[Paraneoplastic Cushing's syndrome, a real diagnostic and therapeutic challenge: A case report and literature review]. / Le syndrome de Cushing paranéoplasique, un vrai défi diagnostique et thérapeutique: à propos d'un cas et revue de la littérature.

INTRODUCTION: Paraneoplastic Cushing's syndrome is a rare cause of endogenous hypercortisolism attributable to ectopic ACTH secretion by non-pituitary tumors. Imaging and biochemical results are often inconclusive and differential diagnosis with Cushing's disease can then be challenging. Moreover, these tumors may be occult and difficult to find and thus the need of new imaging tools such as (18)FDG-PET scan and (18)DOPA-PET scan. CASE REPORT: We report a 50-year-old man who presented with very aggressive clinical features related to Cushing's syndrome. Biological work-up confirmed the hypercortisolism and was consistent with an ectopic ACTH secretion. Conventional localization techniques failed to show any tumor and bilateral adrenalectomy was performed because of life-threatening complications. Two years later, thoracic computed tomography reveals an 11 mm mass in the left lower pulmonary lobe, (18)FDG-PET scan found a non-specific mild hypermetabolism of the lung nodule, and the (18)DOPA-PET scan confirmed the high uptake of this nodule suggesting an endocrine carcinoma. Histology confirmed a typical carcinoid tumor. The tumor cells stained positive for ACTH, CD56, chromogranin and synaptophysin. CONCLUSION: This case illustrates the dilemma between the need for morphological diagnosis of the ectopic ACTH source and control of the life-threatening hypercortisolism. (18)FDG-PET scan and (18)DOPA-PET scan should be considered early as a secondary diagnostic tool when conventional imagery fails to show any tumor.

[Thyroid metastasis of kidney cancer]. / Métastase intrathyroïdienne d'un cancer du rein.

Thyroid metastasis of solid tumors is rare and often asymptomatic. Differential diagnosis with malignant thyroid tumor is difficult. We report a 65-year-old man who presented with a solitary intrathoracic thyroid nodule of the left lobe, inaccessible to fine needle biopsy. His past medical history was remarkable for a nephrectomy for a kidney clear cell carcinoma one year before. The PET-scan did not show any abnormal fixation. A left lobo-isthmectomy was performed. Histologic examination revealed an intrathyroid metastasis of kidney carcinoma.

Diabetes and inflammation: fundamental aspects and clinical implications.

AIM: The aim of this paper is to provide the fundamental background of the inflammation theory associated with type 2 diabetes, to discuss the clinical consequences of low-grade inflammation, particularly in terms of cardiovascular risk, and to infer some clinical therapeutic strategies deriving from drugs that already exist or are in development. METHODS: This non-exhaustive work is the result of a Pubmed(®) research, based on requests including the following keywords: diabetes, inflammation, innate immunity, obesity, reticulum endoplasmic stress, cytokines, endothelial dysfunction. RESULTS: Obesity and type 2 diabetes are linked with a low-grade inflammation state that reflects the activation of innate immunity where metabolic, environmental and genetic factors are implicated. The role of endoplasmic reticulum stress and unfold protein response is underlined. Inflammation markers are predictive for the risk to develop diabetes, and are associated with an increased cardiovascular risk. While lifestyle modifications are followed by an improvement in inflammation markers, treatments inferred from the inflammation theory are of great interest, although quite moderate effects on glycaemic control have been observed with some of them. CONCLUSION: The development of molecules targeting different inflammatory mechanisms could lead in diabetic patients to improvement of both glycaemia and cardiovascular prognosis.

A new simple method for assessing sudomotor function: relevance in type 2 diabetes.

