SUN-769 Chronic PTH deficiency leads to impaired neural plasticity

Abstract Disclosure: E. Sargentini: None. A. Naciu: None. A. Palermo: None. G. Tabacco: None. M. Cereghino: None. F. Motolese: None. G. Musumeci: None. V. Di Lazzaro: None. F. Capone: None. Objective: Chronic hypoparathyroidism (hypoPT) is characterized by low serum calcium levels, accompanied by low or inappropriately normal levels of parathyroid hormone (PTH). The conventional treatment involves the use of activated vitamin D and/or calciumsupplements. Many hypoPT patients experience symptoms that indicate a decline in their quality of life. These symptoms often include physical issues (such as fatigue, increased susceptibility to fatigue, muscle spasms, pain, and paresthesia), cognitive symptoms (such as "brain fog", difficulty concentrating, slow processing speed, executive function, auditory memory, and visual memory), and emotional struggles. Transcranial magnetic stimulation (TMS) is a powerful tool to evaluate, in vivo, cortical excitability and brain circuits functioning. Purpose: we aimed to investigate cortical excitability, circuit functioning, and plasticity propensity in hypoPT in comparison with controls. Material and Methods: we enrolled hypoPT treated with calcium and calcitriol and age-matched controls. All subjects underwent a biochemical examination including calcium-phosphorus metabolism. Moreover, cognitive status was evaluated using the validated Telephone-based Mini-Mental State Examination (itel-MMSE). Participants without significant cognitive impairment underwent transcranial magnetic stimulation (TMS), assessing cortical excitability (motor evoked potentials-MEP), circuit functioning (short-latency afferent inhibition and short intracortical inhibition), and plasticity via intermittent theta burst (iTBS) protocol. MEP amplitude was measured before and after iTBS and compared between patient and age-matched healthy control group. A patient subgroup had TMS recordings repeated after initiating PTH treatment [3 subjects on PTH(1-34) and 3 subjects on Palopegteriparatide]. Results: these are the results of this project that included 44 subjects (32 hypoPT and 12 controls). HypoPT patients had significantly lower PTH and calcium levels (p<0.001) and higher phosphorus levels (p<0.001) than controls. MEP amplitude changes after iTBS differed significantly between patients and controls (-0.02 mV vs 0.33 mV, p:0.03). Patients undergoing PTH replacement therapy showed MEP amplitude responses similar to controls (-0.3 mV vs 0.3 mV, p:0.04). No other statistically significant differences were observed in TMS parameters. Conclusion: our findings suggest that hypoPT present a functional impairment of neural plasticity mechanisms. PTH replacement therapy seems to restore this impairment, but we believe that further comprehensive studies are needed. Presentation: Sunday, July 13, 2025