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Posted on
September 15, 2021
Metyrapone in Cushing's Syndrome

Six decades of clinical use, accompanied by number of prospective and retrospective studies, have established metyrapone as an effective treatment for Cushing's syndrome. What new information will you glean from this helpful, question and answer format, review?

Al-Salama, ZT. Metyrapone in Cushing’s Syndrome: A Profile of its Use. Drugs Ther Perspect  2021. doi.org/10.1007/s40267-021-00853-y

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Posted on
August 24, 2021
A challenge to the current methods of CD investigation

This review explains the recent work of Walia et al. 2021, who have used a novel imaging technique to correctly identify adenomas, some of which were negative on MRI or of ectopic origin. Could this study eventually change how we diagnose CD?

Bertherat J. CRH-Receptor Molecular Imaging Reveals the Intimacy of Corticotroph Adenomas. J Clin Endocrinol Metab. 2021 106:e1902-e1904.

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Posted on
August 3, 2021
Ga-68 corticotrophin-releasing hormone PET-CT

This novel, non-invasive molecular imaging technique potentially expands current diagnostic capabilities – will you investigate?

Walia R, et al. Molecular Imaging Targeting Corticotropin-releasing Hormone Receptor for Corticotropinoma: A Changing Paradigm. J Clin Endocrinol Metab. 2021 106:e1816-e1826

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Posted on
August 3, 2021
Inferior petrosal sinus sampling

Findings from this literature review suggest using a stepwise approach to performing IPSS and interpreting the results. How might your practice be influenced?

Perlman JE, et al. Pitfalls in Performing and Interpreting Inferior Petrosal Sinus Sampling: Personal Experience and Literature Review J Clin Endocrinol Metab. 2021 106:e1953-e1967.

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Posted on
August 3, 2021
Hypercortisolism and atrial fibrillation

This study attempts to establish a causal relationship between hypercortisolism and AF but what were the precise findings and likely mediators?

Larsson SC, et al. Plasma Cortisol and Risk of Atrial Fibrillation: A Mendelian Randomization Study. J Clin Endocrinol Metab. 2021 106:e2521-e2526.

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Posted on
August 3, 2021
Adrenal incidentalomas and mental health

This study evaluated psychiatric and neurocognitive functions in adrenal incidentaloma patients with subclinical hypercortisolism. What recommendations can be made?

Morelli V, et al. Mental Health in Patients with Adrenal Incidentalomas: Is There a Relation with Different Degrees of Cortisol Secretion? J Clin Endocrinol Metab. 2021 106:e130-e139. Open Access

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Posted on
August 3, 2021
Aggressive pituitary tumours and carcinomas

Mutations in the ATRX gene have been implicated in the development of several cancer types. This study examined the ATRX gene in APTs and PCs – what were the findings, and could new techniques identify patients at high risk?

Casar-Borota O, et al. Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations. J Clin Endocrinol Metab. 2021 106:1183-1194 Open Access

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Posted on
July 19, 2021
Hair cortisol and cortisone measurement

This study measured hair cortisol and cortisone in a variety of patients with Cushing's syndrome. Are these measurements of diagnostic value in patients with mild disease?

Brossaud J, et al. Hair cortisol and cortisone measurements for the diagnosis of overt and mild Cushing's syndrome. Eur J Endocrinol. 2021; 184:445-454. Open Access.

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Posted on
July 19, 2021
A new outcome predictor for pituitary adenoma?

While full blood count and serum inflammation-based scores reflect systemic inflammation and predict outcomes in cancer, are these biochemical data of similar value in the treatment of pituitary adenomas?

Marques P, et al. Pre-operative serum inflammation-based scores in patients with pituitary adenomas. Pituitary 2021 24:334-350.

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Posted on
July 19, 2021
In vitro and in vivo models show promise for new medical therapies

Current medical therapies for CD by and large exert no action on tumour growth – could this be about to change?

Zhang D, et al. Targeting Corticotroph HDAC and PI3-Kinase in Cushing Disease. J Clin Endocrinol Metab. 2021 106:e232-e246

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Posted on
July 16, 2021
An update on Carney complex

While there is still no specific medical treatment for Carney complex, what advances have been made in our understanding of this disorder and what recommendations can be made?

