RESUMO
Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.
Assuntos
Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Gravidez , Humanos , Feminino , Hiperprolactinemia/tratamento farmacológico , Prolactinoma/terapia , Agonistas de Dopamina/efeitos adversos , Prolactina , Neoplasias Hipofisárias/terapia , BrasilRESUMO
ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.
RESUMO
Acromegaly/giantism results from the chronic excess of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), in more than 96% of cases, due to a GH-secreting pituitary adenoma. Primary treatment of choice is transsphenoidal resection of the adenoma. More than 30% to 40% of operated cases require adjunctive forms of treatment, be it pharmacological or radiotherapeutical. The multimodal treatment of acromegaly has resulted in substantial improvements in the quality of life and life expectancy of these patients. We herein present the complex case of a patient with acromegaly due to a mammosomatotrope adenoma, with a germ-line AIP (aryl hydrocarbon receptor-interacting protein) mutation, who had a chronic and protracted course of more than 15 years during which he was treated with surgery, somatostatin receptor ligands, dopamine agonist, and the GH receptor antagonist pegvisomant. At one point, he was able to come off medications and was even found to be transiently GH-deficient, only to develop acromegaly again after a couple of years.
RESUMO
PURPOSE: To assess the effect of letrozole, an aromatase inhibitor (AI), in patients with resistant prolactinoma that presented an increase in serum prolactin (PRL) levels during testosterone replacement therapy (TRT). METHODS: A retrospective cohort study in a single tertiary care center. From March 2012 to July 2023, 53 male patients over 18 years with prolactinoma were followed in our Neuroendocrine Unit. Of those, 90.6% presented macroadenomas, 41% of them were resistant to cabergoline and 25% presented persistent hypogonadism to whom TRT was indicated. Among them, five presented a significant increase in PRL levels and AI was initiated. All five patients had resistant prolactinomas. One of them was excluded due to tumor aggressiveness and concomitant use of temozolomide during AI therapy. RESULTS: Four patients were included in the analysis, with a mean age of 28.5 (± 7.5) years, median prolactin of 1060 (600 to 6700) ng/mL and median of the largest tumor diameter of 3.6 (1.5 to 5) cm at the time of prolactinoma diagnosis. On TRT, all presented an increase in serum PRL levels (231 to 396%), with a subsequent decrease (61 to 93%) after adding AI. During AI treatment for a median time of 60.5 (21 to 120) months, tumor shrinkage was observed in two cases (-8 and -3 mm in the maximum diameter) and tumor stability in the other two. No major side effects occurred and AI was well tolerated. CONCLUSION: AI might be an option for men with resistant prolactinoma who have an increase in PRL levels on TRT. Nevertheless, prospective randomized clinical trials are needed to ensure efficacy and security for this approach.
Assuntos
Hipersecreção Hipofisária de ACTH , Gravidez , Feminino , Humanos , Cabergolina , Tretinoína , Colectomia , Estudos RetrospectivosRESUMO
PURPOSE: Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases. We provide here a review of published data about DA intolerance and present a case report concerning the use of intravaginal cabergoline. METHODS: We review the literature on the definition, the pathogenesis, frequency and management of DA intolerance. In addition, the review provides strategies to enhance tolerability and avoid precocious clinical treatment withdrawal. RESULTS: Cabergoline is often cited as the most tolerable DA and its side effects tend to ameliorate within days to weeks. Restarting the same drug at a lower dose or switching to another DA can be used in cases of intolerance. The vaginal route can be tried specifically if there are gastrointestinal side effects in the oral administration. Symptomatic treatment could be attempted, although mainly based on a strategy used in other diseases. CONCLUSIONS: Due to limited data, no guidelines have been developed for the management of intolerance in DA treatment. The most frequent management is to perform transsphenoidal surgery. Nevertheless, this manuscript provides data derived from published literature and expert opinion, suggesting new approaches to this clinical issue.
Assuntos
Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Feminino , Humanos , Prolactinoma/tratamento farmacológico , Prolactinoma/complicações , Agonistas de Dopamina/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Cabergolina/uso terapêutico , Neoplasias Hipofisárias/patologia , Hiperprolactinemia/tratamento farmacológico , Bromocriptina/uso terapêutico , Ergolinas/efeitos adversosRESUMO
SUMMARY OBJECTIVE: In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model. METHODS: A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth. RESULTS: Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively). CONCLUSION: Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.
