Cushing’s disease

Cushing’s disease, or pituitary ACTH dependent Cushing’s syndrome, is a rare disease responsible for increased morbidity and mortality. Signs and symptoms of hypercortisolism are usually non specific: obesity, signs of protein wasting, increased blood pressure, variable levels of hirsutism. Diagnosis is frequently difficult, and requires a strict algorithm. First-line treatment is based on transsphenoidal surgery, which cures 80% of ACTH-secreting microadenomas. The rate of remission is lower in macroadenomas. Other therapeutic modalities including anticortisolic drugs, radiation techniques or bilateral adrenalectomy will thus be necessary to avoid long-term risks (metabolic syndrome, osteoporosis, cardiovascular disease) of hypercortisolism. This review summarizes potential pathophysiological mechanisms, diagnostic approaches, and therapies

Doit-on craindre le syndrome de Nelson ?

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Paragangliome rétropérinéal et polyglobulie (à propos d'un cas)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

LES PSEUDOHYPOPARATHYROIDIES (A PROPOS DE DEUX CAS)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hyperparathyroïdie primaire du sujet jeune (quand faut-il réaliser un dépistage génétique des néoplasies endocriniennes multiples ?)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The use of the glucocorticoid receptor antagonist mifepristone in Cushing's syndrome.

International audiencePURPOSE OF REVIEW: Mifepristone is the first and only available glucocorticoid receptor antagonist. Cushing's syndrome is a rare disease, responsible for increased morbidity and mortality. The treatment of Cushing's syndrome is far from perfect. The aim of this review is to better define the merits and pitfalls of mifepristone in treating Cushing's syndrome, and try to determine its potential roles in the treatment of hypercortisolism. RECENT FINDINGS: Only case reports or series based on a low number of patients had been reported in the literature. A recent retrospective European Study based on about 20 patients with Cushing's syndrome gave more precise data about mifepristone. Coupled with the 20 previously reported patients in various studies, these results determine the profile of patients who could benefit from mifepristone. SUMMARY: High clinical efficacy of mifepristone is counterbalanced by the lack of available biological monitoring data during treatment, and the risk of worsening of hypokalemia and blood pressure levels. However, its rapid efficacy and the fact that the drug uses a mechanism that is different from all currently available treatment should make mifepristone a valuable treatment in particular cases of uncontrolled hypercortisolism despite classical methods

Medical treatment of Cushing's syndrome: glucocorticoid receptor antagonists and mifepristone.

International audienceMifepristone is the first and only available glucocorticoid receptor antagonist. It was initially mainly considered as a so-called 'contragestive' pill due to its antiprogestin activity. In this review, we summarize the results of mifepristone reported in the literature as a treatment of Cushing's syndrome. Most of the patients were treated due to unsuccessful surgery and/or partially effective anticortisolic drugs. The majority of them presented a rapid decrease of clinical signs of hypercortisolism during the first month of treatment; about half experienced a reduction in their elevated blood pressure, and half of the diabetic patients presented improved blood glucose levels. Mifepristone treatment has 2 main drawbacks: (1) the blockade of glucocorticoid receptors leads to increased ACTH and cortisol levels, making it difficult to adapt the treatment and diagnose adrenal deficiency, and (2) increased cortisol levels can also lead to severe hypokalemia. Follow-up of efficacy should only be clinical (weight, blood pressure, skin lesions) and biological (regular blood potassium sampling). Dose adjustment will be performed based on these parameters. The lack of a large available prospective cohort of patients on mifepristone, and the scarcity of data on its long-term effects, does not allow recommending it as a first-line drug in the treatment of hypercortisolism. However, as mifepristone is a rapidly effective drug, it can play a role in the management of hypercortisolism. The main indication is the partial efficacy or bad tolerance of other well-known anticortisolic drugs, either by replacement (bad tolerance, lack of effectiveness) or addition (multimodal approach) of mifepristone

Should routine analysis of the MEN1 gene be performed in all patients with primary hyperparathyroidism under 40 years of age?

International audienceBACKGROUND: Familial hyperparathyroidism, especially Multiple Endocrine Neoplasia Type 1, is more likely to present with primary hyperparathyroidism (1 degrees HPT) at a young age, mandating bilateral exploration of the parathyroid glands. However, the majority of young patients will not be gene carriers or have a family history. Recent evidence suggests that young adults under 40, in whom there is no suspicion of family history, can be managed with the same pre- and perioperative strategy as used for sporadic primary HPT of any age. Our aim was to evaluate the prevalence of mutations in the MEN1 gene in young adults under 40 who present with apparent sporadic 1 degrees HPT. METHODS: A retrospective review was undertaken of all patients who underwent surgery for 1 degrees HPT between 1993 and 2004. From a total of 1253 patients, 87 (6.2%) were under the age of 40. Thirty-three patients provided informed consent to a detailed personal and family history, physical examination, and genetic analysis of the MEN1 gene. Twelve patients were subsequently excluded as they were known gene carriers prior to surgery (10 MEN1 and 2 MEN2A patients). Twenty-one patients underwent genetic analysis. RESULTS: Of the 21 patients who consented to genetic analysis, the mean age was 30.8 years (range = 18-39 years with 43% younger than 30). These patients had no suspicious family or personal histories suggestive of a MEN phenotype. Fifteen patients presented with symptomatic hypercalcemia. All 21 patients underwent parathyroid surgery by conventional cervicotomy (12) or endoscopic parathyroidectomy in cases (9) where the parathyroid gland was localized preoperatively. Nineteen patients (91%) had uniglandular disease. Surgical cure was achieved in all patients. Of the 21 patients, only one patient (4.7%) was found to have a MEN1 gene mutation (exon 3, at codon 190, c;680_681delGGinsC). This patient was found to have double adenomas at surgery with subsequent histological confirmation. The overall prevalence of MEN1 mutation in all patients under 40 was 13%. CONCLUSION: Although young age is often the only criterion to suspect MEN1, our results do not support routine MEN1 analysis in patients under 40. We propose that these patients be managed with the same preoperative and surgical approach as those presenting with sporadic 1 degrees HPT of any age

Long-term control of a MEN1 prolactin secreting pituitary carcinoma after temozolomide treatment.

International audienceWe report here a rare case of a young male patient presenting with a Multiple Endocrine Neoplasia Type 1 - prolactin-secreting pituitary carcinoma, controlled long-term after temozolomide withdrawal. Initial presentation was pituitary apoplexy leading to surgery. Dopamine agonists and radiotherapy allowed control of prolactin secretion and pituitary remnant. Metastasis appeared 10 years after initial presentation, leading to the diagnosis of pituitary carcinoma. At that time, dopamine agonists were no more effective; temozolomide, an oral alkylating agent, was administered for 24 cycles, and allowed decrease of the volume of the pituitary lesion and metastases. The patient is still currently followed in our department, 3 years after temozolomide withdrawal: prolactin level and pituitary tumor volume remain controlled without any chemotherapy. To our knowledge, this is the first case of MEN1 prolactin secreting pituitary carcinoma controlled long-term after temozolomide discontinuation