Bouys L and Bertherat J. Management of Endocrine Disease: Carney complex: clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene. Eur J Endocrinol. 2021; 184:R99-R109. Open Access.

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Posted on
July 16, 2021
Chronic exposure to hypercortisolism and its effect on the brain

The adverse effects of chronic exposure to hypercortisolism on the human brain remain unclear.  This study correlated MRI findings with neuropsychological testing and clinical examination in 97 active and remitted CS patients. What was learned?

Jiang H, et al. Imaging cerebral microbleeds in Cushing's disease evaluated by quantitative susceptibility mapping: an observational cross-sectional study. Eur J Endocrinol. 2021; 184:565-574. Open Access.

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Posted on
July 16, 2021
Muscle atrophy in patients with endogenous Cushing's syndrome

This study looked at individual Insulin-like growth factor I concentrations 6 months after curative surgery for Cushing's syndrome. What were the correlations with adverse long-term myopathy outcomes?

Vogel F, et al. Patients with low IGF-I after curative surgery for Cushing's syndrome have an adverse long-term outcome of hypercortisolism-induced myopathy. Eur J Endocrinol. 2021; 184:813-821. Open Access.

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Posted on
July 16, 2021
Independent risk factors for mortality – results from a 40-year study

This longitudinal cohort study examined the SMRs of 191 CD patients initially presenting with pituitary adenoma. What were the independent risk factors related to increased mortality in this group?

Roldán-Sarmiento P, et al. Diabetes, Active Disease, and Afternoon Serum Cortisol Levels Predict Cushing's Disease Mortality: A Cohort Study. J Clin Endocrinol Metab. 2021; 106:e103-e111

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Posted on
July 16, 2021
A potential new pharmacotherapy?

This study compared the in vitro effects of racemic ketoconazole with levoketoconazole on adrenocortical and pituitary adenoma cells. What effects were seen?

Creemers SG, et al. Levoketoconazole, the 2S,4R Enantiomer of Ketoconazole, a New Steroidogenesis Inhibitor for Cushing's Syndrome Treatment. J Clin Endocrinol Metab. 2021; 106:e1618-e1630.

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Posted on
July 16, 2021
Classification of pituitary tumours – challenge to the status quo?

Results of this study suggests a close association between chromosome instability and aggressive corticotroph tumour behaviour. Could these findings lead to the identification of high-risk tumours and, in turn, a new system of classification?

Reincke M and Theodoropoulou M. Genomics in Cushing's Disease: The Dawn of a New Era. J Clin Endocrinol Metab. 2021 106:e2455-e2456. Open Access

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Posted on
July 16, 2021
Risk assessment and treatment of potentially severe Cushing’s related complications

Experts from the USA, Canada and Austria explore the risk assessment and management of severe complications of Cushing’s disease. What will you learn from this case-based guide?

Varlamov EV, et al. Management of Endocrine Disease: Cardiovascular risk assessment, thromboembolism, and infection prevention in Cushing's syndrome: a practical approach. Eur J Endocrinol. 2021 184:R207-R224 Open Access

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Posted on
June 22, 2021
Thyroid function in Cushing syndrome

This single-center retrospective cohort study examined the records of 123 adult patients seen between 1985 and 2018. What biochemical correlations were found and what degree of thyroid function was restored after successful treatment of Cushing’s syndrome?

Shekhar S, et al. The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome Before and After Curative Surgery. J Clin Endocrinol Metab. 2021;106:e1316-e1331.

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Posted on
June 22, 2021
Raised BMI in children and adolescents with Cushing’s syndrome

Can you predict the likelihood of younger patients remaining overweight or obese following successful treatment and what, if anything, can be done to intervene?

Valdés N, et al. Pediatric Cushing's syndrome: greater risk of being overweight or obese after long-term remission and its predictive factors. Eur J Endocrinol. 2021;184:179-187.

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Posted on
June 22, 2021
Results of the SONICS trial

What is the impact of levoketoconazole treatment on quality-of-life scores, depression, and specific clinical signs and symptoms characteristic of CS?

Geer EB, et al. Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing's syndrome. Pituitary. 2021;F24:104-115.

