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Biomedical subjects

C Invitti

Publications and source records attributed to C Invitti.

At least 19 recordsLinked to original sources
PubMed2006

Metabolic syndrome in obese Caucasian children: prevalence using WHO-derived criteria and association with nontraditional cardiovascular risk factors.

OBJECTIVE: Studies on the prevalence of metabolic syndrome (MS) in European obese children using child-based criteria are scanty. Moreover, it is unknown if nontraditional cardiovascular disease (CVD) risk factors are associated with the MS at this early age in these subjects. DESIGN AND SUBJECTS: We studied the prevalence of the MS in 588 Caucasian obese children and adolescents by devising a World Health Organization derived definition and child-specific criteria, whose deviation from normalcy was based on an age, sex, and ethnically comparable control group of 1363 subjects. In a subgroup of 206 obese children, we investigated the association of the MS with nontraditional CVD risk factors. MEASUREMENTS: Fasting blood samples for glucose and lipids measurements were taken in both control and obese children. In addition, the obese children underwent an oral glucose tolerance test. In the subgroup of 206 obese children, albumin excretion rate , plasma uric acid, fibrinogen, plasminogen activator inhibitor type 1(PAI-1), C-reactive protein, interleukin 6 and white blood cells were also measured. RESULTS: The prevalence of MS was 23.3%. A similar prevalence of 23% of MS was recorded in the subgroup of 206 obese children in whom measurements of nontraditional CVD risk factors were available. After adjustment for the degree of obesity, subjects with MS had significantly higher uric acid (6.6+/-0.23 vs 6.1+/-0.12 mg/dl, P<0.0001) and PAI-1 plasma concentrations (231.4+/-25.50 vs 214.3+/-12.96 ng/ml, P<0.05) and a higher frequency of microalbuminuria (37 vs 20%, P<0.05) than those without MS. Microalbuminuria, uric acid and PAI-1 explained 10.6% of the variance of MS. CONCLUSION: Approximately, a quarter of Caucasian obese children have the MS. The association of MS with several nontraditional risk factors for CVD early in life suggests a heightened CVD risk in these individuals.

Adolescent↗
PubMed2002

[Obesity and low-grade systemic inflammation].

The aim of this review is to deal with the significance of obesity as a promotor of a chronic low-grade inflammatory reaction favouring the development of atherosclerosis and cardiovascular diseases. Adipose tissue synthetizes and releases inflammatory cytokines involved in various atherothrombotic mechanisms and in glucose and lipid metabolism. A local renin-angiotensin system may partially support the obesity related hypertension. Most obese subjects had elevated plasma levels of inflammatory markers which correlate with the degree of obesity and insulin resistance and decrease after weight reduction and exercise. Some evidences suggest that long-chain polyunsaturated fatty acids and thiazolidinediones may be useful in preventing atherosclerosis. Obesity, by itself, has been considered an independent risk factor for cardiovascular diseases. The hypothesis that it is linked to the associated low-grade chronic inflammation is supported by the existence of altered indexes of chronic inflammation also in obese children who are free of other pathological conditions. Further research will be required to determine the pathophysiological meaning of the chronic inflammation associated to obesity.

Adipose Tissue↗
PubMed2001

The corticotropin-releasing hormone test in the diagnosis of ACTH-dependent Cushing's syndrome: a reappraisal.

OBJECTIVE: 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 microg 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.

Adolescent↗
PubMed2001

Unusual association of adrenal angiosarcoma and Cushing's disease.

The 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.

Adrenal Gland Neoplasms↗
PubMed2001

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol.

