Predictors of Mortality, CVD Risk in Cushing's Disease ID'd

(HealthDay News) – A number of factors, including the duration of glucocorticoid exposure, older age at diagnosis, and preoperative adrenocorticotropic hormone (ACTH) concentration, are associated with a higher risk of mortality in patients treated for Cushing's disease (CD), according to research published online Feb. 7 in the Journal of Clinical Endocrinology & Metabolism.

In an effort to identify predictors of mortality, cardiovascular disease, and recurrence with long-term follow-up, Jessica K. Lambert, MD, of the Mount Sinai Medical Center in New York City, and colleagues performed a retrospective chart review of 346 patients with CD who underwent transsphenoidal adenectomy.

The researchers found that the average length of exposure to glucocorticoids was 40 months. The risk of death was higher for those patients who had a longer duration of glucocorticoid exposure, older age at diagnosis, and higher preoperative ACTH concentration. For patients who achieved remission, depressed patients had a higher risk of death. The risk of cardiovascular disease was highest for men, older people, and those with diabetes or depression.

"Our study has identified several predictors of mortality in patients with treated CD, including duration of exposure to excess glucocorticoids, preoperative ACTH concentration, and older age at diagnosis. Depression and male gender predicted mortality among patients who achieved remission," the authors write. "These data illustrate the importance of early recognition and treatment of CD. Long-term follow-up, with management of persistent comorbidities by an experienced endocrinologist, is needed even after successful treatment of CD."

Abstract
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Use of ketoconazole in the treatment of Cushing's syndrome

An older, but still useful, abstract:

J Clin Endocrinol Metab. 1986 Dec;63(6):1365-71.

 

Loli P, Berselli ME, Tagliaferri M.

Abstract

The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period.

Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another.

The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.

From http://www.ncbi.nlm.nih.gov/pubmed/3023421

 

Cushing’s Disease and Idiopathic Intracranial Hypertension

Gabriel Zada, Amir Tirosh, Ursula B. Kaiser, Edward R. Laws and Whitney W. Woodmansee

Department of Neurosurgery (G.Z., E.R.L.) and Division of Endocrinology, Diabetes, and Hypertension (A.T., U.B.K., W.W.W.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Gabriel Zada, M.D., 15 Francis Street, PBB3, Boston, Massachusetts 02115. E-mail: gzada@usc.edu.

Abstract

Case Illustration: A 33-yr-old woman with Cushing’s disease underwent successful surgical resection of a pituitary adenoma and developed IIH 11 months later after inadvertent withdrawal of oral glucocorticoids.

Methods: A review of the literature was conducted to identify previous studies pertaining to IIH in association with neuroendocrine disease, focusing on reports related to HPA axis dysfunction.

Results: A number of patients developing IIH due to a relative deficiency in glucocorticoids, after surgical or medical management for Cushing’s disease, withdrawal from glucocorticoid replacement, or as an initial presentation of Addison’s disease, have been reported. Hypotheses regarding the underlying pathophysiology of IIH in this context and, in particular, the role of cortisol and its relationship to other neuroendocrine and inflammatory mediators that may regulate the homeostasis of cerebrospinal fluid production and absorption are reviewed.

Conclusion: In a subset of patients, dysfunction of the HPA axis appears to play a role in the development of IIH. Hormonal control of cerebrospinal fluid production and absorption may be regulated by inflammatory mediators and the enzyme 11ß-hydroxysteroid dehydrogenase type 1. Further study of neuroendocrine markers in the serum and cerebrospinal fluid may be an avenue for further research in IIH.

Read the entire article at http://jcem.endojournals.org/content/95/11/4850.full

Clinical relevance of cardiac structure and function abnormalities in patients with Cushing's syndrome before and after cure

Authors: Toja, Paola M.1; Branzi, Giovanna2; Ciambellotti, Francesca2; Radaelli, Piero3; De Martin, Martina1; Lonati, Laura Maria2; Scacchi, Massimo; Parati, Gianfranco; Cavagnini, Francesco1; Giraldi, Francesca Pecori

Source: Clinical Endocrinology, Volume 76, Number 3, 1 March 2012 , pp. 332-338(7)

Publisher: Wiley-Blackwell

 

Abstract:

Objectives  Sustained hypercortisolism impacts cardiac function, and, indeed, cardiac disease is one of the major determinants of mortality in patients with Cushing's syndrome. The aim of this study was to assess the clinical relevance of cardiac structure and function alterations by echocardiography in patients with active Cushing's syndrome and after disease remission.

