a comprehensive approach to adrenal incidentalomas

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 4cm 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

The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp(-) somatotropinomas

Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp(-) somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load

Cyclic Cushing's syndrome: an overview.

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Different therapeutic options in patients with Cushing's syndrome due to bilateral macronodular adrenal hyperplasia

Bilateral macronodular adrenal hyperplasia (BMAH) is a relatively rare cause of Cushing's syndrome (CS). In recent years, growing evidence has shown that steroidogenesis is regulated by aberrant G-protein-coupled receptors (GPCR) expression and their ligands, in a significant proportion of patients with BMAH. The screening of patients with overt or subclinical CS demonstrate the frequent expression of several GPCR that opened the option to potential therapeutic applications. Thus, several studies have demonstrated that targeting the involved receptor with specific antagonists, may result in a more or less effective control of cortisol excess. Bilateral adrenalectomy has traditionally been considered the treatment of choice for BMAH. However, unilateral adrenalectomy has been recently proposed as an alternative in selective patients to avoid the long-term necessity of gluco/mineralocorticoid replacement. Adrenal steroidogenesis inhibitors remains a valid option when medical treatment is needed due to high surgical risk

The pathogenic role of the GIP/GIPR axis in human endocrine tumors: emerging clinical mechanisms beyond diabetes

The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone produced in the gastrointestinal tract in response to nutrients. GIP has a variety of effects on different systems, including the potentiation of insulin secretion from pancreatic \u3b2-cells after food intake (i.e. incretin effect), which is probably the most important. GIP effects are mediated by the GIP receptor (GIPR), a G protein-coupled receptor expressed in several tissues, including islet \u3b2-cells, adipocytes, bone cells, and brain. As well as its involvement in metabolic disorders (e.g. it contributes to the impaired postprandial insulin secretion in type 2 diabetes (T2DM), and to the pathogenesis of obesity and associated insulin resistance), an inappropriate GIP/GIPR axis activation of potential diagnostic and prognostic value has been reported in several endocrine tumors in recent years. The ectopic GIPR expression seen in patients with overt Cushing syndrome and primary bilateral macronodular adrenal hyperplasia or unilateral cortisol-producing adenoma has been associated with an inverse rhythm of cortisol secretion, with low fasting morning plasma levels that increase after eating. On the other hand, most acromegalic patients with an unusual GH response to oral glucose suppression have GIPR-positive somatotropinomas, and a milder phenotype, and are more responsive to medical treatment. Neuroendocrine tumors are characterized by a strong GIPR expression that may correlate positively or inversely with the proliferative index MIB-1, and that seems an attractive target for developing novel radioligands. The main purpose of this review is to summarize the role of the GIP/GIPR axis in endocrine neoplasia, in the experimental and the clinical settings

Therapeutic strategies for Cushing's syndrome: An update

ntroduction: Endogenous Cushing's syndrome (CS) is a severe clinical condition caused by excess cortisol secretion. The treatment goals (with surgery, radiotherapy or medical therapy) are to normalize cortisol levels, reverse the clinical symptoms and remove the secreting neoplasm. Areas covered: Medical treatments are increasingly used in CS, especially when surgery fails or is not indicated, or while waiting for radiotherapy to take effect. This review summarizes the different medical approaches for treating CS (adrenal- or pituitary-directed drugs, glucocorticoid receptor antagonist), alone or in combination. Expert opinion: Adrenal steroidogenesis inhibitors have been the mainstay of medical treatment for CS: the most used are ketoconazole (or fluconazole), which inhibits adrenal steroidogenic enzymatic activities; metyrapone and LCI699 that inhibit 11 beta-hydroxylase (the latter is still an experimental compound); mitotane, used in adrenocortical carcinoma. The available glucocorticoid receptor antagonist is mifepristone, recently approved for use in controlling hyperglycemia secondary to hypercortisolism. There has recently been a lot of interest in using agents directly targeting the pituitary corticotroph cells to reduce Adreno Cortico Tropic Hormone secretion and, if possible, control the volume of pituitary adenomas. This is because corticotroph cells contain dopamine receptors (targets of bromocriptine and cabergoline), retinoic acid receptors, PPAR-gamma or somatostatin receptors, the target of the first drug developed and approved for Cushing's disease (pasireotide)