Cushing’s Syndrome

Posted on May 22, 2015 by MaryO
Prof André Lacroix, MDcorrespondence,  Richard A Feelders, MD, Constantine A Stratakis, MD, Lynnette K Nieman, MD
Published Online: 21 May 2015
DOI: http://dx.doi.org/10.1016/S0140-6736(14)61375-1

Summary

Chronic exposure to excess glucorticoids results in diverse manifestations of Cushing’s syndrome, including debilitating morbidities and increased mortality.

Genetic and molecular mechanisms responsible for excess cortisol secretion by primary adrenal lesions and adrenocorticotropic hormone (ACTH) secretion from corticotroph or ectopic tumours have been identified. New biochemical and imaging diagnostic approaches and progress in surgical and radiotherapy techniques have improved the management of patients.

The therapeutic goal is to normalise tissue exposure to cortisol to reverse increased morbidity and mortality. Optimum treatment consisting of selective and complete resection of the causative tumour is necessay to allow eventual normalisation of the hypothalamic-pituitary-adrenal axis, maintenance of pituitary function, and avoidance of tumour recurrence. The development of new drugs offers clinicians several choices to treat patients with residual cortisol excess.

However, for patients affected by this challenging syndrome, the long-term effects and comorbidities associated with hypercortisolism need ongoing care.

Read the entire article (there is a fee of $31.50US) here.

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Mortality in cured Cushing’s disease

Posted on April 29, 2015 by MaryO

In patients diagnosed with Cushing’s disease, mortality is high compared to the general population However, it is not yet known if this mortality remains high even after initial therapy.

Therefore van Haalen et al., performed a systematic review and meta-analysis of follow-up studies in patients cured from Cushing’s disease after initial treatment. They found that mortality remained high in patients with Cushing’s disease even after initial biochemical cure remission, suggesting that cure does not directly reverse the metabolic consequences of long-term overexposure to cortisol.

Read full article by van Haalan et al., titled ‘Mortality remains increased in Cushing’s disease despite biochemical remission: a systematic review and meta-analysis’, European Journal of Endocrinology 172, R143-R149.

DOI: 10.1530/EJE-14-0556

From http://www.ese-hormones.org/news/article.aspx?articleid=9083

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Rare neuroendocrine tumours may be misdiagnosed as Cushing’s disease

Posted on October 31, 2014 by MaryO

By Eleanor McDermid, Senior medwireNews Reporter

Ectopic tumours secreting corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) are very rare in children and can result in a misdiagnosis of Cushing’s disease (CD), say researchers.

Three of the patients in the reported case series had pituitary hyperplasia and underwent transsphenoidal surgery for apparent CD before the tumour that was actually causing their symptoms was located. The hyperplasia was probably caused by release of CRH from the ectopic tumour, which stimulated the pituitary gland, giving the impression of an ACTH-secreting pituitary adenoma, explain Maya Lodish (National Institutes of Health, Bethesda, Maryland, USA) and study co-authors.

These three patients were part of a series of seven, which Lodish et al describe as “a relatively large number of patients, considering the infrequency of this disease.”

The patients were aged between 1.8 and 21.3 years. Three had neuroendocrine tumours located in the pancreas ranging in size from 1.4 to 7.0 cm, two had thymic carcinoids ranging from 6.0 mm to 11.5 cm, one patient had a 12.0 cm tumour in the liver and one had a 1.3 cm bronchogenic carcinoid tumour of the right pulmonary lobe.

Four of the patients had metastatic disease and, during up to 57 months of follow-up, three died of metastatic disease or associated complications and two patients had recurrent disease.

“Our series demonstrates that these are aggressive tumors with a high mortality rate,” write the researchers in the Journal of Clinical Endocrinology & Metabolism. “It is important to follow the appropriate work up, regarding both biochemical and imaging tests, which can lead to the correct diagnosis and to the most beneficial therapeutic approach.”

The team found the CRH stimulation test to be helpful, noting, for example, that none of the patients had a rise in cortisol that was consistent with CD, with all patients showing smaller responses ranging from 2% to 15%. Likewise, just one patient had an ACTH rise higher than 35% on CRH administration, and four patients had a “flat” response, which has previously been associated with ectopic neuroendocrine tumours.

Of note, six patients had normal or high plasma CRH levels, despite all having high cortisol levels, which would be expected to result in undetectable plasma CRH due to negative feedback, implying another source of CRH production. Five patients had blunted diurnal variation of both cortisol and ACTH levels consistent with Cushing’s syndrome.

The patients also underwent a variety of imaging procedures to identify the source of ACTH/CRH production, some of which, such as octreotide scans, are specialist and not available in most hospitals, the researchers note, potentially contributing to inappropriate diagnosis and management.

From http://www.news-medical.net/news/20141030/Rare-neuroendocrine-tumours-may-be-misdiagnosed-as-Cushinge28099s-disease.aspx

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Brains in jars at the Cushing Center in the Yale Medical Library

Posted on October 7, 2014 by MaryO

harvey-cushing-memorial

Sitting quietly in jars in a custom-built room at Yale’s medical library are 550 human brains. The collection once belonged to pioneering neurosurgeon Harvey Cushing, who preserved the brains from 1903 to 1932 as part of his tumor registry. When Cushing died in 1939, his undergraduate alma mater Yale inherited the brains.