AIM: The current sudomotor function tests are too time-consuming to be used for diabetic patients in daily practice. EZSCAN is a new, patented technology that measures electrochemical skin conductance (ESC) through reverse iontophoresis and chronoamperometry. The aim of the present study was to assess the sensitivity, specificity and reproducibility of the method in type 2 diabetic patients in comparison to control subjects with no risk of diabetes. METHODS: A total of 133 type 2 diabetic patients and 41 control subjects were tested. Participants placed their hands and feet on nickel electrodes, and an incremental low direct current was applied to the anode for 2 min. ESC was calculated from the resulting voltage and generated current. ESC diagnostic accuracy was analyzed by ROC curve modeling, and reproducibility was assessed using Bland-Altman analysis. RESULTS: The ESC of hands and feet was significantly reduced in diabetic patients (53±16µSi and 67±14µSi, respectively) compared with control subjects (68±16µSi and 80±7µSi, respectively; P<0.0001). ESC values had a sensitivity of 75% and specificity of 100%, with an area under the ROC curve of 0.88 at a threshold of 50% on the EZSCAN scale. Coefficients of variation in hand and foot measurements were 15 and 7%, respectively. CONCLUSION: The good sensitivity, specificity and reproducibility of EZSCAN make it a feasible alternative for assessing sudomotor dysfunction, a clinical manifestation of autonomic neuropathy in diabetic patients. The test takes<3 min to perform, and requires neither special patient preparation nor medical personnel training.

[Uncommon complication of anticoagulant therapy: pituitary hemorrhage]. / Une complication inhabituelle d'un traitement anticoagulant: l'hémorragie hypophysaire.

Pituitary apoplexy is well known as the first manifestation of pituitary tumour. Conversely, haemorrhage of a pituitary adenoma, revealed by anticoagulant therapy, is very uncommon. Two weeks after initiation of anticoagulant therapy for a deep venous thrombosis, an 83-year-old woman presented with intracranial hypertension and blindness. CT-scan revealed pituitary hematoma within a large adenoma. Three months after surgery, partial visual defect persisted in association with panhypopituitarism. When pituitary disorder is known, hemorrhage risk should be taken into account in the prescription of anticoagulant therapy.

[Hyperparathyroidism during pregnancy: dangerous association for the mother and her infant]. / Hyperparathyroïdie et grossesse : association à risque pour la mère et l'enfant.

Hypercalcaemia during pregnancy is rare but requires a systematic approach for its diagnosis and its treatment. We report a 32-year-old pregnant female at 32 weeks of gestation who presented a severe hypercalcaemia, due to primary hyperparathyroidism. The delivery allowed the birth of a healthy child who had a serum calcium level in the normal range. Eight days later, the mother was operated from a parathyroid adenoma allowing normalisation of calcaemia. Hyperparathyroidism during pregnancy is rarely reported; it can lead to severe complications for both the mother and the infant. The newborn can present tetania due to hypocalcaemia and hypoparathyroidism can be definitive. Surgery should be discussed when serum calcium level of the mother is markedly elevated.

[Type 2 diabetes mellitus associated with pancreatic and renal malformations]. / Diabète de type 2 associé à des malformations rénales et pancréatiques.

A 55-year-old woman presented with a recent diabetes mellitus associated with pancreatic and renal malformations. This atypical diabetes raised the possibility of maturity onset diabetes of the young (MODY) and a genetic research was performed. These malformations led to MODY5 diagnosis that was confirmed by the presence of HNF1beta gene mutation.

Hypoglycaemia and dementia in diabetic patients.

Diabetes and dementia, which have a complex relationship between them, are undergoing extensive growth in their fields. The occurrence of hypoglycaemia, the potential severity of which has just been pointed out in some recent studies, must be included in these relationships. In fact, diabetes is the cause of decline in cognitive functions and most certainly is involved in the occurrence of vascular dementia. The brain, which is highly dependent on glucose for its metabolism, is particularly vulnerable to hypoglycaemia in children and the elderly. Animal studies and pathoanatomical observations confirm the clinical impression of the reality of genuine post-hypoglycaemic encephalopathy. The impact of mild hypoglycaemia however is being debated. Lastly, the existence of dementia promotes the occurrence of hypoglycaemia due to disorders related to eating habits or poor treatment management. This hypoglycaemic risk however must not constitute a pretext for exaggerated laxity in achieving the blood glucose objectives.