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Posted on
June 18, 2021
Intermittent Cushing’s syndrome

This paper describes a diagnostic algorithm for cyclic CS with special regard to hair cortisol analysis and the desmopressin stimulation test – could this tool facilitate faster diagnosis?

Świątkowska-Stodulska R, et al. Cyclic Cushing's Syndrome – A Diagnostic Challenge. Front Endocrinol (Lausanne). 2021:12:658429/fendo.2021.658429.

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Posted on
June 18, 2021
Neuropsychological impairment in Cushing’s syndrome

This systematic review examines the presence and severity of neuropsychological impairment in Cushing’s patients. What reassurance can be given to patients and what studies remain to be done?

Siegel S, et al. Neuropsychological functioning in patients with Cushing's disease and Cushing's syndrome. Clin Endocrinol Diabetes. 2021;129:194-202.

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Posted on
April 29, 2021
Update on Nelson’s Syndrome

This review article summarizes our current understanding of this rare disorder and includes definitions, pathology, and treatment options, together with a subset of tumors undergoing malignant transformation.

Fountas A, Karavitaki N. Nelson's Syndrome: An Update. Endocrinol Metab Clin North Am. 2020 Sep;49(3):413-432.

Posted on
April 29, 2021
Maternal and fetal outcomes after adrenalectomy

A total of 12 pregnant women who underwent adrenalectomy over a 15-year period were identified from a prospectively maintained database. Results show that while maternal outcome is acceptable, fetal outcome is influenced by several factors and is variable.

Gaujoux S, et al. Adrenalectomy during pregnancy: A 15-year experience at a tertiary referral center. Surgery. 2020 Aug;168(2):335-339

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Posted on
April 29, 2021
Long-term outcome following conventional fractionated radiotherapy – are there predictors for disease recurrence?

This is a retrospective case record analysis of 42 patients with Cushing’s Disease who underwent conventional fractionated radiotherapy (CFR) with at least 12 months follow-up. Results show that peri-CRT use of cabergoline is significantly associated with increased recurrence rates of disease.

Thakkar K, et al. Cabergoline may act as a radioprotective agent in Cushing's disease. Clin Endocrinol (Oxf). 2020 Jan;92(1):55-62.

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Posted on
April 29, 2021
Stereotactic radiosurgery following incomplete resection of pituitary adenoma

This study pooled data from 255 patients across 10 institutions participating in the International Radiosurgery Research Foundation. Are endocrine remission rates most improved following early or late stereotactic radiosurgery?

Bunevicius A, et al. Early versus late Gamma Knife radiosurgery for Cushing's disease after prior resection: results of an international, multicenter study. J Neurosurg. 2020 Feb 21:1-9.

Posted on
April 29, 2021
Predictive value of the desmopressin test for disease recurrence following pituitary surgery

This multicentre retrospective study of 95 patients with Cushing’s Disease, responding preoperatively to desmopressin test (DT) and with early post-operative corticotropic insufficiency (COI), underwent a DT within 3 months post-surgery. Results may help stratify patients with COI and refine their follow-up according to the risk of recurrence.

Cambos S, et al. Persistent cortisol response to desmopressin predicts recurrence of Cushing's disease in patients with post-operative corticotropic insufficiency. Eur J Endocrinol. 2020 May;182(5):489-498.

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Posted on
April 29, 2021
Cushing's syndrome – a diagnostic challenge

This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose dexamethasone suppression test. Will the results confirm the accuracy of late-night cortisol and cortisone testing?

Bäcklund N, et al. Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome. Eur J Endocrinol. 2020 Jun;182(6):569-582.

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Posted on
April 29, 2021
Predicting Nelson’s syndrome – an opening of new possibilities?

This tertiary care center study, which looked at 43 patients over a 35-year period, analyzed clinical symptomatology, cortisol, ACTH, and radiology following total bilateral adrenalectomy. Could the findings lead to improved patient care, including a reduction in the need for frequent imaging?

Das L, et al. ACTH increment post total bilateral adrenalectomy for Cushing's disease: a consistent biosignature for predicting Nelson's syndrome. Pituitary. 2020 Oct;23(5):488-497.

