scholarly journals Allgrove syndrome: how to suspect the problem? Endocrinologists experience

2020 ◽  
Vol 66 (1) ◽  
pp. 64-69
Author(s):  
Natalya I. Volkova ◽  
Ilya Y. Davidenko ◽  
Igor B. Reshetnikov ◽  
Snezhana S. Brovkina
Keyword(s):  
Adrenal Insufficiency ◽  
Neurological Disorders ◽  
Autosomal Recessive ◽  
Clinical Observation ◽  
Pathogenic Mutation ◽  
Multisystem Disease ◽  
Allgrove Syndrome ◽  
Interdisciplinary Interaction ◽  
Over Time

Allgrove syndrome (Alacrimia, Achalasia, Adrenal insufficiency, AAAS) is a rare autosomal recessive multisystem disease characterized by chronic adrenal insufficiency, alacrimia and achalasia of the cardia. This disease is often associated with various neurological disorders, amyotrophy, in such cases, it is named 4A and 5A syndrome, but sometimes there is also 2A syndrom. The occurrence of the disease is due to a mutation in the gene AAAS (12q13), which encodes the protein ALADIN. Here is a clinical observation of a patient with Allgrove syndrome. The patient had a typical clinic: alacrimia, achalasia, adrenal insufficiency, convulsive syndrome. However, a neurological disorder, manifested by convulsive syndrome, passed with time. Despite the full clinical picture, the diagnosis was made only after 14 years. Allgrove syndrome was verified through genetic analysis revealed a pathogenic mutation c.43CT gene AAAS. Progression of the severity of alacrimia and need of glucocorticoids over time was noted. We shown the difficulty of diagnosis is due to the lack of awareness of clinicians about the disease, the importance of interdisciplinary interaction, as well as the need for follow-up of such patients.

scholarly journals SAT-219 Allgrove Syndrome: How to Suspect a Problem?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Natalia Volkova ◽  
Ilia Davidenko ◽  
Irina Dzherieva ◽  
Alexander Zibarev ◽  
Lilia Ganenko ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Body Weight Loss ◽  
Pathogenic Mutation ◽  
Neurological Dysfunction ◽  
Triple A Syndrome ◽  
Body Type ◽  
Multisystem Disease ◽  
Allgrove Syndrome ◽  
Surgical Department ◽  
Aaas Gene

Abstract Background: Allgrove syndrome (triple A syndrome) is a rare autosomal recessive multisystem disease characterized by adrenal insufficiency, alacrimia and achalasia. It is caused by a mutation in the AAAS gene (12q13) encoding the protein ALADIN (1). This syndrome is often associated with neurological dysfunction disorders, amyotrophy, in such cases, it is named 4A and 5A syndrome, but sometimes there is also 2A syndrome. Prevalence:<1/1000000. The first description was in 1978. Clinical case: A 18-year patient A. complained of fatigue, weakness, darkening of the skin. From anamnesis of life: born from the first pregnancy without complications, weight 3200g. Parents often turned to the pediatrician with complaints: lethargy, frequent regurgitation, ARVI up to 6–7 times a year. Slow weight gain, dyspeptic syndrome (nausea, vomiting) was noted objectively. At the age of 3, the boy entered the surgical department with acute abdomen, fever, vomiting. Achalasia was revealed, reconstructive surgery was carried out. In the diagnostic search for the causes of body weight loss he was directed to the endocrinologist. There were an increase in ACTH 470 pg/ml (0,0-46 pg/ml), cortisol 0.05 µg/DL. Diagnosis: primary chronic adrenal insufficiency; the dose of hydrocortisone 10 mg/day did not change with age. An in-depth anamnesis found: the patient never cried with tears. Objectively: asthenic body type, BMI 16.5 kg/m2, hyperpigmentation of the palms, armpits; weakness in the proximal muscles of the limbs. Laboratory studies: ACTH 95 PG/ml, cortisol 0.1 µg/DL (3.7–19.4 µg/DL). The secretion of mineralocorticoids was evaluated: plasma aldosterone and renin levels were within the reference values. Ophthalmologist: injected conjunctiva, sclera. Schirmer’s test: mild alacrimia. It allowed to make the diagnosis: “Primary chronic adrenal insufficiency. Condition after surgery for achalasia (1997). Alacrimia. Allgrove Syndrome.” The dose of hydrocortisone was increased to 17.5 mg/day. In 2019, the patient complained of a sharp deterioration of health, darkening of the skin. The dose of hydrocortisone was increased to 25 mg/day (15 mg at 8.00, 10 mg in the afternoon). The ophthalmologist noted an increase in the severity of alacrimia, artificial tear drops was recommended. The diagnosis was confirmed by pathogenic mutation c.43C>T of the AAAS gene. Discussion: Despite the full clinical picture, the right diagnosis was made only after 14 years. We shown the difficulty of diagnosis is due to the lack of awareness of clinicians about the disease, the importance of interdisciplinary interaction, as well as the need for follow-up of such patients. Reference: (1) Handschug K, Sperling S, Yoon SJ, et al. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Human Molecular Genetics. 2001;10:283–290.

