[Neuroendocrine neoplasms : a new era to the top of multidisciplinarity !] / Néoplasies neuroendocrines : une nouvelle ère a l'apogée de la multidisciplinarité !

Neuroendocrine neoplasms are histologically defined by a common neuroendocrine cellular phenotype. These are still considered as rare tumours even though their incidence is increasing. Heterogeneity is everywhere whether in the localization of the primitive cancer, the clinical presentation, the histological classification, the prognosis, as well as in therapeutic options, which clearly justifies specialized multidisciplinary care. Heterogeneity and scarcity explain the still fragmented nature of knowledge in this domain. Thanks to an increase in incidence, a desire for standardization of classification as well as the arrival of major therapeutic advances, such as vectorized internal radiotherapy, the future of neuroendocrine neoplasia seems more than promising and exciting. In our daily clinical practice at CHU Liège, we hope to bring our stone to the building by listing as many cases as possible in national and/or international databases, by centralizing therapeutic discussions within specific multidisciplinary concertations and by participating in multicenter study protocols.

Les néoplasies neuroendocrines sont définies histologiquement par un phénotype cellulaire neuroendocrine commun. Ces néoplasies sont toujours considérées comme des tumeurs rares, bien que leur incidence soit en constante augmentation. L'hétérogénéité est omniprésente, que ce soit dans la localisation du cancer primitif, la présentation clinique, la classification histologique, le pronostic ainsi que dans les diverses options thérapeutiques, justifiant impérativement une prise en charge pluridisciplinaire spécialisée. Cette hétérogénéité et cette rareté expliquent que les connaissances soient parcellaires. Grâce à une majoration d'incidence, une volonté d'uniformisation de classification ainsi que l'arrivée d'avancées thérapeutiques majeures, telles que la radiothérapie interne vectorisée, l'avenir des néoplasies neuroendocrines semble plus que prometteur et palpitant. En pratique clinique quotidienne au CHU de Liège, nous espérons apporter notre pierre à l'édifice en recensant un maximum de cas dans des bases de données nationales et/ou internationales, en centralisant les discussions thérapeutiques au sein de concertations multidisciplinaires dédiées et en participant à des protocoles d'études cliniques multicentriques.

[Chronic autoimmune gastritis : a multidisciplinary management]. / La gastrite chronique auto-immune : une prise en charge multidisciplinaire.

Chronic autoimmune gastritis (CAG) is a continuum of histological changes in gastric mucosa including: atrophy, intestinal metaplasia, dysplasia and finally, the occurrence of a neoplasm (gastric Neuroendocrine Tumors -NETs- and adenocarcinoma). The association with Hashimoto and Graves-Basedow disease is known as the thyrogastric autoimmune syndrome. While Helicobacter pylori (Hp) infection may be associated with CAG, the role of the gastric microbiota is ill-defined. The gastric hypochlorhydria determines a malabsorption of different micronutrients (iron, magnesium, calcium, vitamin B12) as well as drugs (thyroxine, etc.). Pernicious anemia is favoured by the deficit of parietal intrinsic factor that contributes to B12 malabsorption. Serology for Hp, serum pepsinogen I/II, increased gastrin levels, the presence of parietal cell antibodies and intrinsic factor antibodies may reveal CAG. High definition endoscopy associated with virtual chromoendoscopy seems promising for CAG diagnosis and follow-up. NETs type 1 treatment includes: endoscopic and surgical resection, somatostatin analogues and the recent availability of netazepide, a gastrin antagonist. We review herein advances in the treatment and diagnosis of CAG and associated autoimmune disorders, which may involve, in a multidisciplinary way, all practitioners.

