Low bone mineral density for age/osteoporosis in triple A syndrome—an overlooked symptom of unexplained etiology

Dumić, Miroslav; Putarek, Nataša Rojnić; Kušec, Vesna; Barišić, Nikola; Koehler, Katrin; Huebner, Angela

doi:10.1007/s00198-015-3265-0

Cited by 5 publications

(8 citation statements)

References 24 publications

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“…Osteoporosis, confirmed by measurement of low bone density, and presenting as early as childhood, has been reported in sporadic cases 48,49. It has been suggested that steroid supplementation alone could not explain the finding.…”

Section: Endocrinementioning

confidence: 99%

“…It has been suggested that steroid supplementation alone could not explain the finding. The cause may be multifactorial, given decreased or lack of physical activity and sun exposure due to immobilization in progressive neurological disease, malnutrition secondary to achalasia, and low levels of androgens 48. As such, patients and families should be counseled on preventive measures, screening, and nutritional supplementation.…”

Section: Endocrinementioning

confidence: 99%

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<p>Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach</p>

Flokas¹,

Tomani²,

Agdere³

et al. 2019

PHMT

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Allgrove syndrome or triple A (3A) syndrome is a multisystem disorder which classically involves the triad of esophageal achalasia, alacrima, and adrenal insufficiency due to adrenocorticotropin hormone insensitivity. It follows an autosomal recessive pattern of inheritance and is associated with mutations in the AAAS (achalasia–addisonianism–alacrima syndrome) gene. Since its first description in 1978, the knowledge on clinical and genetic characteristics has been expanding; however, the current literature is limited to case reports and case reviews. Early recognition of the syndrome is challenging, given the rarity of the condition and high phenotypic heterogeneity even among members of kin. The coordination of care for these patients requires a multidisciplinary team of specialists, including endocrinologists, neurologists, gastroenterologists, ophthalmologists, developmental specialists, dentists, geneticists, and surgeons. In this review, we aim to summarize the current recommendations for the diagnosis, management, and follow-up of patients with 3A syndrome.

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Section: Endocrinementioning

confidence: 99%

Section: Endocrinementioning

confidence: 99%

<p>Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach</p>

Flokas¹,

Tomani²,

Agdere³

et al. 2019

PHMT

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“…Upstream binding transcription factor ( UBTF ) functions in ribosomal RNA (rRNA) polymerase (Pol I and II)-specific transcription of the ribosomal genes to maintain genome stability, and the inhibition of UBTF leads to DNA damage and genomic instability independent of Pol I transcription [40], Bone cell proliferation and differentiation could be regulated by suppressed rRNA gene transcription due to UBTF acetylation modulated by RUNX2–HDAC1 interaction [41]. The mutation of Aladin WD repeat nucleoporin ( AAAS ) gene causes Triple A syndrome (alacrima, achalasia, adrenal failure, progressive neurodegenerative disease), which leads to osteoporosis due to reduced generation of testosterone and estrogens by adrenal androgens, less physical activity, and decreased exposure to the sun [42]. Meanwhile, our study found that AAAS, nucleoporin 155 (NUP155) , and Cvclin B1 (CCNB1) were significantly enriched in the GO term of mitotic nuclear envelope disassembly and directly interacted with the hub genes of the biological network (Fig.2C).…”

Section: Discussionmentioning

confidence: 99%

Gene-based GWAS analysis for consecutive studies of GEFOS

Zhu

Zhang

et al. 2018

Osteoporos Int

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Purpose Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes. Methods BMD-associated genes were identified by combining the summary statistic P values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential BMD-associated variants were evaluated by estimating the correlation of the P values of the same SNPs/genes between the two consecutive GEFOS studies with largely overlapping samples. Results Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, 3 novel genes (UBTF, AAAS, and C11orf58) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants. Conclusions Gene-based analysis as a supplementary strategy to SNP-based GWAS, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes.

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“…The clinical background of ACTH-independent and -dependent CS differs with regard to adrenal androgens [ 3 ]. Endogenous adrenal androgen is associated with the activation of osteoblasts or bone turnover [ 7 , 8 ]. The osteoporosis seen in adrenal CS has been speculated to be more influenced by CE, especially in women.…”

Section: Introductionmentioning

confidence: 99%

Sex Difference in the Association of Osteoporosis and Osteopenia Prevalence in Patients with Adrenal Adenoma and Different Degrees of Cortisol Excess

Izawa

Matsumoto

Matsuzawa

et al. 2022

International Journal of Endocrinology

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Objective. Osteoporosis and osteopenia (OS/OP) are frequent in patients with adrenal adenomas associated with cortisol excess (CE). However, the relationship between OS/OP and CE severity considering sex differences is unknown. Design. A cross-sectional observational study from January 2006 to December 2015. Patients. 237 patients with adrenal adenoma associated with CE, including Cushing’s syndrome and mild autonomous cortisol secretion (MACS), diagnosed in 10 referral centers in Japan. MACS was defined by 1 mg overnight dexamethasone suppression test (DST) cortisol level >1.8 μg/dL. Measurements. Prevalence of fragility fractures, medication for osteoporosis, and bone mineral density. Results. In total, 112 of 237 patients, who were predominantly female ( P < 0.001 ) and had lower BMI ( P = 0.013 ), had OS/OP. Patients with OS/OP was significantly affected by CE ( P < 0.01 ) than those without. The adjusted odds ratio (OR) for predicting OS/OP was obtained in multivariate logistic regression analysis. Clinical measures of CE, 1 mg DST cortisol levels, were positively associated with OS/OP in total cases (OR 1.124, 95% CI: 1.070–1.181, P < 0.001 ) and the cases with MACS (OR 1.156, 95%CI: 1.046–1.278, P = 0.005 ). A cutoff value of 1 mg DST cortisol level >5.0 μg/dL was associated with OS/OP differently between men and women. OS/OP risk in men with MACS was significantly affected only by 1 mg DST cortisol levels. However, OS/OP risk in women with MACS was significantly affected by 1 mg DST cortisol levels and age. Conclusions. CE severity in adrenal adenoma is positively associated with OS/OP. However, the associated factors of OS/OP in the patients with MACS are different between men and women.

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Low bone mineral density for age/osteoporosis in triple A syndrome—an overlooked symptom of unexplained etiology

Cited by 5 publications

References 24 publications

<p>Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach</p>

<p>Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach</p>

Gene-based GWAS analysis for consecutive studies of GEFOS

Sex Difference in the Association of Osteoporosis and Osteopenia Prevalence in Patients with Adrenal Adenoma and Different Degrees of Cortisol Excess

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