Utility of Adrenocorticotropic Hormone in Assessing the Response to Transsphenoidal Surgery for Cushing's Disease.

OBJECTIVES: To compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing's disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia. METHODS: Following TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage. RESULTS: A total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to <30 pg/mL in 86% and <20 pg/mL in 82% of subjects who subsequently achieved hypocortisolemia. Plasma ACTH declined to <30 pg/mL by a mean of 10 hours and to <20 pg/mL by 13 hours prior to hypocortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels <3 µg/dL and plasma ACTH <20 pg/mL. CONCLUSION: Following TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of <20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission.

The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing's disease.

Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing's disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol <2 mcg/dl or a serum cortisol <5 mcg/dl with the onset of symptoms of adrenal insufficiency within 72 h. We studied 12 subjects, all female, mean age 44.6 years (range 25-55), including 13 surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1-19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.