Pituitary Adenoma

Anatomy and Physiology

  • A midline structure
  • Ant-Post: 15 mm, Sup-Inf: 12 mm
  • In Sella Turcica
    • A cavity of the sphenoid bone
    • Posterior border of the sella
      • = dorsum sellae
        • Two prominences: the posterior clinoids
      • Anterior border of the sella
        • The tuberculum sellae
          • Two lateral projections: anterior clinoid processes.
  • Lateral to the sella —> cavernous sinuses ; include:
    • Internal carotid arteries
      • Surrounded by a plexus of sympathetic nerves
      • Cranial nerves:
        • Third, fourth, and sixth cranial nerves as well as the ophthalmic and maxillary divisions of the fifth cranial nerve.
  • The diaphragm sellae
    • An extension of the dura
    • Separates the pituitary gland from the structures lying above it
      • Optic chiasm
      • Chiasmatic cisterns
      • Anterior cerebral arteries
      • Hypothalamus
      • Floor of the third ventricle
    • Taversed by the pituitary stalk
  • two components of distinct embryologic origins
    • Anterior & intermediate lobes <— Rathke's pouch
      • Evagination of ectodermal tissue <— from the roof of the oral cavity
    • Posterior lobe (neurohypophysis) & stalk <— down-pocketing of the third ventricle
      • Terminal axons from neurons originating in the hypothalamus
        • Secretory granules are synthesized in the supraoptic & paraventricular nuclei
        • Transported along the stalk to the posterior lobe
          • Oxytocin
          • Vasopressin
  • There are eight known releasing or inhibiting hormones from hypothalamus:
      • CRH (corticotropin-releasing hormone)
      • TRH (thyrotropin-releasing hormone)
      • GHRH (growth hormone-releasing hormone)
      • GHIH (growth hormone-inhibiting hormone or SOMATOSTATIN)
      • FSHRH (follicle-stimulating hormone-releasing hormone)
      • LHRH (luteinizing hormone-releasing hormone)
      • ProRH (prolactin-releasing hormone)
      • ProIH (prolactin-inhibiting hormone)


  • ~10% of the healthy adult population has pituitary abnormalities detectable by MRI
  • Pituitary neoplasms —> 10% to 15% of diagnosed primary intracranial neoplasms
  • Pituitary Adenoma
    • ~70% are endocrinological active
    • Macroadenomas: M=F
    • Clinical manifestations of microadenomas: F>M
    • Age: 30-50
    • Etiology:
  • IFS is the rarest of the three syndromes and is defined by the occurrence of two or more cases of acromegaly in a family in the absence of MEN or the Carney complex.

Natural History

  • Local invasiveness
  • Symptoms are commonly present for years prior to diagnosis.
  • Slow progression

Clinical Presentation and Diagnostic Work-Up


  • History and physical examination
  • Neurologic examination (cranial nerves)
    • II, III, IV, V1, V2, VI

Special tests

  • Formal testing of visual fields

Imaging studies

  • MRI
  • Skeletal survey (for acromegaly)

Laboratory studies

  • Complete blood count, blood chemistry, urinalysis
  • Endocrine evaluation of abnormal secretion:
    • Prolactin hypersecretion: prolactin
    • Growth hormone hypersecretion: basal growth hormone, IGF-I, glucose suppression, insulin tolerance, thyrotropin-releasing hormone stimulation
    • ACTH hypersecretion: serum ACTH, 24-h urine for 17-hydroxy-corticosteroids and free cortisol, dexamethasone suppressed CRH test
      • In Cushing's disease with negative neuroimaging studies: selective bilateral simultaneous venous sampling of ACTH from inferior petrosal sinuses

Evaluation of normal endocrine function

  • Gonadal function: FSH, LH, estradiol, testosterone
  • Thyroid function: thyroxine, free thyroxine index, TSH
  • Adrenal function: basal plasma or urinary steroids; cortisol response to insulin-induced hypoglycemia and plasma ACTH response to metyrapone administration

If pituitary adenoma is not functional with normal blood work. Often biopsy is necessary.