[Acromegaly in the elderly]. / L'acromégalie du sujet âgé.

UNLABELLED: Multicentric registers such as The French Acromegaly Register provide data on rare disorders that are otherwise difficult to obtain, so avoiding extrapolation from limited data sets. This study focuses on clinical, hormonal and therapy characteristics of acromegaly in people over 70 years old. The objective was to compare this population with the youngest to disclose if the medical management was similar. PATIENTS AND METHODS: The data were obtained from the 30 centres that have registered patients in the Acromegaly Register since 1999. RESULTS: The register listed 644 acromegaly patients on 1st January 2005, of whom 68 (22 men and 46 women) were over 70 years old, independently of the diagnosis date of their disease. Their average age was 76.8 + or - 5 years (range: 70-95) and they had suffered from acromegaly for 11 + or - 6 years (compared to 7 years in those aged less than 70). Their BMI were similar. Diabetes and hypertension were more frequent than in younger acromegalic patients and in the general French population matched for age. Circulating GH and IGF-1 concentrations were lower than in the younger acromegalic patients on inclusion and 1 year after treatment. There was no significant difference in the tumor size. Only 44% of the patients over 70 underwent surgery, against 90% of patients under 70 years. However, the fractions of young and elderly patients with a controlled disease 1 year after inclusion were the same (51%). CONCLUSION: In the limits of the use of register, these data reveal a high prevalence of diabetes and hypertension in the eldest acromegalic patients. Despite much less frequent surgical intervention, patients' disease under control is equivalent to the younger population 1 year after the initial interview, confirming the effectiveness of the choices of treatment.

[Seizure and Bourneville tuberous sclerosis: think about insulinoma]. / Crise comitiale et sclérose tubéreuse de Bourneville: penser à l'insulinome.

Bourneville tuberous sclerosis is a phacomatosis characterized by skin, neurological and ophthalmological lesions. At first, seizure can reveal cerebral lesions, but other causes may be suspected. We report a case of a Bourneville tuberous sclerosis in a 41-year-old-man with hypoglycemia leading to seizures, resulting from an insulinoma.

What is the role of computed tomographic coronary angiography in diabetic patients?

UNLABELLED: All diabetes specialists are aware of the frequency and severity of coronary disease in diabetics. Non-invasive diagnostic tests perform well, but they could be better. AIM: To assess the role of computed tomographic coronary angiography in diabetics. New cardiac imaging techniques such as CT coronary angiography are promising tools for the selection of patients for conventional X-ray coronary angiography, which remains the key for diagnosis and angioplasty. The limitations of CT coronary angiography, even using the most advanced machines with a 64-slice capacity, are its resolution, the need for an iodine contrast agent and the cumulative radiation from repeated examinations. CONCLUSION: CT coronary angiography appears to have great potential for patients at risk where non-invasive tests cannot absolutely exclude coronary disease and for the follow-up of coronary bypass surgery.

Use of Ni electrodes chronoamperometry for improved diagnostics of diabetes and cardiac diseases.

Low DC active current through Nickel electrodes applied on skin in places like hands, forehead and feet provides a novel non invasive diagnostic tool using reverse iontophoresis. This work describes the electrochemistry reactions involved and some medical applications, such as diagnostics of neuropathy, diabetes and cardiac diseases. Finally we provide evidence for the utility of this method through large clinical studies.

[Recommendations of the French National Health Authority for management of high blood pressure in clinical practice]. / Les recommandations de la Haute Autorité de Santé sur la prise en charge de l'HTA à l'épreuve des faits.

