Alteration in gut microbial characteristics of patients with acromegaly.

PURPOSE: Studies on intestinal microbiota in acromegaly are scant. This study aimed to characterize the gut microbiome in patients with acromegaly. METHOD: Stool samples were collected from 11 patients newly diagnosed with acromegaly and 12 healthy controls matched for body mass index (BMI) and age after three days on a standard diet. Clinical and gut microbial composition assessments were performed for the two participant groups using 16S rRNA gene amplicon sequencing. RESULTS: There was no difference in the alpha diversity of the microbiota between the samples from patients with acromegaly and those from the healthy controls. Based on beta diversity measurements, differences in microbial community structures were found to be significant only when compared using the Jaccard similarity index. The corresponding Firmicutes/Bacteroidota ratio tended to be higher in individuals with acromegaly than in healthy controls. The mean relative abundance of Actinobacteriota was 2.3 times higher in the acromegaly patient group than in the control group. Eggerthellaceae, Christensenellaceae, and Bacteroidaceae were among the significantly abundant bacterial families in the samples from the acromegaly patient group, while Butyricicoccaceae and Tannerellaceae were decreased. At the level of the genus, the most discriminative features were the abundance of Prevotella 7, Bacteroides, Senegalimassilia, Enterohabdus, the Family XIII AD3011 group, Howardella, and Hungatella in the samples from the acromegaly patient group. In contrast, the Butyrivibrio and the Eubacterium eligens group were the most discriminative genera for the healthy controls and were significantly less abundant in patients with acromegaly. While there were no significantly differentiated taxa between the diabetic and non-diabetic subgroups, Prevotella_7 was significantly enriched in the osteoarthritis (OA) subgroup. No significant association was found between individual genera and growth hormone (GH) levels and insulin-like growth factor-1 (IGF-1) levels as well as the upper limit of normal (ULN). CONCLUSION: Although alpha and beta diversity were mainly similar between the two groups, significant differences were observed between the acromegaly group and the control group at the family and genus levels. These results suggest that the differences between the microbial communities in patients with acromegaly and those in healthy individuals consist primarily of compositional differences independent of abundance. Prospective studies are needed to further explore the clinical implications of gut microbiome dysbiosis in patients with acromegaly.

Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Assessment of forearm muscles with ultrasound shear wave elastography in patients with acromegaly.

PURPOSE: The effects of acromegaly on soft tissues, bones and joints are well-documented, but information on its effects on muscle mass and quality remains limited. The primary goal of this study is to assess the sonoelastographic features of forearm muscles in patients with acromegaly. METHOD: Forty-five patients with acromegaly and 45 healthy controls similar in terms of gender, age, and body mass index (BMI) were included in a single-center, multidisciplinary, cross-sectional study. The body composition was analyzed using bioelectrical impedance analysis (BIA), and height-adjusted appendicular skeletal muscle index (hSMI) was calculated. The dominant hand's grip strength was also measured. Two radiologists specialized in the musculoskeletal system employed ultrasound shear wave elastography (SWE) to assess the thickness and stiffness of brachioradialis and biceps brachii muscles. RESULTS: The acromegaly group had significantly higher thickness of both the biceps brachii (p = 0.034) and brachioradialis muscle (p = 0.046) than the control group. However, the stiffness of the biceps brachii (p = 0.001) and brachioradialis muscle (p = 0.001) was lower in the acromegaly group than in the control group. Disease activity has not caused a significant difference in muscle thickness and stiffness in the acromegaly group (p > 0.05). The acromegaly group had a higher hSMI (p = 0.004) than the control group. The hand grip strength was similar between the acromegaly and control group (p = 0.594). CONCLUSION: The patients with acromegaly have an increased muscle thickness but decreased muscle stiffness in the forearm muscles responsible for elbow flexion. Acromegaly can lead to a permanent deterioration of the muscular structure regardless of the disease activity.

A case of pseudogout attack after zoledronic acid treatment in primary hyperparathyroidism.

Pseudogout (PG) is an inflammatory arthropathy that develops due to the accumulation of calcium pyrophosphate dihydrate crystals in synovial structures. Herein, we present a 59-year-old male patient with PG developed as a result of zoledronic acid (ZA) infusion, which was administered due to primary hyperparathyroidism. The patient with parathyroid adenoma was given ZA since the calcium level did not decrease despite intravenous saline and loop diuretic. One day after ZA administration, the patient had severe pain, fever, and swelling in joints. The radiograph showed chondrocalcinosis. Calcium pyrophosphate deposition were observed in the arthrocentesis fluid under polarized light. The patient's symptoms regressed after anakinra and colchicine treatment. To the best of our knowledge, this is the first case report of a PG attack after ZA treatment for primary hyperparathyroidism. Additionally, there have been few cases of PG after bisphosphonate treatment for osteoporosis in the literature, signifying that more care should be taken when administering bisphosphonate therapy in patients with risk factors.

Leukocyte Telomere Length and Neuregulin-4 Levels in Female Patients with Acromegaly: The Relationship between Disease Activity and Body Fat Distribution.

The study aimed to examine leukocyte telomere length (LTL) and serum neuregulin-4 levels and their relationship with disease activity, co-morbidities and body fat distribution in female acromegaly patients. Forty female patients with acromegaly and thirty-nine age and body mass index (BMI) similar healthy female volunteers were included in the study. Patients were classified into two groups: active acromegaly (AA) and controlled acromegaly (CA). The quantitative polymerase chain reaction (PCR) method was used to study LTL, and T/S ratio < 1 was accepted as shortened telomere length. Neuregulin-4 was studied by ELISA. There was no difference in median LTL between acromegaly and the control group (p = 0.530). The percentage of T/S < 1 in patients with acromegaly (60.0%) was similar to that of the control group (43.6%) (p = 0.144). However, serum neuregulin-4 was significantly higher in patients with acromegaly than those in the control group (p = 0.037). There were no significant differences concerning LTL, percentage of T/S < 1 and neuregulin-4 levels between active and controlled acromegaly groups (p > 0.05). Neuregulin-4 correlated positively with fasting glucose, triglyceride (TG), triglyceride/glucose (TyG) index, and lean body mass in the acromegaly group. A negative correlation was observed between LTL and neuregulin-4 in the control group (p = 0.039). When the factors affecting neuregulin-4 were evaluated by multivariate linear regression analysis with an enter method, TG (ß: 0.316, p = 0.025) was independently and positively associated with neuregulin-4. Our findings indicate that acromegaly is associated with unchanged LTL and high neuregulin-4 levels in female patients. However, the relationship between acromegaly, the aging process, and neuregulin-4 involves complex mechanisms, and further studies are needed.