Glucagonoma With Necrolytic Migratory Erythema: Metabolic Profile and Detection of Biallelic Inactivation of DAXX Gene

Tamura, Ai; Ogasawara, Tatsuki; Fujii, Yoichi; Kaneko, Hiromi; Nakayama, Akihiro; Higuchi, Shinji; Hashimoto, Naoko; Miyabayashi, Yui; Fujimoto, Masanori; Komai, Eri; Kobayashi, Takashi; Sakuma, Ichiro; Nagano, Hidekazu; Suzuki, Shohachi; Koide, Hisashi; Yokote, Koutaro; Iseki, Kozue; Oguma, Rena; Matsue, Hiroyuki; Nojima, Hiroyuki; Sugiura, Katsura; Yoshitomi, Hideyuki; Ohtsuka, Masayuki; Rahmutulla, Bahityar; Kaneda, Atsushi; Inoshita, Naoko; Ogawa, Seishi; Tanaka, Tomoaki

doi:10.1210/jc.2017-02646

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…There is a case report of FDG-avid pancreatic glucagonoma on FDG PET/CT in a patient with NME [ 25 ]. In the reported case, mild FDG uptake with SUVmax of 2.3 was seen in the tumor.…”

Section: Classification Of Pdmentioning

confidence: 99%

F-18-FDG PET/CT findings of paraneoplastic dermatoses

Suga

2022

Jpn J Radiol

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Paraneoplastic dermatoses (PD) are defined as nonspecific skin disorders which are associated with internal neoplasms, but without direct association to primary tumors or metastases. Recognition of PD and the following surveillance may lead to the diagnosis of internal malignant neoplasms including early stage ones. Accurate imaging examinations in the following searching is essential in identifying the underlying neoplasms. Since whole-body 18-fluoro-2-deoxyglucose (F-18-FDG)-positron emission (PET)/computed tomography (CT) has been widely used in early diagnosis, staging of various malignant tumors, it may play a role for detection of underlying or occult malignant neoplasms in patients with PD. However, to date, only a few reports of FDG PET/CT findings of the associated neoplasms in PD patients have been cited in the literature. The present paper shows the cases of FDG-avid associated neoplasms in patients with PD in our 10-year experience in our institute, and reviews the well-known and/or relatively common PD and their associated neoplasms, and the previously reported cases of FDG-avid associated neoplasms in these patients.

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“…There is a case report of FDG-avid pancreatic glucagonoma on FDG PET/CT in a patient with NME [ 25 ]. In the reported case, mild FDG uptake with SUVmax of 2.3 was seen in the tumor.…”

Section: Classification Of Pdmentioning

confidence: 99%

F-18-FDG PET/CT findings of paraneoplastic dermatoses

Suga

2022

Jpn J Radiol

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“…Studies have shown that people with elevated circulating concentrations of glucagon over 7-fold higher than normal are at risk of protein wasting, hypoaminoacidaemia and weight loss [42]. Similarly, necrolytic migratory erythema, which is also seen in glucagonoma [43] and with prolonged treatment for congenital hyperinsulinaemia [44], may be linked with a decrease in circulating amino acids [45]. Therefore, because it is unknown whether a decrease in circulating amino acids will increase protein breakdown in lean tissue, the clinical consequences that could arise from the reduction of amino acids seen with NN1177 are currently unclear.…”

Section: Discussionmentioning

confidence: 99%

Glucagon/GLP-1 receptor co-agonist NNC9204-1177 reduced body weight in adults with overweight or obesity but was associated with safety issues

Friedrichsen

Nygård

Endahl

et al. 2022

Preprint

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Glucagon/glucagon-like peptide-1 (GLP-1) receptor co-agonists may provide greater weight loss than agonists targeting the GLP-1 receptor alone. We report results from three phase 1 trials investigating the glucagon/GLP-1 receptor co-agonist NNC9204-1177 (NN1177) for once-weekly subcutaneous use in adults with overweight or obesity. Our focus was a 12–week multiple ascending dose (MAD), placebo-controlled, double-blind trial in which adults (N=99) received NN1177 (dose-escalated to treatment doses of 200, 600, 1,300, 1,900, 2,800, 4,200, and 6,000 µg) or placebo. Two other trials also contribute to the findings in this report: a first human dose (FHD) / single ascending dose (SAD), placebo-controlled, double-blind trial in which adults (N=49) received NN1177 (treatment doses of 10, 40, 120, 350, 700 and 1,100 μg) or placebo, and a drug–drug interaction (DDI), open-label, single-sequence trial in which adults (N=45) received a 4,200 µg dose of NN1177. Pharmacokinetic, safety and tolerability, and pharmacodynamic endpoints were assessed. For the MAD and FHD/SAD trials, baseline characteristics were generally balanced across groups. The half-life of NN1177 was estimated at between 77.3 and 111 hours. NN1177 appeared tolerable across trials; however, a number of safety concerns were observed, including an increase in heart rate (range 5–22 beats per minute) and decrease in reticulocyte count, which were both dose dependent, and increased markers of inflammation (fibrinogen and C-reactive protein), hepatic disturbances (increased aspartate aminotransferase and alanine aminotransferase), impaired glucose tolerance (dose groups 2,800–6,000 ug) and reduced blood levels of some amino acids. Clinically relevant weight loss was achieved (up to 12.6% at week 12; 4,200 ug in the MAD trial), but this was not accompanied by cardiometabolic improvements. In conclusion, although treatment with NN1177 was associated with dose-dependent and clinically relevant weight loss, unacceptable safety concerns precluded further clinical development.

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“…Real-time RT-PCR analysis RT-qPCR experiments were performed as previously described [10][11][12] . The FBP1 gene-speci c mRNA expression values were determined and normalized to those of β-actin as an internal control.…”

Section: Real-time Rt-pcr Analysismentioning

confidence: 99%

Characterization based on genotype–biochemical phenotype association in fructose-1,6-bisphosphatase deficiency

Tanaka

Sakuma²,

Nagano

et al. 2022

Preprint

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Purpose Fructose-1,6-bisphosphatase (FBPase) deficiency, caused by an FBP1 mutation, is an autosomal recessive disorder characterized by hypoglycemic lactic acidosis. The mechanism by which the mutations cause enzyme activity loss is uncertain. Methods We performed whole-exome sequencing in an adult patient with severe hypoglycemic lactic acidosis and identified that the patient carried compound heterozygous missense mutations of FBP1 with c.491G > A (p.G164D) and c.581T > C (p.F194S). Results Biochemical analysis revealed that FBP1 mutant (G164D or F194S) decreased protein expression and enzyme activity loss. The interactome analysis for binding partners demonstrated that G164D and F194S mutants interact with the proteins involved in unfolded protein response. Additionally, G164D and F194S mutants aggregated in the endoplasmic reticulum, suggesting the involvement of protein misfolding in its pathogenesis. All FBP1 missense mutations previously reported were classified into three functional categories: Type 1 mutations, located at pivotal residues in enzyme activity motifs with no effects on protein expression; Type 2 mutations, which mediate changes in amino acid hydrophobicity and structurally cluster around the substrate-binding pocket, are associated with aggregation in the endoplasmic reticulum, and decreased protein expression; and Type 3 mutations, which are likely non-pathogenic mutations. Conclusion Protein misfolding contributes to FBPase deficiency pathogenesis, particularly in Type 2 mutations.

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Glucagonoma With Necrolytic Migratory Erythema: Metabolic Profile and Detection of Biallelic Inactivation of DAXX Gene

Cited by 15 publications

References 19 publications

F-18-FDG PET/CT findings of paraneoplastic dermatoses

F-18-FDG PET/CT findings of paraneoplastic dermatoses

Glucagon/GLP-1 receptor co-agonist NNC9204-1177 reduced body weight in adults with overweight or obesity but was associated with safety issues

Characterization based on genotype–biochemical phenotype association in fructose-1,6-bisphosphatase deficiency

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