What are the guideline sources, guidelines and references for Acromegaly ?
Guideline sources The following summarized guidelines for the evaluation and management of acromegaly are prepared by our editorial team based on guidelines from the European Society of Endocrinology (ESE 2021), the Pituitary Society (PS 2021), the Endocrine Society (ES 2020; 2014), the Acromegaly Consensus Conference (ACC 2018), and the European Thyroid Association (ETA 2018). 1 2 3 4 5 6 7 8 9 9 Definition Acromegaly is a chronic, debilitating disease caused by chronic GH hypersecretion, which results in chronic medical comorbidities, poor quality of life and high mortality rates. 7 Epidemiology Acromegaly is caused by excess GH from a pituitary adenoma (90%). 8 Disease course Chronic excess of GH and insulin-like growth factor 1 results in acromegaly, which causes clinical manifestations of soft-tissue overgrowth, bone and joint disease, impaired glucose tolerance and https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 1/8 6/23/23, 1:35 AM Acromegaly Pathway diabetes, hypertension and cardiovascular complications, gonadal dysfunction, sleep apnea, impaired respiratory function, and colonic neoplasms. 9 Prognosis and risk of recurrence The mortality rate in untreated acromegaly is two to three times higher than that for the general population. 9 Pathway Acromegaly Perioperative management Guidelines 1. Classification and risk stratification Prognostic factors: Use biochemical control as the strongest predictor of patient outcomes, reflecting improvements in glucose metabolism, obstructive sleep apnea, CVD, and vertebral fractures, recognizing that structural heart and joint changes are unlikely to resolve. B Do not use patient age as a predictor of surgical outcomes, recognizing that it does not impact the favorable effects of postsurgical remission on alleviating disease comorbidities. D 2. Diagnostic investigations Insulin-like growth factor-1: obtain IGF-1 level measurement to rule out acromegaly in patients with a pituitary mass. B Show 2 more Growth hormone: Obtain an oral glucose load test to confirm the diagnosis of acromegaly (by finding a lack of suppression of GH to < 1 g/L following documented hyperglycemia) in patients with elevated or equivocal serum IGF-1 levels. B Do not rely on random GH levels to diagnose acromegaly. D Brain imaging: Obtain diagnostic imaging to assess for the presence of a pituitary tumor in patients with biochemical evidence of acromegaly. A Consider obtaining MRI as the imaging modality of choice. Consider obtaining CT if MRI is contraindicated or unavailable. C https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 2/8 6/23/23, 1:35 AM Acromegaly Pathway Visual field testing: consider obtaining formal visual field testing if the pituitary tumor abuts the optic chiasm identified on imaging. C Evaluation of thyroid abnormalities: As per ETA 2018 guidelines, obtain screening for central hypothyroidism in patients with acromegaly and hypothyroid manifestations. A As per ES 2014 guidelines, consider obtaining a thyroid ultrasound if there is palpable thyroid nodularity. C Screening for vertebral fractures: screen for vertebral fractures with the morphometric approach at diagnosis and annually thereafter. A Screening for comorbidities: As per ES 2020 guidelines, consider obtaining a usual lipid profile before and after treatment of GH excess in adult patients with acromegaly. C As per ACC 2018 guidelines: Evaluate for acromegaly-associated comorbidities, such as hypertension, cardiac hypertrophy, diabetes mellitus, glucose intolerance, sleep apnea, and osteopathy, in all patients with acromegaly. A Use screening questionnaires for obstructive sleep apnea and obtain sleep studies to confirm the diagnosis. A As per PS 2014 guidelines, consider obtaining evaluation for associated comorbidities, including hypertension, diabetes mellitus, CVD, OA, and sleep apnea, in all patients presenting with acromegaly. C Screening for cancer: As per PS 2021 guidelines, obtain appropriate evaluations after screening colonoscopy at diagnosis similar to the general population. B As per ACC 2018 guidelines, obtain screening for cancer as recommended for the general population. B As per PS 2014 guidelines, consider obtaining screening for colon neoplasia with colonoscopy at diagnosis of acromegaly. C 3. Medical management Setting of care: manage patients with acromegaly at pituitary tumor centers of excellence to ensure the best and most cost-effective care. A Indications for medical therapy: As per ACC 2018 guidelines, initiate medical therapy in patients with persistent disease after surgical resection of the adenoma or if surgery is not appropriate. A Show 2 more https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 3/8 6/23/23, 1:35 AM Acromegaly Pathway As per ES 2014 guidelines, initiate medical therapy in patients with persistent disease following surgery. A Therapeutic targets: As per ACC 2018 guidelines, monitor biochemical control by measuring GH and IGF-1 levels. A Show 3 more As per PS 2014 guidelines, consider targeting a normal age-adjusted serum IGF-1 level. C Show 2 more Somatostatin receptor ligands: As per PS 2021 guidelines, initiate oral octreotide capsules in patients demonstrated complete or partial biochemical response to injectable octreotide or lanreotide. A Insufficient evidence to recommend oral octreotide capsules in patients with tumor characteristics predictive of