Pharmacological management of acromegaly: a current perspective

Abstract

<jats:p>Acromegaly is a chronic disorder of enhanced growth hormone (GH) secretion and elevated insulin-like growth factor–I (IGF-I) levels, the most frequent cause of which is a pituitary adenoma. Persistently elevated GH and IGF-I levels lead to substantial morbidity and mortality. Treatment goals include complete removal of the tumor causing the disease, symptomatic relief, reduction of multisystem complications, and control of local mass effect. While transsphenoidal tumor resection is considered first-line treatment of patients in whom a surgical cure can be expected, pharmacological therapy is playing an increased role in the armamentarium against acromegaly in patients unsuitable for or refusing surgery, after failure of surgical treatment (inadequate resection, cavernous sinus invasion, or transcapsular intraarachnoid invasion), or in select cases as primary treatment. Three broad drug classes are available for the treatment of acromegaly: somatostatin analogs, dopamine agonists, and GH receptor antagonists.</jats:p> <jats:p>Somatostatin analogs are considered as the first-line pharmacological treatment of acromegaly, although efficacy varies among the different formulations. Octreotide long-acting release (LAR) appears to be more efficacious than lanreotide sustained release (SR). Lanreotide Autogel (ATG) has been shown to result in similar biological control as octreotide LAR, and there may be a benefit in switching from one to the other in some cases of treatment failure. The novel multireceptor somatostatin analog pasireotide, currently in Phase II clinical trials, also shows promise in the treatment of acromegaly. Dopamine agonists have been the earliest and most widely used agents in the treatment of acromegaly but have been found to be less effective than somatostatin analogs. In this class of drugs, cabergoline has shown greater efficacy and tolerability than bromocriptine. Dopamine agonists have the advantage of oral administration, resulting in increased use in select patient groups. Selective GH receptor antagonists, such as pegvisomant, act by blocking the effects of GH, resulting in decreased IGF-I production despite persistent elevation of GH serum levels. Thus far, tumor growth has not been a concern during pegvisomant therapy. However, combination treatment with somatostatin analogs may counteract these effects. The authors discuss the latest guidelines for biochemical cure and highlight the efficacy of combination therapy. In addition, the effects of pharmacological presurgical treatment on surgical outcome are explored.</jats:p>

Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria

“…21,42 In some cases, somatostatin analogs and the GH receptor antagonist pegvisomant or radiotherapy can be considered as additional treatment options after resection of the tumor. 29,42 Although transsphenoidal microsurgery has been considered to be the best surgical approach in the treatment of GH-secreting adenomas, in the last decade endoscopic treatment of sellar lesions proved to be an important option as well. 19,22,30,39 The endoscopic approach has some obvious advantages, including improved surgical visualization, less nasal trauma, increased patient comfort, and potentially better results with respect to total tumor resection.…”

Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

“…Cabergoline is a synthetic ergot alkaloid which performs as a long acting D2-selective dopamine agonist, inhibiting D2 receptor-mediated prolactin secretion in the anterior lobe of the pituitary gland [14]. Pharmacological treatment of pituitary adenomas by cabergoline primarily aims at inhibition of prolactin stimulation, leading to the involution of prolactinomas.…”

“…Side effects of cabergoline include arterial hypotonia, fatigue, depression, dyspepsia, nausea and vomiting, cramps and erythema; an effect of particular concern is cardiac valve pathology, especially valve thickening [14]. The relevance of this has recently been questioned [15].…”

Efficacy of sandostatin LAR in type 1 DM; improvement in glycemic control with less insulin. a case report

“…He has no history of diabetes complications. He continued to receive his prior insulin regimen for four weeks and then IM Sandostatin LAR was added to his regimen in the same prescription as used in patients with acromegaly [9] Thus, the initial dose of Sandostatin LAR was 20 mg. He was followed at intervals of 4 weeks throughout the treatment period lasting 28 weeks.…”