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Over the course of a few years, an obese 52-year-old woman with a 23-year history of hypertension developed a number of abdominal complaints including gall stones. Her blood pressure became increasingly difficult to control and she developed diabetes mellitus and suffered palpitations and headaches. It became noticeable that she had a moon face. Laboratory tests revealed hypercortisolism. CT-scan showed a large inhomogeneous mass of nine centimetres in her left adrenal gland, which was subsequently removed surgically. The histopathological diagnosis was consistent with an adenoma. After a number of months the patient developed bone and liver metastases and the diagnosis was amended to carcinoma of the adrenal cortex. She then underwent radiotherapy and chemotherapy treatment. One year after surgery she developed a pancytopenia and died. Adrenocortical carcinomas are rare tumours with an incidence of about 1-2 cases per million of the population. Symptoms are heterogeneous since both functional (hormonal overproduction) and non-functional (mass effect) tumours exist. Surgical resection is the only curative therapy. It may be difficult to distinguish between benign and malignant cortical tumours.
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PMID:[The adrenocortical carcinoma, a tumour of wide clinical diversity]. 1555 52

In patients with cancer, adrenal enlargement due to either metastatic disease or diffuse non-metastatic hyperplasia is increasingly recognized with modern imaging techniques. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by non-suppressible hypercortisolism, has also been described in neoplasia in the absence of ectopic adrenocorticotrophic hormone (ACTH) production. In the majority of cases of malignancy-associated hypercortisolism, it might be expected that the presence of malignant disease would be clinically apparent, thus rendering a detailed endocrinological evaluation of the HPA axis unnecessary. However, in the present case we describe a patient with occult malignancy presenting with bilateral adrenocortical enlargement and non-suppressible hypercortisolism that was not due to the ectopic ACTH syndrome. There were no clinical Cushingoid features other than hypertension and new-onset diabetes mellitus. Detailed diagnostic investigations for the possibility of Cushing's syndrome were performed before the underlying diagnosis of gastric adenocarcinoma eventually became apparent. Characteristics and potential mechanisms of non-suppressible hypercortisolism in cancer are discussed. We believe that this scenario will occur with greater frequency in the future, given the increasing early use of sophisticated high-resolution imaging for the evaluation of suspected intra-abdominal pathology.
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PMID:Bilateral adrenal enlargement and non-suppressible hypercortisolism as a presenting feature of gastric cancer. 1558 43

Feline endocrinopathies (excluding diabetes mellitus) include hyperthyroidism, hypothyroidism, acromegaly, hyposomatotropism, diabetes insipidus, hyperadrenocorticism, primary sex hormone-secreting adrenal tumors, primary hyperaldosteronism, pheochromocytoma, hypoadrenocorticism, hyperparathyroidism, and hypoparathyroidism. Each of these conditions will be discussed including their prevalence, cause, clinical signs, diagnosis, treatment options, and prognosis.
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PMID:Feline endocrinopathies. 1562 33

Accumulation of dorsocervical fat, or a "buffalo hump" (BH), is commonly reported in adults with HIV-associated lipodystrophy (HIVLD). The pathogenesis underlying this aspect of a syndrome characterized by loss of subcutaneous fat from other body sites is poorly understood. We aimed to identify risk factors for a BH in HIV-infected adults in cross-sectional analyses of 2 HIV-infected ambulatory populations. The first group (Australian Lipodystrophy Prevalence Survey [APS]) consisted of 1348 Australian HIV-infected adults (95% male) irrespective of changes in body composition. The second group (Lipodystrophy Case Definition [LDCD] study) comprised 417 subjects (83% male) with at least 1 reported moderate or severe feature of HIVLD. A BH was reported in 24 (2%) APS subjects and 79 (19%) LDCD study subjects. A BH was not an isolated finding. Patients with a BH had a high prevalence of other features of HIVLD, similar to lipodystrophic patients without a BH, such as facial lipoatrophy reported in 100% and 61% BH-positive subjects from the APS and LDCD study, respectively. In both groups, those with a BH had higher fasting insulin (P<or=0.007), a higher body mass index (P<or=0.003), a higher waist/hip ratio (P<or=0.001), higher limb fat (P<or=0.003), and higher systolic blood pressure (P<0.05). On multivariate analysis, higher serum insulin, systolic blood pressure, age, and duration of exposure to ritonavir were independently associated with a BH in the APS group. In the LDCD group, higher insulin, diastolic blood pressure, and duration of exposure to zidovudine were independently associated with a BH. There was no association between a BH and hyperlipidemia. These data show that a BH is associated with other physical features of the lipodystrophy phenotype and suggest that hyperinsulinemia, a feature common to HIVLD, obesity, and hypercortisolism, is an important component of this phenotype, thus warranting closer monitoring of BH-positive patients for glucose intolerance and diabetes.
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PMID:Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia. 1567

