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At least 19 recordsLinked to original sources
PubMed2024

Molecular characterization of archival adrenal tumor tissue from patients with ACTH-independent Cushing syndrome.

Cushing syndrome represents a multitude of signs and symptoms associated with long-term and excessive exposure to glucocorticoids. Solitary cortisol-producing adenomas (CPAs) account for most cases of ACTH-independent Cushing syndrome (CS). Technological advances in next-generation sequencing have significantly increased our understanding about the genetic landscape of CPAs. However, the conventional approach utilizes fresh/frozen tissue samples, which are not routinely available for most clinical adrenal adenoma specimens. This coupled with the fact that CS is relatively rare reduces the accessibility to CPAs for research. In order to circumvent this issue, our group recently developed a sequencing strategy that allowed the use of formalin-fixed paraffin-embedded (FFPE) CPA samples for mutation analysis. Our streamlined approach includes the visualization and genomic DNA (gDNA) capture of the cortisol-producing regions in the tumor using immunohistochemistry (IHC)-guided techniques followed by targeted and/or whole-exome sequencing analysis. This approach has the advantage of using both prospective and retrospective CPA cohorts since FFPE pathologic specimens are routinely banked. This review discusses this advanced approach using IHC-guided gDNA capture of pathologic tissue followed by NGS as a preferred method for mutational analysis of CPAs.

Humans↗
PubMed2001

Retinoic acid prevents experimental Cushing syndrome.

Cushing syndrome is caused by an excess of adrenocorticotropic hormone (ACTH) production by neuroendocrine tumors, which subsequently results in chronic glucocorticoid excess. We found that retinoic acid inhibits the transcriptional activity of AP-1 and the orphan receptors Nur77 and Nurr1 in ACTH-secreting tumor cells. Retinoic acid treatment resulted in reduced pro-opiomelanocortin transcription and ACTH production. ACTH inhibition was also observed in human pituitary ACTH-secreting tumor cells and a small-cell lung cancer cell line, but not in normal cells. This correlated with the expression of the orphan receptor COUP-TFI, which was found in normal corticotrophs but not in pituitary Cushing tumors. COUP-TFI expression in ACTH-secreting tumor cells blocked retinoic acid action. Retinoic acid also inhibited cell proliferation and, after prolonged treatment, increased caspase-3 activity and induced cell death in ACTH-secreting cells. In adrenal cortex cells, retinoic acid inhibited corticosterone production and cell proliferation. The antiproliferative action and the inhibition of ACTH and corticosterone produced by retinoic acid were confirmed in vivo in experimental ACTH-secreting tumors in nude mice. Thus, we conclude that the effects of retinoic acid combine in vivo to reverse the endocrine alterations and symptoms observed in experimental Cushing syndrome.

Adrenocorticotropic Hormone↗
PubMed1995

[Clinical and preclinical aspects of adrenal Cushing syndrome].

Cushing's syndrome of adrenal origin encompasses different entities: besides the occurrence of adenoma and carcinoma, a not homogeneous group includes the ACTH-independent macro- or micronodular bilateral hyperplasia and the familial pigmented nodular hyperplasia (Carney's syndrome). Moreover, isolated cases of immunological origin and food-dependence have recently described. On clinical grounds no major characteristics may help to identify the adrenal origin of Cushing's syndrome, except for few situations as carcinoma or nodular dysplasia. Laboratory investigations of patients with adrenocortical tumor are based on ACTH and cortisol determinations in basal conditions and in response to high dose dexamethasone and CRH tests. However, isolated diagnostic problems may occur, as the presence of a black adrenocortical adenoma or the uncommon persistence of a circadian rhythmicity of glucocorticoid secretion. The evaluation of new markers of bone turnover (BGP, ICTP) and of collagen turnover (PIIINP) confirms the existence of corticosteroid-induced bone and collagen damages and may also be a useful prognostic index after treatment. Although up to now food-dependent Cushing's syndrome appears to be very rare, the adrenocortical sensitivity to GIP has been investigated in patients with either pituitary Cushing's disease, or clinically silent adrenal masses. No evidence of GIP-dependent cortisol secretion during the peptide infusion or after endogenous stimulation by OGTT was observed in any case. Since the wide availability of sensitive and noninvasive imaging techniques (CT and NMR), in recent years the finding of incidentalomas has become fairly common. In patients with incidentaloma abnormalities of the endocrine function are frequently encountered, and the "preclinical" Cushing's syndrome is increasingly recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMedDate not supplied

[Medical treatment of Cushing syndrome].

