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Objective. Association of primary hyperparathyroidism (pHPT) with phosphaturic mesenchymal tumors (PMT) is rarely reported. This report entertains the hypothesis of the causal association of HPT with tumor-induced osteomalacia (TIO) and of the existence of HPT-PMT syndrome. Case Presentation. A 49-year-old man presented with fragility rib fractures, generalized bone pain, and muscle weakness worsening over the past 3 years. Initial tests demonstrated hypophosphatemia and high PTH. The diagnosis of pHPT was entertained, but parathyroid scan was negative. During a 2-year follow-up, the patient reported minimal improvement of symptoms after intermittent treatment with calcitriol and phosphate. Biochemical evaluation showed persistent hypophosphatemia with renal phosphate wasting, elevated FGF23, and osteopenia on DXA scan. TIO was suspected. Multiple MRIs and whole-body FDG-PET scans were inconclusive. The patient subsequently underwent 68Ga-DOTATATE PET-CT, which revealed a somatostatin receptor-positive lesion in the lung. The resected mass was confirmed as PMT. The patient had dramatically improved symptoms, normal phosphate, calcium, and FGF23. During follow-up over 3 years postsurgery, the patient had slowly rising calcium and persistently elevated PTH. Conclusion. The debate whether the patient had pHPT or tertiary HPT prompted literature review showing that aberrant genes including FGFR1, FGF1, fibronectin 1, and Klotho were mechanistically involved in the HPT-PMT association. This case highlights the pitfalls contributing to delayed diagnosis and treatment of TIO and hypothesizes the association between pHPT and PMT.

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Background: Localization of tumor-induced osteomalacia (TIO) is often challenging. Primary hyperparathyroidism (HPT) following curative surgery for TIO is rarely reported. Clinical Case: A 49-year-old man presented with fragility rib fractures, generalized bone pain, and muscle weakness worsening over the past 3 years. Rheumatologic workup was negative. Initial tests showed elevated levels of parathyroid hormone (PTH) 114.1 pg/mL (14–72 pg/mL) and alkaline phosphatase (ALP) 283 IU/L (44–174 IU/L), reduced levels of 25(OH)D 16 ng/mL (30–100 ng/mL), 1,25(OH)2D 9 pg/mL (18–72 pg/mL), and phosphorus 1.6 mg/dL (2.5–4.9 mg/dL), calcium levels of 9.2 mg/dL (8.5–10.1 mg/dL), and eGFR 58 mL/min/1.73 m2. A sestamibi scan showed normal parathyroid uptake. The diagnosis was secondary HPT due to chronic kidney disease and vitamin D deficiency. The patient was treated with D3 and phosphate. During a 2-year follow-up, the patient reported improvement of pain and weakness with no additional fractures. Further investigations showed persistent hypophosphatemia with elevated urinary fractional phosphate excretion (44%, ref. <20%), indicating renal phosphate wasting. Fibroblast Growth Factor 23 (FGF23) was high, 291 RU/mL (0–180 RU/mL). DXA results were consistent with osteopenia. TIO was suspected. At a 3-year follow-up, investigations included three whole-body 18F-FDG PET-CT scans revealing several areas suspicious for tumor presence. However, multiple MRIs were inconclusive. Laboratory tests showed persistent hypophosphatemia (despite D3 and phosphate treatment), elevated FGF23 (1330 RU/mL) and PTH (274.4 pg/mL), and normal calcium, 25(OH)D, and 1,25(OH)2D. The patient subsequently underwent 68Ga DOTATATE PET-CT, which revealed a somatostatin receptor-positive lesion involving the left upper lobe of the lung. The mass was resected without complications. Histopathology was compatible with a phosphaturic mesenchymal tumor. At a 6-month postoperative follow-up, the patient reported dramatically improved symptoms with decreased weakness and pain, normal phosphate, calcium, ALP, and FGF23 (160 RU/mL) levels, while DXA results were significantly improved. Phosphorus supplementation was discontinued. At follow-up 3 years post-surgery, the patient had slowly rising PTH (126.3 pg/mL) and calcium (10.1–10.6 mg/dL) levels with normal phosphate, 25(OH)D, and FGF23 (174 RU/mL) levels. A diagnosis of primary HPT was made. Further evaluation was deemed unnecessary since the patient did not meet the criteria for surgical treatment. The development of primary HPT was considered mechanistically related to long-standing hypophosphatemia and hypovitaminosis D stimulating PTH production. Conclusion: This case report highlights the pitfalls contributing to delayed diagnosis of TIO and alerts clinicians to the potential development of primary HPT after curative surgery for TIO.

Purpose: Obesity is a chronic disease that is acquiring pandemic proportions. Emerging research suggests that probiotics can be a valuable yet still an underutilized modality for obesity treatment. This review aims to analyze and summarize recent data focusing on published meta-analyses of randomized controlled trials (RCTs) to help understand the role of probiotics in fighting obesity. Materials and Methods: Meta-analyses were sought and reviewed from PubMed, Cochrane Central Library, ScienceDirect, and Google Scholar for body weight and/or BMI changes (two main outcomes of interest). Results: The literature review identified 14 meta-analyses. On average, the meta-analyses dedicated to probiotics included 4-15 trials with 154-994 participants, whereas more inclusive probiotics and/or synbiotics analyses included 15-68 trials with 895-4015 participants. Eleven out of 14 meta-analyses showed that probiotic use in RCTs resulted in reduced body weight and/or BMI compared to placebo. An average weight loss was 0.6 kg, and the most substantial loss was 4.8 kg corresponding to 0.7% and 5.9% reductions in body weight, respectively. Probiotics' use was associated with improved health outcomes in addition to weight loss and was safe. The subgroup analyses showed that the probiotic forms (supplements vs food) and the dosages (lower vs higher than 10 10 CFU/day) did not substantially influence weight loss. The single species particularly helpful for weight loss appeared to be L. gasseri, L. casei, L. delbrueckii, L. reuteri, L. rhamnosus, a combination of L. curvatus and L. plantarum and Bifidobacterium longum. Bacillus subtilis and Akkermansia muciniphila also had a potential as anti-obesity probiotics. Conclusion: Probiotics, despite small effects, could be a valuable addition to the armamentarium of obesity management. Further basic and translational research and clinical trials are required to elucidate mechanisms and specific probiotic and patients' types for the best achievable precision medicine approach to the obesity epidemic.