P'aware Medical Info Site

TESTS & DIAGNOSIS

Testing and diagnosis of Acromegaly

Screening and diagnosis of acromegaly algorithm. *Diabetes mellitus, hypertension and heart disease of uncertain aetiology; **Complaints of headache, obstructive sleep apnoea, colonic polyps, large joint pains, carpal tunnel syndrome, sweaty/oily hands, multiple skin tags; § Please see text below for more information; ¶ Refer to centres with a multidisciplinary team dedicated to management of acromegaly that includes endocrinologists, neurosurgeon and radiologist, and if available a radiation oncologist. IGF-1: insulin like growth factor-1; OGTT: oral glucose tolerance test; MRI: magnetic resonance imaging; CT: computed tomography scan.

MANAGEMENT

Algorithm in Acromegaly Management1

Management and monitoring of acromegaly patients. *Refer to centres with a multidisciplinary team dedicated to management of acromegaly that includes endocrinologists, neurosurgeon and radiologist, and if available a radiation oncologist; ** Refer to section on monitoring for details. MDT: multi-disciplinary team; DA: dopamine agonist; SRL: somatostatin receptor ligands; IGF-1: insulin like growth factor-1; GH: growth hormone

Treatment

Types of Treatment

Regarding treatment, the goal is to restore the pituitary gland to normal function, producing normal levels of growth hormone. Surgery to remove the pituitary tumour is the treatment recommended for most patients with acromegaly; but while surgery is successful in many patients, some will see their levels of GH and IGF-1 remain too high even after surgery.

Non-surgical treatments may include radiation therapy, and injection of growth hormone blocking medications. But left untreated, acromegaly can lead to worsening diabetes mellitus and hypertension, among other risks.

In the treatment of acromegaly today...UNMET NEEDS EXIST.

More Details

Surgery

Medical Therapy

Radiotherapy

Monitoring

DIAGNOSIS

Excess GH and IGF-1

Acromegaly diagnosis may be delayed and surgery frequently is not successful^1,10

Average time from symptom onset to diagnosis of acromegaly is 8 to 10 years¹⁰
Transsphenoidal surgery is recommended by clinical guidelines as the primary treatment in most patients^10,11
Most functional somatotroph pituitary tumours (>66%) at the time of detection are macroadenomas¹²
25-50% of patients with a macroadenoma fail to achieve remission post surgery¹⁰

First-generation somatostatin analogues (SSAs) target the source of acromegaly

But they may deliver inadequate biochemical control for some patients^2,13,14

^b Initial medical therapy for patients for whom surgery fails has typically been a first-generation SSA¹⁵
^c SSAs are designed to target the biochemical imbalance induced by excess GH and IGF-1 when surgery fails or is not feasible^6,11,13-15

REDUCTION

IGF-1 and GH Reduction

Pasireotide reduced IGF-1 and GH in patients previously inadequately controlled on a first-generation SSA ^23,II

REDUCTION

Tumour Reduction

Additional reductions in tumour volume were seen in some patients who switched to Pasireotide ²³

Hyperglycemia may occur and can be managed

Hyperglycaemia can occur in patients treated with Pasireotide²⁴:

Hyperglycaemia is reversible upon Pasireotide discontinuation²⁵

Metformin alone or in combination with other anti-diabetic medication may help control elevations in glucose levels that may occur with Pasireotide treatment^25,†

Most patients who had hyperglycaemia were able to achieve the American Diabetes Association Goal of 7% with medical management²⁵

Key elements in addressing hyperglycaemia include close monitoring, patient education, and prompt action²⁵

There have been post marketing cases of ketoacidosis with Pasireotide in patients with history of diabetes and in patients without history of diabetes. Assess patients who present with signs and symptoms consistent with ketoacidosis during Pasireotide treatment³

^*Importantly, in patients with poorly controlled diabetes mellitus, optimize anti-diabetic treatment before starting Pasireotide³