UNLABELLED: The new recommendations of the French national authority for health (or Haute Autorité de Santé: HAS) concerning management of high blood pressure (HBP) deserve to be compared with real clinical practices in a large population. MATERIAL AND METHODS: [corrected] EPIMIL is a prospective epidemiological study designed to assess the prevalence of the metabolic syndrome and the risk factors in a 2045 French male military personnel coming from Paris area. The different recommendations of the HAS have been applied to these subjects, and the aim of this work is to compare these theoretical objectives to what is done in real practice. RESULTS: Among these 2045 subjects aged of mean 38,6 +/- 8,8 years, 78 (4%) are known and treated for HPB. Although half of them present more than two associated risk factors, the means of systolic blood pressure and diastolic blood pressure stay at high levels. The blood pressure (BP) targets established at 140/90 mmHg are only reached by 33 patients (42%). Among the 1967 subjects considered to have normal BP, the BP considered as optimal (120/80 mmHg) is only found in 695 subjects (35.3%) and 428 (21.7%) do present ignored or neglected HBP, in spite of the presence of important associated risk factors. Then, the cardiovascular risk stratification into levels, as recommended by the HAS, shows that for these subjects considered to have normal BP, risk is finally low for 6%, moderate for 12%, and high for 3.5%. COMMENTS: In a selected and in theory regularly followed population, the recommendations of the HAS are insufficiently applied, as well for detection or treatment of HBP. Then, information of both medical personnel and also the interested parties should be necessary, in order to see these recommendations applied in real practice.

[Hypertension and acromegaly in the elderly: French Registry Data]. / Hypertension artérielle et acromégalie du sujet âgé: données du registre français.

UNLABELLED: Multi centre registries such as the French Acromegaly Registry created in 1999 provide data on rare disorders that are otherwise difficult to obtain. This study focuses on the characteristics of high blood pressure in people aged of over 70 years old. PATIENTS AND METHODS: The data were obtained from the thirty centres where patients had been recorded on the Acromegaly Registry since 1999. RESULTS: The Register listed a total of 644 patients with acromegaly at January 1st 2005, of whom 68 (22 men and 46 women) were aged over 70 years old (10.6%). Their mean age was 76.8 +/- 5 years (range 70 - 95) and they had been presenting acromegaly for 11 +/- 6 years (compared to 7 years in those aged less than 70). Their BMI were 27.9 +/- 4 kg/m2 for men, 27.7 +/- 4 for women (respectively 28.4 +/- 4.3 and 26.7 +/- 4.4 in those aged less than 70 years). Hypertension was particularly frequent in this population, reaching 80% vs. 27% under 70 years (p=0.0001). Prevalence was then higher than in general population (referring to FLAHS study). Mean blood pressure was 143 +/- 12 / 84 +/- 15 mmHg for men and 141 +/- 17 / 79 +/- 9 for women. 46% of men and 30% of women treated or not, had blood pressure over 140 / 90 mmHg. Data showed 12% of arrhythmic cardiopathy, 8% of cardiac insufficiency, 12% of ischemic cardiopathy and 12% of patients suffering from arteritis or stroke. Although various therapeutic strategies had been applied for young and elderly patients, 51% in each group were in remission one year after inclusion. DISCUSSION: More than 10% of patients are aged over 70 years in the French Acromegaly Registry and hypertension is very frequently observed in this population. The increasing life expectancy due to currently available treatments justifies a strict management of patients in order to reduce cardiovascular risks, which stay the main cause of morbidity and mortality.

[Role of nocturnal blood pressure in the onset of diabetic nephropathy]. / Responsabilité de la pression artérielle nocturne dans l'apparition d'une néphropathie chez les diabétiques.

