Thierry Brue

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (230)699.69 Total impact

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    ABSTRACT: Outcomes of congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21OHD) have been widely studied in children and women but less in men. To analyze data from a network of metropolitan French teaching hospitals on the clinical outcome of classic 21OHD in a large sample of CAH/21OHD genotyped adult men, and particularly the impact of 21OHD on the gonadotrope axis, testicular function and fertility. From April 2011 to June 2014, tertiary endocrinology departments provided data for 219 men with 21OHD (18-70 y; 73.6% salt wasters (SW) and 26.4% simple virilizers (SV)). Testicular sonography was performed in 164 men and sperm analysis in 71 men. Mean final height was 7.8 cm lower than in a reference population. Obesity was more common and mean blood pressure was lower than in the reference population. None of the patients was diabetic and lipid status was generally normal. Blood electrolyte status was normal in the vast majority of men, despite markedly elevated ACTH and renin levels. Serum progesterone (PROG), 17OHPROG and androstenedione levels were above-normal in the vast majority of cases. Hormonal profiling variously showed a normal gonadotrope-testicular axis, gonadotropin deficiency, or primary testicular insufficiency. Testicular sonography revealed adrenal rest tumors (TARTs) in 34% of 164 men. Serum inhibin B and FSH levels were respectively significantly lower and higher in patients with TARTs. Severe oligospermia or azoospermia was found in 42% of patients, and was significantly more prevalent in men with TARTs (70%) than in men with normal testes (3.6%;p<0.0001). Among men living with female partners, TARTs were significantly more prevalent in those who had not fathered children. We report the spectrum of testicular/gonadotrope axis impairment in the largest cohort of 21OHD men studied to date. Our results suggest that French men with 21OHD managed in specialized centers frequently have impaired exocrine testicular function but that its reproductive implications are often overlooked.
    The Journal of Clinical Endocrinology and Metabolism 03/2015; DOI:10.1210/jc.2014-4124 · 6.31 Impact Factor
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    ABSTRACT: Predicting the outcome of patients operated on for Cushing's disease (CD) is a challenging task. Our objective was to assess the accuracy of immediate post-surgical plasma cortisol, desmopressin test and the coupled dexamethasone desmopressin test (CDDT) as predictors of outcome. Sixty-seven patients with initial remission and a minimal post-surgical follow-up greater than 18 months were included in this retrospective bicenter study. Follow-up included 3-6 months followed by yearly 24-h urinary free cortisol, ACTH and cortisol plasmatic levels, a 1 mg overnight dexamethasone suppression test (1 mg DST), desmopressin test and the CDDT. ROC curves were performed to define the optimal threshold of immediate post-surgical cortisol level, and 3-6 month desmopressin test and CDDT, as predictors of final outcome in comparison with classical biological markers of recurrence. Eleven patients presented recurrence. The patient's median follow-up was 52 months (range, 18-180). As early predictors of outcome, immediate post-surgical plasma cortisol level < 35 nmol/l predicted the lack of recurrence with 93% negative predictive value (NPV), whereas predictive positive value (PPV) was 25%. During the follow-up, the CDDT was more precise than the desmopressin test in predicting the lack of recurrence (100% NPV) when performed in the first 3 years after surgery. Positivity of the CDDT was defined based on ROC curves by ACTH and cortisol increments > 50%. The CDDT was highly reproducible, as the same response was observed every year in 91% of the patients. Adding the CDDT the first 3 years after surgery to immediate post-surgical cortisol evaluation should allow obtaining an optimal follow-up management of patients operated for Cushing's disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 02/2015; DOI:10.1111/cen.12739 · 3.35 Impact Factor
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    ABSTRACT: Patients suffering from adrenal insufficiency, whether primary (PAI) or secondary (SAI) have an increased mortality risk and increased morbidity. There are no guidelines on hydrocortisone replacement therapy and little is known on patients’ management in current practice. We described patients’ profiles and treatment in a tertiary referral centre.