OBJECTIVE: To compare salivary, plasma and urinary free cortisol (UFC) measurements in patients with anorexia nervosa, in whom an overdrive of the hypothalamic-pituitary-adrenal (HPA) axis is well established but information on salivary cortisol is lacking, in viscerally obese patients in whom subtle abnormalities of cortisol secretion and metabolism are postulated, and in normal-weight healthy women. PARTICIPANTS AND EXPERIMENTAL DESIGN: Measurement of salivary cortisol offers a convenient way to assess the concentrations of free, biologically active cortisol in plasma in different physiopathological settings. Forty-seven drug-free, newly diagnosed women with active restrictive anorexia nervosa, 30 restrictive anorexic women undergoing chronic psychopharmacological treatment, 47 women with mild-to-moderate visceral obesity, 103 women with severe central obesity and 63 normal-weight healthy women entered the study. Salivary and blood samples were collected at 0800 h, 1700 h and 2400 h, together with three consecutive 24-h urine specimens for UFC determination. In controls and patients with anorexia nervosa (n=83), salivary and plasma cortisol were also measured after a 1-mg overnight dexamethasone suppression test (DST). In patients with anorexia nervosa, mood was rated by the Hamilton scale for anxiety and depression. RESULTS: Untreated patients with anorexia nervosa showed increased plasma and salivary cortisol and UFC concentrations (all P<0.001 compared with controls), and decreased cortisol suppression after DST in plasma and saliva (P<0.0001 and P<0.005 respectively compared with controls). These alterations were less pronounced, although still statistically significant, in treated patients with anorexia nervosa. Salivary cortisol was highly correlated with paired plasma cortisol in the whole population and after splitting the participants by group (P<0.0001). However, for plasma cortisol values greater than 500 nmol/l (the corticosteroid-binding globulin saturation point), this parallelism was lost. Taking plasma cortisol as a reference, the level of agreement for post-dexamethasone salivary and plasma cortisol was 58.9% among suppressors and 77.8% among non-suppressors (chi2 test: P<0.01). Decreased 0800 h/2400 h cortisol ratios were observed in plasma and saliva in drug-free patients with anorexia nervosa (P<0.005 and P<0.05 respectively compared with controls), and in saliva in severely obese patients (P<0.05 compared with controls). Depression and anxiety scores were unrelated to cortisol concentrations in any compartment. CONCLUSIONS: Salivary cortisol measurement is a valuable and convenient alternative to plasma cortisol measurement. It enables demonstration of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of the cortisol diurnal rhythm in women with visceral obesity. With the establishment of more specific and widely acceptable cut-off values for dynamic testing, measurement of salivary cortisol could largely replace plasma cortisol measurement.

Adult↗
PubMed2000

Markers of activation of coagulation and fibrinolysis in patients with Cushing's syndrome.

Patients with active Cushing's syndrome have an increased thrombotic tendency. We chose to reassess the mechanism underlying the thrombophilic state associated with this clinical condition using sensitive markers of coagulation and fibrinolysis activation in 17 patients with active disease. The results were compared with those obtained in 12 Cushing's patients successfully treated by surgery and in 20 normal individuals. The general pattern of results in patients with active disease was the finding of increased levels of von Willebrand factor (VWF: Ag), a marker of enhanced metabolic function of endothelial cells (VWF:Ag 181 +/- 42 vs 110 +/- 43, p<0.001 in normal subjects), accompanied by signs of heightened thrombin and plasmin generation, expressed by high levels of thrombin-antithrombin (TAT 5.59+/-3.6 vs 3.06+/-0.92 ng/ml in controls, p<0.01) and plasmin-antiplasmin complexes (PAP 407+/-176 vs 245+/-67 ng/ml in controls, p<0.01). VWF:Ag and TAT values were significantly higher in hypertensive than in normotensive patients with active disease (205+/-40 vs 155+/-26 U/dl, p<0.05 and 7.49+/-3.7 vs 3.45+/-1.8, p<0.01, respectively). Plasma levels of plasminogen activator inhibitor type 1 were higher, though not to a statistically significant extent, in patients with active disease compared to controls (12.8+/-12.3 vs 5.6+/-7.4 IU/ml, NS) and positively correlated with body mass index (r=0.66, p<0.01). After surgical control of Cushing's syndrome, there was a partial or complete reversal of the abnormalities to values similar to those found in normal individuals. Our data suggest that the thrombophilic state present in patients with active Cushing's syndrome is related to an enhanced metabolic function of endothelial cells; this in turn may be caused by an heightened production of thrombin with secondary hyperfibrinolysis. Primary prophylaxis with anticoagulants is recommended in these patients when they are exposed to a thrombophilic condition such as surgery.

Adolescent↗
PubMed2000

Glucocorticoids and neuroendocrine function.

Recent experimental evidence supports the role of glucocorticoids in the neuroendocrine control of food intake and energy expenditure. In particular, glucocorticoids promote food consumption directly through stimulation of NPY and inhibition of CRH and melanocortin release. CRH and NPY are also functionally linked by a mutual regulation. CRH is anorexigenic when secreted acutely while it exerts the opposite effect when, upon sustained secretion, it stimulates the hypothalamo-pituitary-adrenal (HPA) axis. The orexigenic effects of glucocorticoids are counteracted by a steroid-induced rise in leptin levels that closes a regulatory loop regarding food consumption. Furthermore, glucocorticoids may alter body fat distribution, increasing truncal adiposity both directly and by inhibition of growth hormone secretion. No clearcut alterations of the HPA function are apparent in obesity as a whole. However, subtle and specific abnormalities may be noted in subsets of obese patients. Indeed, obesity, mostly visceral type, is associated with an increased cortisol clearance and 11-beta hydroxysteroid dehydrogenase activity in the omental fat. In the same vein, an increased cortisol rise following a mixed meal has been observed in obese subjects. Finally, it has been proposed that adrenal incidentalomas, often characterized by enhanced cortisol secretion, might be a clinical expression of the X syndrome.

