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Inferior petrosal sinus sampling in patients with Cushing's syndrome and contradictory responses to dynamic testing
No full textThe corticotropin-releasing hormone test in the diagnosis of ACTH-dependent Cushing's syndrome: a reappraisal
No full textOBJECTIVE Stimulation with corticotropin-releasing hormone (CRH) is one of principal tools for the differential diagnosis of ACTH-dependent Cushing's syndrome. However, different dosages and species of CRH may be employed; further, ACTH levels can be measured by radioimmunoassay (RIA) or immunoradiometric assay (IRMA). The aims of the present study were to perform a reappraisal of the diagnostic accuracy of the CRH test taking these different testing modalities into consideration and to study the correlation between basal ACTH and cortisol levels and their responses to CRH in patients with Cushing's disease.
PATIENTS: The study population comprised 148 patients with Cushing's disease and 12 patients with ectopic ACTH secretion collected through an Italian multicentre study.
DESIGN Patients were submitted to stimulation with 100 mug human or ovine CRH (36% and 64% of subjects, respectively) and ACTH measured either by RIA or IRMA (28% and 72%, respectively). A 50% increase in ACTH and cortisol levels was considered indicative of Cushing's disease.
RESULTS Mean peak ACTH levels measured by RIA and IRMA were comparable, as was the diagnostic accuracy of the test with the two assays (87% for IRMA and 84% for RIA, ns). In patients with Cushing's disease, stimulation with ovine CRH induced greater hormonal responses compared to testing with human CRH although only the cortisol response reached statistical significance (ACTH: 247.5 +/- 28.0% vs. 168.5 +/- 21.3% over baseline, P = 0.06; cortisol: 89.3 +/- 8.5% vs. 60.8 +/- 9.6% over baseline, P < 0.05 for ovine and human CRH, respectively). No appreciable rise in ACTH and cortisol levels was registered among patients with ectopic ACTH secretion. Diagnostic accuracy of the cortisol response was significantly greater with the ovine than with human peptide (71% vs. 49%, P < 0.05, for ovine and human CRH, respectively) while the ACTH response yielded equal diagnostic accuracy (86% vs. 87%, ns, for the ovine and human peptide, respectively). Interestingly, the correlation between ACTH and cortisol peak responses in patients with Cushing's disease was significantly greater for human than for ovine CRH (r = 0.68 vs. r = 0.41, P < 0.01, respectively). In addition, baseline cortisol levels exhibited a significant negative correlation with both the ACTH and cortisol response to CRH suggesting the persistence of the negative cortisol feedback in patients with Cushing's disease.
CONCLUSIONS (A) Both RIA and IRMA can be used indifferently for the assessment of the ACTH response to CRH. (B) Human and ovine CRH provide the same diagnostic accuracy as regards the ACTH response which, incidentally, represents the most accurate criterion for the evaluation of the CRH test; ovine CRH is superior to the human peptide in the evaluation of the cortisol response. (C) In patients with Cushing's disease, endogenous cortisol maintains the ability to negatively modulate CRH-stimulated corticotropin secretion
Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study
No full textThe past 45 yr' experience with Cushing's syndrome (CS) has led to the awareness of its complex nature and, by the same token, brought about an increase in the diagnostic and therapeutic dilemmas. We carried out a retrospective multicentre study on the diagnostic work-up and treatment in 426 patients with CS, subdivided as follows: 288 with Cushing's disease (CD), 80 with an adrenal adenoma, 24 with an adrenal carcinoma, 25 with ectopic ACTH and/or CRH secretion, and 9 with ACTH-independent nodular adrenal hyperplasia. Normal urinary free cortisol (UFC) values among multiple collections were recorded in about 10% of patients with CS. In 28% of patients with ACTH-independent CS, basal ACTH concentrations were within the normal range but did not respond to CRH stimulation. Measurement of ACTH levels by immunoradiometric assay, rather than by RIA, offered a greater chance of recognizing patients with ACTH-independent CS or ectopic secretion. A 50% increase in ACTH or cortisol levels after CRH yielded a diagnostic accuracy of 86% and 61%, respectively, in the differential diagnosis of ACTH-dependent CS. An 80% decrease in cortisol levels after 8 mg dexamethasone overnight, or in UFC values after the classical 2-day administration, excluded an ectopic secretion but carried a low negative predictive value given the high number of nonsuppressors among patients with CD. Pituitary imaging identified an adenoma in 61% of patients with CD. At inferior petrosal sinus sampling, an ACTH centre: periphery gradient after