Endocrine Abstracts

Investigation of parathyroids in mouse models is hampered by difficulties in identifying the small glands. We developed a microsurgical technique to identify murine parathyroids by dissecting from the distal thyrothymic ligament to the lower thyroid pole (LTP). Parathyroids were identified in 100 mice which comprised: 48 mice deleted for a cell-division-cycle 73 gene allele (Cdc73^+/−), involved in the hyperparathyroidism-jaw tumour syndrome; 10 mice deleted for a multiple endocrine neoplasia type 1 gene allele (Men1^+/−); and 42 wild-type controls (Cdc73^+/+; Men1^+/+). Parathyroid gland length and position relative to the LTP was assessed by histology. Parathyroid tumours from Men1^+/− or Cdc73^+/− mice were significantly larger than normal wild-type glands (mean length (±S.E.M.) was 762.8 μm (±62.0) in Men1^+/− mice; 819.7 μm (±30.4) in Cdc73^+/− mice; and 316.0 μm (±33.6) in Cdc73^+/+;Men1^+/+ mice, P<0.0001). The anatomical locations of the parathyroids relative to the LTP were as follows: ~40% were within 66.5 μm (±35.3) of the LTP; ~25% were 769.9 μm (±72.3) above the LTP in the posterior thyroid capsule; ~21% were 995.0 μm (±153.4) below the LTP in the thyrothymic ligament; ~7% were within the thyroid, 1275.3 μm (±125.4) above the LTP; and ~7% were within the thymus, 2233.3 μm (±68.8) below the LTP. Thus, ~35% of mouse parathyroids, as opposed to <10% of human parathyroids, are in the thyroid, thyrothymic ligament, or thymus. Electron microscopy revealed ultrastructural differences and demonstrated that Men1^+/− parathyroid tumour cells compared to wild-type parathyroid cells: were smaller with a reduced cytoplasmic:nuclear ratio (2.57 (±0.30) vs 40.77 (±15.48), respectively, P<0.05); had more mitochondria per unit cytoplasmic area (13.35 (±1.12) vs 3.78 (±0.43), P<0.0001); and fewer secretory granules (4.75 (±0.67) vs 26.82 (±4.34), P<0.0001). This study, which represents the first anatomical location and ultrastructural characterisation of murine parathyroids, reveals that parathyroid tumours are more frequently located at ectopic sites, contain significantly more mitochondria, but have fewer secretory granules.

Declaration of funding: This work was supported by the United Kingdom Medical Research Council (Grant numbers G9825289, 2004 and G1000467, 2010) and the United Kingdom National Institute of Health Research.