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

Torlontano, Massimo; Chiodini, Iacopo; Pileri, Mauro; Guglielmi, Giuseppe; Cammisa, M; Modoni, Sergio; Carnevale, Vincenzo; Trischitta, Vincenzo; Scillitani, Alfredo

doi:10.1210/jcem.84.7.5856

Cited by 82 publications

(94 citation statements)

References 35 publications

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“…This is in contrast with the results of previous studies, in which SH þ patients showed a reduced BMD. (7,8,12,13,22) This discordance may be due to the fact that the patients included in this study were older (65.0 AE 8.7 years) than those previously studied (ref. 7: 54.0 AE 18.4 years; ref.…”

Section: Discussionmentioning

confidence: 72%

“…In recent years, the majority (5)(6)(7)(8)(9)31) but not all (10) cross-sectional studies have suggested that SH is associated with an increased prevalence of osteoporosis. However, only one longitudinal study specifically investigated the rate of spinal and femoral bone loss in female patients with adrenal incidentalomas so far.…”

Section: Discussionmentioning

confidence: 99%

“…(5)(6)(7)(8)(9)(10)(11)(12)(13) Moreover, data of the incidence of vertebral fractures in these patients are lacking. Some authors have suggested that in patients with SH, vertebral fracture prevalence was increased regardless of bone mineral density ORIGINAL ARTICLE J JBMR (BMD) (12,13) and that the fractures occurred despite a normal or only osteopenic BMD in the most of patients.…”

Section: Introductionmentioning

confidence: 99%

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

Morelli

Eller-Vainicher

Salcuni

et al. 2011

Journal of Bone and Mineral Research

121

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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 þ (n ¼ 27) and SH -(n ¼ 76) groups on the basis of the presence of two or more among urinary free cortisol greater than 70 mg/24 hours, serum cortisol after 1-mg dexamethasone suppression test greater than 3.0 mg/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 þ group showed a higher prevalence of VFx (81.5%) as compared with baseline (55.6%, p ¼ .04) and a worsening of SDI (2.11 AE 1.85 versus 1.11 AE 1.47, p ¼ .032) associated with SH regardless of age, gender, body mass index , BMD, baseline SDI, menopause duration [odds ratio (OR) ¼ 12.3, 95% confidence interval (CI) 4.1-36.5, p ¼ .001]. The incidence of new vertebral fractures was higher in the SH þ group (48%) than in the SH -group (13%; p ¼ .001). It is concluded that subclinical hypercortisolism is associated with an increased risk of VFx and a possible deterioration of bone quality. ß

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Morelli

Eller-Vainicher

Salcuni

et al. 2011

Journal of Bone and Mineral Research

121

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“…Differences in the devices used to estimate bone density and in selection criteria of either patients or controls, along with the small number of subjects studied, are likely explanations for the divergent results. An increased risk of osteoporosis has been documented by the most recent studies that addressed this issue (37)(38)(39)(40). Moreover, in a recent study an increased prevalence of vertebral fractures in women with subclinical Cushing' syndrome was found, corroborating the notion that even subtle glucocorticoid excess can exert a detrimental effect on bone quality, particularly in condition of estrogen deficiency (41).…”

Section: Natural Historymentioning

confidence: 70%

Subclinical Cushing's Syndrome

et al. 2004

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Subclinical Cushing's syndrome (CS) is attracting increasing interest since the serendipitous discovery of an adrenal mass has become a rather frequent event owing to the routine use of sophisticated radiologic techniques. Cortical adenoma is the most frequent type of adrenal incidentaloma accounting for approximately 50% of cases in surgical series and even greater shares in medical series. Incidentally discovered adrenal adenomas may secrete cortisol in an autonomous manner that is not fully restrained by pituitary feedback, in 5 to 20% of cases depending on study protocols and diagnostic criteria. The criteria for qualifying subclinical cortisol excess are controversial and presently there is no consensus on a gold standard for the diagnosis of this condition. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipemia has been described in patients with subclinical CS; however, there is still no clear demonstration of the long-term complications of this condition whose management remains largely empirical. Either adrenalectomy or careful observation associated with treatment of the metabolic syndrome have been suggested as treatment options. RESUMO Síndrome de Cushing Subclínica.A síndrome de Cushing subclínica (SCS) tem atraído interesse cada vez maior desde que a descoberta casual de uma massa adrenal se tornou um evento freqüente devido ao emprego rotineiro de técnicas sofisticadas de imagem. O adenoma cortical é o tipo mais freqüente de incidentaloma adrenal, correspondendo a cerca de 50% dos casos em séries cirúrgicas e até mais do que isso em séries médicas. Adenomas adrenais descobertos incidentalmente podem secretar cortisol de maneira autônoma ou não controlada totalmente pelo feedback hipofisário, em 5 a 20% dos casos, dependendo do protocolo de estudo e dos critérios diagnósticos. Os critérios para qualificar um excesso subclínico de cortisol são controversos e atualmente não existe consenso a respeito de "padrão ouro" para o diagnóstico dessa condição. Em pacientes com SCS, tem sido descrita uma freqüência elevada de hipertensão, obesidade central, intolerância à glicose, diabetes e hiperlipemia; entretanto, ainda não existe uma evidente demonstração de complicações a longo prazo dessa condição, cujo manejo permanece amplamente empírico. Tanto a adrenalectomia como a observação cuidadosa, associada com o tratamento da síndrome metabólica, têm sido sugeridos como opções terapêuticas.

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“…Several studies have suggested that SH patients are at higher risk of complications of overt hypercortisolism, (2,3) such as osteoporosis (4)(5)(6)(7)(8)(9)(10) and vertebral fractures. (11)(12)(13)(14) Interestingly, some previous data has shown that in SH, as in overt hypercortisolism, the risk of fractures is scarcely predicted by bone mineral density (BMD), because fractures occurred in more than 40% of these patients despite a normal or only ''osteopenic'' BMD.…”

Section: Introductionmentioning

confidence: 99%

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

Eller-Vainicher

Morelli

Ulivieri

et al. 2012

Journal of Bone and Mineral Research

127

128

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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 mg/24 h (193.1 nmol/L); (2) cortisol after 1-mg dexamethasone suppression test (1-mg DST) >3.0 mg/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 ¼ 34) had lower LS-BMD (À0.31 AE 1.17), FT-BMD (À0.29 AE 0.91), and TBS (À3.18 AE 1.21) than patients without SH (n ¼ 68, 0.31 AE 1.42, p ¼ 0.03; 0.19 AE 0.97, p ¼ 0.01; À1.70 AE 1.54, p < 0.0001, respectively) and controls (0.42 AE 1.52, p ¼ 0.02; 0.14 AE 0.76, p ¼ 0.02; À1.19 AE 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1-mg DST (b ¼ À0.26, t ¼ À2.79, p ¼ 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 ¼ 0.001) and with the cluster low TBS plus low LS-BMD (OR, 4.37; 95% CI, 1.71-11.4, p ¼ 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, > À1.5) 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 ¼ 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. ß

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

Cited by 82 publications

References 35 publications

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

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

Subclinical Cushing's Syndrome

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

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