Pituitary adenoma
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
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
pituitary apoplexy
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]Barkhoudarian G, Kelly DF. Pituitary apoplexy. Neurosurg Clin N Am. 2019 Oct;30(4):457-63. http://www.ncbi.nlm.nih.gov/pubmed/31471052?tool=bestpractice.com 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
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.
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)
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]Barkhoudarian G, Kelly DF. Pituitary apoplexy. Neurosurg Clin N Am. 2019 Oct;30(4):457-63. http://www.ncbi.nlm.nih.gov/pubmed/31471052?tool=bestpractice.com 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
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)
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.
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
micro-adenoma
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]Orija IB, Weil RJ, Hamrahian AH. Pituitary incidentaloma. Best Pract Res Clin Endocrinol Metab. 2012 Feb;26(1):47-68. http://www.ncbi.nlm.nih.gov/pubmed/22305452?tool=bestpractice.com
macro-adenoma without mass effect and not abutting optic chiasm
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]Orija IB, Weil RJ, Hamrahian AH. Pituitary incidentaloma. Best Pract Res Clin Endocrinol Metab. 2012 Feb;26(1):47-68. http://www.ncbi.nlm.nih.gov/pubmed/22305452?tool=bestpractice.com 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]Yavropoulou MP, Tsoli M, Barkas K, et al. The natural history and treatment of non-functioning pituitary adenomas (non-functioning PitNETs). Endocr Relat Cancer. 2020 Oct;27(10):R375-90. https://erc.bioscientifica.com/view/journals/erc/27/10/ERC-20-0136.xml http://www.ncbi.nlm.nih.gov/pubmed/32674070?tool=bestpractice.com
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)
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
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.
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)
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]Minniti G, Flickinger J. The risk/benefit ratio of radiotherapy in pituitary tumors. Best Pract Res Clin Endocrinol Metab. 2019 Apr;33(2):101269. http://www.ncbi.nlm.nih.gov/pubmed/31053487?tool=bestpractice.com
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]Mercado M, Melgar V, Salame L, et al. Clinically non-functioning pituitary adenomas: pathogenic, diagnostic and therapeutic aspects. [in spa]. Endocrinol Diabetes Nutr. 2017 Aug-Sep;64(7):384-95. http://www.ncbi.nlm.nih.gov/pubmed/28745610?tool=bestpractice.com [73]Greenman Y. Management of endocrine disease: present and future perspectives for medical therapy of nonfunctioning pituitary adenomas. Eur J Endocrinol. 2017 Sep;177(3):R113-24. http://www.ncbi.nlm.nih.gov/pubmed/28468768?tool=bestpractice.com
Dopamine agonists (e.g., bromocriptine, cabergoline) have been used in small studies with mixed results.[73]Greenman Y. Management of endocrine disease: present and future perspectives for medical therapy of nonfunctioning pituitary adenomas. Eur J Endocrinol. 2017 Sep;177(3):R113-24. http://www.ncbi.nlm.nih.gov/pubmed/28468768?tool=bestpractice.com However, their use in CNFPAs remains controversial as the evidence is limited.[74]Wexler TL, Page-Wilson G. Dopamine agonists for the treatment of pituitary tumours: from ergot extracts to next generation therapies. Br J Clin Pharmacol. 2023 Apr;89(4):1304-17. http://www.ncbi.nlm.nih.gov/pubmed/36630197?tool=bestpractice.com Trials using cabergoline in CNFPAs appear to be the most promising in inducing tumour shrinkage and preventing tumour growth.[73]Greenman Y. Management of endocrine disease: present and future perspectives for medical therapy of nonfunctioning pituitary adenomas. Eur J Endocrinol. 2017 Sep;177(3):R113-24. http://www.ncbi.nlm.nih.gov/pubmed/28468768?tool=bestpractice.com [75]Giraldi EA, Ioachimescu AG. The role of dopamine agonists in pituitary adenomas. Endocrinol Metab Clin North Am. 2020 Sep;49(3):453-74. http://www.ncbi.nlm.nih.gov/pubmed/32741482?tool=bestpractice.com [76]Botelho MS, Franzini ÍA, Nunes-Nogueira VDS, et al. Treatment of non-functioning pituitary adenoma with cabergoline: a systematic review and meta-analysis. Pituitary. 2022 Dec;25(6):810-8. http://www.ncbi.nlm.nih.gov/pubmed/35902444?tool=bestpractice.com
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
observation
Patients not willing to proceed with surgery or with significant comorbidities may be closely observed.
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)
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]Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA. 2017 Feb 7;317(5):516-24. http://www.ncbi.nlm.nih.gov/pubmed/28170483?tool=bestpractice.com
macro-adenoma with mass effect
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.
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)
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]Minniti G, Flickinger J. The risk/benefit ratio of radiotherapy in pituitary tumors. Best Pract Res Clin Endocrinol Metab. 2019 Apr;33(2):101269. http://www.ncbi.nlm.nih.gov/pubmed/31053487?tool=bestpractice.com
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]Mercado M, Melgar V, Salame L, et al. Clinically non-functioning pituitary adenomas: pathogenic, diagnostic and therapeutic aspects. [in spa]. Endocrinol Diabetes Nutr. 2017 Aug-Sep;64(7):384-95. http://www.ncbi.nlm.nih.gov/pubmed/28745610?tool=bestpractice.com [73]Greenman Y. Management of endocrine disease: present and future perspectives for medical therapy of nonfunctioning pituitary adenomas. Eur J Endocrinol. 2017 Sep;177(3):R113-24. http://www.ncbi.nlm.nih.gov/pubmed/28468768?tool=bestpractice.com
Dopamine agonists (e.g., bromocriptine, cabergoline) have been used in small studies with mixed results.[73]Greenman Y. Management of endocrine disease: present and future perspectives for medical therapy of nonfunctioning pituitary adenomas. Eur J Endocrinol. 2017 Sep;177(3):R113-24. http://www.ncbi.nlm.nih.gov/pubmed/28468768?tool=bestpractice.com However, their use in CNFPAs remains controversial as the evidence is limited.[74]Wexler TL, Page-Wilson G. Dopamine agonists for the treatment of pituitary tumours: from ergot extracts to next generation therapies. Br J Clin Pharmacol. 2023 Apr;89(4):1304-17. http://www.ncbi.nlm.nih.gov/pubmed/36630197?tool=bestpractice.com Trials using cabergoline in CNFPAs appear to be the most promising in inducing tumour shrinkage and preventing tumour growth.[73]Greenman Y. Management of endocrine disease: present and future perspectives for medical therapy of nonfunctioning pituitary adenomas. Eur J Endocrinol. 2017 Sep;177(3):R113-24. http://www.ncbi.nlm.nih.gov/pubmed/28468768?tool=bestpractice.com [75]Giraldi EA, Ioachimescu AG. The role of dopamine agonists in pituitary adenomas. Endocrinol Metab Clin North Am. 2020 Sep;49(3):453-74. http://www.ncbi.nlm.nih.gov/pubmed/32741482?tool=bestpractice.com [76]Botelho MS, Franzini ÍA, Nunes-Nogueira VDS, et al. Treatment of non-functioning pituitary adenoma with cabergoline: a systematic review and meta-analysis. Pituitary. 2022 Dec;25(6):810-8. http://www.ncbi.nlm.nih.gov/pubmed/35902444?tool=bestpractice.com
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
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
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