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

enclosed pituitary tumor

1st line – transsphenoidal surgery

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ACUTE
|
enclosed pituitary tumor
1st line – 

transsphenoidal surgery

Indicated as a primary treatment approach in cases of enclosed somatotroph microadenomas (<10 mm diameter) and macroadenomas (>10 mm diameter).

Surgical remission rates in centers with experienced neurosurgeons are between 80% and 90% of microadenomas and between 50% and 75% of macroadenomas.​​[13]​​

Complications of transsphenoidal surgery include local complications (cerebrospinal fluid leak, meningitis, hemorrhage): 5%; diabetes insipidus: 1% to 5%; hypopituitarism: 10%.

Consider – dopamine agonist

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ACUTE
|
enclosed pituitary tumor
Consider – 

dopamine agonist

Treatment recommended for SOME patients in selected patient group

Cabergoline, a second-generation dopamine agonist, is considered postoperatively in patients with moderate elevations of insulin-like growth factor 1 (<2.5 the upper normal limit for age) postoperatively.[13]

Primary options

cabergoline: 0.25 to 0.5 mg orally twice weekly initially, increase gradually according to response every 4-6 weeks, maximum 3.5 mg/week

Consider – growth hormone-receptor antagonist (GHRA)

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ACUTE
|
enclosed pituitary tumor
Consider – 

growth hormone-receptor antagonist (GHRA)

Treatment recommended for SOME patients in selected patient group

The only available GHRA is pegvisomant, a recombinant human growth hormone (GH) analog that has been structurally altered to act as a GH antagonist.

It may be used as adjuvant therapy following surgery.[12][13]

Pegvisomant therapy has a high efficacy in the biochemical control of acromegaly with insulin-like growth factor 1 (IGF-1) normalization in about 73% of patients, but it does not induce tumor shrinkage.​​[24]

In patients with diabetes mellitus, pegvisomant treatment improves glucose metabolism.[27]

Primary options

pegvisomant: 40 mg subcutaneously as a loading dose on day 1, followed by 10 mg subcutaneously once daily, then increase by 5 mg/day increments every 4-6 weeks according to response and serum IGF-1 levels, maximum 30 mg/day

2nd line – somatostatin analog (SSA)

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ACUTE
|
enclosed pituitary tumor
2nd line – 

somatostatin analog (SSA)

If surgery fails to achieve remission of acromegaly, SSAs (also known as somatostatin receptor ligands) are the indicated medical treatment.​[13][32]​​

First-generation SSAs include octreotide (available in oral, subcutaneous, or intramuscular depot formulations) and lanreotide (available as a subcutaneous depot formulation). The second-generation SSA, pasireotide, has an enhanced affinity for the SST-5 receptors. It is indicated in patients who have an inadequate response to surgery and is also effective in patients whose disease is not fully controlled on first-generation SSAs.

In terms of efficacy, first-generation SSAs have shown biochemical remission (around 40% of patients), improvement of symptoms, and tumor volume reduction (over 60% of patients).​​[32]​​

Long-acting preparations of octreotide and lanreotide appear to have a similar degree of efficacy in terms of clinical improvement and biochemical control of the disease.​[33]​​ The subcutaneous preparation of rapid-acting, aqueous octreotide is sometimes recommended for headache improvement.

One randomized, double-blind, phase 3 trial of patients with acromegaly found that 72.2% of patients who received a monthly, subcutaneous, depot formulation of octreotide had an insulin-like growth factor-1 (IGF-1) level below or equal to the upper limit of normal (week 22/24 mean) compared with 37.5% of patients who received placebo (P=0.002).[34]

Oral octreotide is approved for the treatment of acromegaly in patients who are controlled on injectable SSAs.[36] In one study, the long-term maintenance of response in patients on oral octreotide was 90%.[37]

In one study, long-acting release formulation pasireotide was found to be effective in normalizing plasma IGF-1 concentration in approximately 50% more patients than long-acting octreotide.[38] A common adverse effect of pasireotide is an increase in the incidence of hyperglycemia or diabetes mellitus.[42][43]​​ Predictive factors for hyperglycemia are high baseline glucose, history of hypertension, and dyslipidemia.[44] Octreotide and lanreotide have a neutral effect on glucose control.[27]​​

