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Inhaled glucocorticosteroids (ICS) are commonly prescribed for chronic obstructive pulmonary disease. No adverse effect on bone mineral density (BMD) has been proven. In a randomized double-blind, placebo-controlled trial at seven centers in North America, we recruited 412 current smokers or recent quitters with mild to moderate chronic obstructive pulmonary disease. They used inhaled triamcinolone acetonide, 600 mcg, or placebo, twice daily. We measured femoral neck and lumbar spine BMD at baseline and after 1 and 3 years, and serum osteocalcin at baseline, 3 months, 1 year, and 3 years. After 3 years, BMD at the femoral neck decreased 1.78% more with ICS than with placebo (p < 0.001). More participants in the ICS group experienced 6% or more loss of femoral neck BMD (p = 0.002). Lumbar spine BMD increased in the placebo group by 0.98% but decreased by 0.35% in the ICS group (a difference of 1.33%, p = 0.007). Changes in osteocalcin did not correlate with changes in BMD. Fractures, lost height, or osteoporosis diagnoses were not increased among ICS users compared with placebo users. In summary, the use of inhaled triamcinolone acetonide was associated with loss of BMD at the femoral neck and lumbar spine after 3 years of treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess whether the type of surgical approach to the sella (sublabial transseptal vs transnasal) affects surgical outcome among patients with Cushing disease. PARTICIPANTS AND METHODS: Both procedures were performed at our institution from January 1, 1995, through January 31, 2003. From a total of 106 patients with Cushing disease who had had surgery, we identified 42 adults undergoing an initial surgery, with microadenoma (<1 cm) determined by magnetic resonance imaging and a minimal follow-up of 3 months. RESULTS: We identified 21 patients (4 male, 17 female) for sublabial transseptal transsphenoidal microsurgery. Mean+/-SD age was 45.0+/-12.9 years (range, 27.0-69.0 years); median duration of symptoms was 2.5 years (range, 1.5-7.5 years). Median follow-up was 1.0 year (range, 0.3-11.0 years). We identified another 21 patients (5 male, 16 female) for endoscopic transsphenoidal microsurgery whose mean+/-SD age was 43.8+/-14.1 years (range, 19.0-70.0 years); median duration of symptoms was 2.4 years (range, 0.2-6.0 years). Median follow-up was 2.5 years (range, 0.3-8.7 years). Complications (cerebrospinal fluid leak and transient diabetes insipidus) and cure (86% initial cure; 76% relapse-included cure) were equivalent between the 2 procedures. However, the endoscopic approach was associated with shorter anesthesia time, less blood loss, and shorter hospital stays. CONCLUSION: The endoscopic transnasal surgical approach led to shorter total anesthesia time, less blood loss, and shorter hospital stay when compared with the sublabial transseptal approach. However, we found no difference between the 2 surgical procedures with respect to cure or complications, suggesting that outcome is more closely related to the experience of the operating team. [ABSTRACT FROM AUTHOR]

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder. Research has shown that even with the growing incidence of children diagnosed as having ADHD, physicians may find providing optimal care to these patients challenging. Our objective was to contrast existing clinical management of ADHD in a family medicine setting with published American Academy of Pediatrics guidelines and review the literature pertinent to differences., Methods: A report was generated for all visits with "ADHD" or "ADD" (attention-deficit disorder) as a current or past medical problem that had been addressed at the family medicine clinic from July 2012 to June 2014. A total of 60 pediatric patients were identified. A retrospective chart review of clinical practice and management patterns for these patients was completed using a standardized data collection form based on the 2011 ADHD treatment guidelines set by the American Academy of Pediatrics., Results: Fifty-seven (95%) patients had documentation of at least one core symptom of ADHD, and 27 (45%) patients had documentation of these symptoms in more than one setting (clinic/school/home). Only 30 (50%) patients were assessed at the initial ADHD visit for coexisting conditions. Coexisting conditions were found to be present in 20 (33.3%) patients. Of these 20 patients, coexisting conditions were not addressed during the visit in 12 (60%) patients before drug therapy for ADHD was initially prescribed. Behavioral therapy was initiated as first-line monotherapy in one of the nine preschool-age patients (4-5 years old). Fifty-two (86.7%) patients received a preferred initial medication as identified by guidelines, and 41 (78.8%) of those patients received an appropriate initial dose. Fifty-one (85%) patients were assessed for improvement of symptoms, and 39 (65%) were assessed for adverse events. Of 62 documented medication adjustments, 54 (87.1%) adjustments coincided with current practice guidelines. Sixteen (26.7%) patients were referred to mental health specialists., Conclusions: This retrospective review identified areas of strength and weakness for attending physicians and medical residents in the diagnosis, evaluation, and treatment of children with ADHD. A significant need was identified for more physician-focused education on the evaluation of coexisting conditions and long-term management associated with ADHD therapy. Further training in the initiation of behavioral therapy as a first-line treatment above drug therapy and proper medication selection in children aged 4 to 5 years also are recommended.

Mineral and bone disorder is common in individuals with kidney transplant as a sequelae of chronic kidney disease. Rapid bone density loss that occurs during the first year after transplant along with pre-existing bone disorder, places these patients at risk of bone fractures at three times higher than the general population. This article examines the efficacy of current evidence-based clinical interventions in reducing the incidence of bone fractures among recipients of kidney transplant.

