[Glucocorticoid-induced osteoporosis: recent findings]. / Osteoporosi indotta da glicocorticoidi: recenti acquisizioni.

The clinical features, pathogenesis and management of bone involvement in Cushing's syndrome are briefly reviewed. Personal data on bone mineral density and markers of bone turnover in Cushing's syndrome and adrenal incidentalomas are also reported. As long ago as 1932, Harvey Cushing recognized osteoporosis as a serious consequence of endogenous hypercortisolism. The introduction of cortisone in the therapy of autoimmune, rheumatic, allergic or dermatologic disorders was followed by several reports of detrimental effects on bone of patients who had undergone prolonged glucocorticoid treatment. Due to the rarity of Cushing's syndrome, most of the studies in the literature on glucocorticoid-induced osteoporosis refer to exogenous over-exposure to cortisone and its synthetic derivatives. Only a small number of works concern endogenous hypercortisolism, even if the characteristics of bone damage seem qualitatively the same. Finally, very few data are reported on the hypothetical detrimental effect on bone in the condition of the silent hypercortisolism of adrenal incidentalomas. Glucocorticoid-induced osteoporosis in Cushing's syndrome often results in vertebral fractures, and bone loss is more evident in trabecular than in cortical bone. Notwithstanding some distinctive features in osteoporosis induced by endogenous and exogenous glucocorticoid excess, the common eventual picture is notable bone damage that involves mainly the trabecular bone. Prompt and effective therapy is mandatory to reduce the risk of fractures. The present options include calcium and vitamin D supplementation, estrogen replacement therapy, bisphosphonates, either oral or parenteral. A novel approach to the clinical problem of glucocorticoid-induced osteoporosis might, in the future, be based on studies on selective glucocorticoid receptor modulators, a new class of synthetic glucocorticoids that exhibit significant anti-inflammatory and immunosuppressive activities, with reduced side effects on bone.

The value of dehydroepiandrosterone sulfate measurement in the differentiation between benign and malignant adrenal masses.

OBJECTIVE: Owing to their increasing rate of discovery as incidental findings, the characterization of adrenal masses is an important diagnostic problem which frequently challenges the clinician's skill. DESIGN: The results of dehydroepiandrosterone sulfate (DHEAS) measurement were evaluated in a consecutive series of 107 patients with an adrenal mass (39 men, 68 women aged 15-81 years, median 56 years). DHEAS levels observed in the patients were categorized as reduced, normal or elevated according to sex- and age-adjusted reference ranges obtained by measuring DHEAS in 214 healthy women and 142 healthy men aged 17-93 years. The working hypothesis was that a low DHEAS level is a marker of benignity. METHODS: In 84 patients, the adrenal mass was discovered serendipitously, while in the remainder the mass was clinically symptomatic. Patients with known extra-adrenal malignancies were excluded. The adrenal masses were categorized as benign or malignant by computerized tomography (CT) criteria. All patients with suspected malignant tumors or with overtly hypersecreting tumors underwent adrenalectomy. The patients with a presumptive benign tumor were followed-up for at least 12 months. RESULTS: In the overall series, the sensitivity and specificity of a low DHEAS level in the identification of a benign lesion were 41% and 100% respectively. Superimposable figures were obtained when considering only adrenal incidentalomas. DHEAS levels in adrenal cancers displayed some overlap with adrenal adenomas, but in only 2/11 adrenal cancers were DHEAS levels normal, while they were elevated in the remainder. CONCLUSIONS: The present data suggest that DHEAS measurement may help to differentiate benign from malignant adrenal masses as a complementary test of CT in a clinical research setting. The value of DHEAS measurement in general practice is limited because it may be difficult to differentiate between low and low-normal values, particularly in the elderly.

Cushing's syndrome due to ACTH-independent bilateral adrenocortical macronodular hyperplasia.

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is a rare cause of Cushing's syndrome in which adrenal glands become very enlarged, occupied and distorted by multiple cortical nodules. We report on such two patients, a 44-year-old man and a 40-year-old woman. Physical examination revealed in both cases a classic cushingoid habit. Laboratory studies showed overt hypercortisolism with high urinary free cortisol excretion and elevated serum cortisol with loss of the circadian rhythm. Serum cortisol levels were not modified after high dose dexamethasone. ACTH levels were undetectable both in baseline conditions and following CRH or metyrapone. In both cases, abdominal CT demonstrated bilaterally enlarged adrenal glands which were distorted by multiple bumps. 131I-Norcholesterol scintiscan showed bilateral uptake of the radionuclide. Pituitary region was normal at neuroradiologic imaging. Bilateral adrenalectomy was performed in both cases. In patient I, adrenal glands weighted 77 and 90 g, respectively, while in patient II they were of 90 and 55 g, respectively. At histological examination, the adrenal cortex was occupied by multiple nodular lesions composed mostly of clear cells. In the internodular regions, no evidence of cortical architecture was observed. At the immunohistochemical evaluation, both cases displayed KI-67 staining comparable with that of ACTH-dependent diffuse hyperplasia. Postoperative course was uneventful and signs of Cushing's syndrome resolved in about three months. At the last follow up, the patients are going well on glucocorticoid and mineralocorticoid supplementation. Plasma ACTH levels are 65 and 107 pg/ml, respectively.

Effects of long-term, low-dose, time-specified melatonin administration on endocrine and cardiovascular variables in adult men.

Six healthy adult male volunteers underwent serial blood drawings at 4-hour intervals over 24 hours for the definition of melatonin (MT), prolactin (PRL), cortisol, and testosterone circadian patterns. Serum levels of triiodotironine (T3) and thyroxine (T4) were determined at 0800. Systolic and diastolic blood pressure and heart rate were automatically recorded every 30 minutes for 24 hours. The responses of luteinizing hormone (LH), follicle stimulating hormone (FSH), PRL, thyroid stimulating hormone (TSH), cortisol, and aldosterone to a stimulation test with gonadotrophin-releasing hormone (Gn-RH), thyrotrophin-releasing hormone (TRH), adrenocorticotrophin (ACTH), and testosterone to human chorionic gonadotrophin (HCG) were also evaluated. The same protocol was repeated after a two-month course of treatment with MT, 2 mg per os daily at 1800. After treatment, we recorded a marked elevation of mean serum MT levels with a significant phase-advance of its circadian rhythm. The 24-hour patterns of cortisol and testosterone displayed an anticipation of the morning acrophase of about 1.5 hour (not significant) for cortisol and three hours (P less than 0.05) for testosterone. PRL pattern was unchanged as well as serum levels of thyroid hormones. The circadian organization of the cardiovascular variables did not show any changes after MT supplementation; the pituitary, adrenal, and testicular responses to specific stimuli were comparable before and after treatment. These results are compatible with the view that the MT signal may provide temporal cues to the neuroendocrine network for the organization of testicular circadian periodicity.