Animals↗
PubMed2000

The desmopressin test in the differential diagnosis between Cushing's disease and pseudo-Cushing states.

Differentiating Cushing's disease (CD) from pseudo-Cushing (PC) states may still be difficult in current practice. Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CD but not in the majority of normal, obese, and depressed subjects, we investigated its ability to discriminate CD from PC states. One hundred seventy-three subjects (76 with active CD, 30 with PC, 36 with simple obesity, and 31 healthy volunteers) were tested with an iv bolus of 10 microg DDAVP. Sixty-one of these subjects also underwent a control study with saline. DDAVP induced marked ACTH and cortisol rises in CD (P < 0.005 vs. saline, for both ACTH and cortisol) but not in PC. A significant ACTH elevation occurred upon DDAVP administration also in normal and obese subjects, but it was much smaller than that observed in patients with CD (P < 0.0001). A peak absolute ACTH increase (> or =6 pmol/L), after DDAVP, allowed us to recognize 66 of 76 patients with CD and 88 of 97 subjects of the other groups. The same criterion correctly identified 18 of 20 patients with mild CD (24-h urinary free cortisol < or = 690 nmol/day) and 29 of 30 PC, resulting in a diagnostic accuracy of 94%, which was definitely higher than that displayed by urinary free cortisol, overnight 1-mg dexamethasone suppression test, and midnight plasma cortisol. In conclusion, the DDAVP test seems to be a useful adjunctive tool for the evaluation of hypercortisolemic patients chiefly because of its ability to differentiate mild CD from PC states.

Adolescent↗
PubMed1999

Glucocorticoid receptors in anorexia nervosa and Cushing's disease.

BACKGROUND: Patients with anorexia nervosa do not display cushingoid features in spite of elevated cortisol plasma levels. Whether a cortisol resistance or a reduced availability of the metabolic substrates necessary to develop the effect of glucocorticoids is responsible for this has not been established. METHODS: Twenty-two patients with severe restrictive anorexia nervosa, 10 patients with active Cushing's disease, and 24 healthy volunteers without psychiatric disorders or mood alterations were investigated. Glucocorticoid receptor characteristics were examined on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which represents an index of DNA synthesis. RESULTS: The number of glucocorticoid receptors on mononuclear leukocytes (MNL) was comparable in patients with anorexia nervosa, patients with active Cushing's disease, and normal subjects (binding capacity 3.3 +/- 0.23 vs. 3.7 +/- 0.30 and 3.5 +/- 0.20 fmol/10(6) cells). Conversely, glucocorticoid receptor affinity was significantly decreased in anorexia nervosa as well as in Cushing's patients compared to control subjects (dissociation constant 4.0 +/- 0.31 and 4.1 +/- 0.34 vs. 2.9 +/- 0.29 nmol/L, p < .001) and inversely correlated with the levels of urinary free cortisol in both groups of patients. Basal [3H]thymidine incorporation in MNL was significantly reduced in anorexia nervosa as well as in Cushing's patients compared to control subjects (p < .001) and was diminished by dexamethasone to an extent similar to control subjects in patients with anorexia nervosa, but significantly (p < .001) less in those with Cushing's disease. In patients with anorexia nervosa, the incorporation of [3H]thymidine into the MNL was inversely correlated with urinary free cortisol levels. CONCLUSIONS: These data indicate that the lack of cushingoid features in patients with anorexia nervosa is not ascribable to a reduced sensitivity to glucocorticoids but is more likely due to the paucity of metabolic substrates.

Adolescent↗
PubMed1999

Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis.

The 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.

Adenoma↗
PubMed1999

Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo and in vitro.

