RESUMO
BACKGROUND: Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on hereditary predisposition to prolactinoma. OBJECTIVE: We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinomas. MATERIALS AND METHODS: A retrospective study was performed combining genetic and clinical data from patients referred for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. SF3B1 was Sanger sequenced in genetically negative patients. RESULTS: About 506 patients with a prolactinoma were included: 80 with microprolactinoma (15.9%), 378 with macroprolactinoma (74.7%), 48 unknown; 49/506 in a familial context (9.7%). Among these, 14 (2.8%) had a (likely) pathogenic variant (LPV) in MEN1 or AIP, and none in CDKN1B. All positive patients had developed a macroprolactinoma before age 30. The prevalence of germline mutations in patients with isolated macroprolactinoma under 30 was 4% (11/258) in a sporadic context and 15% (3/20) in a familial context. Prevalence in sporadic cases younger than 18 was 15% in men (5/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 264 patients with macroprolactinomas. CONCLUSIONS: We did not identify any LPVs in patients over 30 years of age, either in a familial or in a sporadic context, and in a sporadic context in our series or the literature. Special attention should be paid to young patients and to familial context.
Assuntos
Neoplasias Hipofisárias , Prolactinoma , Masculino , Humanos , Feminino , Adulto , Prolactinoma/epidemiologia , Prolactinoma/genética , Prolactinoma/patologia , Estudos de Coortes , Estudos Retrospectivos , Testes Genéticos , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Mutação em Linhagem GerminativaRESUMO
In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging. However, despite active research, clinical relevance of these new parameters remains unclear, and further multicentric studies are needed in order to validate and increase widespread use and integration in clinical routine. Use of AI in PPGLs may detect changes in tumor phenotype that precede classical medical imaging biomarkers, such as shape, texture, and size. Since PPGLs are rare, slow-growing, and heterogeneous, multicentric collaboration will be necessary to have enough data in order to develop new PPGL biomarkers. In this nonsystematic review, our aim is to present an exhaustive pedagogical tool based on real-world cases, dedicated to physicians dealing with PPGLs, augmented by perspectives of artificial intelligence and big data.
RESUMO
Acromegaly is a rare disease with prevalence of approximately 60 cases per million, slight female predominance and peak onset in adults in the fourth decade. Clinical diagnosis is often delayed by several years due to the slowly progressive onset of symptoms. There are multiple clinical criteria that define acromegaly: dysmorphic syndrome of insidious onset, symptoms related to the pituitary tumor (headaches, visual disorders), general signs (sweating, carpal tunnel syndrome, joint pain, etc.), complications of the disease (musculoskeletal, cardiovascular, pneumological, dental, metabolic comorbidities, thyroid nodules, colonic polyps, etc.) or sometimes clinical signs of associated prolactin hypersecretion (erectile dysfunction in men or cycle disorder in women) or concomitant mass-induced hypopituitarism (fatigue and other symptoms related to pituitary hormone deficiencies). Biological confirmation is based initially on elevated IGF-I and lack of GH suppression on oral glucose tolerance test or an elevated mean GH on repeated measurements. In confirmed cases, imaging by pituitary MRI identifies the causal tumor, to best determine management. In a minority of cases, acromegaly can be linked to a genetic predisposition, especially when it occurs at a young age or in a familial context. The first-line treatment is most often surgical removal of the somatotroph pituitary tumor, either immediately or after transient medical treatment. Medical treatments are most often proposed in patients not controlled by surgical removal. Conformal or stereotactic radiotherapy may be discussed on a case-by-case basis, especially in case of drug inefficacy or poor tolerance. Acromegaly should be managed by a multidisciplinary team, preferably within an expert center such as a reference or skill center for rare pituitary diseases.
