Pituitary incidentalomas

INTRODUCTION — The frequent detection of unsuspected anatomic abnormalities in many glands ("incidentalomas"), including the pituitary, made possible by the sensitivity of magnetic resonance imaging (MRI), raises the question of how to evaluate patients who have such an abnormality. The causes, evaluation, and treatment of pituitary incidentaloma are discussed here. The causes, clinical presentation, and evaluation of sellar masses are reviewed separately. (See "Causes, presentation, and evaluation of sellar masses".)

EPIDEMIOLOGY — The term "pituitary incidentaloma" refers to a previously unsuspected lesion that is detected on an imaging study performed for reasons other than pituitary symptoms or disease. Among adults undergoing imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) for reasons other than pituitary symptoms or disease, the frequency of incidentally discovered signal abnormalities (<10 mm) varies among studies from 4 to 20 percent by CT [1-3] and 10 to 38 percent by MRI [4,5].

Not all incidentally discovered sellar masses are pituitary adenomas. In one study of 61 incidentally discovered sellar masses found among 1000 unselected autopsy specimens, there were 37 Rathke's cleft cysts, 18 pituitary adenomas, and 2 each of hyperplasia, infarction, and hemorrhage [6]. However, pituitary adenomas are a common finding, as illustrated by a review of 29 autopsy studies that included over 18,000 pituitary glands [7]. The frequency of pituitary adenomas was approximately 10 percent, and nearly all of the adenomas were microadenomas (<10 mm). The frequencies were similar for males and females and across age groups in adults.

CHARACTERISTICS OF REFERRED PATIENTS

Size — Patients who are referred for evaluation of incidentally discovered magnetic resonance imaging (MRI) signal abnormalities within the sella tend to have larger lesions and a higher incidence of neurologic abnormalities than would be expected from autopsy and MRI series of unselected patients [8,9]. In one series of 328 referred patients, 233 (71 percent) had lesions 10 mm or larger [10]. This presumably reflects the selection process of a referral population.

Adenoma type — In the series of 328 patients with incidentally discovered incidentalomas [10], the following diagnoses were identified:

●179 (55 percent) nonfunctioning pituitary adenomas

●47 (14 percent) Rathke's cleft cysts

●37 (11 percent) lactotroph adenomas

●16 (5 percent) somatotroph adenomas

●7 (2 percent) corticotroph adenomas

●Over one-half had one or more hormonal deficiencies

In a prospective study of 131 patients who had incidentally discovered adenomas, 30 had hypogonadism, 13 had hypothyroidism, and 9 had secondary adrenal insufficiency [11].

The overall frequency of different types of pituitary adenomas is not known, because many large series of incidentally discovered sellar masses intentionally exclude those patients who have lesions that are hypersecreting. In our experience, however, it is common for a sellar mass that is discovered incidentally to be associated, on further evaluation, with obvious clinical consequences, including visual impairment and hormonal hypersecretion. Some of these patients even have obvious clinical manifestations of the hypersecretion (eg, acromegaly) that had been overlooked until the mass was discovered. Severe hormonal hyposecretion, including marked hypothyroidism and hypoadrenalism, can also be seen.

NATURAL HISTORY — Information on the growth of nonfunctioning pituitary incidentalomas is somewhat limited. However, those ≥10 mm have some risk of growth [12-14], while those <10 mm have a very low risk [12,15].

In a systematic review and meta-analysis of studies that included 865 patients with incidentally discovered, nonfunctioning sellar masses, those ≥10 mm were approximately four times more likely to experience growth during follow-up than those <10 mm (incidence 12.5 versus 3.3 per 100 person-years, respectively) [14].

In a retrospective, longitudinal cohort of 177 patients with incidentally discovered nonfunctioning pituitary microadenomas (median size 4 mm) monitored with an average of four MRIs over a median follow-up period of five years, 63 percent of patients experienced no change or a decrease in size of their microadenomas [15]. However, 49 patients (28 percent) did experience an increase in size, but growth was slow with a maximal increase of 6 mm. These findings support the approach of less frequent imaging if the first follow-up MRI after initial diagnosis shows no change in size. (See 'Lesions less than 10 mm' below.)

EVALUATION AND MANAGEMENT — Evaluation of a patient found incidentally to have a lesion within the pituitary depends upon the size of the lesion (algorithm 1). Lesions 10 mm or larger are more likely to be associated with visual and hormonal abnormalities at the time they are discovered and are more likely to enlarge during observation than smaller lesions. (See "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas".)

Lesions 10 mm or larger — These lesions should be evaluated as a symptomatic sellar mass of similar size. Vision should be evaluated clinically and by formal testing of acuity and fields. We suggest that these patients undergo clinical and biochemical evaluation for both hormone hypersecretion and hypopituitarism. For hypersecretion, this includes serum prolactin, insulin-like growth factor-1 (IGF-1) [16], luteinizing hormone (LH), follicle-stimulating hormone (FSH), and alpha subunit, corticotropin (ACTH), and 24-hour urine cortisol [17]. The evaluation of hypopituitarism is reviewed separately.(See "Causes, presentation, and evaluation of sellar masses", section on 'Hormonal evaluation' and "Diagnostic testing for hypopituitarism".)

●Patients with pituitary adenomas resulting in hormonal hypersecretion (eg, hyperprolactinemia, acromegaly, or Cushing disease) should be treated as other patients with these disorders. (See "Management of hyperprolactinemia" and "Treatment of acromegaly" and "Primary therapy of Cushing disease: Transsphenoidal surgery and pituitary irradiation".)

