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1.
Zhonghua Nei Ke Za Zhi ; 60(4): 345-349, 2021 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-33765704

RESUMO

Objective: To explore the clinical characteristics of patients with pituitary thyrotropin-secreting adenoma and evaluate the effect of preoperative short-acting octreotide treatment on hyperthyroidism. Methods: A retrospective analysis was performed in 40 patients with pituitary thyrotropin adenoma diagnosed in Beijing Tiantan Hospital from January 2008 to January 2018. The general data, laboratory examinations and imaging findings were reviewed and analyzed. The clinical effect of preoperative octreotide on hyperthyroidism was evaluated. Results: The age of onset year of the 40 patients (male: female = 24∶16) was (30.5±5.1) years. Among them, 35 patients (87.5%) were with macroadenoma. The most common symptoms were thyroid hypermetabolism syndrome, followed by headache, dizziness, visual field damage and hypogonadism. The thyroid function of 30 patients (75%) recovered to normal within 3-5 days after the octreotide treatment. The total effective rate of the octreotide was 90.0%. The level of free thyroxine (FT4) before treatment in patients with more than 10 times of effective cumulative dose was significantly higher than that in patients with less than 10 doses. Conclusions: Thyroid hypermetabolism syndrome and pituitary occupying effect are the most common clinical manifestations of thyrotropin-secreting adenoma. Preoperative octreotide treatment can effectively control hyperthyroidism. The level of FT4 is a crucial factor affecting the efficacy of octreotide.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/tratamento farmacológico , Feminino , Humanos , Masculino , Octreotida/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Estudos Retrospectivos , Tireotropina
2.
Indian J Ophthalmol ; 69(4): 992-994, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33727476

RESUMO

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery.


Assuntos
Adenoma/diagnóstico , Infecções Oculares Virais/diagnóstico , Apoplexia Hipofisária/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Adenoma/tratamento farmacológico , Adenoma/virologia , Infecções Oculares Virais/tratamento farmacológico , Infecções Oculares Virais/virologia , Glucocorticoides/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Apoplexia Hipofisária/tratamento farmacológico , Apoplexia Hipofisária/virologia , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/virologia
3.
Eur J Endocrinol ; 183(2): 221-231, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32583656

RESUMO

Context: In patients treated with antipsychotics, the rare occurrence of a macroprolactinoma represents a therapeutic challenge. Objective: Our aim was to evaluate the efficacy and psychiatric safety of dopamine agonists (DAs) prescribed for large macroprolactinomas in patients with psychosis treated with antipsychotics. Design: This was a multicenter (France and Belgium) retrospective study. Patients: Eighteen patients treated with antipsychotics were included. Results: Under DA, median PRL levels decreased from 1247 (117-81 132) to 42 (4-573) ng/mL (P = 0.008), from 3850 (449-38 000) to 141 (60-6000) ng/mL (P = 0.037) and from 1664 (94-9400) to 1215 (48-5640) ng/mL (P = 0.56) when given alone (n = 8), before surgery (n = 7), or after surgery (n = 6), respectively. The prolactinoma median largest diameter decreased by 28% (0-57) in patients under DAs alone (P = 0.02) but did not change when given after surgery. Optic chiasm decompression was achieved in 82% of patients. Five patients (28%) were admitted for psychotic relapse while receiving DAs (but three of them had stopped antipsychotic treatment at that time). A more severe underlying psychosis, rather than the DA treatment itself, may explain such psychiatric admissions. Conclusions: Even if the DA efficacy on PRL levels and tumor volume in patients with macroprolactinoma under antipsychotic drugs is less impressive than that typically observed, it may be considered satisfactory for half of our patients, particularly in cases of optic chiasm compression. Psychotic exacerbation was unusual in these patients, occurring mostly in those with the most severe psychotic forms. DAs may therefore be used as antitumor treatment for macroprolactinoma in patients with visual involvement, severe headaches or invasion into the skull base who receive antipsychotics.


