A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure

Abstract

A 40-year-old male was hospitalized with renal impairment and severe hypercalcemia. His concentration of serum IgG4 was high, but serum whole PTH, 1-25(OH) vitamin D3 and PTHrP were not elevated. Computed tomography showed swelling of the bilateral lacrimal glands and systemic lymphadenopathy. The histological findings of lacrimal gland biopsy fulfilled the diagnostic criteria of IgG4-related ophthalmic disease (IgG4ROD). Bone scintigraphy showed increased ectopic uptake in the stomach, heart, lungs, and kidneys. He died on day 16 of admission, although the therapies for hypercalcemia were continued. Autopsy results showed an increase of osteoclasts in the bone marrow and metastatic calcification in multiple organs, and excluded from the differential diagnosis other disorders which present lymph-node swelling and hypercalcemia such as cancer, lymphoma, Castleman's disease, and sarcoidosis. He was given a diagnosis of IgG4ROD with osteolytic hypercalcemia.

IgG4‐related disease presenting as severely symptomatic hypercalcemia: A case report and review of literature

“…The remaining 2 cases 11,15 were similar to our patient, who had non-PTH-related hypercalcemia and the serum PTH levels were decreased. Tranah et al 15 reported a patient diagnosed with IgG4-RD involving thyroid gland, submandibular gland, and lymph nodes, and had a good response to high-dose corticosteroid treatment.…”

“…7,10 Hypercalcemia occurring in patients with IgG4-RD is not common. A literature review showed that only 5 definitely [11][12][13][14][15] (including 1 conference abstract 15 ) and 2 possible (not biopsied) IgG4-RD 16,17 associated hypercalcemia had been reported (Table 1). According to the literature, the pathogenesis of IgG4-RD-associated hypercalcemia can be divided into parathyroid hormone (PTH)-related and non-PTH-related.…”

“…Tranah et al 15 reported a patient diagnosed with IgG4‐RD involving thyroid gland, submandibular gland, and lymph nodes, and had a good response to high‐dose corticosteroid treatment. Kawakita et al 11 reported a patient with IgG4‐related ophthalmic disease who died of cardiac arrest due to severe hypercalcemia that did not respond to medications (including high dose of corticosteroid) and hemodialysis treatments. Autopsy results indicated a high turnover bone status, an increase of osteoclasts in the bone marrow, and metastatic calcification in multiple organs.…”

“…Kawakita et al 11 reported a patient with IgG4-related ophthalmic disease who died of cardiac arrest due to severe hypercalcemia that did not respond to medications (including high dose of corticosteroid) and hemodialysis treatments. Autopsy results indicated a high turnover bone status, an increase of osteoclasts in the bone marrow, and metastatic calcification in multiple organs.…”

Effect of Parathyroid Function After Thyroidectomy and Radioactive-Iodine Therapy for Thyroid Disease

“…Low calcium can lead to circumoral or peripheral paranesthesia, tetany, carpopedal spasm, laryngospasm, and ECG changes from long QT interval to VT arrest [1,2]. While high calcium can cause fatigue, polyuria, polydipsia, nephrolithiasis, peptic ulcer disease, altered mental status, gait instability [3][4][5], myalgia, arthralgia, abdominal pain [4], rare submandibular gland atrophy and sialolithiasis, metastatic pulmonary calcification [6,7], sometimes even inducing acute kidney injury or acute pancreatitis [8][9][10][11][12][13], or being life-threatening [14,15]. The parathyroid gland is an adjacent organ of the thyroid.…”