Purpose: To assess safety, technical success, local control, and survival associated with percutaneous image-guided adrenal ablation., Materials and Methods: Adult patients with adrenal metastases who underwent percutaneous image-guided adrenal ablation during the years 2003-2012 were identified. There were 32 patients with 37 adrenal tumors identified. Technical success, safety, local control, and survival were analyzed according to standard criteria., Results: In 32 patients (25 men and 7 women; mean age, 66 y; age range, 44-88 y) with 37 adrenal tumors, 35 ablation procedures were performed. One patient with an 8.2-cm tumor underwent planned cryoablation debulking fully anticipating untreated margins owing to close proximity of the pancreas (ie, the intent was to diminish tumor burden rather than a curative intervention). Of the 36 patients treated with curative intent, technical success was achieved in 35 (97%) tumors. Follow-up imaging was performed on 34 of 37 tumors (excluding patients with intentional debulking [n = 1], technical failure [n = 1], and absence of follow-up [n = 1]). Local recurrence developed in 3 (8.8%) of 34 tumors. Local tumor control was achieved in 31 lesions at a mean of 22.7 months of follow-up. Recurrence-free survival and overall survival at 36 months were 88% and 52%, respectively, with a median survival of 34.5 months. A Common Terminology Criteria for Adverse Events version 4 grade 3 or 4 complication was observed in three (8.6%) ablation procedures., Conclusions: Image-guided ablation is safe and effective for local control of metastatic adrenal tumors and provides a minimally invasive alternative to surgical resection in appropriately selected patients., (Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess safety, technical success, complications, and hemodynamic changes associated with the adrenal cryoablation procedure., Materials and Methods: This retrospective review was approved by the institutional review board, with waiver of informed consent, and was compliant with the Health Insurance Portability and Accountability Act. Adult patients with adrenal metastasis who were treated with adrenal cryoablation between May 2005 and October 2009 were eligible for this review. Twelve patients (undergoing 13 procedures) with single adrenal tumors were included in the analysis. For statistical analysis, hemodynamic data were averaged for the patient undergoing the procedure twice. Technical success, safety, and local control were analyzed according to standard criteria. Hemodynamic changes during the procedure were analyzed and compared with data from an unmatched cohort of patients who underwent kidney (not in the upper pole) cryoablation (Wilcoxon rank sum test). A further subanalysis of hemodynamic changes was performed on the basis of whether preprocedural α- or β-adrenergic blockade was used., Results: With adrenal cryoablation, local control was achieved following treatment in 11 (92%; 95% confidence interval: 65.1%, 99.6%) of 12 tumors. One patient with known adrenal insufficiency underwent conservative ablation and developed ipsilateral adrenal recurrence, which was retreated. Five patients developed hypertensive crisis during the final, active thaw phase of the cryoablation procedure, and one patient developed hypertensive crisis in the immediate postablation period. Patients undergoing adrenal cryoablation experienced a significant increase in systolic blood pressure (P = .005), pulse pressure (P = .02), and mean arterial pressure (P = .01) when compared with the cohort of kidney cryoablation patients. Adrenal cryoablation patients who were not premedicated with an α-blocker (n = 5) had a higher level of systolic blood pressure increase during the cryoablation procedure when compared with their counterparts who were premedicated (n = 7) (P = .034)., Conclusion: Adrenal cryoablation is technically feasible with a high rate of local control. Patients premedicated with the α-blocker phenoxybenzamine appear to have a reduced risk of hypertensive crisis., (© RSNA, 2010)

Background: Management of patients with bilateral adrenal masses and corticotropin (ACTH)-independent Cushing syndrome (CS) or subclinical CS is problematic. We report our experience with adrenal venous sampling (AVS) in the evaluation of 10 patients with bilateral masses who had ACTH-independent CS or subclinical CS., Patients and Methods: Ten patients (9 women, 1 man, mean age 56.4 years) with bilateral adrenal masses and ACTH-independent CS (n=3) or subclinical CS (n=7) underwent AVS. Autonomous cortisol secretion was documented in all cases with suppressed serum ACTH concentrations and lack of cortisol suppression with dexamethasone administration. Adrenal venous sampling was performed on the second day of dexamethasone administration. Cortisol and epinephrine levels were measured from each adrenal vein (AV) and from a peripheral vein (PV)., Results: Mean (+/-SD) maximal diameter of the adrenal masses on computed tomography was 3.3+/-1.3 cm (range: 1.2-6.0 cm). Successful catheterization was confirmed with AV:PV epinephrine gradients. A cortisol AV:PV gradient>6.5 was consistent with a cortisol-secreting adenoma in 11 adrenal glands; 5 patients had clinically important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol-secreting adenomas, and 2 had ACTH-independent macronodular adrenal hyperplasia. Adrenal venous sampling-guided adrenalectomy was completed in all 10 patients-2 patients had total bilateral adrenalectomy and 2 others had subtotal bilateral adrenalectomy. During a mean follow-up of 36.1 months (range: 0.7-123 months), CS or clinically important cortisol secretory autonomy did not recur., Conclusions: Adrenal venous sampling contributed to the localization of autonomous hypercortisolism in the setting of ACTH-independent CS or subclinical CS in patients with bilateral adrenal masses.

Background: Cushing's syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10-year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management., Materials and Methods: From 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five-year survival rates were calculated where applicable by the Kaplan-Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC)., Results: Two-hundred thirty-one patients (78%) had ACTH-dependent CS and 67 patients (22%) had ACTH-independent CS. One-hundred ninety-six patients (66%) had pituitary-dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty-four patients (18%) had cortisol-secreting adenomas, 10 patients (3%) had cortisol-producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five-year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively., Conclusions: Surgery for CS is highly successful for pituitary-dependent CS and most ACTH-independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross-sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today's management of the complex patient with CS.