scholarly journals Sindrome de allgrove en niños. Reporte de 11 casos

2020 ◽  
Vol 50 (4) ◽  
Author(s):  
María Carmen Álvarez López ◽  
Pedro Coello Ramírez ◽  
Elizabeth García Rodríguez ◽  
Mariana Ordoñez Cárdenas ◽  
Fátima Azereth Reynoso Zarzosa
Keyword(s):  
Adrenal Insufficiency ◽  
Genetic Disease ◽  
High Frequency ◽  
Clinical Characteristics ◽  
Autosomal Recessive ◽  
Allgrove Syndrome ◽  
Documented Case ◽  
Responsible Gene ◽  
Neurological Alterations ◽  
Chronic Vomiting

Background. Allgrove Syndrome is a very rare genetic disease, which is inherited in an autosomal recessive way. The responsible gene is the AAAS, that encodes the protein ALADIN. It occurs most often in children of consanguineous parents. It is characterized by the classic triad of achalasia, alacrima, and adrenal insufficiency due to resistance to ACTH; the presence of two of the three previous manifestation events are required to establish the diagnosis. There is also a high frequency of the neurologic symptoms. Objective. Describe the clinical characteristics, age of presentation and evolution in 11 patients with Allgrove Syndrome. Methods. 11 clinical cases compatible with Allgrove Syndrome of presentation in childhood are retrospectively reviewed. Results. The average age at diagnosis was 5.9 years (range 1-16 years old). There was a predominance of the female sex (n = 7). The most common symptoms were postprandial vomiting and alacrima, present in 100% of the cases at the time of diagnosis. Adrenal insufficiency was not common; it was only documented in one patient. There was consanguinity between parents in 62.5% of the cases. Conclusions. Allgrove Syndrome is an uncommon cause of dysphagia, chronic vomiting and failure to grow in children. In case of any documented case of achalasia it is suggested to question in a directed way the presence of alacrima and adrenal insufficiency data such as seizures, hyperpigmentation of the skin and neurological alterations.

Allgrove syndrome with amyotrophy

2021 ◽  
pp. practneurol-2021-003192
Author(s):  
Míriam Carvalho Soares ◽  
Otávio Gomes Lins ◽  
José Ronaldo Lima de Carvalho ◽  
Cláudia Cristina de Sá ◽  
Vanessa Van der Linden ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Clinical Features ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Symptomatic Treatment ◽  
Neurological Manifestations ◽  
Dry Eyes ◽  
Allgrove Syndrome

Allgrove syndrome is an autosomal recessive disease mostly caused by mutations in the AAAS gene. It has variable clinical features but its cardinal features comprise the triad of achalasia, alacrimia and adrenal insufficiency. It typically develops during the first decade of life, but some cases have second and third decades onset. We describe a 25-year-old woman with Allgrove syndrome who had progressive amyotrophy, achalasia, dry eyes and adrenal insufficiency since childhood. Awareness of its neurological manifestations and multisystem features helps to shorten the time for diagnosis and allow appropriate symptomatic treatment.

Effectiveness of the Chiari Health Index for Pediatrics instrument in measuring postoperative health-related quality of life in pediatric patients with Chiari malformation type I

2020 ◽  
pp. 1-6
Author(s):  
Georgina E. Sellyn ◽  
Alan R. Tang ◽  
Shilin Zhao ◽  
Madeleine Sherburn ◽  
Rachel Pellegrino ◽  
...  
Keyword(s):  
Surgical Intervention ◽  
Type I ◽  
Health Related Quality ◽  
Health Index ◽  
Chiari Malformation Type I ◽  
Related Quality ◽  
Health Related ◽  
Over Time