Assuntos
Acromegalia , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Masculino , Adulto , Humanos , Feminino , Acromegalia/diagnóstico , Acromegalia/etiologia , Acromegalia/terapia , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/metabolismo , Neoplasias Hipofisárias/cirurgia , Teste de Tolerância a Glucose , Protocolos ClínicosRESUMO
BACKGROUND: At metastatic stage, treatment of adrenocortical carcinoma (ACC) relies in first line on mitotane therapy, combination of mitotane with locoregional therapies or cisplatin-based chemotherapy according to initial presentation. In second line, ESMO-EURACAN recommendations favour enrolment of patients in clinical trials investigating experimental therapies. However, the benefit of this approach remains unknown. METHODS: The aim of our retrospective study was to analyse the inclusion and outcomes of all patients of the French cohort ENDOCAN-COMETE included in early clinical trials between 2009 and 2019. RESULTS: Of the 141 patients for whom a local or national multidisciplinary tumour board recommended, as first choice, to look for clinical trial, 27 patients (19%) were enroled in 30 early clinical trials. Median progression-free survival (PFS) was 3.02 months (95% confidence interval [95% CI]; 2.3-4.6) and median overall survival (OS) was 10.2 months (95% CI; 7.13-16.3) while the best response, evaluable in 28 of 30 trial participants according to RECIST 1.1 criteria, was partial response for 3 patients (11%) stable disease for 14 patients (50%) and progressive disease for 11 patients (39%), resulting in a disease control rate of 61%. Median growth modulation index (GMI) in our cohort was 1.32, with a significantly prolonged PFS in 52% of the patients compared to the previous line. The Royal Marsden Hospital (RMH) prognostic score was not associated with OS in this cohort. CONCLUSION: Our study suggests that patients with metastatic ACC benefit from inclusion in early clinical trials in second line. As recommended, if a clinical trial is available, it should be the first choice for suitable patients.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mitotano/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Recent reports have raised concerns about a potential risk of osteonecrosis associated with testosterone treatment (TT). The aim of this pharmacovigilance study was to assess the risk of reporting osteonecrosis associated with the use of TT compared with use of any other medication. METHODS: We performed a disproportionality analysis to investigate the risk of reporting osteonecrosis with TT using the WHO database VigiBase®. We estimated the reporting odds ratio (ROR) and 95% confidence interval (CI) of reporting osteonecrosis with use of TT vs all other drugs, and the adjusted ROR with use of TT vs use of drugs for benign prostatic hyperplasia (BPH). RESULTS: Among men at least 18 years of age between January 1, 2000, and December 31, 2019, we identified 3479 reports of osteonecrosis, 84 of which were associated with TT use, out of a total of 4,667,754 adverse event reports. Reports of osteonecrosis in TT users occurred with both transdermal and injectable forms, and the mean age at report was 55.4 years. TT use was associated with a greater risk of reporting osteonecrosis compared to all other drugs (ROR, 5.13; 95% CI, 4.13-6.37) and compared with use of drugs for BPH (ROR, 3.00; 95% CI, 2.08-4.30). Half of the osteonecrosis reports associated with TT indicated concomitant use of corticosteroids. CONCLUSION: TT was associated with a greater risk of reports of osteonecrosis compared to use of any other drug and use of drugs for BPH. This signal should be confirmed in complementary studies.
Assuntos
Osteonecrose , Hiperplasia Prostática , Masculino , Humanos , Pessoa de Meia-Idade , Farmacovigilância , Testosterona , Bases de Dados Factuais , Sistemas de Notificação de Reações Adversas a MedicamentosRESUMO
BACKGROUND: Surgery is the treatment of choice for pheochromocytoma. However, this surgery carries a risk of hemodynamic instability (HDI). The aim of this study was to report complications associated with this procedure, to identify risk factors for HDI during surgery, and its impact on postoperative outcomes. METHODS: The charts of all patients who underwent adrenalectomy for pheochromocytoma in two academic centers between 2006 and 2020 were retrospectively reviewed. The primary outcome was HDI defined by a systolic blood pressure >160 mmHg or a mean blood pressure <60 mmHg intraoperatively. The secondary outcomes of interest were the total duration of HDI, the occurrence of intraoperative arrhythmia, perioperative cardiovascular events, and postoperative complications. RESULTS: 205 patients were included. HDI occurred intraoperatively in 155 patients (75.6%) but only 6 (3.2%) experienced arrhythmia. Thirty-eight postoperative complications were reported (18.6%) but only nine were ≥3 according to Clavien-Dindo (4.4%). There were 10 postoperative cardiovascular events (5.7%). Patients with intraoperative HDI had higher rates of postoperative complications (21.3% vs 10%; P = .07), major postoperative complications (5.8% vs 0%; P = .12) and cardiovascular events (6.5% vs 0%; P = .12). Factors associated with intraoperative HDI in univariate analysis were age (OR = 8.14; P = .006), high blood pressure preoperatively (OR = 2.16; P = .04), tumor size (OR = 15.83; P = .0001), and urinary normetanephrine level (OR = 9.33; P = .04). DISCUSSION: In multidisciplinary centers, the overall morbidity of adrenalectomy for pheochromocytoma is low. HDI during adrenalectomy for pheochromocytoma is highly prevalent but rarely associated with major cardiovascular events. There might be a link between HDI and postoperative cardiovascular events.
Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Laparoscopia , Feocromocitoma , Humanos , Feocromocitoma/cirurgia , Adrenalectomia/efeitos adversos , Adrenalectomia/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/cirurgia , Pressão Sanguínea , Hipertensão/etiologia , Complicações Pós-Operatórias/etiologia , Arritmias Cardíacas/etiologia , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/cirurgia , Laparoscopia/métodosRESUMO
Cushing's syndrome is defined by prolonged exposure to glucocorticoids, leading to excess morbidity and mortality. Diagnosis of this rare pathology is difficult due to the low specificity of the clinical signs, the variable severity of the clinical presentation, and the difficulties of interpretation associated with the diagnostic methods. The present consensus paper by 38 experts of the French Society of Endocrinology and the French Society of Pediatric Endocrinology and Diabetology aimed firstly to detail the circumstances suggesting diagnosis and the biologic diagnosis tools and their interpretation for positive diagnosis and for etiologic diagnosis according to ACTH-independent and -dependent mechanisms. Secondly, situations making diagnosis complex (pregnancy, intense hypercortisolism, fluctuating Cushing's syndrome, pediatric forms and genetically determined forms) were detailed. Lastly, methods of surveillance and diagnosis of recurrence were dealt with in the final section.
Assuntos
Síndrome de Cushing , Endocrinologia , Criança , Consenso , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Feminino , Glucocorticoides , Humanos , GravidezRESUMO
BACKGROUND: GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome is caused by aberrant expression of the GIP receptor in adrenal lesions. The bilateral nature of this disease suggests germline genetic predisposition. We aimed to identify the genetic driver event responsible for GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. METHODS: We conducted a multicentre, retrospective, cohort study at endocrine hospitals and university hospitals in France, Canada, Italy, Greece, Belgium, and the Netherlands. We collected blood and adrenal samples from patients who had undergone unilateral or bilateral adrenalectomy for GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. Adrenal samples from patients with primary bilateral macronodular adrenal hyperplasia who had undergone an adrenalectomy for overt or mild Cushing's syndrome without evidence of food-dependent cortisol production and those with GIP-dependent unilateral adrenocortical adenomas were used as control groups. We performed whole genome, whole exome, and targeted next generation sequencing, and copy number analyses of blood and adrenal DNA from patients with familial or sporadic disease. We performed RNA sequencing on adrenal samples and functional analyses of the identified genetic defect in the human adrenocortical cell line H295R. FINDINGS: 17 patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome were studied. The median age of patients was 43·3 (95% CI 38·8-47·8) years and most patients (15 [88%]) were women. We identified germline heterozygous pathogenic or most likely pathogenic variants in the KDM1A gene in all 17 patients. We also identified a recurrent deletion in the short p arm of chromosome 1 harboring the KDM1A locus in adrenal lesions of these patients. None of the 29 patients in the control groups had KDM1A germline or somatic alterations. Concomitant genetic inactivation of both KDM1A alleles resulted in loss of KDM1A expression in adrenal lesions. Global gene expression analysis showed GIP receptor upregulation with a log2 fold change of 7·99 (95% CI 7·34-8·66; p=4·4 × 10-125), and differential regulation of several other G protein-coupled receptors in GIP-dependent primary bilateral macronodular hyperplasia samples compared with control samples. In vitro pharmacological inhibition and inactivation of KDM1A by CRISPR-Cas9 genome editing resulted in an increase of GIP receptor transcripts and protein in human adrenocortical H295R cells. INTERPRETATION: We propose that GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome results from a two-hit inactivation of KDM1A, consistent with the tumour suppressor gene model of tumorigenesis. Genetic testing and counselling should be offered to these patients and their relatives. FUNDING: Agence Nationale de la Recherche, Fondation du Grand défi Pierre Lavoie, and the French National Cancer Institute.
