RESUMO
CONTEXT: Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database. OBJECTIVE: We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline. DESIGN: Observational, retrospective, and cross-sectional study. SETTING: This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center. PATIENTS AND METHODS: Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed. RESULTS: We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas' patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P = 0.015), higher serum PRL levels (P = 0.007), larger tumors (P = 0.001), and cabergoline resistance (P < 0.001). CONCLUSIONS: The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants' role and their potential as therapeutic targets.
Assuntos
Neoplasias Hipofisárias , Prolactinoma , Masculino , Humanos , Animais , Camundongos , Prolactinoma/tratamento farmacológico , Prolactinoma/genética , Agonistas de Dopamina/uso terapêutico , Cabergolina/uso terapêutico , Receptores da Prolactina , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/genética , Prolactina/genética , Ergolinas/farmacologia , Ergolinas/uso terapêutico , Estudos Retrospectivos , Estudos Transversais , Camundongos KnockoutRESUMO
The anatomy of the temporal bone is complex, and postoperative imaging evaluation of this bone can be challenging. Surgical approaches to the temporal bone can be categorized didactically into tympanoplasty and ossicular reconstruction, mastoidectomy, and approaches to the cerebellopontine angle and internal auditory canal (IAC). In clinical practice, different approaches can be combined for greater surgical exposure. Postoperative imaging may be required for follow-up of neoplastic lesions and to evaluate unexpected outcomes or complications of surgery. CT is the preferred modality for assessing the continuity of the reconstructed conductive mechanism, from the tympanic membrane to the oval window, with use of grafts or prostheses. It is also used to evaluate aeration of the tympanic and mastoid surgical cavities, as well as the integrity of the labyrinth, ossicular chain, and tegmen. MRI is excellent for evaluation of soft tissue. Use of a contrast-enhanced fat-suppressed MRI sequence is optimal for follow-up after IAC procedures. Non-echo-planar diffusion-weighted imaging is optimal for detection of residual or recurrent cholesteatoma. The expected imaging findings and complications of the most commonly performed surgeries involving the temporal bone are summarized in this review. Online supplemental material is available for this article. ©RSNA, 2021.