Assuntos
Antipsicóticos/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adulto , Bélgica , Interações Medicamentosas , Feminino , França , Humanos , Masculino , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/psicologia , Prolactina/sangue , Prolactinoma/patologia , Prolactinoma/psicologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Recidiva , Estudos Retrospectivos
4.
J Endocrinol ; 244(2): 415-429, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32395971

RESUMO

Among all the hormone-secreting pituitary tumours, prolactinomas are the most frequently found in the clinic. Since dopamine is the primary inhibitor of lactotroph function, dopamine agonists represent the first-line therapy. However, a subset of patients exhibits resistance to these drugs, and therefore, alternative treatments are desired. As activins inhibit prolactin gene expression through the inhibition of Pit-1 involving the p38MAPK pathway, in the present work, we studied the local activin system as an alternative inhibitory system for lactotroph hyperplasia treatment. We used two different mouse models of prolactinoma: transgenic mice with overexpression of the human chorionic gonadotropin ß-subunit (hCGß) and mice lacking dopamine receptor type 2. In both models, females, but not males, develop lactotroph hyperplasia from the fourth month of life. We found reduced expression of pituitary activin subunits and activin receptors in hyperplastic pituitaries from both models compared with wild-type counterparts. Consequently, hyperplastic pituitaries presented a reduced activin-inhibitory action on prolactin secretion. Additionally, while female wild-type lactotrophs presented high levels of phospho-p38MAPK, it was lost in prolactinomas, concomitant with decreased activin expression, increased Pit-1 expression and tumour development. In contrast, male pituitaries express higher mRNA levels of activin subunits ßA and ßB, which would suggest a stronger activin inhibitory function on lactotrophs, protecting this sex from tumour development, despite genotype. The present results highlight the importance of the activin inhibitory action on lactotroph function and place the local activin system as a new target for the treatment of dopamine agonist-resistant prolactinomas.


Assuntos
Ativinas/metabolismo , Lactotrofos/metabolismo , Neoplasias Hipofisárias/genética , Prolactinoma/genética , Animais , Agonistas de Dopamina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genótipo , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos , Camundongos Transgênicos , Hipófise/metabolismo , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/complicações , Prolactinoma/tratamento farmacológico , RNA Mensageiro/metabolismo , Fatores Sexuais , Fator de Transcrição Pit-1/metabolismo
5.
Int J Mol Sci ; 21(5)2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32121432

RESUMO

Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, Graves' orbitopathy, diabetic retinopathy, diabetic macular edema), non-endocrine tumors (breast, colon, prostate, lung, and hepatocellular), and digestive diseases (chronic refractory diarrhea, hepatorenal polycystosis, gastrointestinal hemorrhage, dumping syndrome, and intestinal fistula).


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Somatostatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Edema Macular/tratamento farmacológico , Edema Macular/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Somatostatina/análogos & derivados , Somatostatina/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
6.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32070065

RESUMO

Croton is an extensive flowering plant genus in the spurge family, Euphorbiaceae. Three croton compounds with the common ent-kaurane skeleton have been purified from Croton tonkinensis. METHODS: We examined any modifications of croton components (i.e., croton-01 [ent-18-acetoxy-7α-hydroxykaur-16-en-15-one], croton-02 [ent-7α,14ß-dihydroxykaur-16-en-15-one] and croton-03 [ent-1ß-acetoxy-7α,14ß-dihydroxykaur-16-en-15-one] on either hyperpolarization-activated cation current (Ih) or erg-mediated K+ current identified in pituitary tumor (GH3) cells and in rat insulin-secreting (INS-1) cells via patch-clamp methods. RESULTS: Addition of croton-01, croton-02, or croton-03 effectively and differentially depressed Ih amplitude. Croton-03 (3 µM) shifted the activation curve of Ih to a more negative potential by approximately 11 mV. The voltage-dependent hysteresis of Ih was also diminished by croton-03 administration. Croton-03-induced depression of Ih could not be attenuated by SQ-22536 (10 µM), an inhibitor of adenylate cyclase, but indeed reversed by oxaliplatin (10 µM). The Ih in INS-1 cells was also depressed effectively by croton-03. CONCLUSION: Our study highlights the evidence that these ent-kaurane diterpenoids might conceivably perturb these ionic currents through which they have high influence on the functional activities of endocrine or neuroendocrine cells.