    Annales d Endocrinologie 01/2015; 76(1). DOI:10.1016/j.ando.2014.11.004 · 0.66 Impact Factor
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    ABSTRACT: Objective: A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's disease - including different remission and recurrence criteria, for which there is no consensus. Therefore, a comparative analysis of the best treatment options and patient management strategies is difficult. In this review, we investigated the clinical outcomes of initial TSS in patients with Cushing's disease based on definitions of and assessments for remission and recurrence. Methods: We systematically searched PubMed and identified 44 studies with clear definitions of remission and recurrence. When data were available, additional analyses by time of remission, tumour size, duration of follow-up, surgical experience, year of study publication, and adverse events related to surgery were performed. Results: Of the 44 articles selected, only one reported endoscopic TSS. Data from a total of 6,400 patients who received microscopic TSS were extracted and analysed. A variety of definitions of remission and recurrence of Cushing's disease after initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%; median, 77.9%) and recurrence (3.1-47.4%; median, 11.5%). Better remission and recurrence outcomes were achieved for micro- versus macroadenomas; however, no correlations were found with other parameters, other than improved safety with longer surgical experience. Conclusions: The variety of methodologies used in clinical evaluation of TSS for Cushing's disease strongly support the call for standardization and optimization of studies to inform clinical practice and maximize patient outcomes. Clinically significant rates of failure of initial TSS highlight the need for effective second-line treatments.
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    ABSTRACT: Context: Responses of GH-secreting adenomas to multimodal management of acromegaly varies widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying predictive factors of their evolution is a research priority. Objective: To clarify the relationship between adenoma T2-weighted signal on diagnostic MRI in acromegaly and clinical and biological features at diagnosis. Design: International, multicenter, retrospective analysis. Setting: 10 endocrine tertiary referral centers. Patients: 297 acromegalic recently diagnosed patients with available diagnostic MRI evaluations were included in the study. Main outcome measure: Clinical, biochemical characteristics and MRI signal findings. Results: T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyper- and isointense counterparts (p<0.0001), were associated with higher IGF1 levels (p=0.0001), invaded the cavernous sinus less frequently (p=0.0002) and rarely caused optic chiasm compression (p<0.0001). Acromegalic men tended to be younger at diagnosis than women (p=0.067) and presented higher IGF1 values (p=0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (p<0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (p=0.0067). Most adenomas (45.1%) measured between 11-20mm in maximal diameter and bigger adenomas were diagnosed at younger ages (p=0.0001). Conclusions: T2-weighted signal differentiates GH-secreting adenomas into subgroups with particular behaviors. This raises the question of whether T2-weighted signal could represent a factor in the classification of acromegalic patients in future studies.
    Endocrine Related Cancer 01/2015; 22(2). DOI:10.1530/ERC-14-0305 · 4.91 Impact Factor
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    ABSTRACT: BackgroundDAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. NFKB2 mutations have recently been identified in patients with ACTH and variable immunodeficiency. A similar mutation was previously found in Nfkb2 in the immunodeficient Lym1 mouse strain, but the effect of the mutation on endocrine function was not evaluated.Methods We ascertained six unrelated DAVID syndrome families. We performed whole exome and traditional Sanger sequencing to search for causal genes. Lym1 mice were propagated and examined for endocrine developmental anomalies.ResultsMutations in the NFKB2 gene were identified in three of our families through whole exome sequencing, and in a fourth by direct Sanger sequencing. De novo origin of the mutations could be demonstrated in three of the families. All mutations lie near the C-terminus of the protein-coding region, near signals required for processing of NF¿B2 protein by the alternative pathway. Two of the probands had anatomical pituitary anomalies, and one had growth and thyroid hormone as well as ACTH deficiency; these findings have not been previously reported. Two children of one of the probands carried the mutation and have to date exhibited only an immune phenotype. No mutations were found near the C-terminus of NFKB2 in the remaining two probands; whole exome sequencing has been performed for one of these. Lym1 mice, carrying a similar Nfkb2 C-terminal mutation, showed normal pituitary anatomy and expression of proopiomelanocortin (POMC).Conclusions We confirm previous findings that mutations near the C-terminus of NFKB2 cause combined endocrine and immunodeficiencies. De novo status of the mutations was confirmed in all cases for which both parents were available. The mutations are consistent with a dominant gain-of-function effect, generating an unprocessed NFKB2 super-repressor protein. We expand the potential phenotype of such NFKB2 mutations to include additional pituitary hormone deficiencies as well as anatomical pituitary anomalies. The lack of an observable endocrine phenotype in Lym1 mice suggests that the endocrine component of DAVID syndrome is either not due to a direct role of NFKB pathways on pituitary development, or else that human and mouse pituitary development differ in its requirements for NFKB pathway function.
