Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and <i>in vivo</i> response to cabergoline therapy

Neto, Leonardo Vieira; Wildemberg, Luiz Eduardo; Moraes, Aline Barbosa; Colli, Leandro M.; Kasuki, Leandro; Marques, Nelma Verônica; Gasparetto, Emerson L.; Castro, Margaret de; Takiya, Christina Maeda

doi:10.1111/cen.12684

Cited by 57 publications

(45 citation statements)

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“…Colao and coworkers (18) analyzed 24 studies published between 1981 and 2005, encompassing 199 patients, and report stabilization of over 90% of NFPA masses in patients treated with DA. Five studies (20,21,22,23,24) encompassing 54 patients used cabergoline (mean dose 1-3 mg/week) for the treatment of NFPA (primary treatment or postsurgical remnants) with mean follow-up times between 6 and 12 months. Pooled results indicate that tumor stabilization occurred in 85% of patients (Supplementary Table 4).…”

Section: Discussionmentioning

confidence: 99%

“…However, dopaminergic binding sites (16) as well as D2R mRNA isoforms (17) are less abundant in NFPA than in prolactinomas, perhaps accounting for the modest rate of tumor shrinkage attained by DAs (18). Small studies, including a report from our own group (19), suggested that DA may retard NFPA growth (20,21,22,23,24), but to date, this potential therapeutic modality has not been broadly practiced.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists

Greenman

Cooper

Yaish

et al. 2016

European Journal of Endocrinology

118

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Objective: Clinically nonfunctioning pituitary adenoma (NFPA) remains the only pituitary tumor subtype for which no effective medical therapy is available or recommended. We evaluated dopamine agonist (DA) therapy for preventing growth of postsurgical pituitary tumor remnants. Design: The study design included historical cohort analysis of clinical results at two pituitary referral centers with different standard practices for postoperative NFPA management: DA therapy or conservative follow-up. Methods: Seventy-nine patients followed for 8.8 ± 6.5 years were treated with DA, initiated upon residual tumor detection on postoperative MRI (preventive treatment (PT) group, n = 55), or when tumor growth was subsequently detected during follow-up (remedial treatment (RT) group, n = 24). The control group (n = 60) received no medication. Tumoral dopamine and estrogen receptor expression assessed by quantitative RT-PCR and immunostaining were correlated with response to treatment. Results: Tumor mass decreased, remained stable, or enlarged, respectively, in 38, 49, and 13% of patients in the PT group, and in 0, 53, and 47% of control subjects; shrinkage or stabilization was achieved in 58% of enlarging tumors in the RT group, P < 0.0001. Fifteen-year progression-free survival rate was 0.805, 0.24, and 0.04, respectively, for PT, RT, and control groups (P < 0.001). About 42% of patients in the control group required additional surgery or radiotherapy, compared with 38 and 13% subjects in the RT and PT groups, respectively (P = 0.002). Outcome measures were not related to NFPA D2R abundance. Conclusions: Dopamine agonist therapy in patients with NFPA is associated with decreased prevalence of residual tumor enlargement after transsphenoidal surgical resection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists

Greenman

Cooper

Yaish

et al. 2016

European Journal of Endocrinology

118

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“…A similar result was found by Vieira Neto and cols. (99), who observed tumor reduction of > 25% in 67% (6/9 patients) after 6 months of treatment with CAB. In both studies, the cabergoline dose was titered up to 3 mg/week or to the highest tolerated dose.…”

Section: A -Dopamine Agonistsmentioning

confidence: 99%

“…These drugs act directly on the dopamine receptor type 2 (DR2), present in normal pituitary (96) and pituitary adenoma (96,97). The use of this class of drugs in the treatment of NFPA is based on the observation that these tumors express DR2 (96,98,99). Promising results have been reported on the efficacy of CAB in the control of tumor growth (98,99).…”

Section: A -Dopamine Agonistsmentioning

confidence: 99%

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A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

Neto

Boguszewski

Araújo

et al. 2016

Arch. Endocrinol. Metab.

