Pituitary incidentaloma is a pituitary lesion serendipitously discovered on brain imaging (CT, MRI or PET) performed for some other reason.

Most pituitary tumors are detected during the investigation of symptoms associated with hormonal dysfunction and vision abnormalities.

The wide application of CT, MRI has led to an increasing recognition of such lesions.

A meta-analysis of 10 retrospective studies including slightly more than 3500 patients reported prevalence of 16.7% for pituitary adenoma and of 0.2% for macroadenoma ¹⁾.

Data on the prevalence of pituitary incidentalomas is generally derived from retrospective autopsy and imaging studies. The estimated figures vary widely from 1.5 to 38% depending on the era of the study and the study population. This variability reflects differences in definitions of pituitary incidentaloma used by the authors (asymptomatic, Non-Functioning Pituitary Neuroendocrine Tumor or incidentally noted lesion); the type of the study (autopsy or radiological) and the imaging technique (CT, 1.5 T or 3.0 T MRI) ^{2) 3)}.

In the largest meta-analysis of autopsy studies comprising 18 902 examined pituitaries from 32 series, the mean prevalence of pituitary incidentaloma was 10.7% (range 1.5–31%). Lesions were uniformly distributed between sexes and among adult age groups. Importantly, the prevalence of macroadenomas in autopsy series is <1% ⁴⁾.

Some studies report slightly increased prevalence in the elderly population ⁵⁾.

The prevalence of clinically significant lesions was around 80 per million cases in two studies, one British ⁶⁾ and the other Belgian ⁷⁾.

pituitary neuroendocrine tumor Natural History.

Micro-incidentalomas have maximum diameter of less than 1cm

Macro-incidentalomas are at least 1cm.

Micro-incidentalomas have a reported mean prevalence in normal individuals of around 10%.

Although the etiology of pituitary incidentalomas covers a wide range of pathologies, most of them (∼90%) are benign adenomas.

They may result in visual and/or neurologic abnormalities.

Patients with a pituitary incidentaloma undergo a complete history and physical examination, laboratory evaluations screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm.

Patients with incidentalomas not meeting criteria for surgical removal should be followed with clinical assessments, neuroimaging (magnetic resonance imaging at 6 months for macroincidentalomas, 1 yr for a microincidentaloma, and thereafter progressively less frequently if unchanged in size), visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm (6 months and yearly), and endocrine testing for macroincidentalomas (6 months and yearly) after the initial evaluations ⁸⁾.

The endocrinologist facing a pituitary incidentaloma has to solve two main diagnostic problems: (i) the nature and extent of the lesion, and (ii) whether hormonal excess or deficits result from the lesion. The former is achieved by the use of pituitary MRI and visual field (VF) examination and the latter by basal or dynamic hormonal assessments. The answers to these two questions will guide the treatment and follow-up.

They should all be screened for hypersecretion (prolactin (PRL), IGF-1, midnight salivary cortisol), and those with macroadenomas should also be screened for hypopituitarism (macroadenomas).

Growth of Non-Functioning Pituitary Neuroendocrine Tumors without treatment occurs in about 10% of microadenomas and 24% of macroadenomas ⁹⁾.

Anterior pituitary tumors

 pituitary neuroendocrine tumor

 Pituitary hyperplasia

 Pituitary carcinoma

Posterior pituitary tumors

 Pituicytoma

 Granular cell tumors

Benign parasellar tumors

 Meningioma

 Craniopharyngioma

 Neurinoma

 Lipoma

Malignant tumors

 Glioma

 Germ cell tumor

 Primary lymphoma

 Chordoma

 Chondrosarcoma

 Chondroma

 Ependymoblastoma

 Plasmocytoma

 Pituitary metastases

Malformative lesions

 Rathke’s cleft cyst

 Dermoid cyst

 Epidermoid cyst

 Arachnoid cyst

 Hamartoma

Inflammatory and granulomatous lesions

 Lymphocytic hypophysitis

 Granulomatous hypophysitis

 Langerhans cell histiocytosis

 Tuberculosis

 Sarcoidosis

 Pituitary abscess

Vascular lesions

 Aneurysms

 Cavernous angiomas

 Cavernous sinus thrombosis

Diagnostic, treatment and follow-up strategies should be in alignment with the optimal personalized clinical benefit ¹⁰⁾.

Most cases of pituitary incidentalomas do not meet criteria for surgical excision, but may require follow-up. The follow-up strategy consists of clinical evaluation, pituitary MRI, VF examination and hormonal assessments. Macro-incidentalomas require more extensive initial investigation, as well as closer MRI surveillance, than micro-incidentalomas.