Cushing was among a handful of doctors operating on the brain during the early 20th century. At the time, about a third of patients who underwent brain tumor surgery did not survive the operation. Cushing introduced practices that dramatically lowered the mortality rate, such as monitoring blood pressure during surgery and operating with a local anesthesic instead of ether. He was also the first to use x-rays to diagnose brain tumors.

 

Read the entire article here: Brains in jars at the Cushing Center in the Yale Medical Library.

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Subclinical Cushing’s syndrome and cardiovascular disease

Posted on May 2, 2014 by MaryO
Panagiotis Anagnostis a cEmail Address, Spyridon N Karras b, Vasilios G Athyros c, Dimitri P Mikhailidis d, Asterios Karagiannis c
Guido Di Dalmazi and colleagues1 reported that in patients with adrenal incidentalomas and either stable mild hypercortisolism or worsening of cortisol hypersecretion, all-cause and cardiovascular disease-specific mortality was higher compared with in those with adrenal incidentalomas that did not secrete cortisol, after a mean follow-up of 7·5 years. Moreover, cortisol concentrations measured after dexamethasone-suppression test were associated with all-cause mortality independent of the presence of traditional cardiovascular disease risk factors.
Subclinical Cushing’s syndrome is the most common hormonal abnormality in patients with adrenal incidentalomas (prevalence 1—29%).2 The proportion of adrenal incidentalomas that progress to subclinical Cushing’s syndrome is low (1·7%) and most are lesions of 3 cm or larger.2 Progression to overt Cushing’s syndrome is controversial (because both spontaneous normalisation of hypersecretion and stable disease have been reported during follow-up) and spontaneous normalisation of hypersecretion has been reported in 50% of cases.2 Results of the study by Di Dalmazi and co-workers1 are important because they show, for the first time, that patients with subclinical Cushing’s syndrome are at increased risk of cardiovascular disease and all-cause mortality (mainly attributable to cardiovascular disease). The association of cortisol with all-cause mortality might also be attributable to its potential role in the pathogenesis of metabolic syndrome.3
Findings of previous studies have shown an increased prevalence of cardiovascular disease risk factors in patients with subclinical Cushing’s syndrome, but data for optimum management are conflicting. Some criteria—such as large (>4—6 cm) adrenal incidentalomas, features suggestive of malignancy (eg, heterogeneity, irregular shape, calcification or necrosis, invasion to adjacent tissues), or potentially lethal hormonal hypersecretion (ie, pheochromocytomas)—support the need for adrenalectomy. However, universal surgical management of patients with subclinical Cushing’s syndrome has not been accepted.2, 4 Uncertainty about the most effective management strategy for subclinical Cushing’s syndrome is attributable to the variable definitions used, and the small sample size and retrospective nature of most studies.4 Only one prospective study has been published so far showing that laparoscopic adrenalectomy is more beneficial than is conservative management for the normalisation or improvement of cardiovascular disease risk factors, such as diabetes, dyslipidaemia, hypertension, and obesity.5
Prospective studies and registries are needed to document the effect of different approaches on the incidence of cardiovascular disease events and mortality in patients with adrenal incidentalomas and subclinical Cushing’s syndrome. Until then, individualised treatment seems prudent. Surgical management of subclinical Cushing’s syndrome can be suggested in young patients (age <50 years) and in those with cardiovascular disease risk factors or bone disease associated with hypercortisolism that are of recent onset, difficult to control with drugs, or show progression over time.4
Another message from Di Dalmazi’s study1 is that hormonal deterioration might develop even after 4—5 years, which most studies reported as a reasonable and safe follow-up.2 This possibility should be kept in mind for the management of patients with adrenal incidentalomas, especially if clinical signs of Cushing’s syndrome develop or if cardiovascular disease risk factors become evident or increase in severity (ie, hormonal hypersecretion).
We declare that we have no competing interests.

References

1 Di Dalmazi G, Vicennati V, Garelli S, et al. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing’s syndrome: a 15-year retrospective study. Lancet Diabetes Endocrinol 2014. published online Jan 29 http://dx.doi.org/10.1016/S2213-8587(13)70211-0.
2 Anagnostis P, Karagiannis A, Tziomalos K, Kakafika AI, Athyros VG, Mikhailidis DP. Adrenal incidentaloma: a diagnostic challenge. Hormones (Athens) 2009; 8: 163-184. PubMed
3 Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab 2009; 94:2692-2701. PubMed
4 Terzolo M, Pia A, Reimondo G. Subclinical Cushing’s syndrome: definition and management. Clin Endocrinol (Oxf) 2012; 76: 12-18. PubMed
5 Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E. Surgical versus conservative management for subclinical Cushing syndrome in adrenal incidentalomas: a prospective randomized study. Ann Surg 2009; 249: 388-391. PubMed
a Division of Endocrinology, Police Medical Centre, Thessaloniki, 54 640, Greece
b Department of Endocrinology and Metabolism, Agios Pavlos General Hospital, Thessaloniki, Greece
c Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
d Department of Clinical Biochemistry (Vascular Prevention Clinic) Royal Free Hospital Campus, University College London Medical School, University College London, London, UK

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