Bromocriptine-responsive Cushing's disease; clinical and biochemical remission accompanied by amelioration of impaired ocular movement. (25/151)

A 73-year-old woman presented with disturbance of right eyelid opening with ptosis and impairment of right ocular movement, and later was found to have Cushingoid features. Endocrine examinations revealed that plasma ACTH and cortisol levels were elevated, lack of circadian rhythm, resistant to low-doses (0.5, 1, 2 mg) and high-dose (8 mg) dexamethasone, and responsive to CRH and DDAVP. Magnetic resonance imaging (MRI) revealed a large pituitary tumor invading the right cavernous sinus. After two months treated with bromocriptine (5 mg/day), she showed clinical improvement with normalization of plasma ACTH and cortisol levels, and improvement of right eyelid opening and ocular movement. MRI, however, revealed no apparent reduction in the size of pituitary tumor. This is a rare case of bromocriptine-responsive Cushing's disease.  (+info)

Cortisol as a possible marker of metastatic adrenocortical carcinoma: a case report with 3-year follow-up. (26/151)

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumour, sometimes causing glucocorticoid hypersecretion. Treatment guidelines have not been established, but are currently under investigation. CASE REPORT: A 55-year-old Caucasian woman presented with adrenal Cushing's disease. Histological examination after a left adrenalectomy revealed a benign tumour. Postoperatively, elevated serum cortisol levels normalized. Hypercortisolism occurred again two years later. Diagnostic work-up revealed hepatic metastatic lesions of an ACC which were treated by right hemihepatectomy. Initial histological diagnosis was revised according to the increased proliferative changes. Postoperatively, cortisol declined to normal levels. Treatment with mitotane (o, p'-DDD) as a cytostatic agent was not tolerated. One year later, the patient was diagnosed with a solitary osseous metastasis at the left side of the sacrum because of back pain. Following curettage and stabilization, radiotherapy of this region with 37.5 Gy was performed, improving slightly elevated cortisol levels and neurological symptoms. CONCLUSION: Careful clinical and radiographic follow-up of patients with ACC are important. In this case of oligometastasizing ACC, serum cortisol values correlated with the clinical course. An aggressive multimodal treatment, including repeated surgical approach with consolidating radiotherapy in cases of incomplete resection, might be indicated to provide symptom control and possible long-term survival in oligometastatic disease of ACC.  (+info)

The activation of somatostatinergic receptors by either somatostatin-14 or cortistatin-17 often inhibits ACTH hypersecretion in patients with Cushing's disease. (27/151)

OBJECT: Somatostatin (SS) is known to inhibit GH and insulin, while its effect on corticotrope secretion is controversial: inhibition of ACTH secretion by agonists activating somatostatinergic receptors (sst)-2 and sst-5 was reported in vitro. Cortistatin (CST) not only binds all sst receptor subtypes but also possesses central actions that are not shared by SS. DESIGN: In nine patients with Cushing's disease (CD), ACTH, cortisol, GH, insulin, and glucose levels were studied during 120-min i.v. infusion of SS-14 (2.0 microg/kg per h), CST-17 (2.0 microg/kg per h) or saline. RESULTS: Both SS or CST significantly affected the hypothalamic-pituitary-adrenal axis. Cortisol was decreased to the same extent by either SS or CST (P < 0.05). Both SS and CST decreased ACTH, although statistical difference was reached only during CST (P < 0.05). Analyzing the individual responses as areas under curve (AUCs), a clear and consensual inhibition of ACTH and cortisol under either SS or CST was recorded in five out of nine patients. Both SS or CST inhibited (P < 0.05) insulin, that even showed a rebound (P < 0.01) at the end of infusion. GH was not modified by either peptide. CONCLUSION: SS and CST often display similar inhibitory effects on the HPA axis in CD. The activation of sst receptors by both peptides is followed in almost 50% of patients by a remarkable inhibition of ACTH and cortisol hypersecretion. These findings reinforce the view that sst receptors are involved in the control of the secretory activity of tumoral corticotropic cells.  (+info)

Differential gene expression in ACTH -secreting and non-functioning pituitary tumors. (28/151)