La gastrite chronique auto-immune (GAI) est un continuum d'altérations de la muqueuse gastrique incluant : atrophie, métaplasie intestinale, dysplasie et, enfin, la survenue d'une néoplasie (tumeurs neuroendocrines [NETs] gastriques et adénocarcinome). L'association avec la maladie de Hashimoto et de Graves-Basedow est connue comme syndrome thyrogastrique auto-immun. Alors que l'Helicobacter pylori (Hp) peut s'associer avec la GAI, le rôle du microbiote gastrique est mal défini. L'hypochlorhydrie gastrique détermine une malabsorption de micronutriments (fer, magnésium, calcium, vitamine B12) et de médicaments (thyroxine et autres). L'anémie de Biermer est favorisée par le déficit de production du facteur intrinsèque pariétal, contribuant à la malabsorption de B12. Un rapport diminué de pepsinogène I/II, une augmentation de la gastrine, la présence d'anticorps anti-cellule pariétale, les anticorps anti-facteur intrinsèque et la sérologie pour Hp contribuent à révéler précocement le diagnostic de GAI. L'endoscopie haute définition, associée à la chromoendoscopie virtuelle, semble prometteuse dans le diagnostic et dans le suivi. Le traitement des NETs gastriques de type 1, favorisées par la GAI, inclut : la résection endoscopique/chirurgicale, les analogues de la somatostatine et l'antagoniste de la gastrine nétazépide. Nous résumons ici les avancées diagnostiques et thérapeutiques dans la GAI et dans les affections associées : elles impliquent, de façon multidisciplinaire, l'ensemble des praticiens.

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Cabergoline for Cushing's disease: a large retrospective multicenter study.

OBJECTIVE: The efficacy of cabergoline in Cushing's disease (CD) is controversial. The aim of this study was to assess the efficacy and tolerability of cabergoline in a large contemporary cohort of patients with CD. DESIGN: We conducted a retrospective multicenter study from thirteen French and Belgian university hospitals. METHODS: Sixty-two patients with CD received cabergoline monotherapy or add-on therapy. Symptom score, biological markers of hypercortisolism and adverse effects were recorded. RESULTS: Twenty-one (40%) of 53 patients who received cabergoline monotherapy had normal urinary free cortisol (UFC) values within 12 months (complete responders), and five of these patients developed corticotropic insufficiency. The fall in UFC was associated with significant reductions in midnight cortisol and plasma ACTH, and with clinical improvement. Compared to other patients, complete responders had similar median baseline UFC (2.0 vs 2.5xULN) and plasma prolactin concentrations but received lower doses of cabergoline (1.5 vs 3.5 mg/week, P < 0.05). During long-term treatment (>12 months), cabergoline was withdrawn in 28% of complete responders because of treatment escape or intolerance. Overall, sustained control of hypercortisolism was obtained in 23% of patients for 32.5 months (19-105). Nine patients on steroidogenesis inhibitors received cabergoline add-on therapy for 19 months (1-240). Hypercortisolism was controlled in 56% of these patients during the first year of treatment with cabergoline at 1.0 mg/week (0.5-3.5). CONCLUSIONS: About 20-25% of CD patients are good responders to cabergoline therapy allowing long-term control of hypercortisolism at relatively low dosages and with acceptable tolerability. No single parameter, including the baseline UFC and prolactin levels, predicted the response to cabergoline.

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study.

BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

[Thyroid cancers: from epidemiology to molecular biology]. / Les cancers de la thyroïde: de l'épidémiologie à la biologie moléculaire.

Experts increasingly recognize the hypothesis of "over-diagnosis" as the main factor of the raising incidence of thyroid cancers (TC). The detection of multiple microtumors, mainly of a papillary type, at a sub-clinical stage, with the use of sensitive detection methods supports this hypothesis. However, the intensive management and monitoring of these cancers failed to reduce mortality. Environmental and other risk factors cannot provide a sufficient explanation, as previously thought. In this context, the use of improved tools is needed, and the most promising perspective lies in molecular biology applied to thyroid cancer for diagnosis, evaluation of prognosis and treatment. The next generation sequencing (NGS) has demonstrated its diagnostic performances in recent clinical trials. Its interest in cases with indeterminate cytology is demonstrated and should help better targeting surgical indications. Its promising prognostic and therapeutic applications must be confirmed by additional studies. The integration of NGS in current practice should have a real medical, economic and scientific impact. Indeed, the exponential increase in our knowledge of molecular mechanisms of thyroid tumorigenesis strengthens the will to "reclassify" these cancers into molecular rather than histological subtypes, in order to offer patients more specific and targeted treatment.

[Current update on hypophysitis]. / Quoi de neuf dans les hypophysites?

