Pituitary Adenomas Flashcards
Pituitary adenoma nomenclature
- pituitary adenomas are benign and account for 10-15% of primary brain tumours
- 75% are ‘functional’ tumours while 25% are ‘non functional’ tumours
- ‘functional’ means that these tumours hypersecrete hormones
- ‘non-functional’ tumours are defined as tumours who do not secrete excess hormones
size classification
- microadenomas (<10mm)
- macroadenomas (>= 10mm)
- giant adenomas (>=40mm)
-> pituitary carcinomas are rare (0.1% to 0.2% of cases)
Classification changes in WHO 2016
- pituitary adenomas have previously been classified by histopathology and pituitary hormone content of the tumour cells
- update now classifies adenomas according to their pituitary cell lineage, rather than the hormone they produce
Functional tumours
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functional tumours include:
- lactotroph adenomas (prolactinoma) (30%)
- somatotroph adenomas (Growth Hormone-secreting) (25%)
- corticotroph adenomas (Adrenocorticotrophic ACTH) (15%)
Workup
- tumours impinging on optic chiasm on MRI requires visual field testing
- all patients with macroadenomas and patients with ‘larger’ microadenomas (6-9mm) should be evaluated for hypopituitarism
- approximately two-thirds of pituitary adenomas may secrete excess hormones
General overview of Treatment
- transsphenoidal surgical resection is the initial treatment for all tumours except lactotroph adenomas
- remission rates of 80-90%: microadenomas
- remission rates of 40-70%: macroadenomas
Radiotherapy
RT is reserved for patients who:
- do not achieve adequate reduction in tumour size
- do not achieve adequate reduction in hormone levels
- do not achieve adequate reduction in tumour size AND hormone levels
when using surgery, medical therapy or both
Stereotactic treatment is now favoured over conventional fractionated therapy except:
- in the case of large, invasive tumours
- tumours close to the optic chiasm
?stereotactic results in faster overall reduction in hormone secretion than conventionally fractionated regimens
Risk of hypopituitarism remains high - 20% at 5 years and 80% by 10-15 year
Radiation Techniques
fractionated radiation
- 3D conformal, IMRT (>3cm in size and <2mm from the optic chiasm)
- 45-50.4Gy/28# over 5.5 weeks
- can go up to 54Gy in 1.8Gy dose per # for aggressive adenomas (Nelson’s syndrome - where adrenal glands have been removed due to Cushing’s syndrome)
stereotactic radiosurgery
- small lesions <3cm in size and between 3-5mm from the optic chiasm
- dose 12-16Gy non-functional 18-34Gy functional (literature-based doses)
? Advantages of increased conformity
not proven
- theoretically less brain tissue irradiated should result in less morbidity and less cognitive impairment
- ?? fewer secondary malignancies
pituitary adenoma SRS
- best if tumour 3-5mm from optic chiasm
-> dose = 15-25Gy SRS and 45-50Gy for SRT (SLRON doses) - SRT is increasingly being employed with repeat localiser frames. lower complication rate but slower response (9 months vs. 18 months)
- acromegaly responds better to SRS than SRT
Risk of cerebrovascular accident
There is a long-standing controversy regarding a possible increased risk of death from cerebrovascular disease after radiation therapy to the pituitary gland
- risk factors for cerebrovascular deaths in patients operated on and irradiated for pituitary tumours
Erfurth EM, et al., 2002
Lactrotroph adenomas (Prolactinomas)
- lactotroph adenomas make up about 50% of all pituitary adenomas
- occur most frequently in females aged 20-50 years
- more than 90% of lactotroph adenomas are microadenomas
lactotroph adenoma presentation
high levels of prolactin suppress the hypothalamic-pituitary gonadal axis leading to:
- loss of libido
- infertility
- osteoporosis
- oligomenorrhea / amenorrhea / galactorrhea in females
- erectile dysfunction in males
lactotroph adenoma: goals of treatment
1) to restore normal gonadal function and fertility
2) to reduce tumour size for those patients who present with macroadenomas
lactotroph adenoma treatment
most patients are treated with dopamine agonists
- these activate dopamine receptors on tumours