OBJECTIVEThe authors’ previously published work validated the Chiari Health Index for Pediatrics (CHIP), a new instrument for measuring health-related quality of life (HRQOL) for pediatric Chiari malformation type I (CM-I) patients. In this study, the authors further evaluated the CHIP to assess HRQOL changes over time and correlate changes in HRQOL to changes in symptomatology and radiological factors in CM-I patients who undergo surgical intervention. Strong HRQOL evaluation instruments are currently lacking for pediatric CM-I patients, creating the need for a standardized HRQOL instrument for this patient population. This study serves as the first analysis of the CHIP instrument’s effectiveness in measuring short-term HRQOL changes in pediatric CM-I patients and can be a useful tool in future CM-I HRQOL studies.METHODSThe authors evaluated prospectively collected CHIP scores and clinical factors of surgical intervention in patients younger than 18 years. To be included, patients completed a baseline CHIP captured during the preoperative visit, and at least 1 follow-up CHIP administered postoperatively. CHIP has 2 domains (physical and psychosocial) comprising 4 components, the 3 physical components of pain frequency, pain severity, and nonpain symptoms, and a single psychosocial component. Each CHIP category is scored on a scale, with 0 indicating absent and 1 indicating present, with higher scores indicating better HRQOL. Wilcoxon paired tests, Spearman correlations, and linear regression models were used to evaluate and correlate HRQOL, symptomatology, and radiographic factors.RESULTSSixty-three patients made up the analysis cohort (92% Caucasian, 52% female, mean age 11.8 years, average follow-up time 15.4 months). Dural augmentation was performed in 92% of patients. Of the 63 patients, 48 reported preoperative symptoms and 42 had a preoperative syrinx. From baseline, overall CHIP scores significantly improved over time (from 0.71 to 0.78, p < 0.001). Significant improvement in CHIP scores was seen in patients presenting at baseline with neck/back pain (p = 0.015) and headaches (p < 0.001) and in patients with extremity numbness trending at p = 0.064. Patients with syringomyelia were found to have improvement in CHIP scores over time (0.75 to 0.82, p < 0.001), as well as significant improvement in all 4 components. Additionally, improved CHIP scores were found to be significantly associated with age in patients with cervical (p = 0.009) or thoracic (p = 0.011) syrinxes.CONCLUSIONSThe study data show that the CHIP is an effective instrument for measuring HRQOL over time. Additionally, the CHIP was found to be significantly correlated to changes in symptomatology, a finding indicating that this instrument is a clinically valuable tool for the management of CM-I.

scholarly journals P34 Characteristics, diagnosis and management of Cushing’s disease - A systematic review and meta-analysis

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Chan Hee Koh ◽  
Danyal Z Khan ◽  
Ronneil Digpal ◽  
Hugo Layard Horsfall ◽  
Hani J Marcus ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cushing’S Disease ◽  
Meta Analysis ◽  
A Priori ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Diagnosis And Management ◽  
Over Time

Abstract Introduction The clinical practice and research in the diagnosis and management of Cushing’s disease remains heterogeneous and challenging to this day. We sought to establish the characteristics of Cushing’s disease, and the trends in diagnosis, management and reporting in this field. Methods Searches of PubMed and Embase were conducted. Study protocol was registered a-priori. Random-effects analyses were conducted to establish numerical estimates. Results Our screening returned 159 papers. The average age of adult patients with Cushing’s disease was 39.3, and 13.6 for children. The male:female ratio was 1:3. 8% of patients had undergone previous transsphenoidal resection. The ratio of macroadenomas: microadenomas:imaging-undetectable adenomas was 18:53:29. The most commonly reported preoperative biochemical investigations were serum cortisol (average 26.4µg/dL) and ACTH (77.5pg/dL). Postoperative cortisol was most frequently used to define remission (74.8%), most commonly with threshold of 5µg/dL (44.8%). Average remission rates were 77.8% with recurrence rate of 13.9%. Median follow-up was 38 months. Majority of papers reported age (81.9%) and sex (79.4%). Only 56.6% reported whether their patients had previous pituitary surgery. 45.3% reported whether their adenomas were macroadenoma, microadenoma or undetectable. Only 24.1% reported preoperative cortisol, and this did not improve over time. 60.4% reported numerical thresholds for cortisol in defining remission, and this improved significantly over time (p = 0.004). Visual inspection of bubbleplots showed increasing preference for threshold of 5µg/dL. 70.4% reported the length of follow up. Conclusion We quantified the characteristics of Cushing’s disease, and analysed the trends in investigation and reporting. This review may help to inform future efforts in forming guidelines for research and clinical practice.