RESUMO
ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.
RESUMO
PURPOSE: To make a systematic review and meta-analysis of studies evaluating the effect of cabergoline (CBG) in the treatment of non-functioning pituitary adenomas (NFPAs). METHODS: The primary outcome was tumor shrinkage, using as cut-off a reduction of at least 20% of the NFPA size from baseline. The secondary outcomes were prevention of tumor progression, clinically required additional interventions and adverse events (AE). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Random meta-analysis for the proportion of tumor shrinkage, prevention of tumor progression, clinically required additional interventions and frequency of AE were conducted. RESULTS: Five studies were included. The meta-analysis of proportion was 19% for tumor shrinkage (95% CI 8-38%, 4 studies, 108 participants), 50% for prevention of tumor progression (95% CI 35-64%, 5 studies, 187 participants), 14% for clinically required additional interventions (95% CI 6-30%, 4 studies, 128 participants) and 2% for adverse events (95% CI 1-6%, 3 studies, 157 participants). CONCLUSIONS: Effect of CBG to promote tumor shrinkage in NFPAs was low, while prevention of tumor progression after surgery was seen in half of the cases, with a low frequency of adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020206778.
Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Adenoma/patologia , Cabergolina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológicoRESUMO
Prolactinomas are the most prevalent functional pituitary adenomas. They are usually treated clinically with dopamine agonists. The most widely used and suitable drug is cabergoline (CAB), a specific D2 dopamine agonists. Patients in prolactinoma treatment with CAB commonly report physical side effects, but aberrant behavioral changes such as increased impulsivity have also been reported recently. We report the case of a 47-year-old Brazilian woman with prolactinoma that developed compulsive buying, binge eating, and hypersexuality after four years of CAB treatment. In her psychiatric evaluation, the patient scored high levels on the following scales: Compulsive Buying Scale (CBS), Binge Eating Scale (BES), and Barratt Impulsiveness Scale-11 (BIS11). She also reported financial problems and weight gain in addition to her social and clinical problems. Impulsivity disorders may appear with the use of CAB and other dopamine agonists. We suggest that more observational studies with a large patient sample and specific regular psychiatric evaluations during treatment are necessary for patients in use of CAB, especially those treated for several years.
RESUMO
Introduction: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.
Assuntos
Adenoma , Neoplasias Hipofisárias , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/tratamento farmacológico , Adenoma/patologia , Cabergolina/uso terapêutico , Ergolinas/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Estudos RetrospectivosRESUMO
First-line treatment for Cushing´s disease is transsphenoidal surgery. But in cases of persistent or recurrent disease after surgery, contraindications to surgery, severe hypercortisolism control before surgery, or for patients waiting for radiotherapy effects, medical therapy may be indicated. Pituitary-directed agents include cabergoline and pasireotide. Both drugs present similar potential for biochemical control and pasireotide has additionally been proved to reduce tumor volume. Moreover, pasireotide was evaluated in high quality studies. In respect to safety, both drugs are well tolerated and safe, but special attention should be given for cardiac valve disease and psychiatric disorder for cabergoline, and hyperglycemia for pasireotide.
Assuntos
Cabergolina , Hipersecreção Hipofisária de ACTH , Somatostatina , Humanos , Cabergolina/uso terapêutico , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/patologia , Hipófise/patologia , Somatostatina/uso terapêuticoRESUMO
ABSTRACT Objective: It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Subjects and methods: Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results: Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusions: According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.
RESUMO
Objective: It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Methods: Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results: Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusion: According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.