Context: Ghrelin is a 28-amino-acid Ser(3)-octanoylated peptide, and CRH is a 41-amino-acid peptide, both of which stimulate ACTH secretion. In principle, actions of these agonists could be subject to inhibitory modulation by hypothalamic somatostatin (SS)., Objective: Our objective was to test the hypothesis that endogenous SS restrains ghrelin and CRH-stimulated ACTH secretion, thereby linking all three, ghrelin, CRH, and SS, with ACTH secretion., Design and Setting: We conducted a randomized, double-blind, placebo-controlled, crossover interventional study at an academic medical center., Participants: Ten healthy postmenopausal women participated in the study., Interventions: Interventions included iv injection of saline, ghrelin, human CRH, or both after an infusion of saline vs. l-arginine to putatively inhibit SS outflow (eight visits per subject)., Outcome Measures: ACTH concentrations quantified by repetitive blood sampling and immunochemiluminometry., Results: Infusion of ghrelin induced peak ACTH concentrations [median (range)] of 21 (17-28) compared with 16 (11-20) ng/liter after saline (P = 0.037). CRH and l-arginine infusion evoked ACTH peaks of 23 (14-48) and 31 (21-286) ng/liter, respectively (P = 0.037 and P = 0.005 vs. saline). l-Arginine enhanced stimulation by ghrelin by 1.43-fold (P = 0.028) and that by CRH by 1.91-fold (P = 0.005). Triple stimulation with ghrelin, CRH, and l-arginine potentiated the effect of combined ghrelin/CRH by 1.45-fold (P = 0.028). Downstream cortisol responses mimicked those of ACTH but were time delayed., Conclusions: The present outcomes indicate that the peptide ensemble comprising ghrelin, CRH, and SS (inferred by l-arginine infusion) can regulate ACTH and cortisol secretion in healthy adults.

Context: The definitive diagnosis of Cushing's syndrome (CS) in the setting of mild disease, as well as exclusion of CS in the setting of conditions that might mimic this clinical entity (pseudo-Cushing's syndrome), continues to present a significant challenge to the clinician., Objective: The aim of the study was to review characteristics of the combined dexamethasone-suppressed CRH stimulation test in patients evaluated at an academic center for the possibility of mild CS., Design, Patients, and Methods: We conducted a retrospective review of 66 patients. A total of 51 patients underwent final statistical analysis: 21 (41%) had Cushing's disease, and 30 were considered to have pseudo-CS based on the clinical scenario, comorbidities, and follow-up. Sensitivity, specificity, and diagnostic accuracy of cortisol and ACTH levels for the diagnosis of Cushing's disease were calculated at 1 min before, and 15, 30, 45, and 60 min after CRH administration. Diagnostic cutoffs for each parameter were determined by minimizing the absolute difference between sensitivity and specificity. Diagnostic accuracy was characterized by the area under the receiver operating characteristic curve, determined using the trapezoid rule., Results: The highest diagnostic accuracy was provided by the serum ACTH level at 15 min post-CRH, in which the area under the receiver operating characteristic curve was 99.7%, and a cutoff of more than 27 pg/ml (>5.9 pmol/liter) provided a sensitivity of 95% and specificity of 97% for the diagnosis of CS. A 15-min post-CRH cortisol greater than 2.5 mug/dl (70 nmol/liter) provided a sensitivity and specificity of 90 and 90%, respectively., Conclusions: Our results differ from previous studies because our data suggest that when using the combined dexamethasone-suppressed CRH stimulation test, a 15-min post-CRH ACTH value greater than 27 pg/ml (5.9 pmol/liter) had the highest diagnostic accuracy for the detection of CS. However, the sensitivity and specificity for this test were not statistically different from the sensitivity and specificity of other tests, such as those measuring post-CRH stimulated ACTH levels or post-CRH cortisol levels at other time points. Therefore, clinicians should be cautious about interpretation of suppression and stimulation tests in the diverse population of patients with hypercortisolism.

This discussion reviews the concept and history of ergogenic aides, the penetration of use in society, some benefit/risk information, drug sources in our society, detection and regulation of these agents, and provides a look to the future. It also examines the role of the clinician/endocrinologist for these patients and uses some cases as examples of drug use among adolescents/teens.

Background: Decreased libido is one of several changes in sexual function that are often experienced by female cancer patients. Transdermal testosterone therapy has been associated with increased libido among estrogen-replete women who report low libido., Methods: In a phase III randomized, placebo-controlled crossover clinical trial, we evaluated whether transdermal testosterone would increase sexual desire in female cancer survivors. Postmenopausal women with a history of cancer and no current evidence of disease were eligible if they reported a decrease in sexual desire and had a sexual partner. Eligible women were randomly assigned to receive 2% testosterone in Vanicream for a testosterone dose of 10 mg daily or placebo Vanicream for 4 weeks and were then crossed over to the opposite treatment for an additional 4 weeks. The primary endpoint was sexual desire or libido, as measured using the desire subscales of the Changes in Sexual Functioning Questionnaire, as assessed at baseline and at the end of 4 and 8 weeks of treatment. Serum levels of bioavailable testosterone were measured at the same times. All statistical tests were two-sided., Results: We enrolled 150 women. Women who were on active testosterone cream had higher serum levels of bioavailable testosterone than women on placebo (mean change from baseline, testosterone versus placebo, week 4, 11.57% versus 0%, difference = 11.57%, 95% confidence interval [CI] = 8.49% to 14.65%; week 8, 10.21% versus 0.28%, difference = 9.92%, 95% CI = 5.42% to 14.42%; P<.001 for all). However, the average intrapatient libido change from baseline to weeks 4 and 8 was similar on both arms., Conclusion: Increased testosterone level did not translate into improved libido, possibly because women on this study were estrogen depleted.

