Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that frequently produce and release catecholamines. Catecholamine excess can manifest in several cardiovascular syndromes, including cardiomyopathy. PPGL-induced cardiomyopathies occur in up to 11% of cases and are most often associated with an adrenal pheochromocytoma (90%) and rarely with a paraganglioma derived from the sympathetic ganglia (10%). PPGL-associated cardiomyopathies can be chronic or acute, with takotsubo cardiomyopathy being the most often reported. These two types of PPGL-induced cardiomyopathy seem to have different pathophysiological backgrounds. Acute catecholaminergic stress inundates myocardial β-adrenoceptors and leads to left ventricle stunning and slight histological apoptosis. In chronic cardiomyopathy, prolonged catecholamine exposure leads to extended myocardial fibrosis, inflammation, and necrosis, and ultimately it causes dilated cardiomyopathy with a low ejection fraction. Sometimes, especially in cases associated with hypertension, hypertrophic cardiomyopathy can develop. The prognosis appears to be worse in chronic cases with a higher hospital mortality rate, higher cardiogenic shock rate at initial presentation, and lower left ventricular recovery rate after surgery. Therefore, establishing the correct diagnosis at an early stage of a PPGL is essential. This mini-review summarizes current data on pathophysiological pathways of cardiac damage caused by catecholamines, the clinical presentation of PPGL-induced cardiomyopathies, and discusses treatment options.

Prolonged exposure to an excess of glucocorticosteroids (GCs), both endogenous and exogenous, leads to a wide range of comorbidities, including cardiovascular, metabolic, psychiatric, and musculoskeletal disorders. The latter comprise osteopenia and osteoporosis leading to skeletal fractures and myopathy. Although endogenous hypercortisolemia is a rare disorder, GCs are among the most frequently prescribed drugs, often administered chronically and despite multiple side effects, impossible to taper off due to therapeutic reasons. The pathophysiology of the effect of GC excess on bone often leads to fractures despite normal or low-normal bone mineral density and it includes direct (mainly disturbance in bone formation processes, through inactivation of the Wnt/beta-catenin signalling pathway) and indirect mechanisms (through suppressing the gonadal and somatotrophic axis, and also through antagonizing vitamin D actions). Glucocorticosteroid-induced fast-twitch, glycolytic muscles atrophy occurs due to increased protein catabolism and impaired synthesis. Protein degradation is a result of activation of the ubiquitin proteasome and the lysosomes stimulated through overexpression of several atrogenes (such as FOXO-1 and atrogin-1). This review will discuss pathophysiology, clinical presentation, prevention, and management of GCinduced osteoporosis (including calcium and vitamin D supplementation, and bisphosphonates) and myopathy associated with GC excess.

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, predominantly caused by a single parathyroid adenoma that is responsible for the excessive secretion of parathyroid hormone (PTH)—the hallmark of disease. Excess of this hormone causes remarkable changes in bone metabolism, including an increased level of bone remodeling with a predominance of bone resorption. Those changes lead to deterioration of bone structure and density, especially in cortical bone. The main treatment for PHPT is surgical removal of the adenoma, which normalizes PTH levels and terminates the progression of bone disease and leads to its regeneration. However, because not all the patients are suitable candidates for surgery, alternative therapies are needed. Current non-surgical treatments targeting bone disease secondary to PHPT include bisphosphonates and denosumab. Those antiresorptives prevent further bone loss, but they lack the ability to regenerate already degraded bone. There is ongoing research to find targeted drugs capable of halting resorption alongside stimulating bone formation. This review presents the advancements in understanding the molecular mechanisms responsible for bone disease in PHPT and assesses the efficacy of new potential therapeutic approaches (e.g., allosteric inhibitors of the PTH receptor, V-ATPase, or cathepsin inhibitors) aimed at mitigating bone loss and enhancing bone regeneration in affected patients.

Introduction: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)₂D₃. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild.Aim of the study: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases.Case presentation: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)₂D₃ concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC–MS/MS, which revealed high levels of 25(OH)D₃, low levels of 24,25(OH)₂D₃ and elevated 25(OH)₂D₃/24,25(OH)₂D₃ ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively).Conclusions: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC–MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.

Primary aldosteronism is the most common cause of secondary hypertension, yet most cases remain unrecognized and left without optimal treatment. The diagnostic inertia may be attributed to the lack of specific symptoms, insufficient awareness among physicians, still conflicting indications for screening for primary aldosteronism and first and foremost challenging diagnostics. This review describes the current challenges of biochemical diagnostics of primary aldosteronism, including screening, case confirmation and subtyping. It also discusses immunoassays widely used in assessment of suspected autonomous aldosterone secretion – recent advances in the field and limitations of the method in comparison to the gold standard - liquid chromatography –tandem mass spectrometry. The review focuses on the application of novel “omics” strategies in the diagnostics of primary aldosteronism. Steroidomics and proteomics offer a possibility to simultaneously assess steroids and protein/peptides on a large scale. This multianalyte approach in comparison to the selective quantification of a chosen compound has been proved useful in the diagnostics of primary aldosteronism. It also offers a unique insight into the individual characteristics, underlying mechanisms and even reflects the genetic alterations of primary aldosteronism cases. The “omics” techniques are associated with large amounts of generated data, the interpretation of which may be troublesome and often necessitates the use of artificial intelligence. The novel advances in the biochemical diagnostics of primary aldosteronism, including “omics” techniques, presented in this review may help to address the most emerging problems, increase the number of diagnosed patients and facilitate the choice of an optimal treatment.

The maintenance of skeletal integrity relies on bone remodeling, a dynamic process orchestrated by the interplay between osteoclasts, osteoblasts, and the regulatory network of osteocytes. Traditional bone turnover markers (BTM) provide a non-invasive tool to assess bone metabolic activity. However, their clinical utility is limited by a low specificity and poor reproducibility. Moreover, traditional BTM do not reflect osteocyte function, despite the central role of these cells in bone remodeling. Novel BTM, including proteins (namely sclerostin, DKK-1, RANKL/OPG, and periostin), lipids (namely sphingosine-1-phosphate), and miRNAs, offer more specific insights into the interactions between bone cells and molecular signaling within the bone microenvironment. These markers represent potential therapeutic targets, with anti-sclerostin antibodies already approved for osteoporosis treatment. Another fundamental aspect of skeletal integrity is the process of mineralization, which is tightly regulated by three hormones: parathyroid hormone (PTH), vitamin D, and fibroblast growth factor 23 (FGF-23). These hormones not only maintain systemic calcium-phosphate homeostasis but also exert direct effects on bone cells, thereby influencing bone remodeling. This narrative review summarizes the functions, commonly used analytical methods, and clinical applications of novel BTM. It also presents the mechanisms of action of these hormones on bone tissue, along with new analytical approaches for measuring vitamin D, PTH, and FGF-23. The application of “omics” techniques in bone remodeling assessment is also discussed, with an emphasis on the advantages and limitations of these approaches.