Adrenal Incidentalomas Patients Research Articles

Relationship between thyroid nodules and non-functioning adrenal incidentalomas and their association with insulin resistance

Objective: The relationship between insulin resistance and thyroid nodules in patients with non-functional adrenal incidentalomas (AI) is not clearly understood. The aim of this study was to determine the frequency of thyroid nodules in AI patients, as well as to evaluate any possible associations with disorders of insulin resistance. Methods: Patients diagnosed with a non-functional AI were approached for inclusion in the study. Insulin resistance was evaluated using homeostasis model assessment (HOMA-IR). All participants were screened for the presence of thyroid nodule by ultrasonography, and fine needle aspiration biopsies were obtained from consenting subjects. Results: One-hundred-thirteen patients with AI and 152 age-, BMI- and gender-matched healthy controls were enrolled. AI patients had higher waist circumference and waist/hip ratio than the control group. Metabolic syndrome, hypertension and type 2 diabetes mellitus rates were significantly higher in AI patients. HOMA-IR was similar between the groups. At least one thyroid nodule was observed in 42 (27.6%) of the controls compared to 55 (48.7%) of AI patients (p < 0.001). The mean number of thyroid nodules in AI patients was significantly higher than the control subjects (2.4 ± 0.9 versus 1.7 ± 1.0, p = 0.008). Mean nodule volume was similar between AI patients and the controls. A correlation could not be established between adrenal tumor/thyroid nodule volumes and the number of thyroid nodules, HOMA-IR, waist circumference, waist/hip ratio, BMI and thyroid function tests. Conclusion: A higher prevalence of thyroid nodule and a higher number of thyroid nodules were determined in patients with AI compared to healthy controls.

The role of salivary cortisol measured by liquid chromatography–tandem mass spectrometry in the diagnosis of subclinical hypercortisolism

The use of late-night salivary cortisol (LNSalC) for diagnosing subclinical hypercortisolism (SH) is debated. No data are available regarding the role of LNSalC as measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in SH diagnosis. The aim of this study was to evaluate the diagnostic accuracy of LNSalC measured by LC-MS/MS in SH. Cross-sectional prospective study of outpatients. In 70 consecutive patients with adrenal incidentalomas (AI), without signs and symptoms of hypercortisolism, we diagnosed SH in the presence of at least two of the following: cortisol after 1 mg overnight dexamethasone suppression test (1 mg DST) >83 nmol/l, 24-h urinary free cortisol (UFC) >193 nmol/24 h, and morning ACTH <2.2 pmol/l. The LNSalC levels by LC-MS/MS at 2300 h (normal values <2.8 nmol/l) and the presence of hypertension, type 2 diabetes mellitus (T2DM), and osteoporosis (OP) were assessed. The increased LNSalC levels (>2.8 nmol/l) had an 83.3% specificity (SP) and a 31.3% sensitivity (SN) for predicting the biochemical diagnosis of SH. The increased LNSalC had an 85.2% SP and a 55.6% SN for predicting the presence of hypertension, T2DM, and OP, while the combination of LNSalC >1.4 nmol/l (cutoff with 100% SN) plus 1 mg DST >50 nmol/l had an 88.9% SN and an 85.2% SP (similar to SH criterion at enrollment). In AI patients, LNSalC measured by LC-MS/MS appears to be useful in combination with 1 mg DST for diagnosing SH, while it is not useful as a single criterion.

Nonalcoholic fatty liver disease in subjects with adrenal incidentaloma

Adrenal incidentalomas (AI) are associated with several parameters of the metabolic syndrome (MS). Although nonalcoholic fatty liver disease (NAFLD) is considered a cardiometabolic risk factor, no data exist on its prevalence and clinical relevance in AI. The aim was to investigate the presence of MS and NAFLD in AI subjects. Fifty-six AI subjects and 30 age-, sex- and body mass index (BMI)-matched controls were evaluated. All subjects underwent abdominal computerized tomography scan and hepatic and spleen attenuation measurements. The presence of NAFLD was defined as a mean hepatic minus mean spleen attenuation difference (ΔL-ΔS) <-10HU. Anthropometric variables [BMI and waist-to-hip ratio (W/H)] were recorded, and biochemical parameters were measured. An oral glucose tolerance test was performed, and several insulin resistance (IR) indices were determined. All subjects underwent testing to reveal autonomous cortisol and/or aldosterone (ALD) secretion, while the diagnosis of pheochromocytoma was ruled out. Adrenal incidentaloma subjects' mean age (± standard deviation) was 59.64 (± 8.68) years, BMI 29.84 (± 5.85) kg/m(2) and W/H 0.90 (± 0.07). Twelve subjects with AI had subtle autonomous cortisol, five autonomous ALD and three combined cortisol and ALD secretion. AI subjects exhibited higher IR indices than controls. NAFLD was present in three AI subjects and two controls. In the multiple regression analysis, W/H and triglycerides were independently associated with a low ΔL-ΔS and, hence, degree of hepatic steatosis. There was no significant difference in the presence of NAFLD between AI patients and controls. ΔL-ΔS, an inverse index of NAFLD, was independently associated with abdominal obesity and increased triglycerides.

