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Pituitary adenomas are usually benign tumours arising from the pituitary gland. They are the most frequent space-occupying lesion of the sellar region. Pituitary endocrine neoplasms exhibit a spectrum of behaviours that are not entirely benign and can cause significant morbidity, even when they are not metastatic. For these reasons, recently a novel definition has been suggested: experts recommend to avoid the term “adenoma”, but rather use “Pituitary neuroendocrine tumor (PitNET)”.



They can be classified based on dimensions, hormonal secretion (“functional classification”) and histological features.

Dimensional (Radiological) classification

Dimensional (Radiological) classification:

  • Microadenoma - smaller than 1 cm
  • Macroadenoma - larger than 1 cm
  • Giant - larger than 4 cm

Other radiological classifications are also used, the most common being:

  • Hardy and Vezina classification, to describe dimensions and extensions;
  • Knosp classification, to quantify cavernous sinus (CS) invasion, considered a negative prognostic factors for removal. 

Knosp classification:

  • Grade 0 - No cavernous sinus involvement
  • Grades 1 - Medial involvement of the CS but does not go beyond a hypothetical line extending between the centres of the two segments of the internal carotid artery
  • Grade 2 - The tumour goes beyond the line extending between the centres of the two segments of the internal carotid artery without passing a line tangent to the lateral margins of the artery itself
  • Grade 3 - The tumour extends laterally to the internal carotid artery within the CS
  • Grade 4 - Total encasement of the intracavernous carotid artery

Functional Classification

Non-functional adenomas 

They do not secrete biologically active hormones. They can cause symptoms because of their size as they compress surrounding structures, including hormonal dysfunction, such as hyperprolactinemia due to pituitary compression (so called “stalk effect”) and, rarely, diabetes insipidus.

Diabetes insipidus is a rare presenting symptom in pituitary adenomas, while it is much more common in other lesions of the sellar region, such as craniopharyngiomas, metastases, hypophisitis.

Functional adenomas

They produce hormone over-secretion and are sub-classified accordingly:

  • Corticotrophin (ACTH) secreting adenomas 
  • Prolactin producing adenomas (prolactinomas)
  • Growth hormone secreting adenomas
  • Gonadotropin (LH and FSH) secreting adenomas
  • Thyrotropin (TSH) secreting adenomas
  • Adenomas with secretion of more than one type of hormone (“Plurihormonal” adenomas)

Histological Classification

  • Typical (“Benign”) adenomas, infrequent mitotic figures and a low proliferative index (Ki67 < 3%);
  • Atypical adenomas, with aggressive histological features including elevated mitotic index (Ki67 > 3%) and overexpression of the p53 protein;
  • Pituitary carcinomas, malignant tumours with histologically aggressive features and radiological evidence of metastases.

2017 WHO Classification

In the 2017 WHO classification, the entity "atypical adenomas" has been removed. Other clinical parameters such as tumor invasion (by MRI studies and/or intraoperative impression) should be considered in individual cases to define clinically aggressive adenomas.



Pituitary adenomas are relatively common; they are the third common intracranial neoplasm (about 10% of all intracranial tumours in adults). The peak incidence occurs between 30 and 60 years. Postmortem investigations show a prevalence of incidental pituitary lesions of up to 27% and cranial MRI demonstrates a prevalence of about 10%.

Relative prevalences:

  • Prolactinomas - 50-55%;
  • Non-functional - 30% of pituitary tumours, 80% of pituitary macroadenomas;
  • Somatotroph - 20-25%;
  • Corticotroph - 5-8%;
  • Gonadotroph - 4.1% old literature, 20-25% with new serology technique;
  • Thyrotroph - 0.5-3%.