RESUMO
OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of cabergoline to control hypersomatotropism (HST) and diabetes mellitus (DM) in cats. METHODS: This was a prospective cohort study. Twenty-three cats with HST and concurrent DM were enrolled. Cats received a dose of 10 µg/kg cabergoline q48h PO for 6 months. Serum insulin-like growth factor 1 (IGF-1) and fructosamine concentrations, insulin dose and Insulin Resistance Index (IRI) were measured at the time of diagnosis of HST and at the start of cabergoline treatment (t0), and 3 months (t1) and 6 months (t2) during cabergoline treatment. RESULTS: A decrease and normalization of serum IGF-1 concentration was observed in 35% and 26% of cats, respectively. Median IGF-1 (t0: 1350 ng/ml [range 832-1501]; t1: 1284 ng/ml [range 365-1501]; t2: 1240 ng/ml [range 263-1501]; P = 0.016) decreased significantly. Twelve cats underwent diagnostic imaging of the pituitary area. The median pituitary height at t0 of cats that experienced an IGF-1 reduction (n = 5/12) was significantly lower compared with those that did not experience an IGF-1 reduction (n = 7/12) (3.2 mm [range 3.1-3.7] vs 6 mm [range 3.5-9.5]; P = 0.011). Median fructosamine (t0: 628 µmol/l [range 400-963]; t1: 404 µmol/l [range 249-780]; t2: 400 µmol/l [range 260-815]; P <0.0001), insulin dose (t0: 1.3 IU/kg [range 0.5-4.6]; t0: 0.5 IU/kg [range 0-2.3]; t2: 0.4 IU/kg [range 0-2.1]; P <0.0001) and IRI (t0: 800 µmolIU/kgl [range 257-2700]; t1: 300 µmolIU/kgl [range 0-1498]; t2: 250 µmolIU/kgl [range 0-1498]; P <0.0001) decreased significantly during cabergoline treatment. Eight cats achieved diabetic remission between months 1 and 6 of cabergoline treatment (median time to achieve remission: 3 months [range 1-6]). Three cats experienced asymptomatic hypoglycemia. CONCLUSIONS AND RELEVANCE: Cabergoline was effective in normalizing IGF-1 concentration in 26% of cats. Cabergoline improved diabetes control and was associated with remission of DM in 35% of cases. Cabergoline could be a treatment option for cats with HST and DM, especially in those cases with a relatively small pituitary tumor.
Assuntos
Doenças do Gato , Diabetes Mellitus , Gatos , Animais , Cabergolina/uso terapêutico , Fator de Crescimento Insulin-Like I , Estudos Prospectivos , Diabetes Mellitus/veterinária , Insulina , Doenças do Gato/tratamento farmacológicoRESUMO
INTRODUCTION: Cabergoline is the treatment of choice for prolactinomas. However, 10-20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas. SUBJECTS AND METHODS: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26-61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38-386 ng/mL) under cabergoline treatment (2-7 mg/week) for at least 6 months (6-108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0-2.5 g v.o./day) was given according to patients' tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30-60 days) and long-term (120-180 days) metformin treatment. RESULTS: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30-60 days, and at 120-180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0-2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin. CONCLUSION: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.
Assuntos
Cabergolina/farmacologia , Agonistas de Dopamina/farmacologia , Hiperprolactinemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Síndrome Metabólica/tratamento farmacológico , Metformina/farmacologia , Prolactina/efeitos dos fármacos , Prolactinoma/tratamento farmacológico , Adulto , Cabergolina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Resistência a Medicamentos/fisiologia , Quimioterapia Combinada , Feminino , Humanos , Hiperprolactinemia/sangue , Hipoglicemiantes/administração & dosagem , Síndrome Metabólica/sangue , Metformina/administração & dosagem , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Prolactina/sangue , Prolactinoma/sangue , Estudos ProspectivosRESUMO
Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are the main pathological cause. Prolactinomas lead to signs and symptoms of hormone oversecretion, such as galactorrhea and hypogonadism, as well as symptoms of mass effect, including visual impairment, headaches and intracranial hypertension. Diagnosis involves prolactin measurement and sellar imaging, but several pitfalls are involved in this evaluation, which may difficult the proper management. Treatment is medical in the majority of cases, consisting of dopamine agonists, which present high response rates, with a very favorable safety profile. Major adverse effects that should be monitored consist of cardiac valvulopathy and impulse control disorders. Other treatment options include surgery and radiotherapy. Temozolomide may be used for aggressive or malignant carcinomas. Finally, pregnancy outcomes are similar to general population even when dopamine agonist treatment is maintained.
