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International Journal of Surgery... 2008Amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. Amyloidosis is a rare occurrence in thyroid... (Review)
Review
BACKGROUND AND AIM
Amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. Amyloidosis is a rare occurrence in thyroid gland.
METHODS
A systematic review of the published data on amyloid goiter was carried out by searching Medline and other online databases (such as Scopus and Endnote) for the period from 1951 to March 2008. A total of 127 publications (case series, single case reports and reviews) was found, of which 31 were case series published from February 1995 to March 2008. Six articles have been considered for our review because they regard amyloid goiter as a manifestation of both primary and secondary amyloidosis (a total of 30 cases have been analyzed). Exclusion criterion was the presence of primary thyroid cancer.
RESULTS
The preoperative diagnosis of amyloid goiter should be considered in patients with known systemic amyloidosis or with a long-standing predisposing disease who present a rapidly growing thyroid volume in association with a euthyroid state. Fine-needle aspiration biopsy can be performed to exclude primary malignant lesions of thyroid gland and immunohistochemical studies can identify and characterize the amyloid deposits.
CONCLUSION
Amyloid goiter has to be suspected in all patients with a progressive, rapidly growing, bilateral thyroid enlargement and a concomitant history of chronic inflammatory processes. Moreover, this should be suspected in patients who are known to have disease predisposing to amyloid deposition.
Topics: Amyloidosis; Biopsy, Fine-Needle; Diagnosis, Differential; Goiter; Humans; Thyroid Gland; Tomography, X-Ray Computed; Ultrasonography
PubMed: 19168408
DOI: 10.1016/j.ijsu.2008.12.025 -
International Journal of Molecular... Apr 2021Transthyretin (TTR) is an essential transporter of a thyroid hormone and a holo-retinol binding protein, found abundantly in human plasma and cerebrospinal fluid. In... (Review)
Review
Transthyretin (TTR) is an essential transporter of a thyroid hormone and a holo-retinol binding protein, found abundantly in human plasma and cerebrospinal fluid. In addition, this protein is infamous for its amyloidogenic propensity, causing various amyloidoses in humans, such as senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. It has been known for over two decades that decreased stability of the native tetrameric conformation of TTR is the main cause of these diseases. Yet, mechanistic details on the amyloidogenic transformation of TTR were not clear until recent multidisciplinary investigations on various structural states of TTR. In this review, we discuss recent advancements in the structural understanding of TTR misfolding and amyloidosis processes. Special emphasis has been laid on the observations of novel structural features in various amyloidogenic species of TTR. In addition, proteolysis-induced fragmentation of TTR, a recently proposed mechanism facilitating TTR amyloidosis, has been discussed in light of its structural consequences and relevance to acknowledge the amyloidogenicity of TTR.
Topics: Amyloid; Amyloid Neuropathies, Familial; Animals; Humans; Prealbumin; Protein Folding
PubMed: 33922648
DOI: 10.3390/ijms22094429 -
Current Cardiology Reports Aug 2019We summarize key features pertaining to the two most commonly encountered types of cardiac amyloidosis (CA), monoclonal immunoglobulin light chain (AL) and transthyretin... (Review)
Review
PURPOSE OF REVIEW
We summarize key features pertaining to the two most commonly encountered types of cardiac amyloidosis (CA), monoclonal immunoglobulin light chain (AL) and transthyretin type (ATTR), expanding upon the clinical application and utility of various imaging techniques in diagnosing CA.
RECENT FINDINGS
Advances in imaging have led to earlier identification, improved diagnosis of CA and higher discriminatory power to differentiate CA from other hypertrophic phenocopies. The application of cardiac magnetic resonance imaging (CMR) has led to a deeper understanding of underlying pathophysiological processes in CA, owing largely to its intrinsic tissue characterization properties. The widespread adoption of bone scintigraphy algorithms has reduced the need for cardiac biopsy and improved diagnostic confidence in ATTR CA. As new treatments for CA are rapidly developing, there will be even greater reliance on imaging, as the requirement to diagnose disease earlier, monitor response and amend treatment strategies accordingly intensifies.