●For patients with gonadotroph adenomas and other clinically nonfunctioning lesions causing visual impairment or other neurologic symptoms, transsphenoidal surgery is the treatment of choice for initial therapy. (See "Treatment of gonadotroph and other clinically nonfunctioning adenomas", section on 'Initial therapy: Transsphenoidal surgery'.)

●For patients with adenomas less than 20 mm without clinically important hormonal hypersecretion and no visual or other neurologic abnormalities, we suggest careful observation [18].These patients should be monitored for size of the mass, visual changes, and hormonal hypersecretion in 6 and 12 months, then annually for several years, and perhaps less frequently thereafter. Hormonal hyposecretion should be treated by appropriate replacement. (See "Treatment of hypopituitarism" and "Treatment of gonadotroph and other clinically nonfunctioning adenomas", section on 'Asymptomatic adenomas'.)

●Most patients whose adenomas are greater than 20 mm will have visual impairment or other neurologic symptoms that make reduction in size desirable. If there are no neurologic symptoms and the patient is an older adult and/or a poor surgical risk, observation is a reasonable course.

Lesions less than 10 mm — Patients with smaller lesions should be evaluated clinically for hormonal hypersecretion and biochemically for any hypersecretion suspected clinically. Only serum prolactin should be measured if there is no clinical suspicion of hormonal hypersecretion, an approach that, in one report, was much more cost effective than either measurement of multiple hormones or performance of follow-up magnetic resonance imaging (MRI) at 6 and 12 months [19]. No evaluation for hormonal hyposecretion or visual abnormalities is necessary. Our approach differs from the 2011 Endocrine Society Guidelines, which recommend that patients with an incidentaloma of any size undergo initial testing for hormonal hypersecretion and hypopituitarism [20].

Patients with lesions not associated with hormonal hypersecretion may be treated as follows [19]:

●For patients with lesions 2 to ≤4 mm in diameter, we do not perform further testing as additional tests do not appear to affect outcome [7].

●For patients with lesions >4 to 9 mm in diameter, we monitor with pituitary MRI yearly for two years; if the lesion is stable in this period, the frequency can be decreased to every few years and then even less often.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pituitary tumors and hypopituitarism".)

SUMMARY AND RECOMMENDATIONS

●Definition – A pituitary incidentaloma is a previously unsuspected sellar mass that is detected on an imaging study performed for reasons other than pituitary symptoms or disease.

●Epidemiology – Pituitary incidentalomas are common. In imaging studies, the frequency of incidentally discovered pituitary lesions is 4 to 20 percent by computed tomography (CT) scan and 10 to 38 percent by magnetic resonance imaging (MRI). In autopsy studies, the frequency of previously unsuspected pituitary adenomas is approximately 10 percent. (See 'Epidemiology' above.)

●Clinical characteristics – Patients who are referred for evaluation of incidentally discovered MRI abnormalities within the sella tend to have larger lesions and a higher incidence of neurologic abnormalities than would be expected from autopsy and MRI series of unselected patients. This presumably reflects the selection process of a referral population. (See 'Characteristics of referred patients' above.)

●Natural history – Incidentally discovered sellar masses >10 mm in diameter are more likely to grow than those <10 mm. (See 'Natural history' above.)

●Evaluation and management

•Pituitary incidentalomas ≥10 mm:

-We perform evaluation for hormonal hyper- and hyposecretion (hypopituitarism). (See "Causes, presentation, and evaluation of sellar masses", section on 'Hormonal evaluation' and "Diagnostic testing for hypopituitarism".)

-For patients with gonadotroph adenomas and other clinically nonfunctioning lesions causing visual impairment or other neurologic symptoms, we perform transsphenoidal surgery for initial therapy. This issue is reviewed in detail separately. (See "Treatment of gonadotroph and other clinically nonfunctioning adenomas", section on 'Initial therapy: Transsphenoidal surgery'.)

-For patients with pituitary lesions ≥10 mm and symptoms related to clinically important hormonal hypersecretion (hyperprolactinemia, Cushing syndrome, acromegaly), treatment is described separately. (See "Management of hyperprolactinemia" and "Treatment of acromegaly" and "Primary therapy of Cushing disease: Transsphenoidal surgery and pituitary irradiation".)

-For patients with pituitary lesions ≥10 mm without neurologic symptoms or hormonal hypersecretion, we monitor with hormonal testing (for both hyper- and hyposecretion), visual testing, and pituitary MRI at 6 and 12 months during the first year. (See 'Lesions 10 mm or larger' above and "Treatment of gonadotroph and other clinically nonfunctioning adenomas", section on 'Asymptomatic adenomas'.)

-For patients with pituitary lesions ≥20 mm and visual impairment or other neurologic symptoms, treatment to reduce the size of the adenoma is indicated. However, if there are no neurologic symptoms and the patient is an older adult and/or a poor surgical risk, we choose observation. (See 'Lesions 10 mm or larger' above.)

●For patients with pituitary incidentalomas <10 mm:

•We measure only serum prolactin if there is no clinical suspicion of hormonal hypersecretion.

•For patients with lesions 2 to 4 mm in diameter, we do not perform further imaging tests.

•For those with lesions between 5 to 9 mm in diameter, we perform MRI yearly for two years; if the lesion is stable in this period, the frequency can be decreased to every few years and then less often. (See 'Lesions less than 10 mm' above.)