Assuntos
Croton/química , Diterpenos de Caurano/farmacologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/antagonistas & inibidores , Neoplasias Hipofisárias/tratamento farmacológico , Adenilil Ciclases/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Diterpenos de Caurano/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/química , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Estrutura Molecular , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos
7.
Biomolecules ; 10(2)2020 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991782

RESUMO

: GAL-021 has recently been developed as a novel breathing control modulator. However, modifications of ionic currents produced by this agent remain uncertain, although its efficacy in suppressing the activity of big-conductance Ca2+-activated K+ (BKCa) channels has been reported. In pituitary tumor (GH3) cells, we found that the presence of GAL-021 decreased the amplitude of macroscopic Ca2+-activated K+ current (IK(Ca)) in a concentration-dependent manner with an effective IC50 of 2.33 µM. GAL-021-mediated reduction of IK(Ca) was reversed by subsequent application of verteporfin or ionomycin; however, it was not by that of diazoxide. In inside-out current recordings, the addition of GAL-021 to the bath markedly decreased the open-state probability of BKCa channels. This agent also resulted in a rightward shift in voltage dependence of the activation curve of BKCa channels; however, neither the gating charge of the curve nor single-channel conductance of the channel was changed. There was an evident lengthening of the mean closed time of BKCa channels in the presence of GAL-021, with no change in mean open time. The GAL-021 addition also suppressed M-type K+ current with an effective IC50 of 3.75 µM; however, its presence did not alter the amplitude of erg-mediated K+ current, or mildly suppressed delayed-rectifier K+ current. GAL-021 at a concentration of 30 µM could also suppress hyperpolarization-activated cationic current. In HEK293T cells expressing α-hSlo, the addition of GAL-021 was also able to suppress the BKCa-channel open probabilities, and GAL-021-mediated suppression of BKCa-channel activity was attenuated by further addition of BMS-191011. Collectively, the GAL-021 effects presented herein do not exclusively act on BKCa channels and these modifications on ionic currents exert significant influence on the functional activities of electrically excitable cells occurring in vivo.


Assuntos
Neoplasias Hipofisárias/tratamento farmacológico , Respiração/efeitos dos fármacos , Triazinas/farmacologia , Cálcio/metabolismo , Diazóxido/farmacologia , Células HEK293 , Humanos , Ionomicina/farmacologia , Neoplasias Hipofisárias/patologia , Verteporfina/farmacologia
9.
Pituitary ; 23(1): 65-69, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31792668

RESUMO

Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to the gonadal axis impairment. The gold-standard treatment is dopamine agonist (DA) which can reverse hyperprolactinemia and hypogonadism, and promote tumor shrinkage in the majority of cases. Therefore, reports of pregnancy in such cohort become more common. In this scenario, bromocriptine is still the DA of choice due to its shorter half-life and larger experience as compared to cabergoline. In DA resistant cases, transsphenoidal pituitary surgery is indicated. However, potential risks of DA-induced pregnancies include fetal exposition and symptomatic tumor growth. Dopamine agonist should be discontinued as soon as pregnancy is confirmed in microprolactinomas and intrasellar macroprolactinomas (MAC). Concerning expansive/invasive MAC, DA maintenance should be considered. Periodically clinical evaluation should be performed during pregnancy, being sellar imaging indicated if tumor symptomatic growth is suspected. In such cases, if DA treatment fails, neurosurgery is indicated.


