Case Report: Does a Young Woman with Gitelman Syndrome Have Gout?

Gitelman syndrome causes chronic hypomagnesemia, which has been associated with calcium pyrophosphate deposition disease, because magnesium increases calcium pyrophosphate (CPP) crystal solubility and acts as a cofactor for many enzymes that degrade pyrophosphate, which is the anionic component of the CPP crystal.^5-7

Our patient had no radiographic evidence of chondrocalcinosis, nor did she have positively birefringent crystals in any of her synovial fluid samples. We have found no literature that supports an association between hypocalcemia and hyperuricemia. However, a recent study demonstrated an inverse relationship between magnesium and uric acid levels, so that chronic hypomagnesemia may contribute to hyperuricemia.⁸

Although metabolic abnormalities are recognized as associations with calcium pyrophosphate deposition disease, this case illustrates that electrolyte derangements may contribute to the development of other crystalline arthropathies.⁷

Gitelman syndrome is rare; nonetheless, it should be recognized as another metabolic cause of hyperuricemia and gout based on renal underexcretion of uric acid. In addition, it should be considered as a diagnosis in younger, premenopausal females, who usually are protected from gout by the enhancement of renal acid excretion with estrogen.^1,2,9

Our patient had several comorbidities (e.g., obesity and chronic renal insufficiency) that could have contributed to hyperuricemia; however, her hyperuricemia was out of proportion to the degree of azotemia.^1,2,9 She also had hypercalcemia secondary to primary hyperparathyroidism, which can result in an increased uric acid reabsorption and hyperuricemia.

Studies have demonstrated that uric acid levels decrease following a parathyroidectomy or, contrastingly, that levels increase with teriparatide, a parathyroid hormone agonist.^1,10,11

Gitelman syndrome and concomitant hyperparathyroidism are rare, with only a few cases cited in literature.¹² Although Gitelman syndrome mutations mimic thiazide diuretics, it is rare to see hypercalcemia due to hypomagnesemia impacting calciotropic hormones.¹²

In retrospect, we question our patient’s 2012 diagnosis of spondyloarthritis. Gout is well documented to affect peripheral joints; however, although rare, it can also have axial involvement. A small number of case reports describe gout at the sacroiliac joint.¹³ This can be difficult to diagnose on plain radiographs.^7,14 Radiographs of the pelvis in 2012 initially revealed suspected right-sided sacroiliitis. Later, in 2020, computed tomography (CT) of the abdomen and pelvis revealed bilateral sacroiliac joint erosions and resorption, and a diffuse sclerotic appearance of the osseous structures. We believe this is more consistent with her hyperparathyroidism, metabolic derangements or possible tophi.⁷

No dual-energy CT scan was performed. Her initial imaging of MTP and calcaneal erosions were likely most representative of gouty erosions, rather than enthesitis due to spondyloarthritis (see Figure 2). Tumor necrosis factor-α inhibitors have not been associated with hyperuricemia.