Prospective evaluation of transsphenoidal pituitary surgery in 108 patients with Cushing's disease

Abstract

Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4% and 28.6% (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9% vs. 73.9%; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4% (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative. O tratamento de escolha para a doença de Cushing (DC) ainda é a cirurgia transesfenoidal (CTE) para ressecção do adenoma hipofisário produtor de ACTH. Porém, a indicação de uma segunda CTE representa uma questão controversa, tanto nos pacientes não curados após a primeira cirurgia quanto nos casos de recidiva. Neste trabalho, relatamos os resultados da CTE em 108 pacientes com DC (totalizando 117 cirurgias). O tempo médio de seguimento foi de 6 anos. Critérios de cura: ocorrên-cia de insuficiência adrenal (clínica ou laboratorial), período de dependência ao glicocorticóide, supressão do cortisol sérico pós-1 mg de dexametasona overnight e remissão clínica do hipercortisolismo. Foram avaliados 103 pacientes com DC submetidos à primeira CTE. Quatorze pacientes foram submetidos a uma segunda CTE (5 já tinham sido operados em outros centros; a primeira cirurgia não fora curativa em 5; 4 pacientes com recidiva da DC). Índices de cura: 85,4% e 28,6% (p < 0,001) após a primeira e segunda CTE, respectivamente. Nos microadenomas, remissão maior que nos macroadenomas (94,9% vs. 73,9%; p = 0,006). Nos pacientes com imagem hipofisária negativa, cura foi de 71,4% (p = 0,003; vs. micro). Complicações pós-operatórias: diabetes insipidus transitório e definitivo, hipopituitarismo, acidente vascular cerebral e um óbito. Apenas a ocorrência de hipopituitarismo foi mais freqüente após a segun...

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

“…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).…”

“…Higher remission rates are generally reported in patients with discrete, easily operated tumors, with improved outcomes achieved with microadenomas vs macroadenomas (6,13,15,16,17,18) and with adenomas identified at surgery or by radiology or histopathology vs no adenomas identified (19,20). Other factors suggested to increase the success of initial TSS include extensive surgical experience and younger patient age (!25 years) (6).…”

Budget impact of pasireotide for the treatment of Cushing’s disease, a rare endocrine disorder associated with considerable comorbidities

“…A literature review was conducted and eight studies identified as the most appropriate clinical studies for inclusion in the total budget impact model 37,38,[40][41][42][43][44][45] . Fourteen unique AEs were identified, of which hypopituitarism was associated with TSS, RS, and RT.…”

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

“…A taxa de remissão após CTE observada em bons centros varia entre 53%-96% (9,(25)(26)(27)(28), chegando a 96% nos microadenomas (26) e tão baixas quanto 53% nos macroadenomas (27). Além disso, as taxas de cura na segunda CTE são inferiores às da primeira CTE e variam em torno de 28%-67% (9,28-31), já as chances de hipopituitarismo aumentam nas reintervenções, alcançando taxas de 46%-100% após a segunda CTE (28)(29)(30)(31).…”

“…A recidiva da DC ocorre em 5% a 64% das vezes em até cinco anos após a CTE (9,28,30,33). Essas discrepâncias entre os diferentes centros devem--se aos diferentes critérios de remissão adotados, à quantidade de reintervenções cirúrgicas e à duração do seguimento dos pacientes.…”