Assuntos
Síndrome de Cushing , Glândulas Suprarrenais/patologia , Adulto , Estudos de Coortes , Síndrome de Cushing/complicações , Feminino , Histona Desmetilases/metabolismo , Humanos , Hidrocortisona/metabolismo , Hiperplasia/complicações , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: Adrenal ganglioneuromas are rare, differentiated, neuroblastic tumors that originate from the peripheral sympathetic nervous system. Because of their rarity, information is limited, derived from small cases series. Our objective was to characterize this tumor and provide help for its management. METHODS: A retrospective multicenter analysis of adrenal ganglioneuromas from 20 French centers belonging to the COMETE network and one Belgian center. RESULTS: Among the 104 cases identified, 59.6% were women (n = 62/104), median age at diagnosis was 29 years, with 24 pediatric cases. 60.6% (n = 63/104) were incidentalomas. Ganglioneuromas were non-secreting tumors in 90.8% of cases (n = 89/98), whereas the preoperative hormonal evaluation was indeterminate for 9.2% of patients (n = 9/98). CT imaging, performed on 96 patients, revealed large tumors (median diameter of 50 mm) with a non-contrast density > 10 Hounsfield units in 98.1% (n = 52/53) and calcifications in 64.6% of cases (n = 31/48). Increased uptake on 123I-MIBG scintigraphy and 18F-FDG-PET/CT was observed in 26.7% (n = 8/30) and 42.2% (n = 19/45) of the tumors, respectively. All 104 patients underwent surgery. No recurrence was observed among the 42 patients who had an imaging follow-up (mean 29.6 months, median 18 months (4-156)). CONCLUSION: Adrenal ganglioneuromas are large tumors, mostly nonfunctioning, without benign imaging features. Although the duration of follow-up was limited in our series, no recurrence was identified. A review of the literature confirms the absence of postoperative recurrence. Based on all available data, in the absence of special circumstances (genetic form, uncertain histological diagnosis), long-term follow-up is not necessary after complete surgery for patients with an adrenal ganglioneuroma.
Assuntos
Neoplasias das Glândulas Suprarrenais , Ganglioneuroma , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/terapia , Adulto , Idade de Início , Idoso , Bélgica/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Redes Comunitárias , Feminino , Seguimentos , França/epidemiologia , Ganglioneuroma/diagnóstico , Ganglioneuroma/epidemiologia , Ganglioneuroma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
In 1953, for the first time, Paul Wermer described a family presenting endocrine gland neoplasms over several generations. The transmission was autosomal dominant and the penetrance was high. Forty years later in 1997, the multiple endocrine neoplasia type 1 (MEN1) gene was sequenced, thus enabling diagnosis and early optimal treatment. Patients carrying the MEN1 gene present endocrine but also non-endocrine tumors. Parathyroid, pancreatic and pituitary impairment are the three main types of endocrine involvement. The present article details therapeutic management of hyperparathyroidism, neuroendocrine pancreatic tumors and pituitary adenomas in patients carrying the MEN1 gene. Significant therapeutic progress has in fact been made in the last few years. As concerns the parathyroid glands, screening of family members and regular monitoring of affected subjects now raise the question of early management of parathyroid lesions and optimal timing of parathyroid surgery. As concerns the duodenum-pancreas, proton-pump inhibitors are able to control gastrin-secreting syndrome, reducing mortality in MEN1 patients. Mortality in MEN1 patients is no longer mainly secondary to uncontrolled hormonal secretion but to metastatic (mainly pancreatic) disease progression. Tumor risk requires regular monitoring of morphological assessment, leading to iterative pancreatic surgery in a large number of patients. Finally, pituitary adenomas in MEN1 patients are traditionally described as aggressive, invasive and resistant to medical treatment. However, regular pituitary screening showed them to be in fact infra-centimetric and non-secreting in the majority of patients. Consequently, it is necessary to regularly monitor MEN1 patients, with regular clinical, biological and morphological work-up. Several studies showed that this regular monitoring impairs quality of life. Building a relationship of trust between patients and care provider is therefore essential. It enables the patient to be referred for psychological or psychiatric care in difficult times, providing long-term support and preventing any breakdown in continuity of care.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/terapia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Gastrinoma/genética , Gastrinoma/terapia , Predisposição Genética para Doença , Humanos , Hiperparatireoidismo/genética , Hiperparatireoidismo/terapia , Insulinoma/genética , Insulinoma/terapia , Masculino , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Paratireoidectomia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/terapia , Neoplasias do Timo/genética , Neoplasias do Timo/terapiaRESUMO
