Necessity of therapy for post-thyroidectomy hypocalcaemia: a multi-centre experience.

PURPOSE: Hypoparathyroidism is one of the most common and most feared complications of total thyroidectomy (TT). The aim of this study is to detect possible markers that may facilitate early tracing of hypocalcaemia-prone patients in order to reduce clinical cost by optimizing patient discharge and to avoid unnecessary treatment. METHODS: Over an 18-month period, 995 patients, 23 % male and 77 % female, aged 52.9 ± 13.4 years, underwent TT in ten Lombardy hospitals. The following parameters were analyzed: calcaemia before and 12-24 and 48 h after surgery, pre- and post-operative parathyroid hormone (PTH) at 24 h and pre-operative 25OH vitamin D. RESULTS: Mortality was nil and morbidity was 22.4 %. Mean 24-h calcaemia and PTH were 2.17 ± 0.15 mmol/l and 31.81 ± 20.35 pg/ml, respectively; mean 24-h PTH decay was 36.7 ± 34.12 %. Four hundred seventy-three (47.5 %) patients were hypocalcaemic at discharge; 142 of whom had transient hypoparathyroidism that became permanent in 27. Patients developing hypocalcaemia had significantly higher values of PTH and calcium decay. At multiple logistic regression, only 24-h calcium decay, PTH drop and the presence of symptoms and parathyroid auto-grafting were significantly related to hypoparathyroidism. The association of these factors had a 99.2 % negative predictive value (NPV) for the development of hypoparathyroidism. A 70 % PTH drop had a 93.75 NPV for transient hypoparathyroidism. A 12 % calcaemia decay had a 95.7 NPV for hypoparathyroidism. CONCLUSIONS: Hypocalcaemic asymptomatic patients with less than 70 % PTH and 12 % calcaemia decay may be safely discharged without treatment. Symptomatic patients and those with parathyroid grafting should receive calcium and vitamin D.

Tumour-associated fibroblasts contribute to neoangiogenesis in human parathyroid neoplasia.

Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) showed an abundant periacinar distribution of α-SMA(+) cells in normal parathyroid glands (n=3). This pattern was progressively lost in parathyroid adenomas (PAds; n=6) where α-SMA(+)cells were found to surround new microvessels, as observed in foetal parathyroid glands (n=2). Moreover, in atypical adenomas (n=5) and carcinomas (n=4), α-SMA(+) cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (n=37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation.