Defining non-functioning adrenal adenomas on the basis of the occurrence of hypocortisolism after adrenalectomy

Background In patients with adrenal incidentalomas (AI), there is uncertainty on how to rule out hypercortisolism. The occurrence of post-surgical (unilateral adrenalectomy) hypocortisolism (PSH) has been proposed as a proof of the presence of a pre-surgical hypercortisolism in AI patients. The aim of this study was to define the thresholds of cortisol level after 1 mg overnight dexamethasone suppression test (F-1mgDST), urinary free cortisol (UFC), midnight serum cortisol (MSC) and adrenocorticotroph hormone (ACTH) able to predict the absence of PSH in AI patients undergoing surgery. Methods In 60 patients who underwent AI excision, cortisol secretion was assessed by low-dose corticotropin stimulation test or insulin tolerance test, when needed. We searched for the lowest pre-surgical value of F-1mgDST, UFC and MSC and the highest value for ACTH in AI patients with PSH as indexes of normal cortisol secretion. Results the lowest values of F-1mgDST, UFC and MSC and the highest value for ACTH in PSH patients were 1.2 \ub5g/dL (33 nmol/L), 10.4 \ub5g/24h (29 nmol/24h), 1.2 \ub5g/dL (33 nmol/L) and 26.9 pg/ml (6 pmol/L), respectively, but only F-1mgDST <1.2 \ub5g/dL (33 nmol/L) was able to predict the absence of PSH. Among AI patients with F-1mgDST <1.2 \ub5g/dL (33 nmol/L) no subjects had diabetes mellitus and/or metabolic syndrome and these subjects tended to have a better metabolic profile than those with F-1mgDST 651.2 \ub5g/dL (33nmol/L) Conclusion in AI patients a F-1mgDST <1.2 \u3bcg/dL (33 nmol/L) rules out PSH and could be used to exclude hypercortisolism in AI patients

Adrenalectomy reduces the risk of vertebral fractures in patients with monolateral adrenal incidentalomas and subclinical hypercortisolism

Objective: Subclinical hypercortisolism (SH) is associated with increased risk of vertebral fractures (VFx). The effect on bone following recovery from SH is unknown. Design: Of the 605 subjects consecutively referred for monolateral adrenal incidentalomas (AIs) to our outpatient clinics, 55 SH patients (recruited on the basis of the exclusion criteria) were enrolled. We suggested to all patients to undergo adrenalectomy, which was accepted by 32 patients (surgical group, age 61.3\ub18.1 years) and refused by 23 patients, who were followed with a conservative management (non-surgical group, age 65.4\ub17.1 years). Methods:We diagnosed SH in patients with serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST)O5.0 mg/dl or with greater than or equal to two criteria among 1 mg-DST >3.0 \u3bcg/dl, urinary free cortisol >70 \u3bcg/24 h and ACTH <10 pg/ml.We assessed: bone mineral density (BMD) at lumbar spine (LS) and femoral neck (as Z-score) by dual-energy X-ray absorptiometry and the VFx presence by X-ray at baseline and at the end of follow up (surgical group 39.9\ub120.9 months and non-surgical group 27.7\ub111.1 months). Results: The LS Z-score (DZ-score/year) tended to increase in the surgical group (0.10\ub10.20) compared with the non-surgical group (K0.01\ub10.27, PZ0.08) and in the former, the percentage of patients with new VFx was lower (9.4%) than in the latter (52.2%, P<0.0001). Surgery in AI patients with SH was associated with a 30% VFx risk reduction (odds ratio 0.7, 95% CI 0.01-0.05, PZ0.008) regardless of age, gender, follow up duration, 1 mg-DST, LS BMD, and presence of VFx at baseline. Conclusion: In patients with monolateral AI and SH, adrenalectomy reduces the risk of VFx

Carboxyl-terminal parathyroid hormone fragments: biologic effects

Carboxyl-terminal PTH fragments (C-PTH), are generated by both direct secretion from parathyroids in relation to serum calcium levels and catabolism of PTH operated by the Kupffer cells in the liver. These molecular fragments have been till recently regarded as inert byproducts of PTH metabolism, since they do not interact with the PTH/PTH-related peptide (rP) receptor, which mediates the classical hormone actions. Current findings instead indicate that C-PTH would interact with a putative C-PTH receptor. This way, C-PTH seem to exert specific effects on calcium homeostasis and bone metabolism, opposite to those of the synthetic agonist of PTH/PTHrP receptor (i.e. PTH 1-34). In vitro and in vivo data actually indicate that C-PTH, by interacting with specific receptors, could have an anti-calcemic action, as well as a pro-apoptotic effect on both osteocytes and osteoclasts. This in turn could result in a reduced activity of the latter cells, with a consequent inhibition of bone resorption

Role of adrenal gland scintigraphy in patients with subclinical hypercortisolism and incidentally discovered adrenal mass

