(11.07) A rare case of Paget’s disease of the bone in a young Filipino male with Graves’ disease.

Paget’s disease of the bone (osteitis deformans) is a focal disorder of bone metabolism that occurs in the aging skeleton; it is characterized by an accelerated rate of bone remodeling, resulting in overgrowth of bone at single or multiple sites and impaired integrity of affected bone. Commonly affected areas include the axial skeleton and long bones of the lower extremities. 

Case(s) Description : A 39-year-old man of Filipino descent with no known past medical history presented to our endocrinology clinic referred by his primary care physician due to abnormal thyroid function tests suggesting thyrotoxicosis. Review of systems was positive for an unintentional weight loss of 5 to 10 pounds over the past year. Vital signs were remarkable for an elevated blood pressure of 143/98 mmHg, otherwise within normal limits. On physical examination, he had a mild tremor on outstretched hands, otherwise unremarkable. Initial laboratories showed a low thyroid-stimulating hormone (TSH) level of 0.005 mIU/L, high free T4 of 4.70 ng/dL, high thyroid antibodies including high antithyroglobulin antibody (anti-TG) of 2.1 IU/mL, thyroid stimulating immunoglobulin (TSI) of 1.14 IU/L, thyroid peroxidase antibody (anti-TPO of 232 IU/mL), and thyrotropin receptor antibody (TRAb) of 2.52 IU/l. Treatment with methimazole 10 mg and propranolol 10 mg was started and new laboratories were ordered for follow-up in 6 weeks, which showed an elevated alkaline phosphatase (ALP) level of 258 IU/L and improvement of free T4 levels (2.12 μg/dL). Laboratories continued showing persistently elevated ALP level of 246 UI/L and bone-specific alkaline phosphatase (BAP) of 164.4 µg/L, despite normal thyroid function tests, and parathyroid hormone (26 pg/mL). An NM whole-body bone scan with Tc-99m was ordered and showed diffusely prominent osseus uptake, most pronounced in the skull, consistent with Paget’s disease of the bone. Treatment with single 5 mg IV dose of zoledronic acid was started and follow-up yearly was indicated. Follow-up laboratories 7 months later were remarkable for improvement of ALP levels (155 IU/L), BAP levels (35.9 µg/L), TSH levels normalized (0.936 mIU/L), low 25-OH vitamin D (23.7 ng/dL), and otherwise within normal limits. Low 25-OH vitamin D was treated with supplementation. Follow-up laboratories 10 months later were remarkable for normalized ALP levels (102 UI/L), BAP levels (15.1 µg/L), 25-OH vitamin D levels (52.4 ng/dL), and otherwise within normal limits. Treatment was adjusted to methimazole 10 mg three times a week. Follow-up laboratories 11 months later were within normal limits.

Discussion :

An intriguing aspect of Paget’s disease of the bone is the striking geographic variation in its prevalence. The disease predominantly affects people of European descent and is rare in Africans, people from the Indian subcontinent, and Asians. Case reports of Paget’s disease of the bone in patients from Filipino descent are extremely rare. The association of Paget’s disease and Graves’ disease has been described in very few reports and it isn’t understood yet. This case illustrates the necessity for further investigation between thyroid disease and metabolic bone disorders.