Clinical Manifestations of hormonal excess

  • Acromegaly
    • Changes in skull, facial features, jaws, hands, feet
    • Hyperhidrosis
    • Heat intolerance
    • Fatigue
    • Weight gain
    • Paresthesias
    • Arthralgias
    • Glucose intolerance (50% of patients)
    • Hypogonadism (>50% of patients)
    • Hypoadrenalism or hypothyroidism(rare)
    • Elevated basal state serum growth hormone (in excess of 10 ng/mL in 90% of patients); if normal or borderline, nonsuppressibility with hyperglycemia establishes diagnosis; elevated insulin growth factor-I (IGF-I)
  • Hyperprolactinemia
    • Amenorrhea
    • Oligomenorrhea
    • Infertility in women
    • Decreased libido or impotence in men
    • Galactorrhea (mild, transient, if present)
    • Osteoporosis
    • Hypopituitarism (more common with large tumors and sellar enlargement)
    • Basal serum prolactin level > 100ng/ml(normal —> 5-20 ng/mL); 30-100 mg/mL may indicate microadenoma or loss of suppression; hyperprolactinemia with demonstration of pituitary tumor on imaging confirms diagnosis
  • Cushing's disease
    • Obesity (central distribution)
    • Hypertension
    • Glucose intolerance
    • Hirsutism
    • Easy bruising
    • Striae
    • Osteoporosis
    • Psychological changes
    • Hypogonadism
    • Hypopituitarism(rare)
    • Plasma cortisol >10 ng/mL 8-9 h after 1 mg dexamethasone is diagnostic in 95% of cases; Urinary Fred Cortisol UFC of >10 mg/24 h; plasma ACTH often normal to moderately elevated.

Differential diagnosis of suprasellar mass:

  • Pituitary Macroadenom
  • Meningioma
  • Saccular Aneurysm
  • Pituitary hyperplasia
    • Secondary to end-organ failure ( in young adult )
  • Craniopharyngioma
  • Infectious
  • Abcess
  • Cysts
  • Lymphocytic hypophysitis
  • Lymphoma
  • Cordoma
  • Germ Cell Tumour
  • Metastatic Tumour

Pituitary apoplexy
*‌ Rare clinical syndrome

  • Acute hemorrhage or infarction of the pituitary gland
  • Headache
  • Nausea
  • Photophobia
  • Hypopituitarism
  • Visual defects
  • Ocular palsy
  • Can lead to altered consciousness —> urgent surgical decompression of the pituitary fossa.


  • According to both endocrine function
    • Functional
    • Non-functional
  • According to size:
    • microadenoma —> <1cm
    • macroadenoma —> >1cm
    • giant adenoma —> >4cm)
  • According to the extent of expansion or erosion of the sella:
    • Grade 0: Intrapituitary microadenoma with normal seller appearance
    • Grade I: Normal-sized sella with asymmetry of the floor
    • Grade II: Enlarged sella with an intact floor
    • Grade III: Localized erosion or destruction of the seller floor
    • Grade IV: Diffusely eroded or destroyed floor
  • According to extension into the brain
    • from A (bulging into the chiasmatic cistern) to D (extension into the temporal or frontal fossae). This system assigns a lesser degree of importance to involvement of brain, cavernous sinus, or optic apparatus, which all have a significant impact on both selection and effectiveness of therapy.

A bit of pathology!

  • Tumors arising from the neural components of the posterior pituitary gland—> rare
    • Pituicytomas
    • Gangliogliomas
    • Choristomas

Anterior pituitary —> ADENOMA

General Management

Goals of management:

  • remove or control tumor masses
  • control hypersecretion
  • correct endocrine deficiencies while minimizing the risk of hypopituitarism or injury to adjacent structures

Asymptomatic pituitary tumor

  • If not treated—> yearly imagine
  • Observation is an option for nonsecreting microadenomas and small asymptomatic prolactinomas (Fig. 33.3). Tumor growth on imaging,

When to treat:

  • Tumour growth on imaging
  • Symptoms of hypersecretion
  • Development of visual field deficits

How to treat:

  • Any need for rapid relief of mass effect?
  • Symptoms related to hormonal abnormalities?
  • Need for histologic confirmation?
  • Always think about potential morbidity of a given therapy

Medical Management

  • Medical management is the modality of choice for most prolactinomas
  • Dopamine agonists
  • Somatostatin analogues
  • GH receptor antagonist —> Pegvisomant
  • Chemotherapy for locally aggressive or metastatic tumors
    • Anecdotal
    • Responses rates are disappointing

Surgical Management

  • Transsphenoidal microsurgery
    • Mortality rate of approximately 0.5%
    • Major complications (1.5%)
      • Meningitis
      • Cerebrospinal fluid leak
      • Hemorrhage
      • Stroke
      • Visual loss
    • Contraindications:
      • Sphenoid sinusitis
      • Ectatic midline carotid arteries
      • Significant lateral suprasellar extent—>A transcranial approach is preferred in the latter situations.