Galanin, a brain-gut peptide, is also synthesized and released by the pituitary. In man, galanin-like immunoreactivity and galanin messenger RNA have been detected specifically in normal and tumoral corticotropes, but little is known about the production and release of galanin by the human pituitary. We evaluated galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients with Cushing's disease before and after CRH administration. For comparison, the galanin response to CRH was evaluated in 8 normal controls. Galanin secretion by pituitary tumor cultures ranged from 30-230 pmol/4 h. Incubation with CRH induced an increase in galanin concentrations (100 pM CRH: 151 +/- 32%; 1 nM CRH: 232 +/- 43%; 10 nM CRH: 246 +/- 35%; and 100 nM CRH: 270 +/- 44% unstimulated levels at 24 h, P < 0.05). The stimulatory effect of CRH seemed to be dose-dependent. Basal and CRH-stimulated ACTH and galanin concentrations also exhibited a strong positive correlation in single tumor cultures. At IPS sampling, mean basal plasma galanin concentrations in the dominant IPS were somewhat higher than those registered at the periphery (18.6 +/- 1.94 vs. 15.8 +/- 1.60 pmol/L, P = 0.05). Administration of CRH induced a modest but significant increase in galanin concentrations at all three sampling sites. No correlations were found between ACTH and galanin levels in the IPSs and at the periphery. Different from what was observed in patients with Cushing's disease, CRH did not modify plasma galanin concentrations in normal subjects. In conclusion, this study demonstrates that galanin is released by human tumoral corticotropes and responds to CRH. The role of locally produced galanin is, as yet, unknown but may possibly be that of a autocrine/paracrine modulator.

Adenoma↗
PubMed1998

Altered morning and nighttime pulsatile corticotropin and cortisol release in polycystic ovary syndrome.

An overdrive of the hypothalamic-pituitary-adrenal (HPA) axis has been postulated in patients with polycystic ovary syndrome (PCOS). However, little is known concerning the pulsatile modes of corticotropin (ACTH) and cortisol secretion in these patients. To further investigate this issue, spontaneous ACTH and cortisol release were evaluated in 16 normal-weight patients with PCOS and 16 control women. Nine PCOS patients and eight controls were studied between 8 AM and 12 AM (noon), and seven PCOS patients and eight controls between 11 PM and 3 AM. Venous blood samples were taken at 10-minute intervals. Cluster analysis was used to assess ACTH and cortisol pulse frequency and amplitude, deconvolution to calculate mean hormone secretion rates, and approximative entropy (ApEn) to measure the orderliness of ACTH and cortisol time-series data. PCOS patients compared with controls displayed increased ACTH and cortisol release (area under the curve [AUC] and mean plasma concentration) both in the morning and at night. This was not due to increased hormonal secretory burst frequency, but to higher hormonal interpeak valley concentrations and, in the case of ACTH, nighttime pulse amplitudes. Mean ACTH and cortisol secretion rates also were increased in PCOS patients. Further, both controls and PCOS patients exhibited significant (0 to 20 minutes lagged) concordance between individual daytime pulsatile ACTH and cortisol release episodes. As shown by increased ApEn values, PCOS patients had more disorderly daytime cortisol release. In addition, the normal daytime correlation between the amount of pulsatile ACTH and cortisol release as observed in the controls was lost in PCOS patients. Finally, cross-correlation analysis showed a more prominent negative correlation in PCOS patients versus controls between plasma cortisol and 40- to 120-minute delayed ACTH concentrations in the morning, indicating a more sustained negative feedback of cortisol on ACTH release in PCOS at this time. Taken together, these findings demonstrate the existence of multifaceted dysregulation of the HPA axis in PCOS.

Adolescent↗
PubMed1996

Effect of chronic treatment with octreotide nasal powder on serum levels of growth hormone, insulin-like growth factor I, insulin-like growth factor binding proteins 1 and 3 in acromegalic patients.

Octreotide nasal powder is a delivery system of the somatostatin analogue developed to overcome the inconvenience of repeated subcutaneous administrations. Eight patients with clinically active acromegaly were treated for three months with octreotide nasal powder which was administered at the initial dosage of 0.125 mg tid, doubling the dosage up to 2 mg tid in order to obtain a mean GH value below 5 micrograms/l during 8 daytime hours. In 4 of these patients, treatment was prolonged till the sixth month. Blood samples were taken on days 15, 29, 43, 55, 90, 120, 150, 180 for GH, IGF-I, IGFBP-3, IGFBP-1 and insulin measurements. Before treatment, mean daytime GH and morning IGF-I serum levels were both increased but not correlated with each other. Serum IGFBP-3 levels were higher than normal and positively correlated with those of GH, IGF-I and insulin. Insulin levels were elevated and positively correlated with those of GH but not with those of IGF-I and IGFBP-1. Serum IGFBP-1 levels were in the low normal range and not correlated with any of the other parameters. Treatment with octreotide nasal powder induced in all patients a marked decrease of GH which lowered below 5 micrograms/l in 7/8 patients and IGF-I levels, which fell within the normal range in 1 patient. Serum IGFBP-3 and insulin concentrations decreased by 26% and 71%, respectively, and those of IGFBP-1 underwent an only transient increase in 5/8 patients. Opposite changes of insulin and IGFBP-1 levels, with a decrease of the former followed by an increase of the latter were noted during the 8 hours following an octreotide nasal insufflation. During chronic octreotide treatment, positive correlations were found between GH and IGF-I, GH and IGFBP-3, IGF-I and IGFBP-3, insulin and IGFBP-3 and insulin and IGF-I. An improvement of the clinical picture was registered in all patients after a few days of octreotide nasal powder administration. Treatment was well tolerated, with only mild side effects and no significant changes in the nasal mucosa, and the patients' compliance was excellent.