    BMC Medical Genetics 12/2014; 15(1):139. DOI:10.1186/s12881-014-0139-9 · 2.45 Impact Factor
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    ABSTRACT: Objective: Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen-4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up. Design and patients: Fifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone hospital, Marseille. Methods: Symptoms, pituitary function, and pituitary imaging at diagnosis of hypophysitis and during the follow-up were recorded. Results: 15 of 131 patients treated with ipilimumab (10 mg/kg in 11/15) or a placebo presented with hypophysitis (≥11.5%) at 9.5 ± 5.9 weeks (mean ± SD) after treatment start, occurring in 66% after the third infusion. Main initial symptoms were headache (n=13) and asthenia (n=11). All patients but one had at least one hormonal defect: thyrotroph (n=13), gonadotroph (n=12), or corticotroph (n=11) deficiencies. None had diabetes insipidus. Pituitary imaging showed a moderately enlarged gland in 12 patients. Clinical symptoms improved rapidly on high-dose glucocorticoids (n=11) or physiological replacement doses (n=4). At the end of follow-up (median 33.6 months, range 7-53.5), corticotroph deficiency remained in 13 patients, 11 recovered thyrotroph and 10 gonadotroph functions. Pituitary imaging remained abnormal in 11 patients. Conclusion: Ipilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis. Usually, hormonal deficiencies improved, except for corticotroph function. Patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at risk of adrenal insufficiency in the long-term.
    European Journal of Endocrinology 11/2014; 172(2). DOI:10.1530/EJE-14-0845 · 3.69 Impact Factor
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    ABSTRACT: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) raise difficult therapeutic problems despite the emergence of targeted therapies. Somatostatin analogues (SSA) remain pivotal therapeutic drugs. However, the tachyphylaxis and the limited antitumoral effects observed under the classical sst2 agonists (octreotide, lanreotide) led to the development of new SSA, such as the pan somatostatin receptor (sst) agonist pasireotide. Our aim was to compare pasireotide and octreotide effects on cell survival, chromogranin A (CgA) secretion, and sst2 phosphorylation/trafficking in pNET primary cells from 15 tumors. We established and characterized primary cultures of human pancreatic tumors (pNETs) as powerful preclinical models to understand the biological impacts of SSA. At clinically relevant concentrations (1-10 nM), pasireotide was at least as efficient as octreotide in inhibiting CgA secretion and cell viability through caspase-dependent apoptosis during short treatments, whatever the expression levels of the different sst receptors or the WHO grade of the parental tumor. Interestingly, contrary to octreotide, which induces a rapid and persistent partial internalization of sst2 associated to its phosphorylation on Ser341-343, pasireotide did not phosphorylate sst2 and induced a rapid and transient internalization of the receptor followed by a persistent recycling at the cell surface. These results provide the first evidence of striking differences in the dynamics of sst2 trafficking in pNET cells under the two SSA but similar efficiency in the control of CgA secretion and cell viability.
    Endocrine Related Cancer 10/2014; 21(5):691-704. DOI:10.1530/ERC-14-0086 · 4.91 Impact Factor
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    ABSTRACT: Context: The ghrelin receptor GHS-R1a, is highly expressed in human somatotroph adenomas and exhibits unusual high basal signaling activity. In humans, the suppression of this constitutive activity by mutation induces a short stature. Objective: Using a GHS-R1a inverse agonist, MSP, we explored the role of GHS-R1a constitutive activity in GH hypersecretion from somatotroph adenomas and as putative therapeutic target. Design: The effects of MSP were assessed on GH secretion from 19 human somatotroph tumors in vitro. Moreover, these effects were compared with those of octreotide (sst2 agonist) and with the combination of both drugs. Expression and localization of GHS-R1a and sst2 were studied. Results: For all tumors, MSP inhibited GH secretion in a dose dependent manner, from 13 to 64%. Moreover, MSP enhanced octreotide-induced GH inhibition. For 5 tumors, the effects of combined MSP + octreotide treatment were significantly higher than the sum of effects of each drug alone. MSP increased the membrane localization of GHS-R1a and of microdomains colocalizing sst2-GHS-R1a, highlighting the cooperation between the two drugs. Conclusions: The GHS-R1a inverse agonist could open new therapeutic options for acromegalic patients, particularly patients partially sensitive to octreotide whose GH secretion is not completely controlled by the sst2 agonist.
