We reviewed our experience with 21 patients who had Cushing's disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical features of ACTH-dependent hypercortisolism. Their mean maximal tumor diameter was 1.6 +/- 0.1 cm, and the range was 1.0-2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sella, and nine had suprasellar extension. The observed remission rate was significantly lower in macroadenoma patients than in microadenoma patients (67% vs. 91%; chi 2 = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6-475; P < 0.008) and presence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95% confidence interval, 1.4-124; P < 0.02) emerged as the only predictors of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma patients (36% vs. 12%; chi 2 = 4.2; P < 0.05). Macroadenoma patients tended to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not identify any predictors of disease recurrence in macroadenoma patients. Eight macroadenoma patients underwent a total of nine repeat surgical procedures, but none of these resulted in clinical remissions. Only four of seven (57%) patients followed for a sufficient period of time achieved normal urinary free cortisol levels after conventional radiotherapy. Three (75%) of these four patients had re-recurrent hypercortisolism after brief periods of eucortisolism. Pharmacological agents and adrenalectomy were effective in the management of hypercortisolism in patients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional treatments than are ACTH-secreting microadenomas.

ObjectiveTo compare the first 20 patients who underwent minimally invasive radioguided parathyroidectomies (MIRPs) performed at the authors' institution with 20 similar patients who underwent a more conventional surgical approach for primary hyperparathyroidism. Summary Background DataThe technique of parathyroidectomy has traditionally involved a bilateral exploration of the neck with the intent of visualizing four parathyroid glands and resecting enlarged parathyroid glands. Parathyroid scanning using radioisotopes has evolved and now can localize adenomas in 80% to 90% of patients. MIRP combines parathyroid scanning with a hand-held intraoperative detector that guides the surgeon to the adenoma. MethodsForty patients with documented primary hyperparathyroidism who underwent surgery by a single surgeon between January 1998 and May 1999 were included in this study. Twenty of these patients underwent MIRP. The technique involved injecting 20 mCi technetium-99m sestamibi 2 hours before surgery and performing a parathyroid scan. If the scan was considered positive for a single adenoma, patients were taken to the operating room and given the choice of either general anesthesia or intravenous sedation with local anesthesia. Using an incision of 4 cm or less, the dissection down to the adenoma was guided by the Navigator miniature hand-held probe. An additional 20 patients who underwent more conventional bilateral or unilateral neck exploration were chosen to match the MIRP patient population. Both groups included four patients undergoing repeat surgery for persistent or recurrent primary hyperparathyroidism and one patient with multiple endocrine neoplasia type 1 syndrome. Patient demographics, preoperative calcium and parathyroid hormone levels, operative time, total time in the operating room, time in the recovery room, complications, hospital charges for the operating room, and total hospital charges were analyzed. ResultsThere were no differences in patient demographics, presenting symptoms, or preoperative calcium level between patients undergoing the standard procedure versus MIRP. Operative time, total time in the operating room, operative charges, and total hospital charges were significantly reduced in the MIRP group. All 40 patients were cured of primary hyperparathyroidism. There were no recurrent laryngeal nerve injures in either group. The mean length of stay in the standard group was 1.35 days; in the MIRP group, 65% of patients were discharged within 5 hours after surgery. ConclusionsThe MIRP technique resulted in excellent cure rates for primary hyperparathyroidism while simultaneously decreasing operative time and hospital stays. These resulted in significant cost reductions without compromising patient safety. The technique may significantly change the management of primary hyperparathyroidism.

Currently, the most popular test for adrenal insufficiency is the conventional rapid ACTH stimulation test (250 microg ACTH). This method is quick and safe, but incorporates a dose of ACTH that is supraphysiological and capable of transiently stimulating the adrenal cortex in many patients with documented central adrenal insufficiency. In recent years, several investigators have published substantial evidence for a more sensitive ACTH stimulation test using a lower dose of ACTH (1 microg). Further analysis of these data, including the calculation of likelihood ratios, demonstrates that the 1-microg test performs significantly better than the 250-microg test compared to the gold standard, insulin tolerance test. We suggest that the 1-microg ACTH stimulation test replace the conventional 250-microg test when evaluating for central adrenal insufficiency. A cortisol level below 500 nmol/L after 30 min signifies impaired adrenocortical reserve. An insulin tolerance test should be performed if this low dose test results in a borderline value and the diagnosis is questioned. The 1-microg test should not be used if recent pituitary injury is suspected. Pharmaceutical companies should be encouraged to provide synthetic ACTH in 1-microg vials.

In the largest series to date, SCAs exhibited comparable size, but increased cavernous sinus invasion and progression/recurrence vs HNAs. SCAs exhibit deficient pro-opiomelanocortin to ACTH conversion. Close follow-up is warranted for SCAs.