Improvements in abdominal imaging techniques have increased the detection of clinically inapparent adrenal masses, or incidentalomas (AI), the appropriate diagnosis and management of which have become a common clinical problem for health care professionals. Once an adrenal mass has been detected, the clinician needs to address two questions: 1) is the tumor hormonally active? and 2) is there any chance of the mass being malignant? The majority of AI is non-hypersecretory cortical adenomas, but an endocrine evaluation can lead to the identification of subtle hormone excess. An overnight low-dose dexamethasone suppression test, fractionated urinary or plasma metanephrine assay and, in hypertensive patients, establishing the upright plasma aldosterone/plasma renin activity ratio are recommended as preliminary screening steps. Masses greater than 4 cm are at greater risk of malignancy. Morphological imaging features may be helpful in the distinction between benign and malignant forms. Fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients to establish any metastatic disease. Adrenalectomy is indicated by evidence of a functional adrenal mass, or a suspected malignant form. We advocate adrenalectomy of subtle hypercortisolism, especially in the presence of hypertension, obesity, diabetes or osteoporosis potentially aggravated by glucocorticoid excess. A close follow-up is needed, particularly in the first year after diagnosis.
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PMID:A comprehensive approach to adrenal incidentalomas. 1576 28

The measurement of cortisol in saliva is becoming more widely accepted as a screening test for the diagnosis of hypercortisolism. Since 1986, cortisol measurement in saliva has been continuously used in our department. In this study we compared salivary cortisol profiles from proven Cushing's disease patients with profiles from healthy subjects and obese children. The purpose was to evaluate the predictive value of the method for the diagnosis of hypercortisolism and to define cut-off levels to exclude or identify hypercortisolism. Cortisol in saliva was measured in 150 Cushing's disease patients (30 children, 120 adults, ranging from age 4-70), 100 healthy subjects (55 children, 45 adults, ranging from age 6-60), and 31 children (age 7-15) with an age-related body-mass-index above the 90th percentile. Generally, five saliva samples were taken over the day at 6:00-8:00 a.m., 11:00-12:00 a.m., 4:00-6:00 p.m., 7:00-8:00 p.m., and 10:00 p.m. The samples were measured using a radioimmuno-assay (INCSTAR Corporation, Stillwater, Minnesota, USA). For healthy subjects, morning levels of cortisol in saliva between 3-19 microg/l were found. These levels dropped to levels in between <1-11 microg/l at 11:00-12:00 a.m., <1-6 microg/l at 4:00-6:00 p.m., <1-4.5 microg/l at 7:00-8:00 p.m., and <1-2.9 microg/l at 10:00 p.m. The measured values showed a correlation with age, height, and weight. In Cushing's disease patients, the circadian salivary cortisol rhythm was missing, compared to healthy subjects. There was no significant difference in salivary cortisol levels or circadian rhythm between healthy or obese children. We found a high sensitivity for the detection of hypercortisolism at the 10:00 p.m. salivary cortisol measurement. The following, age dependent cut-off levels for salivary cortisol at 10:00 p.m. were calculated for the exclusion of hypercortisolism. Age 6-10: 1.0 microg/l (specificity 100%, sensitivity 87.5%); age 11-15: 1.7 microg/l (specificity 100%, sensitivity 100%); age 16-20: 1.6 microg/l (specificity 100%, sensitivity 76.2%); age 21-60: 1.6 microg/l (specificity 100%, sensitivity 90.9%) [corrected] For the proof of Cushing's syndrome, the following age-dependent cut-off levels at 10:00 p.m. were found: age 6-10: 1.9 microg/l (specificity 100%, sensitivity 80%); age 11-15: 1.7 microg/l (specificity 100%, sensitivity 100%); age 16-20: 2.5 microg/l (specificity 100%, sensitivity 84.2%); age 21-60: 1.9 microg/l (specificity 100%, sensitivity 97.6 %) [corrected] The cortisol assessment in saliva is a sensitive and reliable method to discriminate normocortisolemic from hypercortisolemic patients. From our view, the major advantages of this method are the reliability, non-invasiveness, and use in ambulatory patients.
Exp Clin Endocrinol Diabetes 2005 Apr
PMID:Salivary cortisol measurement--a reliable method for the diagnosis of Cushing's syndrome. 1589 59

