Quality of Life in Patients after Long-Term Biochemical Cure of Cushing’s Disease

Aken, Maarten O. van; Pereira, Alberto M.; Biermasz, Nienke R.; Thiel, Sjoerd W. van; Hoftijzer, Hendrieke C.; Smit, Johannes W. A.; Roelfsema, Ferdinand; Lamberts, Steven W. J.; Romijn, Johannes A.

doi:10.1210/jc.2004-1375

Cited by 229 publications

(220 citation statements)

References 39 publications

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“…However, only two studies have taken the possible role of GHD into account (6,7). In the present study, a significant improvement in QoL was observed after 3 years of GH treatment.…”

Section: Analysis Bsupporting

confidence: 45%

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Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

Höybye¹,

Ragnarsson²,

Jönsson³

et al. 2010

European Journal of Endocrinology

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Objective: Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. Design and methods: Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (nZ684, 74% women) and nonfunctioning pituitary adenoma (NFPA; nZ2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (nZ322) and NFPA (nZ748) matched for age and gender was performed. Results: The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (K6 CD group versus K5 NFPA group, P!0.01). Conclusion: In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.

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“…However, only two studies have taken the possible role of GHD into account (6,7). In the present study, a significant improvement in QoL was observed after 3 years of GH treatment.…”

Section: Analysis Bsupporting

confidence: 45%

“…QoL has previously been shown to be impaired in patients with controlled Cushing's disease (6,7,17,18). However, only two studies have taken the possible role of GHD into account (6,7).…”

Section: Analysis Bmentioning

confidence: 99%

Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

Höybye¹,

Ragnarsson²,

Jönsson³

et al. 2010

European Journal of Endocrinology

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“…These clinical improvements are very important to the patien- t's quality of life, once it represents the return to normal activities. Some studies suggest that even cured patients might continue to have a poor quality of life (43)(44)(45)(46). Possible explanations for this observation are the definitive systemic damage caused by CD or are associated to the poor biochemical criteria adopted.…”

Section: Clinical Featuresmentioning

confidence: 99%

Criteria of cure and remission in Cushing's disease: an update

Czepielewski

Rollin

Casagrande

et al. 2007

Arq Bras Endocrinol Metab

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We review the clinical and biochemical criteria used for evaluation of the transsphenoidal pituitary surgery results in the treatment of Cushing's disease (CD). Firstly, we discuss the pathophysiology of the hypothalamic-pituitary-adrenal axis in normal subjects and patients with CD. Considering the series published in the last 25 years, we observed a significant variation in the remission or cure criteria, including the choice of biochemical tests, timing, threshold values to define remission, and the interference of glucocorticoid replacement or previous treatment. In this context we emphasize serum cortisol levels obtained early (from hours to 12 days) in the postoperative period without any glucocorticoid replacement or treatment. Our experience demonstrates that: (i) early cortisol < 5 to 7 µg/dl, (ii) a period of glucocorticoid dependence > 6 mo, (iii) absence of response of cortisol/ACTH to CRH or DDAVP, (iv) return of dexamethasone suppression, and circadian rhythm of cortisol are appropriate indices of remission of CD. In patients with undetectable cortisol levels early after surgery, recurrence seems to be low. Finally, although certain biochemical patterns are more suggestive of remission or surgical failure, none has been proven to be completely accurate, with recurrence observed in approximately 10 to 15% of the patients in long-term follow-up. We recommended that patients with CD should have long-term monitoring of the CRH-ACTH-cortisol axis and associated co-morbidities, especially hypopituitarism, diabetes mellitus, hypertension, cardiovascular disturbances, and osteoporosis. RESUMOCritérios de Cura e Remissão na Doença de Cushing: Uma Atualização. Neste artigo, são revisados os principais critérios clínicos e hormonais utilizados para avaliação do tratamento cirúrgico da Doença de Cushing (DC). Inicialmente são comentados aspectos fisiopatológicos que orientam a avaliação hormonal e os principais fatores clínicos, laboratoriais, cirúrgicos e histológicos associados com melhores resultados, observados nas principais séries da literatura e em pacientes acompanhados prospectivamente pelos autores. Foram revisados, também, critérios adotados nas principais séries da literatura, nos últimos 25 anos, chamando-se atenção para as dosagens hormonais, o momento em que foram realizadas, a possibilidade de interferência de tratamentos prévios e da reposição glicocorticóide. À seguir, essas dosagens são discutidas salientando-se a importância do cortisol obtido seqüencialmente no pós-operatório e sem a interferência de reposição glicocorticóide. A experiência prospectiva dos autores, recentemente referendada na literatura, demonstra que valores de cortisol < 5 a 7 µg/dl associados com um período de dependência aos glicocorticóides > 6 meses, ausência de resposta do ACTH/cortisol ao DDAVP e/ou CRH, retorno da supressão à dexametasona e do ritmo circadiano, estão associados com remissão da DC. Em pacientes com cortisol indetectável após cirurgia transesfenoidal, a chance de recidiva parece ser menor d...

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“…4,17 However, many patients do not achieve a premorbid level of functioning and experience persistent impairment of QoL and cognitive function. 24,35 Brain morphologic changes, including cerebral atrophy and decreased hippocampal volume associated with cognitive decrement and depressive symptoms, have been reported in adults with active CS and are partially reversible after cure. 5,36,37 These data highlight the need for prospective research to investigate the long-term psychological and cognitive morbidities.…”

Section: Discussionmentioning

confidence: 99%

Cases of Psychiatric Morbidity in Pediatric Patients After Remission of Cushing Syndrome

Keil

Zametkin²,

Ryder

et al. 2016

Pediatrics

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Endogenous Cushing syndrome (CS) may have different effects in children than what has been described in adults. Previous studies of children and adolescents with CS have identified cognitive decline despite reversal of brain atrophy after remission of CS. Although the observations of parents of children and adolescents with CS support personality changes, significant psychopathology has not been described in the literature. We report 9 children who underwent successful surgery (transsphenoidal surgery [TSS] or resection of bronchial carcinoid) for treatment of CS and subsequently developed significant affective pathology. Affective symptoms included anger–rage outbursts, suicidal ideation, irritability, anxiety, and depression. One child, who committed suicide 60 months after TSS, had recently discontinued antidepressant medication. She had a history of anxiety during active CS and was treated with an anxiolytic. The 7 patients with onset of symptoms within 7 months of TSS were on glucocorticoid replacement, and 1-year follow-up evaluation showed recovery of hypothalamic–pituitary–adrenal axis and biochemical evidence of remission. The 2 patients who presented with onset of symptoms at 48 months or later underwent endocrine evaluation that showed biochemical evidence of remission and normal anterior pituitary hormone levels. This is the first report of affective symptoms and behavioral dysregulation, including suicidal ideation, in a subgroup of children and adolescents after remission of CS. Health care providers caring for children with CS who have been cured should continue to screen for mental illness, monitor for changes in behavior, and refer as appropriate to mental health professionals.

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Quality of Life in Patients after Long-Term Biochemical Cure of Cushing’s Disease

Cited by 229 publications

References 39 publications

Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

Criteria of cure and remission in Cushing's disease: an update

Cases of Psychiatric Morbidity in Pediatric Patients After Remission of Cushing Syndrome

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