Topics: Amyloid Neuropathies, Familial; Amyloidosis; Biopsy; Cardiomyopathies; Humans; Immunoglobulin Light Chains
PubMed: 31375984
DOI: 10.1007/s11886-019-1180-2 -
Anais Brasileiros de Dermatologia 2018Primary cutaneous amyloidosis is limited to the skin without involving any other tissue. Nodular amyloidosis is rare, and atrophic nodular cutaneous amyloidosis is even... (Review)
Review
Primary cutaneous amyloidosis is limited to the skin without involving any other tissue. Nodular amyloidosis is rare, and atrophic nodular cutaneous amyloidosis is even rarer. We describe the fourth case of atrophic nodular cutaneous amyloidosis by searching PubMed databases. A 52-year-old female presented to our hospital with a 2-year history of orange papules and nodules without subjective symptom on her right abdomen. Review of systems was negative. Atrophic nodular amyloidosis may progress to primary systemic disease in up to 7% of cases. Because our patient had no systemic involvement, she was diagnosed with atrophic nodular cutaneous amyloidosis based on characteristic symptoms and histopathologic examination. Routine follow-up for this patient is necessary to detect any potential disease progression.
Topics: Abdominal Wall; Amyloidosis; Atrophy; Female; Humans; Middle Aged; Skin Diseases
PubMed: 29641709
DOI: 10.1590/abd1806-4841.20186504 -
Kidney International May 2010LECT2 amyloidosis is the latest systemic type of amyloidosis to be described. It was discovered in patients with nephrotic syndrome and renal failure and is...
LECT2 amyloidosis is the latest systemic type of amyloidosis to be described. It was discovered in patients with nephrotic syndrome and renal failure and is characterized by amyloid deposition in glomeruli, renal vessels, and interstitium. Clinical and pathological features of earlier phases of this type of amyloidosis have yet to be determined.
Topics: Amyloidosis; Humans; Kidney; Kidney Glomerulus; Nephrotic Syndrome; Renal Insufficiency
PubMed: 20393490
DOI: 10.1038/ki.2010.18 -
Orphanet Journal of Rare Diseases Aug 2012DEFINITION OF THE DISEASE: AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of... (Review)
Review
UNLABELLED
DEFINITION OF THE DISEASE: AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils.
EPIDEMIOLOGY
AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50.
CLINICAL DESCRIPTION
The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis.
DIAGNOSTIC METHODS
The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence. Due to the systemic nature of the disease, non-invasive biopsies such as abdominal fat aspiration should be considered before taking biopsies from involved organs, in order to reduce the risk of bleeding complications.
DIFFERENTIAL DIAGNOSIS
Systemic AL amyloidosis should be distinguished from other diseases related to deposition of monoclonal LC, and from other forms of systemic amyloidosis. When pathological studies have failed to identify the nature of amyloid deposits, genetic studies should be performed to diagnose hereditary amyloidosis.
MANAGEMENT
Treatment of AL amyloidosis is based on chemotherapy, aimed at controlling the underlying plasma clone that produces amyloidogenic LC. The hematological response should be carefully checked by serial measurements of serum free LC. The association of an alkylating agent with high-dose dexamethasone has proven to be effective in two thirds of patients and is considered as the current reference treatment. New agents used in the treatment of multiple myeloma are under investigation and appear to increase hematological response rates. Symptomatic measures and supportive care is necessary in patients with organ failure. Noticeably, usual treatments for cardiac failure (i.e. calcium inhibitors, β-blockers, angiotensin converting enzyme inhibitors) are inefficient or even dangerous in patients with amyloid heart disease, that should be managed using diuretics. Amiodarone and pace maker implantation should be considered in patients with rhythm or conduction abnormalities. In selected cases, heart and kidney transplantation may be associated with prolonged patient and graft survival.
PROGNOSIS
Survival in AL amyloidosis depends on the spectrum of organ involvement (amyloid heart disease being the main prognosis factor), the severity of individual organs involved and haematological response to treatment.
Topics: Aged; Amyloidosis; Diagnosis, Differential; Humans; Middle Aged; Prognosis
PubMed: 22909024
DOI: 10.1186/1750-1172-7-54 -
Expert Review of Proteomics Sep 2019: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is... (Review)
Review
: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is essential in determining the causative protein and initiating proper treatment. Mass spectrometry-based proteomics is currently the most sensitive and accurate means of typing amyloid. : Amyloidosis can be systemic or localized, acquired or hereditary, and can affect any organ or tissue. Diagnosis requires biopsy, histological analysis, and typing of the causative protein to determine treatment. The kidneys are the most commonly affected organ in systemic disease. Fibrinogen alpha chain amyloidosis (AFib) is the most prevalent form of hereditary renal amyloidosis. Select mutations in the fibrinogen Aα (FGA) gene lead to AFib. : Mass spectrometry is currently the most specific and sensitive method for amyloid typing. Identification of the mutated fibrinogen alpha chain can be difficult in the case of 'private' frameshift mutations, which dramatically change the sequences of the expressed fibrinogen alpha chain. A combination of expert pathologist review, mass spectrometry, and gene sequencing can allow for confident diagnosis and determination of the fibrinogen alpha chain mutated sequence.