Cushing's syndrome is a serious endocrine condition for which no treatment has been proven fully satisfactory at least for its pituitary dependent form (Cushing's disease). Indeed, despite some advances in pharmacology (cyproheptadine, bromocriptine, lisuride) and in surgical and radiation procedures at pituitary level, a definitive cure is often delayed. The inhibitors of steroids synthesis (ketoconazole, aminoglutethimide, metyrapone, mitotane) are still very valuable tools in its management as a palliative treatment.

Cushing Syndrome↗
PubMed1991

A case of neonatal McCune-Albright syndrome with Cushing syndrome and hyperthyroidism.

We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T 4 276 nmol/l; free T 4 125 pmol/l; TSH less than 1 mU/l; serum cortisol greater than 2210 nmol/l; plasma ACTH less than 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3 beta-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.

Adrenal Cortex↗
PubMed1998

[Equine Cushing syndrome (ECS). Case report, review of its diagnosis and therapy and substantial differences from Cushing syndrome in dogs].

Equine and canine Cushing's syndrome, both of which are the result of elevated cortisol levels, show some different pathogenetical and clinical features and require different therapeutical approaches. In older horses the equine Cushing's syndrome (ECS) is not uncommon. Nearly all cases result from excessive hormone production in cells of the pars intermedia of the pituitary. Besides elevated levels of adrenocorticotrope hormone (ACTH), high peripheral levels of pro-opiomelanocortin, beta-endorphines and alpha-melanocyte-stimulating hormone can be measured. In middle-aged and geriatric dogs, Cushing's syndrome is the most frequently diagnosed endocrinologic abnormality. 80-85% of cases are pituitary-dependent and 15-20% are caused by cortisol producing tumors of the adrenals. 90% of pituitary lesions can be identified as adenomas, which are localised in most cases in the pars distalis of the gland, but may occur rarely in the pars intermedia, too. Clinical symptoms in both species are characterised by wasting despite good appetite or polyphagia, reduction of muscle mass with altered fat deposition and lethargy. Whereas polydipsia/polyuria is a very common feature in dogs with Cushing's syndrome, in horses it is almost invariably a sign of concurrent secondary diabetes mellitus. A typical symptom in ECS is a continuously growing haircoat (hirsutism), whereas in canine Cushing's syndrome generalised alopecia may bring the owner to consult a veterinarian. The symptoms and diagnostic procedures in a 33-year-old mare are described. Useful diagnostic tests are reviewed with special attention to species differences in reacting to them. The therapeutic approach with dopamine-agonists such as bromocriptine and pergolide as well as cyproheptadine to ECS is reviewed.

Animals↗
PubMed1995

Morning plasma free cortisol: inability to distinguish patients with mild Cushing syndrome from patients with pseudo-Cushing states.

Patients with Cushing syndrome have elevated 24 h urinary free cortisol excretion and loss of diurnal rhythm of plasma cortisol, however, morning total plasma cortisol concentrations are often similar to those of normal individuals. To test the hypothesis that an elevated morning plasma free cortisol could distinguish patients with Cushing syndrome from those without the disorder, we measured plasma free cortisol levels at 08:00 in 20 patients with surgically-confirmed mild Cushing syndrome, 19 patients with pseudo-Cushing states, and 9 normal volunteers. We then determined the sensitivity, specificity and diagnostic accuracy of plasma free cortisol for the diagnosis of hypercortisolism and for the diagnosis of Cushing syndrome. Plasma free cortisol was compared to 08:00 total plasma cortisol and to basal 24 hour urinary free cortisol. Morning plasma free cortisol was significantly elevated in patients with mild Cushing syndrome (58 +/- 6 nmol/L; mean +/- SE) compared to plasma free cortisol in patients with pseudo-Cushing states (36 +/- 6 nmol/L) (p < 0.005) and normal volunteers (22 +/- 4 nmol/L) (p < 0.0005). Total morning cortisol was significantly greater in patients with mild Cushing syndrome (470 +/- 28 nmol/L) than in normal volunteers (310 +/- 33 nmol/L, p < 0.05) but was not different from patients with pseudo-Cushing states (410 +/- 47 nmol/L, p = NS). Urinary free cortisol was also significantly greater in mild Cushing syndrome (540 +/- 50 nmol/d) than in patients with pseudo-Cushing states (430 +/- 41 nmol/d, p < 0.05) or normal volunteers (160 +/- 28 nmol/d, p < 0.0001). However, there was considerable overlap of plasma free cortisol, plasma total cortisol and urinary free cortisol between the three groups precluding these tests alone from being useful to distinguish patients with mild Cushing syndrome from patients with pseudo-Cushing states. To achieve 100% sensitivity for the diagnosis of Cushing syndrome, the specificity for plasma free cortisol, plasma total cortisol and urinary free cortisol was 0.11, 0.32 and 0.32, respectively. We conclude that plasma free cortisol is of limited value in the differential diagnosis of hypercortisolism.

