Cabergolina como alternativa no tratamento clínico de prolactinomas. experiência na intolerância/resistência à bromocriptina

Musolino, Nina Rosa Castro; Neto, Malebranche B. C. Cunha; Bronstein, Marcello D.

doi:10.1590/s0004-27302000000200006

Cited by 9 publications

(4 citation statements)

References 13 publications

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“…The few data available from the literature seem to indicate that only acute or subacute BCR treatments have been applied to NS patients, being the drug able to lower ACTH plasma titers in the short term [12, 13, 14]. The failure of BCR could be due to the small dose administered (7.5 mg/day), i.e., the dose usually administered to women suffering from hyperprolactinemia [20]. This is because some patients with CD respond only to high doses of BCR ranging from 17.5 to 40 mg [21, 22, 23].…”

Section: Discussionmentioning

confidence: 99%

Nelson’s Syndrome: Complete Remission with Cabergoline but Not with Bromocriptine or Cyproheptadine Treatment

Casulari¹,

Naves²,

Mello

et al. 2004

Horm Res Paediatr

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A woman affected by Cushing’s disease underwent bilateral adrenalectomy followed by radiotherapy of the hypothalamic-pituitary area when she was 18 years old. Thereafter, she used hydrocortisone acetate replacement therapy (35.5 mg divided into two daily doses). At the age of 26 years, the patient exhibited the clinical signs of the Nelson’s syndrome, i.e. skin and gingival hyperpigmentation accompanied by amenorrhea, and elevated ACTH plasma levels (2,850 pg/ml, normal range 15–80 pg/ml). The magnetic resonance imaging (MRI) analysis of the sellar region evidenced a pituitary macroadenoma, measuring 14 × 13 mm. The patient was initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months. There was a partial improvement of the symptoms, with a reduction of the ACTH plasma levels to 112 pg/ml, but without any modification of the tumor mass. Due to sleepiness and weight gain, the cyproheptadine treatment was interrupted and substituted by a cabergoline (0.5 mg twice a week) therapy. Soon after cabergoline was applied an improvement of the clinical symptoms and signs was observed such as a regression of the tumor mass and the normalization of the ACTH plasma titers (38 pg/ml). Later, cabergoline was substituted by bromocriptine (7.5 mg/day) and the plasma levels of ACTH increased again (247 pg/ml), and headache and cutaneous hyperpigmentation were recorded. When cabergoline was reintroduced there was a clinical improvement and normalization of ACTH plasma levels (64 pg/ml). The MRI analysis of the sella region demonstrated a complete remission of the pituitary adenoma. The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson’s syndrome in the presence of a pituitary macroadenoma.

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Section: Discussionmentioning

confidence: 99%

Nelson’s Syndrome: Complete Remission with Cabergoline but Not with Bromocriptine or Cyproheptadine Treatment

Casulari¹,

Naves²,

Mello

et al. 2004

Horm Res Paediatr

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“…Cabergoline is a DA that presents prolonged action and better tolerability. Some authors [5, 6] showed that cabergoline has higher efficacy in normalizing prolactin (PRL) as compared to bromocriptine [7, 8]. Verhelst et al [9] obtained PRL normalization in 86% of 455 patients with hyperprolactinemia (including patients with prolactinomas or idiopathic hyperprolactinemia) during cabergoline treatment.…”

Section: Introductionmentioning

confidence: 99%

Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Passos¹,

Fortes

Giannella-Neto

et al. 2008

Neuroendocrinology

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Background/Aims: Prolactin (PRL) secretion and its gene expression are inhibited by dopamine. Prolactinomas are the most common secreting pituitary adenomas, and dopamine agonists (DA) are the first choice for their treatment. However, a subset of patients is resistant to DA. As the mechanisms involved in DA resistance are not fully understood, the aim of this study was to obtain new insights regarding the molecular differences between the prolactinomas that are responsive to DA and those that are resistant. Methods: Tumor tissue samples were collected from 17 patients who harbored prolactinomas, which were classified as responsive or resistant according to their clinical and laboratorial reaction to DA. The expression of 6 genes was evaluated by real-time polymerase chain reaction: dopamine receptor type 2 (DRD₂), nerve growth factor-β (NGFB) and its receptor (NGFR), estrogen receptor-α (ERA), estrogen receptor-β (ERB) and the pituitary tumor transforming gene (PTTG). Results: Median DRD₂ and NGFR expression in responsive patients was significantly higher than in resistant ones (p = 0.029 and p = 0.020, respectively). Moreover, the expressions of DRD₂ and NGFR were positively correlated with PRL decrease during treatment (r = 0.66, p = 0.005 and r = 0.57, p = 0.044, respectively). Furthermore, ERB expression was positively correlated to PTTG expression (r = 0.68, p = 0.032) and negatively correlated to NGFB expression (r = –0.75, p = 0.02). Conclusions: DRD₂ and NGFR expressions are related to the responsiveness of prolactinoma to DA. However, PTTG, ERB and ERA expressions are not. Also ERB, ERA and PTTG expressions did not present a clear correlation to tumor aggressiveness. Furthermore, the response of prolactinomas to DA should be viewed as a spectrum ranging from the most responsive to the most resistant ones.

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“…Estudos correlacionando este espectro de resistência/sensibilidade e expressão gênica são escassos na literatura. Aumento progressivo da dose do AD, desde que bem tolerado, é outra opção, embora tanto em nossa experiência como na de outros autores (29,37), a maior parte dos pacientes responsivos atingem o objetivo com doses habituais. Em estudo de Di Sarno e cols.…”

Section: Mecanismos Envolvidos Na Resistênciaunclassified

Prolactinomas resistentes a agonistas dopaminérgicos: diagnóstico e manejo

Musolino

Passos

2005

Arq Bras Endocrinol Metab

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Prolactinomas are the more prevalent functioning pituitary tumors, and dopamine agonist drugs (DA) are the main therapeutic option for patients harboring such tumors. Bromocriptine (BRC) resistance, defined as failure to normalize prolactin (PRL) and/or to shrink the tumor is reported in 5 to 18% of the patients treated with this drug, the first DA widely used. Cabergoline (CBG) can bring PRL to normalization and reduce tumor size in up to 86% and 92% of the patients, respectively. Even with this newer DA, a subset of patients does not respond to therapy and are truly resistant. The mechanisms for resistance are not yet fully clarified, so the treatment for the resistant prolactinoma is still a challenge. Transsphenoidal surgery associated or not to radiotherapy is an important tool, but PRL may not normalize, mainly in macroprolactinomas. Treatment with sex steroids or ovulation induction can solve the hypogonadism or infertility, when the tumor growth is under control. New drugs as anti-estrogens, new DA, specific analogs for somatostatin receptor subtypes, chimeric molecules associating dopamine and somatostatin effect, and PRL antagonists are under investigation and can be future alternatives for DA resistance.

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Cabergolina como alternativa no tratamento clínico de prolactinomas. experiência na intolerância/resistência à bromocriptina

Cited by 9 publications

References 13 publications

Nelson’s Syndrome: Complete Remission with Cabergoline but Not with Bromocriptine or Cyproheptadine Treatment

Nelson’s Syndrome: Complete Remission with Cabergoline but Not with Bromocriptine or Cyproheptadine Treatment

Genes Differentially Expressed in Prolactinomas Responsive and Resistant to Dopamine Agonists

Prolactinomas resistentes a agonistas dopaminérgicos: diagnóstico e manejo

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