somatostatin_analogs_in_acromegaly

Somatostatin Analogs in Acromegaly

Consists of lanreotide and octreotide for medical therapy of acromegaly.

Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after Somatostatin analog treatment 1)

As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of growth hormone GH and IGF-1 by subcutaneous injection every 4-6 weeks.

Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration 2).


Medical therapies for GHPAs, including somatostatin analogs and GH receptor antagonists, are becoming increasingly important adjuncts to surgical intervention. Stereotactic radiosurgery serves as an important fallback therapy for tumors that cannot be cured with surgery and medications. Data suggests that patients with aggressive and refractory GHPAs are best treated at dedicated tertiary pituitary centers with multidisciplinary teams of neuroendocrinologists, neurosurgeons, radiation oncologists and other specialists who routinely provide advanced care to GHPA patients. Future research will help clarify the defining features of “aggressive” and “atypical” PAs, likely based on tumor behavior, preoperative imaging characteristics, histopathological characteristics, and molecular markers 3).


In vitro, native somatostatin retains its inhibitory effect on GH secretion in many GH-secreting tumors, and this led to the development of analogs of somatostatin for clinical use in the treatment of acromegaly 4).

The two analogs of somatostatin available for clinical use are the cyclic octapeptides octreotide (Dphe-cys-phe-Dtrp-lys-thr-cys-thr-ol) and lanreotide (Dnal-cys-tyr-Dtrp-lys-val-cys-thr) (1, 5–7). Octreotide is the only analog currently available for clinical use in the treatment of acromegaly in the United States.


Clinically available somatostatin analogs control GH or IGF-I excess in about 50–60% of patients whether used as primary or secondary therapy. Signs and symptoms of the disease improve in most patients. Tumor shrinkage occurs with somatostatin analogs used as adjunctive therapy in about 30% of patients and with their use as primary therapy in about 48% of patients. The shrinkage in most patients is greater than 20%, but less than 50% of tumor size 5).


Current data suggest that response to these drugs is better analyzed by taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA 6).


Somatostatin analogues may be used when complete recovery cannot be achieved by surgical excision of GH-secreting pituitary adenomas or the patient declines surgery. This position statement is established based on the consensus of opinion among experts and evidence from published data regarding the use of somatostatin analogs in patients with acromegaly. However, this position statement cannot be considered as complete, given the clinical characteristics of acromegaly and the absence of large-scale clinical data in Korea; at this time, the clinical judgment of the physician should take precedence over this statement. This position statement will be revised as needed when additional data for Korean patients become available 7).


Shao et al. retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After Somatostatin Analogs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, the study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly 8).


1)
Dagistanli FK, Ozkaya HM, Kucukyoruk B, Biceroglu H, Metin D, Gazioglu N, Oz B, Kadioglu P, Ozturk M. Preoperative Somatostatin Analogue Treatment Might Trigger Apoptosis and Autophagy in Tumor Tissues of Patients with Acromegaly: A Pilot Study. Exp Clin Endocrinol Diabetes. 2016 Jun 20. [Epub ahead of print] PubMed PMID: 27322826.
2)
Wang JW, Li Y, Mao ZG, Hu B, Jiang XB, Song BB, Wang X, Zhu YH, Wang HJ. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas. Patient Prefer Adherence. 2014 Jan 6;8:43-51. eCollection 2014. Review. PubMed PMID: 24421637; PubMed Central PMCID: PMC3888346.
3)
Donoho DA, Bose N, Zada G, Carmichael JD. Management of aggressive growth hormone secreting pituitary adenomas. Pituitary. 2017 Feb;20(1):169-178. doi: 10.1007/s11102-016-0781-7. Review. PubMed PMID: 27987061.
4)
Lamberts SW. The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors. Endocr Rev. 1988 Nov;9(4):417-36. doi: 10.1210/edrv-9-4-417. PMID: 2905987.
5)
Freda PU. Somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2002 Jul;87(7):3013-8. doi: 10.1210/jcem.87.7.8665. PMID: 12107192.
6)
Colao A, Auriemma RS, Lombardi G, Pivonello R. Resistance to somatostatin analogs in acromegaly. Endocr Rev. 2011 Apr;32(2):247-71. doi: 10.1210/er.2010-0002. Epub 2010 Dec 1. PMID: 21123741.
7)
Chin SO, Ku CR, Kim BJ, Kim SW, Park KH, Song KH, Oh S, Yoon HK, Lee EJ, Lee JM, Lim JS, Kim JH, Kim KJ, Jin HY, Kim DJ, Lee KA, Moon SS, Lim DJ, Shin DY, Kim SH, Kwon MJ, Kim HY, Kim JH, Kim DS, Kim CH. Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement. Endocrinol Metab (Seoul). 2019 Mar;34(1):53-62. doi: 10.3803/EnM.2019.34.1.53. PMID: 30912339; PMCID: PMC6435847.
8)
Shao XQ, Chen ZY, Wang M, Yang YP, Yu YF, Liu WJ, Wang Y, Zeng FF, Gong W, Ye HY, Wang YF, Zhao Y, Zhang L, Zhang ZY, He M, Li YM. Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases. Horm Metab Res. 2022 Jan;54(1):25-32. doi: 10.1055/a-1717-9332. Epub 2022 Jan 5. PMID: 34986497.
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  • Last modified: 2022/11/24 12:47
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