CONTEXT: The behavior of locally advanced pheochromocytoma (LAP) remains unknown. OBJECTIVE: We characterized the population with LAP and recurrence-free survival (RFS). METHODS: This retrospective multicentric study was run within the ENDOCAN-COMETE network and French Group of Endocrine Tumors (GTE) from 2003 to 2018, including patients from 11 French referral centers with LAP as defined by capsular invasion, vascular invasion, adipose tissue invasion, and/or positive locoregional lymph nodes at diagnosis without evidence of distant metastasis. The main outcome measure was recurrence, defined as tumor reappearance, including local site and/or distant metastasis. The primary endpoint was RFS analysis; secondary endpoints were characterization, overall survival (OS), and prognostic factors of recurrence. RESULTS: Among 950 patients, 90 (9%) exhibited LAP criteria and 55 met inclusion criteria (median age, 53 years; 61% males; 14% with germline mutation; 84% with catecholamine excess). LAP was defined by 31 (56%) capsular invasions, 27 (49%) fat invasions, 6 (11%) positive lymph nodes, and 22 (40%) vascular invasions. After median follow-up of 54 months (range, 6-180), 12 patients (22%) had recurrences and 3 (5%) died of metastatic disease. Median RFS was 115 months (range, 6-168). Recurrences were local in 2 patients, distant in 2, and both local and distant in 8 patients. Median OS of patients was not reached. Size above 6.5 cm (P = 0.019) and Ki-67 > 2% (P = 0.028) were identified as independent significant prognostic factors in multivariate analysis. CONCLUSION: LAP represents 9% of pheochromocytoma's population and has a metastatic behavior. This study paves the way for future pathological TNM classification.
Assuntos
Neoplasias das Glândulas Suprarrenais/mortalidade , Recidiva Local de Neoplasia/mortalidade , Feocromocitoma/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Feocromocitoma/patologia , Prognóstico , Estudos RetrospectivosRESUMO
DESIGN: Hypercortisolism during pregnancy is a risk factor for prematurity. Long-term exposure to hypercortisolism may lead to permanent comorbidities, such as hypertension or diabetes, even after remission. Our aim was to determine whether women with a history of Cushing's disease (and being eu-, hypo- or hypercortisolic at the time of pregnancy) had the same risks of comorbidities, and especially prematurity, during pregnancy. METHODS: It was a retrospective multicentric study focusing on mothers with a history of Cushing's disease or diagnosed during pregnancy, followed in French tertiary referral centers. We compared the outcomes of pregnancies depending on the cortisolic status at the time of pregnancy. RESULTS: A total of 60 patients (78 pregnancies including 21 with hypercortisolism, 32 with hypocortisolism and 25 in eucortisolism in 25) were evaluated. The overall rate of preterm birth was 24.3%, with a peak in women diagnosed during pregnancy (62.5%), a high risk in hypercortisolic (33%) and hypocortisolic (19.3%), and a low risk (8%) in eucortisolic women Gestational diabetes and hypertension were observed in 21% and 10.4% of the whole cohort, with a higher risk in hypercortisolic women. Cesarean delivery was performed in 33.7% of the cohort. CONCLUSIONS: Being non-eucortisolic at the time of pregnancy increases the risk of prematurity and comorbidities compared to the general population. Women with a history of Cushing's disease should thus be carefully monitored during pregnancy. The high rate of cesarean delivery emphasizes the fact that these pregnancies should always be considered at risk.
Assuntos
Hipersecreção Hipofisária de ACTH/epidemiologia , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/etiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Few data are available on the risks of first-generation somatostatin receptor ligands (SRLs) during pregnancy in women treated for acromegaly. Current recommendations suggest the withdrawal of treatment at diagnosis of pregnancy. The aims of this literature review were to evaluate the teratogenic effects and the potential impact of SRLs on maternal and fetal outcomes by comparing acromegalic patients treated or not during pregnancy. PATIENTS AND METHODS: This study concerns 141 pregnancies in 127 women with acromegaly: 67 pregnancies in 62 women treated with SRLs during pregnancy and 74 pregnancies in 65 women not medically treated during pregnancy. A second analysis was then realized comparing women treated during 1st trimester only (36 pregnancies) and women treated longer (20 pregnancies). RESULTS: One malformation (ureteral stenosis) was reported in a newborn of a woman treated with SRL during pregnancy. No difference was found concerning maternal outcomes (gestational diabetes, hypertension, headaches, and delivery mode) and fetal outcomes (birth term, height, and weight). These results were also confirmed for the second analysis. CONCLUSIONS: This review of the literature did report one malformation without being able to prove a specific link with the first-generation SRL treatment. No significant impact on maternal and fetal outcomes is related to first-generation SRL treatment in women with acromegaly. The number of pregnancies is still low and more data are necessary to conclude on the total safety of this treatment during gestation. In the meantime, based on the nonthreatening data from this review of literature, SRL treatment can be continued and/or reintroduced during pregnancy if necessary (mainly for persistent headaches) in women with acromegaly.