Study design  Seventy-one patients (61 women, 10 men) with Cushing's syndrome and 70 age-, sex- and blood pressure-matched controls were enrolled. Echocardiography was performed in 49 patients with active disease and at several time points after remission in 44 patients (median follow-up 46·4 months), and prevalence of abnormal left ventricular mass measurements and systolic and diastolic functions indices was compared between patients with active disease, after remission and controls. Twenty-two patients were evaluated both before and after remission.

Results  Up to 70% of patients with active Cushing's syndrome presented abnormal left ventricular mass parameters; 42% presented concentric hypertrophy and 23% concentric remodelling. Major indices of systolic and diastolic functions, i.e. ejection fraction and E/A ratio, respectively, were normal. Upon remission of hypercortisolism, left ventricular mass parameters ameliorated considerably, although abnormal values were still more frequent than in controls. Both cortisol excess and hypertension contribute to cardiac mass alterations and increase the prevalence of target organ damage.

Conclusions  Cushing's syndrome is associated with an increased risk for abnormalities of cardiac mass, which ameliorates, but does not fully disappear after remission. Systolic and diastolic functions are largely within the normal range in these patients.

 

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2265.2011.04206.x

Affiliations: 1: Ospedale San Luca, Neuroendocrinology Research Lab, Istituto Auxologico Italiano IRCCS 2: Department of Cardiology, Ospedale San Luca, Istituto Auxologico Italiano IRCCS 3: Department of Medical Sciences, University of Milan

Buy this article here: http://www.ingentaconnect.com/content/bsc/cend/2012/00000076/00000003/art00004

Pregnancy-induced Cushing’s Syndrome: A Case Report

 

Cushing’s syndrome(CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause.The other causes include tumors in hypothalamus and pituitary. Ectopic ACTH secretion has been reported to cause CS.

There is a very rare condition. Cushing’s syndrome develops in pregnancy and resolving after delivery. The mechanisms underlying these conditions are poorly understood.

There are non-significant differences in the clinical features of pregnant and non-pregnant women with CS.The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, The normal gestational changes in the HPA axis alter these parameters and complicate the screening process for CS.

Comparing with non-pregnant women with CS, the treatment is different in Cushing’s syndrome during pregnancy.

We described here the case of a 25-year-old woman with CS during her forth [sic] pregnancy. Hypertension, diabetes, hypopotassaemia, purple striae and acne are present. Cushing’s syndrome in the patient resolved within four weeks of artificial termination. Eight months after artificial termination, the patient became pregnant again and rapidly developed Cushing’s syndrome with typical clinical symptoms and signs and laboratory results.

Title: Pregnancy-induced Cushing’s Syndrome: A Case Report

Category: Tumor Biology

Filename: Pregnancy-induced Cushing’s Syndrome: A Case Report.pdf

Pages: 101

Price: US$48.00

Buy this pater at http://www.tumorres.com/tumor-biology/25201.htm

 

Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature

PITUITARY

DOI: 10.1007/s11102-011-0368-2

Mustafa Berker, Derya Burcu Hazer, Taşkın Yücel, Alper Gürlek,Ayşenur Cila, Mustafa Aldur and Metin Önerci

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Abstract

Endoscopic transsphenoidal surgery is emerging as a minimally invasive and maximally effective procedure for pituitary adenomas. In this report we analyzed the complications in 624 procedures of endonasal transsphenoidal endoscopic surgery in the treatment of 570 patients with pituitary adenomas. The leading author (MB) operated pituitary adenomas via pure endoscopic endonasal transsphenoidal surgery between January 2006 and August 2011 at the Hacettepe University, Department of Neurosurgery in Ankara. Complications were assessed in 624 surgical procedures under five groups; rhinological, CSF leaks, infection, vascular and endocrinologic complications. We observed a total of 76 complications (12.1%). Rhinological complications occurred in 8 patients (1.3%): 4 epistaxis (0.6%) and 4 hyposmia (0.6%). Postoperative CSF leaks occurred in 8 patients (1.3%), and infectious complications occurred in 8 patients: 3 cases of sphenoidal sinusitis (0.4%), 5 cases of meningitis (0.8%). Only 1 case of internal carotid aneurysm rupture during the opening of sellar floor (0.16%) was observed. Endocrinologic complications occurred in 51 (8.1%) patients: Anterior pituitary deficiency in 12 (1.9%), transient diabetes insipidus (DI) in 29 (4.6%), permanent DI in 3 (0.4%) and inappropriate antidiuretic hormone secretion syndrome occurred in 7 (1.1%). There was no mortality directly related to the surgical procedure. The complication rates observed in our study suggests that the endoscopic pituitary surgery is at least as safe as microscopic transphenoidal surgery. These rates were obtained with due experience and well-coordinated teamwork. To further improve these rates, new technological developments will be helpful.