Context: Ghrelin is a 28-amino acid, Ser(3)-octanoylated peptide that stimulates GH secretion in vivo and in vitro. Beyond the capability of ghrelin to synergize with GHRH, little is known about multipeptide modulation of ghrelin's actions in humans., Objective: The objective of this study was to test the hypothesis that ghrelin can stimulate GH secretion in the absence or presence of somatostatin withdrawal (induced by l-arginine infusion) and stress-like drive by CRH., Design: This was a randomized, double-blind, placebo-controlled, cross-over interventional study., Setting: This study was performed at an academic medical center., Participants: Nine healthy postmenopausal women not receiving sex hormones were studied., Interventions: Subjects were given an iv infusion of saline and/or l-arginine or human CRH, followed by a bolus iv injection of ghrelin., Outcome Measures: The outcome measures were pulsatile GH secretion quantified by repetitive blood sampling, immunochemiluminometry, and deconvolution analysis., Results: Consecutive saline/ghrelin infusion increased pulsatile GH secretion from 2.7 +/- 1.0 (saline/saline; mean +/- sem) to 20 +/- 5.0 microg/liter.3 h (P < 0.01). The magnitude of the effect of l-arginine/saline was comparable at 20 +/- 4.5 microg/liter.3 h (P < 0.01). In contrast, sequential l-arginine/ghrelin evoked true synergy of GH release (93 +/- 14 microg/liter.3 h; P = 0.003 vs. l-arginine alone and P = 0.008 vs. ghrelin alone). Human CRH did not affect GH responses to saline/saline (3.9 +/- 1.1 microg/liter.3 h), saline/ghrelin (19 +/- 3.3 microg/liter.3 h), l-arginine/saline (16 +/- 2.7 microg/liter.3 h), or l-arginine/ghrelin (90 +/- 13 microg/liter.3 h)., Conclusions: Assuming that l-arginine reduces somatostatin outflow, we infer that ghrelin can activate hypothalamo-pituitary pathways that are both dependent upon and independent of somatostatinergic restraint even in the face of a strong stress-related signal.

The authors present the case of a 58-year-old woman who presented with symptoms of diabetes insipidus (DI) 1 year after she was found to have a Stage 3 (of 4) estrogen receptor-positive infiltrating ductal adenocarcinoma of the left breast with pulmonary and bone metastases. Magnetic resonance images demonstrated a solitary site of metastasis in the patient's pituitary stalk, and gamma knife surgery (GKS) was performed to treat the lesion. Three months after GKS the patient was able to reduce the medication she required for the DI. There was no evidence of pituitary failure and no negative effect on her vision.

Objective: Distinguishing between pituitary-dependent Cushing's syndrome (CS) and occult ectopic ACTH syndrome can be extremely difficult. Bilateral inferior petrosal sinus sampling has been shown to have the highest diagnostic accuracy in this subtype evaluation. Internal jugular vein sampling (IJVS) has been reported as a potentially safer invasive alternative, but data are limited. Our objective was to compare the sensitivity and specificity of bilateral IJVS and bilateral inferior petrosal sinus sampling (IPSS) in patients with ACTH-dependent CS., Design: We prospectively collected blood samples from the inferior petrosal sinus and internal jugular vein of consecutive patients with ACTH-dependent CS., Patients: The study group included 35 patients: 32 with pituitary-dependent CS (positive immunohistochemical findings for ACTH pituitary tumour or biochemical cure after pituitary surgery) and three with histologically proven ectopic ACTH syndrome., Measurements: Inferior petrosal sinus sampling and bilateral IJVS were performed simultaneously before and after administration of corticotropin-releasing hormone (CRH), and ratios of central-to-peripheral ACTH concentrations were calculated., Results: The basal IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent CS (> 2) in 15 patients (46.9%), as were basal inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 29 patients (90.6%). The post-CRH IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent disease (> 3) in 24 patients (75%), as were post-CRH inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 28 patients (87.5%). In the three patients with ectopic ACTH CS, the IJVS and inferior petrosal sinus sampling pre- and post-CRH ACTH ratios were correctly negative. The overall sensitivity of combined pre- or post-CRH was 81.3% for IJVS and 93.8% for inferior petrosal sinus sampling. Because of the difference between mean ratios in the two techniques, new criteria for IJVS were mathematically calculated: a pre-CRH central-to-peripheral ACTH ratio of 1.59 and a post-CRH central-to-peripheral ACTH ratio of 2.47 maximized sensitivity and specificity when both of these are equally taken into consideration., Conclusion: In conclusion, IJVS is not superior to inferior petrosal sinus sampling for establishing the cause of ACTH-dependent CS. When new criteria of basal (> 1.6) and post-CRH (> 2.5) central-to-peripheral ACTH gradients were applied to ACTH ratios from IJVS, the sensitivity of this test was maximized. However, confirmatory inferior petrosal sinus sampling is recommended when there is a lack of a central-to-peripheral ACTH gradient and when there is only a gradient above the cut-off on basal (pre-CRH) sampling.

Objective: To evaluate tumor control rates and complications after stereotactic radiosurgery for patients with nonfunctioning pituitary adenomas., Methods: Between 1992 and 2000, 33 patients underwent radiosurgery for treatment of nonfunctioning pituitary adenomas. Thirty-two patients (97%) had undergone one or more previous tumor resections. Twenty-two patients (67%) had enlarging tumors before radiosurgery. The median tumor margin dose was 16 Gy (range, 12-20 Gy). The median follow-up period after radiosurgery was 43 months (range, 16-106 mo)., Results: Tumor size decreased for 16 patients, remained unchanged for 16 patients, and increased for 1 patient. The actuarial tumor growth control rates at 2 and 5 years after radiosurgery were 97%. No patient demonstrated any decline in visual function. Five of 18 patients (28%) with anterior pituitary function before radiosurgery developed new deficits, at a median of 24 months after radiosurgery. The actuarial risks of developing new anterior pituitary deficits were 18 and 41% at 2 and 5 years, respectively. No patient developed diabetes insipidus., Conclusion: Stereotactic radiosurgery safely provides a high tumor control rate for patients with recurrent or residual nonfunctioning pituitary adenomas. However, despite encouraging early results, more long-term information is needed to determine whether radiosurgery is associated with lower risks of new endocrine deficits and radiation-induced neoplasms, compared with fractionated radiotherapy.

Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 micro g/d), epinephrine (66 micro g/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 micro g/dl and decreased to 12.9 and 4.5 micro g/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was -4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 micro g/d), epinephrine (0 micro g/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing's syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.

