Management of pituitary incidentaloma

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Pituitary incidentalomas (PIs) represent a modern clinical entity increasingly recognized due to advances and easier accessibility to imaging techniques. By definition, PIs should be detected during brain imaging performed for investigation of a non-pituitary disease. Although anatomic variations, technical artefacts or pituitary hyperplasia might also be interpreted as PIs, the most relevant incidentally detected lesions are those that fulfill radiological criteria for a pituitary adenoma in asymptomatic patients or in the presence of subclinical diseases. The natural history of PIs is not fully determined, but there is a wealth of evidence indicating that most microincidentalomas (lesions < 10 mm) have a benign course, whereas macroincidentalomas (≥10 mm) deserve more attention due to an increased risk for hormone abnormalities and mass effects. This concept is important to keep in mind for an optimal diagnostic and therapeutic management of PIs that avoids harmful iatrogenesis and unnecessary health care costs.

Introduction

Pituitary incidentalomas (PIs) can be defined as unexpected abnormalities of pituitary or non-pituitary origin detected during brain imaging performed for unrelated indications. They are classified in micro (<10 mm or 1 cm) or macroincidentalomas (≥10 mm or 1 cm) according to their size. In most cases, PIs are detected by computed tomography (CT) or magnetic resonance imaging (MRI) during evaluation of non-specific neurological symptoms, headaches or head trauma [1]. Nevertheless, the definition of PIs is not necessarily as straightforward as it appears ∗[2], [3]. In some studies, only lesions that fulfill imaging criteria for a pituitary adenoma are considered as PIs [4], [5], while in other series there is no such distinction, and even technical artefacts or physiological pituitary enlargement are included in the definition [6], [7], ∗[8]. It is also clear that not all detected lesions are true PIs, as some signs and symptoms that are not readily linked to a pituitary disease are only recognized late in the diagnostic workup [9], ∗[10].

Differences in the definition of PIs and the type of technique employed in imaging studies are the main factors affecting their prevalence. In retrospective MRI studies carried out in unselected individuals, the rate of microincidentalomas varies from 10 to 38%, while the percentages of macroincidentalomas are much lower, varying from 0.16 to 0.3% [8]. These numbers have a fairly good degree of correspondence with that seen in post-mortem studies. An analysis of 32 autopsy series revealed 2023 adenomas in 18,902 pituitaries, resulting in a mean prevalence of 10.7%, with frequency of identified PIs ranging from 1.5 to 31% among the 32 studies [11]. Noteworthy, only 7 (0.34%) macroincidentalomas were identified, suggesting that most pituitary macroadenomas probably come to clinical attention at some point in life [7], [11]. Accordingly, pituitary macroadenomas are commonly seen in the clinical practice, distributed equally in adult men and women throughout all age groups, and in many cases, they are erroneously interpreted as incidentalomas [7], [9], [11], [12], [13].

Although the natural history of PIs is not fully established, the findings from both imaging and post-mortem studies indicate that an incidentally discovered pituitary microadenoma rarely transforms into a pituitary macroadenoma ∗[8], [9], ∗[10]. As intuitively expected, solid lesions and macroadenomas have a greater tendency for growth over the years than cystic lesions and microadenomas, with visual deterioration occurring almost exclusively in macroadenomas and pituitary apoplexy rarely seen in observational studies [5], [6], [9], [13], [14], ∗[15]. Immunohistochemistry of PIs found at autopsies has shown that roughly two-thirds of incidentally detected pituitary adenomas are apparently null cells tumors or stained for prolactin [16].