Primary options

octreotide: 50 micrograms subcutaneously three times daily initially, adjust dose according to response, maximum 1500 micrograms/day; 20 mg intramuscularly (long-acting depot) every 4 weeks for 3 months initially, adjust dose according to response, maximum 40 mg every 4 weeks; 20 mg orally twice daily initially, adjust dose according to response, maximum 80 mg/day

More

OR

lanreotide: 90 mg subcutaneously (long-acting depot) every 4 weeks for 3 months initially, adjust dose according to response, maximum 120 mg every 6-8 weeks

More

OR

pasireotide: 40 mg intramuscularly (long-acting depot) every 4 weeks for 3 months initially, adjust dose according to response, maximum 60 mg every 4 weeks

More

Consider – dopamine agonist

Back
ACUTE
|
enclosed pituitary tumor
Consider – 

dopamine agonist

Treatment recommended for SOME patients in selected patient group

Cabergoline, a second-generation dopamine agonist, is considered as add-on therapy in patients who do not achieve biochemical control with maximal doses of somatostatin analog treatment.[13]​​

Primary options

cabergoline: 0.25 to 0.5 mg orally twice weekly initially, increase gradually according to response every 4-6 weeks, maximum 3.5 mg/week

Consider – growth hormone-receptor antagonist (GHRA)

Back
ACUTE
|
enclosed pituitary tumor
Consider – 

growth hormone-receptor antagonist (GHRA)

Treatment recommended for SOME patients in selected patient group

The only available GHRA is pegvisomant, a recombinant human growth hormone (GH) analog that has been structurally altered to act as a GH antagonist.

Combination treatment with a somatostatin analog (SSA), either first- or second-generation, and pegvisomant can be considered in certain patients (e.g., partial response to SSA therapy).[50]

Pegvisomant therapy has a high efficacy in the biochemical control of acromegaly with insulin-like growth factor 1 (IGF-1) normalization in about 73% of patients, but it does not induce tumor shrinkage.[24]

In patients with diabetes mellitus, pegvisomant treatment improves glucose metabolism.[27]

Primary options

pegvisomant: 40 mg subcutaneously as a loading dose on day 1, followed by 10 mg subcutaneously once daily, then increase by 5 mg/day increments every 4-6 weeks according to response and serum IGF-1 levels, maximum 30 mg/day

2nd line – growth hormone-receptor antagonist (GHRA)

Back
ACUTE
|
enclosed pituitary tumor
2nd line – 

growth hormone-receptor antagonist (GHRA)

GHRA monotherapy may be considered in patients who have not responded adequately to surgery, somatostatin analogs, or when these therapies are unsuitable or not tolerated.[12][13]​​[45]​

The only available GHRA is pegvisomant, a recombinant human growth hormone analog that has been structurally altered to act as a GH antagonist.

Pegvisomant therapy has a high efficacy in the biochemical control of acromegaly with insulin-like growth factor 1 (IGF-1) normalization in about 73% of patients, but it does not induce tumor shrinkage.​​[24]​​

In patients with diabetes mellitus, pegvisomant treatment improves glucose metabolism.[27]

Primary options

pegvisomant: 40 mg subcutaneously as a loading dose on day 1, followed by 10 mg subcutaneously once daily, then increase by 5 mg/day increments every 4-6 weeks according to response and serum IGF-1 levels, maximum 30 mg/day

3rd line – radiation therapy

Back
ACUTE
|
enclosed pituitary tumor
3rd line – 

radiation therapy

Radiation therapy is indicated for patients with aggressive adenomas uncured by surgery and resistant to medical treatment, or patients who are unfit for, or declined surgical and/or medical therapy.[13]​ Stereotactic radiation therapy, such as a single dose (gamma knife radiosurgery) or delivered as a small number of fractions, is suggested over conventional radiation therapy in patients with acromegaly, unless there is significant residual tumor burden, or if the tumor is too close to the optic chiasm.[12]​ The most common complication after the administration of radiation therapy (regardless of type) is hypopituitarism, which develops slowly over time in parallel with the achievement of control over GH and IGF-I levels.[46]​ Hypopituitarism levels appear to be lower with stereotactic radiosurgery (SRS); however, the reported mean follow-up for those undergoing SRS is shorter than the follow-up period documented for fractionated radiation.[47][48]​ 

unresectable pituitary tumor (with neural or vascular impingement/invasion)

1st line – somatostatin analog (SSA)

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
1st line – 

somatostatin analog (SSA)

In cases of tumors (macroadenomas) unlikely to be completely resected (those invading a cavernous sinus or the sella turcica floor) medical therapy with SSAs (also known as somatostatin receptor ligands) may be indicated.​[32]​​ However, even partial tumor debulking leading to a substantial decline of growth hormone (GH) concentrations improves the efficacy of subsequent drug therapy and radiation modalities.[31]

First-generation SSAs include octreotide (available in oral, subcutaneous, or intramuscular depot formulations) and lanreotide (available as a subcutaneous depot formulation). Pasireotide is a second-generation SSA with an enhanced affinity for the SST-5 receptors.