Objective: Speech recognition promises to reduce information entry costs for clinical information systems. It is most likely to be accepted across an organization if physicians can dictate without concerning themselves with real-time recognition and editing; assistants can then edit and process the computer-generated document. Our objective was to evaluate the use of speech-recognition technology in a randomized controlled trial using our institutional infrastructure., Design: Clinical note dictation from physicians in two specialty divisions was randomized to either a standard transcription process or a speech-recognition process. Secretaries and transcriptionists also were assigned randomly to each of these processes., Measurements: The duration of each dictation was measured. The amount of time spent processing a dictation to yield a finished document also was measured. Secretarial and transcriptionist productivity, defined as hours of secretary work per minute of dictation processed, was determined for speech recognition and standard transcription., Results: Secretaries in the endocrinology division were 87.3% (confidence interval, 83.3%, 92.3%) as productive with the speech-recognition technology as implemented in this study as they were using standard transcription. Psychiatry transcriptionists and secretaries were similarly less productive. Author, secretary, and type of clinical note were significant (p < 0.05) predictors of productivity., Conclusion: When implemented in an organization with an existing document-processing infrastructure (which included training and interfaces of the speech-recognition editor with the existing document entry application), speech recognition did not improve the productivity of secretaries or transcriptionists.

Background and Purpose: Determining the cause of Cushing's syndrome can be difficult. Bilateral inferior petrosal sinus (IPS) sampling after ovine corticotropin-releasing hormone (oCRH) stimulation is an established technique for the differentiation of pituitary from nonpituitary sources of adrenocorticotropic hormone (ACTH) production. The purpose of this study was to review our experience to determine the sensitivity and specificity of bilateral IPS sampling., Methods: Between January 1990 and February 1997, 92 patients underwent 94 IPS sampling procedures. Indications for these patients with Cushing's syndrome included no discrete lesion on MR images or CT scans, a discrete lesion present on images but equivocal peripheral ACTH sampling after oCRH stimulation, and persistent Cushing's syndrome after trans-sphenoidal surgery., Results: IPS sampling yielded six false-negative results and one false-positive result, manifesting an overall sensitivity of 92.2% and a specificity of 90.0% for detection of a pituitary source of ACTH after oCRH stimulation. Microadenoma lateralization by IPS sampling after oCRH stimulation agreed with the surgical location in 70.0% of the patients. The technical success rate of initial (presampling) bilateral IPS catheterization was 93.6%. Two serious complications occurred and consisted of a venous subarachnoid hemorrhage and a lower extremity deep venous thrombosis., Conclusion: Bilateral IPS sampling after oCRH stimulation is helpful in the evaluation of ACTH-dependent Cushing's syndrome. False-negative results, however, suggest that the possibility of a pituitary source must still be considered when no response to oCRH is documented. Interpetrosal ACTH gradient alone is not sufficient to lateralize the tumor reliably.

Neurologic complications associated with inferior petrosal sinus sampling for adrenocorticotropic hormone in the diagnosis of Cushing syndrome are rare. Previously reported complications include brain stem infarction and pontine hemorrhage. We report a case of venous subarachnoid hemorrhage with subsequent acute obstructive hydrocephalus occurring during inferior petrosal sinus sampling for Cushing syndrome.

A decrease in blood androgen levels is well documented in women who experience natural or surgical menopause. This change may be associated with various negative effects on bone metabolism in addition to psychosocial and sexuality aspects of life. A review of published information on androgen replacement therapy shows that major benefits may be achieved; unfortunately, only minimal quality information is available to help clinicians make decisions about this type of therapy. In this review, we point out the potential benefits and risks to bone, lipid and carbohydrate metabolism, and sexuality; in addition, we discuss potential risks of neoplasms and virilizing somatic changes. Long-term, physiologic, and well-designed androgen replacement studies should be performed to obtain the knowledge needed to guide therapy in this important area.

This paper describes the implementation of clinically defined episodes of care and the introduction of an episode-based summary list of patient problems across Mayo Clinic Rochester in 1996 and 1997. Although Mayo's traditional paper-based system has always relied on a type of 'episode of care' (called the "registration") for patient and history management, a new, more clinically relevant definition of episode of care was put into practice in November 1996. This was done to improve care management and operational processes and to provide a basic construct for the electronic medical record. Also since November 1996, a computer-generated summary list of patient problems, the "Master Sheet Summary Report," organized by episode, has been placed in all patient histories. In the third quarter of 1997, the ability to view the episode-based problem summary online was made available to the 3000+ EMR-capable workstations deployed across the Mayo Rochester campus. In addition, the clinically oriented problem summarization process produces an improved basic "package" of clinical information expected to lead to improved analytic decision support, outcomes analysis and epidemiological research.

Unlabelled: VOCABULARY: The Mayo problem list vocabulary is a clinically derived lexicon created from the entries made to the Mayo Clinic's Master Sheet Index and the problem list entries made to the Impression/ Report/Plan section of the Clinical Notes System over the last three years. The vocabulary was reduced by eliminating repetition including lexical variants, spelling errors, and qualifiers (Administrative or Operational terms). Qualifiers are re-coordinated with other terms, at run-time, which greatly increased the number of input strings which our system is capable of recognizing., Implementation: The Problem Manager is implemented using standard windows tools in a Windows NT environment. The interface is designed using Object Pascal. HTTP calls are passed over the World Wide Web to a UNIX based vocabulary server. The server returns a document, which is read into Object Pascal structures, parsed, filtered and displayed., Study: This paper reports the results of a recent Usability Trial focused on assessing the viability of this mechanism for standardized problem entry. Eight clinicians engaged in eleven scenarios and responded as to their satisfaction with the systems performance. These responses were observed, videotaped and tabulated. Clinicians in this study were able to find acceptable diagnoses in 91.1% of the scenarios. The response time was acceptable in 92.5% of the scenarios. The presentation of related terms was stated to be useful in at least one scenario by seven of the eight participants. All clinicians wanted to make use of shortcuts which would minimize the amount of typing necessary to encode the concept they were searching for (e.g. Abbreviations, Word Completion)., Conclusions: Clinicians are willing to choose a canonical term from a suggested list (as opposed to their own wording). Clinicians want an "intelligent" system, which would suggest terms within a category (e.g. Types of "Migraine"). They are able to make functional use of our system, in its current state of development. Finally, all clinicians appreciate the value of encoding their problems in a standardized vocabulary, toward improved research, education and practice.