The role of adrenal scintigraphy (AS) in the diagnosis of subclinical hypercortisolism (SH) in adrenal incidentaloma (AI) is debated

Accuracy of several parameters of hypothalamic-pituitary-adrenal axis activity in predicting before surgery the metabolic effects of the removal of an adrenal incidentalomA

Context: It is unknown whether the metabolic effects of the removal of an adrenal incidentaloma (AI) can be predicted by the assessment of cortisol hypersecretion before surgery. Objective: To evaluate the accuracy of several criteria of hypothalamic-pituitary-adrenal axis activity in predicting the metabolic outcome after adrenalectomy. Design: Retrospective longitudinal study. Patients: In 55 surgically treated AI patients (Group 1) before surgery and in 53 nontreated AI patients (Group 2) at the baseline, urinary free cortisol (UFC), cortisol after 1 mg overnight dexamethasone-suppression test (1 mg-DST), ACTH, and midnight serum cortisol (MSC) were measured. In Groups 1 and 2, metabolic parameters were evaluated before and 29.6 \ub1 13.8 months after surgery and at the baseline and after 35.2 \ub1 10.9 months respectively. Main outcome measures: The improvement/worsening of weight, blood pressure, glucose, and cholesterol levels (endpoints) was defined by the presence of a > 5% weight decrease/increase and following the European Society of Cardiology or the ATP III criteria respectively. The accuracy of UFC, 1 mg-DST, ACTH, and MSC, singularly taken or in combination, in predicting the improvement/worsening of 65 2 endpoints was calculated. Results: The presence of 65 2 among UFC > 70 \u3bcg/24 h (193 nmol/l), ACTH 3.0 \u3bcg/dl (83 nmol/l) (UFC-ACTH-DST criterion) had the best accuracy in predicting the endpoints' improvement (sensitivity (SN) 65.2%, specificity (SP) 68.8%) after surgery. In the nontreated AI patients, this criterion predicted the worsening of 65 2 endpoints (SN 55.6%, SP 82.9%). Conclusions: The UFC-ACTH-DST criterion seems to be the best for predicting the metabolic outcome in surgically treated AI patients

Factors associated with vertebral fracture risk in patients with primary hyperparathyroidism

Objective: To examine factors, in addition to bone mineral density (BMD), such as the common calcium-sensing receptor (CASR) gene polymorphisms, associated with vertebral fracture (VFx) risk in primary hyperparathyroidism (PHPT).Design and methods: A cross-sectional analysis of 266 Caucasian PHPT seen as outpatients. Serum calcium (sCa) phosphate metabolism parameters were measured. BMD was assessed by dual-energy X-ray absorptiometry (expressed as Z-score) at lumbar spine (Z-LS) and femoral neck, morphometric VFx by radiograph, and CASR A986S/R990G genotypes by PCR amplification and genomic DNA sequencing.Results: Fractured patients (n=100, 37.6%) had lower sCa (10.8\ub10.7mg/dl) and Z-LS BMD (-1.0\ub11.44), higher age (61\ub110 years), and prevalence (51%) of 651 S alleles of the CASR A986S single-nucleotide polymorphism (SNP; AS/SS), than those not fractured (nZ166, 11.2\ub11.0 mg/dl, -0.57\ub10.97, 58\ub113 years, and 38% AS/SS, respectively, P!0.05 for all comparisons). Logistic regression, with VFx as dependent variable, showed independent risks associated with increased age (OR 1.03, 95% CI 1.01-1.06, P=0.006), decreased sCa (OR 1.86, 95% CI 1.28-2.7, P=0.001), and Z-LS BMD (OR 1.4, 95% CI 1.12-1.7, P=0.002) and presence of AS/SS (OR 1.8, 95% CI 1.1-2.9, P=0.05). The presence of two out of three factors (age 6558 years, sCa <10.8 and Z-LS BMD 64-1.0, and AS/SS genotype) gave an overall OR of 4.2 (95% CI 2.25-7.85, P<0.0001).Conclusions: In PHPT, VFx is associated positively with age, negatively with sCa and spinal BMD, and presence of at least one copy of the CASR A986S SNP

Post-surgical hypocortisolism after removal of an adrenal incidentaloma : is it predictable by an accurate endocrinological work-up before surgery?