Keywords  Pituitary – Adenoma – Endonasal endoscopic surgery – Complication

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From http://www.springerlink.com/content/y17223k8481p64r0/

Cushing’s Syndrome Clinical Analysis of 77 Cases

OBJECTIVE To analyze the cause of Cushing’s syndrome classification, the major clinical manifestations and laboratory features of frequency of occurrence, and the efficiency of various diagnostic methods to evaluate the clinical doctors to improve diagnosis and treatment of disease, improve patient prognosis.

METHODS from 2004 to 2009 in our hospital by clinical or pathological diagnosis of Cushing’s syndrome in patients with clinical data, of which 57 cases of females, 20 males. For the 77 cases of clinical manifestations, laboratory examination, imaging studies, clinical diagnostic tests, pathological characteristics and with the results of literature analysis and summary of them were analyzed retrospectively.

RESULTS 1. From 2004 to 2009 were diagnosed 77 cases of Cushing’s syndrome, of which 20 males, female 57 cases, male: female = 2:2.85, adrenal adenoma 80% of female patients of childbearing age women.

2. In Cushing’s disease causes the most common (35 cases), followed by adrenal cortical adenoma (30 cases, the left side of 21 cases), there is a growing trend in the latter. Cushing’s disease course and age of onset of adrenal adenomas were higher than those, the difference was statistically significant (P <0.05), the shortest duration of adrenal carcinoma.

3. Clinical performance, the performance of the diversity of its starter, Hypertension and central obesity were the most frequently occur in 75%, and 79.22% suffering from hypertension, Hypertension 1 11.48%, Hypertension 2 62.30%, Hypertension 3 grade 26.23%, and the incidence of abnormal glucose metabolism and hyperlipidemia, respectively 41% and 68%, of which the proportion of diabetes by 30%, 65% of patients had hypokalemia, mostly mild to moderate, adrenal cortex carcinoma 100% of patients with a low potassium, and is of moderate to severe hypokalemia. Cushing’s disease and adrenal adenoma in serum potassium, blood pressure and gender showed no significant difference.

4. In the diagnosis of Cushing’s syndrome test, blood cortisol circadian rhythm disappeared (98.65%), elevated midnight serum cortisol (98.55%), 4Pm serum cortisol increased (97.14%), low-dose dexamethasone suppression test (94.59%), 24hUFC increased (91.22%), morning serum cortisol increased (71.62%). Low-dose dexamethasone suppression of serum cortisol in the morning the next day the basis of 8:00 of serum cortisol of 50% and 275,200,138,50 nmol/Lthe sensitivity of the cut-off point were 94.6%, 95.9%, 97.3% , 97.3% and 100%.

5. Patients with Cushing’s syndrome in the differential diagnosis, 80% of Cushing’s patients can be high-dose dexamethasone suppression, while more than 95% of patients with adrenal cortical adenoma can not be high-dose dexamethasone suppression. Cushing’s patients compared with blood cortisol and ACTH levels were significantly higher in patients with adrenal tumors, while the latter’s rhythmic performance is worse, the differences were statistically significant (P<0.05). Both urinary free cortisol showed no significant difference.6. imaging examination, pituitary MRI can detect 88% of Cushing’s disease there is pituitary adenoma, while the adrenal CT 100% can find out the adrenal tumors, adrenal CT of adrenal tumors and hyperplasia pathology consistent rate of 97.5%.

CONCLUSION 1. The present study in Cushing’s disease and adrenal cortical adenoma is still the most common cause of this group a high proportion of cases of adrenal adenoma, left more common. Cushing’s syndrome more common in women of childbearing age women, more common adrenal adenoma, Hypertension is the most common symptoms, mostly moderate to severe hypertension, diabetes, low potassium, high incidence of dyslipidemia.

2. Diagnostic tests in the CS, the morning cortisol increase the sensitivity of the worst, and serum cortisol circadian rhythm disappeared, midnight serum cortisol increased, 4PM cortisol rise, low-dose dexamethasone suppression test, 24hUFC elevated. There was no significant difference。

3. Patients with Cushing’s disease course, age of onset, blood cortisol and ACTH levels were higher than the adrenal adenoma, the latter comparison rhythm of blood cortisol rhythm performance is worse. The serum potassium, blood pressure and no significant difference in gender.