Hypophysitis is a rare disorder. As clinical manifestations and radiologic signs are non specific, the diagnosis is difficult. Pathogenesis of hypophysitis remains largely unknown but new histological and etiological variants have been recently reported. Primary hypophysitis is the main form. For the first time, hypophysitis in ANCA-associated vasculitides has been reported. An entity of IgG4 related plasmatic hypophysitis has been described and well-defined diagnostic criteria have been proposed. Monoclonal antibodies directed against the cytotoxic T-lymphocyte antigen-4 (CTLA-4), investigated in metastatic cancer, can induce hypophysitis. Several candidate pituitary auto-antigens have been described in the last decade, although none has proven to be useful as a diagnostic tool.

MRI measurement of liver fat content predicts the metabolic syndrome.

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk.

[Hypophysitis: increasingly complex clinicopathological spectrum!]. / Hypophysite: un spectre étiologique de plus en plus large!

Hypophysitis is a chronic inflammation of the pituitary gland that comprises an increasingly complex clinicopathological spectrum. Lymphocytic and granulomatous hypophysitis are the most common forms, but new variants have recently been reported such as IgG4-related hypophysitis that is identified by well-defined criteria. For the first time, hypophysitis in ANCA-associated vasculitides has been reported. Monoclonal antibodies directed against the cytotoxic T-lymphocyte antigen-4 (CTLA-4), investigated in metastatic melanoma, can induce hypophysitis. Hypophysitis's pathogenesis remains obscure but several candidate pituitary autoantigens have been described in the last decade, although none has proven useful as a diagnostic tool.

Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database.

OBJECTIVE: Limited data regarding adrenal involvement in multiple endocrine neoplasia type 1 (MEN1) is available. We describe the characteristics of MEN1-associated adrenal lesions in a large cohort to provide a rationale for their management. METHODS: Analysis of records from 715 MEN1 patients from a multicentre database between 1956 and 2008. Adrenal lesions were compared with those from a multicentre cohort of 144 patients with adrenal sporadic incidentalomas. RESULTS: Adrenal enlargement was reported in 20.4% (146/715) of patients. Adrenal tumours (>10 mm in size) accounted for 58.1% of these cases (10.1% of the whole patient cohort). Tumours were bilateral and >40 mm in size in 12.5 and 19.4% of cases respectively. Hormonal hypersecretion was restricted to patients with tumours and occurred in 15.3% of them. Compared with incidentalomas, MEN1-related tumours exhibited more cases of primary hyperaldosteronism, fewer pheochromocytomas and more adrenocortical carcinomas (ACCs; 13.8 vs 1.3%). Ten ACCs occurred in eight patients. Interestingly, ACCs occurred after several years of follow-up of small adrenal tumours in two of the eight affected patients. Nine of the ten ACCs were classified as stage I or II according to the European Network for the Study of Adrenal Tumors. No evident genotype/phenotype correlation was found for the occurrence of adrenal lesions, endocrine hypersecretion or ACC. CONCLUSIONS: Adrenal pathology in MEN1 differs from that observed in sporadic incidentalomas. In the absence of relevant symptoms, endocrine biology can be restricted to patients with adrenal tumours and should focus on steroid secretion including the aldosterone-renin system. MEN1 is a high-risk condition for the occurrence of ACCs. It should be considered regardless of the size of the tumour.

Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d'Etude des Tumeurs Endocrines.

