Sensitivity of Different ACTH and Cortisol Concentration Values in Corticotropin-Releasing Hormone Based Tests in Cushing's Disease.

PURPOSE: In Cushing's disease (CD) patients, the aim of the present study is to confirm sensitivity of several ACTH and cortisol concentration values in different time points, during corticotropin-releasing hormone (CRH) stimulation test and during CRH stimulation following dexamethasone suppression (DEX-CRH) test. METHODS: We retrospectively analyzed cortisol and ACTH concentration increment during CRH and DEX-CRH tests in 23 patients with confirmed CD. Cortisol and ACTH concentrations were determined immediately before, 15 min and 30 min after CRH stimulation. We evaluated the sensitivity of different cutoff values including those reported in previous studies, in the diagnosis of CD. RESULTS: During DEX-CRH test, 15 min serum cortisol concentration of 1.4 µg/dl (38 nmol/L) had a sensitivity of 90.9%, and serum cortisol concentration ≥1.27 µg/dl (35 nmol/L) had a sensitivity of 100%. For plasma ACTH, sensitivity of 100% was obtained using ACTH ≥3.5pmol/L (16 pg/ml) at 30 min. During CRH test, 35% increase from baseline in ACTH concentration had a sensitivity of 72.7%. Twenty percent increase in cortisol 30 minutes after stimulation yielded a sensitivity of 85.7%. The best sensitivity of ACTH and cortisol increment was obtained 15 min after stimulation, using 19% and 9% increase, respectively (sensitivity of 100% and 92.8%, respectively). CONCLUSION: During CRH and DEX-CRH tests, the study findings agree with the good sensitivity of ACTH and cortisol cutoff values suggested in previous studies; yet, other cutoff values may give a higher diagnostic sensitivity.

High Prevalence of Acromegaly in Different Industrial Areas: A Population-based Study from Haifa and Western Galilee District in Northern Israel.

BACKGROUND: National registries for acromegaly and population-based data make an important contribution to disease understanding and management. Data concerning the epidemiology of acromegaly in Israel is scanty. OBJECTIVES: To evaluate the epidemiology of acromegaly in different industrial areas in northern Israel. METHODS: Data from adult patients diagnosed with acromegaly from 2000 to 2020, living in Haifa and the western Galilee District were collected using the electronic database and medical records from Clalit Health Services. The prevalence of acromegaly in three distinct areas and overall were reported. In addition, other epidemiological data including associated co-morbidities, pituitary tumor size, and treatment modalities were collected. RESULTS: We identified 77 patients with a confirmed diagnosis of acromegaly. The overall prevalence was 155 cases/106 inhabitants without statistically significant differences between the three areas. The mean age at diagnosis was 50 ± 1.8 years and the male to female ratio was 1.1. Macroadenoma and microadenoma were identified in 44 (57%) and 25 (33%), respectively. The frequency rate of acromegaly-associated co-morbidities such as diabetes, hypertension, carpal tunnel syndrome, and osteoporosis was similar to previously reported studies. The mean body mass index (BMI) was 29 ± 5.6 kg/m2 .Obesity, with a BMI ≥ of 30 kg/m2, was found in 29 patients (38%). The majority of patients underwent transsphenoidal surgery 67 (87%). Normalized insulin-like growth factor 1 was reported in 64 (83%). CONCLUSIONS: A high prevalence of acromegaly was found in northern Israel. The pituitary microadenoma frequency rate is the highest reported.

Fracture Prevention Clinic Targeting Patients with Fragility Fracture of the Distal Radius: A Pilot Study.

BACKGROUND: Identifying and treating patients with fragility fractures may be effective in prevention of subsequent fractures because a first fragility fracture often predicts a second fracture. OBJECTIVES: To evaluate a multidisciplinary anti-osteoporotic clinic for patients with prior distal radius fragility fractures (DRFF). To assess whether addressing this early fracture may prevent a second fracture. METHODS: A retrospective case-control study was performed. Cases included patients treated surgically for DRFF who were assessed at a tertiary, multidisciplinary, fracture-prevention clinic. Controls were a series of similarly treated patients who did not attend the clinic. The primary outcome measure was a second fracture. RESULTS: Average follow-up was 42 months for the treated group and 85 months for the untreated group. The treated group received more treatment for osteoporosis than controls; however, despite one new fracture in the treated group and six new fractures in the control group, there was no significant difference in fracture occurrence. CONCLUSIONS: This pilot study supports the effectiveness of our multidisciplinary anti-osteoporotic clinic in treating osteoporosis but not in reducing subsequent fractures. Further study with larger cohorts and longer follow-up is needed to improve our ability to implement effective prevention of fragility fractures.

Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study.

INTRODUCTION: Pasireotide, a multi-somatostatin receptor (SSTR)-ligand with high affinity for SSTR5 was recently approved for acromegaly treatment. PATIENTS AND METHODS: A retrospective multicenter study investigating the efficacy and safety of long-acting (LAR) pasireotide treatment in 35 patients (20 males) with active acromegaly (28 macroadenomas). RESULTS: Mean baseline insulin-like growth factor-1 (IGF-1) at diagnosis was 3.1 ± 1.3 × ULN. All but five patients have undergone pituitary surgery and six received sellar radiotherapy. All remained with active acromegaly despite first-generation somatostatin analogue (SSA) treatment. Immediately before pasireotide-LAR initiation, eighteen patients were under SSA monotherapy and one with pegvisomant. The remaining patients received combination therapy with SSA and pegvisomant, n = 9 (two received cabergoline also); SSA and cabergoline, n = 4; pegvisomant and cabergoline, n = 1. Two were untreated. Mean IGF-1 was 1.76 ± 0.9 ULN before pasireotide. Pasireotide-LAR starting dose was 40 mg/4 weeks in most patients. IGF-1 normalized in 19 patients, IGF-1 between 1-1.2 × ULN was reached in five, and in additional two patients IGF-1 was significantly suppressed. No effect was seen in nine patients. Pasireotide dose was reduced by 20 mg in six patients with excellent response, with preserved IGF-1 control in five. Severe headaches in six patients disappeared or improved with pasireotide. Side effects consisted of symptomatic cholelithiasis in one patient and deterioration of glucose control in 22 patients, requiring initiation or intensification of antidiabetic treatment in seventeen. One patient developed diabetic ketoacidosis. CONCLUSIONS: In the real-life scenario ~54% of patients with acromegaly resistant to first-generation SSA, may normalize IGF-1 with pasireotide; however, 63% experienced glucose control deterioration.