Acromegaly

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

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

Back

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%.

2nd line – somatostatin analog (SSA)

Back

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 leading to clinical improvement and biochemical control of the disease.[33] The subcutaneous preparation of rapid-acting, aqueous octreotide is sometimes recommended for headache improvement.

Oral octreotide is approved for the treatment of acromegaly in patients who are controlled on injectable SSAs.[34] In one study, the long-term maintenance of response in patients on oral octreotide was 90%.[35]

Pasireotide was found to be effective in normalizing plasma IGF-1 concentration in approximately 50% more patients than long-acting octreotide.[36] A common adverse effect of pasireotide is an increase in the incidence of hyperglycemia or diabetes mellitus.[40][41] Predictive factors for hyperglycemia are high baseline glucose, history of hypertension, and dyslipidemia.[42] Octreotide and lanreotide have a neutral effect on glucose control.[27]

Combination treatment of an SSA (either first- or second-generation) and pegvisomant can be considered in certain patients.[48]

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

Adjust dose according to clinical response, growth hormone level, and serum insulin-like growth factor 1 (IGF-1) level (every 2 weeks for subcutaneous and oral formulations). The intramuscular depot formulation is only recommended for patients who have responded to, and tolerated, subcutaneous octreotide. The oral formulation is only recommended for patients who have responded to, and tolerated, parenteral octreotide or lanreotide.

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

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

Consider – dopamine agonist

Back

Consider –

dopamine agonist

Treatment recommended for SOME patients in selected patient group

Cabergoline, a second-generation dopamine agonist, is considered in patients with moderate elevations of insulin-like growth factor 1 (IGF-1) (<2.5 the upper normal limit for age) postoperatively or as add-on therapy in patients who do not achieve biochemical control with maximal doses of somatostatin analog (also known as somatostatin receptor ligand) treatment.[13]

Primary options

cabergoline: 0.25 mg orally twice weekly initially, increase by 0.25 mg twice weekly increments every 4 weeks according to response, maximum 4 mg/week

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

Back

2nd line –

growth hormone-receptor antagonist (GHRA)

GHRA treatment may be considered in patients who have not responded adequately to surgery, radiation therapy, or somatostatin analogs, or when these therapies are unsuitable or not tolerated.[43] The only available GHRA is pegvisomant, a recombinant human GH analog that has been structurally altered to act as a GH antagonist.

It is used as adjuvant therapy following surgery, as monotherapy, or in combination with other medical therapies.[12][13] Pegvisomant can also be used as an equal line treatment to SSAs in certain patients.

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.[25]

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

Primary options

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

3rd line – radiation therapy

Back

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.[44] 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.[45][46]

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

1st line – somatostatin analog (SSA)

Back

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]

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]

Oral octreotide is approved for the treatment of acromegaly in patients who are controlled on injectable SSAs.[34] 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%.[35]

Combination treatment of an SSA (either first-or second-generation) and pegvisomant can be considered in certain patients.[48]

Primary options

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

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

Consider – dopamine agonist

Back

Consider –

dopamine agonist

Treatment recommended for SOME patients in selected patient group

Primary options

cabergoline: 0.25 mg orally twice weekly initially, increase by 0.25 mg twice weekly increments every 4 weeks according to response, maximum 4mg/week

Consider – debulking surgery

Back

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 with adjuvant medical or radiation therapy.[31]

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

Back

2nd line –

growth hormone-receptor antagonist (GHRA)

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.[25]

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

Primary options

3rd line – radiation therapy

Back

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.[44] 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.[45][46]

nonpituitary adenoma etiology

1st line – medical and surgical interventions

Back

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

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.[49]

2nd line – repeat radiation

Back

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.[47] 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%.

Use of this content is subject to our disclaimer

Acromegaly

Treatment algorithm

enclosed pituitary tumor

transsphenoidal surgery

somatostatin analog (SSA)

Primary options

dopamine agonist

Primary options

growth hormone-receptor antagonist (GHRA)

Primary options

radiation therapy

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

somatostatin analog (SSA)

Primary options

dopamine agonist

Primary options

debulking surgery

growth hormone-receptor antagonist (GHRA)

Primary options

radiation therapy

nonpituitary adenoma etiology

medical and surgical interventions

pituitary adenoma progression or recurrence

repeat surgery

repeat radiation