In terms of efficacy, first-generation SSAs have shown biochemical remission (around 40% of patients), improvement of symptoms, and tumor volume reduction (over 60% of patients).​​[32]​​

Long-acting preparations of octreotide and lanreotide appear to have a similar degree of efficacy in terms of clinical improvement and biochemical control of the disease.​[33]​​ The subcutaneous preparation of rapid-acting, aqueous octreotide is sometimes recommended for headache improvement.

One randomized, double-blind, phase 3 trial of patients with acromegaly found that 72.2% of patients who received a monthly, subcutaneous, depot formulation of octreotide had an insulin-like growth factor-1 (IGF-1) level below or equal to the upper limit of normal (week 22/24 mean) compared with 37.5% of patients who received placebo (P=0.002).[34]

Oral octreotide is approved for the treatment of acromegaly in patients who are controlled on injectable SSAs.[36] An oral capsule of octreotide has been shown to facilitate intestinal absorption of octreotide by its novel transient permeability enhancer formulation. In one study, the long-term maintenance of response in patients on oral octreotide was 90%.[37]

Pasireotide was found to be effective in normalizing plasma IGF-1 concentration in approximately 50% more patients than long-acting octreotide.[38] A common adverse effect of pasireotide is an increase in the incidence of hyperglycemia or diabetes mellitus.[42][43]​​ Predictive factors for hyperglycemia are high baseline glucose, history of hypertension, and dyslipidemia.[44] Octreotide and lanreotide have a neutral effect on glucose control.[27]​​

Primary options

octreotide: 50 micrograms subcutaneously three times daily initially, adjust dose according to response, maximum 1500 micrograms/day; 20 mg intramuscularly (long-acting depot) every 4 weeks for 3 months initially, adjust dose according to response, maximum 40 mg every 4 weeks; 20 mg orally twice daily initially, adjust dose according to response, maximum 80 mg/day

More

OR

lanreotide: 90 mg subcutaneously (long-acting depot) every 4 weeks for 3 months initially, adjust dose according to response, maximum 120 mg every 6-8 weeks

More

OR

pasireotide: 40 mg intramuscularly (long-acting depot) every 4 weeks for 3 months initially, adjust dose according to response, maximum 60 mg every 4 weeks

More

Consider – growth hormone-receptor antagonist (GHRA)

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
Consider – 

growth hormone-receptor antagonist (GHRA)

Treatment recommended for SOME patients in selected patient group

The only available GHRA is pegvisomant, a recombinant human ​growth hormone (GH) analog that has been structurally altered to act as a GH antagonist.

Combination treatment with a somatostatin analog (SSA), either first-or second-generation, and pegvisomant can be considered in certain patients (e.g., partial response to SSA therapy).[50]

Pegvisomant therapy has a high efficacy in the biochemical control of acromegaly with insulin-like growth factor 1 (IGF-1) normalization in about 73% of patients, but it does not induce tumor shrinkage.[24]

In patients with diabetes mellitus, pegvisomant treatment improves glucose metabolism.[27]

Primary options

pegvisomant: 40 mg subcutaneously as a loading dose on day 1, followed by 10 mg subcutaneously once daily, then increase by 5 mg/day increments every 4-6 weeks according to response and serum IGF-1 levels, maximum 30 mg/day

Consider – dopamine agonist

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
Consider – 

dopamine agonist

Treatment recommended for SOME patients in selected patient group

Cabergoline, a second-generation dopamine agonist, is considered as add-on therapy in patients who do not achieve biochemical control with maximal doses of somatostatin analog treatment.[13]​​

Primary options

cabergoline: 0.25 to 0.5 mg orally twice weekly initially, increase gradually according to response every 4-6 weeks, maximum 3.5 mg/week

Consider – debulking surgery

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
Consider – 

debulking surgery

Treatment recommended for SOME patients in selected patient group

For tumors (macroadenomas) unlikely to be completely resected, debulking surgery is indicated in cases with compression of neural structures, such as optic tracts. It may also aid biochemical control when combined medical therapy.[31]

2nd line – growth hormone-receptor antagonist (GHRA)

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
2nd line – 

growth hormone-receptor antagonist (GHRA)

GHRA treatment may be considered in patients who have not responded adequately to somatostatin analogs, or when this therapy is unsuitable or not tolerated.[45]

​The only available GHRA is pegvisomant, a recombinant human growth hormone (GH) analog that has been structurally altered to act as a GH antagonist.