4. High-dose dexamethasone suppression test is to identify Cushing’s disease and adrenal cortical adenoma of the most appropriate method, CT of the adrenal lesion positive rate and help confirm the diagnosis and localization, B super-positive rate was significantly lower than CT, head MRI in Cushing’s disease positive rate.

From http://www.tumorres.com/tumor-metastasis/15968.htm

J Clin Endocrinol Metab. 2011 Oct;96(10):E1670-4. Epub 2011 Aug 3.

Overt immune dysfunction after Cushing's syndrome remission: a consecutive case series and review of the literature.

da Mota F, Murray C, Ezzat S.

Source

Department of Medicine, University Health Network, Toronto, Ontario, Canada M5G 2M9.

Abstract

CONTEXT:

Autoimmune diseases frequently improve during active Cushing's syndrome. Several studies have reported new onset or exacerbation of these conditions upon cortisol normalization.

OBJECTIVE:

Our objective was to investigate the incidence and clinical characteristics of patients with autoimmune or allergic diseases after Cushing's syndrome remission.

METHODS:

Consecutive cases of confirmed Cushing's syndrome were characterized. A review of the literature was conducted to identify previous descriptions of immune dysfunction upon remission and evidence of the hypothalamic-pituitary-adrenal axis influence on the immune system.

RESULTS:

Among 66 patients who achieved Cushing's syndrome remission, the incidence of immune dysfunction was 16.7%, where eight cases (72.7%) were noted for the first time and three (27.3%) were exacerbated. All had an ACTH-dependent cause. Glucocorticoids reduce proinflammatory cytokines and interact with other transcription factors affecting T cell and mast cell survival.

CONCLUSION:

Hypercortisolism induces a state of immunosuppression. After Cushing's syndrome remission, rebound immunity frequently results in overt conditions extending beyond thyroid dysfunction.

from http://www.ncbi.nlm.nih.gov/pubmed/21816785

Pituitary apoplexy in non-functioning pituitary adenomas: long term follow up is important because of significant numbers of tumour recurrences

Authors: Pal, A.1; Capatina, C.1; Tenreiro, A.P.1; Guardiola, P.D.1; Byrne, J.V.2; Cudlip, S.3; Karavitaki, N.1; Wass, J.A.H.1

Source: Clinical Endocrinology, Volume 75, Number 4, 1 October 2011, pp. 501-504(4)

Publisher: Wiley-Blackwell

Abstract

Pal A et al. – Patients with classical pituitary apoplexy may show recurrent pituitary tumour growth and therefore these patients need continued post–operative surveillance if they have not had post–operative radiotherapy.

Objectives  The frequency of pituitary tumour regrowth after an episode of classical pituitary apoplexy is unknown. It is thus unclear whether regrowth, if it occurs, does so less frequently than with non-apoplectic non-functioning pituitary macroadenomas that have undergone surgery without postoperative irradiation. This has important repercussions on follow up protocols for these patients.

 

Design  Retrospective cohort study of patients diagnosed with classical pituitary apoplexy in Oxford in the last 24 years.

 

Measurements  MRI/CT scans of the pituitary were performed post-operatively and in those patients who did not receive pituitary irradiation, this was repeated yearly for 5 years and 2 yearly thereafter.

 

Results  Thirty-two patients with non-functioning pituitary adenomas who presented with classical pituitary apoplexy were studied. There were 23 men and the mean age was 56·6 years (range 29-85). The mean follow up period was 81 months (range 6-248). Five patients received adjuvant radiotherapy within 6 months of surgery and were excluded from further analysis. In this group, there were no recurrences during a mean follow up of 83 months (range 20-150). In the remaining 27 cases there were 3 recurrences, with a mean of 79 months follow up (range 6-248) occurring 12, 51 and 86 months after surgery. This gives a recurrence rate of 11·1% at a mean follow up of 6·6 years post surgery. All recurrences had residual tumour on the post operative scan.

 

Conclusions  Patients with classical pituitary apoplexy may show recurrent pituitary tumour growth and therefore these patients need continued post-operative surveillance if they have not had post-operative radiotherapy.

Document Type: Research article

DOI: 10.1111/j.1365-2265.2011.04068.x

 

From http://www.ingentaconnect.com/content/bsc/cend/2011/00000075/00000004/art00015