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1-mg dexamethasone suppression test (1-mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X-ray absorptiometry and TBS was assessed in the region of LS-BMD; BMD and TBS data were reported as Z-scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS-BMD (-0.31 ± 1.17), FT-BMD (-0.29 ± 0.91), and TBS (-3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; -1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; -1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1-mg DST (β = -0.26, t = -2.79, p = 0.006) regardless of age, LS-BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85-12.42, p = 0.001) and with the cluster low TBS plus low LS-BMD (OR, 4.37; 95% CI, 1.71-11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS-BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > -1.5) plus normal LS-BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71-71.41, p = 0.012) regardless of LS-BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures.

Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: A multicenter longitudinal study

In patients with adrenal incidentalomas (AIs), cross-sectional studies suggested the presence of an association between subclinical hypercortisolism (SH) and an increased prevalence of vertebral fractures (VFx) and spinal deformity index (SDI), which is a clinical index of bone quality. No longitudinal studies investigated the incidence of VFx and SDI changes over time in SH. The aim of this study was to evaluate VFx risk and SDI changes in SH over time. One-hundred-three consecutive AI patients were studied at baseline and after 12 and 24 months. Patients were divided into SH(+) (n = 27) and SH(-) (n = 76) groups on the basis of the presence of two or more among urinary free cortisol greater than 70 µg/24 hours, serum cortisol after 1-mg dexamethasone suppression test greater than 3.0 µg/dL, and adrenocorticotropic hormone (ACTH) less than 10 pg/mL in 2 or more of the 3 evaluations. At baseline and after 24 months, bone mineral density (BMD) by dual-energy X-ray absorptiometry and the presence of VFx and SDI by summing the grade of deformity for each vertebra were evaluated. At the end of follow-up, the SH(+) group showed a higher prevalence of VFx (81.5%) as compared with baseline (55.6%, p = .04) and a worsening of SDI (2.11 ± 1.85 versus 1.11 ± 1.47, p = .032) associated with SH regardless of age, gender, body mass index , BMD, baseline SDI, menopause duration [odds ratio (OR) = 12.3, 95% confidence interval (CI) 4.1-36.5, p = .001]. The incidence of new vertebral fractures was higher in the SH(+) group (48%) than in the SH(-) group (13%; p = .001). It is concluded that subclinical hypercortisolism is associated with an increased risk of VFx and a possible deterioration of bone quality.

Role of glucocorticoid receptor polymorphism in adrenal incidentalomas

Adrenal incidentalomas (AI) have been associated with and an increased prevalence of metabolic and bone complications. The N363S and BclI polymorphisms of the glucocorticoid receptor (GR) have been associated with an increased sensitivity to glucocorticoid (GC). This observational study aims to evaluate whether BclI and N363S polymorphisms play a role in the development of complications in AI. We enrolled 100 patients with AI (66 F; 34M). The presence of diabetes, arterial hypertension (AH), dyslipidaemia, osteoporosis and vertebral fracture (Fx), waist circumference and the Body Mass Index (BMI) were assessed. DNA samples were genotyped. Patients with wild-type BclI, wild-type N363S and heterozygous BclI polymorphism were classified as carriers of haplotype 1 (H1; n = 86), patients with homozygous BclI and heterozygous N363S polymorphism of GR of haplotype 2 (H2; n = 14). We found no clinical or biochemical differences between haplotype 1 and 2 groups, but a higher prevalence of the simultaneous presence of Fx plus AH in H2 patients (H2 n = 7, H1 n = 16, P = 0.01). Logistic regression analysis showed that the presence of Fx and of AH and the combination of the presence of Fx plus AH were associated with the H2 genotype regardless of the degree of cortisol secretion, age, BMI and BMD (OR 4.88, 95%CI 1.47-18.40, P = 0.05; OR 8.25, 95%CI 0.98-69.52, P = 0.05; OR 7.25, 95%CI 1.57-35.78, P = 0.011; respectively). In AI patients, the presence of the haplotype 2 of BclI and N363S is associated with the presence of AH, Fx and with the combination of Fx and AH.

Eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures

Subclinical hypercortisolism (SH) is suggested to exert a deleterious effect on bone. This effect and the role of gonadal status in male subjects are not fully elucidated. We evaluated bone mineral density (BMD) and prevalence of vertebral fractures in eugonadal male subjects with adrenal incidentalomas (AI) and without SH. This 12-month observational multicentre study was performed between January and December 2006 on inpatient basis in three referral Italian centres. Eighty-eight consecutive eugonadal male patients with AI and 90 matched control subjects were studied. All subjects underwent the determination of BMD by dual-energy X-ray absorptiometry at lumbar spine (LS) and femoral neck (FN), and spinal radiograph. In AI patients SH was diagnosed in the presence of two of the following: urinary free cortisol > 193.1 nmol/l, cortisol after 1 mg dexamethasone suppression test > 82.8 nmol/l, ACTH levels < 2.2 pmol/l. As compared to patients without SH (SH-, n = 66) and controls, patients with SH (SH+, n = 22) had lower BMD at LS (Z-score: SH+, -1.04 +/- 1.84; SH-, 0.19 +/- 1.34, Controls 0.20 +/- 1.28, P = 0.001 and FN (Z-score: SH+, -0.63 +/- 1.01; SH-, 0.01 +/- 1.01, Controls 0.26 +/- 1.06, P = 0.002) and higher prevalence of fractures (SH+, 72.7%; SH-, 21.2%, Controls 20.0%, P = 0.0001). Multivariable analyses showed that SH was associated to BMD at LS (beta = -0.378, P = 0.0001) and vertebral fractures (OR = 7.81, 95% CI 1.96-31.17, P = 0.004). In eugonadal male patients with AI, SH is associated with low BMD and high prevalence of vertebral fractures.

Bone involvement in eugonadal male patients with adrenal incidentaloma and subclinical hypercortisolism.

Adrenal incidentalomas (AI) are not associated, by definition, with clinically evident syndromes; however, some AI patients may show biochemical indexes of subclinical hypercortisolism (SH). Previous data on female AI patients indicated that SH may lead to bone loss, at least at spine. No data are available on bone involvement in samples of only AI male patients. We measured bone metabolism and bone mineral density at spine and femur by dual-energy x-ray absorptiometry in 38 consecutive eugonadal male AI patients and 38 healthy matched control subjects. Patients were subdivided according to the presence or absence of SH (group SH+ and group SH-, respectively). Mean Z-score levels of spinal bone mineral density measured by dual-energy x-ray absorptiometry were lower (P < 0.05) in group SH+ (-0.42 +/- 1.62) in comparison with group SH- (0.6 +/- 1.13) and controls (0.47 +/- 1.06). Thus, in order for the most appropriate management to be individually tailored, bone mass evaluation is strongly indicated in AI male patients with SH, irrespective of their gonadal status.

Altered Bone Mass and Turnover in Female Patients with Adrenal Incidentaloma: The Effect of Subclinical Hypercortisolism

The strategy of treatment for patients with adrenal incidentalomas (AI) may depend upon the presence of hormonal hypersecretion. Although alterations of bone turnover have been recently reported, data on bone mineral density (BMD) are not available in AI patients. We evaluated bone turnover and BMD in 32 female AI patients and 64 matched controls. Spinal and femoral BMD were similar in patients and controls. Serum bone GLA protein (6.8 ± 3.5 vs. 8.8 ± 3.2 ng/mL; P < 0.005) and PTH (48.8 ± 15.1 vs. 37.2 ± 10.9 pg/mL; P < 0.0001) were different in patients and controls. Patients were then subdivided into 2 groups: with (n = 8; group A) or without (n= 24; group B) subclinical hypercortisolism. PTH was higher (P < 0.05) in group A than in group B and in both groups than in controls (57.1 ± 13.6, 46.0 ± 14.8, and 37.2 ± 10.9 pg/mL, respectively), and bone GLA protein was lower in group A than in group B and controls (3.8 ± 2.3, 7.5 ± 3.1, and 8.8 ± 3.2 ng/mL, respectively; P < 0.05). Serum type I cross-linked C telopeptide and fasting urinary deoxypyridinoline/creatinine were not different in the three groups. BMD at each site was lower (P < 0.05) in group A than in group B and controls. Bone mass and metabolism are altered in AI patients with subclinical hypercortisolism and should be taken into account, therefore, when addressing the treatment of choice for these patients.

Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism.

The strategy of treatment for patients with adrenal incidentalomas (AI) may depend upon the presence of hormonal hypersecretion. Although alterations of bone turnover have been recently reported, data on bone mineral density (BMD) are not available in AI patients. We evaluated bone turnover and BMD in 32 female AI patients and 64 matched controls. Spinal and femoral BMD were similar in patients and controls. Serum bone GLA protein (6.8+/-3.5 vs. 8.8+/-3.2 ng/mL; P<0.005) and PTH (48.8+/-15.1 vs. 37.2+/-10.9 pg/mL; P<0.0001) were different in patients and controls. Patients were then subdivided into 2 groups: with (n = 8; group A) or without (n = 24; group B) subclinical hypercortisolism. PTH was higher (P<0.05) in group A than in group B and in both groups than in controls (57.1+/-13.6, 46.0+/-14.8, and 37.2+/-10.9 pg/mL, respectively), and bone GLA protein was lower in group A than in group B and controls (3.8+/-2.3, 7.5+/-3.1, and 8.8+/-3.2 ng/mL, respectively; P<0.05). Serum type I cross-linked C telopeptide and fasting urinary deoxypyridinoline/ creatinine were not different in the three groups. BMD at each site was lower (P<0.05) in group A than in group B and controls. Bone mass and metabolism are altered in AI patients with subclinical hypercortisolism and should be taken into account, therefore, when addressing the treatment of choice for these patients.