Assuntos
Agonistas de Dopamina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Bromocriptina/uso terapêutico , Feminino , Humanos , Gravidez
10.
Pituitary ; 23(1): 52-57, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31802331

RESUMO

CONTEXT: Prolactinomas in men are usually large and invasive, presenting with signs and symptoms of hypogonadism and mass effects, including visual damage. Prolactin levels are high, associated with low testosterone, anemia, metabolic syndrome and if long-standing also osteoporosis. RESULTS: Medical treatment with the dopamine agonist, cabergoline, became the preferred first-line treatment for male prolactinomas as well as for giant tumors, leading to prolactin normalization in ~ 80% of treated men, and tumor shrinkage, improved visual fields and recovery of hypogonadism in most patients. Multi-modal approach including surgery and occasionally radiotherapy together with a high-dose cabergoline is saved for resistant and invasive adenomas. Experimental treatments including temozolomide or pasireotide may improve clinical response in men harboring resistant prolactinomas. CONCLUSIONS: Compared to other pituitary adenomas, secreting and non-secreting, where pituitary surgery is the recommended first-line treatment, men with prolactinomas will usually respond to medical treatment with no need for any additional treatment.


Assuntos
Prolactinoma/tratamento farmacológico , Cabergolina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Humanos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/cirurgia , Masculino , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/cirurgia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Temozolomida/uso terapêutico
11.
Eur J Endocrinol ; 182(2): 177-183, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31770105

RESUMO

Objective: The association between prolactin level variation and prolactinoma size reduction remains unclear. This study aimed to determine the prolactin level cut-off predictive of a tumor size reduction. Design: Retrospective cohort study. Methods: We reviewed medical records of patients with prolactinoma who received primary cabergoline therapy and for whom complete data on pituitary hormone assays and sellar MRI at baseline and 3 months post treatment were available. We tested whether the certain prolactin level after 3 months post treatment predicted better response. Results: Prolactin levels normalized in 109 (88.6%) of 123 included macroprolactinoma patients. The mean tumor size reduction was 22.9%, and patients in the lowest prolactin tertile (≤0.7) had the highest frequency of tumor size reductions of ≥20% (73.7 vs 52.9% and 45.9% in tertiles 2 (>0.7 to 2.6) and 3 (>2.6 to 20), P = 0.015). Patients with prolactin levels ≤1 ng/mL exhibited larger tumor size reductions vs those with prolactin levels of 1-20 (27.2 ± 18.3% vs 19.5 ± 13.9%, P = 0.014), 1-10 (19.3 ± 13.7%, P = 0.017) and 1-5 ng/mL (19.2 ± 14.3%, P = 0.039). A multivariable logistic regression analysis revealed that a prolactin level ≤1 ng/mL at 3 months and high-dose cabergoline therapy were significantly associated with tumor size reductions of ≥20% (odds ratio (OR): 2.8, 95% confidence interval (CI): 1.2-6.7, P = 0.017; OR: 2.0, 95% CI: 1.0-3.9, P = 0.043). Conclusions: A prolactin level ≤1 ng/mL at 3 months after cabergoline treatment was correlated with a significant tumor size reduction in patients with macroprolactinoma. This finding may help clinical decision making when treating macroprolactinoma patients.


Assuntos
Cabergolina/uso terapêutico , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/tratamento farmacológico , Prolactina/sangue , Prolactinoma/sangue , Prolactinoma/tratamento farmacológico , Adulto , Tomada de Decisões , Feminino , Humanos , Masculino , Neoplasias Hipofisárias/patologia , Prolactinoma/patologia , Estudos Retrospectivos
12.
Eur J Endocrinol ; 182(1): R1-R13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705792

RESUMO

Although effective treatment regimens (surgical resection, drug treatment with dopamine agonists or somatostatin analogues, radiotherapy) have been established for the therapy of most pituitary tumours, a considerable proportion of affected patients cannot completely cured due to incomplete resection or drug resistance. Moreover, even if hormone levels have been normalized, patients with hormone-secreting tumours still show persistent pathophysiological alterations in metabolic, cardiovascular or neuropsychiatric parameters and have an impaired quality of life. In this review reasons for the discrepancy between biochemical cure and incomplete recovery from tumour-associated comorbidities are discussed and the clinical management is delineated exemplarily for patients with acromegaly and Cushing's disease. In view of the development of additional treatment concepts for the treatment of pituitary adenomas we speculate about the relevance of RSUME as a potential target for the development of an anti-angiogenic therapy. Moreover, the role of BMP-4 which stimulates prolactinoma development through the Smad signalling cascade is described and its role as putative drug target for the treatment of prolactinomas is discussed. Regarding the well-known resistance of a part of somatotropinomas to somatostatin analogue treatment, recently identified mechanisms responsible for the drug resistance are summarized and ways to overcome them in future treatment concepts are presented. Concerning novel therapeutic options for patients with Cushing's disease the impact of retinoic acid, which is currently tested in clinical studies, is shown, and the action and putative therapeutic impact of silibinin to resolve glucocorticoid resistance in these patients is critically discussed.