CRH less than 3, correctly classified all patients with ectopic secretion but misdiagnosed 15% of 76 patients with CD. Transsphenoidal pituitary surgery, the standard therapy for CD, resulted in complete remission (appearance of clinical signs of adrenal insufficiency associated with low/normal UFC excretion and, when available, low/normal morning plasma ACTH and cortisol levels) in 69% of patients. The overall relapse rate after pituitary surgery was 17%. The probability of relapse-free survival, as assessed by Kaplan-Meier analysis, was 95% at 12 months, 84% at 2 yr, and 80% at 3 yr. Risk of relapse was significantly correlated with postoperative baseline plasma ACTH and cortisol peak after CRH. No relapses were observed among patients who did not respond to CRH. Other therapeutic approaches for CD, such as pituitary irradiation and medical therapy, resulted in normalization of cortisol secretion in about half of treated cases. In summary, an accurate selection of the available diagnostic tools leads to the correct diagnosis in the majority of patients with CS. The therapeutic options for CD, adrenal carcinoma, and ectopic secretion are, as yet, not fully satisfactory. The high incidence of relapse after pituitary surgery calls for a prolonged follow-up
Unusual association of adrenal angiosarcoma and Cushing's disease
No full textThe occurrence of an angiosarcoma in the adrenal gland is exceedingly rare as only 21 patients have been reported in the literature since its first description 30 years ago. We report the clinicopathological features of a 34-year-old patient presenting with overt Cushing's syndrome due to a ACTH-secreting pituitary adenoma and an adrenal spindle cell angiosarcoma. This association made the diagnosis of Cushing's disease particularly puzzling in view of the results of biochemical tests which were compatible in part with adrenal and in part with paraneoplastic hypercortisolism and the negative pituitary imaging. The unique appearance of this tumor and its diagnostic implications are discussed
Reduced taste responsiveness and increased food neophobia characterize obese adults
Full text linkThe aim of the present study was to investigate the relationship between two well-established markers of taste perception, 6-n-propylthiouracil (PROP) responsiveness and fungiform papillae number, in obese and healthy-weight subjects. The association between taste responsiveness and food neophobia attitude was evaluated to understand if these variables are linked to nutritional status of subjects. Forty healthy-weight (Body Mass Index: 22.67 ± 0.43 kg/m2) and forty-five obese (Body Mass Index: 37.57 ± 0.77 kg/m2) subjects were involved. PROP responsiveness and fungiform papillae number were positively correlated to each other in both groups of subjects (healthy-weight: r = 0.67, p < 0.001; obese: r = 0.83, p < 0.001). PROP responsiveness ratings and fungiform papillae number were significantly negatively correlated with food neophobia scores in both group of subjects (p < 0.01). Subjects characterized as significantly less sensitive and more neophobics had a higher Body Mass Index. Especially, obese men showed significant lower taste responsiveness (p < 0.05) and higher food neophobia scores (p < 0.05) compared to obese women and healthy-weight subjects, both sexes. The nutritional status of the subjects seems to be linked to taste responsiveness and food neophobic attitude. These data suggest that, between several factors which could play a role in the control of body weight, understand how sensory perception affects eating behavior could give important information to study variables which may determine food habits
Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in obese subjects
No full textObjective: The role of glucocorticoids production in adipose tissue in the development of metabolic disorders in humans has not been fully characterized. We investigated whether in obese subjects, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression in subcutaneous (SAT) and visceral (VAT) adipose tissue is associated with the occurrence of metabolic disorders and the expression of adiponectin and tumor necrosis factor α (TNFα) and two glucocorticoid-regulated adipokines able to influence the metabolic control. Design and subjects: Sixty-two obese patients were enrolled in the study. SAT and VAT samples were obtained from 13 patients undergoing bariatric surgery (body mass index (BMI) 39.1±5.3 kg/m2). SAT samples were obtained from 49 patients who underwent periumbilical biopsy (BMI 36.9±5.1 kg/m2). Measurements: Oral glucose tolerance tests in subjects without known diabetes. Circulating glucose, lipid, insulin, adiponectin, TNFα and urinary-free cortisol levels. Real-time PCR to quantify mRNA levels of 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), adiponectin and TNFα. Western