Pegvisomant therapy has a high efficacy in the biochemical control of acromegaly with insulin-like growth factor 1 (IGF-1) normalization in about 73% but it does not induce tumor shrinkage.​​[24]​​

In patients with diabetes mellitus, pegvisomant treatment improves glucose metabolism.[27]

Primary options

pegvisomant: 40 mg subcutaneously as a loading dose on day 1, followed by 10 mg subcutaneously once daily, then increase by 5 mg/day increments every 4-6 weeks according to response and serum IGF-1 levels, maximum 30 mg/day

Consider – debulking surgery

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
Consider – 

debulking surgery

Treatment recommended for SOME patients in selected patient group

For tumors (macroadenomas) unlikely to be completely resected, debulking surgery is indicated when neural structure compression is present.

Debulking surgery may aid biochemical control when combined with adjuvant medical therapy.[31]

3rd line – radiation therapy

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
3rd line – 

radiation therapy

Radiation therapy is indicated for patients with aggressive adenomas uncured by surgery and resistant to medical treatment, or patients who are unfit for, or declined surgical and/or medical therapy.[13]​ Stereotactic radiation therapy, such as a single dose (gamma knife) or delivered as a small number of fractions, is suggested over conventional radiation therapy in patients with acromegaly, unless there is significant residual tumor burden, or if the tumor is too close to the optic chiasm.[12]​ The most common complication after the administration of radiation therapy (regardless of type) is hypopituitarism, which develops slowly over time in parallel with the achievement of control over GH and IGF-I levels.[46] Hypopituitarism levels appear to be lower with stereotactic radiosurgery (SRS); however, the reported mean follow-up for those undergoing SRS is shorter than the follow-up period documented for fractionated radiation.[47][48]​​

Consider – debulking surgery

Back
ACUTE
|
unresectable pituitary tumor (with neural or vascular impingement/invasion)
Consider – 

debulking surgery

Treatment recommended for SOME patients in selected patient group

For tumors (macroadenomas) unlikely to be completely resected, debulking surgery is indicated when neural structure compression is present.

Debulking surgery may aid biochemical control when combined with radiation therapy.[31]

nonpituitary adenoma etiology

1st line – medical and surgical interventions

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ACUTE
|
nonpituitary adenoma etiology
1st line – 

medical and surgical interventions

In rare cases where acromegaly results from ectopic production (e.g., hypothalamic, bronchial, pancreatic, adrenal tumors) of growth hormone (GH) or GH-releasing hormone, treatment consists of medical (somatostatin analog) and surgical interventions (tumor resection) to address the specific lesion (e.g., bronchial carcinoid, pancreatic islet cell tumor).

ONGOING

pituitary adenoma progression or recurrence

1st line – repeat surgery

Back
ONGOING
|
pituitary adenoma progression or recurrence
1st line – 

repeat surgery

Repeat pituitary surgery (either debulking surgery or tumor mass removal depending on tumor characteristics) may be indicated for patients who fail to benefit (i.e., improved biochemical measures, reduced tumor size) from initial surgical (adenoma resection or debulking), medical, and radiation therapy interventions, but its efficacy is usually lower than that of the first intervention.[51]

2nd line – repeat radiation

Back
ONGOING
|
pituitary adenoma progression or recurrence
2nd line – 

repeat radiation

Repeat stereotactic radiosurgery may further increase delayed radiation-related complications. However, some patients have an enlarging tumor despite previous surgery and radiation and medical treatment and need additional therapy, including radiation. One large multi-institutional series showed that repeat gamma knife radiosurgery for patients with acromegaly was well tolerated, with 81.0% of patients reporting no radiosurgery-induced toxicity.[49] All reported toxicities were related to endocrine or cranial nerve dysfunction. The endocrine control rate was 42.9%, with a median follow-up of 3.8 years and tumor control 83.3%. 

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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