Radiation Oncology: A Question-Based Review

Pituitary Tumor

Boris Hristov and Timothy A. Chan

image Background

What is the % of pituitary tumors in relation to all primary brain tumors?

~10%–15% of all primary brain tumors are of pituitary origin.

What % of pituitary tumors are functional vs. nonfunctional?

75% of pituitary tumors are functional, while 25% are nonfunctional.

What are the gender and age predilection for pituitary tumors with symptomatic presentations?

Pituitary tumors with symptomatic presentations occur mostly in females. 70% occur from age 30–50 yrs.

What are some heritable syndromes that predispose to pituitary tumors?

MEN 1 and MEN 2 predispose to pituitary tumors.

What are the embryonic derivatives of the ant pituitary vs. post pituitary?

1.     Anterior: Rathke pouch

2.     Posterior: extension of the 3rd ventricle

What is the name for the bony structure that houses the pituitary?

The sella turcica houses the pituitary.

What hormones are secreted by the ant pituitary vs. the post pituitary?

1.     Anterior: prolactin (PL), GH, ACTH, TSH, LH, FSH

2.     Posterior: ADH, oxytocin

What is the histo-pathologic description of the cells of nonfunctional tumors?

Histopathologically, the cells of nonfunctional tumors are chromophobic.

What hormones are secreted by basophilic cells? Acidophilic cells?

1.     Basophilic: ACTH, TSH, LH, FSH

2.     Acidophilic: GH, PL

What is the most common functional pituitary tumor? 2nd most common? 3rd most common?

Prolactinoma (30%) > GH (25%) > ACTH (~15%)

Which pituitary tumors are more common in males and the elderly? Which are more common in females?

1.     Males and the elderly: nonfunctioning or GH

2.     Females: PL and ACTH secreting

Which are the more common pituitary tumors: micro- or macroadenomas?

Macroadenomas are the more common pituitary tumors.

Which are the most common pituitary tumors in females?

Microadenomas are the most common pituitary tumors in females, particularly those that are PL secreting.

What autosomal dominant syndrome has been associated with pituitary adenomas?

MEN 1 (3 “P's”: pituitary, parathyroid, pancreas), 11q13 mutant/menin

Which CNs are found in the cavernous sinus?

CNs III–IV, V1–2, and VI are found in the cavernous sinus.

What is Nelson syndrome?

Nelson syndrome is ACTH-secreting adenoma in pts with a Hx of adrenalectomy (pts can develop hyperpigmentation of the skin due to α-melanocyte-stimulating hormone).

What is the most common cause of pituitary dysfunction in adults? Children?

1.     Adults: pituitary adenoma

2.     Children: craniopharyngioma

What histologic features are prominent in prolactinomas?

Calcifications and amyloid deposits are prominent in prolactinomas.

What immuno-histochemical stains are positive in pituitary adenomas?

Synaptophysin, chromogranin, and hormone-specific stains

image Workup/Staging

With what signs/Sx do pts with pituitary tumors present?

Bitemporal hemianopsia, HA, and oculomotor deficits (CNs III–IV, VI, V1–V2)

What is the workup of a pt with a pituitary tumor?

Pituitary tumor workup: H&P (physical: CNs, visual field, endocrinopathy), check of hormone levels, thin-slice MRI, and tissue Dx (transsphenoidal resection)

What is the DDx of a pt with a pituitary mass?

Pituitary tumor, craniopharyngioma, meningioma, glioma, suprasellar germ cell, mets, and benign lesions (cyst, aneurysm, empty sella syndrome)

How do pts with prolactinomas present?

Galactorrhea, amenorrhea, ↓libido, and infertility (PL typically >20–25)

What pituitary tumors have a high recurrence rate after resection?

TSH-secreting tumors (risk factors: Hx of thyroid ablation, Hashimoto thyroiditis, prior RT/surgery)

How do nonsecretory tumors commonly present?

Mass effect, visual defect, and hypopituitarism

How do GH-secreting tumors present? ACTH-secreting tumors?

1.     GH: acromegaly, gigantism (kids)

2.     ACTH: Cushing Dz

What lab findings are suggestive of a GH adenoma?

GH > 10 (not suppressed by glucose) and elevated IGF-1 are findings that suggest GH adenoma.

What is considered a normal level of PL after RT?

<25 ng/mL is a normal level of PL after RT.

What lab abnormalities are noted in Cushing Dz?

High cortisol not suppressed by low-dose dexamethasone and normal or ↑ ACTH

What is Cushing syndrome?

Cushing syndrome is elevated cortisol due to a variety of causes (e.g., adrenal production, exogenous use). Pts have low ACTH, unlike in Cushing Dz.

What is the definition of micro-, macro-, and picoadenoma?

1.     Microadenoma: <1 cm

2.     Macroadenoma: >1 cm

3.     Picoadenoma: <0.3 cm

image Treatment/Prognosis

What are the two Tx paradigms of choice for the management of pituitary adenomas?

Pituitary adenoma Tx paradigms:

1.     Surgical resection if hypersecreting or symptomatic (for nonsecreting tumors) → observation or postop RT

2.     Definitive RT alone

What is the Tx paradigm for nonfunctioning pituitary adenomas?

Nonfunctioning pituitary adenoma Tx paradigm: surgery → observation or RT vs. definitive RT alone

What is the hormone normalization rate after surgery for a hyperfunctioning pituitary tumor?

Initially, the hormone normalization rate after surgery is 70%–80%, but it declines to 30%–40% with time.

What types of surgical resection are used for pituitary tumors, and what are the indications?

