Non-Functioning Pituitary Adenoma

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Retrieved

2021-01-23

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Orphanet

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MEN1, AIP, CDKN1B, CDKN1A, CDKN2B, CDKN2C, GH1, BRD2, IGF1, SST, PRL, SSTR2, TBX19, ADM, TRHR, NR2C2, TP53, USP14, SSTR5, TGFB1, PREB, PTTG1, BCL2L11, GADD45G, SLC27A2, WIF1, PART1, SNED1, MEG3, MIB1

MEN1, AIP, CDKN1B, CDKN1A, CDKN2B, CDKN2C, GH1, BRD2, IGF1, SST, PRL, SSTR2, TBX19, ADM, TRHR, NR2C2, TP53, USP14, SSTR5, TGFB1, PREB, PTTG1, BCL2L11, GADD45G, SLC27A2, WIF1, PART1, SNED1, MEG3, MIB1, QTRT1, C5orf66-AS1, SSTR4, POMC, SSTR1, AKT1, CCND1, CDK2, CDKN2A, DRD2, EGFR, ESR1, FGFR2, FSHR, GATM, GNAI2, GNAS, HSD11B1, ITGA6, ITGB4, LIF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, H3P10

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A rare pituitary tumor originating from normally hormone-producing cells of the adenohypophysis, characterized by a sellar or extrasellar mass manifesting with clinical signs secondary to mass effect, but without evidence for hormonal hypersecretion. Typical manifestations are visual disturbances, headaches, cranial nerve dysfunction, and hypopituitarism but the mass may also be discovered incidentally.

Epidemiology

Prevalence of pituitary adenoma in the general population ranges between 1/1000 - 1,300; non-functioning pituitary adenoma (NFPA) accounts for 15-30% of these. Annual incidence is estimated at 1/100,000 worldwide.

Clinical description

NFPA is most often diagnosed in middle-aged adults (average age 50-60 years). The vast majority of NFPAs are revealed by mass effects on anatomic structures in the vicinity of the pituitary (headache, optic chiasm compression) and/or on pituitary hormonal function, leading to hypopituitarism. Pituitary stalk compression can also produce hyperprolactinemia causing amenorrhea and galactorrhea. Pituitary apoplexy may be the presenting feature of NFPA, with severe headaches of sudden onset, meningismus, a variably depressed sensorium, and visual disturbances. However, an increasing proportion of pituitary tumors are detected incidentally on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain performed for unrelated reasons. Very rarely, gonadotropin hypersecretion can stimulate the gonads: macro-orchidism has been reported in males and an ovarian hyperstimulation syndrome in premenopausal women with FSH (Follicle Stimulating Hormone)-secreting tumors.

Etiology

NFPAs are sporadic in the vast majority. The gene aryl hydrocarbon receptor interacting protein, AIP (11q13.3), has been identified as a susceptibility factor, particularly in cases of familial isolated pituitary adenomas (FIPA) or when NFPA begins in childhood or adolescence. NFPA may also be part of multiple endocrine neoplasia syndrome such as MEN1 (gene MEN1, 11q13).

Diagnostic methods

Assessment of tumor volume and extension is based on imaging studies (MRI). Potential visual problems related to compression of optic pathways are diagnosed by evaluation of visual acuity, visual fields and occasionally optic coherence tomography (OCT). Hypopituitarism is diagnosed by measurement of the various pituitary hormones and hormones from the target glands (cortisol, thyroid hormones, etc.). Dynamic tests may be necessary, particularly for assessment of corticotropic axis. Hyperprolactinemia may be found related to pituitary stalk compression and disinhibition of the dopaminergic tone that normally acts at the level of pituitary lactotrophs. Gonadotropins serum levels, particularly FSH may be increased arguing for the gonadotroph nature of the NFPA.

Differential diagnosis

In case of hyperprolactinemia, prolactin (PRL) serum levels are always below 150-200 ng/ml in patients with NFPAs. This distinguishes them from macroprolactinomas, which are associated with much higher PRL levels proportional to tumor size. Other differential diagnoses include other tumors of the sellar region (meningiomas, craniopharyngiomas, metastasis, etc.) and inflammatory process (hypophysitis, sarcoidosis, histiocytosis).

Management and treatment

Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion. Transsphenoidal surgery is often the first-line treatment. If a tumor remnant persists (a frequent situation in patients with large and often invasive adenomas), watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow. NFPA can sometimes recur even after complete resection. Postoperative irradiation is only considered in case of residual tumor growth or relapse. NFPA discovered incidentally may require a different approach, especially when they are small and/or remote from the optic pathways. If hypopituitarism persists, adequate hormone replacement is indicated.

Prognosis

A small excess mortality rate in women and in patients with a young age at diagnosis has been reported.