Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

Filopanti, Marcello; Barbieri, Anna Maria; Angioni, A. R.; Colao, Annamaria; Gasco, Valentina; Grottoli, Silvia; Peri, Alessandro; Baglioni, Silvana; Fustini, Mattia; Pigliaru, Francesco; Monte, P. Del; Borretta, Giorgio; Ambrosi, Bruno; Jaffrain-Rea, Marie Lise; Gasperi, Maurizio; Brogioni, Sandra; Cannavò, Salvatore; Mantovani, Giovanna; Beck‐Peccoz, Paolo; Lania, Andrea; Spada, Anna

doi:10.1038/tpj.2008.1

Cited by 37 publications

(22 citation statements)

References 34 publications

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“…The biological basis of pharmacological resistance remains poorly understood (9,18). Research has mainly focused on the D2R, reporting a reduced number of binding sites (19), reduced gene expression (20), impaired balance between its short and long isoforms (21), and genetic polymorphisms (22). Additional factors involved in the aggressiveness of prolactinomas may interfere with D2R signaling or exert opposing biological effects on lactotroph cells.…”

Section: Discussionmentioning

confidence: 99%

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Vroonen

Jaffrain-Rea

Pétrossians

et al. 2012

European Journal of Endocrinology

173

104

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Background: Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. Design and methods: A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB R2.0 mg weekly.

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Section: Discussionmentioning

confidence: 99%

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Vroonen

Jaffrain-Rea

Pétrossians

et al. 2012

European Journal of Endocrinology

173

104

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“…Prolactinomas are initially treated with dopamine agonists, mainly cabergoline, which is efficient in controlling tumor growth and PRL levels in most cases [76]. Resistance to dopamine agonists presenting as escalating PRL levels and/or tumor growth can be an early indicator of aggressiveness, but this may not always be the case, as some ‘benign' prolactinomas may show resistance due to polymorphisms in the dopamine receptor [77]. For prolactinomas refractory to medical treatment, maximizing cabergoline dosage beyond conventional doses has been proposed, as long as adverse effects are tolerable [76].…”

Section: Treatmentmentioning

confidence: 99%

Aggressive Pituitary Tumors

et al. 2015

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Pituitary adenomas are common intracranial tumors that are mainly considered as benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by gross invasion of the surrounding tissues, resistance to conventional treatment leading to early and frequent recurrences. Even more rarely, pituitary tumors can give rise to cerebrospinal or systemic metastases qualifying as pituitary carcinomas according to the latest WHO definition. In the same classification, a subset of tumors with relatively distinct histopathological features was identified and defined as atypical adenomas designated to follow a more aggressive clinical course. This classification, although clinically useful, does not provide an accurate correlation between histopathological findings and the clinical behavior of these tumors, neither is it adequate to convey the precise features of ‘aggressive' tumors. Thus, ‘aggressive' pituitary adenomas need to be properly defined with clinical, radiological, histological and molecular markers in order to identify patients at increased risk of early recurrence or subsequent tumor progression. At present, no single marker or classification system of pituitary tumor aggressiveness exists, and clinically useful information in the literature is insufficient to guide diagnostic and therapeutic decisions. Treatment of patients with aggressive pituitary tumors is challenging since conventional treatments often fail, necessitating multiple surgical procedures with additional radiotherapy. Although traditional chemotherapy applied in other neuroendocrine tumors has not been shown to be efficacious, newer agents, particularly temozolomide, have shown promising results and are currently used despite the lack of data from a randomized prospective trial. Molecular targeted therapies such as mTOR and epidermal growth factor inhibitors have also been applied and might prove to be useful in the management of these patients. In the present review, we provide information regarding the epidemiology and clinical, histopathological and molecular features of aggressive pituitary tumors using recent employed definitions. In addition, we review currently employed therapeutic means providing a therapeutic algorithm and highlight the need to identify more specific disease-related and prognostic markers and the necessity for central registration of these tumors.

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“…Correlations with polymorphisms were studied by both considering the three groups (two of homozygotes and one of heterozygotes) and two groups (carriers of the less frequent allele or not) of genotypes, as in previous studies (17,18). Data were reported as meanGS.D.…”

Section: Discussionmentioning

confidence: 99%

Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients

Filopanti

Barbieri

Mantovani

et al. 2014

European Journal of Endocrinology

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Context: Hepatotoxicity is one of the most serious adverse effects in acromegalic patients treated with pegvisomant (PEG-V). Recent studies have found an association between this adverse event and the UGT1A1 allele 28 polymorphism associated with Gilbert's syndrome. Objective: To determine whether UGT1A1*28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment. Design and setting: Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy. Patients: A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled. Interventions: Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping. Results: No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalities and overt hepatotoxicity developed in 17 and 4.5% of patients respectively. Logistic and linear regression analyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratioZ1.25; PZ0.04) and the number of concomitant medications, other than SSTa (BZ3.9; PZ0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found. Conclusions: UGT1A1 allele 28 and ADH1C and B polymorphisms do not predict increased risk of hepatotoxicity during PEG-V therapy. Conversely, patients with multi-therapies and with previous episodes of liver disease should be carefully managed, due to the observed association between these conditions and LFT abnormalities during PEG-V therapy.

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Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

Cited by 37 publications

References 34 publications

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Aggressive Pituitary Tumors

Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients

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