    Journal of Clinical Endocrinology &amp Metabolism 10/2014; DOI:10.1210/jc.2014-2753 · 6.31 Impact Factor
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    ABSTRACT: Objectif L’objectif de cette étude était d’évaluer la pertinence du test couplé déxaméthasone desmopressine (TCDD) comme facteur prédictif de récidive de maladie de Cushing après chirurgie trans-sphénoïdale. Matériel et méthodes Nous avons rétrospectivement étudié 67 patients dans deux centres tertiaires (Marseille et Grenoble), en rémission initiale après chirurgie transsphénoïdale et suivis au moins 18 mois. Nous avons évalué à 3 mois puis annuellement le cortisol libre urinaire sur 24 h, les taux d’ACTH et de cortisol plasmatiques, la réponse aux tests de freinage minute et à la desmopressine et le TCDD. Après TCDD, un ratio d’ACTH (ACTHr) et de cortisol (cortisolr) étaient déterminés par la formule (pic – valeur basale)/valeur basale. Résultats Onze patients avaient récidivé après un suivi médian de 52 mois (18–180). L’association ACTHr et cortisole supérieur ou égal à 0,5 était présente chez tous les patients ayant récidivé et chez 14/56 patients en rémission (sensibilité = 100 %, spécificité = 75 %). La positivité du TCDD précédait de 6-76 mois les marqueurs classiques d’hypercorticisme chez 10/11 patients ayant récidivé. Six patients avaient récidivé malgré une cortisolémie à 8 h en postopératoire immédiat inférieur à 50 nmol/L : tous avaient un TCDD positif dans les 3 ans suivant la chirurgie. La réponse au TCDD était reproductible au cours des évaluations chez 91 % des patients. Conclusion Le TCDD est un facteur prédictif précoce et fiable de récidive de maladie de Cushing et a un intérêt majeur dans les 3 ans postopératoire pour optimiser la surveillance à long terme.
    Annales d Endocrinologie 10/2014; 75(s 5–6):264. DOI:10.1016/j.ando.2014.07.049 · 0.66 Impact Factor
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    ABSTRACT: Background Many patients with acromegaly do not achieve biochemical control despite receiving high doses of the first-generation somatostatin analogues octreotide or lanreotide. In the PAOLA trial, we aimed to assess the efficacy and safety of two different doses of the somatostatin analogue pasireotide long-acting release compared with active control (octreotide or lanreotide) in patients with inadequately controlled acromegaly. Methods In a multicentre, randomised, phase 3 trial, we enrolled eligible patients aged 18 years or older with acromegaly who were inadequately controlled (5-point, 2 h mean growth hormone concentration >2·5 μg/L and insulin-like growth factor 1 [IGF-1] concentration >1·3 times the upper normal limit) and had received 30 mg octreotide long-acting repeatable or 120 mg lanreotide (Somatuline Autogel; Ipsen, UK) as monotherapy for 6 months or longer. We randomly assigned patients in a 1:1:1 ratio with an interactive voice-web response system to receive 40 mg pasireotide long-acting release once every 28 days for 24 weeks, 60 mg pasireotide long-acting release once every 28 days for 24 weeks, or continued treatment with octreotide or lanreotide (active control). Patients were stratified according to previous treatment (octreotide or lanreotide) and growth hormone concentrations at screening (2·5–10 μg/L and >10 μg/L). Patients and study investigators were not masked to study drug assignment but were masked to pasireotide dose allocation. The primary endpoint was number of patients achieving biochemical control, defined as mean growth hormone concentration less than 2·5 μg/L and normalised IGF-1 concentration. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01137682. Findings Between Dec 17, 2010, and Aug 6, 2012, 198 patients were enrolled and randomly assigned to pasireotide 40 mg (n=65), pasireotide 60 mg (n=65), or active control (n=68) groups. At 24 weeks, ten (15%) patients in the pasireotide 40 mg group and 13 (20%) patients in the pasireotide 60 mg group achieved biochemical control, compared with no patients in the active control group (absolute difference from control group 15·4%, 95% CI 7·6–26·5, p=0·0006 for pasireotide 40 mg group, 20·0%, 11·1–31·8, p<0·0001 for pasireotide 60 mg group). The most common adverse events were hyperglycaemia (21 [33%] for treatment with 40 mg pasireotide, 19 [31%] with 60 mg pasireotide, and nine [14%] with active control), diabetes (13 [21%], 16 [26%], and five [8%]), and diarrhoea (ten [16%], 12 [19%], and three [5%]); most were grade 1 or 2 in severity. Serious adverse events were reported in six (10%) patients in the pasireotide 40 mg group, two (3%) in the pasireotide 60 mg group, and three (5%) in the active control group. Interpretation Pasireotide provides superior efficacy compared with continued treatment with octreotide or lanreotide, and could become the new standard pituitary-directed treatment in patients with acromegaly who are inadequately controlled using first-generation somatostatin analogues. Funding Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.
