Long Term Follow-Up of Eight Patients with Sub-Clinical Cushing’s Syndrome and Aberrant Adrenal Hormone Receptors.

ObjectiveTo evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas.Design and methodsA total of 118 patients (77 F and 47 M; age 62.3±1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1–10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery.ResultsAt entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%,P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic–cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement.ConclusionsThe risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.

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Pediatric Cushing’s syndrome: greater risk of being overweight or obese after long-term remission and its predictive factors

Acta Endocrinologica ◽

10.1530/eje-20-0848 ◽

2021 ◽

Vol 184 (1) ◽

pp. 179-187

Author(s):

Nuria Valdés ◽

Amit Tirosh ◽

Meg Keil ◽

Constantine A Stratakis ◽

Maya Lodish

Keyword(s):

At Risk ◽

Children And Adolescents ◽

Cushing’S Syndrome ◽

Predictive Factors ◽

Cushing's Syndrome ◽

Normal Weight ◽

Z Score ◽

Initial Weight Loss

Objective Due to the rarity of Cushing’s syndrome (CS) in children and adolescents, data are scarce about BMI during active disease and following remission. Therefore, our aim was to analyze BMI after long-term remission and determine predictive factors for promptly identifying patients at risk of being overweight or obese after remission for CS. Design Retrospective cohort study. Patients 73 patients: 58 (79.4%) had Cushing disease, 40 males (58%), median age of 12 years (IQR: 9–15). The mean follow-up time was 22.4 ± 18.2 months (range: 4–98). Methods Main outcome measures: BMI, lipid profile, blood pressure, HOMA-IR. Results At diagnosis, only eight (11%) patients had a normal weight. Although the BMI z-score at the last follow-up improved (2.0 ± 0.7 to 1.0 ± 1.2, P < 0.001), 44% remained overweight or obese after 2 years of remission according to the Kaplan-Meier curves. The BMI z-scores at the last follow-up correlated only with HOMA-IR levels (r: 0.49, P = 0.027). We found two independent factors related to reaching a normal weight: BMI z-score at diagnosis (HR: 0.156, 95% CI: 0.038–0.644; P = 0.01) and BMI z-score change at 6 ± 2 months (HR: 2.980, 95% CI:1.473–6.028; P = 0.002), which had high accuracy when a cut-off of 0.5 was used for ROC analysis (AUC = 0.828 (0.67–0.97); P < 0.001). Conclusions Children and adolescents with CS have a high risk of being overweight or obese after successful treatment for their disease. At risk patients can be identified quickly based on their baseline BMI and initial weight loss after surgery. Efforts should focus on adopting healthy diet and lifestyle in the immediate postoperative period.

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A Novel Tool in the Diagnosis and Follow-Up of (Cyclic) Cushing's Syndrome: Measurement of Long-Term Cortisol in Scalp Hair

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-1852 ◽

2012 ◽

Vol 97 (10) ◽

pp. E1836-E1843 ◽

Cited By ~ 69

Author(s):

L. Manenschijn ◽

J. W. Koper ◽

E. L. T. van den Akker ◽

L. J. M. de Heide ◽

E. A. M. Geerdink ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Scalp Hair ◽

Cushing's Syndrome

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Are Ectopic or Abnormal Membrane Hormone Receptors Frequently Present in Adrenal Cushing’s Syndrome?1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.10.6865 ◽

2000 ◽

Vol 85 (10) ◽

pp. 3531-3536 ◽

Cited By ~ 1

Author(s):

Hortensia Mircescu ◽

Jose Jilwan ◽

Nina N′Diaye ◽

Isabelle Bourdeau ◽

Johanne Tremblay ◽

...

