PTH-related disorders have a major impact on bone metabolism and skeletal properties because of the pivotal role of PTH in calcium and phosphate homeostasis and bone remodeling. Hyperparathyroidism is characterized by continuous exposure to excessive endogenous PTH, causing increased bone turnover in favor of bone resorption. Depending on the background of PTH overproduction, hyperparathyroidism is divided into primary, secondary, and tertiary hyperparathyroidism. The clinical presentation varies from deterioration of bone microarchitecture and decreased bone mineral density to profound bone involvement, such as osteitis fibrosa cystica and fragility fractures. Although successful parathyroidectomy represents the definitive treatment and may promote regression of most of the skeletal defects, the medical approach of calcimimetics and antiresorptive agents is a promising alternative in cases where parathyroidectomy is not feasible or unsuccessful. Hypoparathyroidism is the pathophysiological counterpart of hyperparathyroidism and also leads to disorders of bone metabolism and structure. Chronic PTH deprivation is associated with low bone remodeling and increased bone mineral density. The defective microarchitecture might affect bone strength and raise the risk for adverse skeletal events. Recombinant human PTH acts as a replacement therapy and is safe and efficient in restoring calcium/phosphate homeostasis and bone turnover. However, it is approved only for refractory cases, as conventional management with calcium and active vitamin D remains the first-line treatment. This article reviews the skeletal involvement in the most frequent parathyroid disorders, hyperparathyroidism and hypoparathyroidism, and rare familial disorders of PTH metabolism, as assessed by clinical, laboratory, and imaging parameters, and the effect of the available treatment strategies.

The last decade has been revolutionary regarding the management of rare bone diseases caused by impaired calcium and phosphate metabolism. Elucidation of the underlying genetic basis and pathophysiologic alterations has been the determinant factor for the development of new, disease-specific treatment agents. The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) possesses a critical role in the pathogenesis of various hypophosphatemic disorders. Among them, the genetic disorder of X-linked hypophosphatemia and the acquired syndrome of tumor-induced osteomalacia, although very rare, have attracted the scientific community’s attention towards designing an FGF23-inhibitor as a potential specific therapy. The monoclonal antibody burosumab was approved for the treatment of children and adult patients with X-linked hypophosphatemia and recently for tumor-induced osteomalacia patients, demonstrating benefits regarding their symptoms, biochemical profile and bone mineralization status. Asfotase alfa is a hydroxyapatite-targeted recombinant alkaline phosphatase, an enzymatic replacement therapy, substituting the defective activity of tissue non-specific alkaline phosphatase, in patients suffering from hypophosphatasia. Promising data regarding its favorable effect on survival rate, bone quality, fracture healing, muscle strength, mobility, respiratory function, and general quality of life have led to the approval of the drug for the treatment of childhood-onset hypophosphatasia. Given the high costs of treatment for both agents and their limited clinical use until now, more data are needed to define patients’ characteristics that make them ideal candidates for therapy. Long-term safety issues also need to be clarified.

DICER1 syndrome (DICERs) represents a tumor predisposition genetic syndrome, inherited in an autosomal dominant manner. Germline loss-of-function variants of the DICER1 gene lead to impaired processing of microRNA, gene expression, and increased risk of tumorigenesis. Although pleuropulmonary blastoma (PPB) is the hallmark of the syndrome, multiple extrapulmonary malignant and non-malignant conditions have also been described, including multinodular goiter (MNG) and sex-cord stromal tumors. MNG is one of the most common components and is associated with an increased risk of thyroid carcinoma. Sertoli–Leydig cell tumor (SLCT) represents the most prevalent type of sex-cord stromal tumor associated with the syndrome, whereas juvenile granulosa cell tumor (JGCT) is considered to be a very rare phenotype. They both may present with abdominal pain due to mass effect and menstrual irregularities in case of hormone production. Although they exhibit low rates of mortality, recurrence rates highly depend on the grade of malignancy. Herein, we report a novel pathogenic DICER1 variant associated with MNG, bilateral ovarian SLCT, and JGCT in a young Greek patient. Clinicians should be aware of a potential germline DICER1 variant when evaluating MNG in young patients, especially if it coexists with other neoplasms.

The pituitary gland is an uncommon site of tumor metastasis and is predominantly associated with malignancies of the lung and breast. Metastatic involvement of the pituitary gland in lung cancer (LC) typically indicates advanced disease and is associated with poor prognosis and pituitary insufficiency, which often remains underdiagnosed and significantly affects quality of life and survival. We present four cases of pituitary metastasis (PM) originating from LC, characterized by distinct histological subtypes, variable timing from initial diagnosis, and diverse clinical manifestations. Clinical presentation was heterogeneous: two patients had involvement of both pituitary lobes with multiple pituitary hormone deficiencies, one had anterior lobe involvement with anterior pituitary deficiency following immune checkpoint inhibitor-associated hypophysitis, and one remained asymptomatic. Therapeutic approaches included partial surgical resection followed by radiotherapy in two patients and radiotherapy alone in the other two; all patients continued systemic antineoplastic therapy and received hormone replacement as indicated. Mean overall survival was 7.5 months. PM can occur across all histological subtypes of LC and typically signifies advanced disease with poor prognosis. Early identification and appropriate management of hypopituitarism may improve quality of life and clinical outcomes.

Turnersyndrome (TS) is a genetic chromosomal disorder including various manifestations depending on the karyotype;endocrine, gastrointestinal, respiratory, neurological, urogenital, musculoskeletal, and cardiovascular disorders contribute to increased morbidity and mortality. Liver function abnormalitiesare less well studiedand mostly associated withinsulinresistance, obesity, diabetes, hypogonadism, hypothyroidism, and autoimmune conditions. The association of liver pathology with architectural changes of various etiologies and the metabolicdysfunction-associated liver diseaseis of particular interest. Herein, we presentthree cases of adult women with TSand persistent elevation of liver enzymesdue toporto-sinusoidal vascular disorder(PSVD). In one case,the diagnosis of TS followedthe liver biopsy results.The absence of cardiometabolic risk factors, the low liver stiffness andthe cardiovascular malformationsmay predict this histological diagnosis. Liver function impairment in TS may derive from a broad spectrum of liver pathology, including PSVD, and requires careful evaluation,to decrease the risk of complications.

Background/Objectives: Turner syndrome (TS) is a genetic chromosomal disorder including various manifestations depending on the karyotype; endocrine, gastrointestinal, respiratory, neurological, urogenital, musculoskeletal, and cardiovascular disorders contribute to increased morbidity and mortality. Liver function abnormalities are less well studied and mostly associated with insulin resistance, obesity, diabetes, hypogonadism, hypothyroidism, and autoimmune conditions. The association of liver pathology with architectural changes in various etiologies and the metabolic dysfunction-associated liver disease is of particular interest. Methods: Herein, we present three cases of adult women with TS and the persistent elevation of liver enzymes due to porto-sinusoidal vascular disorder (PSVD). Results: In one case, the diagnosis of TS followed the liver biopsy results. The absence of cardiometabolic risk factors, low liver stiffness and cardiovascular malformations may predict this histological diagnosis. Conclusions: Liver function impairment in TS may derive from a broad spectrum of liver pathology, including PSVD, and requires careful evaluation to decrease the risk of complications.