scholarly journals Orbital manifestations of hypercorticism

2021 ◽  
Vol 16 (4) ◽  
pp. 4-13
Author(s):  
Maria O. Korchagina ◽  
Alexey A. Trukhin ◽  
Natalya Yu. Sviridenko
Keyword(s):  
Cushing’S Syndrome ◽  
Molecular Mechanisms ◽  
Cushing's Syndrome ◽  
The Body ◽  
Graves Disease ◽  
Fatty Tissue ◽  
Factors Affecting ◽  
Ocular Manifestations

Nowadays, Cushing's syndrome (hypercortisolism) and its manifestations are well studied. The main symptoms of hyper-cortisolism are obesity, osteoporosis, cardiomyopathy, muscle atrophy, skin thinning and purple stretch marks (striae) on the body. In practice, obesity and osteoporosis are the most frequent symptoms that are found in 90% of cases. However, there are some patients with an implicit clinical picture of hypercorticism. Some cases might concomitant with exophthalmos. This review describes a rare symptom of hypercortisolism — exophthalmos. Exophthalmos is a pathological protruding of eyeballs. This symptom is known in the context of TED that occurs most commonly in patients with Graves' disease. The article compares the mechanisms of development of eye symptoms in Cushing's syndrome and thyroid diseases, especially the Graves' disease. It discusses possible molecular mechanisms leading to exophthalmia in patients with Cushing's syndrome. Factors affecting adipogenesis in vitro and in vivo are studied, in particular factors leading to an increase of orbital fatty tissue against of elevated cortisol levels. Hormonal signaling and transcription cascades responsible for adipocyte differentiation into mature fat cells are presented. Other orbital manifestations of hypercortisolism, which occur relatively rare in practice, are also discussed in the article. These include glaucoma as well as cataract, Lisha nodules and central serous chorioretinopathy. Clinical cases of Cushing's syndrome with different ocular manifestations are considered and appropriate conclusions have been drawn.

scholarly journals TXNIP is highly regulated in bone biopsies from patients with endogenous Cushing's syndrome and related to bone turnover

2012 ◽  
Vol 166 (6) ◽  
pp. 1039-1048 ◽  
Author(s):  
Tove Lekva ◽  
Thor Ueland ◽  
Hege Bøyum ◽  
Johan Arild Evang ◽  
Kristin Godang ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Cushing’S Syndrome ◽  
Bone Cells ◽  
Cushing's Syndrome ◽  
Gene Encoding ◽  
Osteoclast Activity ◽  
Bone Biopsies ◽  
Before And After

ObjectivePatients with endogenous Cushing's Syndrome (CS), as long-time treated patients with exogenous glucocorticoids (GCs), have severe systemic manifestations including secondary osteoporosis and low-energy fractures. The aim of the present study was to investigate the functional role ofTXNIPin bone with focus on osteoblast (OB) differentiation and OB-mediated osteoclast activity and functionin vitro.Design and methodsNine bone biopsies from CS before and after surgical treatment were screened for expressional candidate genes. Microarray analyses revealed that the gene encodingTXNIPranked among the most upregulated genes. Subsequentin vitroandin vivostudies were performed.ResultsWe found thatTXNIPgene in bone is downregulated in CS following surgical treatment. Furthermore, ourin vivodata indicate novel associations between thioredoxin andTXNIP. Ourin vitrostudies showed that silencingTXNIPin OBs was followed by increased differentiation and expression and secretion of osteocalcin as well as enhanced activity of alkaline phosphatase. Moreover, treating osteoclasts with silenced TXNIP OB media showed an increased osteoclast activity.ConclusionsTXNIPexpression in bone is highly regulated during the treatment of active CS, and by GC in bone cellsin vitro. Our data indicate that TXNIP may mediate some of the detrimental effects of GC on OB function as well as modulate OB-mediated osteoclastogenesis by regulating the OPG/RANKL ratio.