OBJECTIVE: Differential expression of several genes between ACTH-secreting pituitary tumors causing Cushing' disease (CD), silent corticotroph adenoma (SCA), and non-functioning pituitary tumors (NFT) was investigated. DESIGN AND METHODS: We used tissue specimens from 35 pituitary tumors (12 CD, 8 SCA, and 15 NFT). Steady-state mRNA levels of the genes related to proopiomelanocortin (POMC) transcription, synthesis, processing, and secretion, such as neurogenic differentiation 1 (NeuroD1), T-box 19 (Tpit), corticotropin releasing hormone receptor (CRHR), vasopressin receptor 1b (V1bR), prohormone convertase (PC) 1/3 and PC2, 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2, glucocorticoid receptor alpha (GRalpha), annexin A1, histone deacetylase 2 (HDAC2), and BRM/SWI2-related gene 1, were determined by real-time RT-PCR. RESULTS AND CONCLUSION: POMC and Tpit mRNA levels were greater in CD and SCA than those in NFT. NeuroD1 mRNA levels were less in CD than those in NFT, but almost comparable between SCA and NFT. PC1/3 mRNA levels were greater in CD, but less in SCA than those in NFT. PC2 mRNA levels in CD and SCA were less than those in NFT. CRHR, V1bR, and 11beta-HSD2 mRNA levels in CD were greater than those in SCA and NFT. HDAC2 mRNA levels in CD and SCA were lower than those in NFT. In conclusion, our study demonstrated that the genes related to transcription, synthesis, processing, and secretion of POMC are differentially regulated in ACTH-secreting pituitary tumors causing CD and SCA compared with those in NFT. This may partly explain the development of clinically active and inactive CD.  (+info)

Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease. (29/151)

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Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment. (30/151)

Cushing's syndrome (CS) results from prolonged exposure to supraphysiological levels of circulating glucocorticoids, endogenously or exogenously derived. Although rare in childhood, CS remains a difficult condition to diagnose and treat. A multidisciplinary approach and close collaboration with adult colleagues is adopted at most large centres that manage pediatric CS patients. Although pediatric protocols are derived from adult data, significant differences exist between adult and childhood CS. Furthermore, long term outcome parameters including final height, bone mineral density, reproductive function, body composition and psychological health pose challenges for pediatric care. This article will aim to provide an overall view of pediatric CS highlighting some of the differences between adult and pediatric CS.  (+info)

Prospective evaluation of transsphenoidal pituitary surgery in 108 patients with Cushing's disease. (31/151)

Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4% and 28.6% (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9% vs. 73.9%; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4% (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative.  (+info)

Criteria of cure and remission in Cushing's disease: an update. (32/151)

We review the clinical and biochemical criteria used for evaluation of the transsphenoidal pituitary surgery results in the treatment of Cushing's disease (CD). Firstly, we discuss the pathophysiology of the hypothalamic-pituitary-adrenal axis in normal subjects and patients with CD. Considering the series published in the last 25 years, we observed a significant variation in the remission or cure criteria, including the choice of biochemical tests, timing, threshold values to define remission, and the interference of glucocorticoid replacement or previous treatment. In this context we emphasize serum cortisol levels obtained early (from hours to 12 days) in the postoperative period without any glucocorticoid replacement or treatment. Our experience demonstrates that: (i) early cortisol < 5 to 7 microg/dl, (ii) a period of glucocorticoid dependence > 6 mo, (iii) absence of response of cortisol/ACTH to CRH or DDAVP, (iv) return of dexamethasone suppression, and circadian rhythm of cortisol are appropriate indices of remission of CD. In patients with undetectable cortisol levels early after surgery, recurrence seems to be low. Finally, although certain biochemical patterns are more suggestive of remission or surgical failure, none has been proven to be completely accurate, with recurrence observed in approximately 10 to 15% of the patients in long-term follow-up. We recommended that patients with CD should have long-term monitoring of the CRH-ACTH-cortisol axis and associated co-morbidities, especially hypopituitarism, diabetes mellitus, hypertension, cardiovascular disturbances, and osteoporosis.  (+info)