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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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Posted on
April 26, 2021
Cushing’s disease – what factors may contribute to an earlier diagnosis?

The aim of this meta-analysis, based on 5367 patients in different populations, is to assess the time span between first symptoms and diagnosis to identify what factors, if any, are associated with earlier rates of detection.

Rubinstein G, et al. Time to Diagnosis in Cushing's Syndrome: A Meta-Analysis Based on 5367 Patients. J Clin Endocrinol Metab. 2020 Mar 1;105:dgz136.

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Posted on
April 26, 2021
Patients with adrenal incidentalomas and autonomous cortisol secretion at risk of atrial fibrillation

This is a retrospective study of 632 non-Cushing’s patients evaluated for adrenal incidentalomas. Results show that affected patients are at risk of atrial fibrillation. Do these findings have implications for Cushing’s disease?

Di Dalmazi G, et al. Prevalence and Incidence of Atrial Fibrillation in a Large Cohort of Adrenal Incidentalomas: A Long-Term Study. J Clin Endocrinol Metab. 2020 Aug 1;105:dgaa270.

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Posted on
April 26, 2021
Excess mortality after long-term disease remission

This retrospective, nationwide study explored outcomes in 502 patients with confirmed Cushing’s disease identified in the Swedish National Patient Register between 1987 and 2013.

Papakokkinou E, et al. Excess Morbidity Persists in Patients With Cushing's Disease During Long-term Remission: A Swedish Nationwide Study. J Clin Endocrinol Metab. 2020;105:dgaa291.

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Posted on
March 29, 2021
Replacement for inferior petrosal sinus sampling?

This retrospective study involving 194 patients at two centers tested a non-invasive diagnostic strategy associated with 100% positive predictive value for Cushing’s disease. Will this diagnostic algorithm eventually replace the highly invasive IPSS?

Frete C, et al. Non-invasive Diagnostic Strategy in ACTH-dependent Cushing's Syndrome. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa409.

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Posted on
March 29, 2021
Impact of successful tumor resection on thyroid function

This retrospective cohort study of 123 adult patients at a clinical research center explores the prevalence of abnormal thyroid function in Cushing's syndrome and whether it is reversible after cure.

Shekhar S, et al. The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome before and after Curative Surgery. J Clin Endocrinol Metab. 2020 Nov 25:dgaa858.

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Posted on
March 29, 2021
Impact of successful tumor resection on bone metabolism

This follow-up study looks at the impact of surgery on bone mineral density and fracture rates in patients with confirmed Cushing's syndrome at the time of diagnosis and 2 years after successful tumor resection. Could successful surgery reduce the rate of Cushing’s-linked osteoporosis?

Braun LT, et al. The Effect of Biochemical Remission on Bone Metabolism in Cushing's Syndrome: A 2-Year Follow-Up Study. J Bone Miner Res. 2020;35:1711-1717. Open access.

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Posted on
March 29, 2021
Use of the desmopressin test

This review examines the potential role, and limitations, of the desmopressin test as an early and reliable predictive marker of long-term disease remission in surgical patients.

Vassiliadi DA, Tsagarakis S. Cushing's disease: the desmopressin test as a compelling predictive marker of long-term remission after transsphenoidal surgery. Eur J Endocrinol. 2020 Jun;182(6):C17-C19. Open access.

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Posted on
March 29, 2021
Recent development of a novel chronotherapy provides promise for patients on glucocorticoids

This review explains the recent advances in our understanding of hypothalamic-pituitary-adrenal axis regulation and the resulting emergence of a promising novel chronotherapy.

Lightman SL, et al.  Dynamics of ACTH and Cortisol Secretion and Implications for Disease. Endocr Rev. 2020;41:470-490. Open access.

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Posted on
March 29, 2021
Acute and life-threatening complications in Cushing’s syndrome

This single-center retrospective cohort study examined the records of 242 patients with Cushing’s syndrome highlighting the range of acute and life-threatening complications and their high prevalence, even before diagnosis and after successful surgery.

Schernthaner-Reiter MH, et al. Acute and life-threatening complications in Cushing’s syndrome: prevalence, predictors and mortality. J Clin Endocrinol Metab. 2021. Jan 31;dgab058.

