Transsphenoidal pituitary surgery is the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure, there is no agreement regarding the definition of successful treatment. We prospectively studied postoperative serum cortisol dynamics in 41 patients with CD (including a total of 45 surgeries). The mean postoperative follow-up period was 4.8 yr. Remission was defined as clinical and laboratory signs of adrenal insufficiency, glucocorticoid dependence, and serum cortisol suppression on overnight oral 1-mg dexamethasone suppression test. Serum cortisol was measured preoperatively and postoperatively at 6, 12, and 24 h (28 surgeries) and at 10-12 d (45 surgeries). No statistical difference was detected in mean preoperative and 6-h postoperative cortisol levels between surgically induced remission patients [22.1 +/- 7.73 microg/dl (610 +/- 213.3 nmol/liter) and 25.2 +/- 19 microg/dl (695.2 +/- 524.4 nmol/liter)] and surgical failure patients [23.6 +/- 6.95 micro g/dl (651.4 +/- 161.8 nmol/liter) and 37.5 +/- 18.1 microg/dl (1035 +/- 499.6 nmol/liter); P = 0.50 and P = 0.17]. At 12 and 24 h after surgery, the difference was significant (P = 0.009 and P < 0.0001). Mean cortisol levels were 12.44 +/- 13.3 microg/dl (343.3 +/- 367.1 nmol/liter) and 4.72 +/- 6.72 microg/dl (130.3 +/- 185.5 nmol/liter) in the remission group and 26.3 +/- 7.06 microg/dl (725.9 +/- 194.8 nmol/liter) and 23.5 +/- 6.86 microg/dl (648.6 +/- 189.3 nmol/liter) in the failure group (P = 0.009; P < 0.0001). At 10-12 d after the procedure, the difference was also significant (P < 0.0001): cortisol levels were 2.52 +/- 3.32 microg/dl (69.5 +/- 91.6 nmol/liter) in the remission group and 24.9 +/- 13.3 microg/dl (687.2 +/- 367.1 nmol/liter) in the failure group. In conclusion, in the immediate postoperative period of transsphenoidal surgery, remission of CD is not necessarily defined by undetectable serum cortisol. During the first 10-12 d after surgery, cortisol nadir correctly classified the remission [cortisol, 7.0 microg/dl (193.2 nmol/liter) or less] and the failure groups [cortisol, 8.0 microg/dl (220.8 nmol/liter) or more]. Glucocorticoid should be administered only after laboratory and/or clinical evidence of adrenal insufficiency.

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...

At hospital discharge, the s-cortisol nadir within 48 h after TSS was already able to predict surgical remission for some patients, and the s-cortisol nadir within 10-12 days of TSS was able to predict cohort-wide surgical remission.

The proposed system of analysis and reporting could prove clinically relevant in the decision whether to repeat targeted biopsies.