Sandbox:AR

Screening

Screening for pituitary adenomas is performed in three main clinical settings:

1. Individuals with a known or suspected germline predisposition to pituitary adenomas.
2. Patients with clinical features suggesting pituitary hormone excess.
3. Patients with an incidentally discovered sellar lesion.

1. Individuals with a germline predisposition

Indications for genetic evaluation

Genetic evaluation should be considered in patients with pituitary adenomas when the clinical presentation or family history suggests an inherited predisposition.

The 2026 Pituitary Society international consensus statement recommends (R2) or suggests (R3) germline genetic testing in the following circumstances:

Recommended indications (R2):

• Somatotrophinoma or prolactinoma diagnosed at or before 18 years of age.
• A personal history of pituitary adenoma and a blood relative with a pituitary adenoma.
• A personal or family history of non-pituitary tumors associated with an established pituitary tumor predisposition gene.

Suggested indications (R3):

• Other pituitary adenoma subtypes diagnosed at or before 18 years of age.
• Somatotrophinoma or macroprolactinoma diagnosed between 19 and 30 years of age, depending on the clinical context.

The recommended core germline gene panel includes:

• AIP
• MEN1
• CDKN1B
• PRKAR1A

Additional genes that may be considered include:

• SDHA
• SDHB
• SDHC
• SDHD
• MAX

Gene panels should include copy-number variant (CNV) detection, using dedicated CNV-calling pipelines or multiplex ligation-dependent probe amplification (MLPA), because exon-level, whole-gene, and larger deletions may be missed by sequencing alone.

The NCCN suggests considering genetic risk evaluation and testing in:

• Patients younger than 30 years with an apparently sporadic functioning pituitary adenoma or a nonfunctioning pituitary adenoma larger than 1 cm.
• Children and adolescents with an apparently sporadic pituitary adenoma (category 2A).

X-linked acrogigantism (X-LAG)

X-linked acrogigantism should be considered in patients with very early-onset pituitary gigantism, particularly when excessive growth begins during infancy or early childhood.

• Germline chromosomal microarray analysis is recommended, using either a single-nucleotide polymorphism (SNP) array or array comparative genomic hybridization (array CGH).
• Identified Xq26.3 duplications should be confirmed to contain the VGLL1 region, which is essential for the X-LAG phenotype.
• GPR101-containing duplications that lack the VGLL1 region have been reported in unaffected kindreds.

Cascade testing

Cascade genetic testing should be offered to at-risk blood relatives of individuals with a pathogenic or likely pathogenic germline variant (R12). Cascade testing in children should be offered before the recommended starting age for gene-specific tumor surveillance (R13).

Suggested ages by which to offer cascade testing in children include:

• AIP: 4 years.
• MEN1: 5–10 years.
• CDKN1B and MAX: 10 years.
• PRKAR1A: birth to 24 months.

These suggested ages are based on the earliest reported manifestations and available surveillance recommendations. Except for MEN1 and SDHx-associated conditions, the evidence supporting specific starting ages is limited; these ages should therefore be individualized according to family history and clinical context.

X-linked acrogigantism is a partial exception to routine cascade testing of unaffected non-infant relatives because the condition is fully penetrant and typically manifests in infancy. However, cascade testing remains applicable to:

• Clinically affected relatives.
• Unaffected infant siblings and offspring.
• Parents of the proband who plan further children, irrespective of clinical status, because a parent may carry the duplication in mosaic form.

Both parents should be tested if the proband is female; only the mother should be tested if the proband is male. When performed, testing should use chromosomal microarray.

MEN1-associated pituitary adenomas

Patients with multiple endocrine neoplasia type 1 (MEN1) require surveillance for pituitary tumors as part of their broader syndrome-specific follow-up.

The 2026 Pituitary Society consensus estimates pituitary adenoma penetrance at approximately 40–60% in individuals with MEN1 and approximately 20% in individuals with pathogenic AIP variants.

The 2025 American Association of Clinical Endocrinology (AACE) consensus recommends pituitary tumor screening in all individuals with MEN1, including annual serum prolactin and IGF-1 measurement and periodic pituitary MRI.

MEN1-associated pituitary tumor surveillance

Guideline / consensus	Starting age	Clinical surveillance	Biochemical surveillance	MRI surveillance
Brandi et al. 2025	Clinical and biochemical surveillance from age 10 years; MRI from age 15 years	Annual history, physical examination, and visual field assessment	Prolactin and IGF-1 every 1–3 years	Every 3–5 years
NCCN 2026	Age 8–15 years	Not specified	Prolactin, IGF-1, and previously abnormal pituitary hormones every 3–5 years or as symptoms indicate	MRI with contrast every 3–5 years
AACE 2025	≥16 years (suggested for asymptomatic individuals)	Not specified	Prolactin and IGF-1 annually in all individuals with MEN1	Periodic MRI; for example, every 1–3 years

The AACE consensus also recommends assessment for hypopituitarism in patients with MEN1-associated pituitary lesions larger than 6 mm or in those with symptoms suggestive of pituitary hormone deficiency. Assessment may include:

• Free thyroxine (FT4) and thyroid-stimulating hormone (TSH).
• Morning serum cortisol.
• IGF-1.
• Testosterone in men.
• Menstrual history in premenopausal women.