scholarly journals 325 - Relationship quality in dementia: Preliminary longitudinal analyses of the EU-JPND Actifcare cohort study

2020 ◽  
Vol 32 (S1) ◽  
pp. 83-83
Author(s):  
Maria J. Marques ◽  
Bob Woods ◽  
Eva Y.L. Tan ◽  
Marjolein de Vugt ◽  
Frans Verhey ◽  
...  
Keyword(s):  
Social Support ◽  
Cohort Study ◽  
Relationship Quality ◽  
Sense Of Coherence ◽  
Unmet Needs ◽  
Neuropsychiatric Symptoms ◽  
Longitudinal Analyses ◽  
Family Carers ◽  
Over Time

INTRODUCTIONRelationship quality (RQ) in dyads of persons with dementia and their family carers is important both as a clinical outcome and as a determinant of health and quality of life. In previous work we studied RQ using baseline data of a large-scale European longitudinal study on timely access to and use of community formal services in dementia (EU-JPND Acticare). We concluded that neuropsychiatric symptoms and carer stress contributed to discrepancies in RQ ratings within the dyad, which were less favourable when reported by family carers. This and other associations (e.g. between carer-rated RQ and sense of coherence) were cautiously interpreted, in the context of a cross-sectional analysis.OBJECTIVESTo analyse how carer-reported RQ varies over time and to examine its most important influencing factors.METHODSWe present preliminary longitudinal analyses from the Actifcare cohort study of 451 community-dwelling persons with dementia and their primary carers in eight European countries (12-month follow-up). Comprehensive assessments included the Positive Affect Index (PAI) to assess RQ, persons with dementia’s neuropsychiatric symptoms, persons with dementia and carers’ unmet needs, carers’ anxiety and depression, social support, sense of coherence and stress.RESULTSCarers’ mean PAI scores decreased over the 12 -month period. The person with dementia neuropsychiatric symptoms and unmet needs, and carers’ perceived social support were significant predictors of carers’ RQ change.DISCUSSION AND CONCLUSIONWe analysed carer-reported RQ variation over time and predictors in a large European sample of persons with dementia and their family carers. As expected, RQ decreased over the oneyear follow-up period as the disease progressed. Its main predictors in this sample (neuropsychiatric symptoms and the person’s unmet needs, together with carers’ social support) can all influence the impact that caregiving has on the carer and on how time and energy-consuming caregiving is. The role of increased clinical symptoms (also affecting communication difficulties), together with carers’ exhaustion, must be equated. Overall, these results may help us to tailor interventions addressing RQ and potentially improve dementia outcomes.

scholarly journals Global Sensory Impairment Independently Predicts Decreased Social Function Over Time

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 414-414
Author(s):  
Anna Huang ◽  
Kristen Wroblewski ◽  
Ashwin Kotwal ◽  
Linda Waite ◽  
Martha McClintock ◽  
...  
Keyword(s):  
Mental Health ◽  
Logistic Regression ◽  
Cognitive Function ◽  
Social Engagement ◽  
Social Function ◽  
Ordinal Logistic Regression ◽  
Sensory Function ◽  
Sensory Impairment ◽  
Over Time

Abstract The classical senses (vision, hearing, touch, taste, and smell) play a key role in social function by allowing interaction and communication. We assessed whether sensory impairment across all 5 modalities (global sensory impairment [GSI]) was associated with social function in older adults. Sensory function was measured in 3,005 home-dwelling older U.S. adults at baseline in the National Social Life, Health, and Aging Project and GSI, a validated measure, was calculated. Social network size and kin composition, number of close friends, and social engagement were assessed at baseline and 5- and 10-year follow-up. Ordinal logistic regression and mixed effects ordinal logistic regression analyzed cross-sectional and longitudinal relationships respectively, controlling for demographics, physical/mental health, disability, and cognitive function (at baseline). Adults with worse GSI had smaller networks (β=-0.159, p=0.021), fewer close friends (β=-0.262, p=0.003) and lower engagement (β=-0.252, p=0.006) at baseline, relationships that persisted at 5 and 10 year follow-up. Men, older people, African-Americans, and those with less education, fewer assets, poor mental health, worse cognitive function, and more disability had worse GSI. Men and those with fewer assets, worse cognitive function, and less education had smaller networks and lower engagement. African-American and Hispanic individuals had smaller networks and fewer close friends, but more engagement. Older respondents also had more engagement. In summary, GSI independently predicts smaller social networks, fewer close friends, and lower social engagement over time, suggesting that sensory decline results in decreased social function. Thus, rehabilitating multisensory impairment may be a strategy to enhance social function as people age.