Section snippets

Neuroradiological differential diagnosis

When a pituitary lesion is incidentally disclosed by a head imaging examination, the differential diagnosis includes virtually all tumorous and nontumorous diseases that can be found in the sellar and perisellar regions [17]. By far, pituitary adenomas are the most common cause of PIs, accounting for 70–80% of the cases in neuroradiological and surgical cohorts, followed by Rathke's cleft cysts and craniopharyngiomas [18], [19]. This contrasts with the findings of a postmortem Japanese study,

Initial evaluation

A careful anamnesis and physical examination, looking for primarily unsuspected signals or symptoms of pituitary hyper or hypofunction and subtle neuroophthalmological complaints, are essential part of the initial evaluation of a patient with either a micro or a macro PI. In lesions reaching optic chiasm, a visual evaluation is mandatory, including Goldman perimetry, even in patients with no visual complaints, and examination of III, IV and VI cranial nerves, in cases with cavernous sinus

Observation versus surgery or medical therapy

As previously mentioned, after exclusion of other unrelated lesions, PIs can be divided after the initial hormonal screening in different pituitary adenomas subtypes [2]. This definition will directly impact on the management of these tumors. Functioning tumors almost always require treatment, while for NFPA some factors like age, presence of compressive symptoms and proximity of the optic pathways should be considered to define the best approach (surgery vs observation) [40].

The primary

Personal experience and conclusions

The lack of clear definition of PIs and the paucity of long-term prospective studies on their natural history has resulted in different opinions about their optimal management. In Fig. 2, we present a practical approach according to our personal experience, which is based on the premise that a true PI is not associated with any signal and symptom directly related to it, either at an initial evaluation or retrospectively after its detection by imaging. In this clinical context, the next step is

Conflicts of interest

The authors have no conflict of interest to declare.

Role of the funding source

There are no sources of funding related to this article.

Practice points

  • Many PIs seen in clinical practice refer to anatomical variations, technical artifacts and lesions smaller than 5 mm that do not need any further investigation

  • A true PI should not be associated with any signal and symptom directly related to it, either at an initial evaluation or retrospectively after its detection by imaging

  • Most microincidentalomas have a benign course and do not need an extensive and prolonged diagnostic

References (51)

  • J. Feldkamp et al.

    Incidentally discovered pituitary lesions: high frequency of macroadenomas and hormone-secreting adenomas - results of a prospective study

    Clin Endocrinol (Oxf)

    (1999)
  • K. Arita et al.

    Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination

    J Neurosurg

    (2006)
  • N. Sanno et al.

    A survey of pituitary incidentaloma in Japan

    Eur J Endocrinol

    (2003)
  • P.F. Day et al.

    Retrospective multicentric study of pituitary incidentalomas

    Pituitary

    (2004)
  • V. Vasilev et al.

    MANAGEMENT OF ENDOCRINE DISEASE: pituitary 'incidentaloma': neuroradiological assessment and differential diagnosis

    Eur J Endocrinol

    (2016)
  • N. Karavitaki et al.

    What is the natural history of nonoperated nonfunctioning pituitary adenomas?

    Clin Endocrinol (Oxf)

    (2007)
  • W. Huang et al.

    Management of nonfunctioning pituitary adenomas (NFAs): observation

    Pituitary

    (2018)
  • O.M. Dekkers et al.

    The natural course of non-functioning pituitary macroadenomas

    Eur J Endocrinol

    (2007)
  • P. Iglesias et al.

    Prevalence, clinical features, and natural history of incidental clinically non-functioning pituitary adenomas

    Horm Metab Res

    (2017)
  • L.E. Donovan et al.

    The natural history of the pituitary incidentaloma

    Arch Intern Med

    (1995)
  • M.M. Fernández-Balsells et al.

    Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis

    J Clin Endocrinol Metab

    (2011)
  • H. Buurman et al.

    Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data

    Eur J Endocrinol

    (2006)
  • C. Esteves et al.

    Pituitary incidentalomas: analysis of a neuroradiological cohort

    Pituitary

    (2015)
  • A. Teramoto et al.

    Incidental pituitary lesions in 1,000 unselected autopsy specimens

    Radiology

    (1994)
  • M.C. Machado et al.

    Persistence of intrasellar trigeminal artery and simultaneous pituitary adenoma: description of two cases and their importance for the differential diagnosis of sellar lesions

    Arq Bras Endocrinol Metabol

    (2014)
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