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Clinically nonfunctioning pituitary adenomas (NFPA) are the most common pituitary tumors after prolactinomas. The absence of clinical symptoms of hormonal hypersecretion can contribute to the late diagnosis of the disease. Thus, the majority of patients seek medical attention for signs and symptoms resulting from mass effect, such as neuro-ophthalmologic symptoms and hypopituitarism. Other presentations include pituitary apoplexy or an incidental finding on imaging studies. Mass effect and hypopituitarism impose high morbidity and mortality. However, early diagnosis and effective treatment minimizes morbidity and mortality. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism is to provide a review of the diagnosis and treatment of patients with NFPA, emphasizing that the treatment should be performed in reference centers. This review is based on data published in the literature and the authors' experience. Arch Endocrinol Metab. 2016;60(4):374-90

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Diagnosis and Treatment of Pituitary Adenomas

Molitch

2017

JAMA

811

578

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pproximately 10% of unselected pituitaries (meaning those from individuals without known pituitary disease) examined at autopsy contain pituitary adenomas. 1 Magnetic resonance imaging (MRI) scans of normal volunteers also show a 10% prevalence, 2 but other pathologic entities may have a similar appearance, such as Rathke cleft cysts and metastatic tumors. 3 Not all patients with pituitary tumors develop symptoms because most tumors remain small and most do not secrete hormones in excessive amounts. Clinical case-finding studies, in which all hospitals and practices in a geographic area were queried about cases with pituitary tumors over a defined period, have suggested a prevalence of pituitary adenoma ranging from 1 in 865 persons to 1 in 2688 persons (Table 1). 4,[6][7][8][9][10][11] Pituitary adenomas are classified into microadenomas (<10 mm), macroadenomas (Ն10 mm), and giant adenomas (Ն40 mm) (Figure 1). 12,13 Pituitary carcinomas with distant metastases are rare, occurring in 0.1% to 0.2% of cases. 12 If an MRI shows the tumor impinging on the optic chiasm, then formal visual field testing is indicated. 13 An evaluation for hypopituitarism should be carried out in all patients with macroadenomas and even large (6-9 mm) microadenomas. 1 Diabetes insipidus is rarely seen with pituitary adenomas. 1 About two-thirds of pituitary adenomas may secrete excess hormones. In the studies 4,6-11 that included 1718 patients, about 50% of cases were macroadenomas and 32% to 66% of tumors were secreting prolactin, 14% to 54% were clinically nonfunction-IMPORTANCE Pituitary adenomas may hypersecrete hormones or cause mass effects. Therefore, early diagnosis and treatment are important.OBSERVATIONS Prevalence of pituitary adenomas ranges from 1 in 865 adults to 1 in 2688 adults. Approximately 50% are microadenomas (<10 mm); the remainder are macroadenomas (Ն10 mm). Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy. Prolactinomas account for 32% to 66% of adenomas and present with amenorrhea, loss of libido, galactorrhea, and infertility in women and loss of libido, erectile dysfunction, and infertility in men; they are generally treated with the dopamine agonists cabergoline and bromocriptine. Growth hormone-secreting tumors account for 8% to 16% of tumors and usually present with enlargement of the lips, tongue, nose, hands, and feet and are diagnosed by elevated insulin-like growth factor 1 levels and growth hormone levels; initial treatment is surgical. Medical therapy with somatostatin analogues, cabergoline, and pegvisomant is often also needed. Adrenocorticotropic hormone (ACTH)-secreting tumors account for 2% to 6% of adenomas and are associated with obesity, hypertension, diabetes, and other morbidity. Measurement of a late-night salivary cortisol level is the best screening test but petrosal sinus sampling for ACTH may be necessary to distinguish a pituitary from an ectopic source. The primary treatment of Cushin...

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Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and in vivo response to cabergoline therapy

Abstract: In conclusion, DR2 is expressed in all adenomas and the majority of the patients in this study displayed tumour shrinkage on cabergoline (CAB) therapy. Thus, CAB might be useful in adjuvant therapy in NFPA patients with residual tumours after surgery.

Cited by 57 publications

References 34 publications

Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists

Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists

A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

Diagnosis and Treatment of Pituitary Adenomas

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