Assuntos
Neoplasias Hipofisárias/tratamento farmacológico , Pesquisa Médica Translacional/métodos , Animais , Humanos , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/fisiopatologia , Neoplasias Hipofisárias/fisiopatologia , Prolactinoma/tratamento farmacológico , Prolactinoma/fisiopatologia , Qualidade de Vida , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
13.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746334

RESUMO

CONTEXT: Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging. OBJECTIVE: We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness. DESIGN AND SUBJECTS: Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients. RESULTS: Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated. CONCLUSION: We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.


Assuntos
Adenoma/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Temozolomida/uso terapêutico , Adulto , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
14.
Horm Metab Res ; 52(1): 8-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31863423

RESUMO

Pituitary adenomas represent approximately 15% of brain tumors; incidence is significantly on the increase due to widespread use of magnetic resonance imaging. Surgery remains the first-line treatment for most tumors overall. The role of dopaminergic agonists (DAs) and somatostatin receptor ligands (SRLs) in the treatment of pituitary adenomas is quite well established for prolactinomas and growth hormone (GH) excess. However, over the last decade new multi-receptor binding SRLs are increasingly used for treatment of acromegaly and Cushing's disease. SRLs/DA chimeric compounds seem to have enhanced potency and efficacy when compared to that of individual SRLs or DA receptor agonists according to preclinical data. However, following negative results, more research is needed to determine if this interesting mechanism will translate into positive clinical effects for acromegaly patients. Furthermore, new agents that block adrenal steroidogenesis have been developed in phase III clinical trials for Cushing's disease and several new compounds working at the pituitary level and/or blocking the glucocorticoid receptor are also in development. Combination therapy of drugs with similar or different mechanisms (possibly synergistic) are also on the increase. A growing awareness regarding all mechanisms involved in both control of pituitary secretion and cellular proliferation might allow for sole medical treatment of pituitary adenomas, especially macroadenomas, rather than surgery and/or radiation therapy, in the future. Moreover, the underlying decision on how to treat patients with pituitary adenomas should be individualized on a case-by-case basis with not only a goal of tumor shrinkage and biochemical control, but also of improving patients' quality of life.


Assuntos
Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Agonistas de Dopamina/administração & dosagem , Humanos , Hipersecreção Hipofisária de ACTH/genética , Hipersecreção Hipofisária de ACTH/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Receptores de Somatostatina/agonistas
15.
Clin Cancer Res ; 26(4): 957-969, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31624102

RESUMO

PURPOSE: Somatostatin analogues (SSA) are efficacious and safe treatments for a variety of neuroendocrine tumors, especially pituitary neuroendocrine tumors (PitNET). Their therapeutic effects are mainly mediated by somatostatin receptors SST2 and SST5. Most SSAs, such as octreotide/lanreotide/pasireotide, are either nonselective or activate mainly SST2. However, nonfunctioning pituitary tumors (NFPTs), the most common PitNET type, mainly express SST3 and finding peptides that activate this particular somatostatin receptor has been very challenging. Therefore, the main objective of this study was to identify SST3-agonists and characterize their effects on experimental NFPT models. EXPERIMENTAL DESIGN: Binding to SSTs and cAMP level determinations were used to screen a peptide library and identify SST3-agonists. Key functional parameters (cell viability/caspase activity/chromogranin-A secretion/mRNA expression/intracellular signaling pathways) were assessed on NFPT primary cell cultures in response to SST3-agonists. Tumor growth was assessed in a preclinical PitNET mouse model treated with a SST3-agonist. RESULTS: We successfully identified the first SST3-agonist peptides. SST3-agonists lowered cell viability and chromogranin-A secretion, increased apoptosis in vitro, and reduced tumor growth in a preclinical PitNET model. As expected, inhibition of cell viability in response to SST3-agonists defined two NFPT populations: responsive and unresponsive, wherein responsive NFPTs expressed more SST3 than unresponsive NFPTs and exhibited a profound reduction of MAPK, PI3K-AKT/mTOR, and JAK/STAT signaling pathways upon SST3-agonist treatments. Concurrently, SSTR3 silencing increased cell viability in a subset of NFPTs. CONCLUSIONS: This study demonstrates that SST3-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST3, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.