UNLABELLED: The aim of this study was to assess the responsibility of night-time blood pressure in the onset of nephropathy in diabetic patients. PATIENTS AND METHODS: This study included 98 diabetic patients (mean age: 54 +/- 15 years, diabetes duration: 15 +/- 10 years). An evaluation of diabetes and a 24-h ambulatory blood pressure were performed at the initial evaluation (Y0) and about five years later (Y5). At Y0, all patients had normal urinary albumin excretion (UAE) (<30 mg/24h). They were separated into two groups according to urinary albumin excretion at Y5: group (N +): UAE>30 mg/24h and group (N-): UAE<30 mg/24h. Twenty four hours ambulatory blood pressure, clinical and biological parameters recorded at Y0 were compared in both. RESULTS: At Y5, there was 18 patients in group (N +) and 78 in group (N-). Patients of group (N +) were older than those of group (N-): 62.9 +/- 9.5 vs. 52.6 +/- 15.7 years, p<0.01, and their BMI was higher (28 +/- 5 vs. 25 +/- 4 kg/m2, p<0.03). Diabetes duration and Hb A1c levels did not differ from significant manner in both. At Y0, UAE was significantly higher in group (N +) than in group (N-): 13 +/- 7 vs. 8 +/- 6 mg/24h, p<0.01. At the initial evaluation, daytime systolic and diastolic blood pressures did not differ from significant manner in both. Systolic and diastolic BP night-time were higher in diabetic patients who developed microalbuminuria (SBP: 122 +/- 19 vs. 113 +/- 13 mmHg, p<0.05 and DBP: 70 +/- 6 vs. 65 +/- 10 mmHg, p<0.03). UAE collected at Y5 was correlated to night-time BP recorded at Y0 (SBP: r=0.381, p=0.001 and PAD: r=0.294, p=0.004) and night-time systolic BP explained 12.3% of the UAE variance. Progression of UAE between the two evaluations was found to be correlated to the night-time systolic BP recorded at Y0 (r=0.335, p=0.0008) and night-time systolic BP explained 11.7% of the progression variance. There was a negative correlation between UAE at A5 and the difference between daytime and night-time BP recorded during the same evaluation (r=- 0.230, p=0.024 with SBP and r=- 0.243, p=0.017 with DBP). CONCLUSION: The results underlign the resposability of night-time blood pressure, and more especially of nighttime systolic blood pressure, for the onset of nephropathy in diabetic patients.

[Modifications of 24-h blood pressure profile associated with reduction of the heart rate variability in type 1 diabetic patients]. / Modifications du profil tensionnel nycthéméral associées à la réduction de la variabilité de la fréquence cardiaque chez le diabétique de type 1.

UNLABELLED: The purpose of this study was to assess the blood pressure modifications in type 1 diabetic patients who present reduction of heart rate variability. PATIENTS AND METHODS: This study included 70 type 1 diabetic patients (mean age: 42 +/- 13 years, diabetes duration: 13.2 +/- 9 years. They were free for complications and did not receive other treatment than insulin. Heart rate variability was evaluated using 24-h continuous ECG record spectral analysis. Patients were divided into two groups according to whether log high frequency power was lower (group 1, N=36) or higher (group 2, N=3 4) than 70 patients'mean. Clinical and biological features and 24-h ambulatory blood pressure measurement were compared in both groups. RESULTS: Patients of group 1 were older than group 2 (47.8 +/- 11.2 vs. 35.7 +/- 12.2 years, p<0.0001) and diabetes duration was higher (16.9 +/- 8.4 vs. 9.4 +/- 8 years, p<0.001). BMI and Hb A1c did not differ from significant in both. Night-time blood pressure was upper in group 1 (SBP: 112 +/- 13 vs. 103 +/- 11 mmHg, p<0.01 and DBP: 66 +/- 8 vs. 60 +/- 7 mmHg, p<0.001). The difference between blood pressures during day and night (DeltaBP) were lower in group 1 than in group 2 (DeltaSBP: 10 +/- 9 vs. 15 +/- 7 mmHg, p<0.02 and DeltaDeltaBP: 9 +/- 7 vs. 12 +/- 5 mmHg, p<0.04). DSBP and DDBP were found to be correlated with log HF power (r=0.356, p<0.003), which could explain 11.8% and 12% of their variance. Urinary albumin excretion rate was higher in group 1 (8 +/- 4 vs. 5 +/- 3 mg/24h, p<0.01). CONCLUSION: In type 1 diabetic patients free for complications, reduction in heart rate variability linked to age and diabetes duration is associated with a reduction in nighttime BP fall. These two parameters of autonomic neuropathy could have a pathogenic role in the development of incipient nephropathy.