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Posted on
March 29, 2021
The challenge of clinical steroidogenesis inhibition

This review examines the complexity of clinical steroidogenesis inhibition from the establishment of initial dosage and drug scheduling to the monitoring of efficacy and side effects. Four agents are considered − ketoconazole, levoketoconazole, metyrapone and osilodrostat − in mono- and combination therapy.

Castinetti F, et al. Approach to the Patient Treated with Steroidogenesis Inhibitors. J Clin Endocrinol Metab. 2021 Mar 2:dgab122.

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Posted on
March 29, 2021
Metformin in patients on systemic glucocorticoid therapy

This phase 2 trial analyzes whether metformin can improve metabolic profiles and clinical outcomes for glucocorticoid-treated patients with inflammatory disease.

Pernicova I, et al. Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial. Lancet Diabetes Endocrinol. 2020;8:278-91.

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Posted on
March 29, 2021
Outcomes after pituitary surgery

This meta-analysis looks at remission and recurrence rates after trans-sphenoidal surgery, with a focus on factors predictive of remission.

Stroud A, et al. Outcomes of pituitary surgery for Cushing's disease: a systematic review and meta-analysis. Pituitary. 2020;23:595-609.

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Posted on
March 11, 2021
Late night salivary cortisol and response to treatment

An exploratory analysis looking at the use of late-night salivary cortisol (LNSC) to monitor pharmacological response to medical treatment in Cushing’s disease.

Newell-Price J, et al. Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease. Eur J Endocrinol. 2020;182:207-17. Open access.

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Posted on
March 11, 2021
Cushing’s syndrome due to ectopic ACTH secretion

Expert review of diagnostic and therapeutic strategies surrounding ectopic ACTH syndrome, including currently available tools and comment on effectiveness of operational care via a multidisciplinary team.

Young J, et al. Management of endocrine disease: Cushing's syndrome due to ectopic ACTH secretion: an expert operational opinion. Eur J Endocrinol. 2020;182:R29-58. Open access.

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Posted on
March 11, 2021
Endocrine testing in obesity

A systematic review and associated guidance from the European Society of Endocrinology providing a rational approach to endocrine testing and treatment in people with obesity. Could this help optimize the diagnosis of Cushing syndrome?

Wilding JPH. Endocrine testing in obesity. Eur J Endocrinol. 2020;182:C13-5. Commentary. Open access.

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Posted on
March 11, 2021
Thrombotic events in Cushing’s syndrome

This retrospective, single-center, longitudinal study looks at the prevalence of thrombotic events in patients with Cushing’s syndrome after surgical and medical treatment.

Suarez MG, et al. Hypercoagulability in Cushing syndrome, prevalence of thrombotic events: a large, single-center, retrospective study. J Endocr Soc. 2019;4:bvz033. Open access.

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Posted on
March 11, 2021
Long-term muscle function in remission of endogenous Cushing’s syndrome

An observational study focusing on long-term muscle function, exploring how glucocorticoid-induced myopathy resolves following remission of endogenous Cushing’s syndrome.

Vogel F, et al. Persisting muscle dysfunction in Cushing's syndrome despite biochemical remission. J Clin Endocrinol Metab. 2020;105:e4490–8. Open access.

Image credit: © iStock 2021, with permission.
Posted on
February 17, 2021
Targeting tumor growth in Cushing’s syndrome

Current medical therapies for Cushing’s disease do not generally have an action on tumor growth. High throughput screening using a novel ‘gain of signal’ adrenocorticotropic hormone (ACTH) assay is helping identify drugs that inhibit corticotroph tumor ACTH secretion and growth, which may be of promise in Cushing’s syndrome.

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

Image credit: © Pixabay 2021, with permission.
Posted on
February 17, 2021
Management of Cushing’s syndrome in the time of COVID-19

Patients with active Cushing's syndrome may be immunocompromised, and so require strict adherence to barrier methods to prevent infection with COVID-19. Clinical practice guidelines lay out the key principles of care of these patients during the pandemic, including algorithms for investigations and management of the syndrome.

