A single-institution experience in image-guided thermal ablation of adrenal gland metastases.

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.

Percutaneous image-guided adrenal cryoablation: procedural considerations and technical success.

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 ß-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.

Putative somatostatin suppression potentiates adrenocorticotropin secretion driven by ghrelin and human corticotropin-releasing hormone.

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.

Dexamethasone-suppressed corticotropin-releasing hormone stimulation test for diagnosis of mild hypercortisolism.

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.

Performance-enhancing drugs in sport.

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.

Ghrelin potentiates growth hormone secretion driven by putative somatostatin withdrawal and resists inhibition by human corticotropin-releasing hormone.

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.

Speech recognition as a transcription aid: a randomized comparison with standard transcription.

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.

Stereotactic radiosurgery as an alternative to fractionated radiotherapy for patients with recurrent or residual nonfunctioning pituitary adenomas.

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.

Resolution of diabetes insipidus following gamma knife surgery for a solitary metastasis to the pituitary stalk. Case report.

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.

Sublabial transseptal vs transnasal combined endoscopic microsurgery in patients with Cushing disease and MRI-depicted microadenomas.

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.

The clinical conundrum of corticotropin-independent autonomous cortisol secretion in patients with bilateral adrenal masses.

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.

Surgery for Cushing's syndrome: an historical review and recent ten-year experience.

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.

Randomized controlled trial to evaluate transdermal testosterone in female cancer survivors with decreased libido; North Central Cancer Treatment Group protocol N02C3.

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.

Internal jugular vein sampling in adrenocorticotropic hormone-dependent Cushing's syndrome: a comparison with inferior petrosal sinus sampling.

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.

Loss of bone density with inhaled triamcinolone in Lung Health Study II.

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.