This MEN1-specific threshold should not be confused with the general incidentaloma recommendation for baseline hormonal assessment regardless of lesion size.

There is no consensus on whether all patients with pituitary adenomas should routinely undergo screening for MEN1. However, measuring serum calcium in all patients diagnosed with a pituitary adenoma is a reasonable screen for MEN1-associated primary hyperparathyroidism. If hyperparathyroidism is absent, the likelihood of MEN1 is low. In patients with suspected MEN1, the NCCN recommends further evaluation when serum calcium is ≥10 mg/dL; normocalcemic hyperparathyroidism may also occur in MEN1.

Evidence supporting MEN1 pituitary tumor surveillance

A retrospective longitudinal NIH cohort of 320 patients with genetically confirmed MEN1 evaluated radiological surveillance of pituitary adenomas. Among 95 patients with nonfunctioning adenomas, 21 (22%) eventually required intervention. Of the 48 nonfunctioning adenomas with serial volume measurements, 38 (79%) remained stable. All patients who required intervention had symptoms or abnormal pituitary function tests at the time of intervention. These findings support continued clinical and biochemical surveillance when imaging follow-up is individualized; they do not establish that imaging can be discontinued in all patients.

In the DutchMEN1 cohort, 91% of 35 nonfunctioning pituitary tumors detected through screening did not require intervention during a median follow-up of 6 years. This supports the generally indolent course of many screen-detected nonfunctioning pituitary tumors in MEN1, although individual follow-up should be guided by tumor characteristics and clinical findings.

AIP-related familial isolated pituitary adenoma

Germline AIP variants are associated with familial isolated pituitary adenoma, most commonly presenting with somatotrophinomas and gigantism or acromegaly. The estimated pituitary adenoma penetrance is approximately 20% in individuals with pathogenic AIP variants.

Surveillance recommendations summarized in GeneReviews include:

Suggested surveillance for individuals with pathogenic AIP variants

Assessment	Suggested schedule
Clinical assessment, including growth, height, and pubertal development	Annually from age 4 years
Biochemical assessment	Annually from age 4 to 30 years: IGF-1, prolactin, LH, FSH, estradiol or testosterone, TSH, and FT4. After age 30, perform blood tests if symptomatic.
Biochemical assessment in children aged 4–10 years	When annual blood sampling is difficult, monitoring symptoms and growth may be an acceptable alternative, as non-GH-secreting tumors before age 10 are rare.
Visual field assessment	From age 10 years
Baseline pituitary MRI	At age 10 years, or earlier if clinically indicated
Repeat MRI	Every 5 years until age 30 years if clinical assessment and pituitary function tests remain normal; between ages 30 and 50 years only if clinical or biochemical abnormalities develop.
Clinical surveillance after age 30 years	Every 5 years between ages 30 and 50 years; earlier if symptomatic.

No secreting pituitary tumors have been reported after age 30 in AIP variant carriers who had normal clinical and biochemical findings at that age. These surveillance recommendations represent expert guidance and should be individualized according to family history, clinical findings, and age of onset in affected relatives.

A separate 2026 expert review proposes a different surveillance approach, including annual clinical review, IGF-1 and prolactin measurement from the time the variant is identified, and MRI every 5 years beginning at variant detection or age 10 years, whichever is later. It proposes less frequent surveillance between ages 21 and 30 and discontinuation after age 30 if findings remain normal. This differs from the GeneReviews schedule, which continues clinical surveillance every 5 years until age 50. No international consensus guideline currently standardizes AIP surveillance intervals.

2. Patients with suspected pituitary hormone excess

Hormonal screening should be guided by the patient's clinical presentation and features suggestive of hormone excess.

Suspected acromegaly

Screening for acromegaly is indicated in patients with characteristic clinical features, such as progressive enlargement of the hands and feet, facial changes, prognathism, or macroglossia. Associated conditions that may prompt testing include sleep apnea, carpal tunnel syndrome, arthralgia, and metabolic disease.

• Serum IGF-1 is the recommended initial screening test.
• An IGF-1 concentration greater than 1.3 times the age-adjusted upper limit of normal, in a patient with typical clinical features, is considered diagnostic of acromegaly according to the 2024 consensus.
• An IGF-1 concentration above the age-adjusted upper limit of normal is approximately 90–95% sensitive and specific for acromegaly, except during adolescence (12–18 years) and pregnancy. IGF-1 should be repeated when the result does not align with the clinical presentation.
• Random serum growth hormone (GH) measurement should not be used as a standalone screening test.

Further interpretation of borderline or discordant IGF-1 results, including repeat testing and oral glucose tolerance testing, is discussed in the Laboratory Findings microchapter.

Suspected prolactinoma

Serum prolactin should be measured in patients presenting with clinical features suggestive of hyperprolactinemia, including:

• Galactorrhea.
• Menstrual irregularities or amenorrhea.
• Infertility.
• Reduced libido or erectile dysfunction.
• Hypogonadism.
• Symptoms associated with a sellar mass, including headache or visual disturbance.