Topics: Amyloid; Amyloidosis; Fibrinogen; Humans; Kidney; Mass Spectrometry; Mutation; Proteomics
PubMed: 31443619
DOI: 10.1080/14789450.2019.1659137 -
European Heart Journal Dec 2022To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological...
AIMS
To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors.
METHODS AND RESULTS
In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95-7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01).
CONCLUSIONS
Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors.
Topics: Humans; Amyloidosis; Magnetic Resonance Imaging; Immunoglobulin Light-chain Amyloidosis; Heart; Prognosis; Magnetic Resonance Spectroscopy; Myocardium; Magnetic Resonance Imaging, Cine; Predictive Value of Tests
PubMed: 36239754
DOI: 10.1093/eurheartj/ehac363 -
JACC. Cardiovascular Imaging Nov 2019Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes... (Review)
Review
Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes a major source of heart failure with excess cardiac morbidity and mortality. Myocardial fibrosis (defined as excess myocardial collagen concentration that distorts myocardial architecture) is prevalent and causes cardiac symptoms and ultimately adverse cardiac events, such as heart failure, arrhythmia, and death. Conversely, cardiac amyloidosis is far less prevalent than myocardial fibrosis but represents a more extreme form of interstitial heart disease with marked interstitial expansion, profound architectural distortion, and then rapid clinical decline. Myocardial extracellular volume measures fundamentally advance the understanding of myocardium and specifically highlights the role of the interstitium. Rather than conceptualizing myocardium as a homogenous tissue, dichotomizing the myocardium into its interstitial (including the microvasculature) and cardiomyocyte phenotypes promotes additional understanding of heart failure pathophysiology that may spur the development of more effective therapies.
Topics: Amyloidosis; Cardiomyopathies; Disease Progression; Extracellular Space; Fibrosis; Heart Failure; Humans; Myocardium; Prognosis; Ventricular Remodeling
PubMed: 31422140
DOI: 10.1016/j.jcmg.2019.04.025 -
Dermatology (Basel, Switzerland) 2022Quick and accurate diagnosis of primary cutaneous amyloidosis (PCA) may be difficult because its symptoms are often subtle and nonspecific. (Review)
Review
BACKGROUND
Quick and accurate diagnosis of primary cutaneous amyloidosis (PCA) may be difficult because its symptoms are often subtle and nonspecific.
OBJECTIVE
We sought to review the literature on the roles of various staining methods in the diagnosis of amyloidosis and demonstrate added benefits of using rapid 4,6-diamidino-2-phenylindole (DAPI) staining in the diagnosis of PCA.
METHODS
Three groups of cases, namely, PCA, neurodermatitis, and prurigo nodularis, were retrieved from a computerized pathology database for study, and their paraffin-embedded tissue blocks were cut following standard procedures. The tissue sections were stained with three stains: hematoxylin-eosin (HE), Congo red, and DAPI stains, and examined under the microscope to compare the staining patterns of these three methods. We also performed amyloid keratin and apolipoprotein E (APOE) staining on the sections of PCA in order to further support our conclusion. The PCA sections were read by junior and senior dermatopathologists for comparison.
RESULTS
The sensitivity of DAPI staining for PCA was significantly higher than that of Congo red staining and HE staining (p < 0.001). This statement holds true whether the experiment was grouped in one sample or was divided into groups of junior and senior dermatopathologists (p < 0.001). The DAPI-positive staining areas, except for the nuclei, were consistent with the amyloid deposition areas. In this study, DAPI staining had a sensitivity of 98.6% and a specificity of 100%.
CONCLUSION
DAPI staining could serve as a useful technique to establish the diagnosis of PCA, and its high efficacy in diagnosing PCA makes it less dependent on the experience levels of the evaluators. Additionally, the binding of DAPI to the A-T-rich sequence of double-stranded DNA suggests that amyloid may contain DNA or a similarly structured nucleic acid.
Topics: Amyloidosis; Congo Red; Humans; Indoles; Staining and Labeling
PubMed: 34515096
DOI: 10.1159/000518082