Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow-up.

OBJECTIVE: Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR) and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up. DESIGN: Prospective study in a tertiary hospital. PATIENTS AND MEASUREMENTS: Seventy-one patients with AI [51 nonfunctioning (NFAI) and 20 ACS] and 5·54 ± 1·7 years follow-up underwent testing for ACS and oral glucose tolerance test to determine IR indices and adrenal imaging. RESULTS: At follow-up, 16/51 (31%) NFAI patients converted to ACS, while two with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary-free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9·8% NFAI and 15% ACS, respectively) and 14 IR (17·6% NFAI and 25% ACS, respectively). Adenoma size increased from 2·1 ± 0·8 to 2·3 ± 0·8 cm, whereas IR correlated with postdexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, C-ACS and ACS patients. CONCLUSIONS: New-onset ACS developed in 31% patients with NFAI, whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients.

A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism.

CONTEXT: Primary aldosteronism (PA) is the most common cause of endocrine hypertension that is diagnosed following a two-step process: an initial screening test, based on the serum aldosterone-to-renin ratio (ARR), followed by a relatively laborious and time-consuming confirmatory test to document autonomous aldosterone (ALD) secretion. OBJECTIVE: The aim of this study is to develop a simple overnight test for the early and definite diagnosis of PA. PATIENTS AND METHODS: Totally, 148 hypertensive patients underwent a fludrocortisone-dexamethasone suppression test (FDST) and the new overnight diagnostic test (DCVT) using pharmaceutical RAAS (renin-angiotensin-aldosterone system) blockade with dexamethasone, captopril and valsartan. RESULTS: Of the 148 patients, 45 were diagnosed as having PA and they all normalized their elevated blood pressure (BP) after administration of spironolactone or eplerenone. The remaining 103 patients were considered as having essential hypertension and served as controls. Using ROC analysis, the estimated sensitivity and specificity were 91 and 100%, respectively, for the post-FDST ARR, whereas 98% and 89% and 100% and 82% for the post-DCVT ARR and post-DCVT ALD, respectively, with selected cutoffs of 0.32ng/dL/µU/mL and 3ng/dL respectively. However, considering these cutoffs simultaneously, the estimated sensitivity and specificity were 98 and 100% respectively. Applying these cutoffs, the diagnosis of PA was confirmed in 44 (98%) of the 45 patients who were considered to have the disease. CONCLUSIONS: In this study, a highly sensitive and specific, low-cost, rapid, safe, and easy-to-perform diagnostic test (DCVT) for PA is described, which could be utilized on an outpatient basis potentially substituting conventional laborious testing.

Evidence of primary aldosteronism in a predominantly female cohort of normotensive individuals: a very high odds ratio for progression into arterial hypertension.

CONTEXT: Primary aldosteronism (PA) is an established cause of hypertension, whereas high-normal serum aldosterone levels have been linked to an increased risk for hypertension. OBJECTIVE: We aimed to define the post-fludrocortisone-dexamethasone suppression test (FDST) normal cutoff values of aldosterone and the aldosterone to renin ratio and evaluate the presence of PA in normotensive individuals. DESIGN: This study was designed as a case-control study. SETTING: The study was performed in a tertiary general hospital. PATIENTS: One hundred normotensive participants (80 females), mean age 53 years, were studied. MAIN OUTCOME MEASURES: All participants underwent baseline biochemical and hormonal evaluation, FDST, and adrenal computerized tomography. Blood pressure was assessed at baseline and after 5 years. RESULTS: Sixty-nine participants with normal adrenal computerized tomography who remained normotensive after 5 years were used as a control population to calculate the cutoff values of adequate aldosterone suppression. PA was defined as a combination of post-FDST aldosterone to renin ratio of 0.93 ng/dL · µU/mL or greater (100% sensitivity and 96% specificity) and post-FDST aldosterone of 2.96 ng/dL or greater (100% sensitivity and 61% specificity on receiver-operating characteristic analysis). Thirteen of 100 participants had PA at baseline and 11 (85%) developed hypertension, whereas only 20 of 87 without PA (23%) developed hypertension at 5 years [odds ratio (OR) 18.42, 95% confidence intervals (CI) 3.76-90.10, P < .0001]. Logistic regression analysis showed a positive relation of PA [odds ratio (OR) 16.30, confidence interval (CI) 1.78-150.30, P = .01] and a negative relation of serum potassium (OR 0.39, CI 0.19-0.79, P = .01) with the development of hypertension. CONCLUSIONS: Normotensive PA represents a clinical entity referring to normotensive individuals with PA who are at increased risk for hypertension.

Nonalcoholic fatty liver disease in subjects with adrenal incidentaloma.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pattern of adrenal hormonal secretion in patients with adrenal adenomas: the relevance of aldosterone in arterial hypertension.