References

Gatto F, Barbieri F, Arvigo M, et al. Biological and biochemical basis of the differential efficacy of first and second generation somatostatin receptor ligands in neuroendocrine neoplasms. Int J Mol Sci. 2019;20(16):3940. 2. Poullot A-G, Chevalier N. New options in the treatment of Cushing’s disease: a focus on pasireotide. Res Rep Endocr Disord. 2013;3:31-38. 3. SIGNIFOR LAR (pasireotide) for injectable suspension, for intramuscular use [prescribing information]. Lebanon, NJ: Recordati Rare Diseases Inc.; 2020. 4. Acromegaly. UCLA Health System. https://www.uclahealth.org/medical-services/surgery/endocrine-surgery/patient-resources/patient-education/endocrine-surgery-encyclopedia/acromegaly. Accessed August 23, 2022. 5. Malaysia Consensus Statement for The Diagnosis and Management of Acromegaly 1st Edition. https://mems.my/wp-content/uploads/2019/07/Acromegaly-manuscript-and-booklet_20190705_v21_FINAL.pdf. Published July 05, 2019. Accessed Dec 23, 2024. 6. Christofides EA. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly. Patient Prefer Adherence. 2016;10:1217-1225. 7. Acromegaly. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/endocrine-diseases/acromegaly. Accessed August 23, 2022. 8. Carmichael JD, Bonert VS, Nu.o M, Ly D, Melmed S. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab. 2014;99(5):1825-1833. 9. Carroll PV, Jenkins PJ. Acromegaly. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2016 10. Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: A consensus. Rev Endocr Metab Disord. 2020;21(4):667-678. 11. Katznelson L, Laws ER Jr, Melmed S, et al. Endocrine Society Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. 12. Lavrentaki A, Paluzzi A, Wass JA, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4-9. 13. SOMATULINE® DEPOT (lanreotide) injection, for subcutaneous use [prescribing information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; 2019 14. SANDOSTATIN LAR DEPOT (octreotide acetate) for injectable suspension, for gluteal intramuscular use [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021. 15. Coopmans EC, Muhammad A, van der Lely AD, et al. How to position pasireotide LAR treatment in acromegaly. J Clin Endocrinol Metab. 2019;104(6):1978-1988. 16. Shanik MH, Cao PD, Ludlam WH. Historical response rates of somatostatin analogues in the treatment of acromegaly: a systematic review. Endocr Pract. 2016;22(3):350-356. 17. Casar-Borota O, Heck A, Schulz S, et al. Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide. J Clin Endocrinol Metab. 2013;98(11):E1730-E1739. 18. Silverstein JM. Hyperglycemia induced by pasireotide in patients with Cushing’s disease or acromegaly. Pituitary. 2016;19:536-543. 19. Zambre Y, Ling Z, Chen MC, et al. Inhibition of human pancreatic islet insulin release by receptor-selective somatostatin analogs directed to somatostatin receptor subtype 5. Biochem Pharmacol. 1999;57(10):1159-1164. 20. Singh V, Brendel MD, Zacharias S, et al. Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic islets. J Clin Endocrinol Metab. 2007;92(2):673-680. 21. Breitschaft A, Hu K, Hermosillo Res.ndiz K, Darstein C, Golor G. Management of hyperglycemia associated with pasireotide (SOM230): healthy volunteer study. Diabetes Res Clin Pract. 2014;103(3):458-465. 22. Henry RR, Ciaraldi TP, Armstrong D, Burke P, Ligueros-Saylan M, Mudaliar S. Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. J Clin Endocrinol Metab. 2013;98(8):3446-3453. 23. Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2(11):875-884. 24. Colao A, Bronstein MD, Freda P, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014;99(3):791-799. 25. Gadelha MR, Gu F, Bronstein MD, et al. Risk factors and management of pasireotide-associated hyperglycemia in acromegaly. Endocr Connect. 2020;9(12):1178-1190. 26. American Diabetes Association. Standards of Medical Care in Diabetes-2020 Abridged for Primary Care Providers. Clin Diabetes. 2020;38(1):10-38. doi:10.2337/cd20-as01. 27. Samson SL, Gu F, Feldt-Rasmussen U, Zhang S, Yu Y, et al. Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study. Pituitary. 2021;24(6):887-903.

Treatment for
Acromegaly Disease

Diagnosing and treating acromegaly

Testing and diagnosis of Acromegaly

Algorithm in Acromegaly Management1

Types of Treatment

Excess GH and IGF-1

Acromegaly diagnosis may be delayed and surgery frequently is not successful^1,10

First-generation somatostatin analogues (SSAs) target the source of acromegaly

IGF-1 and GH Reduction

Pasireotide reduced IGF-1 and GH in patients previously inadequately controlled on a first-generation SSA ^23,II

Tumour Reduction

Additional reductions in tumour volume were seen in some patients who switched to Pasireotide ²³

Hyperglycemia may occur and can be managed

Treatment forAcromegaly Disease

Diagnosing and treating acromegaly

Testing and diagnosis of Acromegaly

Algorithm in Acromegaly Management1

Types of Treatment

Excess GH and IGF-1

Acromegaly diagnosis may be delayed and surgery frequently is not successful1,10

First-generation somatostatin analogues (SSAs) target the source of acromegaly

IGF-1 and GH Reduction

Pasireotide reduced IGF-1 and GH in patients previously inadequately controlled on a first-generation SSA 23,II

Tumour Reduction

Additional reductions in tumour volume were seen in some patients who switched to Pasireotide 23

Hyperglycemia may occur and can be managed

Welcome to P'aware

Treatment for
Acromegaly Disease

Acromegaly diagnosis may be delayed and surgery frequently is not successful^1,10

Pasireotide reduced IGF-1 and GH in patients previously inadequately controlled on a first-generation SSA ^23,II

Additional reductions in tumour volume were seen in some patients who switched to Pasireotide ²³