Assuntos
Acromegalia , Diabetes Gestacional , Acromegalia/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Ligantes , Gravidez , Primeiro Trimestre da Gravidez , Receptores de SomatostatinaRESUMO
OBJECTIVE: Familial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss-of-function mutations of the calcium-sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1. DESIGN AND PATIENTS: This observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012. RESULTS: Hypercalcaemia was diagnosed at a median age of 53 years [IQR: 38-61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63-2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1-7.1], and the median 24-hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9-4.0]. Osteoporosis (dual X-ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established. CONCLUSION: This large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.
Assuntos
Hipercalcemia , Hiperparatireoidismo Primário , Adulto , Cálcio , Estudos de Coortes , Humanos , Hipercalcemia/congênito , Hipercalcemia/diagnóstico , Hipercalcemia/genética , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/genética , Pessoa de Meia-Idade , Receptores de Detecção de Cálcio/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare entity associated with a dismal prognosis. Usually, CR-TMA is associated with mucin-producing carcinomas among which stomach, breast, prostate, lung and pancreas tumours are the most frequent. CASES PRESENTATION: We describe for the first time three cases of CR-TMA due to adrenocortical carcinoma (ACC). All of them had mechanical hemolytic anemia and thrombocytopenia without any other identifiable cause. Bicytopenia was diagnosed either simultaneously with ACC or at the time of metastatic evolution. Two patients had acute kidney injury (AKI) with severe pathological findings on kidney biopsy. Despite total adrenalectomy, chemotherapy, and specific treatment of TMA with plasma-exchanges, renal failure and hemolytic anemia remained. The only manifestation of CR-TMA in the third patient was hemolytic anemia, which resolved after surgical removal of ACC. The evolutions in these patients suggests ACC-related TMA may be related to a circulating factor. CONCLUSIONS: CR-TMAs are rare. Here we describe the first case series of ACC-related TMA, among which two had renal involvement. This entity is associated with dismal renal prognosis despite specific treatment of TMA. According to patients' evolution, the persistence of TMA may reflect an uncontrolled malignancy.
Assuntos
Injúria Renal Aguda/etiologia , Neoplasias do Córtex Suprarrenal/complicações , Carcinoma Adrenocortical/complicações , Microangiopatias Trombóticas/etiologia , Injúria Renal Aguda/patologia , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/terapia , Adulto , Idoso de 80 Anos ou mais , Anemia Hemolítica/etiologia , Feminino , Humanos , Trombocitopenia/etiologia , Adulto JovemRESUMO
Following publication of the original article [1], we have been notified that the name of one author was spelled incorrectly as Julien Haddoux, when the correct spelling is Julien Hadoux.
RESUMO
INTRODUCTION: Excess catecholamine stimulates heat production in brown adipose tissue (BAT). Activation of BAT can be detected in patients presenting pheochromocytoma. CASE STUDY: A 58-year-old female patient sought medical advice due to 13 kg weight loss over 2 years accompanied by sweating and high blood pressure. Thoracic-abdominal-pelvic CT-scan revealed a solid 40 mm mass in the left adrenal compartment with peri-adrenal nodules and a solid 80 mm mass at the lower end of the right kidney. 18FDG-PET scan exhibited intense uptake in the supraclavicular, intercostal, mediastinal, peri-renal, mesenteric, iliac and inguinal spaces. Renal tumor with locoregional infiltration and remote metastases was initially considered. Diagnosis of pheochromocytoma was subsequently confirmed by a 10-fold increase in urinary catecholamine, metanephrine and normetanephrine levels. Left adrenalectomy confirmed the diagnosis of pheochromocytoma, with 3 lymph-node metastases in the adjacent adipose tissue surrounded by brown fat. The patient was clinically asymptomatic with normal blood pressure at 3 months post-surgery. A weight gain of 6 kg was recorded, with normalisation of catecholamines/metanephrine/normetanephrine levels. Bilateral peri-renal infiltration (including the right renal mass) disappeared on CT-scan, and TEP-18-FDG no longer showed hypermetabolism. Recurrent mediastinal metastases were diagnosed 6 months after surgery. CONCLUSION: Brown fat activation may mislead diagnosis of pheochromocytoma, suggesting multi-metastatic extra-adrenal tumor, if clinicians are not aware of it.