The following tests should be performed: MRI at 1 year for micro-incidentalomas, at 6 months for macro-incidentalomas and then less frequently if unchanged in size, visual field examination for lesions enlarging to abut or compress the optic nerves or chiasm (6 months and yearly) and endocrine testing for macro-incidentalomas (6 months and yearly) ¹¹⁾.

Patients with a pituitary incidentaloma should be referred for surgery if they have a visual field deficit; signs of compression by the tumor leading to other visual abnormalities, such as ophthalmoplegia, or neurological compromise due to compression by the lesion; a lesion abutting the optic nerves or chiasm; pituitary apoplexy with visual disturbance; or if the incidentaloma is a hypersecreting tumor other than a prolactinoma.

VF deficits or neurological disturbances are the strongest recommendations for surgery. Furthermore, hormonally active incidentalomas, with the exception of prolactinomas, should be treated by surgery.

Esteves et al. detected 71 pituitary incidentalomas, 3 in children/adolescents. In adult patients, mean age was 51.6 ± 18.46 years and 42 were female (61.8 %). The most frequent reason for imaging was headache (33.8 %). The image that first detected the incidentaloma was CT scan in 63.2 and 17.6 % patients presented symptoms that could have led to earlier diagnosis. pituitary neuroendocrine tumor is the most prevalent lesion (n 48; 70.6 %), followed by Rathke's cleft cyst (n 9; 13.2 %). Hormonal evaluation revealed hypopituitarism in 14 patients and hypersecretion in 6: 5 prolactinomas and 1 pituitary somatotroph adenoma. Twenty-one (28.8 %) patients underwent surgery and there was no malignancy.

In concordance with available literature, adenomas are the most frequent incidentally found pituitary lesions. Hormonal dysfunction is quite prevalent, including symptomatic presentations, which suggests that there seems to be a low sensitivity for the diagnosis of pituitary disease ¹²⁾.

A 41-year-old Thai woman presented with elevated serum thyroid hormone levels and non-suppressed thyrotropin (TSH). Magnetic resonance imaging showed a 4 mm × 2 mm pituitary neuroendocrine tumor. Five of her relatives had similar thyroid tests abnormalities, but a sister had Graves' disease. Thyroperoxidase and thyroglobulin antibodies were positive in all affected family members, except for the proband's 4.5-year-old niece. Lack of thyrotoxic symptoms and TSH suppression by triiodothyronine indicated incidentaloma rather than a TSH-secreting pituitary neuroendocrine tumor. Genetic analysis revealed a THRB gene mutation (c.1037G>T), resulting in p.G251V ¹³⁾.

A 54-year-old woman, presenting with upper and lower extremity paresthesia, salt cravings, episodes of hypotension, fatigue and a long term history of depression. Physical exam was unremarkable. Cervical and brain MRI ordered by her neurologist three years ago revealed sella and pituitary normal in size, stable very small 3 mm pituitary incidentaloma and mild disc bulging. Basal pituitary hormonal screening showed low cortisol and ACTH levels. Insulin Tolerance Test and Glucagon Stimulation Test confirmed secondary ACTH deficiency with concomitant GH deficiency. In spite of medical counseling the patient refused glucocorticoid replacement. Due to the non-specific symptoms of this condition it remains a challenge to be diagnosed by clinicians. In conclusion: The case shows that hormonal deficiencies may occur in small tumors less than 6 mm ¹⁴⁾.

MRI of the Pituitary Gland By Jean-François Bonneville, Fabrice Bonneville, Françoise Cattin, Sonia Nagi

This clinically oriented book will familiarize the reader with all aspects of the diagnosis of tumors and other disorders of the pituitary gland by means of magnetic resonance imaging (MRI). The coverage includes acromegaly, Cushing’s disease, Rathke cleft cysts, prolactinomas, incidentalomas, Clinically nonfunctioning pituitary neuroendocrine tumors, other lesions of the sellar region, hypophysitis, and central diabetes insipidus. Normal radiologic anatomy and the numerous normal variants are described, and guidance is also provided on difficulties, artifacts, and other pitfalls. The book combines concise text and high-quality images with a question and answer format geared toward the needs of the practitioner. MRI is today considered the cornerstone in the diagnosis of diseases of the hypophyseal-hypothalamic region but the relatively small size of the pituitary gland, its deep location, the many normal anatomic variants, and the often tiny size of lesions can hinder precise evaluation of the anatomic structures and particularly the pituitary gland itself. Radiologists and endocrinologists will find MRI of the Pituitary Gland to be full of helpful information on this essential examination, and the book will also be of interest to internists and neurosurgeons.