Assuntos
Neoplasias Hipofisárias , Prolactinoma , Antineoplásicos Alquilantes/uso terapêutico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Agonistas de Dopamina/uso terapêutico , Feminino , Galactorreia/etiologia , Humanos , Hiperprolactinemia/etiologia , Hipogonadismo/etiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/terapia , Gravidez , Prolactina/sangue , Prolactinoma/complicações , Prolactinoma/diagnóstico , Prolactinoma/epidemiologia , Prolactinoma/terapia , Sela Túrcica/diagnóstico por imagem , Temozolomida/uso terapêuticoRESUMO
CASE SUMMARY: A 7-year-old spayed female domestic shorthair cat weighing 5 kg was referred with polyuria, polydipsia, lethargy, abdominal distension and dermatologic abnormalities. Diabetes mellitus was diagnosed and treatment was started with a diet for diabetic cats and insulin glargine (1 IU q12h SC). Hyperadrenocorticism (HAC) was suspected and diagnosed based on clinical signs, increased urinary cortisol:creatinine ratio, lack of suppression on low-dose dexamethasone suppression test and abdominal ultrasonography demonstrating bilateral adrenal enlargement. Oral cabergoline (10 µg/kg every other day) was initiated. After the second administration of cabergoline, the cat suffered from clinical hypoglycemia and no longer required insulin. One month after insulin withdrawal, blood work and urine analysis results showed normoglycemia, a normal serum fructosamine concentration (244 µmol/l) and normal urine analysis without glycosuria. Diabetic remission persisted until its death 7 months later. In addition, cabergoline treatment was associated with improvement in clinical signs such as lethargy, seborrhea, alopecia and abdominal distension. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first reported case of the use of cabergoline in a cat with HAC, as well as the first reported case of diabetic remission in a cat with HAC after cabergoline treatment. Cabergoline could be an alternative treatment for diabetic cats with pituitary-dependent HAC. Further work should focus on different protocols with greater number of cases.
RESUMO
OBJECTIVE: The cyclicity (CIC) of cortisol spontaneously occurs in a minority of patients with Cushing syndrome (CS). When it arises, diagnostic and therapeutic approaches become more challenging. This study aimed to report a patient with Cushing disease (CD) who achieved normalization of cortisol and CIC pattern with pasireotide long-acting release (pasi/LAR). METHODS: A 43-year-old female patient related an 8-month history of CS. An 8-mm pituitary nodule depicted by magnetic resonance imaging, serum cortisol suppression of >50% after 8 mg of dexamethasone therapy, and the absence of other lesions were compatible with a CD diagnosis. The patient presented with a CIC pattern with 1 episode before and 17 episodes after an unsuccessful pituitary surgery. RESULTS: Medical treatment with cabergoline alone up to 3.5 mg/wk and a combined treatment with ketoconazole 400 mg/d did not improve CIC CS. Pasi/LAR was initiated at a dose of 20 mg/mo. A few days after the first dose, the patient experienced symptoms suggestive of adrenal insufficiency. The medication and dose were maintained for 24 months. During this period, there was a normalization of UFC levels and progressive clinical improvement. Additionally, new episodes of CIC were not observed. CONCLUSION: A CD patient with a challenging issue of CIC was reported. The condition was not controlled after pituitary surgery and by the combined treatment with cabergoline and ketoconazole, although hypercortisolism was abated by the continuous use of pasi/LAR. To our knowledge, this is the first report as regards the use of this medication to control CIC in a patient with CD.
RESUMO
WHAT IS KNOWN AND OBJECTIVE: Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. METHODS: Randomized clinical trials (RCT) were retrieved through PubMed, Web of Science and Scopus databases. The efficacy and safety of the drugs were compared, considering the following outcomes: prolactin (PRL) levels, number of patients with galactorrhoea, menstrual irregularities and adverse drug reactions. NMA was built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals. Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA) and Stochastic multicriteria acceptability analysis (SMAA). RESULTS AND DISCUSSION: Seventeen RCTs were included in the systematic review and fifteen in the meta-analyses. The drugs had similar efficacy, considering the PRL levels. The SUCRA analysis showed that quinagolide (0.075 and 0.05 mg/day) was superior for reducing irregular menstruation, whereas bromocriptine was the best (97%) for galactorrhoea. Cabergoline proved to be the safest drug, except for abdominal pain at a dose of 1 mg/week. The SMAA demonstrated similar results to SUCRA. WHAT IS NEW AND CONCLUSION: This is the first network meta-analysis that evaluated the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. The results of this review revealed that these drugs have similar efficacy, but cabergoline has a better safety profile.