octreotide resistance. B Show 5 more As per ACC 2018 guidelines, consider initiating primary medical therapy with a first-generation long-acting somatostatin receptor ligand if surgery is contraindicated or if a poor likelihood of success is expected owing to patient-specific and/or tumor-specific factors. C Show 3 more As per ES 2014 guidelines, consider initiating somatostatin receptor ligands as primary therapy in patients ineligible for surgery (unable to be cured or poor surgical candidates), having extensive cavernous sinus invasion, or not having chiasmal compression. C Growth hormone receptor antagonists: As per PS 2021 guidelines, initiate pegvisomant at higher doses and undertake more rapid up- titration to achieve IGF-1 normalization in patients with diabetes mellitus or a higher BMI. Recognize that pegvisomant improves glucose metabolism in patients with diabetes mellitus independent of IGF-1 control, but does not affect glycemic endpoints in patients without diabetes mellitus. B As per ACC 2018 guidelines, consider initiating pegvisomant (at doses of 10-30 mg/day, increased to the recommended highest dose as needed) as an alternative option in patients with impaired glucose metabolism and/or experiencing worsening hyperglycemia on somatostatin receptor ligand therapy. C Show 2 more As per ES 2014 guidelines: Consider initiating either a somatostatin receptor ligand or pegvisomant as initial adjuvant medical therapy in patients with moderate-to-severe signs and symptoms of GH excess without local mass effects. C Consider adding pegvisomant in patients with inadequate response to somatostatin receptor ligands. C Combination therapy: initiate low-dose octreotide long-acting release or lanreotide with weekly pegvisomant in patients requiring combination therapy. A https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 4/8 6/23/23, 1:35 AM Acromegaly Pathway Show 2 more Dopamine agonists: As per ACC 2018 guidelines: Consider initiating cabergoline as first-line medical therapy in patients with acromegaly and mildly elevated IGF-1 levels (< 2.5 the ULN). C Consider initiating cabergoline as an alternative option in patients with impaired glucose metabolism and/or experiencing worsening hyperglycemia on somatostatin receptor ligand therapy. C As per ES 2014 guidelines: Consider initiating a trial of a dopamine agonist, usually cabergoline, as initial adjuvant medical therapy in patients with only modest elevations of serum IGF-1 and mild signs and symptoms of GH excess. C Consider adding cabergoline to somatostatin receptor ligand therapy in patients with moderate-to-severe signs and symptoms of GH excess without local mass effects exhibiting inadequate response to somatostatin receptor ligands. C Temozolomide: initiate temozolomide only in patients with unusually aggressive or proven malignant pituitary tumors. Ensure close cooperation with a neuro-oncologist for such treatment. B Pituitary hormone replacement: assess patients with acromegaly for hypopituitarism and replace hormone deficits. B Management of comorbidities: manage disease-associated comorbidities, specifically hypertension, cardiac hypertrophy, glucose intolerance, diabetes mellitus, sleep apnea, and osteopathy. A Show 3 more 4. Therapeutic procedures Radiotherapy: consider offering radiotherapy in patients with residual tumor mass following surgery, or if medical therapy is unavailable, unsuccessful, or not tolerated. C Show 3 more 5. Perioperative care Preoperative somatostatin receptor ligands: As per ACC 2018 guidelines, avoid administering somatostatin receptor ligands preoperatively to reduce the tumor size and improve surgical cure rates in patients with macroadenomas. D As per ES 2014 guidelines: Avoid administering routine preoperative medical therapy to improve biochemical control after surgery. D https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 5/8 6/23/23, 1:35 AM Acromegaly Pathway Consider administering preoperative somatostatin receptor ligands to reduce surgical risk from severe comorbidities in patients with severe pharyngeal thickness and sleep apnea, or high- output HF. C 6. Surgical interventions Surgical resection: As per ACC 2018 guidelines, perform surgical resection of the pituitary adenoma, where possible, by an experienced neurosurgeon as the primary treatment for acromegaly. A As per PS 2014 guidelines: Perform transsphenoidal surgery as the primary treatment in most patients with acromegaly. B Consider performing repeat surgery in patients with residual intrasellar disease following initial surgery. C Surgical debulking: consider performing surgical debulking to improve subsequent response to medical therapy in patients with parasellar disease making total surgical resection unlikely. C 7. Specific circumstances Pregnant patients, preconception care: As per ESE 2021 guidelines, manage female patients of reproductive age contemplating pregnancy with a diagnosis of pituitary adenoma, functioning or nonfunctioning, by an endocrinologist. B Show 7 more As per ES 2014 guidelines, consider discontinuing long-acting somatostatin receptor ligands formulations and pegvisomant approximately 2 months before attempting to conceive, with the use of short-acting octreotide as necessary until conception. C Pregnant patients (evaluation): Obtain MRI without contrast during pregnancy in case of symptoms of tumor progression or apoplexy. B Obtain neuro-ophthalmologic evaluation during pregnancy for