CONCURRENT 3β-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY IN ADRENAL AND SCLEROCYSTIC OVARY

1965 ◽  
Vol 48 (3) ◽  
pp. 392-412 ◽  
Author(s):  
Leonard R. Axelrod ◽  
Joseph W. Goldzieher ◽  
S. David Ross
Keyword(s):  
Cushing’S Syndrome ◽  
Dehydrogenase Deficiency ◽  
Clinical Manifestations ◽  
Regulatory System ◽  
Hydroxysteroid Dehydrogenase ◽  
Cushing's Syndrome ◽  
Hypothalamic Pituitary Adrenal ◽  
Relative Deficiency

ABSTRACT In vivo and in vitro studies were performed in a virilized patient with enlarged sclerocystic ovaries, in whom urinary corticoid excretion was not suppressed by dexamethasone. Both ovarian and adrenal tissues were incubated with 5-pregnenolone-4-14C and the metabolites isolated and definitively identified. Both tissues showed a relative deficiency of 3β-hydroxysteroid dehydrogenase. The ovarian aromatizing mechanism was intact. 5-Androstene-3β,17β-diol was the major adrenal biosynthetic product, and its metabolites were identified in the urine. The abnormality of the hypothalamic-pituitary-adrenal regulatory system resembled that seen in Cushing's syndrome, but the clinical manifestations were altered by the steroid enzyme abnormality.

New Thoughts about the Cause and Treatment of the Severe Ocular Manifestations of Graves' Disease

1974 ◽  
Vol 19 (4) ◽  
pp. 165-169 ◽  
Author(s):  
I. R. McDougall ◽  
J. P. Kriss
Keyword(s):  
Corticosteroid Treatment ◽  
Immunosuppressive Drugs ◽  
Definitive Treatment ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
High Dose ◽  
Ocular Manifestations ◽  
Dose Corticosteroid

The ocular manifestations of Graves' disease are probably due to autoimmunity. Thyroglobulin and complexes of thyroglobulin and antithyroglobulin have a predilection to attach to extraocular muscle membranes in vitro. It is suggested that in vivo these molecules are directed, probably via lymphatics, to the orbit where they attach to the muscle cell membranes. B lymphocytes, which have been shown to be capable of combining with both thyroglobulin and complexes, attach on to these molecules. The tissue damage is probably caused by the complexes, the lymphocytes, or both. Treatment of hyperthyroidism in a patient with ophthalmopathy should be cautious and with antithyroid drugs. This will reduce, though not completely eliminate, the possibility of a post-treatment exacerbation. If for some reason definitive treatment of the hyperthyroidism is essential, worsening of the ophthalmopathy may be prevented by prescribing steroids or immunosuppressive drugs at the time of surgical or radioiodine treatment. When progressive eye disease has arisen, orbital radiotherapy is a safe effective alternative to high dose corticosteroid treatment or surgical decompression.

scholarly journals Cushing’s Syndrome in a Patient with Bilateral Macronodular Adrenal Hyperplasia Responding to Cisapride: An in Vivo and in Vitro Study

2003 ◽  
Vol 88 (10) ◽  
pp. 4616-4622 ◽  
Author(s):  
Massimo Mannelli ◽  
Pietro Ferruzzi ◽  
Paola Luciani ◽  
Clara Crescioli ◽  
Lisa Buci ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
In Vitro Study ◽  
Cushing's Syndrome ◽  
Vitro Study ◽  
Adrenal Hyperplasia

scholarly journals Demonstration of reduced in vivo surface expression of activating mutant thyrotrophin receptors in thyroid sections

2002 ◽  
pp. 163-171 ◽  
Author(s):  
M Sequeira ◽  
B Jasani ◽  
D Fuhrer ◽  
M Wheeler ◽  
M Ludgate
Keyword(s):  
Molecular Mechanisms ◽  
Thyroid Tissue ◽  
Surface Expression ◽  
Germline Mutations ◽  
Antigen Retrieval ◽  
Graves Disease ◽  
Paraffin Sections ◽  
Gain Of Function