1.     Transsphenoidal microsurgery: for microadenomas, decompression, debulking of large tumors, reducing hyperfunctioning tumors

2.     Frontal craniotomy: for large tumors with invasion into cavernous sinus, frontal/temporal lobes

Where is the scar located after transsphenoidal resection?

There is no visible scar. Transsphenoidal resection is done through the nose or alternatively from behind the upper lip.

What are the LC rates after transsphenoidal resection? Are they better for macroadenomas or microadenomas?

95%. LC rates are better for microadenomas after surgical resection.

What are some poor prognostic factors after transsphenoidal resection of prolactinoma?

Size >2 cm, high preop PL level, ↑ age, and longer duration of amenorrhea

What are some poor prognostic factors after surgical resection of GH-secreting tumors?

High preop GH and somatomedin C levels, tumors >1 cm, and extrasellar extension

What are the indications for radiotherapy in the Tx of pituitary tumors?

Pituitary tumor indications for radiotherapy:

1.     Medically inoperable

2.     Persistence of hormone defect after surgery

3.     Macroadenoma with STR or decompression

4.     Recurrent tumor after surgery

What are the long-term control rates for hormone-secreting tumors after RT?

Best outcomes with RT for GH-secreting tumors (80%) > ACTH (50%–80%) > PL (30%–40%)

What should be done with medical/pharmacologic Tx before initiating RT for pituitary adenomas?

Medical Tx needs to be D/C b/c of lower RT sensitivity with concurrent medical Tx. (Landolt AM et al., J Clin Endocrinol Metab 2000)

What is the preferred Tx paradigm for prolactinoma?

Prolactinoma Tx paradigm: bromocriptine, but 30% cannot tolerate it due to nausea, HA, and fatigue.

How long does it take for normalization of the PL level to occur after initiating pharmacologic suppression?

Normalization of the PL level takes 1–2 mos following the initiation of pharmacologic suppression.

What is the typical LC rate with RT for pituitary tumors?

The LC after RT is >90% for most pituitary tumors.

What are the typical RT volumes and doses used for pituitary tumors?

Tumor + 1.5–2 cm, IMRT or FSR; 45–50.4 Gy if no gross Dz, 54 Gy for gross Dz

How long does it typically take for hormone stabilization to occur after Tx with RT?

It takes yrs for hormone stabilization after Tx with RT (GH: 50% normalize at 2–5 yrs, 70% after 10 yrs).

What evidence supports at least 45 Gy as the min effective RT dose for pituitary tumor control?

Older Florida data (McCollough WM et al., IJROBP 1991): 10-yr LC was 95%.

What are the indications for and the benefits of SRS in the Tx of pituitary adenomas?

SRS is used for microadenomas and yields better control of hormone secretion (same LC as FSR).

What are the typical SRS doses used for functional vs. nonfunctional tumors?

1.     Functional SRS dose: ~20 Gy

2.     Nonfunctional SRS dose: ~14–16 Gy

What are the differences between LINAC-based and Gamma Knife (GK)-based SRS for pituitary tumors?

With GK, there is less homogeneous dose to the tumor, more precise setup, and slightly less normal tissue treated (similar outcomes/conformality can be achieved with LINAC-based SRS, however).

When is FSR preferred instead of SRS for pituitary adenomas?

FSR is preferred when the pituitary lesion is >3 cm and/or the lesion is <2 mm from the chiasm.

What pharmacologic agents are used for GH-secreting pituitary adenomas?

Somatostatin, octreotide, and pegvisomant (GH receptor antagonist)

What pharmacologic agents are used for ACTH-secreting pituitary adenomas?

Ketoconazole (best), cyproheptadine (inhibits ACTH secretion), mitotane (↓ cortisol synthesis), RU-486 (blocks glucocorticoid receptor), and metyrapone

What RT doses are used with fractionated EBRT? When is EBRT typically used?

45–50 Gy (nonfunctioning), 50–54 Gy (functioning). Fractionated EBRT is typically used for large adenomas.

image Toxicity

What is the RT TD 5/5 dose threshold for developing hypopituitarism?

The TD 5/5 is 40–45 Gy. GH levels ↓ 1st, then LH/FSH → TSH/ACTH.

What is the tolerance of the optic nerves/chiasm with the use of conventional RT?

With conventional RT, 50–54 Gy is the tolerance of the optic nerves/chiasm.

What is the TD of the optic nerve to single-fx SRS?

8 Gy is the TD of the optic nerve with single-fx SRS.

What are the main benefits of using SRS for pituitary adenomas?

Benefits of SRS include ↓ neurocognitive sequelae and possible preservation of normal pituitary function by reducing the dose to the hypothalamus (↑risk of damage to the optic nerve/chiasm).

What is the best way to assess the response to RT in GH-secreting tumors?

The response to RT can be assessed by monitoring IGF-1 levels.

What hormone is the 1st to respond/decrease after RT?

GH is the 1st hormone to respond/decrease after RT.

What is the operative mortality/complication rate after surgery?

1.     Mortality: 1%–2%

2.     Complication rate: 15%–20%

What are the most common surgical complications after resection of pituitary tumors?

Diabetes insipidus (6%) → hyponatremia and CSF leak

How long does it take for hormone normal-ization to occur after RT for pituitary tumors?

It takes mos to yrs for hormone normalization after RT for pituitary tumors.

What is the most common side effect after RT for pituitary tumors?

For pituitary tumors, hypopituitarism is the most common side effect after RT.

Which pituitary pts/tumor types are prone to increased rates of 2nd malignancies after Tx with RT?

Men with GH-secreting pituitary adenomas have increased rates of 2nd malignancies after RT. (Norberg L et al., Clin Endocrinol 2007)