Transsphenoidal removal of pituitary adenomas has become the accepted treatment for Cushing's disease. As Cushing's disease is rare in childhood, few reports describe extended follow-up after transsphenoidal surgery for this disease in children. Twenty-two patients less than 19 yr of age were diagnosed with Cushing's disease by standard testing. All patients underwent transsphenoidal surgery (TSS) as primary treatment at Mayo Clinic between 1975 and 1990. Follow-up was available in all patients and averaged 6.7 yr. Adenomas were identified pathologically in 19 patients and visualized by the surgeon in the remainder. There was 1 macroadenoma. Ten patients are considered cured with a mean follow-up of 5.5 yr. Five patients had evidence of persistent disease within 6 months of TSS and required further treatment. Seven patients had remission lasting greater than 6 months with subsequent relapse (mean time to recurrence, 7.0 yr). In children treated with TSS for Cushing's disease, the rate of cure with extended follow-up is only approximately 50%. This rate is much lower than that in adults and may indicate that Cushing's disease is more aggressive in childhood. As TSS is associated with low morbidity, we feel it is still the treatment of choice for Cushing's disease in children.

Background: Patients with endogenous hypercortisolism are thought to be at high risk for adrenalectomy and may experience significant postoperative surgical mortality/morbidity., Methods: From 1981 through 1991, 91 patients underwent adrenal resection for endogenous hypercortisolism. Causes were adrenal-dependent Cushing's syndrome (50%), pituitary-dependent Cushing's syndrome (27%), and an ectopic adrenocorticotropic hormone-secreting tumor (23%). Causes of adrenal-dependent Cushing's syndrome were adrenocortical adenoma (72%), bilateral nodular hyperplasia (20%), and adrenocortical carcinoma (8%). Comparative mean length of hospitalization for patients undergoing unilateral anterior versus posterior approach was 8 versus 6 days, and bilateral anterior versus posterior was 11 versus 6 days., Results: Operative mortality was 2.6%. Only one patient had a wound infection, and no patient had either a venous thrombosis or a pulmonary embolism. Delayed wound healing occurred in three patients., Conclusions: (1) Adrenal surgery can be performed today with low morbidity/mortality. (2) Although there is an effect of hypercortisolism on wound healing, infection, diabetes, hypertension, coronary artery disease, and pulmonary embolism, it was possible to perform adrenalectomy surgically with acceptable morbidity and mortality. (3) These results may serve as a standard against which laparoscopic adrenalectomy may be compared.

ACTH-independent Cushing's syndrome (CS) usually results from a solitary adrenocortical adenoma. We recently encountered a patient with ACTH-independent CS associated with bilateral adrenal enlargement. The evaluation led us to consider some rare but interesting entities. The patient was a 69 year-old woman who had a 10-15 year history of controlled hypertension, back pain associated with osteoporosis, easy bruising, and truncal obesity. Her medications included conjugated estrogens. Physical examination revealed classical features of CS. She had a raised blue lesion on her buccal mucosa. Plasma cortisol concentrations were elevated at 36 (a.m.) and 38 (p.m.) microg/dL. Urinary free cortisol was normal at baseline (65 microg/24 hours) but failed to suppress adequately in response to the low-dose dexamethasone suppression test (75 microg/24 hours). The plasma ACTH concentration was undetectable. Plasma cortisol concentrations failed to suppress (37 microg/dL) with an 8 mg overnight dexamethasone test. A CT scan of the abdomen revealed bilateral adrenal masses. The possibilities of food-induced CS and primary pigmented nodular adrenal disease were excluded by a lack of marked stimulation in cortisol secretion to a mixed-meal and dermatologic confirmation of the buccal mucosa lesion as an angioma and not a blue nevus. Adrenal venous sampling showed cortisol secretion from both adrenals. The patient underwent bilateral adrenalectomy with pathology confirming bilateral adenomas. This case illustrates an unusual application of selective venous sampling in the CS evaluation and raises questions about the pathogenesis of cortisol-secreting adrenocortical adenomas.

The implementation of an electronic medical record system in any large organization is as complex a task as the design of the system. During implementation, it is necessary that health care providers using the electronic system are able to communicate with colleagues who are continuing to work with the paper record. The Mayo Clinic in Rochester, Minnesota, is well along the path to implementing an electronic medical record system. One of the key issues addressed has been the need for the electronic system to integrate with the paper record. This need to function in the dual electronic/paper environment has placed new demands on printers, required revision of some paper forms, and required the electronic system to create facsimilies of paper record forms. In addition, new security issues have been raised. Dual paper/electronic environment issues are an important challenge in the implementation of an electronic medical record.

On 1 January 1993, the Electronic Medical Record Task Force at Mayo Clinic published its report. Charged by the Mayo Foundation to define the Electronic Medical Record (EMR) for Mayo, the task force mapped the goals, strategies and time-lines for implementation of the EMR in that institution. The task force was composed predominantly of caregivers (physicians and nurses) with assistance from members of Mayo's information systems and administrative departments. The focus of the effort was care of the patient with the consensus belief that the EMR will improve that process and, if designed robustly, will serve the other information needs of claims, research, education and practice management. The recommendations of this report have been accepted by the Mayo Foundation leadership resulting in the generation of a master plan and the creation of the governance structure for implementation at Mayo. This paper abstracts key portions of the report.

The broad-based need for a standard, robust patient identifier is reviewed. Advantages and difficulties of the Social Security Number are considered. An alternative number, composed of birthdate, location, and check digits, is proposed. Logistic extensions of the geographically based schema are made for provider and facility identification. Several variations of representation are described in base 34, which make the composite number short, easily derived and decoded, and robust.