OBJECTIVE: Thyroid function and growth are controlled by TSH. Hyperthyroidism can be due to Graves' Disease (GD), in which thyroid-stimulating antibodies mimic TSH, or gain-of-function mutations in the TSH receptor (TSHR). These activating mutations have poor surface expression when assessed in non-thyroidal cells in vitro but nothing is known of their in vivo behaviour. Several TSHR antibodies have been produced but none has been applied to thyroid paraffin sections. This study aimed to develop a technique suitable for use on paraffin sections and apply it to investigate TSHR expression in thyroids harbouring activating TSHR germline mutations compared with normal and GD thyroids. DESIGN AND METHODS: Immunocytochemistry coupled with antigen retrieval, using a spectrum of antibodies to the TSHR, was applied to paraffin sections of GD thyroid tissue. Subsequently, TSHR immunoreactivity was examined in three normal thyroids, three patients with GD and three patients with familial hyperthyroidism, due to different gain-of-function TSHR germline mutations, using the optimised protocol. RESULTS: Two antibodies, A10 and T3-495, to the extracellular domain (ECD) and membrane spanning region (MSR) of the TSHR respectively, produced specific basolateral staining of thyroid follicular cells. In normal and GD thyroids, basolateral staining with T3-495 was generally more intense than with A10, suggesting a possible surfeit of MSR over ECD. Graves' Disease thyroids have more abundant TSHR than normal glands. In contrast, thyroids harbouring gain-of-function mutations have the lowest expression in vivo, mirroring in vitro findings. CONCLUSIONS: The development of an immunocytochemical method applicable to paraffin sections has demonstrated that different molecular mechanisms causing hyperthyroidism result in the lowest (mutation) and highest (autoimmunity) levels of receptor at the thyrocyte surface.

scholarly journals IN VIVO AND IN VITRO STUDIES OF ADRENAL SECRETIONS IN CUSHING'S SYNDROME AND PRIMARY ALDOSTERONISM*

1963 ◽  
Vol 42 (4) ◽  
pp. 516-524 ◽  
Author(s):  
Edward G. Biglieri ◽  
Satoshi Hane ◽  
Paul E. Slaton ◽  
Peter H. Forsham
Keyword(s):  
Cushing’S Syndrome ◽  
Primary Aldosteronism ◽  
Cushing's Syndrome ◽  
In Vitro Studies

scholarly journals Structure–Biological Activity Relationships of Extra-Virgin Olive Oil Phenolic Compounds: Health Properties and Bioavailability

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 685 ◽  
Author(s):  
Paloma Rodríguez-López ◽  
Jesús Lozano-Sanchez ◽  
Isabel Borrás-Linares ◽  
Tatiana Emanuelli ◽  
Javier A. Menéndez ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Olive Oil ◽  
Functional Food ◽  
Molecular Mechanisms ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
The Body ◽  
Phenolic Fraction

Extra-virgin olive oil is regarded as functional food since epidemiological studies and multidisciplinary research have reported convincing evidence that its intake affects beneficially one or more target functions in the body, improves health, and reduces the risk of disease. Its health properties have been related to the major and minor fractions of extra-virgin olive oil. Among olive oil chemical composition, the phenolic fraction has received considerable attention due to its bioactivity in different chronic diseases. The bioactivity of the phenolic compounds could be related to different properties such as antioxidant and anti-inflammatory, although the molecular mechanism of these compounds in relation to many diseases could have different cellular targets. The aim of this review is focused on the extra-virgin olive oil phenolic fraction with particular emphasis on (a) biosynthesis, chemical structure, and influence factors on the final extra-virgin olive oil phenolic composition; (b) structure–antioxidant activity relationships and other molecular mechanisms in relation to many diseases; (c) bioavailability and controlled delivery strategies; (d) alternative sources of olive biophenols. To achieve this goal, a comprehensive review was developed, with particular emphasis on in vitro and in vivo assays as well as clinical trials. This report provides an overview of extra-virgin olive oil phenolic compounds as a tool for functional food, nutraceutical, and pharmaceutical applications.