BACKGROUND: In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent. OBJECTIVES: To identify and characterize prognostic factors associated with disease-free survival (DFS) in children from HMTC families. DESIGN: We conducted a retrospective analysis of a multi-center cohort of 170 patients below age 21 at surgery. Demographic, clinical, genetic, biological data [basal and pentagastrine-stimulated calcitonin (CT and CT/Pg, respectively)], and tumor node metastasis (TNM) status were collected. DFS was assessed based on basal CT levels. Kaplan-Meier curves, Cox regression, and logistic regression models were used to determine factors associated with DFS and TNM staging. RESULTS: No patients with a preoperative basal CT <31 ng/ml had persistent or recurrent disease. Medullary thyroid carcinoma defined by a diameter ≥10 mm [hazard ratio (HR): 6.0; 95% confidence interval (95% CI): 1.8-19.8] and N1 status (HR: 20.8; 95% CI: 3.9-109.8) were independently associated with DFS. Class D genotype [odds ratio (OR): 48.5, 95% CI: 10.6-225.1], preoperative basal CT >30 ng/liter (OR: 43.4, 95% CI: 5.2-359.8), and age >10 (OR: 5.5, 95% CI: 1.4-21.8) were associated with medullary thyroid carcinoma ≥10 mm. No patient with a preoperative basal CT <31 ng/ml had a N1 status. Class D genotype (OR: 48.6, 95% CI: 8.6-274.1), and age >10 (OR: 4.6, 95% CI: 1.1-19.0) were associated with N1 status. CONCLUSION: In HMTC patients, DFS is best predicted by TNM staging and preoperative basal CT level below 30 pg/ml. Basal CT, class D genotype, and age constitute key determinants to decide preoperatively timely surgery.

Clinical and metabolic characteristics of patients with latent autoimmune diabetes in adults (LADA): absence of rapid beta-cell loss in patients with tight metabolic control.

AIM AND METHODS: The present study compared the clinical and metabolic characteristics of latent autoimmune diabetes in adults (LADA) with type 2 diabetes, as well as the residual beta-cell function and progression to insulin treatment, over a 2-year follow-up period, of antibody (Ab)-positive and Ab-negative patients who achieved tight glycaemic control (HbA(1c) 7.0+/-0.8% and 6.5+/-0.9%, respectively, at the time of entry into the study). RESULTS: Glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA) were detected in 10% of patients presenting with non-insulin-dependent diabetes. Around half of Ab-positive patients required insulin treatment during the follow-up. Ab-positive patients displayed lower stimulated C-peptide levels both at entry and during the follow-up compared with Ab-negative patients, although no significant decline in C-peptide levels was observed in either subgroup over two years. Nevertheless, Ab-positive patients progressed more frequently to insulin treatment, and stimulated C-peptide tended to decrease in LADA patients who subsequently required insulin, whereas it remained stable in those who were non-insulin-dependent. In those who progressed, the trend towards C-peptide decline persisted even after starting insulin treatment. CONCLUSION: LADA patients demonstrate lower residual beta-cell function than do type 2 diabetes patients. However, those who achieve tight metabolic control do not present with a rapid decline in beta-cell function. Further studies are needed to determine the optimal treatment strategy in such patients.

[Somatostatin receptor-based imaging and therapy of digestive endocrine tumors]. / Imageries et traitements basés sur les récepteurs à la somatostatine dans les tumeurs endocrines digestives.

The management of gastroenteropancreatic endocrine tumors is greatly linked to the localization of primary tumor. Morphological imaging methods are thus necessary. However, the expression of somatostatin receptors in endocrine tumors makes their detection possible thanks to radiolabeled somastotatin analogs. [(111)In-DTPA] octreotide is the main radiolabeled analog for somatostatin receptor scintigraphy. Positron emission tomography uses other tracers and currently allows improvement of the diagnosis and the tumoral staging. It also allows to affect the therapeutic management. A further step is about to be taken as far as the therapy of endocrine tumors is concerned with the peptide receptor radionuclide therapy. Those therapies are now being offered in some European and American centers for progressive metastatic tumors. Their place in the therapeutic strategy has to be defined, especially in comparison to targeted therapy. The sudden and delayed adverse events as well as the current legislation on the use of radioactive therapy-aimed products have limited their development in France so far.

Hypochloremia and hyponatremia as the initial presentation of cystic fibrosis in three adults.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Most diagnoses of CF are made during infancy or childhood, and are based on respiratory or digestive involvement. Initial extracellular dehydration leading to the diagnosis of CF is usual in infants but has only exceptionally been reported in adults. We describe three new adult cases of CF initially presenting with depletive hyponatremia and hypochloremia following exposure to heat. At first consultation, these patients had no symptoms suggestive of CF. One patient presented with a seizure induced by hyponatremia. The two other patients were siblings carrying a novel c.4434insA mutation in exon 24 of CFTR. Acute dehydration is a very rare initial manifestation of CF but may be life-threatening. The possibility of CF should not be ignored in cases of depletive hyponatremia, hypochloremia or hypokalemic metabolic alkalosis, even in otherwise healthy patients.