Assuntos
Tecido Adiposo Marrom/fisiologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Feocromocitoma/diagnóstico , Redução de Peso , Tecido Adiposo Marrom/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Adrenalectomia , Catecolaminas/urina , Feminino , Humanos , Hipertensão , Metástase Linfática/patologia , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Feocromocitoma/patologia , Feocromocitoma/fisiopatologia , Tomografia por Emissão de Pósitrons , Sudorese , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: The prevalence of gestational diabetes (GD) in women with acromegaly is rarely reported. The aims of this study were to evaluate the prevalence of GD in acromegalic women submitted to a systematic screening for GD and then to compare women with or without GD. PATIENTS AND METHODS: We studied 14 pregnancies in 11 women (34.0 ± 3.6 years) treated with somatostatin analogues after a pituitary surgery (n = 6) or as primary (n = 5) therapy, and treatment was discontinued at the time of pregnancy diagnosis for 13 pregnancies. One woman was diagnosed with acromegaly during pregnancy and was treated with octreotide LAR between 12 and 18 weeks of gestation. Before pregnancy, no women had diabetes mellitus, and GH/IGF-1 hypersecretion was uncontrolled in 6 women. RESULTS: Gestational diabetes was diagnosed during 7 pregnancies (50%) in 6 women (one woman had GD during her 2 pregnancies), according to fasting blood glucose (n = 5) or to an oral glucose tolerance test (n = 2). Before pregnancy, IGF-1 was not controlled in 4 GD+ and in 2 GD- women. Women with GD were not significantly older and had increased pregestational BMI (P = .02), with a more frequent family history of type 2 diabetes, no personal history of GD but of macrosomia for one patient. CONCLUSION: The prevalence of GD in our women is higher than that reported in the literature, probably resulting from the systematic GD screening and to the age of women. Therefore, routine screening of GD should be considered in women with acromegaly, particularly in those with risk factors for GD and with uncontrolled IGF-1 levels before pregnancy.
Assuntos
Acromegalia/diagnóstico , Diabetes Gestacional/diagnóstico , Acromegalia/sangue , Acromegalia/metabolismo , Adulto , Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Gravidez , Somatostatina/uso terapêuticoRESUMO
CONTEXT: While the only curative treatment for patients with endogenous hypoglycaemia related to inappropriate insulin or to insulin growth factor 2 (IGF2) secretion is surgery, medical treatment to normalize plasma glucose levels can be useful. OBJECTIVE: The aim of this prospective single centre study was to assess whether patients with endogenous hypoglycaemia, considered euglycaemic with medical treatments, experienced asymptomatic hypo- or hyperglycaemic excursions. PATIENTS AND METHODS: All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self-monitoring blood glucose in the normal range) were enroled and underwent a six-day continuous glucose monitoring (CGM) recording. RESULTS: Twenty-seven patients (inappropriate insulin secretion n = 25 and IGF2 secretion n = 2), treated with diazoxide (n = 16), somatostatin analogues (n = 7), glucocorticoids (n = 3) or a combination of these treatments (n = 1) were enroled. Twenty-five CGMs were analysed. CGM confirmed normoglycaemia in 11/25 patients (44%). Hypoglycaemias below 0.60 g/L were present in seven patients (28%) and were associated with hyperglycaemic excursions above 1.40 g/L in five patients. Seven patients (28%) had only hyperglycaemic excursions. Based on these results, treatment was modified in 14 patients (56%). CONCLUSION: Despite the disappearance of hypoglycaemia-related clinical symptoms and normalization of blood glucose self-monitoring data, 56% of the patients with endogenous hypoglycaemia treated with medical therapy experienced asymptomatic hypo- and/or hyperglycaemia. Continuous glucose monitoring could be a useful approach to reveal and prevent hypo- or hyperglycaemic excursions.