Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

pituitary apoplexy

Back
1st line – 

glucocorticoid ± levothyroxine

Pituitary apoplexy is a potentially life-threatening condition because it may be associated with acute hypopituitarism with resulting adrenocorticotrophic hormone and cortisol deficiency.[11]​​ Prompt recognition of the condition should be followed by administration of parenteral corticosteroids along with intravenous fluids and parenteral analgesia. If left untreated it may be fatal.

If levothyroxine is required, it should be started once glucocorticoids have been initiated.

Primary options

hydrocortisone: 100 mg intravenously every 8 hours

or

dexamethasone: 4 mg intravenously every 8 hours

-- AND / OR --

levothyroxine: 1 microgram/kg/day initially, adjust according to thyroid function tests

Back
Plus – 

observation

Treatment recommended for ALL patients in selected patient group

MRI should be repeated in 6 to 12 months to assess for any tumour growth, with further follow-up intervals based on the tumour size. Visual field testing needs to be monitored in intervals if the tumour is abutting the optic chiasm. Pituitary function testing should be repeated if the tumour grows or there is clinical evidence suggestive of hypopituitarism. Patients with macro-adenomas need follow-up for life because of the potential risk for tumour growth.

Back
Consider – 

evaluation for trans-sphenoidal surgery (trans-nasal or trans-labial or endoscopic) + ongoing hormone replacement

Additional treatment recommended for SOME patients in selected patient group

Trans-sphenoidal surgery may be considered for some patients, based on the tumour size and proximity to optic pathway.

Ongoing hormone replacement involves glucocorticoids ± levothyroxine ± oestrogen/androgen ± growth hormone. Women with an intact uterus receiving daily oestrogen should take progesterone to prevent cystic hyperplasia of the endometrium and possible transformation to cancer.

Primary options

levothyroxine: 1 microgram/kg/day orally initially, adjust according to thyroid function tests

-- AND / OR --

hydrocortisone: 10-20 mg/day orally given in 2-3 divided doses

-- AND / OR --

testosterone cipionate: 100-200 mg intramuscularly every 1-2 weeks

or

testosterone topical: (1%) 5 g (50 mg of testosterone) once daily in the morning initially, adjust dose according to response and serum testosterone level, maximum 10 g/day

or

testosterone transdermal: 5 mg/day patch once daily initially, adjust dose according to response and serum testosterone level, maximum 7.5 mg/day

-- AND / OR --

somatropin (recombinant): 0.15 to 0.3 mg subcutaneously once daily, increase by 0.1 to 0.2 mg/day every 1-2 months based on response and serum insulin-like growth factor 1 level

-- AND / OR --

estradiol: 0.5 to 2 mg orally once daily for 21 days of each 28-day cycle; 0.025 to 0.05 mg/day patch once weekly

-- AND / OR --

progesterone micronised: 200 mg orally once daily for 12 days of each 28-day cycle (if intact uterus)

or

medroxyprogesterone: 5-10 mg orally once daily for 14 days of each 28-day cycle (if intact uterus)

Back
1st line – 

parenteral glucocorticoid

Pituitary apoplexy is a potentially life-threatening condition because it may be associated with acute hypopituitarism with resulting adrenocorticotrophic hormone and cortisol deficiency.[11]​​ Prompt recognition of the condition should be followed by administration of parenteral corticosteroids, along with intravenous fluids and parenteral analgesia. If left untreated it may be fatal.

Primary options

dexamethasone: 4 mg intravenously every 8 hours

OR

hydrocortisone: 100 mg intravenously every 8 hours

Back
Plus – 

trans-sphenoidal surgery (trans-nasal or trans-labial or endoscopic) + ongoing hormone replacement

Treatment recommended for ALL patients in selected patient group

Surgical intervention, preferably within 24 to 48 hours of onset, is generally recommended in cases with progressive vision loss or cranial neuropathy to minimise the risk of permanent neurological deficit.

Sex steroids and growth hormone therapy may be initiated later on if clinically indicated.

Ongoing hormone replacement can involve glucocorticoids ± levothyroxine ± oestrogen/androgen ± growth hormone. Women with an intact uterus receiving daily oestrogen should take progesterone to prevent cystic hyperplasia of the endometrium and possible transformation to cancer.

