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ABSTRACT: Incidentally discovered adrenal masses are mostly benign, asymptomatic lesions, often arbitrarily considered as nonfunctioning tumors. Recent studies, however, have reported increasing evidence that subtle cortisol production and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are more frequent than previously thought. The purpose of this study was to investigate the clinical and hormonal features of patients with incidentally discovered adrenal adenomas, in relation to their clinical outcome. Fifty consecutive patients with incidentally detected adrenal adenomas, selected from a total of 65 cases of adrenal incidentalomas, were prospectively evaluated. All of them underwent abdominal computed tomography scan and hormonal assays of the HPA axis function: circadian rhythm of plasma cortisol and ACTH, urinary cortisol excretion, 17-hydroxyprogesterone, androgens, corticotropin stimulation test and low-dose (2 mg) dexamethasone test. The patients were reevaluated at regular intervals (6, 12, and 24 months) for a median period of 38 months. Subtle hypercortisolism, defined as abnormal response to at least 2 standard tests of the HPA axis function in the absence of clinical signs of Cushing's syndrome (CS), was defined as subclinical CS. Mild-to-severe hypertension was found in 24 of 50 (48%) patients, type-2 diabetes in 12 of 50 (24%), and glucose intolerance in 6 of 50 (12%) patients. Moreover, 18 of 50 patients (36%) were diffusely obese (body mass index, determined as weight/height2, > 25), and 14 patients (28%) had serum lipid concentration abnormalities (cholesterol > or = 6.21 mmol/L, low-density lipoprotein cholesterol > or = 4.14 mmol/L and/or triglycerides > or = 1.8 mmol/L). Compared with a healthy population, bone mineral density Z-score, determined by the DEXA technique, tended to be slightly (but not significantly) lower in patients with adrenal adenoma (-0.41 SD). Endocrine data were compared with 107 sex- and age-matched controls, and patients with adenomas were found to have heterogeneous hormonal abnormalities. In particular, significantly higher serum cortisol values (P < 0.001), lower ACTH concentration (P < 0.05), and impaired cortisol suppression by dexamethasone (P < 0.001) were observed. Moreover, in patients with adenomas, cortisol, 17-OH progesterone, and androstenedione responses to corticotropin were significantly increased (P < 0.001, all), whereas dehydroepiandrosterone sulfate levels were significantly lower at baseline, with blunted response to corticotropin (P < 0.001, both). However, the criteria for subclinical CS were met by 12 of 50 (24%) patients. Of these, 6 (50%) were diffusely obese, 11 (91.6%) had mild-to-severe hypertension, 5 (41.6%) had type-2 diabetes mellitus, and 6 (50%) had abnormal serum lipids. The clinical and hormonal features improved in all patients treated by adrenalectomy, but seemed unchanged in all those who did not undergo surgery (follow-up, 9 to 73 months), except for one, who was previously found as having nonfunctioning adenoma and then revealed to have subclinical CS. In conclusion, an unexpectedly high prevalence of subtle autonomous cortisol secretion, associated with high occurrence of hypertension, diabetes mellitus, elevated lipids, and diffuse obesity, was found in incidentally discovered adrenal adenomas. Although the pathological entity of a subclinical hypercortisolism state remained mostly stable in time during follow-up, hypertension, metabolic disorders, and hormonal abnormalities improved in all patients treated by adrenalectomy. These findings support the hypothesis that clinically silent hypercortisolism is probably not completely asymptomatic.
Journal of Clinical Endocrinology & Metabolism 04/2000; 85(4):1440-8. · 6.50 Impact Factor
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S Savastano,
V Cannavale,
R Valentino,
A P Tommaselli,
R Rossi, A Luciano,
L Tauchmanovà,
A Mariano,
L Mazzitelli,
V Macchia,
G Lombardi
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ABSTRACT: The pituitary-thyroid axis and neurohumoral activation indexes were simultaneously investigated in 16 in-patients hospitalized for cardiac heart failure (CHF), New York Heart Association (NYHA), class II-IV, and Killip clinical scale, class II-III, to evaluate their relationship with CHF morbidity and the relative prognostic value. At entry the patients were divided into two subgroups (A and B), according to the severity of CHF. Patients were further classified into two subgroups, according to the subsequent clinical course (C, poor outcome and D, improved clinical course). Blood samples were obtained every day for the radioimmunoassay measurement of plasma alpha-atrial natriuretic peptide (alphaANP), arginine vasopressin (AVP), and thyroid hormones, and the results were compared with those of 12 control subjects. At admission, alphaANP and 3,3',5'-triiodothyronine (rT3) values were higher, while 3,3',5-triiodothyronine (T3) to rT3 (T3/rT3) ratio was lower in subgroups A and B than in controls (p<0.001), respectively, and in C than in D (p<0.001), respectively, according to the prognosis. Conversely, no differences in other thyroid indexes, nor a significant correlation between alphaANP and either rT3 or T3/rT3 ratio were present in any of the subgroups. AVP plasma levels in subgroup A were not statistically different from those of controls, whereas they were significantly decreased in subgroups B and C (p<0.05) and D (p<0.001). In conclusion, these results indicate that in CHF the pituitary-thyroid axis is not altered, that alphaANP and T3/rT3 ratio are non-invasive and reliable predictors of severity and prognosis, while AVP might be affected by the different pathological processes leading to CHF or by the concomitant use of drugs.
