Francesca Coletti

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 microg per 24 h (193 nmol per 24 h), cortisol after 1 mg dexamethasone suppression test greater than 3.0 microg/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.

Cortisol Secretion in Patients With Type 2 Diabetes Relationship with chronic complications

OBJECTIVE—The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS—In all subjects, we evaluated ACTH at 8:00 a.m. in basal conditions and serum cortisol levels at 12:00 p.m. (F24) and at 9:00 a.m. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n = 53) or presence (group 2, n = 117) of diabetes complications. RESULTS—In group 2, UFC (125.2 ± 4.6 nmol/24 h) and F24 (120.6 ± 4.1 nmol/l) were higher than in group 1 (109.2 ± 6.8 nmol/24 h, P = 0.057, and 99.7 ± 6.1 nmol/l, P = 0.005, respectively) and in nondiabetic patients (101.7 ± 5.9 nmol/24 h, P = 0.002, and 100.3 ± 5.3 nmol/l, P = 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R = 0.345; P < 0.0001) and diabetes duration (R = 0.39; P < 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin. CONCLUSIONS—In type 2 diabetic subjects, hypothalmic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications.

Bone Mineral Density, Prevalence of Vertebral Fractures, and Bone Quality in Patients with Adrenal Incidentalomas with and without Subclinical Hypercortisolism: An Italian Multicenter Study

CONTEXT In patients with adrenal incidentalomas and subclinical hypercortisolism (SH), the factors influencing bone and the prevalence of vertebral fractures are debated. Spinal deformity index (SDI), which reflects bone quality, has never been evaluated. OBJECTIVE The objective of the study was to investigate in these patients SDI and factors influencing the prevalence of fractures. DESIGN This was a retrospective, multicenter study. SETTING The study was conducted on an in- and outpatient basis. PATIENTS Patients included 287 adrenal incidentaloma patients (111 eugonadal males, 31 premenopausal, 145 postmenopausal females) and 194 controls (90 eugonadal males, 29 premenopausal, 75 postmenopausal females). MAIN OUTCOME MEASURE Bone mineral density (BMD) was measured by dual X-ray absorptiometry at lumbar spine and femoral neck. By radiograph each vertebra was assessed as intact (grade 0) or grade 1 (20-25%), 2 (25-40%), or 3 (>40%) deformity; SDI was calculated by summing the grade of deformity for each vertebra. SH was diagnosed in the presence of at least two of the following: urinary free cortisol greater than 70 microg per 24 h (193.1 nmol/liter), cortisol after 1-mg dexamethasone test greater than 3.0 microg/dl (>82.8 nmol/liter), ACTH less than 10 pg/ml (<2.2 pmol/liter). RESULTS BMD was significantly lower in SH+ than SH- patients and controls (lumbar spine -0.73 +/- 1.43, 0.17 +/- 1.33, 0.12 +/- 1.21, respectively; femoral neck -0.37 +/- 1.06, 0.07 +/- 1.09, 0.17 +/- 1.02). Patients with SH had higher fracture prevalence and SDI than those without SH and controls (70.6, 22.2, 21.8%, respectively, P < 0.0001; 0.31 +/- 0.68, 0.39 +/- 0.93, 1.35 +/- 1.27, respectively, P < 0.0001). Fractures and SDI were associated with SH (odds ratio 7.27, 95% confidence interval 3.94-13.41, P = 0.0001; beta = 0.352, t = 6.241, P = 0.0001, respectively) regardless of age, BMD, menopause, and gender. CONCLUSION SH is associated with low BMD, high fracture prevalence, and reduced bone quality as measured by SDI.

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.

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.

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-pituitary-adrenal (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 microg/24 h, cortisol after 1-mg dexamethasone suppression test (1 mg-DST)>3.0 microg/dl, ACTH levels<10 pg/ml, midnight serum cortisol (MSC)>5.4 microg/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 microg/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 2.54-42.95, 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.

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

Objective  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.

d3-Growth hormone receptor polymorphism in acromegaly: effects on metabolic phenotype.

