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Primary biliary cholangitis and primary sclerosing cholangitis (PSC) are the most common cholestatic liver diseases (CLD) in adults and are both characterized by an immune pathogenesis. While primary biliary cholangitis is a model autoimmune disease, with over 90% of patients presenting very specific autoantibodies against mitochondrial antigens, PSC is considered an immune mediated disease. Osteoporosis is the most common bone disease in CLD, resulting in frequent fractures and leading to significant morbidity. Further, sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients. The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected. Although timely diagnosis, prevention, and management of osteosarcopenia are crucial to limit the consequences, there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD. International guidelines recommend screening for bone disease at the time of diagnosis of CLD. However, the optimal monitoring strategies and treatments have not been defined yet and vary among centers. We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD, and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.

The four regulatory subunits (R1A, R1B, R2A, R2B) of protein kinase A (PKA) are differentially expressed in several cancer cell lines and exert distinct roles in both cell growth and cell differentiation control. Mutations of the PRKAR1A gene have been found in patients with Carney complex and in a minority of sporadic anaplastic thyroid carcinomas. The aim of the study was to retrospectively evaluate the expression of different PKA regulatory subunits in benign and non benign human thyroid tumours and to correlate their expression with clinical phenotype. Immunohistochemistry demonstrated a significant increase in PRKAR2B expression in both differentiated and undifferentiated (anaplastic) thyroid tumors in comparison with normal thyroid tissues. Conversely, a significant increase in PRKAR1A expression was only demonstrated in undifferentiated thyroid carcinomas in comparison with normal thyroid tissue and differentiated thyroid tumors. In thyroid cancers without lymph nodal metastases PRKAR1A expression was higher in tumours of more than 2 cm in size (T2 and T3) compared to smaller ones (T1). In conclusion, our data shows that an increased PRKAR1A expression is associated with aggressive and undifferentiated thyroid tumors.

Some authors proposed to lower the present postglucose GH nadir cut-off (i.e.1 microg/l) to that obtained in healthy subjects to establish remission of acromegaly. The aim of the study was to correlate GH nadir with hormonal and metabolic parameters and to confirm the adequacy of the current limit to define disease remission.Retrospective study of 40 acromegalic patients cured by surgery, followed by radiotherapy when appropriate, studied at the time of disease remission (Phase 1) and re-evaluated after at least 3 years' follow-up (median 6.5 year, Phase 2). GH nadir was evaluated in 44 sex- and age-matched controls.Symptom score, pituitary function, neuroradiological imaging, metabolic parameters (BMI, glucose metabolism, insulin sensitivity, lipid profile, blood pressure).The upper limit of the 'normal' GH nadir was fixed at 0.26 microg/l (mean + 2SD of controls). In Phase 1, GH nadir was0.26 microg/l in 16 patients (Group A) and0.26 microg/l in 24 patients (Group B). Group B had only slightly higher IGF-1 SDS (0.4 +/- 1.0 vs.- 0.1 +/- 1.0, P = ns) and lower body mass index (BMI) than Group A (26.2 +/- 2.4 vs. 30.6 +/- 4.5 kg/m(2), P0.005). GH nadir positively correlated with IGF-1 (P0.05, r = 0.32) and negatively with BMI (P0.05, r = 0.42). In Phase 2, all patients had IGF-1 levels in the normal range and GH nadir1 microg/l, both parameters being even lower than those found at the time of remission. No patient had either clinical or neuroradiological evidence of disease recurrence.The current GH nadir limit is still adequate to define both short- and long-lasting remission of acromegaly, independently of the type of definitive treatment. Patients with the lowest GH nadir should probably be monitored long-term for adequacy of their GH secretion.