Adolescent↗
PubMed2002

[Secondary forms of hypertension. 5. Hypertension caused by Cushing syndrome and Conn's disease].

The Conn syndrome and the Cushing syndrome are major differential diagnoses in the investigation of hypertension. Primary aldosteronism (Conn syndrome) is found in < 0.5% of hypertensives. In addition to the usual laboratory investigations, magnetic resonance angiography should be performed at the start of the diagnostic work-up, since it enables a very good representation of the adrenals, and saves many diagnostic tests. Minimally invasive microsurgical techniques and the development of new drugs have greatly simplified the treatment of this form of secondary hypertension. In the case of the Cushing syndrome, which leads to hypertension in about 70% of the patients, the general practitioner should look for the typical cutaneous changes that inevitably accompany this syndrome. Only when the Cushing syndrome has been confirmed clinically and biochemically, should an imaging procedure be performed.

Adenoma↗
PubMed1975

Cortisol secretion in Nelson syndrome: Persistence after "total" adrenalectomy for Cushing syndrome.

In two patients who were severely pigmented (Nelson syndrome) following bilateral adrenalectomy for Cushing syndrome, symptoms of hyper-cortisolism developed while they were receiving only physiologic steroid replacement. Cortical assays proved that endogenous cortisol production had not been obliterated. Even after total adrenalectomy, steroid measurement should be performed to guard against adrenocortical excess.

17-Hydroxycorticosteroids↗
PubMed1995

Cushing syndrome in pregnancy secondary to an adrenal cortical adenoma.

Cushing syndrome in pregnancy is rare. This is explained by the syndrome's association with amenorrhoea, oligomenorrhoea, infertility and abortions. Cushing syndrome commonly presents with hypertension, weight gain, diabetes, striae or truncal obesity, all of which can be consistent with pregnancy in women without Cushing syndrome. We describe a case of Cushing syndrome in pregnancy secondary to an adrenal cortical tumour which was discovered after an abnormal glucose tolerance test. The woman developed classical features of Cushing syndrome including gestational diabetes and hypertension and was managed successfully to term after a unilateral adrenalectomy at 23 weeks. The case is reported not only because of its rarity but also because the diagnosis was made after a routine screening test for gestational diabetes. Early diagnosis and treatment of adrenal adenoma causing Cushing syndrome in pregnancy reduces maternal and fetal morbidity and mortality.

Adenoma↗
PubMed1996

Factitious Cushing syndrome.

There have been few reports of factitious Cushing syndrome. To characterize the clinical and laboratory features leading to this unusual diagnosis, we describe 6 patients (5 women, 1 man), ages 31-44, identified retrospectively among 860 patients evaluated for hypercortisolism at the National Institutes of Health Clinical Center. All six patients had multiple surgeries unrelated to Cushing syndrome and a history of depression or anxiety. Four patients had close contact with the medical profession, three a history of drug abuse, and three had undergone previous treatment for Cushing syndrome. The physical features of Cushing syndrome were variable and not helpful in the differential diagnosis with endogenous Cushing syndrome. Four patients had striking variability in urine-free cortisol (UFC) and 17-hydroxysteroid (17-OHCS) values from low to high. Adrenal computed tomography, performed in two patients, showed small adrenal glands (n = 1) or a left-sided mass (n = 1), and adrenal magnetic resonance imaging, performed in one patient, showed atrophic glands. Pituitary magnetic resonance imaging, carried out in four patients, was either normal (n = 1) or exhibited questionable signs of microadenoma (n = 3). Determination of synthetic glucocorticoids by high pressure liquid chromatography (HPLC) was positive in the four patients in whom it was performed. Factitious Cushing syndrome is a difficult diagnosis. To conserve time and resources, high pressure liquid chromatography analysis of urine steroids, the most definitive test for the factitious disorder, should be performed whenever there is clinical suspicion of glucocorticoid abuse.

Adrenal Glands↗