adenomas impinging visual pathways or in case of suspected tumor progression or pituitary apoplexy. B Pregnant patients, management: As per ESE 2021 guidelines, consider discontinuing drugs for acromegaly once pregnancy is established. B Show 3 more As per ES 2014 guidelines, discontinue medical therapy for acromegaly during pregnancy. Initiate or re-initiate treatment only for tumor and headache control. B Pregnant patients, monitoring: https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 6/8 6/23/23, 1:35 AM Acromegaly Pathway As per ESE 2021 guidelines, monitor pregnant patients with a known pituitary adenoma, particularly in large sizes (> 1 cm) and with acromegaly, by an endocrinologist and an advanced nurse practitioner where relevant. Decide on the frequency based on the underlying condition and individualized needs. B Show 2 more As per ES 2014 guidelines: Consider obtaining serial visual field testing during pregnancy in patients with macroadenomas. C Avoid obtaining monitoring GH and/or IGF-1 levels during pregnancy. D Pregnant patients (delivery and breastfeeding): consider providing standard obstetrical care with close maternal and fetal surveillance in pregnant patients with pituitary adenomas. C Show 3 more Patients with gigantism: follow the standard approaches to normalizing GH and IGF-1 hypersecretion in patients with the rare presentation of gigantism. B 8. Follow-up and surveillance Serial laboratory assessment, after surgery: As per PS 2021 guidelines, consider obtaining IGF-1 level measurement 6 weeks after surgery to assess remission in most patients with acromegaly, recognizing that patients with mildly elevated IGF-1 may yet normalize by 3-6 months. B As per ES 2014 guidelines, obtain IGF-1 and a random GH level measurement at 12 weeks or later following surgery. B Show 2 more Serial laboratory assessment (after radiotherapy): Obtain annual GH/IGF-1 reassessment following medication withdrawal to monitor the efficacy of radiotherapy. B Obtain annual hormonal testing following radiotherapy to monitor for hypopituitarism and other delayed radiation effects. A Serial imaging assessment (after surgery): obtain imaging at least 12 weeks after surgery to visualize the residual tumor and adjacent structures. B Consider obtaining MRI as the imaging modality of choice. Obtain CT if MRI is contraindicated or unavailable. B Serial imaging assessment, on medical therapy: As per ACC 2018 guidelines, obtain ongoing imaging surveillance in patients with notable residual tumor treated with pegvisomant. A As per ES 2014 guidelines: Consider obtaining serial MRI to evaluate tumor size in patients receiving pegvisomant. C Avoid obtaining routine abdominal ultrasound to monitor for gallstone disease in patients receiving somatostatin receptor ligands. Obtain an ultrasound in patients with signs and https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 7/8 6/23/23, 1:35 AM Acromegaly Pathway symptoms of gallstone disease. D Management of postoperative residual disease (repeat surgery): consider performing repeat surgery in patients with residual intrasellar disease following initial surgery. C Management of postoperative residual disease (radiotherapy): Consider offering radiotherapy in patients with residual tumor mass following surgery, or if medical therapy is unavailable, unsuccessful, or not tolerated. C Consider offering stereotactic radiotherapy over conventional radiotherapy in patients with acromegaly unless the technique is not available, there is significant residual tumor burden, or the tumor is too close to the optic chiasm resulting in exposure of > 8 Gy. C Management of incomplete treatment response: initiate additional therapies if first-line medical therapy is not successful in normalizing levels of IGF-1. A Show 7 more References 1. Katznelson L, Laws ER Jr, Melmed S et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99 11 3933 51. Open 2. Melmed S, Bronstein MD, Chanson P et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018 Sep;14 9 552 561. Open 3. Connie B Newman, Michael J Blaha, Jeffrey B Boord et al. Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2020 Dec 1;105 12):dgaa674. Open 4. Persani L, Brabant G, Dattani M et al. 2018 European Thyroid Association ETA Guidelines on the Diagnosis and Management of Central Hypothyroidism. Eur Thyroid J. 2018 Oct;7 5 225 237. Open 5. A Luger, L H A Broersen, N R Biermasz et al. ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. Eur J Endocrinol. 2021 Aug 23;185 3 G1 G33. Open 6. Maria Fleseriu Beverly M. K. Biller Pamela U. Freda Monica R. Gadelha Andrea Giustina Laurence Katznelson Mark E. Molitch Susan L. Samson Christian J. Strasburger A. J. van der Lely Shlomo Melmed. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021; 24 1 1 13. Open 7. Zachary M Bush, Mary Lee Vance. Management of acromegaly: is there a role for primary medical therapy?. 2008 Mar;9 1 83 94.2008 Mar;9 1 83 94. Open 8. Annamaria Colao, Renata S Auriemma, Rosario Pivonello. The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. 2016 Apr;19 2 210 21.2016 Apr;19 2 210 21. Open 9. Daphne T Adelman, Karen Jp Liebert, Lisa B Nachtigall et al. Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment. 2013;6 31 8.2013;6 31 8. Open 10. A Luger, L H A Broersen, N R Biermasz et al. ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. Eur J Endocrinol. 2021 Aug 23;185 3 G1 G33. Open https://web.pathway.md/diseases/recMfZl2zvw4mzEbH 8/8