Clinically inapparent adrenal masses, or adrenal incidentalomas, are discovered inadvertently in the course of workup or treatment of unrelated disorders. 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 feed-back, in 5 to 20% of cases depending on study protocols and diagnostic criteria. A number of different alterations in the endocrine tests aimed to assess the function of the hypothalamic-pituitary-adrenal axis has been demonstrated in such patients. This heterogeneous condition has been termed as subclinical Cushing's syndrome, a definition that is more accurate than preclinical Cushing's syndrome since the evolution towards clinically overt hypercortisolism does occur rarely, if ever. The criteria for qualifying subclinical cortisol excess are controversial and we presently do not have sufficient evidence to define a gold standard for the diagnosis of subclinical Cushing's syndrome. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipoproteinemia has been described in patients with subclinical Cushing's syndrome; however, there is not evidence-based demonstration of its long-term complications and, consequently, the management of this condition is largely empirical. Either adrenalectomy or careful observation associated with treatment of metabolic syndrome has been suggested as treatment options because data are insufficient to indicate the superiority of a surgical or nonsurgical approach to manage patients with subclinical hyperfunctioning adrenal cortical adenomas.
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PMID:Subclinical Cushing's syndrome. 1613

The frequency of hypercalciuria is increasing in western countries with an incidence of nephrolithiasis which can reach 13%. Hypercalciuria appears as an alteration of the calcium transport system (kidney, bowel, bone) which is regulated by calcitriol and parathormone. The aim of this review was to screen etiologies of hypercalciuria taking into account recent genetic advances (calcium epithelial channel and calcium sensing receptor). Hypercalciuria may be favored by nutritional causes (diet rich in calcium, sodium, carbohydrates, proteins, poor in phosphates and potassium). It may also be related to an increase in calcium absorption (vitamin D excess, primary hyperparathyroidism, sarcoidosis, lymphoma, estrogens, and certain genetic causes), an increase in osteoresorption (bone metastasis, myeloma, Paget, hyperthyroidism, immobilization, hypercortisolism and corticosteroid therapy), or a decrease of kidney tubular resorption (diuretics, Cacci and Ricci, acromegally, Bartter, familial dominant hypocalcemia, Fanconi, Dent, familial hypomagnesemia-hypercalciuria syndrome, type 1 distal tubular acidosis, pseudohypoaldosteronism, diabetes). If no cause is identified, persistence of hypercalciuria after instituting a correct diet is defined as idiopathic hypercalciuria. Treatment of the cause is essential in secondary hypercalciuria, in addition to diet (low sodium intake, normocalcic diet, hydration), associated with thiazide diuretics and biphosphonates if necessary.
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PMID:[Hypercalciuria]. 1635 16

Chronic cortisol hypersecretion causes central obesity, hypertension, insulin resistance, dyslipidemia, protrombotic state, manifestations which form a metabolic syndrome in all patients with Cushing's syndrome. These associated abnormalities determine an increased cardiovascular risk not only during the active phase of the disease but also long after the "biomedical remission". Clinical management of these patients should be particularly careful in identifying global cardiovascular risk. Considering that remission from hypercortisolism is often difficult to achieve care and control of all cardiovascular risk factors should be one of the primary goals during the follow up of these patients. Extending the indications of the recent consensus on Cushing's syndrome, we suggest to carry out an OGTT to avoid underestimation of diabetes mellitus, an echocardiography and Doppler ultrasonography of the epiaortic vessels in all patients at diagnosis and during follow-up.
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PMID:Cardiovascular risk in Cushing's syndrome. 1641 38

The majority of pituitary tumors that cause Cushing's disease are small (<1 cm diameter), and most disease morbidity is due to the effects of elevated, non-suppressible, ACTH levels that these tumors secrete. Tumor-derived ACTH leads to adrenal-derived steroid hypersecretion and results in many disabling and sometimes life-threatening symptoms including abnormal fat deposition, skin thinning, psychological disturbances, hypertension, diabetes, osteoporosis and muscle weakness. Cushing's disease is associated with high morbidity and ultimately mortality. In experienced specialized centers, 70% of corticotroph microadenomas can be successfully resected by transsphenoidal pituitary surgery. However, surgical "cure" rates for larger ACTH-secreting pituitary tumors are achieved in only 30% of cases, and recent reports highlight a significant recurrence rate after longer term follow-up even in smaller tumors. Post-surgical persistence of ACTH hypersecretion may require pituitary-directed radiation, but this treatment may take some time to be effective, and like extensive surgical pituitary tumor resection, ultimately leads to partial- or total hypopituitarism in approximately 80% of cases. Although hypercortisolism may be completely resolved by adrenalectomy, this procedure does not suppress, and may act as a stimulus to pituitary tumor growth, and is associated with other co-morbidity. Although some currently available drug-based treatments for Cushing's disease effectively control hypercortisolism, their drawback has been that they do not impact on pituitary tumor growth. Recent studies have identified the potential utility of peroxisome-proliferator activating receptor-gamma (PPAR-gamma) novel ligands in in vitro, and in vivo Cushing's disease models, and have paved the way for early clinical studies to develop novel therapeutic approaches in Cushing's disease.
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PMID:PPAR-gamma in Cushing's disease. 1641 39


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