Erythropoiesis in Cushing syndrome: sex-related and subtype-specific differences. Results from a monocentric study

Detomas, Mario; Deutschbein, Timo; Tamburello, Mariangela; Chifu, Irina; Kimpel, Otilia; Sbiera, Silviu; Kroiß, Matthias; Fassnacht, Martin; Altieri, Barbara

doi:10.1007/s40618-023-02128-x

Cited by 12 publications

(15 citation statements)

References 37 publications

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“…Thus, similar non-invasive protocols should be evaluated and validated in other settings using these and other emerging modalities such as desmopressin stimulation test, and CRH-receptor targeted molecular imaging (68Ga-CRH-PET-CT) [31,32]. Recent studies have also shown subtype-specific differences in hematological parameters between CD and EAS [33,34]; further validation of these findings and incorporation in future non-invasive models would add value. To conclude, using simple and non-invasive alternative strategies, BIPSS could be avoided in 41 % and peripheral CRH stimulation in 22 % of patients with ACTH-dependent CS and no macroadenoma, in whom these procedures would have otherwise been recommended.…”

Section: Discussionmentioning

confidence: 99%

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome

Attri,

Goyal,

Kalaivani

et al. 2023

Horm Metab Res

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We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. We performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH <97.3 pg/mL, HDDST ≥57% cortisol suppression, CRH stimulation ≥77% ACTH increase and ≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

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Section: Discussionmentioning

confidence: 99%

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome

Attri,

Goyal,

Kalaivani

et al. 2023

Horm Metab Res

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“…Alterations of hematological parameters which are observed in patients with CS (e.g. neutrophilia, lymphopenia, anemia in males) typically improve after remission of hypercortisolism [45,46]. However, detailed information on the distinct changes of hematological parameters during medical therapy have not been reported yet.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…However, as mineralocorticoid precursors often increase under 11β-hydroxylase inhibitors, potassium levels may also worsen during treatment [3]. Alterations of hematological parameters observed in patients with CS (e. g., neutrophilia, lymphopenia, anemia in males) typically improve after remission of hypercortisolism [45,46]. However, detailed information on the distinct changes in hematological parameters during medical therapy has not been reported yet.…”

Section: Drug Monitoringmentioning

confidence: 99%

Medical Therapy of Endogenous Cushing’s Syndrome with Steroidogenesis Inhibitors: Treatment Rationale, Available Drugs, and Therapeutic Effects

Detomas,

Deutschbein,

Altieri

2024

Exp Clin Endocrinol Diabetes

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Endogenous Cushing’s syndrome (CS) is a rare disease characterized by a glucocorticoid excess. If inadequately treated, the latter can lead to increased morbidity and mortality. Surgical removal of the underlying tumor is the first line treatment but is sometimes not feasible or even contraindicated. Additionally, in cases with severe CS, rapid control of hypercortisolism may be required. In these scenarios steroidogenesis inhibitors represent a therapeutic alternative to surgery. Over the last years, the knowledge on the broad therapeutic effects of steroidogenesis inhibitors and the number of available drugs have increased. However, large comparative studies are still lacking. Accordingly, the decision on which drug to be used in a certain patient or clinical setting may be difficult. The aim of this review is to summarize the main characteristics of steroidogenesis inhibitors.

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“…In addition to the classic constellation of signs and symptoms, CS has been shown to in uence patients' hematological pro les: anemia [9,10], polycythemia [11][12][13], leukocytosis [9,14,15], lymphopenia [16], and proliferation of in ammatory markers [17] have all been reported. Most trends were identi ed in particular demographic groups of a patient population.…”

Section: Introductionmentioning

confidence: 99%

Impact of etiology, sex, diabetes mellitus and remission status on erythrocytic profile in patients with cushing’s syndrome: a large population database study

Dery,

Stern,

Shimon

et al. 2024

Pituitary

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The study aimed to characterize the erythrocytic pro le in patients with Cushing's syndrome (CS) versus controls from the normal population according to etiology, sex, presence of diabetes mellitus (DM) and hypercortisolemia remission status. MethodsThis retrospective cohort analysis compared erythrocytic parameters between patients with CS of pituitary (CD) and adrenal (aCS) etiology and age, sex, body mass index (BMI) and socioeconomic status-matched controls in a 1:5 ratio. Laboratory values at baseline were calculated as mean values during the year preceding CS diagnosis, and over one year thereafter. ResultsThe cohort included 397 CS patients (68.26% female; mean age 51.11 ± 16.85 years) and 1970 controls. Patients with CS had signi cantly higher baseline median levels of hemoglobin (Hgb) (13.70 g/dL vs. 13.12 g/dL [p < 0.0001]) and hematocrit (Hct) (41.64% vs. 39.80% [p < 0.0001]) compared to controls. These differences were observed for both CD and aCS and for both sexes. Patients who attained remission had Hgb and Hct levels comparable to controls (13.20 g/dL and 40.08% in patients with CD and aCS vs. 13.20 g/dL and 39.98% in controls). Meanwhile, those with persistent/recurrent disease maintained elevated levels. Patients with comorbid DM had similar Hgb but higher Hct (p = 0.0419), while patients without DM showed elevated erythrocytic values compared to controls (p < 0.0001). ConclusionOur data illustrates that erythrocytic parameters are directly in uenced by glucocorticoid excess as Hgb and Hct are higher in patients with CS, and normalize after remission. We have identi ed the in uence of DM on erythrocytic parameters in patients with CS for the rst time. ParticipantsAfter the initial screening of patients with an ICD-10 diagnosis of CS, cases had to meet one of the following criteria: (a) any recorded 24-hour urinary free cortisol (UFC) > 4 × upper limit of normal (ULN), (b) 24-hour UFC > 3 × ULN and a surgical intervention to remove the pituitary or adrenal adenoma, (c) a 24hour UFC > 2 × ULN and treatment with metyrapone, ketoconazole, osilodrostat, cabergoline, or pasireotide.Each diagnosis was retrospectively con rmed by the authors AA and YR during data collection, by a thorough review of documented biochemical and imaging test results, as well as information about management and follow-up. For each patient, the time of diagnosis was de ned as the earliest occurrence of either an elevated UFC result, the rst pituitary or adrenal gland resection, or the initial diagnosis of CS. Each patient with CS was paired with ve, age, sex, BMI and socioeconomic status-matched controls.All patients with adrenocorticotropic hormone (ACTH)-dependent CS were screened to con rm exclusion of ectopic CS. Patients with adrenocortical carcinoma that were identi ed within 5 years of CS detection or patients with ectopic CS were excluded from the study. De nitionsThe etiology of CS was established based on the available biochemical and radiological data, pharmacotherapy, radiotherapy, and surgical interventions for C...

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Erythropoiesis in Cushing syndrome: sex-related and subtype-specific differences. Results from a monocentric study

Cited by 12 publications

References 37 publications

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome

Medical Therapy of Endogenous Cushing’s Syndrome with Steroidogenesis Inhibitors: Treatment Rationale, Available Drugs, and Therapeutic Effects

Impact of etiology, sex, diabetes mellitus and remission status on erythrocytic profile in patients with cushing’s syndrome: a large population database study

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