scholarly journals POS0204 AUTOANTIBODIES AND SYSTEMIC LUPUS ERYTHEMATOSUS INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA THERAPY IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 318.1-318
Author(s):  
D. Santos Oliveira ◽  
A. Martins ◽  
F. R. Martins ◽  
F. Oliveira Pinheiro ◽  
M. Rato ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Disease Duration ◽  
Seroconversion Rate ◽  
Necrosis Factor Alpha ◽  
Malar Rash ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Over Time

Background:Anti-tumour necrosis factor alpha (anti-TNF-α) therapy is commonly used to treat inflammatory conditions such as rheumatoid arthritis (RA). Autoantibodies namely antinuclear antibodies (ANA) induced by these treatments are well established. However, anti-TNF-α-induced systemic lupus erythematosus (SLE) is rarely described and its incidence is yet unknown.Objectives:This study aimed to determine the prevalence of ANA seroconversion and to characterize the development of SLE induced by anti-TNF-α therapy in patients with RA over time.Methods:An observational retrospective cohort study was conducted with at least one year of follow-up. Patients with diagnosis of RA, according to American College of Rheumatology criteria (ACR), and registered on Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2003 and 2019 were included. Patients with positive ANA (titer ≥100) and/or positive double-strand DNA (dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. As there are no recognized criteria for drug-induced SLE, the diagnosis of SLE induced by anti-TNF-α was considered if there is a temporal relationship between clinical manifestations and anti-TNF-α-therapy, the presence of at least 1 serologic ACR criteria (ANA or anti-dsDNA) and at least 1 nonserologic ACR criteria (arthritis, serositis, hematologic disorder or malar rash) [1]. Continuous variables are presented with mean, standard deviation, median, quartile 1 and quartile 3. Categorical variables are presented with absolute and relative frequencies.Results:A total of 211 patients (mean age of 49.9±10.9 years old; 84.4% female) were included with a median follow-up time of 6 [3-14] years. We found a seroconversion rate for ANA of 75.4% (n=159) with median treatment duration of 31 [8.5-70.5] months. The most common titre was 1/100 with diffuse and speckled patterns. ANA seroconversion was higher for etanercept (47.8%, n=76) than with adalimumab (23.9%, n=38), infliximab (13.8%, n=22), golimumab (12.6%, n=20) or certolizumab (1.9%, n=3). SLE induced by anti-TNF-α occurred in two patients (0.9%) with erosive and seropositive (rheumatoid factor and anti-citrullinated protein antibodies) RA previously treated with two conventional synthetic disease-modifying antirheumatic drugs, including methotrexate. The first patient, a female with 66 years old and 17 years of disease duration, developed SLE after 16 months of infliximab, with constitutional symptoms, abrupt worsening of polyarthritis, ANA titer of 1/320 diffuse pattern and positive dsDNA (248 UI/mL) antibodies. The second patient, a woman with 43 years old and 11 years of disease duration, developed SLE after 41 months of adalimumab with malar rash and ANA titer of 1/320 diffuse pattern, positive dsDNA (285 UI/mL), positive anti-histone antibodies and hypocomplementemia. In these two cases, anti-TNF-α therapy was stopped and recovery was spontaneous without treatment. The first patient switched to adalimumab and the second switched to golimumab without recurrence of SLE for more than ten years.Conclusion:We found a high rate of ANA seroconversion induced by anti-TNFα therapy in patients with RA. However, similar to previous literature, only 0.9% of patients developed SLE with mild manifestations without major organ involvement. Although the drug with the highest ANA seroconversion rate was etanercept, those responsible for induced SLE were infliximab and adalimumab. Patients improved after discontinuation of therapy and tolerated an alternative anti-TNF-α drug without recurrence of induced SLE over time. Therefore, ANA and SLE induced by anti-TNF-α should be considered and reported in the follow-up of RA patients. Further research is needed to explore the impact of this adverse event on the outcomes of treatment over time.References:[1]Hochberg MC. Arthritis Rheum. 1997;40(9):1725.Disclosure of Interests:None declared

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