Acromegaly is associated with serious complications and premature death. Prior to the routine implementation of more effective treatment modalities, the mean mortality estimate for acromegaly was 2- to 3-fold the expected level in the general population.[24]Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021 Feb;24(1):1-13.
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33079318
http://www.ncbi.nlm.nih.gov/pubmed/33079318?tool=bestpractice.com
Prognosis has improved due to modern surgical and pharmacological treatment strategies; life expectancy is now close to that of the general population.[24]Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021 Feb;24(1):1-13.
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33079318
http://www.ncbi.nlm.nih.gov/pubmed/33079318?tool=bestpractice.com
Patients' survival, as well as their quality of life, has been improved by the definition of strict criteria of biochemical control and more aggressive treatment of acromegaly comorbidities such as hypertension, diabetes mellitus, and sleep apnoea.[26]Giustina A, Barkan A, Beckers A, et al. A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz096.
http://www.ncbi.nlm.nih.gov/pubmed/31606735?tool=bestpractice.com
There have been several attempts to develop and validate a tool to measure disease activity in acromegaly patients to support decision-making in clinical practice.[59]van der Lely AJ, Gomez R, Pleil A, et al. Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly. Pituitary. 2017 Dec;20(6):692-701.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655576
http://www.ncbi.nlm.nih.gov/pubmed/28887782?tool=bestpractice.com
[60]Giustina A, Bevan JS, Bronstein MD, et al. SAGIT®: clinician-reported outcome instrument for managing acromegaly in clinical practice--development and results from a pilot study. Pituitary. 2016 Feb;19(1):39-49.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710645
http://www.ncbi.nlm.nih.gov/pubmed/26377024?tool=bestpractice.com
Quality of life
Quality of life (QoL) in patients with acromegaly is reduced irrespective of disease state. Strong predictors of poor QoL include diagnostic factors, including diagnostic delay and lack of diagnostic acumen in medical care provision.[61]Kreitschmann-Andermahr I, Buchfelder M, Kleist B, et al. Predictors of quality of life in 165 patients with acromegaly: results from a single-center study. Endocr Pract. 2017 Jan;23(1):79-88.
http://www.ncbi.nlm.nih.gov/pubmed/27749131?tool=bestpractice.com
Biochemical control, or treatment of acromegaly overall, might not be followed by improved QoL in some patients.[62]Geraedts VJ, Andela CD, Stalla GK, et al. Predictors of quality of life in acromegaly: no consensus on biochemical parameters. Front Endocrinol (Lausanne). 2017 Mar 3;8:40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334635
http://www.ncbi.nlm.nih.gov/pubmed/28316591?tool=bestpractice.com
[63]Kimball A, Dichtel LE, Yuen KCJ, et al. Quality of life after long-term biochemical control of acromegaly. Pituitary. 2022 Jun;25(3):531-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080999
http://www.ncbi.nlm.nih.gov/pubmed/35476257?tool=bestpractice.com
A meta-analysis using the goal of improvement in symptom control and health-related QOL (measured by the acromegaly QoL questionnaire) as the primary outcome, determined that acromegaly treatments improve symptoms and health-related QOL.[64]Broersen LHA, Zamanipoor Najafabadi AH, Pereira AM, et al. Improvement in symptoms and health-related quality of life in acromegaly patients: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2021 Jan 23;106(2):577-87.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823264
http://www.ncbi.nlm.nih.gov/pubmed/33245343?tool=bestpractice.com
It concluded that as symptoms may be only partly caused by growth hormone (GH) overproduction or may be only partly reversible, ongoing attention to symptom improvement is required even after biochemical disease control is established.[64]Broersen LHA, Zamanipoor Najafabadi AH, Pereira AM, et al. Improvement in symptoms and health-related quality of life in acromegaly patients: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2021 Jan 23;106(2):577-87.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823264
http://www.ncbi.nlm.nih.gov/pubmed/33245343?tool=bestpractice.com
It is important that treatment algorithms not only focus on normalising biochemical markers, but also attempt to improve QoL.
Surgical remission
Surgery is effective in the biochemical control of 80% to 90% of enclosed microadenomas (<10 mm diameter) and 50% to 75% of macroadenomas.[13]Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: a consensus. Rev Endocr Metab Disord. 2020 Dec;21(4):667-78.
http://www.ncbi.nlm.nih.gov/pubmed/32914330?tool=bestpractice.com
It is potentially a one-time treatment that can result in GH normalisation in the immediate post-surgical period. Insulin-like growth factor 1 (IGF-1) levels decline more slowly with normalisation in successful cases, taking 2 to 3 months.
Somatostatin analogue (SSA) responders
In cases of tumour persistence or recurrence after surgery or as first-line treatment, first-generation SSAs are effective in disease control in about 40% of patients, with a GH/IGF-1 decrease in 3 to 6 months.[31]Gadelha MR, Wildemberg LE, Kasuki L. The future of somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab. 2022 Jan 18;107(2):297-308.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764337
http://www.ncbi.nlm.nih.gov/pubmed/34618894?tool=bestpractice.com
Tachyphylaxis has not been seen with long-term SSA treatment. Discontinuation of first-generation SSA treatment leads to loss of biochemical control of the disease and sometimes tumour growth rebound. Cost for this lifelong treatment is significant.[31]Gadelha MR, Wildemberg LE, Kasuki L. The future of somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab. 2022 Jan 18;107(2):297-308.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764337
http://www.ncbi.nlm.nih.gov/pubmed/34618894?tool=bestpractice.com
[65]Carmichael JD, Bonert VS, Nuño M, et al. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab. 2014 May;99(5):1825-33.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010703
http://www.ncbi.nlm.nih.gov/pubmed/24606084?tool=bestpractice.com
SSA resistance or intolerance
Patients are considered resistant to first-generation SSA when acromegaly is not biochemically controlled after 6 months of treatment despite maximum recommended doses.
There are now several factors described to predict resistance to SSA, mainly sparsely granulated tumours and T2 characteristics on MRI.[66]Potorac I, Petrossians P, Daly AF, et al. T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly. Endocr Relat Cancer. 2016 Nov;23(11):871-81.
http://www.ncbi.nlm.nih.gov/pubmed/27649724?tool=bestpractice.com
In cases of SSA resistance or intolerance, pegvisomant treatment should be considered, if available. While this treatment is effective in normalising IGF-1 levels in over 70%, it has no effect on GH secretion and does not arrest tumour growth.[24]Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021 Feb;24(1):1-13.
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33079318
http://www.ncbi.nlm.nih.gov/pubmed/33079318?tool=bestpractice.com
Pasireotide has been studied in patients previously controlled with pegvisomant and first-generation SSA, and induced a pegvisomant sparing effect in 66% of patients; however, hyperglycaemia and diabetes mellitus increased from 32.8% at baseline to 68.9% at 24 weeks.[67]Muhammad A, van der Lely AJ, Delhanty PJD, et al. Efficacy and safety of switching to pasireotide in patients with acromegaly controlled with pegvisomant and first-generation somatostatin analogues (PAPE study). J Clin Endocrinol Metab. 2018 Feb 1;103(2):586-95.
http://www.ncbi.nlm.nih.gov/pubmed/29155991?tool=bestpractice.com
Aggressive tumours
Though rare, aggressive GH-secreting tumours represent a clinical conundrum and usually require multimodal therapy (surgery, medication, and radiation).[68]Donoho DA, Bose N, Zada G, et al. Management of aggressive growth hormone secreting pituitary adenomas. Pituitary. 2017 Feb;20(1):169-78.
http://www.ncbi.nlm.nih.gov/pubmed/27987061?tool=bestpractice.com