Management of Incidentally Found Nonfunctional Pituitary Tumors

Clinically nonfunctioning pituitary adenomas range from those causing significant hypothalamic/pituitary dysfunction and visual field compromise to those being completely asymptomatic, detected either at autopsy or as incidental findings on imaging scans performed for other reasons (often referred to as pituitary incidentalomas). Growth of nonfunctioning pituitary adenomas without treatment occurs in about 10% of microadenomas and 24% of macroadenomas. In the absence of hypersecretion, hypopituitarism, or visual-field defects, periodic screening by magnetic resonance imaging may detect enlargement. Potential indications for surgery are growth of a pituitary incidentaloma, the development of visual-field defects, or the development of hypopituitarism.

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Patients with pituitary incidentalomas should be evaluated for tumor hypersecretion.
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Those with macroadenomas should be evaluated for hypopituitarism, visual-field defects, and other mass effects.
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Visual-field defects, tumor growth, and hypopituitarism are indications for surgery.
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Deficiencies in corticotropin/cortisol and thyrotropin/thyroxine should be corrected before any surgery.
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Tumor growth in patients who do not undergo surgery can be expected in 10.6% of microadenomas and 24.1% of macroadenomas.
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For patients without specific indications for surgery, surveillance magnetic resonance imaging may need to be performed for up to 20 years.

Key Points

Introduction

Clinically nonfunctioning adenomas (CNFA) of the pituitary, by definition, produce no clinical syndrome related to overproduction of tumor hormones. Studies have shown, however, that 70% to 80% of CNFAs produce gonadotropins or their subunits, and thus are actually gonadotroph adenomas. A few per cent also stain for corticotropin, growth hormone (GH), prolactin (PRL), or thyrotropin; because these hormones are not secreted in sufficient quantities to cause clinical syndromes, such tumors are referred to as “silent” corticotroph, somatotroph, lactotroph, or thyrotroph adenomas.

Although large CNFAs often present because they cause significant hypothalamic/pituitary dysfunction or visual symptoms, others may be completely asymptomatic, being detected either at autopsy or as incidental findings on magnetic resonance imaging (MRI) or computed tomography (CT) scans performed for other reasons. These asymptomatic adenomas are referred to as pituitary incidentalomas. Several other lesions also may be found in the sellar area and may mimic a pituitary adenoma, including craniopharyngiomas, Rathke cleft cysts, meningiomas, gliomas, dysgerminomas, cysts, hamartomas, metastases, and focal areas of infarction. Lymphocytic infiltration of the pituitary can also masquerade as a pituitary adenoma.

Statistically, some normal individuals must have pituitaries that exceed the normal size boundary of 9 mm (+3 standard deviations in healthy subjects ). Chanson and colleagues reported several patients with “normal pituitary hypertrophy”; on MRI, these pituitaries had homogeneous isointense signals, enhanced homogeneously with contrast, and in 2 cases had normal pituitary tissue found at surgery.

This article reviews the epidemiology and management of patients with pituitary mass lesions incidentally found on head MRI or CT done for some reason other than suspected pituitary disease; that is, pituitary incidentalomas.

Prevalence of pituitary incidentalomas

Autopsy Findings

Pituitary adenomas have been found at autopsy in 1.5% to 31% of subjects not suspected of having pituitary disease while alive ( Table 1 ). The average frequency of finding an adenoma for these studies, which examined a total of 19,387 pituitaries, is 10.7%. The tumors are distributed equally throughout the age groups (range 16–86 years) and between the sexes. In the studies in which PRL immunohistochemistry was performed, 22% to 66% stained positively for PRL. Detailed immunohistochemical analysis of 334 pituitary adenomas found in 316 pituitaries of 3048 autopsy cases in one series showed that 39.5% stained for PRL, 13.8% for corticotropin, 7.2% for gonadotropins or α subunits, 1.8% for GH, 0.6% for thyrotropin, and 3.0% for multiple hormones.

Table 1

Frequency of pituitary adenomas found at autopsy

Authors, ^Ref.Year	No. of Pituitaries Examined	No. of Adenomas Found	Frequency (%)	No. of Macroadenomas Found	Stain Positive for Prolactin (%)
Susman, 1933	260	23	8.8	—	—
Close, 1934	250	23	9.2	—	—
Costello, 1936	1000	225	22.5	0	—
Sommers, 1959	400	26	6.5	0	—
McCormick and Halmi, 1971	1600	140	8.8	0	—
Haugen, 1973	170	33	19.4	—	—
Kovacs et al, 1980	152	20	13.2	2	53
Landolt, 1980	100	13	13.0	0	—
Mosca et al, 1980	100	24	24.0	0	23
Burrows et al, 1981	120	32	26.7	0	41
Parent et al, 1981	500	42	8.4	1	—
Muhr et al, 1981	205	3	1.5	0	—
Max et al, 1981	500	9	1.8	—	—
Schwezinger and Warzok, 1982	5100	485	9.5	0	—
Chambers et al, 1982	100	14	14.0	0	—
Coulon et al, 1983	100	10	10.0	0	60
Siqueira and Guembarovski, 1984	450	39	8.7	0	—
Char and Persaud, 1986	350	35	10.0	0	—
Gorczyca and Hardy, 1988	100	27	27.0	0	30
El-Hamid et al, 1988	486	97	20.0	0	48
Scheithauer et al, 1989	251	41	16.3	0	66
Kontogeorgos et al, 1991	470	49	10.4	0	—
Marin et al, 1992	210	35	16.7	0	32
Sano et al, 1993	166	15	9.0	0	47
Teramoto et al, 1994	1000	51	5.1	0	30
Camaris et al, 1995	423	14	3.2	0	44
Tomita and Gates, 1999	100	24	24.0	—	—
Kurosaki et al, 2001	692	79	11.4	1	24
Buurman and Saeger, 2006	3048	334	11.0	3	40
Rittierodt and Hori, 2007	228	7	3.0	0	—
Furgal-Borzych et al, 2007	151	47	31.1	0	21
Kim et al, 2007	120	7	6.7	0	29
Adhakhani et al, 2011	485	61	—	—	—
Total	19,387	2084	10.7%	7	—