Serum prolactin should also be assessed in patients with incidentally discovered pituitary lesions as part of the baseline hormonal evaluation.

Assay-related pitfalls and interpretation of prolactin results are discussed in the Laboratory Findings microchapter.

Suspected Cushing disease

Screening for endogenous hypercortisolism is indicated in patients with clinical features suggestive of Cushing syndrome, particularly when multiple or progressive features are present.

Relevant clinical features include:

• Easy bruising and thin skin.
• Facial plethora.
• Proximal muscle weakness.
• Wide violaceous striae.
• Unexplained osteoporosis or fragility fractures.
• Early-onset or difficult-to-control hypertension or diabetes.
• Unexplained hypokalemia.
• In children, weight gain accompanied by a declining height percentile or reduced linear growth.

Before biochemical screening, exogenous glucocorticoid exposure should be excluded, including oral, injectable, inhaled, topical, and other glucocorticoid-containing preparations.

Recommended initial biochemical screening tests include:

• 24-hour urinary free cortisol (UFC), with at least two measurements.
• Late-night salivary cortisol (LNSC), with at least two measurements.
• 1-mg overnight dexamethasone suppression test (DST).

The number of initial tests should be guided by clinical suspicion. Hamidi et al. (2026) describe one appropriate screening test for patients with low clinical suspicion and two or more tests for patients with moderate or elevated clinical suspicion. If one or more initial results are abnormal, one or two screening tests should be repeated, and non-neoplastic causes of hypercortisolism should be considered.

Guideline difference: The 2025 Nature Reviews Disease Primers review by Nieman et al. recommends screening patients with moderate-to-high pretest probability and using at least two biochemical tests. This is more restrictive than the low-suspicion, single-test approach described by Hamidi et al. The differing approaches should be considered when selecting tests according to the patient's clinical presentation and pretest probability.

Random serum cortisol and plasma ACTH measurements are not appropriate initial screening tests for Cushing syndrome.

In pregnancy, urinary free cortisol is preferred and the dexamethasone suppression test should generally be avoided. Further details on pregnancy-related test interpretation and limitations are discussed in the Laboratory Findings microchapter.

3. Incidentally discovered sellar lesions

All patients with an incidentally discovered pituitary lesion should undergo baseline hormonal evaluation, regardless of lesion size. This includes incidentally identified pituitary adenomas and empty sella.

Baseline hormonal assessment

The baseline hormonal assessment should evaluate both pituitary hormone hypersecretion and hypopituitarism.

Screening for hormone hypersecretion:

• Serum prolactin.
• Serum IGF-1.
• Screening for cortisol excess when clinical features or comorbidities suggest Cushing disease, even in the absence of classic signs of hypercortisolism.

Screening for hypopituitarism:

• Free thyroxine (FT4).
• Thyroid-stimulating hormone (TSH).
• Morning serum cortisol.
• Adrenocorticotropic hormone (ACTH) as part of the assessment of the hypothalamic-pituitary-adrenal axis.
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
• Testosterone in men and estradiol in women when clinically indicated.

Premenopausal women with regular menstrual cycles do not routinely require gonadal hormone testing in the absence of clinical indications.

The 2025 Pituitary Society consensus recommends baseline hormonal assessment regardless of lesion size. The need for subsequent testing should be individualized according to the initial findings, symptoms, and interval changes in the lesion.

Visual field assessment

Visual assessment is an important component of the evaluation of patients with pituitary incidentalomas.

• Ophthalmological consultation and visual field testing are recommended for patients with visual complaints or lesions abutting the optic nerves or optic chiasm, regardless of lesion size (R18).
• Visual field testing is suggested for lesions ≥10 mm and for lesions <10 mm located close to the optic chiasm, approximately <3–5 mm (R19).
• Repeat visual field testing is suggested after 6 months in patients with suprasellar extension if surgery is not performed (R20).
• Repeat visual field testing is suggested at 1–2 years in all patients with macroadenomas (R21).
• For macroadenomas not compressing the optic chiasm that are followed with annual MRI, visual field testing at 6–12 months is suggested (R22).
• Patients with abnormal visual field results should be evaluated by a neuro-ophthalmologist (R23).

Follow-up hormonal assessment

Follow-up hormonal evaluation should be determined by the initial hormonal findings, lesion characteristics, and clinical course.

• Patients with documented hormone hypersecretion or hypopituitarism should be followed according to current guidelines for those conditions (R15).
• Repeat pituitary hormone evaluation is suggested in all patients with microadenomas and macroadenomas at 1–2 years, or earlier if new clinical symptoms develop, because new hypopituitarism may occur without lesion growth (R16).
• Repeat hormonal evaluation is recommended in patients with enlarging microadenomas and macroadenomas (R17).

For dedicated pituitary MRI protocols, contrast administration, and radiological follow-up details, refer to the MRI Findings microchapter.

For detailed interpretation of hormonal tests, assay interference, and dynamic testing, refer to the Laboratory Findings microchapter.