Persistent improvement of bone mineral density up to 20 years after treatment of Cushing's syndrome.

OBJECTIVE: Cushing's syndrome (CS) is associated with osteoporosis and high fracture risk. Besides male sex, it is unknown which variables influence bone mineral density (BMD) at diagnosis and it is unclear to what extent BMD normalizes during long-term follow-up after treatment of CS. The aim of this study was to determine factors associated with BMD at diagnosis of CS and to determine the long-term course of BMD and fracture rate after successful treatment of CS. DESIGN: Retrospective cross-sectional and longitudinal cohort study. METHODS: Data were collected from 231 patients with CS who were treated at the Radboud University Medical Centre between 1968 and 2020. RESULTS: At diagnosis, male sex was associated with lower Z-scores at the lumbar spine (LS) compared with female sex: -0.97s.d. (-1.45 to -0.49) after correction for possible confounders. Shorter duration of symptoms and younger age were also associated with lower Z-scores at diagnosis, while etiology of CS, urinary cortisol excretion and gonadal status were not associated with Z-scores at diagnosis. Z-scores improved up to 20 years after treatment. Fifteen years after treatment, men showed larger improvements of Z-scores than women; +2.56 (1.82-3.30) increase in LS Z-score vs +1.48 (0.96-2.00) respectively. Fracture incidence was highest during the 2 years before diagnosis and decreased after treatment. CONCLUSION: Male sex, younger age and shorter duration of symptoms are associated with lower BMD at diagnosis of CS. BMD continues to improve up to 20 years after treatment of CS. Fracture rate decreases after treatment of CS.

Persistent centripetal fat distribution and metabolic abnormalities in patients in long-term remission of Cushing's syndrome.

OBJECTIVE: Centripetal obesity is associated with systemic low-grade inflammation and an increased cardiovascular risk. Patients in long-term remission of Cushing's syndrome (CS) report persisting abdominal fat accumulation. However, this has previously not been adequately objectified. Therefore, we investigated the adipose tissue distribution and adipocytokine profiles of patients in long-term remission of CS. DESIGN: Cross-sectional case-control study in a tertiary referral centre. PATIENTS: Fifty-eight patients, in remission of CS for at least 5 years, were compared to 58 age-, gender- and BMI-matched healthy control subjects. MEASUREMENTS: Measures of body composition (assessed with clinical evaluation and dual-energy X-ray absorptiometry (DEXA) scanning) and serum adipocytokine profiles. RESULTS: Compared to the matched control subjects, patients in long-term remission of CS had a greater waist circumference (P < 0·01), a smaller thigh circumference (P < 0·01), a higher waist-to-hip ratio (P < 0·01) and a higher hip-to-thigh ratio (P < 0·01). As measured with DEXA scanning, patients had a higher percentage of truncal fat mass (P = 0·01), and the truncal fat mass to leg fat mass ratio was greater (P < 0·01). Patients had lower adiponectin levels (P < 0·01), higher leptin levels (P < 0·01) and higher resistin levels (P = 0·04) than control subjects. CONCLUSION: Even after long-term remission, patients who suffered from CS in the past continue to have a centripetal adipose tissue distribution and an adverse adipokine profile. This is independent of aetiology of the CS, treatment strategies, hormonal deficiencies and comorbidity, and probably contributes to the persistent increased cardiovascular risk.

Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology.

CONTEXT: Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy. OBJECTIVE: The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS. DESIGN: We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years. PATIENTS: We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease. RESULTS: The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses. CONCLUSIONS: Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Blood pressure in pediatric patients with Cushing syndrome.

CONTEXT: Hypertension (HTN) has been reported in up to 60% of children with Cushing syndrome (CS), but its course, side effects, and potential differences among various causes of CS have not been adequately studied. OBJECTIVE: The objective of the study was to measure blood pressure in pediatric patients with CS before and after transphenoidal surgery or adrenalectomy and identify side effects and rates of residual HTN. DESIGN: Data from 86 children with corticotropinomas [Cushing disease (CD)] and 27 children with ACTH-independent CS (AICS) were analyzed. RESULTS: Patients with CD and AICS had significant HTN before surgery; more patients with AICS had systolic HTN (SHTN) than with CD (74 vs. 44%, P = 0.0077), but the rate of diastolic HTN (DHTN) was similar. Both groups experienced significant decreases in SHTN immediately after transphenoidal surgery and adrenalectomy. One year postoperatively, both SHTN and DHTN were lower than the preoperative values in all patients, but as many as 16 and 4% of the patients with CD and 21 and 5% of the patients with AICS still had SHTN and DHTN, respectively. Higher blood pressure preoperatively correlated with cortisol levels. Two patients suffered serious side effects: one with multiple infarcts and another with hypertensive encephalopathy. CONCLUSIONS: Children with CS are at risk for residual HTN despite a significant improvement after surgical cure. HTN appears to correlate with the degree of hypercortisolemia. Serious HTN-related side effects, although rare, may occur during the perioperative period.

Cushing's syndrome from the patient's perspective.

Forty-one patients with Cushing's syndrome described the physical, mental, and emotional effects of the disease, and the effects that the disease has on their families and performance at work or school. The majority of patients reported that Cushing's syndrome greatly affected everyday life. Areas in which physicians and nurses can provide critical assistance and support are described.

Síndrome de Cushing

El síndrome de Cushing es una constelación de signosy síntomas que se deben a un exceso de cortisol. El síndrome puede ser endógeno si la fuente del cortisol es la glándula suprarrenal o exógeno si se produce por la administración de glucocorticoides. El síndrome de Cushing endógeno puede ser Corticotropina plasmática dependiente o no dependiente. El corticotropina dependiente generalmente se debe a un exceso en la producción de la hormona por un adenoma hipofisiario o por tumores extrahipofisiarios (carcinoide y otros). La superproducción de corticotropina por la hipófisis puede deberse a aumento de la producciòn de hormona liberadora de corticotropina porel hipotálamo o por tumores extrahipotalámicos. El síndrome de Cushing no dependiente de corticotropina es producido por tumores benignos o malignos de la glándula suprarrenal. El diagnóstico de síndrome de Cushing se sospecha clínicamente y se confirma al demostrar falla de supresión de cortisol en respues a la administración de dexametasona o un aumento de la excreción urinaria de cortisol. La estimulación de hormona liberadora de corticotropina, la medición de corticotropina en el seno petroso, la tomografía computarizada y la resonancia magnética permiten identificar los diferentes tipos del síndrome de Cushing es la extirpación quirúrgica de un adenoma hipofisiario, un tumor suprarrenal o un tumor no hipofisiario secretor de corticotropina. También se dispone de terapia radiante de la hipófisis y de inhibidores del cortisol

Rehabilitación dental con implantes oseointegrados en pacientes con sindrome de Cushing, artritis reumatoidea y osteoporosis asociada / Dental rehabilitation with osseointegrated implants in patient with Cushing's syndrome, rheumatoid arthritis and related osteoporosis

Siempre que se diagnostica sindrome de Cushing o artritis reumatoide en un paciente, la inclinación más generalizada es contraindicar cualquier tratamiento en el que se involucren estructuras óseas por la presencia de osteoporosis asociada. El presente artículo es un caso clínico en el cual se comprueba lo relativo de este criterio, ya que a pesar de los antecedentes, la oseointegración de los implantes fue total