although complications of surgery are infrequent, they are not negligible and include hypopituitarism, cerebrospinal fluid leakage, meningitis, cranial nerve damage, visual compromise and a mortality rate of 0.3-0.5 % (12). The series published on CNFPA to date, both worldwide and nationally, are quite scarce, with a wide variability of results when analysing the incidence and prevalence, as well as analysing the clinical evolution of PAs (3,4) (13,16) In this doctoral thesis it has been decided to know and quantify the extent of the disease in A Coruña health area as a whole. To this end, we have described the clinical characteristics, procedures, diagnoses, treatments, anatomopathological findings, clinical evolution and complications of patients with CNFPA who were treated in the last 4 decades (13) at the Complexo Hospitalario Universitario of A Coruña (CHUAC). For this purpose, data from patients attending the specific neuroendocrine clinic were used. In our study, the sample of CNFPA presenting to the neuroendocrinology department were sporadic and symptomatic macroadenomas associated with headache and visual disturbances, mostly diagnosed in men in the 40-60 age group. At diagnosis, hypopituitarism occurs in about half of the patients, but recovers after surgery. Tumour size is a predictor of hypopituitarism. Endoscopic endonasal surgery seems to behave as a positive predictor of absence of tumour imaging at follow-up. The tumour was an incidental finding in 26.2% of patients. The Ki-67 cell proliferation index is generally low (< 3 %) and a high value (≥ 3 %) is associated with older age. There are very few cases of complete cure (no adenoma and no hypotuitarism). There is tumour recurrence during follow-up, as well as increased hypopituitarism, but visual symptoms improve. This implies lifelong follow-up with reduced life expectancy due to hypopituitarism and treatment-related morbidity.