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Posted on
April 29, 2021
Intravenous etomidate infusion – not just for ITU?

This study of fourteen patients − with severe and complicated Cushing’s syndrome related to adrenal carcinoma or ectopic ACTH secretion − compared data from those treated with high starting doses of etomidate in ICU or with lower starting doses in non-ICU medical wards. Results suggest that low doses of etomidate in medical wards should be considered.

Constantinescu SM, et al. Etomidate infusion at low doses is an effective and safe treatment for severe Cushing's syndrome outside intensive care. Eur J Endocrinol. 2020 Aug;183(2):161-167.

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Posted on
April 29, 2021
Genetic modifier identified in primary pigmented nodular adrenocortical disease

Primary pigmented nodular adrenocortical disease (PPNAD) and primary bilateral macronodular adrenocortical hyperplasia are linked to respective gene mutations. This study aims to determine the potential influence of ARMC5 genes – which have many non-pathological variants in the general population – on PRKAR1A mutations, the defect that causes PPNAD.  What was shown?

Maria AG, et al. ARMC5 variants in PRKAR1A-mutated patients modify cortisol levels and Cushing's syndrome. Endocr Relat Cancer. 2020 Sep;27(9):509-517.

Posted on
April 29, 2021
Systematic review − characteristics and outcomes of ACTH- and/or CRH-secreting pheochromocytomas

This review identified 91 articles, which included original articles, case reports and case series, reporting on 99 cases of ectopic adrenocorticotropic hormone and/or corticotrophin-releasing-hormone secreting pheochromocytomas. What do we currently know about disease characteristics, management, and outcomes in these patients?

Elliott PF, et al. Ectopic ACTH- and/or CRH-producing pheochromocytomas. J Clin Endocrinol Metab. 2021 Jan 23;106(2):598-608.

Posted on
April 29, 2021
Osilodrostat − results from LINC 3

Read the findings of the prospective, multicentre, open-label, double-blind randomized withdrawal period phase III study (LINC 3).

Pivonello R, et al. Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020 Sep;8(9):748-761.

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Posted on
April 29, 2021
Real-life experience in pituitary and adrenal disease testing

This cross-sectional study of 200 patients took place in a referral University Hospital Center from 2010 to 2019.  The human corticotropin-releasing hormone (CRH) test was performed mainly for the differential diagnosis of ACTH-dependent CS or adrenal lesions but what were the findings?

F Ceccato, et al. Human Corticotropin-Releasing Hormone Tests: 10 Years of Real-Life Experience in Pituitary and Adrenal Disease. J Clin Endocrinol Metab. 2020 Nov 1;105(11):dgaa564.

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Posted on
April 29, 2021
PET/CT scan biomarker identified for the diagnosis of malignancy

This study of 64 patients confirms earlier findings that tumor-to-liver standardized uptake value ratio (SUV)max (>1.5) is a useful biomarker for the diagnosis of malignancy in adrenal masses but was a predictive model also identified?

Salgues B, et al. Risk stratification of adrenal masses by [(18) F] FDG PET/CT: Changing tactics. Clin Endocrinol (Oxf) 2021 Feb;94(2):133-140.

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Posted on
April 29, 2021
Validation of machine-learning models for delayed disease remission

This study was designed to identify predictive features of delayed post-operative disease remission using machine-based algorithms. Findings, which were based on 201 patients, identified a model with predictive ability that was significantly better than using Knosp grading and postoperative immediate morning serum cortisol alone. Could this effective approach lead to better patient care?

Yanghua Fan, et al. Development of Machine Learning Models for Predicting Postoperative Delayed Remission in Patients with Cushing's Disease. J Clin Endocrinol Metab. 2021 Jan 1;106(1):e217-e231.

Posted on
April 26, 2021
Persistent Cushing’s disease after surgery, a patient in the LINC-3 trial

This case study highlights the importance of monitoring ACTH and corticotroph tumor size in patients with persistent Cushing’s syndrome, either under effective treatment with steroidogenesis inhibitors or after bilateral adrenalectomy.

Fontaine-Sylvestre C, et al. Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing's disease. Clin. Endocrinol. 2020 Sep 25.