Primary options

levothyroxine: 1 microgram/kg/day initially, adjust according to thyroid function tests

-- AND / OR --

hydrocortisone: 10-20 mg/day orally given in 2-3 divided doses

-- AND / OR --

testosterone cipionate: 100-200 mg intramuscularly every 1-2 weeks

or

testosterone topical: (1%) 5 g (50 mg of testosterone) once daily in the morning initially, adjust dose according to response and serum testosterone level, maximum 10 g/day

or

testosterone transdermal: 5 mg/day patch once daily initially, adjust dose according to response and serum testosterone level, maximum 7.5 mg/day

-- AND / OR --

somatropin (recombinant): 0.15 to 0.3 mg subcutaneously once daily, increase by 0.1 to 0.2 mg/day every 1-2 months based on response and serum insulin-like growth factor 1 level

-- AND / OR --

estradiol: 0.5 to 2 mg orally once daily for 21 days of each 28-day cycle; 0.025 to 0.05 mg/day patch once weekly

-- AND / OR --

progesterone micronised: 200 mg orally once daily for 12 days of each 28-day cycle (if intact uterus)

or

medroxyprogesterone: 5-10 mg orally once daily for 14 days of each 28-day cycle (if intact uterus)

Back
Consider – 

parenteral analgesia + intravenous fluid hydration

Additional treatment recommended for SOME patients in selected patient group

Neurosurgeons provide pain control for patients presenting with pituitary apoplexy based on their personal preference.

Patients need to be closely monitored for any evidence of water imbalance secondary to dysfunctional and/or deficient arginine vasopressin release.

Back
Consider – 

levothyroxine

Additional treatment recommended for SOME patients in selected patient group

Thyroid hormone replacement should be initiated if patient has low T4 levels after glucocorticoid therapy has been initiated.

Primary options

levothyroxine: 1 microgram/kg/day initially, adjust according to thyroid function tests

ONGOING

micro-adenoma

Back
1st line – 

observation

There are good observational data that the natural course of these tumours is such that observation alone should suffice in their management.​ About 10% of micro-adenomas grow, 6% shrink, and 84% remain unchanged.[57]​​

macro-adenoma without mass effect and not abutting optic chiasm

Back
1st line – 

observation

Observation may be adequate for this group of patients.​ The risk for tumour growth should be discussed. About 20% of macro-adenomas grow, 11% shrink, and the rest remain unchanged.[57] One paper reported that 20% of patients with non-functioning-macro-adenomas on active surveillance may require further intervention during a follow-up period of 7 years.​​​[58]

Back
Consider – 

hormone replacement

Additional treatment recommended for SOME patients in selected patient group

Levothyroxine, corticosteroids, androgens, oestrogens, and growth hormone replacement need to be initiated based on biochemical work-up.

Women with an intact uterus receiving daily oestrogen should take progesterone to prevent cystic hyperplasia of the endometrium and possible transformation to cancer.

Primary options

levothyroxine: 1 microgram/kg/day orally initially, adjust according to thyroid function tests

-- AND / OR --

hydrocortisone: 10-20 mg/day orally given in 2-3 divided doses

-- AND / OR --

testosterone cipionate: 100-200 mg intramuscularly every 1-2 weeks

or

testosterone topical: (1%) 5 g (50 mg of testosterone) once daily in the morning initially, adjust dose according to response and serum testosterone level, maximum 10 g/day

or

testosterone transdermal: 5 mg/day patch once daily initially, adjust dose according to response and serum testosterone level, maximum 7.5 mg/day

-- AND / OR --

somatropin (recombinant): 0.15 to 0.3 mg subcutaneously once daily, increase by 0.1 to 0.2 mg/day every 1-2 months based on response and serum insulin-like growth factor 1 level

-- AND / OR --

estradiol: 0.5 to 2 mg orally once daily for 21 days of each 28-day cycle; 0.025 to 0.05 mg/day patch once weekly

-- AND / OR --

progesterone micronised: 200 mg orally once daily for 12 days of each 28-day cycle (if intact uterus)

or

medroxyprogesterone: 5-10 mg orally once daily for 14 days of each 28-day cycle (if intact uterus)

