Early morning cortisol levels as predictors of short-term and long-term adrenal function after endonasal transsphenoidal surgery for pituitary adenomas and Rathke's cleft cysts.

OBJECTIVE: Patients undergoing pituitary adenoma or Rathke cleft cyst (RCC) removal are often administered perioperative glucocorticoids regardless of lesion size and preoperative adrenocorticotropic hormone/cortisol levels. To minimize unnecessary glucocorticoid therapy, we describe a protocol in which patients with normal preoperative serum cortisol and adrenocorticotropic hormone levels are given glucocorticoids only if postoperative day 1 or 2 (POD1 or POD2) cortisol levels decrease below normal. METHODS: A total of 207 consecutive patients undergoing endonasal surgery for an adenoma or RCC were considered for study. Of these, 68 patients with preoperative adrenal insufficiency or Cushing disease were excluded. Glucocorticoids were withheld unless POD1 or POD2 morning cortisol values were below normal (≤4 µg/dL). Subsequent adrenal status was assessed through follow-up biochemical and clinical evaluations. RESULTS: The 139 patients included 119 with macroadenomas, 14 microadenomas, and 6 RCCs (follow-up, 3-41 months; median, 10 months). Nine patients (6.5%), all with macroadenomas (mean diameter, 26 ± 10 mm) had low POD1 or POD2 cortisol values and received glucocorticoids; of these, five patients were weaned off within 3-28 weeks of surgery. Overall, 12 of 139 patients (8.6%) were treated for early (n = 9) or delayed (n = 3) adrenal insufficiency but only 5 patients (3.6%) remain on glucocorticoid replacement. No patient experienced an adrenal crisis. Using morning POD1 or POD2 cortisol values >4 µg/dL as a measure of adequate hypothalamic-pituitary-adrenal axis function, yields a sensitivity of 96%, a specificity of 57%, and a positive predictive value of 98%. CONCLUSIONS: In patients with normal preoperative cortisol levels undergoing endonasal removal of a pituitary adenoma or RCC, normal morning cortisol values on POD1 and POD2 reliably predicts adequate and safe adrenal function in 98% of patients. This simple protocol of withholding postoperative glucocorticoids avoids unnecessary steroid exposure and poses minimal risk to the well-informed closely monitored patient.

Gastric electrical stimulation with the TANTALUS System in obese type 2 diabetes patients: effect on weight and glycemic control.

BACKGROUND: The TANTALUS System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption. METHOD: Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 +/- 1 kg/m(2), hemoglobin A1c [HbA1c] 8.5 +/- 0.2%).Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period. RESULTS: Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 +/- 0.7% to 7.6 +/- 1%, p < .01. Weight was also significantly reduced from 107.7 +/- 21.1 to 102.4 +/- 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss (R(2) = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only). CONCLUSIONS: Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.

Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency.

GH secretion is decreased in obese subjects, whereas age-adjusted IGF-I concentrations are normal. This study was undertaken to rigorously delineate the extent of obesity [elevated body mass index (BMI)] associated with decreased somatotrope secretory function resulting in apparent adult GH deficiency. The peak GH response evoked by combined arginine (0.5 g/kg infused iv over 30 min) and GHRH (1 microg/kg iv bolus) was measured in 59 healthy male subjects with BMIs ranging from normal to obese. BMI correlated with the peak evoked GH response (Pearson r = -0.59; P < 0.01), and the percentage of subjects exhibiting an abnormal evoked GH response, i.e. less than 9 ng/ml, increased from 5% for those with a BMI less than 25 (normal), to 13% for those with a BMI of 25-26.9 (mildly overweight), to 33% for those with a BMI of 27-29.9 (moderately overweight), and to 64% for those with a BMI of 30 or more (obese). BMI is a major determinant of evoked adult GH response to provocative testing. The diagnosis of adult GH deficiency using the evoked GH response in patients with even mild BMI elevation does not accurately distinguish normal from deficient responses and may result in the erroneous classification of obese subjects as GH deficient and thus unnecessarily requiring GH replacement.

Somatostatin and somatostatin receptor physiology.

Since the discovery of somatostatin (SST) over three decades ago, its ubiquitous distribution and manifold functions are still being documented. SST is synthesized in the hypothalamus and transported to the anterior pituitary gland where it tonicaly inhibits GH and TSH secretion as well as being responsible for GH pulsatile release. Several internal feedback loops, sleep, exercise, and chemical agents control and influence SST release. SST also impacts the function of a wide variety of cells and organ systems throughout the body. Knowledge of the structures of the SSTs has resulted in recognition of the essential four core conserved residues responsible for their actions. The SSTs act through six separate SST cell surface receptors (SSTRs), members of the family of G protein-coupled receptors. Receptor ligand binding (SST/SSTR) results in cellular activities specific for each receptor, or receptor combinations, and their tissue/cell localization. Understanding the structure/function relationship of the SSTs and their receptors, including the internalization of SST/SSTR complexes, has facilitated the development of a variety of novel pharmacologic agents for the diagnosis and treatment of neuroendocrine tumors and unfolding new applications.