blot analysis to evaluate 11β-HSD1 protein expression. Results: In the majority of the obese subjects, VAT expresses more 11β-HSD1 than SAT. VAT 11β-HSD1 expression was not associated with metabolic disorders. SAT 11β-HSD1 mRNA levels were higher in subjects with than in those without metabolic syndrome (P<0.05) and in patients with type 2 diabetes compared to patients with impaired or normal glucose tolerance (P<0.0001). SAT 11β-HSD1 expression was independently related to fasting glucose (P<0.0001) and urinary-free cortisol levels (P<0.01), and increased expression of 11β-HSD1 was associated with increased adiponectin and TNFα expression and decreased serum adiponectin levels (all P's <0.05). Conclusions: In obese subjects, increased 11β-HSD1 expression in SAT, but not in VAT, is associated with the worsening of metabolic conditions. We hypothesize that higher glucocorticoid production in adipose tissue would favor the development of metabolic disorders through a decrease in adiponectin release
Enhanced prolactin responsiveness to galanin in patients with Cushing's disease
No full textObjective: Galanin is believed to play a role in the control of prolactin (PRL) secretion in the rat. Such a role is uncertain in humans where the neuropeptide is expressed by the corticotrophs. However, in clinical conditions of enhanced ACTH secretion, increased PRL levels are often observed. Therefore, we evaluated the effect of galanin infusion on serum PRL levels in patients with Cushing's disease and in control subjects. For comparison, the PRL responses to TRH and metoclopramide were also investigated in the same patients. Design - Four tests were performed: (a) 40-minute infusion of 0.3 μg/kg/min of galanin; (b) infusion of normal saline only; (c) metoclopramide test (10 mg as i.v. bolus); (d) TRH test (200 mg as i.v. bolus). Patients: Twenty-four normal subjects and nine patients suffering from active Cushing's disease were investigated. Measurements: Serum concentrations of PRL were measured by radioimmunoassay on blood samples collected before and for 90 minutes after drug or saline administration. Results: Serum baseline PRL levels were superimposable in normal subjects and in patients with Cushing's disease. In normal subjects, infusion of galanin induced a distinct PRL increase compared to saline (mean ±SEM incremental areas 6514 ± 2572 vs 540 ± 571 mU/l/90 min, P = 0.05, respectively). In patients with Cushing's disease, galanin evoked a remarkable PRL rise with hormone levels which were significantly greater (p < 0.001) than those observed in the same patients after infusion of saline (21908 ± 4180 vs 534 ± 1556 mU/l/90 min) or after galanin administration in controls (P < 0.01). The PRL response to TRH, and, much more so, to metoclopramine was significantly lower in patients with Cushing's disease than in normal subjects (42125 ± 8000 vs 73181 ± 7246 mU/l/90 min, P < 0.01 after TRH and 79095 ± 27265 vs 229049 ± 10602 mU/l/90 min, P < 0.01 after metoclopramide). Conclusions: Galanin appears to be a specific, though weak, PRL secretagogue in normal subjects. The galanin-induced PRL release was significantly increased in patients with Cushing's disease. A number of hypothetical mechanisms may underlie the enhanced PRL reactivity to galanin in Cushing's disease. This finding together with the impaired PRL responsiveness to TRH and metoclopramide, also observed in this study, is a further example of a dysregulation of PRL secretion in patients with Cushing's disease
Cross-modal interactions for custard desserts differ in obese and normal weight Italian women
No full textThe effects of variation in odors and thickening agents on sensory properties and acceptability of a model custard dessert were investigated in normal weight and obese women. Subjects rated their liking and the intensity of sensory properties (sweetness, vanilla and butter flavors, and creaminess) of 3 block samples (the first varied in vanilla aroma, the second varied in butter aroma and the third varied in xanthan gum). Significant differences were found in acceptability and intensity ratings in relation to body mass index. The addition of butter aroma in the custard was the most effective way to elicit odor-taste, odor-flavor and odor-texture interactions in obese women. In this group, butter aroma, signaling energy dense products, increased the perception of sweetness, vanilla flavor and creaminess, which are all desirable properties in a custard, while maintaining a high liking degree. Understanding cross-modal interactions in relation to nutritional status is interesting in order to develop new food products with reduced sugar and fat, that are still satisfying for the consumer. This could have important implications to reduce caloric intake and tackle the obesity epidemic
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