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Posted on
April 26, 2021
Epidemiology, long-term prognosis, and replacement therapies for adrenal Cushing syndrome in Korea

This retrospective cohort study identified 1199 new adrenal Cushing’s syndrome patients presenting between 2002 and 2017. Results show a high risk of pre- and post-operative comorbidities. The major types of glucocorticoids prescribed are given.

Ahn CH, et al. Epidemiology and Comorbidity of Adrenal Cushing's Syndrome: A Nationwide Cohort Study. J Clin Endocrinol Metab. 2020 Oct 19:dgaa752.

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Posted on
April 26, 2021
Gallium-68 tagged corticotrophin-releasing hormone PET-CT delineates corticotropinoma

Patients with ACTH-dependent Cushing's syndrome (n = 27) underwent 68-Ga CRH PET-CT. Information provided by medical imaging provided surgeons with valuable information for intraoperative tumor navigation, and helped in differentiating pituitary from extra-pituitary sources of ACTH-dependent CS.

Walia R, et al. Molecular Imaging Targeting Corticotropin Releasing Hormone Receptor for Corticotropinoma: A Changing Paradigm. J Clin Endocrinol Metab. 2020 Oct 20:dgaa755.

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Posted on
April 26, 2021
Biomarker identified for long-term disease recurrence after neurosurgery

Postoperative day 1 morning serum cortisol value is shown to be a helpful predictor of long-term disease recurrence in the statistical analysis of 260 patients with Cushing’s disease.

Wang F, et al. Postoperative Day 1 Morning Cortisol Value as a Biomarker to Predict Long-term Remission of Cushing Disease. J Clin Endocrinol Metab. 2021 Jan 1;106:e94-e102.

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Posted on
April 26, 2021
Cushing’s disease mortality predictors

This longitudinal cohort study of patients with Cushing’s disease (1979−2018) identified the main predictors for mortality, which is mainly linked to cardiovascular disease.

Roldán-Sarmiento P, et al. Diabetes, Active Disease, and Afternoon Serum Cortisol Levels Predict Cushing's Disease Mortality: A Cohort Study. J Clin Endocrinol Metab. 2021 Jan 1;106:e103-e111.

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Posted on
April 26, 2021
Children and adolescents at high risk of remaining overweight or obese

This retrospective cohort study of 73 pediatric patients with Cushing’s disease analyzed BMI after long-term remission and determined predictive factors for those at risk of remaining overweight or obese following successful treatment.

Valdés N, et al. Pediatric Cushing's syndrome: greater risk of being overweight or obese after long-term remission and its predictive factors. Eur J Endocrinol. 2021 Jan;184:179-187.

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Posted on
April 26, 2021
Use of adrenally directed medical therapies

This review article examines the use of adrenally acting medical therapies, including ketoconazole, metyrapone, osilodrostat, mitotane, and etomidate. Use of these drugs mandates adequate patient instruction and close monitoring to that ensure treatment goals are met while untoward adverse effects are minimized.

Tritos NA. Adrenally Directed Medical Therapies for Cushing Syndrome. J Clin Endocrinol Metab. 2021 Jan 1;106:16-25.

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Posted on
April 26, 2021
Intramuscular fatty infiltration in Cushing’s disease is associated with deteriorating muscle performance

This cross-sectional study at a tertiary referral center examines 36 women in disease remission. The study aims to quantify the degree of fatty infiltration in thigh muscle and evaluate the relationship between these changes and physical performance.

Martel-Duguech L, et al. Thigh Muscle Fat Infiltration Is Associated With Impaired Physical Performance Despite Remission in Cushing's Syndrome. J Clin Endocrinol Metab. 2020 May 1;105:dgz329.

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Posted on
April 26, 2021
Effect of mild autonomous cortisol secretion on bone metabolism in patients with adrenal adenomas

This cross-sectional study with prospective enrolment (2014− 2019), involved 213 patients with adrenal adenomas, with and without Cushing’s syndrome. Bone turnover markers within three patient subgroups are discussed, together with the impact of adrenalectomy.

Athimulam S, et al. The Impact of Mild Autonomous Cortisol Secretion on Bone Turnover Markers. J Clin Endocrinol Metab. 2020 May 1;105:1469-77.

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