Acromegaly↗
PubMed1995

Effect of injectable bromocriptine in patients with Cushing's disease.

The therapeutic efficacy of sustained dopaminergic stimulation in Cushing's disease (CD), was investigated performing a three-month trial with monthly 50-100 mg injections of a bromocriptine depot preparation (Parlodel LAR, Sandoz) in six patients with CD. Dopaminergic treatment did not consistently influence pituitary-adrenal activity, as judged by plasma ACTH, cortisol and urinary free cortisol levels as well as by clinical findings. Interestingly, treatment with bromocriptine was associated with reappearance of menses in the three patients who were amenorrheic. In the five patients submitted to inferior petrosal sinus sampling, a parallelism between ACTH and PRL concentrations could be observed with a PRL rise, ipsilateral to that of ACTH, ensuing in three patients after administration of corticotropin-releasing hormone. In one patient a 55% reduction in the size of the pituitary adenoma was demonstrated by MRI carried out at the end of treatment. Our findings lead to the following conclusions: a) administration of depot injections of bromocriptine to patients with CD appears unable to correct hypercortisolism, although it can induce restoration of menses in amenorrheic patients; b) enhanced PRL concentrations at the pituitary level are probably involved in the amenorrhea often accompanying Cushing's disease.

Adenoma↗
PubMed1995

High prevalence of nodular thyroid disease in patients with Cushing's disease.

OBJECTIVES: In the recent past, we have noted a frequent occurrence of thyroid nodules in our patients with Cushing's disease. We therefore elected to evaluate thyroid structure and function in these patients and also in patients with Cushing's syndrome of primary adrenal origin. PATIENTS AND METHODS: In 33 of the 37 patients (30 women and 3 men aged 19-66 years) with endogenous hypercortisolism referred to our Institution during the last five years, measurement of T4, T3, FT4, FT3, TSH serum levels and thyroid ultrasonography were performed, at first admission in 15 cases and subsequently in the course of follow-up in 18 cases. At the time of the study, 16 of the 33 patients had active Cushing's disease while 9 were in remission after successful surgery, 6 patients had an adrenal tumour and 2 patients had previously undergone unilateral adrenalectomy for an adrenal adenoma. Thyroid function and ultrasonography were also evaluated in 55 normal subjects, 40 women and 15 men aged 20-73 years. RESULTS: In 25 patients with Cushing's disease, we found a significantly higher prevalence of thyroid nodular disease than that recorded in 55 control subjects (60.0 vs 20.0%, chi 2 = 10.779, P < 0.005) and comparable to that in patients with active disease (56.2%) and those in remission (66.6%). Multiple nodules were present in 8 Cushing's patients and in 4 normal subjects while a single nodule was detected in 7 patients and in 7 controls. A markedly lower occurrence of thyroid abnormality was found in the 8 patients with adrenal tumours (25.0%, NS vs controls). In 9/17 (52.9%) patients with ultrasonographic evidence of thyroid nodules, these were palpable. As expected, serum thyroid hormone and TSH levels were reduced in patients with active Cushing's syndrome compared to normal controls. CONCLUSIONS: We found a significantly higher prevalence of nodular thyroid disease in patients with Cushing's disease with respect to a group of controls in whom the prevalence of thyroid nodules was comparable to that reported for the general population in Europe. The possibility that glucocorticoid excess is responsible for the development of thyroid changes does not seem likely since in our small series of patients with adrenal tumours the prevalence was only slightly higher than that observed in control subjects. Other factors related to hyperactivity of the corticotrophic cell, or a growth factor stimulating both corticotroph and thyrocyte proliferation might be involved. Evaluation of a larger series of patients with adrenal tumours may help to distinguish between these possibilities.

Adult↗