Assuntos
Tumores Neuroendócrinos/tratamento farmacológico , Peptídeos/farmacologia , Neoplasias Hipofisárias/tratamento farmacológico , Receptores de Somatostatina/agonistas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Janus Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Peptídeos/química , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Transdução de Sinais , Células Tumorais Cultivadas , Adulto Jovem
16.
Intern Med ; 59(4): 545-550, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31611532

RESUMO

A 30-year-old woman with multiple ovarian cysts presented with high serum estradiol levels. She had a pituitary adenoma, but the follicle-stimulating hormone (FSH) concentration was within the normal range. The patient complained of neck pain and palpitations during the disease course, and laboratory results revealed thyrotoxicosis and a systemic inflammatory response with negative findings for anti-thyroid stimulating hormone (TSH) receptor antibody and positive findings for anti-thyroglobulin and anti-thyroid peroxidase antibodies. Prednisolone improved the symptoms and the thyroid function and was discontinued after two months. A histological examination of the pituitary tumor confirmed it to be FSH-producing pituitary adenoma, with subsequent normalization of the serum estradiol concentration.


Assuntos
Adenoma/complicações , Adenoma/tratamento farmacológico , Adenoma/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/cirurgia , Prednisolona/uso terapêutico , Tireoidite/complicações , Adenoma/fisiopatologia , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Japão , Imagem por Ressonância Magnética , Neoplasias Hipofisárias/fisiopatologia , Tireoidite/fisiopatologia , Resultado do Tratamento
17.
Pituitary ; 23(1): 70-77, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31617128

RESUMO

PURPOSE: Aggressive prolactinomas are defined as radiologically invasive tumors which cannot be cured by surgery, and that have an unusually rapid rate of tumor growth despite dopamine agonist treatment and surgery. In some cases, metastasis occurs, defining prolactin carcinoma which is the second most frequent pituitary carcinoma. METHODS: A literature search was performed to review the available data on the treatment of aggressive pituitary prolactinomas or carcinomas. RESULTS: When optimal standard therapies (high dose cabergoline, surgery and radiotherapy) failed, temozolomide, an alkylating drug, is currently the best option, allowing to control tumor growth in about 50% of treated prolactinomas and improving overall survival of these patients. However, long-term complete response occurs in a limited subgroup of tumors. Alternative drugs could be discussed in a subset of aggressive prolactinomas either before temozolomide (pasireotide, peptide receptor radionuclide therapy…) or after temozolomide failure. CONCLUSION: Despite the significant improvement obtained with the use of temozolomide, a need for alternative drugs persists since a majority of these tumors are resistant or will recur during the follow-up. Patients suffering from such a rare condition should have access to clinical trials available for other types of rare cancers, such as tyrosine kinase inhibitors or immunotherapy.