Objective: Few data are available regarding the need of steroid substitutive therapy after unilateral adrenalectomy for adrenal incidentaloma (AI). It is unknown whether, before surgery, the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis secretion parameters can predict post-surgical hypocortisolism. Aim: This study aimed to evaluate whether, in AI patients undergoing unilateral adrenalectomy, post-surgical hypocortisolism could be predicted by the parameters of HPA axis function. Design: Prospective, multicenter. Methods: A total of 60 patients underwent surgical removal of AI (surgical indication: 29 subclinical hypercortisolism (SH); 31 AI dimension). Before surgery, SH was diagnosed in patients presenting at least three criteria out of urinary free cortisol (UFC) levels>60 \ub5g/24 h, cortisol after 1-mg dexamethasone suppression test (1 mg-DST)>3.0 \ub5g/dl, ACTH levels5.4 \ub5g/dl. Two months after surgery, HPA axis function was assessed by low dose ACTH stimulation test or insulin tolerance test when needed: 39 patients were affected (Group B) and 21 were not affected (Group A) with hypocortisolism. The accuracy in predicting hypocortisolism of pre-surgical HPA axis parameters or their combinations was evaluated. Results: The presence of >2 alterations among 1 mg-DST>5.0 \ub5g/dl, ACTH<10 pg/ml, elevated UFC and MSC has the highest odds ratio (OR) for predicting post-surgical hypocortisolism (OR 10.45, 95% confidence interval, CI 2.54\u201342.95, P=0.001). Post-surgical hypocortisolism was predicted with 100% probability by elevated UFC plus MSC levels, but not ruled out even in the presence of the normality of all HPA axis parameters. Conclusion: Post-surgical hypocortisolism cannot be pre-surgically ruled out. A steroid substitutive therapy is indicated after unilateral adrenalectomy for SH or size of the adenoma

Subclinical hypercortisolism : correlation between biochemical diagnostic criteria and clinical aspects

Objective Subclinical hypercortisolism (SH) has been associated with increased prevalence of hypertension, type 2 diabetes mellitus, dyslipidaemia, central obesity, osteoporosis and vertebral fractures. We aimed to investigate the accuracy of different SH diagnostic criteria in predicting the presence of complications. Design This was a retrospective study. Patients We evaluated data from 231 patients (120 women and 111 men) affected with adrenal incidentalomas (AI). Measurements We studied the accuracy of different SH diagnostic criteria (cortisol after 1 mg overnight dexamethasone suppression test - 1mg-DST - at different cut-off such as 49\ub77, 82\ub78, 137\ub79 nmoll, elevated urinary free cortisol, reduced adrenal corticotroph hormone (ACTH) levels alone or various combination of these parameters) in predicting the concomitant presence of the following three complications: hypertension, type 2 diabetes and vertebral fractures. Results The criterion characterized by the presence of two of 1mg-DST >82\ub78 nmoll, elevated UFC and reduced ACTH struck the best balance between sensitivity and specificity, reaching a good accuracy in predicting the cluster of complications (61\ub79%; 77\ub71% and 75\ub78%, respectively). The presence of this cluster was associated with this criterion (OR 4\ub775, 95%CI 1\ub78-12\ub77, P = 0\ub7002) regardless of gonadal status, body mass index (BMI) and age. Conclusions The SH criterion characterized by the presence of two of 1mg-DST >82\ub78 nmoll, elevated UFC and reduced ACTH seems the best in predicting the presence of chronic manifestations of subtle cortisol excess

Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism

Context: In patients with adrenal incidentalomas, subclinical hypercortisolism (SH) is associated with an increased prevalence of the metabolic syndrome. The effect of surgical/conservative approach is debated. Objective: The objective of the study was to determine the effect of the surgical and conservative approaches on the metabolic syndrome in patients with adrenal incidentalomas. Design: This was a retrospective longitudinal study (18-48 months follow-up). Setting: The study was conducted on an in- and outpatient basis. Patients: One hundred eight patients with adrenal incidentalomas were studied for the presence of SH, which was diagnosed in the presence of more than two of the following: urinary free cortisol greater than 70 \u3bcg per 24 h (193 nmol per 24 h), cortisol after 1 mg dexamethasone suppression test greater than 3.0 \u3bcg/dl (83 nmol/liter), ACTH less than 10 pg/ml (2.2 pmol/liter). Interventions: Surgery was performed in 25 patients with SH (group TrSH+) and 30 without SH (group TrSH-), whereas the conservative approach was chosen by 16 patients with SH (group UntrSH+) and 37 without SH (group UntrSH-). Main Outcome Measures: During the follow-up, the improvement/worsening of body weight, blood pressure, or glucose and cholesterol levels was defined in the presence of a greater than 5% weight decrease/increase and following the European Society of Cardiology or the Adult Treatment Panel III criteria, respectively. Results: In group TrSH+, weight, blood pressure, and glucose levels improved (32, 56, and 48%, respectively) more frequently than in group UntrSH+ (12.5%, P = 0.05; 0.0%, P < 0.0001; 0.0%, P = 0.001; and 0.0%, P = 0.0014, respectively). In group UntrSH+, blood pressure, glucose, and low-density lipoprotein levels worsened more frequently (50.0, 37.5, and 50.0%, respectively) than in group TrSH+ (0.0%, P < 0.0001; 0.0%, P = 0.001; and 20.0%, P = 0.05, respectively). Conclusions: Regarding the various components of the metabolic syndrome, in patients with adrenal incidentalomas and SH, surgery is beneficial. Copyrigh