Objectives: To define the clinical spectrum of bronchial carcinoid tumors in patients presenting with the Cushing syndrome, to evaluate the role of chest radiographs and computed tomography in their diagnosis, to review the characteristic histologic features, and to determine patient outcome., Design: Retrospective analysis of consecutive patients., Setting: A referral-based medical center., Patients: Fifteen consecutive patients with the Cushing syndrome evaluated at the Mayo Clinic with histologically proven bronchial carcinoid tumors., Measurements: Clinical, radiographic, and histologic features., Results: The Cushing syndrome was the initial clinical presentation, and bronchial carcinoid tumors were found later in all 15 patients. The diagnosis of carcinoid tumor was proved histologically in all cases. Ten biopsies showed typical carcinoid tumors, three were histologically atypical, and three were metastatic. Corticotropin was detected by immunostaining in seven of these tumors. Biochemical analysis showed marked elevations of circulating corticotropin with a mean serum value of 156 +/- 58 pmol/L (normal, 4 to 22 pmol/L). Additional clinical features included hypokalemia in six patients and glucocorticoid response to either high-dose dexamethasone or metyrapone in 6 of 13. These hormonally active carcinoid tumors were frequently radiographically occult, with 10 of 15 patients initially having normal chest radiographs. Computed tomography was successful in locating carcinoid tumors in five patients with negative chest radiographs evaluated after 1980. All five remaining patients with normal chest radiographs evaluated before 1980 eventually developed nodular lesions on standard chest radiography from 1 to 10 years later. Ten patients achieved complete remission and two patients, partial remission of the Cushing syndrome after surgical resection. Three patients continued to have symptomatic glucocorticoid excess due to metastatic disease., Conclusions: Although uncommon, the Cushing syndrome may be the initial clinical manifestation of an otherwise indolent bronchial carcinoid tumor. Radiographic imaging of occult lesions can be successfully accomplished with computed tomography. Surgical resection is curative in most patients with this disorder.

We determined the pituitary-adrenal response to 1 microgram/kg of ovine corticotropin releasing hormone (oCRH) administered as an intravenous bolus injection in 50 normal subjects. Brief facial flushing was noted in 44% of the subjects; no other side effects were reported. Plasma corticotropin levels increased from a median of 30.2 pg/ml at baseline to a median peak level of 77.8 pg/ml after administration of oCRH; the peak response occurred at the 30- to 45-minute or the 45- to 60-minute time point. Plasma cortisol levels increased from a median of 10.8 micrograms/dl at baseline to a median peak level of 22.0 micrograms/dl after administration of oCRH; the peak response occurred at the 45- to 60-minute time point. Plasma beta-endorphin levels increased from a median of 9.5 pg/ml at baseline to a median peak level of 23.0 pg/ml after administration of oCRH; the peak response occurred at the 15- to 30-minute or the 30- to 45-minute time point. The responsiveness to oCRH was unaffected by age, sex, or body mass index of the subjects.

Twenty-five patients were identified with non-pituitary, nonadrenal ACTH-secreting tumors (bronchial carcinoid, bronchial small cell carcinoma, pancreatic islet cell carcinoma, medullary thyroid carcinoma, thymic carcinoids, metastatic adenocarcinoma, and pancreatic cystadenoma). Clinical features were weakness, hypertension, cushingoid appearance, peripheral edema, personality disorders, and hyperpigmentation. Biochemical features were a markedly increased urinary free cortisol level (all patients), hypokalemia (71 percent of patients), and an elevated ACTH level (72 percent of patients). Surgical therapy consisted of bilateral total adrenalectomy (56 percent of patients). Twelve percent underwent transsphenoidal hypophysectomy and 36 percent had excision of their tumor. No surgical therapy was undertaken in 28 percent. Bilateral total adrenalectomy in patients with a slow-growing malignancy or an unknown tumor secreting ACTH is beneficial in relieving symptoms and prolonging life. Excision of nonmalignant ACTH-producing tumors yields an excellent long-term prognosis.

Four patients (two males and two females, ages 12-21 years) had clinical features of the Cushing syndrome. Results of biochemical tests (in three patients tested) suggested the presence of an autonomously functioning adrenocortical neoplasm. However, radiologic examination of the adrenals did not show an adrenal tumor. The four patients underwent curative bilateral total adrenalectomy and did not manifest the Nelson syndrome postoperatively (follow-up, 2-22 years). The adrenal pathologic findings in these patients were similar. Gross findings included: 1) decreased, normal, or slightly increased total gland weight; 2) studding of the external and cut surfaces by small (less than 4 mm) black, brown, dark-green , red, or (rarely) yellow nodules; and 3) cortical atrophy and disorganization of the normal zonation between the nodules. Microscopically, the nodules were composed predominantly of enlarged, globular, cortical cells with granular eosinophilic cytoplasm that often contained lipofuscin. Twenty-four similar cases have been reported. Findings in these plus our four cases identify a special type of adrenocortical pathology associated with Cushing syndrome, for which we suggest the name "primary pigmented nodular adrenocortical disease."

Plasma aldosterone increases briskly during upright posture in patients with idiopathic hyperaldosteronism, despite only small increases in PRA and presumably small increases in angiotensin II. To examine the postulate that small increments in angiotensin II mediate these brisk increases in aldosterone, we infused graded doses of angiotensin II into normal subjects and patients with idiopathic hyperaldosteronism and compared the changes in levels of plasma aldosterone in the two groups. Supplemental sodium and dexamethasone were given before the infusion to minimize the influence of endogenous angiotensin II and ACTH. In response to the infusion of angiotensin II, increases in the levels of plasma aldosterone of patients with idiopathic hyperaldosteronism were significantly greater than those of normal subjects. In addition, levels of plasma aldosterone increased at a lower rate of infusion of angiotensin II in patients than in normal subjects. It is concluded that patients with idiopathic hyperaldosteronism have increased adrenal sensitivity to angiotensin II. This increased sensitivity may explain the brisk increases in aldosterone that occur during upright posture in these patients.