Keyword(s):

Medical Therapy ◽

Cushing’S Syndrome ◽

Hormone Receptors ◽

Gastric Inhibitory Polypeptide ◽

Cushing's Syndrome ◽

Adrenergic Agonists ◽

Adrenal Hyperplasia ◽

Clinical Screening ◽

Adrenal Hormone

Twenty consecutive patients with adrenal Cushing’s syndrome were studied with an in vivo protocol to determine the prevalence and diversity of the presence of ectopic or abnormal hormone receptors in their adrenal tissues. All six patients with bilateral ACTH-independent macronodular adrenal hyperplasia were found to have one or two abnormal adrenal receptors, including those for gastric inhibitory polypeptide, vasopressin (V1-vasopressin),β -adrenergic agonists, LH/human CG, or serotonin 5-HT4. The presence of abnormal hormone receptors was found to be less frequently present in unilateral adenomas or carcinomas (3 of 14). The identification of abnormal adrenal hormone receptors can allow new pharmacological therapies of hypercortisolism. We suggest that the clinical screening for the presence of abnormal hormone receptors should be conducted in patients with adrenal Cushing’s syndrome and, more particularly, in those with ACTH-independent macronodular adrenal hyperplasia, in the hope of offering medical therapy as an alternative to bilateral adrenalectomy.

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Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: A prospective, long-term study

Acta Endocrinologica ◽

10.1530/eje.1.02067 ◽

2006 ◽

Vol 154 (1) ◽

pp. 109-118 ◽

Cited By ~ 82

Author(s):

Cybèle Kristo ◽

Rune Jemtland ◽

Thor Ueland ◽

Kristin Godang ◽

Jens Bollerslev

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Bone Mineral ◽

Cushing’S Syndrome ◽

Biochemical Markers ◽

Cushing's Syndrome ◽

Mineral Density ◽

Long Term Outcome

Objective: Endogenous Cushing’s syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified. Design: We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 (n = 25) and 71 months (n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally. Methods: Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1). Results: Mann–Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% (P < 0.001), 15.7% (P < 0.001), and 9.2% (P < 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin (P = 0.014) and increased CTX-1 (P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P < 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS (r = 0.59; P = 0.002) and FN (r = 0.52; P = 0.007); Spearman’s rank correlation), in CS was paralleled by increased osteocalcin (275%, P < 0.001) and correlation between biochemical markers (r = 0.92, P < 0.001; Pearson’s correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments. Conclusion: Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).

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Surviving ectopic Cushing’s syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushing’s disease during long-term follow-up

Acta Endocrinologica ◽

10.1530/eje-18-0212 ◽

2018 ◽

Vol 179 (2) ◽

pp. 109-116 ◽

Cited By ~ 11

Author(s):

Andrea Osswald ◽

Timo Deutschbein ◽

Christina M Berr ◽

Eva Plomer ◽

Anne Mickisch ◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Syndrome ◽

Psychiatric Morbidity ◽

Serum Cortisol ◽

Cushing's Syndrome ◽

Ectopic Cushing’S Syndrome ◽

Cortisol Levels

Objective Aim of our study was to analyze long-term outcome of patients with the ectopic Cushing’s syndrome (ECS) compared to patients with Cushing’s disease (CD) regarding cardiovascular, metabolic, musculoskeletal and psychiatric comorbidities. Design Cross-sectional study in patients with ECS and CD in two German academic tertiary care centers. Methods Standardized clinical follow-up examination was performed including health-related quality of life (QoL) in 21 ECS patients in long-term remission (≥18 months since successful surgery). Fifty-nine patients with CD in remission served as controls. Results Time from first symptoms to diagnosis of Cushing’s syndrome (CS) was shorter in ECS than in CD (8.5 (IQR: 30.3) vs 25 (IQR: 39.0) months, P = 0.050). ECS patients had lower self-reported psychiatric morbidity compared to CD (19% vs 43%, P = 0.050) at follow-up. Moreover, female ECS patients reported favorable scores for QoL in the SF-36 questionnaire (mental health: 92 (IQR: 30) vs 64 (IQR: 32) in CD, P = 0.010) and a Cushing-specific QoL questionnaire (73 (IQR: 18) vs 59 (IQR: 36) in CD, P = 0.030). In a pooled analysis of ECS and CD patients, QoL correlated with time from first symptoms until diagnosis of CS, but not with urinary free cortisol levels or serum cortisol after dexamethasone at the time of diagnosis. Long-term outcomes regarding hypertension, metabolic parameters, bone mineral density and grip strength were comparable in ECS and CD. Conclusions Our data support the concept that time of exposure to glucocorticoid excess appears to be a better predictor than peak serum cortisol levels at the time of diagnosis regarding long-term psychiatric morbidity and QoL.

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