Early Morning Cortisol Levels as a Predictor of Remission After Transsphenoidal Surgery for Cushing’s Disease

Esposito, Felice; Dusick, Joshua R.; Cohan, Pejman; Moftakhar, Parham; McArthur, David L.; Wang, Christina; Swerdloff, Ronald S.; Kelly, Daniel F.

doi:10.1210/jc.2005-1204

Cited by 171 publications

(143 citation statements)

References 41 publications

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“…In 2004, applying the above proposal in more than 100 patients with CD, we showed that serum cortisol less than 5 to 7 µg/dl defines cure with sensitivity and specificity of around of 100% (26). Our findings, similarly to those of Esposito et al (48), verify that cortisol levels less than 140 nmol/L in the first and second days after surgery were associated with CD resolution. Recently, Acebes et al (36) observed that cortisol levels more than 585 nmol/L 24 h post-surgery indicates disease persistence.…”

Section: Serum Cortisolsupporting

confidence: 80%

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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Section: Serum Cortisolsupporting

confidence: 80%

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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“…A variety of definitions of remission of Cushing's disease after initial microscopic TSS is used in the literature: symptoms of hypercortisolism remitted (25), a continuous need for corticosteroid replacement for O6 months after TSS (26), no need for additional treatment because of clinical remission of the disease (27), resolution of symptoms and signs of hypercortisolism (28) or of clinical features (16,19), clinical evidence of eucortisolemia (23), appearance of clinical signs of adrenal insufficiency (29), regression of the clinical signs (30), presence of clinical and laboratory signs of adrenal insufficiency (17,22), and reversal of the clinical stigmata (31). Clinical parameters were never used alone to define remission; clinical evaluation was always combined with serum cortisol, UFC, and/or LDDST biochemical tests ( Table 1).…”

Section: Remission Ratesmentioning

confidence: 99%

“…Although hypocortisolism after TSS has been shown to be a reliable prognostic factor for success of surgery (21,22,23), indicating remission and a lower risk of recurrence, there is currently no consensus on predictors of these outcomes. The broad range of remission and recurrence rates reported in the literature may be due to different remission and recurrence criteria used in the studies.…”

Section: Introductionmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

Petersenn¹,

Beckers²,

Ferone³

et al. 2015

European Journal of Endocrinology

123

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Objective: A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's diseaseincluding different remission and recurrence criteria, for which there is no consensus. Therefore, a comparative analysis of the best treatment options and patient management strategies is difficult. In this review, we investigated the clinical outcomes of initial TSS in patients with Cushing's disease based on definitions of and assessments for remission and recurrence. Methods: We systematically searched PubMed and identified 44 studies with clear definitions of remission and recurrence. When data were available, additional analyses by time of remission, tumor size, duration of follow-up, surgical experience, year of study publication and adverse events related to surgery were performed. Results: Data from a total of 6400 patients who received microscopic TSS were extracted and analyzed. A variety of definitions of remission and recurrence of Cushing's disease after initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%; median, 77.9%) and recurrence (0-47.4%; median, 11.5%). Better remission and recurrence outcomes were achieved for microadenomas vs macroadenomas; however, no correlations were found with other parameters, other than improved safety with longer surgical experience.

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“…A menor confirmação histológica de adenoma nesses pacientes com queda mais lenta dos níveis do cortisol no PO, sugerindo necrose "in situ", reforçaria essa teoria (57). Sugere-se, ainda, que pacientes com DC mais leve teriam menor inibição dos corticotrofos saudáveis, e a redução do cortisol PO poderia ser mais gradual (52,55). Além disso, Pereira e cols.…”

Section: Dosagem Do Cortisol Pós-operatóriounclassified

Avaliação do eixo hipotálamo-hipófise adrenal no diagnóstico e na remissão da doença de Cushing

Costenaro

Rodrigues

Rollin

et al. 2012

Arq Bras Endocrinol Metab

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A doença de Cushing (DC) permanece um desafio médico com muitas questões ainda não respondidas. O sucesso terapêutico dos pacientes com DC está ligado à correta investigação do diagnóstico síndrômico e etiológico, além da experiência e talento do neurocirurgião. A adenomectomia hipofisária transesfenoidal constitui-se no tratamento de escolha para a DC. A avaliação da remissão da doença no pós-operatório e da recorrência em longo prazo constitui um desafio ainda maior. Especial destaque deve ser dado para o cortisol sérico no pós-operatório como marcador de remissão. Adicionalmente, o uso de corticoide exógeno no pós-operatório apenas em vigência de insuficiência adrenal tem sido sugerido por alguns autores como requisito essencial para permitir a correta interpretação do cortisol sérico nesse cenário. Neste artigo, revisamos as formas de avaliação da atividade da DC e os marcadores de remissão e recidiva da DC após a realização da cirurgia transesfenoidal. Arq Bras Endocrinol Metab. 2012;56(3):159-67 Descritores Doença de Cushing; cortisol sérico; remissão; cirurgia hipofisária summArY Cushing's disease (CD) remains a medical challenge, with many questions still unanswered. Successful treatment of CD patients is closely related to correct approach to syndromic and etiological diagnosis, besides the experience and talent of the neurosurgeon. Pituitary transsphenoidal adenomectomy is the treatment of choice for DC. Assessment of remission after surgery and recurrence in the long term is an even greater challenge. In this regard, special attention should be paid to the role of postoperative serum cortisol as a marker of CD remission. Additionally, the postoperative use of exogenous glucocorticoids only in cases of adrenal insufficiency has been suggested by some authors as an essential practice to enable the use of serum cortisol in this scenario. In this article, we review the forms of evaluation of DC activity, and markers of remission and relapse of CD after transsphenoidal surgery. iNTroDuÇÃo A doença de Cushing (DC) apresenta incidência estimada de 0,7 a 3 casos/milhão/ano (1-3), com prevalência de 39,1 casos por milhão de habitantes (4). Acomete adultos jovens com pico de incidência entre a terceira e quarta décadas de vida (5) e predominantemente mulheres.Para o sucesso no manejo desses pacientes, é necessário que a investigação diagnóstica obedeça a uma sequência lógica: inicialmente o diagnóstico sindrômico e posteriormente o diagnóstico etiológico.O risco relativo de morbidade e mortalidade na DC é de 2 a 5 vezes acima da população em geral (2,3), podendo equiparar-se ao risco da população em geral durante a remissão da doença (2).

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Early Morning Cortisol Levels as a Predictor of Remission After Transsphenoidal Surgery for Cushing’s Disease

Cited by 171 publications

References 41 publications

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

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

THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

Avaliação do eixo hipotálamo-hipófise adrenal no diagnóstico e na remissão da doença de Cushing

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