Referral patterns from internists to departments of nuclear medicine or radiology are important determinants of whether adrenal glands are imaged by computed tomography (CT) or by radioisotope scintigraphy. To assist clinicians in making an informed choice, computed tomographic scans were compared with isotope scintigrams using 131I-19-iodocholesterol (19-IC) and 131I-6 beta-iodomethyl-19-norcholesterol (NP-59). In general, imaging techniques serve to localize diseases that are diagnosed on the basis of biochemical tests of adrenal function. Computed tomographic scanning and NP-59 scanning are of comparable diagnostic accuracy. Both are superior to 19-IC scanning in the diagnosis of Cushing's syndrome and primary aldosteronism. Computed tomographic scanning is faster and less expensive, and involves lower radiation doses to the patient than scintigraphy. Adrenocortical isotope scanning as a routine procedure has been superseded by computed tomographic scanning at the Mayo Clinic.

Adrenal imaging in the past has been limited in its clinical application by the long interval between administration of dose and visualization of adrenal glands. We review our experience with the use of a newer labeling agent, NP-59, in 29 patients with various adrenal disorders and in 4 normal subjects. With this agent, identification of adrenal lesions is possible with a high degree of accuracy, and diagnostic information is usually available within 48 hours. NP-59 is particularly useful in evaluating primary aldosteronism and selected cases of Cushing's syndrome.

The records of 62 patients (36 female and 26 male) with pathologically confirmed adrenal cortical carcinoma who had operations between 1960 and 1980 were reviewed. The mean age was 48 years. There were 36 (58%) functioning tumors and 26 (42%) nonfunctioning tumors. Curative resection was performed in 31 patients, palliative resection in 14, and open biopsy alone in 17 with an overall operative mortality rate of 9.7% and a 5-year survival rate of 16%. There was no significant difference in survival rates between patients who had operations alone and those who had operations plus adjunctive therapy. Patients with stages I to III lesions or those who underwent curative resections had significantly longer survival than had those with stage IV disease or those who had palliative resections, respectively. Factors that failed to influence survival rates included palliative resection versus biopsy, tumor size, grade, function, and patient sex or age. We conclude that operative staging is prognostically valuable, aggressive surgical treatment is recommended in stages I to III lesions, and a prospective randomized study of adjuvant treatment for all stages of adrenal cortical carcinoma is indicated.

Two patients with overproduction of thyroid-stimulating hormone (TSH) are described. The first patient, a 25-year-old man with recurrent hyperthyroidism, had a pituitary adenoma and highly elevated levels of TSH. While the patient was receiving 0.3 mg of thyroid daily, and basal TSH level was 161 microM/ml. Despite an increase in the thyroid hormone therapy, serum TSH levels remained elevated. The administration of thyrotropin-releasing hormone (TRH) or dexamethasone resulted in no changes in TSH level. The second patient was an 18-year-old man who had inappropriately elevated levels of TSH 3 months after radioiodine therapy for hyperthyroidism. A gradual increase in thyroid hormone replacement therapy decreased the serum TSH levels from 250 to 14.8 microM/ml. The administration of TRH led to huge increases of TSH. Dexamethasone inhibited basal TSH but not TRH-stimulated TSH levels. The overproduction of TSH was attributed to autonomous, neoplastic secretion in the first case and to partial, selective pituitary thyrotroph resistance to thyroid hormone in the second.

Rarely, acromegaly is produced by neuroendocrine neoplasms elaborating a substance similar to or identical with growth hormone-releasing factor. This report reviews the cases described to date and presents the clinicopathologic features of a patient with acromegaly, mild sellar enlargement, and elevated growth hormone levels associated with a large bronchial carcinoid tumor. Normalization of serum growth hormone levels and regression of acromegaly followed resection of the bronchial tumor, which was shown, by bioassay and immunocytochemistry, to contain a growth hormone-releasing factor.

Twenty-two of 32 patients with Cushing's disease seen at the Mayo Clinic during a 3-year period were carefully studied radiologically (triaxial spiral tomograms of the sella and bilateral carotid arteriograms with magnification and subtraction techniques). Eighteen of these 22 pat-ents had radiologic evidence of small pituitary gland tumors and underwent transsphenoidal microsurgical exploration of the pituitary. A microadenoma (less than 10 mm) was found in 17 of the 18 patients. Hypercortisolism was corrected, and a clinical remission occurred in 16 of the 18 patients; the hypercortisolism persisted in 2 patients. A period of hypocortisolism occurred after removal of the pituitary tumor in all patients who experienced a remission. Remissions have been associated with normal anterior pituitary and adrenocortical function in a large percentage of patients who were adequately studied 6 months or more after pituitary surgery.

Although considerable advances have been made in the understanding of Cushing's syndrome in the recent past, many difficulties persist in the diagnosis and management of patients with hypercortisolism. Precision in the diagnosis of Cushing's syndrome and the differentiation of its various forms have gradually improved, but a substantial number of cases have laboratory or radiologic findings that can be misleading or at least difficult to interpret. Furthermore, other conditions may mimic Cushing's syndrome and add to the diagnostic difficulties. Surgical extirpation of primary adrenal lesions that cause the hypercortisolism or of the neoplasms responsible for the ectopic production of adrenocorticotropic hormone remains the treatment of choice for these problems. Currently, transsphenoidal surgical exploration is the treatment of choice for Cushing's disease.

The regulation of ACTH-cortisol production in the pathophysiology of the various forms of Cushing's syndrome is discussed. The diagnostic algorithms for the differential diagnosis of Cushing's syndrome are reviewed with emphasis on the precision of the evaluation, diagnostic pitfalls, and the influence of some of the more recently developed procedures on this diagnostic evaluation.