Abstract

As the most common sellar tumors, pituitary tumors feature a diagnostic and therapeutic framework integrated with pathological innovations, advances in imaging techniques and the philosophy of multidisciplinary collaboration. Based on the 2022 WHO Classification, international guidelines and domestic consensus statements, this paper systematically elaborates on their pathological mechanisms, clinical manifestations, differential diagnostic subtyping and individualized therapeutic strategies.

I. Nature and Evolution of Pituitary Tumor Classification

1. Terminology Update and Pathological Basis

The 2022 WHO Classification renamed "pituitary adenoma" to pituitary neuroendocrine tumor (PitNET) to emphasize its neuroendocrine origin. The updated classification stratifies tumors into three major lineages according to transcription factor expression profiles:

• PIT1-lineage tumors: Including densely granulated and sparsely granulated GH-secreting adenomas, PRL-secreting adenomas and TSH-secreting adenomas; sparsely granulated subtypes exhibit more aggressive biological behavior.

• TPIT-lineage tumors: Predominantly ACTH-secreting adenomas; Crooke cell tumors carry high risks of recurrence and metastasis.

• SF1-lineage tumors: Mostly clinically silent gonadotroph adenomas.

2. Epidemiological Characteristics

Autopsy studies reveal a prevalence of approximately 10%, among which 97% are microadenomas. Among clinically symptomatic patients, non-functioning pituitary tumors account for 30%. Functional tumors are dominated by prolactinomas (53%), followed by growth hormone-secreting adenomas (12%) and ACTH-secreting adenomas (4%).

II. Clinical Manifestations of Pituitary Tumors

1. Syndromes Caused by Hormonal Dysregulation

• Prolactinomas: Amenorrhea-galactorrhea syndrome occurs in 93% of female patients, while 78% of male patients present with hypogonadism; long-standing hyperprolactinemia may lead to osteoporosis.

• GH-secreting adenomas (acromegaly): Associated comorbidities include diabetes mellitus (50%), hypertension (35%) and obstructive sleep apnea (65%).

• ACTH-secreting adenomas (Cushing’s disease): Manifestations comprise central obesity (90%), hypertension (60%) and psychiatric disturbances (50%).

• TSH-secreting adenomas: Present with hyperthyroidism accompanied by tachycardia and goiter, and are frequently misdiagnosed as primary hyperthyroidism.

2. Mass Effect and Emergency Presentations

Compression of the optic chiasm causes visual field defects in 18%–78% of patients, and cavernous sinus invasion results in ophthalmoplegia in 50% of cases. Pituitary apoplexy manifests as sudden headache and acute visual loss, which necessitates urgent surgical decompression.

III. Diagnostic Algorithm for Pituitary Tumors

1. Precise Localization via Imaging

Dynamic contrast-enhanced sellar MRI serves as the gold standard; 1-mm thin-slice scanning is mandatory for detecting microadenomas. CT is used to evaluate bony erosion of the sella turcica, while PET/MRI differentiates postoperative scar tissue from residual tumor.

2. Stratified Endocrine Workup

• Prolactinomas: A serum prolactin level >250 μg/L supports definitive diagnosis; drug-induced hyperprolactinemia must be excluded.

• GH-secreting adenomas: Confirmed by elevated IGF-1 plus a GH nadir <1 μg/L during oral glucose tolerance test (OGTT).

• ACTH-secreting adenomas: Combined late-night salivary cortisol (sensitivity 95.8%) and dexamethasone suppression test.

• TSH-secreting adenomas: Elevated free T4 with normal or elevated TSH; differential diagnosis with thyroid hormone resistance syndrome is required.

3. Pathological Subtyping and Prognostic Stratification

Immunohistochemistry is performed to detect PIT1/TPIT/SF1 transcription factors. A Ki-67 labeling index >3% indicates proliferative activity. Sparsely granulated GH adenomas and Crooke cell tumors are classified as highly aggressive subtypes.

IV. Therapeutic Strategies for Pituitary Tumors

1. Refined Surgical Management

Transsphenoidal surgery: Endoscopic techniques achieve gross total resection rates of 52%–77% for macroadenomas; intraoperative neuronavigation reduces the risk of internal carotid artery injury.

Craniotomy: Reserved for giant suprasellar tumors, with special attention to hypothalamic function preservation.

2. Individualized Medical Therapy

Prolactinomas: Cabergoline (0.5–2.0 mg weekly) yields an efficacy rate exceeding 80%; serial tumor monitoring is required during pregnancy.

Acromegaly: Preoperative somatostatin analogues (octreotide) improve surgical remission rates; pegvisomant is indicated for drug-resistant cases.

Cushing’s disease: Pasireotide achieves biochemical control of cortisol in 40% of patients; mifepristone alleviates concomitant glucose metabolism disorders.

3. Indications and Advances in Radiotherapy

Gamma knife radiosurgery (marginal dose 12–25 Gy) achieves local tumor control rates of 90% for residual lesions, though hypopituitarism develops in approximately 50% of patients within 5 years. Proton beam radiotherapy enables precise sparing of the visual pathway.

V. Long-Term Clinical Management of Pituitary Tumors

1. Emergency Management of Pituitary Apoplexy

The Pituitary Apoplexy Score (PAS) guides surgical timing for patients with a score ≥4. Emergency decompressive surgery improves visual function in 74% of patients, with careful preservation of residual normal pituitary tissue intraoperatively.

2. Multimodal Management of Recurrent Tumors

Overall recurrence rates range from 5% to 15%. The extent of cavernous sinus invasion must be assessed prior to reoperation. Temozolomide is administered for refractory tumors with Ki-67 index >10%.

3. Management During Pregnancy

For macroprolactinomas, tumor volume reduction to a safe threshold is recommended prior to conception. Quarterly visual field testing is performed throughout gestation; dopamine agonist therapy is reinstated if tumor progression occurs.

VI. Prospects and Unmet Challenges in Pituitary Tumor Care

Molecular subtyping is driving the development of targeted therapies (e.g., ESR1 antagonists for prolactinomas), and liquid biopsy techniques hold promise for real-time therapeutic response monitoring. Multidisciplinary team (MDT) consultation has become the standard of care, paired with a lifelong long-term surveillance framework.