Radiation Therapy

To choose RT for pituitary adenoma think about:

  • Availability
  • Patient and physician preference
  • Differences in toxicity

Conventional External-Beam Radiation Therapy

  • Control of hypersecretion
    • Acromegaly —> in 80%
    • Cushing's dis —> 50-80%
    • Hyperprolactinemia —> 30%
  • Mass effects


Literature does suggest a high freedom from local tumor progression and variable biochemical cure rates.

Radiosurgery remains an accepted and appropriate treatment for selected cases:

  • Smaller
  • Radiologically well-defined tumors located at a distance (3 to 5 mm) from the optic apparatus
  • Sufficient to limit the dose to the optic chiasm and optic nerves to <8 to 10 Gy.

Fractionated Stereotactic Radiation Therapy (FSRT)

  • Early results with respect to tumor control compare favorably with those reported for conformal radiation therapy.
  • The data are insufficient to draw conclusions on hormonal response.
  • No neurocognitive changes, second malignancies, brain necrosis, or cerebrovascular events have been reported.

Charged Particle Therapy

Protons have been used to deliver either single fractions (proton radiosurgery) or fractionated conformal therapy.

Tumor control (100%), hormonal cure (38% to 52%), and induced hypopituitarism (22% to 44%) are not different than those with photon therapy.

Intensity Modulated Radiation Therapy (IMRT)

Pituitary adenoma targets generally do not present significant concave surfaces. They are small and do not require differential dosing. Consequently, pituitary adenomas are not ideal targets for inverse-planned IMRT. This is borne out by dosimetric studies in which IMRT shows similar conformality and sparing when compared to noncoplanar conformal therapy. The use of IMRT is thus limited to the occasional large, irregular tumour.

Posttherapy Evaluations

  • MRI yearly
  • Regular yearly visual field
  • Hormonal level monitoring
    • The most commonly used —> posttreatment GH value of less than 1 mg/L.
    • insulin growth factor-I (somatomedin-C or IGF-I)
    • GH levels
    • Plasma and urine steroid
    • Plasma ACTH
    • Gonadal, thyroid, adrenal function ( R/O hypopituitarism in F/U after RT)

Treatment Results

Nonfunctioning Pituitary Tumors

Goal —> Relief of any mass effect

If not completely resectable —> decompression of the chiasm (if indicated) followed by radiation provides excellent long-term results.

  • In a series of 252 patients treated with radiation therapy at the Royal Marsden Hospital, the actuarial 20-year progression-free survival rate following definitive irradiation was 94%, which was not significantly different from the 91% progression-free survival seen following combined debulking and adjuvant irradiation.
  • Radiation decrease the recurrence after surgery
  • Not quite clear if should be given adjuvantly after Sx or at time of progression

Indications of RT post-Sx:

  • Local invasion
  • Suprasellar extent
  • Residual tumor

Rest can be observed. However all need yearly imaging.

Fractionated External-Beam Radiation Therapy and Radiosurgery
Park et al. (75) reported on 258 patients operated for nonfunctioning adenomas. Seventy patients were treated with immediate postoperative radiotherapy. The remaining 168 were followed with serial imaging studiesโ€”80% of these patients had been assigned to observation based on total or near-total tumor resection. The 10-year recurrence rate was 2.3% in irradiated patients and 50.5% in those observed. Symptomatic recurrences were limited to patients lost to follow-up. These findings are corroborated by a series of 126 patients from Gittoes et al. (34) in which the 15-year recurrence rate was 7% with adjuvant radiotherapy and 67% following surgery alone.
The retrospective series of radiosurgery for nonfunctioning tumors are small, selected, and heterogeneous. However, the available data suggest a high probability of local control, similar to that provided by fractionated radiation. Series of 20 patients or more are presented in Table 33.5.
Functioning Pituitary Tumors
The goals of radiation for functioning pituitary tumors are similar across tumor types: arrest tumor progression and suppress hormone secretion. Radiation is generally used as an adjuvant or salvage to other failed or incompletely effective therapies. Control of mass effect is more readily achieved than cure, as defined by suppression of inappropriate hormone secretion. This is illustrated by a large series of hormonally active tumors treated at the Princess Margaret Hospital (100) in which 145 patients received 50 Gy of conventionally fractionated external-beam radiation therapy. The local control rate was 96%, with a 10-year disease-specific survival rate of 97%. However, the hormonal cure rate at 10 years was only 39% without the addition of medical therapies.