Should we have more definitions of metabolic syndrome or simply take waist measurement?

The disorder now known as metabolic syndrome has been recognized for 50 years, but its multiple definitions have led to some confusion and even doubt about its very nature. Metabolic syndrome is directly linked to the presence of android obesity, which indicates insulin resistance and lies at the root of all risk factors and early indications of type 2 diabetes. It is diagnosed by systematic measurements of waist size and its direct interpretation taking ethnic origin into account. This pragmatic approach avoids the uncertainties generated by differing definitions and is subtler than the presence or absence of metabolic syndrome in a given patient. Drug-free treatment of an android obese patient is inexpensive and effective, but this apparently simple approach masks difficulties of application. However, these are sociological problems.

[Nelson's syndrome management: current knowledge]. / Prise en charge du syndrome de Nelson: données actuelles.

PURPOSE: Nelson's syndrome is a severe complication of bilateral adrenalectomy performed in the treatment of some Cushing's diseases, and its management remains difficult. Trough the observation of a patient suffering from a severe form of Nelson's syndrome for more than 10 years, the authors review the literature and discuss the main current therapeutic possibilities. CURRENT KNOWLEDGE AND KEY POINTS: Many molecules have been used with variable results. In our observation cabergoline at 2 mg per week seems to be efficient after a 3 and a half years follow-up, in accordance with some recent publications. More than bromocriptine, this dopamine agonist provides interesting prospects for this disease's management. Moreover, if the conventional treatments as valproic acid or cyproheptadine are not very efficient, somatostatin analogs seem to be of some therapeutic interest. FUTURE PROSPECTS AND PROJECTS: New molecules are currently evaluated, but studies are difficult to conduct because of the low disease prevalence. Tumour receptors analysis undoubtedly constitutes an attractive way to find new therapeutic targets.

[Inappropriate ADH secretion-induced hyponatremia and associated with paroxetine use]. / Hyponatrémie par sécrétion inappropriée d'ADH associée à la prise de paroxétine.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressants prescribed for elderly people. Although they are generally better tolerated than other antidepressant treatment classes, they can be responsible for potentially life-threatening hyponatremia, related to syndrome of inappropriate antidiuretic hormone secretion (SIADH). OBSERVATION: A 64 years-old woman was hospitalized for cognitive function alteration and vomiting after introduction of paroxetine for depressive symptoms. Serum investigations revealed hyponatremia (121 mmol/l) with low plasma osmolarity and normal natriuria consistent with diagnosis of SIADH. Hyponatremia was reversible after paroxetine withdrawal. DISCUSSION: Hyponatremia induced by SIADH is a serious but underestimated complication of SSRI treatment. This complication occurs in the elderly people within the first month of treatment. Monitoring of the serum sodium concentration during the first month of treatment is recommended for older patients.

[Silent thyroiditis in a patient under lithium therapy]. / Thyroïdite silencieuse chez un patient traité par lithium.

While hypothyroidism secondary to treatments by lithium are well known, cases of hyperthyroidism are less common. A 48 years old patient under lithium carbonate from about 10 years ago presents hyperthyroidism without any auto-immunity biological markers, associated with a very low thyroid tracer uptake on scintigraphy. Treatments by anti thyroid agents will be necessary during months in order to normalize the hormone level, whereas lithium is maintained. Only few tens of cases of hyperthyroidism related to lithium have been reported in the literature. This observation shows the importance of the thyroid hormonal follow up for patients under lithium, in order to treat them before the outbreak of a thyroid dysfunction. The causal toxic mechanism is still unclear, and may be related with a direct damage of lithium to follicular cells.