scholarly journals A Novel Phenotype of Familial Hyperaldosteronism Type III: Concurrence of Aldosteronism and Cushing’s Syndrome

2016 ◽  
Vol 101 (11) ◽  
pp. 4290-4297 ◽  
Author(s):  
Anli Tong ◽  
Guanghua Liu ◽  
Fen Wang ◽  
Jun Jiang ◽  
Zhaoli Yan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Channel Blockers ◽  
Type Iii ◽  
Adrenal Hormone ◽  
Familial Hyperaldosteronism ◽  
Bilateral Adrenal Hyperplasia

Context: To date, all the familial hyperaldosteronism type III (FH-III) patients reported presenting with typical primary aldosteronism (PA), without showing other adrenal hormone abnormalities. Objective: This study characterized a novel phenotype of FH-III and explored the possible pathogenesis. Patients and Methods: A male patient presented with severe hypertension and hypokalemia at the age of 2 years and developed Cushing’s syndrome at 20 years. He was diagnosed with PA and Cushing’s syndrome on the basis of typical biochemical findings. He had massive bilateral adrenal hyperplasia and underwent left adrenalectomy. KCNJ5 was sequenced, and secretion of aldosterone and cortisol were observed both in vivo and in vitro. Results: A heterozygous germline p.Glu145Gln mutation of KCNJ5 was identified. ARMC5, PRKAR1A, PDE8B, PDE11A, and PRKACA genes and β-catenin, P53 immunoactivity were normal in the adrenal. CYP11B2 was highly expressed, whereas mRNA expression of CYP11B1, CYP17A1, and STAR was relatively low in the hyperplastic adrenal, compared with normal adrenal cortex and other adrenal diseases. In the primary cell culture of the resected hyperplastic adrenal, verapamil and nifedipine, two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol and the mRNA expression of CYP11B1, CYP11B2, CYP17A1, and STAR. Conclusions: We presented the first FH-III patient who had both severe PA and Cushing’s syndrome. Hypersecretion of cortisol might be ascribed to overly large size of the hyperplastic adrenal because CYP11B1 expression was relatively low in his adrenal. Like aldosterone, synthesis and secretion of cortisol in the mutant adrenal may be mediated by voltage-gated Ca2+ channels.

scholarly journals PRKACA Somatic Mutations Are Rare Findings in Aldosterone-Producing Adenomas

2016 ◽  
Vol 101 (8) ◽  
pp. 3010-3017 ◽  
Author(s):  
Yara Rhayem ◽  
Luis G. Perez-Rivas ◽  
Anna Dietz ◽  
Kerstin Bathon ◽  
Christian Gebhard ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Primary Aldosteronism ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Functional Characterization ◽  
Cushing's Syndrome ◽  
Antihypertensive Medications ◽  
Unilateral Adrenalectomy ◽  
Vitro Analysis

Context: Somatic mutations have been found causative for endocrine autonomy in aldosterone-producing adenomas (APAs). Whereas mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas, the presence of PRKACA variants in APAs is unknown, especially in those that display cosecretion of cortisol. Objective: The objective of the study was to investigate PRKACA somatic variants identified in APA cases. Design: Identification of PRKACA somatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues. Setting and Patients: APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for primary aldosteronism between 2005 and 2015 at a single institution. Results: PRKACA somatic mutations were identified in two APA cases (1.6%). One APA carried a newly identified p.His88Asp variant, whereas in a second case, a p.Leu206Arg mutation was found, previously described only in cortisol-producing adenomas with overt Cushing's syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. Although CYP11B2 was strongly expressed in the p.His88Asp-mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndrome was present only in the patient with the p.Leu206Arg mutation. After adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized serum potassium levels. Conclusions: We describe for the first time PRKACA mutations as rare findings associated with unilateral primary aldosteronism. As cortisol cosecretion occurs in a subgroup of APAs, other molecular mechanisms are likely to exist.

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