    09/2014; DOI:10.1016/S2213-8587(14)70169-X
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    ABSTRACT: Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype-genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple pituitary deficiencies, the etiology of most (80-90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed pituitary deficiencies, differential diagnosis of a pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined pituitary hormone deficiencies, associated or not with extra-pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.
    Journal of endocrinological investigation 09/2014; DOI:10.1007/s40618-014-0141-2 · 1.55 Impact Factor
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    ABSTRACT: To describe the results of growth hormone (GH) therapy in adult GH-deficient patients treated in a tertiary referral center, with a focus on quality of life and adherence.
    Annales d Endocrinologie 07/2014; DOI:10.1016/j.ando.2014.05.002 · 0.66 Impact Factor
  • 04/2014; DOI:10.1530/endoabs.35.P905
  • 04/2014; DOI:10.1530/endoabs.35.OC5.1
  • 04/2014; DOI:10.1530/endoabs.35.P907
  • 04/2014; DOI:10.1530/endoabs.35.P875
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    ABSTRACT: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0·57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications. European Union, German Cancer Foundation, Arthur Blank Foundation, Italian Government, Charles University, Czech Ministry of Health, Nanjing Military Command, National Science Centre Poland, National Research Council for Scientific and Technological Development, and State of São Paulo Research Foundation.
    The Lancet Oncology 04/2014; DOI:10.1016/S1470-2045(14)70154-8 · 24.73 Impact Factor
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    ABSTRACT: Introduction:Focused parathyroidectomy is the treatment of choice for patients with concordant positive imaging. Bilateral cervical exploration is performed for cases with discordant imaging, yet more than 70% of those cases are the result of a single gland disease. As focused parathyroidectomy is generally costless and harmless, for cases with discordant imaging, we tried to determine whether pre-operative characteristics can lead to a diagnosis of single disease.Methods:This study included 182 patients treated for primary hyperparathyroidism by bilateral exploration from 2009 to 2012 at La Timone Hospital, Marseille, France. We classified the patients on preoperative images and pathological results (single or multiglandular disease). We then compared the demographical, laboratory and imaging results. We also asked a senior nuclear medicine practitioner who was blind to the ultrasound and pathological results to perform a second reading.Results:15.4% of patients had negative, 54.4% discordant, and 30.2% concordant imaging. After reviewing the scintigraphy results, 8% of the cases with discordant imaging would have been classified as concordant with ultrasound. Subtraction scintigraphy obtained better results than dual-phase scintigraphy (concordance with ultrasound in 50 vs 31% with classical scintigraphy). For the cases of discordant imaging, no predictive factors of single gland disease could be identified. Ultrasound and scintigraphy were similarly effective in determining the correct location of the abnormal gland.Conclusion:Discordant results of preoperative imaging modalities do not discriminate between uniglandular and multiglandular disease in hyperparathyroidism. Diagnostic differentiation between the different causes of hyperparathyroidism requires improvements in imaging techniques, and might benefit from subtraction scintigraphy.
    European Journal of Endocrinology 02/2014; DOI:10.1530/EJE-13-0796 · 3.69 Impact Factor

Publication Stats

4k Citations
699.69 Total Impact Points

Institutions

  • 2005–2015
    • Aix-Marseille Université
      • Faculté de Médecine
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France
  • 1996–2014
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2008–2012
    • Assistance Publique Hôpitaux de Marseille
      • Service de neurochirurgie infantile
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2001–2012
    • Institut de recherches cliniques de Montréal
      Montréal, Quebec, Canada
    • Harvard University
      Cambridge, Massachusetts, United States
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
  • 2007–2011
    • Centre Hospitalier Universitaire de Liège
      Luik, Walloon Region, Belgium
    • The Jikei University School of Medicine
      • Department of Pediatrics
      Tokyo, Tokyo-to, Japan
  • 2010
    • CHRU de Strasbourg
      Strasburg, Alsace, France
    • Institut de Recherche sur les Phénomènes Hors Equilibre
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2009
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
    • Université Paul Cézanne
      Aix, Provence-Alpes-Côte d'Azur, France
  • 2005–2008
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 1999–2007
    • University of Liège
      Luik, Walloon, Belgium
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
  • 2006
    • McGill University
      • Department of Medicine
      Montréal, Quebec, Canada
    • University of Naples Federico II
      Napoli, Campania, Italy
    • University of Chicago
      • Pritzker School of Medicine
      Chicago, Illinois, United States
  • 2004
    • University of Sousse
      Susa, Sūsah, Tunisia
  • 1992
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
    • Polytech Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Centre Hospitalier Universitaire de Nancy
      Nancy, Lorraine, France