Journal of endocrinological investigation 11/1999; 22(10):766-71. · 1.57 Impact Factor
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ABSTRACT: The aim of this study was to determine the validity of our previous hypothesis of adrenal 11 beta-hydroxylase (11-OH) dysregulation in "essential" low-renin hypertension.
A comparison was made between 30 hypertensive patients and 30 age-matched controls (NC) in basal conditions and after ACTH stimulation (ACTH 1-17) test. The 11-deoxycortisol (S) and deoxycorticosterone (DOC) integrated areas under the curve (AUCs) of stimulus were significantly higher in the hypertensives (p < 0.001) and pointed to adrenal 11-OH dysregulation.
The ACTH 1-17 test detects impairment of 11-OH activity of probable genetic origin. The relative mineralocorticoid excess thus provoked could be an additional cause of "essential" low-renin hypertension.
Nutrition Metabolism and Cardiovascular Diseases 08/1999; 9(4):192-5. · 3.73 Impact Factor
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ABSTRACT: The antiphospholipid syndrome is characterized by clinical evidence of arterial or venous thrombosis, thrombocytopaenia, recurrent fetal loss and repeated positivity of antiphospholipid autoantibodies. The association of antiphospholipid syndrome with the development of adrenal failure has been reported in more than 40 patients in the last 20 years, mostly due to bilateral cortical haemorrhage or thrombosis of adrenal vessels. The presence of antibodies against adrenal cortex was never documented in these patients. Here we report a case of recurrent thrombophlebitis, acute adrenal failure, and chronic hepatitis occurring in a young man found to have antiphospholipid antibodies and lupus anticoagulant. Autoantibodies against adrenal cortex were detected and abdominal ultrasonography showed morphologically normal adrenals. Mild thrombocytopaenia, Coomb's positive anaemia, increase in alanine- and aspartate-aminotransferases and increase in urinary protein excretion were found. Autoantibodies against liver/kidney microsomes were positive and liver biopsy was compatible with autoimmune hepatitis. The patient was treated with cortisone acetate, fludrocortisone and warfarin. Dilated cardiomyopathy was revealed one year later and coronarography did not document any occlusive coronary disease. Three years later, titres of autoantibodies, including those directed towards the adrenal cortex, were increased and others, previously absent, were detected. Nevertheless, the patient's clinical conditions seemed unchanged. At this time, an abdominal CT scan showed adrenal dysmorphisms with bilateral annular calcifications and central hypodensities suggesting previous bilateral adrenal haematomas. The hypercoagulable state that occurs in antiphospholipid syndrome can induce a localized inflammatory response generated by tissue injury, with a consequent release of intracellular antigens and antibodies production. Consequently, tissue-specific autoantibodies positivity may persist until the cells involved in antigen production are completely destroyed.
European Journal of Endocrinology 01/1999; 139(6):641-5. · 3.42 Impact Factor
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ABSTRACT: To study the involvement of gonadotropin-releasing hormone (GnRH) in glycosylation of circulating gonadotropin isoforms in anorexia nervosa (AN), 14 amenorrhoic patients with AN, 14 age-matched volunteers in early follicular phase, and five normal-weight re-fed patients with AN were investigated under baseline conditions and after acute administration of GnRH. Plasma gonadotropins were assayed using IRMA before and after concanavalin A affinity chromatography. Baseline plasma gonadotropin levels were lower for both AN and re-fed AN patients than in controls (P<0.005). The increase in FSH and LH after GnRH administration was lower than in controls for AN (P<0.005) and re-fed AN (P<0.005 and P<0.05 respectively) patients. Percentages of total gonadotropin not bound to concanavalin A (complex carbohydrate chains) under baseline conditions were higher in patients with AN than in controls (P<0.005) but decreased after GnRH administration (P<0.001). In re-fed AN patients, the percentage of unbound FSH was higher than in controls (P<0.05), and decreased after GnRH administration (P<0.001), whereas the percentages of unbound LH were not significantly different from controls either before or after GnRH administration. These data suggest that: (a) the acute administration of GnRH induces quantitative and qualitative changes in circulating gonadotropin isoforms in both normal controls and AN patients; (b) during recovery the LH response in re-fed AN patients is associated with a glycosylation pattern that is the same as that for controls.
