Matteo Corbetta

Background: Articular and psychological complications of acromegaly are known to impair patients’ quality of life (QoL). This multicenter prospective observational study aimed to (1) identify clinical predictors of the progression of these complications, (2) evaluate their progression in relation to disease activity, and (3) assess their impact on QoL. Materials and Methods: Ninety-five patients with acromegaly were enrolled, excluding those with inflammatory rheumatic diseases. Clinical history, hormonal, and physical exams were collected at baseline and after 42 months. Specific questionnaires assessing joint and psychological discomfort (WOMAC, AIMS, VAS) and QoL (AcroQoL) were administered. Results: A regression model identified clinical predictors of progression. Female sex was significantly associated with worsening joint symptoms (VAS P = .0302; AIMS symptoms P = .0328), as was prior radiotherapy (AIMS P = .0071). Use of dopamine agonists (DAs) was linked to higher AIMS depression scores (P = .0224). Interestingly, patients with disease recurrence showed lower joint pain scores compared with baseline. In contrast, mood scores improved with disease remission. Notably, suicide emerged as a relevant cause of death in this cohort, underscoring the need for comprehensive psychological care. Conclusions: Female sex and prior radiotherapy emerged as predictors of progressive joint symptom worsening. Changes in depression and joint complaints alongside disease course suggest a complex involvement of IGF1. Dopamine agonists may negatively affect mood, though further studies are needed. Overall, joint disease had a greater and independent negative impact on QoL compared to mood disorder. Articular and psychological complications remain a significant burden, particularly in women with acromegaly.

Diagnosis of primary hyperparathyroidism (PHPT) relies on the detection of hypercalcemia and increased circulating parathormone (PTH) levels. However, the disease induces a deep deregulation of phosphate metabolism. A total of 960 PHPT patients (848 females, 112 males) were retrospectively enrolled; biochemical and clinical data were collected at PHPT diagnosis. At variance with previous studies, hypophosphatemia was diagnosed using sex- and age-specific serum phosphate reference range. Reduced serum phosphate levels were detectable in 49% of PHPT males and 55% of PHPT females. Moderate hypophosphatemia (≤2.0 mg/dL) was more frequent in men than in women, and serum phosphate levels were lower in postmenopausal than premenopausal PHPT women. Vitamin D status did not alter the prevalence of hypophosphatemia. Serum phosphate levels negatively correlated with ionized calcium and PTH levels across PHPT premenopausal women, postmenopausal women, and men. Cluster analysis integrating the three interrelated parameters identified three distinct PHPT phenotypes: bone and kidney complications were more frequent in patients with more severe hypercalcemia and hypophosphatemia, though fractures were more abundant in the less severe phenotypes. Finally, considering the whole cohort, ionized calcium and PTH levels displayed a negative non-linear correlation with phosphate levels. In conclusion, hypophosphatemia in PHPT patients is common, and moderate hypophosphatemia is more frequent in males compared to females. Menopausal status is associated with less severe hypophosphatemia and PHPT disease. Hypophosphatemia is mainly determined by parathyroid tumor cells’ dysfunction. The non-linear negative relationships between phosphate, PTH and ionized calcium may suggest heterogeneous insensitivity of tumor parathyroid cells to extracellular phosphate.