Exploration and management of adrenal incidentalomas. French Society of Endocrinology Consensus.

The French Society of Endocrinology convened a multidisciplinary panel of endocrinologists, radiologists, nuclear physicians and surgeons to address the appropriate evaluation and treatment of adrenal incidentalomas. The panel conducted a systematic review of medical literature on the following issues: epidemiology, natural history, radiological and scintigraphic evaluation, endocrine assessment, surgical management and appropriate follow-up. The following text reports the recommendations of experts on behalf of the French Society of Endocrinology. The authors emphasize the paucity of published scientific data that hampers evidence-based medicine recommendations. The crucial points of the French consensus are: the usefulness of CT-scanning evaluation of adrenal incidentalomas, the systematic screening for pheochromocytoma, the usefulness of the 1mg overnight dexamethasone test to screen for latent hypercortisolism, the difficulty to interpret mild biological abnormalities of the HPA axis, the consensus to remove surgically most of tumours greater than 4cm, the necessity to follow clinically glucorticoid tissular targets in the follow-up of non operated benign adrenocortical incidentalomas.

[Transoral resection of thyroid cancer metastasis to retropharyngeal lymph node]. / Abord transoral d'une adénopathie rétropharyngée métastatique d'un carcinome thyroïdien papillaire.

OBJECTIVES: Retropharyngeal lymph node metastasis from papillary thyroid carcinoma is uncommon. Traditional extirpative procedures include cervical, cervical-parotid, and transmandibular approaches. The authors report the case of a patient with a retropharyngeal node metastasis originating from papillary carcinoma of the thyroid gland that was successfully removed by a transoral approach. METHOD: A 49-year-old man presented for removal of a retropharyngeal lymph node metastasis measuring 21 mm x 27 mm from papillary thyroid carcinoma. Surgical excision was performed through a transoral approach using a surgical navigation system to assess the location of the node precisely. RESULT: The postoperative course was uneventful with return to a normal diet on the first postoperative day and hospital discharge on the second postoperative day. Three months after surgery, TSH-stimulated thyroglobulin was undetectable. CONCLUSION: The transoral approach to retropharyngeal space is a reliable procedure with low morbidity compared to other approaches. The limited surgical access provided by this approach should limit its use to removal of well-circumscribed lesions not invading adjacent structures.

Distribution of adipose tissue: quantification and relationship with hepatic steatosis and vascular profiles of type 2 diabetic patients with metabolic syndrome.

AIM: As the distribution of fat is increasingly related to cardiovascular events, we examined whether or not abdominal-fat quantification using magnetic resonance imaging (MRI) software is reliable, and whether or not it is related to clinical markers of fat distribution as well as to metabolic and vascular status. METHODS: We recorded the anthropometric measurements of 34 obese type 2 diabetic patients with metabolic syndrome. The patients were enrolled to evaluate their abdominal (visceral and subcutaneous) adipose tissue by single-slice L3-L4 MRI. Manual and automated analyses were compared. The relationships between anthropometric measurements, biological markers and intima-media thickness of the common carotid artery were also assessed. RESULTS: We validated the automated software to quantify abdominal-fat deposition with MRI compared with manual measurements (r2=0.95). The waist-to-hip-circumference ratio (WHR) was the only clinical parameter that correlated with the proportion and quantity of visceral and subcutaneous abdominal-adipose tissue evaluated by MRI (r=0.60). In addition, fat repartition as evaluated by WHR was related to hepatic steatosis parameters (ferritin and ALAT) and to intima-media thickness, whereas simple waist circumference was not a determinant in these obese patients. We also showed that the adiponectin-to-leptin ratio was related to adipose tissue distribution. CONCLUSION: Distribution of abdominal fat, as evaluated by MRI, can be reflected by clinical determination of the WHR. Differences in regional accumulations of abdominal fat may be specifically related to variations in the risks of steatosis and vascular rigidity among obese type 2 diabetic patients.