European Journal of Endocrinology 01/1998; 138(1):76-81. · 3.42 Impact Factor
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ABSTRACT: The adrenal scintiscan with 123I-metaiodobenzylguanidine (MIBG), a reliable morphofunctional technique to evaluate catecholamine turnover in adrenal tumors, can be a useful method to investigate adrenal incidentalomas with arterial hypertension. A male patient, 44 yr old with diabetes, unstable arterial hypertension, and sudden paroxysms of tachycardia is described. The presence of a disomogeneous right juxta-adrenal neoplasm with calcifications was evidenced with ultrasound tomography and confirmed by computerized tomography (CT) scan. Adrenal 123I-MIBG scintiscan revealed a unilateral uptake at level of the right juxta-adrenal region, sized similarly to the neoplasm previously evidence by CT scan. Histological findings of the surgically removed neoplasm were consistent with an ancient schwannoma. Apart from pheochromocytomas, the MIBG uptake is commonly reported in neuroblastomas. In neuroblastoma, a bidirectional process of transdifferentiation has been previously reported in vitro between two coexistent cells: cells with specific uptake system for norepinephrine, with 123I-MIBG uptake capability, and cells oriented toward schwann/melanocytic line. The evidence of in vivo MIBG uptake in our schwannoma may be caused by the same possible phenotypic interconversion of above mentioned cell types. In conclusion, the presence of adrenal tumors with MIBG uptake capability, apart from pheochromocytomas, neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, must be considered in the diagnosis of adrenal tumors.
Journal of Clinical Endocrinology & Metabolism 03/1996; 81(2):843-6. · 6.50 Impact Factor
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ABSTRACT: The feasibility, safety and effectiveness of percutaneous computed tomography-guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [75Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hours after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasma levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized 1 month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels even on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were still present. Thus, we suggest PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA.
European Journal of Endocrinology 04/1995; 132(3):302-5. · 3.42 Impact Factor
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ABSTRACT: Complex and bidirectional relationships operate between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system (IS) and either in vivo or in vitro evidence supports a physiological role of the HPA axis-IS network. A part of the well-known pharmacological effects of glucocorticoid hormones (GC) as immunodepressive agents, the direct effects of many HPA axis hormones on IS functions are actually documented also in physiologic conditions. Conversely, numerous IS soluble mediators are reported to affect the HPA axis functions at various steps of HPA axis regulation, in both physiologic and pathologic conditions. Stress and aging may represent two paradigmatic conditions to show the relevance of the bidirectional network between HPA axis and IS, as in both HPA activation and IS impairment are frequently coexistent. Finally, in the context of the wide spectrum of HIV-related HPA axis abnormalities, a case of a Cushing's syndrome associated to an acquired immunodeficiency syndrome (AIDS-related complex) in a 24-year-old homosexual drug abuser is reported.
Acta neurologica 09/1994; 16(4):206-13.
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ABSTRACT: The etiologic diagnosis of hirsutism is often difficult. Previous studies have reported normal basal androgen and SHBG concentrations in 33-50% of hirsute women, suggesting the presence of an "idiopathic" form of hirsutism as the most frequent cause of this problem. The recent use of GnRH-analogues together with the corticotropin stimulation test allows better understanding of whether the cause of hirsutism is androgen excess and, if so, whether the origin of the latter is ovarian, adrenal or both. The present study evaluated adrenal and ovarian function in 48 young hirsute women as well as in 78 normal women matched for body mass index and age, who acted as control group. To determine ovarian function, a single 100-microg dose of GnRH analogue triptorelin was injected s.c.; thereafter, gonadotropins, 17-hydroxyprogesterone (17-OHP), delta4-androstenedione (delta4), total testosterone (T) and estradiol were determined. To better understand the adrenal function, 250 microg of 1,24 ACTH were administrated as i.v. infusion for 5 h, and plasma cortisol (F), 17-OHP, A4, DHEAS, T, 11-desossicortisol were measured. The combined use of these two stimulation tests was able to detect mild to moderate abnormalities in the steroidogenesis of ovaries alone (23%), adrenals alone (16.6%), or both (35.4%) in most hirsute women (75%) with otherwise normal baseline androgen concentrations. In particular, patients showed significantly increased responses of 17-OHP, delta4, total T, 11-desossicortisol, and F to 1,24-ACTH administration. Moreover, they also had significantly higher 17-OHP and T responses to triptorelin. In conclusion, milder forms of functional ovarian and/or adrenal hyperandrogenism, similar to those found in clearly hyperandrogenic women, were observed and could be an underlying mechanism of idiopathic hirsutism.
Journal of endocrinological investigation 24(7):491-8. · 1.57 Impact Factor
