Evaluation and treatment of Cushing's syndrome

Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md, USA.
The American journal of medicine (Impact Factor: 5). 01/2006; 118(12):1340-6. DOI: 10.1016/j.amjmed.2005.01.059
Source: PubMed


Cushing's syndrome results from sustained pathologic hypercortisolism caused by excessive corticotropin (ACTH) secretion by tumors in the pituitary gland (Cushing's disease, 70%) or elsewhere (15%), or by ACTH-independent cortisol secretion from adrenal tumors (15%). The clinical features are variable, and no single pattern is seen in all patients. Those features most specific for Cushing's syndrome include abnormal fat distribution, particularly in the supraclavicular and temporal fossae, proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in a child. Patients with characteristics of glucocorticoid excess should be screened with measurements of saliva or urine cortisol or dexamethasone suppression testing. The diagnosis of Cushing's syndrome should be followed by the measurement of plasma ACTH concentration to determine whether the hypercortisolism is ACTH-independent. In ACTH-dependent patients, bilateral inferior petrosal sinus sampling with measurement of ACTH before and after administration of ACTH-releasing hormone most accurately distinguishes pituitary from ectopic ACTH secretion. Surgical resection of tumor is the optimal treatment for all forms of Cushing's syndrome; bilateral adrenalectomy, medical treatment, or radiotherapy are sought in inoperable or recurrent cases. The medical treatment of choice is ketoconazole. The prognosis is better for Cushing's disease and benign adrenal causes of Cushing's syndrome than adrenocortical cancer and malignant ACTH-producing tumors.

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    • "In fact, glucocorticoids are able to inhibit GnRH release and consequently the whole reproductive axis function. Moreover, glucocorticoids may also suppress the adrenal source of androgens [52]. The role of cyclosporine-A treatment in inducing Leydig cell damage cannot be excluded as it is known to exert a severe gonadotoxic effect on testicles in long-term treatments [53, 54]. "
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    ABSTRACT: Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.
    Full-text · Article · Apr 2014
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    • "Cushing's disease is caused by an adrenocorticotropic hormone (ACTH) producing pituitary adenoma, which in turn causes hypercortisolism (Nieman and Ilias, 2005). Hypercortisolism is associated with severe physical and psychological symptoms and cognitive impairments (Forget et al., 2000; Leon-Carrion et al., 2009; Michaud et al., 2009; Newell-Price et al., 2006; Nieman and Ilias, 2005). "
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    ABSTRACT: Background Hypercortisolism leads to various physical, psychological and cognitive symptoms, which may partly persist after treatment of Cushing's disease. The aim of the present study was to investigate abnormalities in white matter integrity in patients with long-term remission of Cushing's disease, and their relation with psychological symptoms, cognitive impairment and clinical characteristics. Methods In patients with long-term remission of Cushing's disease (n = 22) and matched healthy controls (n = 22) we examined fractional anisotropy (FA) values of white matter in a region-of-interest (ROI; bilateral cingulate cingulum, bilateral hippocampal cingulum, bilateral uncinate fasciculus and corpus callosum) and the whole brain, using 3 T diffusion tensor imaging (DTI) and a tract-based spatial statistics (TBSS) approach. Psychological and cognitive functioning were assessed with validated questionnaires and clinical severity was assessed using the Cushing's syndrome Severity Index. Results The ROI analysis showed FA reductions in all of the hypothesized regions, with the exception of the bilateral hippocampal cingulum, in patients when compared to controls. The exploratory whole brain analysis showed multiple regions with lower FA values throughout the brain. Patients reported more apathy (p = .003) and more depressive symptoms (p < .001), whereas depression symptom severity in the patient group was negatively associated with FA in the left uncinate fasciculus (p < 0.05). Post-hoc analyses showed increased radial and mean diffusivity in the patient group. Conclusion Patients with a history of endogenous hypercortisolism in present remission show widespread changes of white matter integrity in the brain, with abnormalities in the integrity of the uncinate fasciculus being related to severity of depressive symptoms, suggesting persistent structural effects of hypercortisolism.
    Full-text · Article · Feb 2014 · Clinical neuroimaging
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    • "after operation could be life threatening to patients with CS, steroid replacement therapy after adrenalectomy should be optimized to minimize the possible risks. However, replacement therapeutic methods of perioperative hormone maintenance remain controversial up to date [5] [6]. How to establish the most appropriate therapeutic modality to avoid the risks caused by the sharp reduction of cortisol is still of great significance. "
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    ABSTRACT: Objectives . To investigate the efficacy and safety of perioperative endocrine therapy (PET) for patients with Cushing’s syndrome (CS) undergoing retroperitoneal laparoscopic adrenalectomy (RLA). Methods . The novel, simplified PET modality of 82 patients who underwent RLA procedures for CS were studied. Clinical manifestations were observed for all patients on days 1 and 5 postoperatively, and clinical data, such as blood pressure (BP), levels of serum cortisol, adrenocorticotropin (ACTH), blood glucose, and electrolytes, were acquired and analyzed. Results . Supraphysiological doses of glucocorticoid were administered during the perioperative period, and the dosage was reduced gradually. In all 82 cases, the RLAs were performed successfully without any perioperative complication, such as steroid withdrawal symptoms. The patient’s symptoms and signs were improved quickly and safely during the hospital days. The serum cortisol and potassium levels were rather stable on days 1 and 5 postoperatively, and most were within the normal range. The clinical manifestations, serum levels of cortisol, ACTH, and potassium in most patients restored to normal gradually after several months (mean, 6.7 ± 1.2 months), except for one patient undergoing bilateral adrenalectomy. Conclusions . This perioperative endocrine therapy for patients with Cushing’s syndrome (mainly for adrenocortical adenoma) undergoing retro-laparoscopic adrenalectomy is both effective and safe.
    Full-text · Article · Oct 2012 · International Journal of Endocrinology
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