RESUMO
Not required for Clinical Vignette.
Assuntos
Síndrome de ACTH Ectópico , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/etiologia , Hormônio Adrenocorticotrópico , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Hipófise/metabolismoRESUMO
Not required for a Clinical Vignette.
Assuntos
Tumores Neuroendócrinos , Apoplexia Hipofisária , Neoplasias Hipofisárias , Humanos , Apoplexia Hipofisária/complicações , Apoplexia Hipofisária/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/diagnóstico por imagemRESUMO
Not required for Clinical Vignette.
Assuntos
Neoplasias , Hipersecreção Hipofisária de ACTH , Humanos , Corticotrofos , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , ImidazóisRESUMO
Endogenous Cushing's syndrome (CS) is associated with increased morbidity and mortality. Early diagnosis and initiation of therapy are essential, but effective treatment remains a challenge. In a long-term follow-up, biochemical control of hypercortisolemia, especially when severe, is difficult to achieve. Life-threatening hypercortisolemia is difficult to control due to the limitations of pharmacotherapy, including its side effects, and may require etomidate infusion in the intensive care unit (ICU) to rapidly lower cortisol levels. The effectiveness of hypercortisolemia management can be increased by a dual blockade of cortisol production. We report the efficacy, safety, and tolerability of combined therapy with two steroidogenesis inhibitors, etomidate, and osilodrostat, in a 32-year-old woman diagnosed with severe ACTH-dependent hypercortisolemia, subsequently maintaining a stable level of cortisol with osilodrostat monotherapy. This approach enabled achievement of relatively rapid control of the hypercortisolemia while using an etomidate infusion and concomitant increasing doses of oral osilodrostat applying a "titrations strategy." Our experience shows that it is worth taking advantage of the synergistic anticortisolic action of etomidate with osilodrostat.
Assuntos
Síndrome de Cushing , Etomidato , Feminino , Humanos , Adulto , Síndrome de Cushing/induzido quimicamente , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/tratamento farmacológico , Etomidato/efeitos adversos , Hidrocortisona/uso terapêutico , Imidazóis/uso terapêuticoRESUMO
Objective: The aim of the study was to evaluate glucose metabolism, as measured by glycated hemoglobin (HbA1c) levels and the need for antidiabetic medical treatment, in patients with acromegaly resistant to first-generation somatostatin receptors ligands (SRLs) treated with pasireotide long-acting release (LAR) in real-world clinical practice. Biochemical control of acromegaly, as measured by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, was also assessed. Study Design: Two-center retrospective cohort of consecutive patients with acromegaly treated with first-generation SRLs at maximum doses, who had not achieved biochemical disease control. After SRLs were discontinued, patients were given pasireotide LAR 40 mg i.m. every 28 days. The dose was increased to 60 mg i.m. in patients for whom adequate control was not achieved after 3 months. Patients were given dietary and lifestyle advice, and antihyperglycemic treatment was modified as needed. Main Outcome Measures: Biochemical disease control parameters (GH and IGF-1 concentration), as well as HbA1c level at baseline and after 6 months. Results: In total, 39 patients with acromegaly were enrolled. GH concentration decreased (Δme =-1.56 µg/L, range -21.38-3.62, p <0.001) during 6 months of pasireotide LAR treatment. A worsening of metabolic status was observed, with an increase of median HbA1c (Δme =0.40%, range -0.20%-2.30%, p <0.001), and antihyperglycemic treatment intensification in 23 (59.0%) patients. The median decline in IGF-1 concentration was: -283.0 µg/L, range -682.7-171.6, p <0.001. IGF-1 reached the age- and gender-specific upper level of normal in 23 (59%) patients. Conclusions: Pasireotide LAR is an effective therapeutic option in patients with acromegaly refractory to first-generation SRLs. However, this therapy may result in pasireotide LAR-associated hyperglycemia, which requires early and aggressive antidiabetic medical therapy to prevent glucose homeostasis alterations.
Assuntos
Acromegalia/tratamento farmacológico , Preparações de Ação Retardada/farmacologia , Glucose/metabolismo , Somatostatina/análogos & derivados , Acromegalia/metabolismo , Adulto , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Hormônio do Crescimento/sangue , Humanos , Hipoglicemiantes/farmacologia , Fator de Crescimento Insulin-Like I/biossíntese , Estilo de Vida , Ligantes , Masculino , Pessoa de Meia-Idade , Receptores de Somatostatina/metabolismo , Estudos Retrospectivos , Somatostatina/farmacologia , Resultado do TratamentoRESUMO
INTRODUCTION: Transsphenoidal surgery is the treatment of choice in Cushing's disease (CD), although even late recurrences occur in some patients. Low expression of O-6-methylguanine-DNA methyltransferase (MGMT) has been linked to a high risk of relapse in pituitary tumours, but the evidence for corticotroph adenomas is limited. Therefore, we investigated whether MGMT expression was associated with CD remission or clinicopathological markers of tumour aggressiveness among patients with corticotroph adenomas. MATERIAL AND METHODS: We included 72 consecutive patients (83% female, mean age ±SD: 44.15 ±15.15 years) with CD, who underwent transsphenoidal adenomectomy between 2012 and 2018. The invasiveness of corticotroph tumours was assessed based on the Knosp scale. Immunohistochemistry was used to analyse MGMT expression as well as the proliferation markers (Ki-67, p53, mitotic index). Electron microscopy was used to categorise tumours into densely or sparsely granulated. Early biochemical remission was evaluated in all patients 6 months after pituitary surgery. RESULTS: Early remission was observed in 47 (65%) patients 6 months after surgery. MGMT expression was > 75% in half of all tumours, < 25% in 14 tumours, and 25-50% or 50-75% in 11 tumours. Lower MGMT expression was associated with a larger tumour diameter (p = 0.001), higher adrenocorticotropic hormone (ACTH) concentration (p = 0.002), higher p53 expression (p = 0.026), and higher frequency of sparsely granulated corticotroph adenomas (p = 0.009). Low MGMT expression was significantly related to lower frequency of early clinical remission (p = 0.005). CONCLUSIONS: MGMT predicted the outcomes of transsphenoidal surgery for CD. Pituitary corticotroph adenomas with low MGMT expression may be associated with increased invasiveness and poorer prognosis.