- cabergoline is preferable to bromocriptine as it is more effective in reducing prolactin levels and reducing tumour size
transsphenoidal resection is an option
- achieves a normalisation of prolactin in
-> 65-85% microadenoma patients
-> 40-40% macroadenoma patients
recurrence rate of 20% over 10 years
RT is reserved for those patients where medical/surgical management has failed (rare)
Somatotroph adenomas
Growth hormone (GH) secreting tumours
- GH disturbance can result in acromegaly (thickening of facial features)
- Increased production of GH stimulates the release of insulin-like growth factor (IGF-1) from primarily the liver
- presents with systemic complications
-> Diabetes Mellitus, hypertension, arthritis, carpal tunnel, sleep apnoea, enlargement of feet and hands
-> Tongue, lip and nose enlargement and prominent forehead
GH-secreting tumours
Initial test is measuring IGF-1 level
- Elevated, age-adjusted IGF-1 level is 90% specific for a GH-secreting adenoma of the pituitary
- About two-thirds of GH-secreting tumours are macroadenomas
- Patients have an increased risk of colon neoplasia so colonoscopy is required at time of diagnosis
- Also risk of thyroid dysplasia, so a thyroid ultrasound is advised
GH-secreting tumours treatment
- primary aim is to achieve biochemical control (reduction in GH levels to < 1 ug/L and IGF-levels to normal age-adjusted level)
- secondary aim is to reduce or remove tumour mass
- transsphenoidal surgery is recommended as primary treatment
-> achieves therapeutic goals in 80-90% microadenomas and 40-60% macroadenomas
-> 5 year recurrence rate is 2-8% - repeat IGF-1 and GH levels and MRI should be repeated 12 weeks post surgery
- if therapeutic goals are not met, then repeat surgery can achieve biochemical control in 50% of patients
- dopamine agonist (Cabergoline), somatostatin analogs (Octreotide, Lanreotide, Pasireotide) and GH receptor blockers (Pegvisomant) can be utilised to medically reach biochemical control
- no role for radiotherapy
Corticotroph adenomas
Adrenocortitropic hormone (ACTH)-screting tumour
- ACTH-secreting pituitary adenoma is the cause of Cushing syndrome in 65-70% of cases
- Presentation is one or more of the symptoms of hypercortisolism: weight gain, increase in centripetal obesity, facial rounding, skin striae, diabetes mellitus, hypertension, mood disorders (depression), osteoporosis
ACTH feedback loop
ACTH is secreted from the anterior pituitary in response to corticotropin-releasing hormone from the hypothalamus. Corticotropin-releasing hormone is secreted in response to many types of stress, which makes sense in view of the “stress management” functions of glucocorticoids. Corticotropin-releasing hormone itself is inhibited by glucocorticoids, making it part of a classical negative feedback
ACTH-secreting tumour
- initial test is to confirm presence of hypercortisolism with the late-night salivary cortisol level (diurnal pattern is lost)
- > 80% are microadenomas and may have normal MRI in up to 50% of cases
ACTH-secreting tumour treatment
- preferred treatment is transsphenoidal resection
- cure rates are 80-90% with recurrence rates at 10-20%
- if not cured at initial surgery, then options are repeat surgery (50% success rate), medical therapy, RT or bilateral adrenalectomy
- RT can take 2-5 years to be effective, so medical therapy required during that period to control hypercortisol over-secretion
Non-functioning adenomas
- defined as no secretion of excess hormones
- make up about a third of all adenomas
- can range from symptomless to causing significant hypothalamic or pituitary dysfunction, if a large size
- if symptoms are present, they are:
headaches, visual field defects (bitemporal hemianopia, central scotoma, homonymous hemianopia), hypopituitarism (signs of mass effect)
non-functioning adenomas treatment
- transsphenoidal resection for large or symptomatic tumours
- RT as primary treatment is rare-reserved for patients who are medically unfit for surgery
- RT is more commonly delivered adjuvantly if residual tumour is present on MRI
-> Kamer et al (2009) tumour control of 88-97% of 904 patients in 28 series using stereotactic techniques, but only over a 4-year period