Back
Consider – 

evaluation for trans-sphenoidal surgery (trans-nasal or trans-labial or endoscopic)

Additional treatment recommended for SOME patients in selected patient group

Tumour growth is an indication for surgery in the absence of mass effect of optic chiasm encroachment.

macro-adenoma without mass effect but abutting optic chiasm

Back
1st line – 

trans-sphenoidal surgery (trans-nasal or trans-labial or endoscopic)

Surgery is usually the first line of treatment in this group of patients, secondary to tumour size and close proximity to optic tract with potential for causing visual field deficits in future if untreated.

Back
Consider – 

hormone replacement

Additional treatment recommended for SOME patients in selected patient group

Glucocorticoids, levothyroxine, androgens, oestrogens, and growth hormone replacement therapy may need to be initiated based on biochemical work-up.

Women with an intact uterus receiving daily oestrogen should take progesterone to prevent cystic hyperplasia of the endometrium and possible transformation to cancer.

Primary options

levothyroxine: 1 microgram/kg/day initially, adjust according to thyroid function tests

-- AND / OR --

hydrocortisone: 10-20 mg/day orally given in 2-3 divided doses

-- AND / OR --

testosterone cipionate: 100-200 mg intramuscularly every 1-2 weeks

or

testosterone topical: (1%) 5 g (50 mg of testosterone) once daily in the morning initially, adjust dose according to response and serum testosterone level, maximum 10 g/day

or

testosterone transdermal: 5 mg/day patch once daily initially, adjust dose according to response and serum testosterone level, maximum 7.5 mg/day

-- AND / OR --

somatropin (recombinant): 0.15 to 0.3 mg subcutaneously once daily, increase by 0.1 to 0.2 mg/day every 1-2 months based on response and serum insulin-like growth factor 1 level

-- AND / OR --

estradiol: 0.5 to 2 mg orally once daily for 21 days of each 28-day cycle; 0.025 to 0.05 mg/day patch once weekly

-- AND / OR --

progesterone micronised: 200 mg orally once daily for 12 days of each 28-day cycle (if intact uterus)

or

medroxyprogesterone: 5-10 mg orally once daily for 14 days of each 28-day cycle (if intact uterus)

Back
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy, preferably via stereotactic gamma knife, may be indicated if there is significant residual tumour after surgery or with the first sign of recurrence after an initially successful tumour removal.[65]

Back
Consider – 

dopamine agonist or somatostatin analogue

Additional treatment recommended for SOME patients in selected patient group

Pharmacological therapy may be considered for patients with significant residual tumour or recurrence when surgery and radiotherapy have failed to achieve tumour control.

Compared with somatostatin analogues, dopamine agonists are more effective in reducing tumour volume.[37][73]​​​

Dopamine agonists (e.g., bromocriptine, cabergoline) have been used in small studies with mixed results.[73] However, their use in CNFPAs remains controversial as the evidence is limited.​[74] Trials using cabergoline in CNFPAs appear to be the most promising in inducing tumour shrinkage and preventing tumour growth.​[73][75][76]​​​​

Primary options

cabergoline: 0.25 to 1 mg orally twice weekly

OR

bromocriptine: 1.25 to 2.5 mg orally once daily initially, increase by 2.5 mg/day increments every 2-7 days according to response, maximum 30 mg/day

OR

octreotide: consult specialist for guidance on dose

Back
2nd line – 

observation

Patients not willing to proceed with surgery or with significant comorbidities may be closely observed.

Back
Consider – 

hormone replacement

Additional treatment recommended for SOME patients in selected patient group

Glucocorticoids, levothyroxine, androgens, oestrogens, and growth hormone replacement therapy may need to be initiated based on biochemical work-up.

Women with an intact uterus receiving daily oestrogen should take progesterone to prevent cystic hyperplasia of the endometrium and possible transformation to cancer.

