The 1 mg overnight dexamethasone suppression test: a danger to the adrenal gland?

PURPOSE OF REVIEW: The 1 mg overnight dexamethasone suppression test (ONDST) with a cutoff cortisol value of 1.8 mcg/dl (50 nmol/l) is routinely used for the assessment of incidental, benign adrenal nodules. Patients with an abnormal test are diagnosed with mild autonomous cortisol secretion (MACS). This timely commentary reviews the origins of the ONDST, its relationship to the diagnoses of MACS, and whether this is clinically relevant for clinical care. RECENT FINDINGS: Millions of incidental adrenal nodules are found on CT scans annually. Several papers in the last three years discuss and advocate for the diagnose of MACS via the ONDST. SUMMARY: An ONDST cutoff of 1.8 mcg/dl (50 nmol/l) in patients with no clinical features of Cushing's syndrome will produce false positive results and a diagnosis of MACS that could result in unnecessary adrenalectomy.

Expanding the net: The re-evaluation of the multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) in the setting of secondary hyperparathyroidism and the development of the MultIdimensional Predictive hyperparaTHyroid model (Mi-PTH).

BACKGROUND: The multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) model identifies a personalized upper limit of normal parathyroid hormone (PTH) and successfully predicts classical primary hyperparathyroidism (PHP). We aimed to assess whether maxPTH can distinguish normocalcemic PHP (NCPHP) from secondary hyperparathyroidism (SHP), including subjects who underwent bariatric surgery (BrS). METHODS: A total of 172 subjects with 359 complete datasets of serum calcium (Ca), 25-OH vitamin D, and intact PTH from Oregon were analyzed: 123 subjects (212 datasets) with PHP and 47 (143) with SHP, including 28 (100) with previous BrS. An improved prediction model, MultIdimensional evaluation for Primary hyperparaTHyroidism (Mi-PTH), was created with the same variables as maxPTH by the use of a combined cohort (995 subjects) including participants from previous studies. RESULTS: In the Oregon cohort, maxPTH's sensitivity was 100% for classical PHP and 89% for NCPHP, but only 50% for normohormonal PHP (NHPHP) and 40% specific for SHP. In comparison, although sensitivity for NCPHP was similar (89%), Mi-PTH vastly improved SHP specificity (85%). In the combined cohort, Mi-PTH had better sensitivity of 98.5% (vs 95%) and specificity 97% (vs 85%). CONCLUSION: MaxPTH was sensitive in detecting PHP; however, there was low specificity for SHP, especially in patients who underwent BrS. The creation of Mi-PTH provided improved performance measures but requires further prospective evaluation.

Evaluation of teriparatide treatment in adults with osteogenesis imperfecta.

BACKGROUND: Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies have not been tested in clinical trials for OI treatment. METHODS: 79 adults with OI were randomized to receive 20 µg recombinant human parathyroid hormone (teriparatide) or placebo for 18 months in a double-blind, placebo-controlled trial. The primary endpoint was the percent change in areal bone mineral density (aBMD) of the lumbar spine (LS), as determined by dual-energy X-ray absorptiometry. Secondary endpoints included percent change in bone remodeling markers and vertebral volumetric BMD (vBMD) by quantitative computed tomography, estimated vertebral strength by finite element analysis, and self-reported fractures. RESULTS: Compared with the placebo group, the teriparatide group showed increased LS aBMD (6.1% ± 1.0% vs. 2.8% ± 1.0% change from baseline; P < 0.05) and total hip aBMD (2.6% ± 1.0% vs. -2.4% ± 1.0% change; P < 0.001). Vertebral vBMD and strength improved with teriparatide therapy (18% ± 6% and 15% ± 3% change, respectively), but declined with placebo (-5.0% ± 6% and -2.0% ± 3% change; P < 0.05 for both comparisons). Serum procollagen type 1 N-terminal propeptide (P1NP) and urine collagen N-telopeptide (NTx) levels increased with teriparatide therapy (135% ± 14% and 64% ± 10% change, respectively). Teriparatide-induced elevation of P1NP levels was less pronounced in severe forms of OI (type III/IV) compared with the milder form (type I). Type I OI patients exhibited robust BMD increases with teriparatide; however, there was no observed benefit for those with type III/IV OI. There was no difference in self-reported fractures between the 2 groups. CONCLUSIONS: Adults with OI, particularly those with less severe disease (type I), displayed a teriparatide-induced anabolic response, as well as increased hip and spine aBMD, vertebral vBMD, and estimated vertebral strength. Trial registration. Clinicaltrials.gov NCT00131469. Funding. The Osteoporosis Imperfecta Foundation, Eli Lilly and Co., the National Center for Advancing Translational Science (NCATS) at the NIH (grant no. UL1RR024140), and the Baylor College of Medicine General Clinical Research Center (grant no. RR00188).