Assuntos
Prolactinoma/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Humanos , Neoplasias Hipofisárias/tratamento farmacológico , Temozolomida/uso terapêutico
18.
Rev. chil. endocrinol. diabetes ; 13(4): 150-153, 2020. ilus
Artigo em Espanhol | LILACS | ID: biblio-1123620

RESUMO

Los adenomas hipofisarios ectópicos (EPA) constituyen un reto diagnóstico, dada su escasa prevalencia y variada presentación en la que puede incluirse un síndrome de hipersecreción de hormonas hipofisarias. La clínica suele ser larvada e inespecífica, no presentan ninguna característica radiológica diferencial y el diagnóstico habitualmente es anatomopatológico. Sin embargo, a pesar de ser tumores benignos, pueden presentar un comportamiento agresivo, con invasión ósea y difícil resección completa, por lo que un diagnóstico de sospecha precoz podría resultar en un tratamiento más eficaz y con un menor número de complicaciones. Presentamos el caso de una paciente con un adenoma hipofisario ectópico silente en el seno esfenoidal con inmunohistoquímica positiva para Hormona de crecimiento (GH) y prolactina que presentaba restos tumorales tras la intervención quirúrgica y ha sido manejada con tratamiento médico conservado, con buenos resultados.


Ectopic pituitary adenomas constitute a diagnostic challenge, given their low prevalence and varied presentation in which a pituitary hormone hypersecretion syndrome may be included. Clinical symptoms are usually latent and nonspecific, they have no differential radiological characteristics and the diagnosis is usually anatomopathological. However, despite being benign tumors, they can exhibit aggressive behavior, with bone invasion and difficult complete resection, so a diagnosis of early suspicion could result in more effective treatment and fewer complications. We present the case of a patient with a silent ectopic pituitary adenoma in the sphenoid sinus with positive immunohistochemistry for Growth Hormone (GH) and prolactin who had tumor remnants after surgery and was managed with conservative medical treatment, with good results.


Assuntos
Humanos , Feminino , Idoso , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/tratamento farmacológico , Seio Esfenoidal , Adenoma/diagnóstico , Adenoma/tratamento farmacológico , Período Pós-Operatório , Prolactina/metabolismo , Hormônio do Crescimento/metabolismo , Imuno-Histoquímica , Imagem por Ressonância Magnética , Cintilografia , Tomografia Computadorizada por Raios X , Agonistas de Dopamina/uso terapêutico , Cabergolina/uso terapêutico
19.
Rev. chil. endocrinol. diabetes ; 13(3): 98-101, 2020. ilus
Artigo em Espanhol | LILACS | ID: biblio-1116920

RESUMO

Los adenomas pituitarios son los tumores hipofisarios más frecuentes siendo una entidad rara cuando se trata de adenomas ectópicos, es decir, sin conexión con la glándula pituitaria. Se cree que derivan de células residuales del tracto de migración embriológico desde la bolsa de Rathke. Su presentación clínica es muy variable porque depende de la producción hormonal y del efecto masa en estructuras adyacentes. Generalmente suponen un reto diagnóstico debido a su baja frecuencia, la clínica variable de presentación y que no presentan características específicas en las pruebas de imagen. Generalmente el diagnóstico se realiza de manera retrospectiva tras la resección quirúrgica. Presentamos el caso de un varón de 56 años que se presentó con unos valores de prolactina de 6647.5 ng/ml (2.2-17.7) con clínica de hipogonadismo aislada que se resolvió con tratamiento médico sin precisar resección quirúrgica, con una disminución de la densidad radiológica y estabilización del tamaño y sin clínica compresiva ni alteración visual.


Pituitary adenomas are the most common hypophyseal tumors being a rare entity when they are ectopic, without connection to the pituitary gland. They are thought to arise from residual cells in the migration tract from Rathke´s pouch. Its clinical presentation is variable depending on the hormonal production and the pressure effect on adjacent structures. They usually are a diagnostic challenge due to their low frequency, wide range of clinical presentation and not showing specific features on imaging techniques. The diagnosis is made usually retrospectively after surgical resection. We report the case of a 56 years old male that presented with a prolactine value of 6647.5 ng/ml (2.2-17.7) and isolated hypogonadism symptoms that resolved with medical treatment without surgery, diminishing the radiological density and stabilizing the size without having compresive symptoms nor visual disturbances.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Neoplasias da Base do Crânio/diagnóstico , Fossa Craniana Posterior , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adenoma , Neoplasias da Base do Crânio/tratamento farmacológico , Cabergolina/uso terapêutico
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