CONTEXT: Approximately 10% of hypertensives are considered to exhibit autonomous aldosterone secretion (AAS). Although adrenal incidentalomas (AI) can be found in up to 19% of hypertensive individuals, data on the incidence of AAS in hypertensive patients with AI remain scarce. OBJECTIVE: The aim was to study adrenal aldosterone (ALD) secretory pattern in patients with adrenal adenomas with and without arterial hypertension. DESIGN AND SETTING: We conducted a case-control study in a tertiary general hospital. PATIENTS AND MAIN OUTCOME MEASURES: We investigated 72 normotensive subjects with normal adrenal morphology and 191 subjects divided in three groups: 46 normotensive individuals with an AI (NAI), 89 hypertensive patients with an AI (HAI), and 56 hypertensive patients with an adrenal adenoma identified after investigation for arterial hypertension (HAA). Evaluation of autonomous cortisol secretion was based on a low-dose dexamethasone suppression test. Autonomous ALD secretion was based on a modified saline infusion test (MSI). Normal cutoff levels were obtained from the control matched population. RESULTS: Post-MSI ALD levels and the ALD/renin (REN) ratios were significantly elevated in HAI and HAA patients compared to NAI subjects. To evaluate the prevalence of AAS, we applied the combination of post-MSI ALD level and the ALD/REN ratio simultaneously (post-MSI cutoffs, ALD levels, 2.41 ng/dl; ALD/REN ratio, 0.35 ng/dl/µU/ml). Based on these cutoffs, 12% of NAI, 36.4% of HAI, and 54.2% of HAA patients had AAS. The prevalence of autonomous cortisol secretion did not differ among the three groups. CONCLUSIONS: Using a MSI test, we found a remarkably increased prevalence of AAS in hypertensive patients with adrenal adenomas, even when the latter represented an incidental finding.

Pattern of adrenal morphology and function in patients with acromegaly.

BACKGROUND: Acromegaly is well known to induce hypertrophic and hyperplastic changes in various organs and is commonly accompanied by arterial hypertension. In our study, we assess the adrenal morphology and function in a series of patients with acromegaly and possible associations with the activity of the disease and arterial hypertension. MATERIALS AND METHODS: Sixty patients with acromegaly, admitted to two endocrinology departments in the time period 2005-2010, were studied prospectively. Basal IGF-1 and growth hormone levels after oral glucose tolerance test were used to assess the disease activity. All subjects underwent adrenal CT scan, basal adrenal hormonal investigation and evaluation with 24-h urinary free cortisol and cortisol levels following low-dose dexamethasone suppression test. In 33 acromegalics, the 'modified' saline infusion test (MSI), i.e. saline infusion after dexamethasone administration, was performed to identify autonomous aldosterone (ALD) secretion. RESULTS: Abnormal adrenal morphology was present in 48% of our patients, and a significant association was found between the presence of arterial hypertension and adrenal morphology. Among patients with adrenal morphological changes, 55% exhibited no adrenal secretory hyperactivity, 34% autonomous cortisol, 7% ALD and 4% combined autonomous cortisol and ALD secretion, when applying recently proposed modified cut-off levels compared to widely used criteria. An increased prevalence of autonomous ALD secretion was shown among the subgroup of patients with acromegaly tested with MSI. CONCLUSIONS: This study provides evidence of an increased prevalence of anatomic and functional adrenal alterations in patients with acromegaly; further studies will clarify the importance of evaluating these subjects with baseline hormonal investigation along with dynamic testing and modified cut-offs.

Coexistence of tumor-induced osteomalacia and primary hyperparathyroidism.

OBJECTIVE: To present an unusual case of coexisting tumor-induced osteomalacia (TIO) and primary hyperparathyroidism (PHPT). METHODS: We report the clinical features, imaging studies, and the results of laboratory investigations before and after surgical resection of both a soft-tissue tumor and a parathyroid adenoma. RESULTS: A 44-year-old woman was referred to the endocrinology department with a diagnosis of PHPT accompanied by unusually severe hypophosphatemia, despite having received treatment with cinacalcet. Debilitating muscle weakness and bone pain, severe phosphaturia and hypophosphatemia, inappropriately normal calcitriol, and elevated fibroblast growth factor-23 and intact parathyroid hormone levels raised the suspicion of coexisting TIO and PHPT. Imaging studies were negative, but histologic characteristics of a palpable subcutaneous mass from the patient's thigh revealed a phosphaturic mesenchymal tumor. Complete remission after surgical removal of both the soft-tissue tumor and the parathyroid adenoma confirmed the diagnosis. CONCLUSION: The coexistence of TIO and PHPT has not been described before and can cause life-threatening hypophosphatemia. Diagnosis and localization of the tumor is of paramount importance since surgery is the treatment of choice for both TIO and PHPT.