Parathyroid Diseases and T Cells.

PURPOSE OF REVIEW: This review summarizes studies into the permissive role of T cells in the bone catabolic effects of hyperparathyroidism and parathyroid hormone (PTH). RECENT FINDINGS: Work in animals combined with recent translational studies in humans now highlight the potent amplificatory action of T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a complex pathway by which PTH exploits natural self-renewal functions of CD4+ T cells, to drive TNFα production that promotes formation of IL-17A secreting Th17 T cells. TNFα and IL-17 further amplify osteoblastic receptor activator of NF-κB ligand (RANKL) production and down-modulate osteoprotegerin (OPG), establishing conditions propitious for osteoclastic bone resorption. These findings are consistent with, and add to, the traditional view of PTH-induced bone loss involving only osteoblast-lineage cells. T cells potently amplify traditional pathways and provide permissive costimulatory signals to bone marrow stromal cells, facilitating the development of an increased RANKL/OPG ratio favourable to bone resorption and bone loss.

[Inflammation of the parathyroid glands]. / Entzündungen der Nebenschilddrüsen.

Inflammation of the parathyroid glands is rare when compared to other endocrine organs. This leads to the use of descriptive terms as well as the lack of a generally accepted classification for inflammatory disorders of the parathyroid glands. This review article proposes that parathyroid inflammation be subdivided morphologically into (a) non-specific lymphocytic infiltration, which is more an expression of damage to small vessels, due to e. g. severe systemic inflammation or myocardial infarction, (b) autoimmunogenic lymphocytic parathyroiditis, (c) nonimmunogenic inflammation caused by granulomatous diseases or infections and (d) invasive sclerosing (peri) parathyroiditis. As only parathyroid glands removed due to hyperparathyroidism and normal parathyroid glands incidentally removed during thyroid surgery are seen almost exclusively in routine histopathology, virtually no information about the morphological correlate of hypoparathyroidism is available.

Parathyroid and autoimmunity.

Data in favor of chronic hypoparathyroidism as an autoimmune disease are examined. The article takes into consideration the different clinical forms, genetic patterns, histopathology, animal models, cellular immunity, circulating autoantibodies, target autoantigens, clinical manifestations, laboratory diagnosis and therapy. Furthermore, data on 71 Italian patients with chronic hypoparathyroidism are presented.

Immunoheterogeneity of parathyroid hormone in parathyroid cysts: diagnostic implications.

Parathyroid cysts are uncommon lesions of the neck leading to hypercalcemia in a significant percentage of cases. The distinction between parathyroid and thyroid cysts is difficult to make on a clinical basis alone and relies on the demonstration of elevated PTH levels in cyst fluid. We describe a case of a parathyroid cyst in which intact PTH (1-84) levels were misleadingly low while midmolecule 44-68 PTH was markedly elevated. To explain this discrepancy, we studied cyst fluid from this and two other patients using Sephadex G-75 gel chromatography. Fractions were analyzed using an immunoradiometric assay for intact hPTH (1-84) and a RIA specific for the midmolecular 44-68 region of hPTH. Immunoreactivity corresponding to hPTH (1-84) was absent in the first case but present in the remaining two. Immunoreactive peaks corresponding to PTH fragments were demonstrable in all three cyst samples. Patients with elevated hPTH (1-84) in cyst fluid were hypercalcemic; in contrast, the patient with a low cyst level of hPTH (1-84) was normocalcemic despite having markedly elevated levels of midmolecule PTH (44-68) in both serum and cyst fluid. Parathyroid cysts may thus produce fragments rather than intact PTH; reliance on an intact hPTH assay could lead to misdiagnosis. The measurement of PTH by a midmolecular assay may be preferable to the measurement of intact PTH in the evaluation of fluid from cystic neck masses.

The presence of immunoglobulin D in endocrine disorders and diseases of immunoregulation, including the acquired immunodeficiency syndrome.

Immunoglobulin D (IgD) was determined by double diffusion in the serum from 26 patients with endocrine disorders and diseases of immune imbalance along with controls. IgD was detected in the serum of nine patients that included two with primary parathyroidism, one with insulin-resistant diabetes, four with immunodeficiencies, and two with Hodgkin's disease. IgD was absent in the serum of seven patients with the same diagnoses after treatment. IgD was present in the serum of the majority of acquired immune deficiency syndrome patients (in eight of ten cases). The presence of IgD in the serum of these patients suggests that it plays a role in receptor-mediated events.

Hyperplastic parathyroiditis--a new autoimmune disease?

A case of parathyroiditis with epithelial hyperplasia is reported in which the histological features suggest an autoimmune process analogous to Hashimoto's disease.