Most pituitary adenomas occur spontaneously, only very rare cases are familial, approximately 5% of all pituitary adenomas. There is an association with some recognized inherited syndromes that involve pituitary tumorigenesis:

  • Multiple endocrine neoplasia type 1 (MEN 1)
  • Multiple endocrine neoplasia type 4 (MEN 4)
  • Carney complex (CNC)
  • Familial isolated pituitary adenomas (FIPA)


Symptoms and signs

Non-functioning pituitary adenomas typically cause signs and symptoms related to the mass effect on surrounding structures. Macroadenomas can compress the optic chiasm typically leading to bitemporal hemianopia and can cause hypopituitarism and hyperprolactinemia. Hormonal deficits typically initially involve only GH and gonadotroph axes and are then followed by TSH and ACTH; high PRL levels due to the “stalk effect” can be absent when hypopituitarism is advanced.

Clinical signs and symptoms are typically slow and progressively worsening. In 2%-12% of pituitary adenomas, an abrupt haemorrhage or infarction causes a sudden increase in mass effect; the clinical picture includes a severe headache with neurological deficits (visual disturbances or ocular palsy). This condition is defined pituitary apoplexy and it is a medical and surgical emergency. Pituitary function is frequently impaired due to the abrupt compression: corticotropic deficiency with adrenal insufficiency may be life threatening if left untreated.



The diagnosis is based on clinical manifestation, medical history and hormonal testing. Incidental diagnosis on neuroradiological investigations is not uncommon.

Hormone testing

They can demonstrate if there is an abnormal secretion or deficit of a specific hormonal axis. Endocrine assessment should always include basal values of pituitary tropine (prolactin, TSH, GH, ACTH, FSH) and basal values of hormones produced by the target organs (fT4, IGF-1, cortisol, testosterone). Sometimes inhibition and stimulation tests are needed to reach a diagnosis (Insulin Tolerance test, Growth Hormone stimulation test, Oral Glucose Tolerance Test, Dexamethasone suppression test).

Neuroradiological diagnosis

The most useful radiological examination to detect pituitary adenomas and define their extension is magnetic resonance imaging (MRI). Sensitivity and specificity can be increased, especially in cases of microadenomas, can be increased by specific sequences and dynamic studies (i.e. images are taken at various times after contrast administration to optimize normal pituitary gland and microadenoma differentiation). Computed tomography (CT) scan better shows bone and nasal anatomy, which is helpful to plan surgical treatment.

Petrosal sinus sampling

It is considered a useful method if there is the suspicion of a ACTH microadenoma in the presence of a negative MRI. In a patient with Cushing’s disease, it can confirm the presence of a microadenoma and exclude ectopic ACTH production, e.g. paraneoplastic syndromes or neuroendocrine tumours.


Differential diagnosis

Other sellar tumors may mimic symptoms of a pituitary adenoma, but typically present different radiological and clinical features:

  • Craniopharyngioma
  • Rathke’s cleft cyst
  • Arachnoid cyst
  • Chordoma
  • Meningioma
  • Granulomatous disease
  • Metastases
  • Hypothalamic and chiasm glioma



Treatment depends on several factors like adenoma size and extension, hormone over-secretion, age and general conditions of the patient.

Pharmacologic management

Prolactinomas are generally treated with dopamine agonist and rarely require surgery. In Cushing’s syndrome and acromegaly a pharmacologic treatment can help. Adequate hormonal replacement of ACTH and TSH axes is essential in cases of hypopituitarism, especially before surgery.
Medical therapies are available for GH and ACTH adenomas and are usually part of a multidisciplinary treatment.

Surgery treatment

When surgery is required, an endonasal endoscopic transphenoidal approach is usually used. The approach can be tailored to the adenoma dimensions and extensions. Surgical team experience and expertise are important to achieve optimal results.
A transcranial approach might be necessary in a minority of adenomas, usually giant or with irregular and complex intracranial extensions. 

Radiation therapy

Radiation therapy is indicated when a pituitary adenoma cannot be controlled with surgery and medical therapy, typically because of extensions in the cavernous sinus. Radiosurgery is typically recommended.



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Elena Roca, MD

Neurosurgery Resident
University of Milan (Italy)
"Spedali Civili" Hospital Brescia (Italy)
Scientific Team UpSurgeOn

Francesco Doglietto, MD, PhD

Neurosurgeon Consultant
Assistant Professor in Neurosurgery
University of Brescia
"Spedali Civili" Hospital Brescia (Italy)