Objective  A common polymorphic variant of the growth hormone receptor (GHR) is because of genomic deletion of exon 3 and has been linked with increased responsiveness to exogenous GH. The impact of this polymorphism in acromegaly, a disease characterized by endogenous excess of GH and partial loss of IGF‐I feedback on tumoural GH secretion, is not clear. The aim of this study was to investigate possible influences of d3GHR on the GH/IGF‐I relationship and metabolic parameters in acromegaly.

Detection of small bowel tumors by videocapsule endoscopy in patients with acromegaly

The prevalence of colon polyposis and malignancies is increased in acromegalic patients as compared to the general population. An epidemiological study suggests a high prevalence also of small bowel (SB) tumors that nowadays may be detected by videocapsule endoscopy (VCE). The aim of the study was to assess the prevalence of SB neoplasms using VCE in acromegalic patients in comparison to control subjects and to correlate it with cancer risk factors and acromegaly-related parameters. Eighteen acromegalic patients (6 males and 12 females, age±SD: 54±10 yr), 5 cured after surgery (followed by radiotherapy in 3 cases) and 13 on pharmacological treatment were enrolled, and 36 sex- and age-matched non-acromegalic subjects served as a control group. Cancer risk factors, duration of acromegaly, GH and IGF-I levels, IGF binding protein 3 and IGF-II concentrations, metabolic parameters, tumor markers, colonic lesions by total colonoscopy, and SB lesions by VCE were investigated. VCE images suggestive of SB lesions were detected in 5/36 controls [14%, 4 described as gastrointestinal stromal nodular tumors (GIST), and 1 as polyp] and in 5/18 acromegalic patients [28%, 2 GIST and 3 polyps]. In acromegaly, the calculated relative risk for all SB lesions was 1.69 [95% confidence interval (CI): 0.78–3.65], while the relative risk for SB polyps was 2.50 (95% CI: 1.23–5.07). The effective duration of active disease was longer in patients with positive than in those with negative VCE (112±89 vs 49±40 months, p=0.06). In conclusion, these preliminary results suggest that acromegalic patients might have a high risk of SB polyp development. VCE might be a useful adjunctive diagnostic tool in acromegaly.

Un caso complesso di iponatremia

guidata con inaspettata diagnosi is tologica di epatocarcinoma. L’aldosterone e la renina risultavano nella norma, con un ACTH di 150 pg/ml e un cort isolo di 4 μg/dl. L’ipotesi diagnostica finale era pertanto di iponatremia a verosimile genesi multifattoriale (sindrome da inappropriata secrezione di ADH paraneoplastica, iniziale iposurrenalismo primario da metastasi surrenaliche bilaterali con ancora conservata funzione dell’asse renina-angiotensina-aldosterone e secondo i colleghi oncologi, probabile duplice neoplasia primitiva (polmonare ed epatica). Una donna di 86 anni giungeva al Pronto Soccorso per vomito ed episodio lipotimico. La paziente, euvolemica, era in follow-up per un nodulo polmonare sospetto, pur in assenza di diagnosi istologica. Si riscontrava un’iponatremia ipotonica (Na 124 mEq/l, osmolarità plasmatica 248 mOsm/kg) con potassiemia normale (4,7 mEq/l), osmolari tà urinaria di 427 mOsm e sodiuria di 94 mEq/l. Il dosaggio del cortisolo basale risultava ai limiti inferiori (4,7 μg/dl). Veniva posta diagnosi di SIAD paraneoplastica e somministrata un’unica dose di tolvaptan 15 mg, con pronta risalita dei livelli di sodio. Una TAC torace mostrava una massa polmonare di 3 cm (Figura 1) , aumentata di dimensioni rispetto ai controlli precedenti, associata ad alcuni linfonodi di aspetto metastatico in sede mediastinica. A livello epatico si evidenziavano alla tomografia assiale computerizzata (TAC) due lesioni localizzate nel VII e IV segmento, di 2,3 e 1,5 cm, interpretate inizialmente come secondarie (Figura 2). Era inoltre presente un ingrandimento di entrambi i surreni , specie del destro, che aveva un diametro massimo di 4,7 cm, di significato sostitutivo secondario (Figura 3). La lesione epatica del IV segmento