See also the Publication Highlight

Newell-Price J et al. Endocrinology in the time of COVID-19: Management of Cushing's syndrome. Eur J Endocrinol. 2020;1831:G1-7. Open access

Image credit: © AdobeStock 2021, with permission.
Posted on
February 17, 2021
Outcomes of patients with Nelson’s syndrome

A multicenter study in patients with Nelson’s syndrome exploring the predictors of long-term prognosis and tumor progression.

See also the Animated abstract

Fountas A et al. Outcomes of Patients with Nelson’s Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers. J Clin Endocrinol Metab. 2020;105:1527–37. Open access.

Posted on
February 17, 2021
Ketoconazole: Q&A for clinical use

Ketoconazole is indicated in the European Union for the treatment of endogenous Cushing’s syndrome in adults and adolescents aged over 12.

Shirley M. Ketoconazole in Cushing’s syndrome: a profile of its use. Drugs Ther Perspect. 2021; doi.org/10.1007/s40267-020-00799-7. Open access.

Image credit: © Pixabay 2021, with permission.
Posted on
February 17, 2021
Recurrence after pituitary surgery

Systematic review of 40 years of research in Cushing’s syndrome underlines the importance of annual clinical and biochemical follow-up.

Braun LT et al. Recurrence after pituitary surgery in adult Cushing's disease: a systematic review on diagnosis and treatment. Endocrine. 2020;70:218-31. Open access.

Image credit: © Unsplash 2021, with permission.
Posted on
February 17, 2021
Corticotroph aggressive pituitary tumours and ATRX mutations

ATRX mutations occur in a subset of aggressive pituitary tumors and are more common in corticotroph tumors. Could ATRX immunohistochemistry help identify patients at risk of developing aggressive and potentially metastatic pituitary tumors?

Casar-Borota O et al. Corticotroph aggressive pituitary tumours and carcinomas frequently harbour ATRX mutations. J Clin Endocrinol Metab. 2020 Oct 26:dgaa749. Open access.

Image credit: © Unsplash 2021, with permission.
Posted on
February 17, 2021
Levoketoconazole and patient-reported outcomes

A subanalysis of the open-label phase 3 SONICS trial reports the impact of levoketoconazole treatment on clinical signs and symptoms, depression, patient-reported outcomes and quality of life.

Geer EB et al. Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing’s syndrome. Pituitary. 2020; doi.org/10.1007/s11102-020-01103-6. Open Access.

Image credit: © Pixabay 2021, with permission.
Posted on
February 17, 2021
Sensitivity of screening tests for Cushing’s syndrome

Late-night salivary cortisol measured by enzyme immunoassay is a first-line screening test for Cushing syndrome with reported sensitivity and specificity of >90%. This study asked whether liquid chromatography-tandem mass spectrometry to measure salivary cortisol and cortisone could improve the sensitivity of this test.

Kannankeril J et al. Prospective evaluation of late-night salivary cortisol and cortisone by EIA and LC-MS/MS in suspected Cushing syndrome. J Endocr Soc. 2020;4:bvaa107. Open Access.

Image credit: © AdobeStock 2021, with permission.
Posted on
February 17, 2021
A meta-analysis of diagnostic tests for Cushing’s syndrome

It is still unclear which diagnostic tests for Cushing’s syndrome are the most accurate. This study employs meta-analytical techniques to compare the sensitivity and specificity of the most common diagnostic tests.

Galm BP et al. Accuracy of Laboratory Tests for the Diagnosis of Cushing Syndrome. J Clin Endocrinol Metab. 2020;105:dgaa105. Open Access.

Image credit: © iStock 2021, with permission.
Posted on
February 17, 2021
Caution advised for combination of ketoconazole and PD-1 inhibitor

Two consecutive clinical cases on hepatic function in Cushing syndrome patients receiving concomitant ketoconazole and PD-1 inhibitor.

Yang Y et al. Caution advised using combination ketoconazole and PD-1 inhibitors. AACE Clin Case Rep. 2020;6:e239-e242. Open access.

Image credit: © Unsplash 2021, with permission.