Primary options

levothyroxine: 1 microgram/kg/day orally initially, adjust according to thyroid function tests

-- AND / OR --

hydrocortisone: 10-20 mg/day orally given in 2-3 divided doses

-- AND / OR --

testosterone cipionate: 100-200 mg intramuscularly every 1-2 weeks

or

testosterone topical: (1%) 5 g (50 mg of testosterone) once daily in the morning initially, adjust dose according to response and serum testosterone level, maximum 10 g/day

or

testosterone transdermal: 5 mg/day patch once daily initially, adjust dose according to response and serum testosterone level, maximum 7.5 mg/day

-- AND / OR --

somatropin (recombinant): 0.15 to 0.3 mg subcutaneously once daily, increase by 0.1 to 0.2 mg/day every 1-2 months based on response and serum insulin-like growth factor 1 level

-- AND / OR --

estradiol: 0.5 to 2 mg orally once daily for 21 days of each 28-day cycle; 0.025 to 0.05 mg/day patch once weekly

-- AND / OR --

progesterone micronised: 200 mg orally once daily for 12 days of each 28-day cycle (if intact uterus)

or

medroxyprogesterone: 5-10 mg orally once daily for 14 days of each 28-day cycle (if intact uterus)

Back
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy may be used for tumour growth control if surgery is not an option.[6]

macro-adenoma with mass effect

Back
1st line – 

trans-sphenoidal surgery (trans-nasal or trans-labial or endoscopic)

Trans-sphenoidal surgery is first-line therapy. Trans-cranial approach may be indicated for large tumours with significant suprasellar components.

Back
Consider – 

hormone replacement

Additional treatment recommended for SOME patients in selected patient group

Glucocorticoids, levothyroxine, androgens, oestrogens, and growth hormone replacement therapy may need to be initiated based on biochemical work-up.

Women with an intact uterus receiving daily oestrogen should take progesterone to prevent cystic hyperplasia of the endometrium and possible transformation to cancer.

Primary options

levothyroxine: 1 microgram/kg/day initially, adjust according to thyroid function tests

-- AND / OR --

hydrocortisone: 10-20 mg/day orally given in 2-3 divided doses

-- AND / OR --

testosterone cipionate: 100-200 mg intramuscularly every 1-2 weeks

or

testosterone topical: (1%) 5 g (50 mg of testosterone) once daily in the morning initially, adjust dose according to response and serum testosterone level, maximum 10 g/day

or

testosterone transdermal: 5 mg/day patch once daily initially, adjust dose according to response and serum testosterone level, maximum 7.5 mg/day

-- AND / OR --

somatropin (recombinant): 0.15 to 0.3 mg subcutaneously once daily, increase by 0.1 to 0.2 mg/day every 1-2 months based on response and serum insulin-like growth factor 1 level

-- AND / OR --

estradiol: 0.5 to 2 mg orally once daily for 21 days of each 28-day cycle; 0.025 to 0.05 mg/day patch once weekly

-- AND / OR --

progesterone micronised: 200 mg orally once daily for 12 days of each 28-day cycle (if intact uterus)

or

medroxyprogesterone: 5-10 mg orally once daily for 14 days of each 28-day cycle (if intact uterus)

Back
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy, preferably via stereotactic Gamma Knife, may be indicated if there is significant residual tumour after surgery or with the first sign of recurrence following an initially successful tumour removal.[65]

Back
Consider – 

dopamine agonist or somatostatin analogue

Additional treatment recommended for SOME patients in selected patient group

Pharmacological therapy may be considered for patients with significant residual tumour or recurrence when surgery and radiotherapy have failed to achieve tumour control.

Compared with somatostatin analogues, dopamine agonists are more effective in reducing tumour volume.[37][73]​​​

Dopamine agonists (e.g., bromocriptine, cabergoline) have been used in small studies with mixed results.[73] However, their use in CNFPAs remains controversial as the evidence is limited.​[74] Trials using cabergoline in CNFPAs appear to be the most promising in inducing tumour shrinkage and preventing tumour growth.​[73][75][76]​​​​

Primary options

cabergoline: 0.25 to 1 mg orally twice weekly

OR

bromocriptine: 1.25 to 2.5 mg orally once daily initially, increase by 2.5 mg/day increments every 2-7 days according to response, maximum 30 mg/day

OR

octreotide: consult specialist for guidance on dose

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer