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Cushing's Syndrome (cushing's + syndrome)
Selected AbstractsCushing's Syndrome With Uncontrolled Hypertension, Occasional Hypokalemia, and Two PregnanciesJOURNAL OF CLINICAL HYPERTENSION, Issue 7 2010Joel Handler MD First page of article [source] ES08 DIAGNOSTIC AND THERAPEUTIC STRATEGIES OF ADRENOCORTICAL CARCINOMA-A 3-INSTITUTION EXPERIENCEANZ JOURNAL OF SURGERY, Issue 2007A. H. Imisairi Objective This paper reviews the diagnostic, therapeutic strategies and outcomes of ADCC in 3 Institutions between Newcastle and Sheffield in United Kingdom and Putrajaya, Malaysia. Patients and Methods A 10-year retrospective analysis of proven cases of ADCC was collected from January 1997 to December 2006. The patients' demographic data, clinical manifestation, site and size of the tumour were analysed. The record of metastasis, and therapeutic modality and outcomes were evaluated. Results A total of 22 cases of ADCC were documented in United Kingdom with 11 cases in each respective center. 16 cases were reviewed from Putrajaya. There was no gender preponderance and age significance. Cushing's Syndrome was the most common clinical manifestation (36.4%) in United Kingdom and (37.5%) in Putrajaya. The mean size of the ADCC was 9.3 cm (5,15 cm) in Newcastle and 9.8 cm (6,15 cm) in Sheffield as compared to 15.7 cm (5,25 cm) in Putrajaya. There were 12(75%) of patients in Putrajaya were diagnosed with Stage IV disease upon presentation whilst only 3(27.3%) and 5(45.4%) patients had metastasis noted in Newcastle and Sheffield respectively. Of note, 7(63.3%) patients in Sheffield were offered radical adrenalectomy. Our data revealed that the 2 years survival of patients who had radical approach in Sheffield has the highest rate of survival of 8(72.7%) as compared to 5(45.4%) in Newcastle and 2(12.5%) in Putrajaya. Conclusions Surgical removal remains the only form of curative therapy and hope of prolonged survival. The poorer prognosis of patients in Putrajaya may be attributed to the advanced stage of the disease. [source] Cyclical Cushing's syndrome due to an ectopic adrenocorticotropic hormone-producing adenomaINTERNAL MEDICINE JOURNAL, Issue 9 2007P. Sumithran No abstract is available for this article. [source] Cushing's syndrome caused by mucosal corticosteroid therapyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2009Michelle Pramick MD No abstract is available for this article. [source] Efficacy and safety of laparoscopic surgery for pheochromocytomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2005YUKIO NAYA Abstract Objective: Laparoscopic surgery for primary aldosteronoma and Cushing's syndrome is well established. We report on our experiences with laparoscopic adrenalectomy for pheochromocytoma, and assess the efficacy and safety of the laparoscopic approach. Methods: Between April 1998 and April 2003, a total of 23 patients underwent laparoscopic adrenalectomy for pheochromocytoma at Chiba University Hospital and Yokohama Rosai Hospital, Japan. We compared the surgical outcomes of these patients with those of 106 patients with adrenal tumors due to other pathologies who underwent laparoscopic adrenalectomy during the same period. Results: The mean tumor size of pheochromocytoma was 4.96 cm. Mean operative time was 192.7 min, and mean estimated blood loss was 130 mL. Neither mean operative time nor mean estimated blood loss was greater for patients with pheochromocytoma. Intraoperative hypertension (systolic blood pressure > 180 mmHg) occurred in 39.1% (9/23) of patients with pheochromocytoma. During the follow-up period, there were no mortalities or recurrences of endocrinopathy. Conclusions: Laparoscopic adrenalectomy for pheochromocytoma is a safe and minimally invasive procedure. [source] Portless endoscopic adrenalectomy via a single minimal incision using a retroperitoneal approach: Experience with initial 30 casesINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2004YUKIO KAGEYAMA Abstract Aim: To assess the feasibility of portless endoscopic adrenalectomy via a single minimum incision that narrowly permits extraction of the specimen. Methods: For, 30 cases of adrenal tumor, portless endoscopic surgery through a single flank incision (3,9 cm; mean, 5.6 cm) was performed without gas inflation or trocar port placement. All of the instruments used during surgery were reusable. The cases included primary aldosteronism (12), Cushing's syndrome (6), preclinical Cushing's syndrome (3), pheochromocytoma (1), non-functioning cortical adenoma (6), adrenocortical carcinoma (1) and adrenocortical hemorrhage (1). Results: Resection of the tumor was successfully completed, without complications, in all of the cases. Operative time was between 83 and 240 min (mean, 147 min). Estimated blood loss was 5,470 mL (mean, 139 mL). None of the patients required blood transfusion. Postoperative course was uneventful. Wound pain was mild and walking and full oral feeding were resumed on the first and second postoperative day, respectively, in the majority of cases. Conclusions: Adrenal tumors are good candidates for portless endoscopic surgery, which is safe, cost-effective, minimally invasive and matches favorably with laparoscopic surgery. [source] Combined adrenal adenoma and myelolipoma in a patient with Cushing's syndrome: Case report and review of the literatureINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2004HIROSHI HISAMATSU Abstract Myelolipoma is an uncommon benign tumor of unknown etiology and adrenal myelolipoma is rarely associated with endocrine disorders. We report a 67-year-old woman with Cushing's syndrome due to left adrenal adenoma associated with myelolipoma. The patient underwent laparoscopic left adrenalectomy and pathological examination revealed an adrenocortical adenoma associated with myelolipoma. To the best of our knowledge, 25 cases of endocrine dysfunction associated with myelolipoma have been reported in the English and Japanese literature. We review and discuss the pathogenesis of adrenal myelolipoma. [source] Electron microscopic study to compare preclinical Cushing's syndrome with overt Cushing's syndromeINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2002Daisaku Hirano Abstract Background: No significant differences in gross and light- microscopic features have been reported between preclinical and overt Cushing's adenomas. In this study, the ultrastructural differences between the two syndromes was attempted to be clarified. Methods: Two preclinical Cushing's syndrome adenomas and two overt Cushing's syndrome adenomas obtained from surgical extirpation were examined in an electron microscopic study. Results: Light microscopically, the adenomas of both syndromes were composed predominantly of clear cells, with few compact cells. Ultrastructurally, the prominent differences were of development in each organelle: the preclinical Cushing's adenomas had undeveloped mitochondria, which were smaller in size and had sparse cristae, lysosomes and polysomes, whereas the overt Cushing's adenomas contained well-developed mitochondria which were larger in size and were filled with abundant cristae, smooth endoplasmic reticulum (SER), lysosomes and polysomes. Conclusions: Preclinical Cushing's syndrome adenomas were ultrastructurally characterized by a reduced number of cellular organelles such as mitochondria and SER, which are necessary to synthesize glucocorticoid hormones. However, examination of a greater number of adenomas will be required to be able to draw conclusions on the ultrastructural differences between the two syndromes. [source] Preclinical Cushing's syndrome: Report of seven cases and a review of the literatureINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2000Masaaki Morioka Abstract Background: Adrenal adenomas showing autonomous cortisol secretion without specific endocrine symptoms are sometimes discovered in patients with adrenal incidentalomas. This entity has been described as subclinical or preclinical Cushing's syndrome (PCS), but the endocrine data of reported cases have varied and the diagnostic criteria of PCS have been uncertain. Methods: We report seven Japanese cases of PCS due to a unilateral, solitary adrenal adenoma with examination of the endocrine data of these patients. The diagnostic parameters of subtle hypercortisolism and the risk of postoperative adrenal insufficiency and surgical indications are discussed and reviewed. Results: In the present cases, the most frequently found biochemical parameters of autonomous cortisol secretion were a low adrenocorticotropic hormone (ACTH) level (100%) and insufficient suppression of cortisol by low-dose dexamethasone (85.7%). Unilateral accumulation of radiopharmaceuticals in tumors was also frequently observed (100%). A postoperative hydrocortisone supplement was given to six of the seven patients for 5,122 days. It was not given to case 4, because a moderate response of 11-deoxycortisol to metyrapone was identified. Plasma ACTH levels and the diurnal rhythm of plasma cortisol rapidly recovered within 3 weeks postoperatively in six of the seven cases. Conclusion: This entity is heterogeneous and various degrees of cortisol excess have been observed. It should be diagnosed in the wide spectrum and the risk of adrenal insufficiency after surgery should be evaluated by dynamic tests such as the corticotropin-releasing hormone (CRH) test. Based on the results of the present study and a review of the literature, PCS patients may not require hydrocortisone supplement therapy for a long period. [source] Glucocorticoid Excess During Adolescence Leads to a Major Persistent Deficit in Bone Mass and an Increase in Central Body FatJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001Veronica Abad Abstract Endogenous Cushing's syndrome (CS) in children causes growth retardation, decreased bone mass, and increased total body fat. No prospective controlled studies have been performed in children to determine the long-term sequelae of CS on peak bone mass and body composition. A 15-year-old girl with Cushing disease (CD), and her healthy identical co-twin, were followed for 6 years after the CD was cured. At the 6-year follow-up both twins had areal bone mineral density (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA) and three-dimensional quantitative computed tomography (3DQCT). Z scores for height, weight, and body mass index (BMI) were ,2.3, ,0.8 and 0.2, and 1.2, 0.2, and ,0.6, in the twin with CD and her co-twin, respectively. In the twin with CD, areal BMD and bone mineral apparent density (BMAD) at different sites varied from 0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was ,0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was 42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin, respectively. The relationship between total body fat and L2-L4 BMAD was inverse in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and direct (p < 0.001). In the twin with CD, despite cure, there was a persistent deficit in bone mass and increase in total and visceral body fat. These observations suggest that hypercortisolism (exogenous or endogenous) during adolescence may have persistent adverse effects on bone and fat mass. [source] Therapeutic doses of glucocorticoids: implications for oral medicineORAL DISEASES, Issue 5 2006SK Baid Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic,pituitary,adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use. [source] Case of combined adrenal cortical adenoma and myelolipomaPATHOLOGY INTERNATIONAL, Issue 9 2004Takaharu Matsuda We report a case of myelolipoma 10 mm in size within a functional cortical adenoma that was 33 × 22 × 17 mm in size. A 29-year-old woman was referred to hospital for transient hypertension. A right adrenal tumor was detected by computed tomography (CT) scan and magnetic resonance imaging (MRI). Her cortisol levels indicated a loss of the normal diurnal pattern, and urinary 17-hydroxycorticosteroids was elevated. She underwent a right adrenalectomy under the diagnosis of adrenal adenoma with Cushing's syndrome. The tumor was fairly well encapsulated by a thin layer of connective tissue. The major tumor portion was composed of two distinct cell types, clear cells and eosinophilic cells, arranged in an alveolar structure. These findings were representative of cortical adenoma. The adrenal cortical adenoma centrally included well-demarcated adipose tissue admixed with scattered islands of myelopoietic elements: erythroblasts, myeloid cell series and lymphocytic cells, which was eventually recognized as myelolipoma. Recently, adrenal myelolipoma has commonly been found because of the ease of detecting it as an incidentaloma by CT scan or MRI. However, the present adrenal myelolipoma case is uncommon because it is combined with a functioning cortical adenoma. Only six similar cases have previously been reported in English and Japanese publications. Furthermore, in the present case, the myelolipoma formed a tumor nodule, and to our knowledge, this is the first reported case of a radiographically recognizable tumor nodule. We discuss the etiology of myelolipoma and suggest that myelolipoma can develop in the course of endocrine hyperfunction. [source] Pro-Opiomelanocortin Expression in a Metastatic Breast Carcinoma with Ectopic ACTH SecretionTHE BREAST JOURNAL, Issue 4 2004Marie-Françoise Pelte MD Abstract: Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation., [source] Pregnancy-dependent Cushing's syndrome in three pregnanciesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2000Anna A. Kasperlik-Zaluska Professor (Medicine) No abstract is available for this article. [source] Nine cases of childhood adrenal tumour presenting with hypertension and a review of the literatureACTA PAEDIATRICA, Issue 6 2007Xiumin Wang Abstract Aim: To describe the clinical features, treatment and outcome of children adrenal tumors presenting with hypertension. Methods: The records of nine children under 16 years of age with adrenal tumours presenting with hypertension were analysed. Details were recorded for family history, clinical presentation, biochemistry, imaging, histology, treatment and outcome. Results: Abdominal mass was palpable only in one patient at diagnosis. Besides hypertension-associated symptoms, Cushing's syndrome was the common presentation form (n = 4). Abdominal computed topography showed adrenal mass in all patients. Tumours were completely resected for each patient. The median tumour weight was 73 g (11,530 g) and the size ranged from 1.5 × 1.5 to 12 × 14 cm2. Pheochromocytoma (n = 2), adrenocortical adenoma (n = 3), adrenocortical carcinoma (n = 1), neuroblastoma (n = 2) and ganglioneuromas (n = 1) were found. In one case, adrenal pheochromocytoma first occurred and non-functioning islet cell tumour successively occurred at pancreas. A better status is common at a median follow-up time of 3.5 years. Conclusions: Childhood adrenal tumours presented with hypertension showed an atypical course, variable presentation. We report a unique case of adrenal pheochromocytoma followed by the occurrence of non-functioning islet cell tumour. Reversal of hypertension by surgery is crucial. Imaging techniques are important to detect adrenal tumours. [source] Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunctionCLINICAL ENDOCRINOLOGY, Issue 1 2010André Lacroix Summary The aberrant adrenal expression and function of one or several G-protein coupled receptors can lead to cell proliferation and abnormal regulation of steroidogenesis in unilateral adenomas, carcinomas or in ACTH-independent macronodular adrenal hyperplasia (AIMAH). Excess cortisol secretion leading to either sub-clinical or overt Cushing's syndrome is the most prevalent phenotype reported to date. In a few patients, aberrant regulation of androgen excess has been reported. More recently, initial studies suggest that similar mechanisms are involved in the renin-independent regulation of aldosterone secretion in primary aldosteronism. In recent years, cases of familial AIMAH have been identified, and specific aberrant hormone receptors are functional in the adrenal of affected members. The identification of aberrant receptors can offer specific pharmacological approach to prevent disease progression and control abnormal steroidogenesis; alternatively, unilateral or bilateral adrenalectomy remains the treatment of choice. [source] The 4-mg intravenous dexamethasone suppression test in the diagnosis of Cushing's syndromeCLINICAL ENDOCRINOLOGY, Issue 1 2010Caroline Jung Summary Objective, Optimal diagnostic criteria for the 4-mg intravenous dexamethasone suppression test (IVDST) in patients with Cushing's syndrome (CS), compared with normal subjects, have not been established. We evaluated the performance of the 4-mg IVDST for differentiating CS from normal subjects and to define the responses in CS of various aetiologies. Design, subjects, measurements, Thirty-two control subjects [normal and overweight/obese participants with or without type 2 diabetes) were prospectively studied, and data from 66 patients with Cushing's disease (CD), three with ectopic ACTH syndrome (EAS), 14 with adrenal Cushing's (AC)] and 15 with low probability of CS (LPC) from three tertiary hospitals were retrospectively evaluated. Dexamethasone was infused at 1 mg/h for 4 h. Plasma cortisol and ACTH were measured at ,60 min (baseline), ,5 min, +3 h, +4 h, +5 h and at +23 and +23·5 h on Day 2. Results, Control subjects (including those with type 2 diabetes) exhibited a marked suppression of cortisol which was maintained until Day 2. Two of 15 patients with LPC had Day 2 cortisol results that overlapped with CS. Patients with CD demonstrated partial suppression, with rebound hypercortisolism on Day 2. Patients with AC and EAS did not suppress cortisol levels. Day 2 cortisol level of >130 nmol/l (or >20% of the baseline) diagnosed CS with 100% sensitivity and 96% specificity. Conclusion, While the IVDST allowed complete discrimination between control subjects and CS, 13% of LPC overlapped with CS. Given the small number of EAS, no conclusion can be drawn regarding the utility of this test in the differential diagnosis of CS. [source] Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindredsCLINICAL ENDOCRINOLOGY, Issue 6 2009Lucia Gagliardi Summary Objective, Cushing's syndrome due to familial ACTH-independent macronodular adrenal hyperplasia (AIMAH) has been reported in small kindreds. In vasopressin-sensitive AIMAH (VPs-AIMAH), VP stimulates an aberrant, ACTH-independent increase in cortisol. The aims of this study were to (i) delineate the preclinical phenotype of VPs-AIMAH in a three-generation kindred (AIMAH-01) and two smaller kindreds (AIMAH-02 and AIMAH-03) and (ii) investigate the aetiology of VP sensitivity in AIMAH-01. Design, Clinical studies of three kindreds for adrenal tumours or early Cushing's and molecular studies of adrenal tumours (AIMAH-01). Patients, Thirty-three individuals, from three kindreds, were screened for perturbations of the hypothalamic,pituitary,adrenal axis or adrenal tumours. Measurements, Patients underwent clinical, biochemical and adrenal imaging investigations. Evaluation included low-dose (1 IU/70 kg) VP stimulation. Adrenal VP receptor (AVPR1A, AVPR1B, AVPR2) expression (AIMAH-01) was assessed using RT-PCR and immunohistochemistry (IHC). IHC for VP was also performed. Results, AIMAH-01 had three siblings with Cushing's, and four individuals with suppressed ACTH/aberrant VP responses and/or adrenal nodules. In AIMAH-02, a father and son were affected. AIMAH-03 had three siblings with Cushing's. RT-PCR showed adrenal overexpression of AVPR1A and AVPR1B. IHC detected AVPR1A. The adrenal tumour from one patient also stained weakly for VP and AVPR2. Conclusion, Adrenal nodules, suppressed ACTH and increased VP sensitivity may represent preclinical disease, allowing early detection, and treatment, of affected individuals. In AIMAH-01, increased VP sensitivity may be due to adrenal VP receptor overexpression. In these kindreds, VPs-AIMAH is familial, and autosomal dominant inheritance is most likely. [source] Screening of Cushing's syndrome in adult patients with newly diagnosed diabetes mellitusCLINICAL ENDOCRINOLOGY, Issue 2 2007Giuseppe Reimondo Summary Objective Recent studies have shown that a relatively high number of diabetic patients may have unsuspected Cushing's syndrome (CS). The aim of the present study was to screen for CS in adult patients with newly diagnosed diabetes mellitus who were not selected for clinical characteristics, such as poor control and obesity, which may increase the pre-test probability of CS. Design, patients and measurement We prospectively evaluated 100 consecutive diabetic patients at diagnosis from 2003 to 2004. No patient had clear Cushingoid features. Screening was performed by using the overnight 1-mg dexamethasone suppression test (DST) after complete recovery from acute concomitant illnesses and attainment of satisfactory glycaemic control. The threshold of adequate suppression after DST was set at 110 nmol/l. Results Five patients failed to suppress cortisol after DST and underwent a repeated DST and a confirmatory standard 2-day, 2-mg DST after 3,6 months from the baseline evaluation. In one woman, a definitive diagnosis of CS was made by a surgically proven pituitary adenoma, and glycaemic control improved after cure of CS. Conclusions The results of the present study support the view that unknown CS is not rare among patients with diabetes mellitus. This is the first demonstration that screening for CS may be feasible at the clinical onset of diabetes in an unselected cohort of patients. Therefore, early diagnosis and treatment of CS may provide the opportunity to improve the prognosis of diabetes. [source] The role of desmopressin in bilateral and simultaneous inferior petrosal sinus sampling for differential diagnosis of ACTH-dependent Cushing's syndromeCLINICAL ENDOCRINOLOGY, Issue 1 2007Marcio Carlos Machado Summary Objective, ,Bilateral inferior petrosal sinus sampling (BIPSS) with corticotrophin-releasing hormone (CRH) stimulation is currently the gold standard test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Reports on the use of desmopressin in this approach are limited. The aim of this study was to evaluate the use of desmopressin during BIPSS in a cohort of patients with ACTH-dependent Cushing's syndrome. Design, ,A retrospective case-record study. Patients,, Fifty-six patients with confirmed ACTH-dependent Cushing's syndrome underwent BIPSS with desmopressin stimulation when presenting negative pituitary tumour imaging. Measurements,, Central to peripheral (CEN:PER) ACTH gradient, lateralization of the ACTH source and surgical tumour confirmation were evaluated. Results,, A CEN:PER ACTH gradient was found in 40 patients under basal conditions (CEN:PER , 2) and in 47 patients after desmopressin stimulation (CEN:PER , 3). Ectopic ACTH-producing tumours (three lung carcinoid tumour, one thymus carcinoid tumour and one thymus hyperplasia) were confirmed in five out of nine patients without the CEN:PER ACTH gradient, and four cases were false negative for Cushing's disease. Lateralization (IPS:IPS , 1·4) was observed in 80·8% of patients under basal conditions (38/47) and in 97·8% after desmopressin (46/47), and it was surgically confirmed in 78·7%. There were no false-positive cases. Sensitivity and specificity were 92·1% and 100%, respectively. Conclusions, ,Desmopressin improves the differential diagnosis of ACTH-dependent Cushing's syndrome by amplifying the CEN:PER and IPS:IPS ACTH gradients, and is therefore a useful ACTH secretagogue in BIPSS. [source] Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillanceCLINICAL ENDOCRINOLOGY, Issue 5 2005A. Brew Atkinson Summary Objective, There have been a few reports on long-term remission rates after apparent early remission following pituitary surgery in the management of Cushing's disease. An undetectable postoperative serum cortisol has been regarded as the result most likely to predict long-term remission. Our objective was to assess the relapse rates in patients who underwent transsphenoidal surgery in order to determine whether undetectable cortisol following surgery was predictive of long-term remission and whether it was possible to have long-term remission when early morning cortisol was measurable but not grossly elevated. Endocrinological factors associated with late relapse were also studied. Patients, We reviewed the long-term outcome in 63 patients who had pituitary surgery for the treatment of Cushing's disease between 1979 and 2000. Measurements, Case notes were reviewed and the current clinical and biochemical status assessed. Our usual practice was that early after the operation, an 08:00 h serum cortisol was measured 24 h after the last dose of hydrocortisone. This was followed by a formal low-dose dexamethasone suppression test. Current clinical status and recent 24-h urinary free cortisol values were used as an index of activity of the Cushing's disease. If there was evidence suggesting relapse, a low-dose dexamethasone suppression test was performed. In many patients, sequential collections of early morning urine specimens for urinary cortisol to creatinine ratio were also performed in an attempt to diagnose cyclical and intermittent forms of recurrent hypercortisolism. We did this if there was conflicting endocrine data, or if patients were slow to lose abnormal clinical features. Results, Mean age at diagnosis was 40·3 years (range 14,70 years). Mean follow-up up time was 9·6 years (range 1,21 years). Forty-five patients (9 males/36 females) achieved apparent remission immediately after surgery and were subsequently studied long term. Of these 45 patients, four have subsequently died while in remission from hypercortisolism. Ten of the remaining 41 patients have relapsed. Of those 10, six demonstrated definite cyclical cortisol secretion. Two of the 10 had undetectable basal serum cortisol levels in the immediate postoperative period. Thirty-one patients are still alive and in remission. Fourteen (45%) of the 31 who remained in remission had detectable serum cortisol levels (> 50 nmol/l) immediately postoperatively, and remain in remission after a mean of 8·8 years. Our relapse rate was therefore 10/45 (22%), after a mean follow-up time of 9·6 years, with mean time to relapse 5·3 years. Conclusions, The overall remission rate of 56% (35/63) at 9·6 years follow-up is disappointing and merits some re-appraisal of the widely accepted principle that pituitary surgery must be the initial treatment of choice in pituitary-dependent Cushing's syndrome. Following pituitary surgery, careful ongoing expert endocrine assessment is mandatory as the incidence of relapse increases with time and also with increasing rigour of the endocrine evaluation. A significant number of our patients were shown to have relapsed with a cyclical form of hypercortisolism. [source] A dose,response study of salivary cortisol after dexamethasone suppression test in Cushing's disease and its potential use in the differential diagnosis of Cushing's syndromeCLINICAL ENDOCRINOLOGY, Issue 6 2003Margaret Castro Summary objective, A dose,response study with different doses of dexamethasone (dex) to assess the corticotrophic resistance in Cushing's disease (CD) using salivary cortisol as an end point has not yet been evaluated. We also reported our experience with salivary cortisol compared to plasma cortisol determination during dex suppression test (DST) and after ovine corticotrophin release hormone (oCRH) test in the differential diagnosis of Cushing's syndrome (CS). design, We studied 46 patients with CS, including 28 patients with CD, 16 with adrenal disease and two with occult ectopic adrenocorticotropic hormone (ACTH) tumours. Salivary cortisol was compared to plasma cortisol and ACTH during a DST 2 mg for 2 days, 8 mg for 2 days and 24 mg for 1 day, and after oCRH test. results, We observed a dose-dependent suppression of salivary cortisol, plasma cortisol and ACTH in CD patients. Salivary cortisol presented a higher percentage of suppression than plasma cortisol: 42%vs. 15% (P < 0·002), 82%vs. 67% (P < 0·002) and 90%vs. 83% (P < 0·03) after 2, 8 and 24 mg/day dex, respectively. The lowest percentage of suppression was observed for plasma ACTH. The parallelism of these lines identified that the criterion of 65% suppression of salivary cortisol corresponding to 50% suppression of plasma cortisol after 8 mg/day for 2 days is consistent with CD. The sensitivity and specificity using 50% suppression for plasma cortisol were 81% and 83%, respectively, for 8 mg DST. Using the criterion of 65% suppression of salivary cortisol, the sensitivity and specificity were 86% and 100%, respectively, for 8 mg DST. After oCRH test the sensitivity and specificity were 86% and 91%, respectively, for ACTH, 100% and 64%, respectively, for plasma cortisol and 93% and 91%, respectively, (20% of increment) or 86% and 100%, respectively, (35% increment) for salivary cortisol. conclusion, In conclusion, salivary cortisol presents more profound suppression than plasma cortisol or ACTH in a dose,response pattern after different doses of dex in patients with CD. In addition, our data suggest that measurement of salivary cortisol might improve the DST as compared to plasma cortisol in the differential diagnosis of CS. [source] Ectopic ACTH syndrome caused by pulmonary carcinoid tumourletsCLINICAL ENDOCRINOLOGY, Issue 6 2001S. Tofé Povedano The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions. [source] Alternaria infections: laboratory diagnosis and relevant clinical featuresCLINICAL MICROBIOLOGY AND INFECTION, Issue 8 2008F. J. Pastor Abstract The genus Alternaria contains several species of melanized hyphomycetes that cause opportunistic human infections. The published literature contains 210 reported cases of human alternarioses between 1933 and the present day. The most frequent clinical manifestations are cutaneous and subcutaneous infections (74.3%), followed by oculomycosis (9.5%), invasive and non-invasive rhinosinusitis (8.1%) and onychomycosis (8.1%). Immunosuppression is frequently associated with cutaneous and subcutaneous infections and rhinosinusitis. The most important risk factors for cutaneous and subcutaneous infections are solid organ transplantation and Cushing's syndrome, and those for rhinosinusitis are bone marrow transplants. Having been exposed to soil and garbage is common in all cases of oculomycosis, with corticotherapy being a risk factor in 50% of these cases. Previous contact with soil and/or trauma to the nails is associated with most cases of onychomycosis. In general, alternariosis shows a good response to conventional antifungal drugs. On some occasions, steroid suppression or reduction is sufficient to resolve an infection. Itraconazole is the antifungal drug used most frequently to successfully treat onychomycosis and cutaneous and subcutaneous infections. Posaconazole and voriconazole are promising therapeutic options, with the latter being especially so for oculomycosis. [source] Cushing's syndrome in pregnancy and neonatal hypertrophic obstructive cardiomyopathyACTA PAEDIATRICA, Issue 10 2004L Fayol Cushing's syndrome is rare in pregnancy but can cause spontaneous abortion, stillbirth or premature birth. We report a case of transient hypertrophic obstructive cardiomyopathy in a newborn whose mother had hypercortisolism due to a primary adrenal lesion. There was no family history of hypertrophic obstructive cardiomyopathy. Follow-up revealed complete resolution of the cardiac abnormalities in the infant. Cushing's syndrome in the mother resolved after delivery. Although maternal hypercortisolism seldom results in symptomatic hypercortisolism in the newborn, hypertrophic obstructive cardiomyopathy can occur. [source] Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patientACTA PAEDIATRICA, Issue 9 2002KM Main Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1600 ,g budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo. Conclusion: This observation suggests that the metabolic clearance of budesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge. [source] | ||||||||||