3.1 Patient demographics, imaging, and biochemical work-up
The patient details were included in Table 1. There were six male and
three female patients. The median age at diagnosis was 53 years
(interquartile range [IQR], 41–63 years), the median follow-up
after initial resection was 64 months (IQR, 20–98 months), and the
median maximum tumor size was 20 mm (IQR, 11–36 mm).
The patient’s symptoms on presentation to a doctor were bone or joint
pain in multiple locations. The time elapsed between the initial
patient’s complaints and the diagnosis of TIO ranged from 5 to 126
months with a median delay of 72 months. Only 22% of patients were
correctly diagnosed within 2 years, while 56% were correctly diagnosed
between 5 and 10 years after the onset of symptoms. X-rays revealed
pseudofractures in all of the patients (Fig. 1a–e). Whole-body99mTc bone scintigraphy demonstrated increased uptake
in multiple bones, including ribs, vertebrae, and femur, in four
available cases. The endocrine work-up revealed the following laboratory
findings: low serum phosphate (median 1.3 [IQR, 1.2–1.7] mg/dL,
normal range, 2.7–4.6 mg/dL), high serum ALP (median 281 [IQR,
251–355] U/L, normal range, 38–113 U/L), normal to low serum
corrected calcium (median 8.7 [IQR, 8.5–9.0] mg/dL, normal range,
8.8–10.1 mg/dL), and normal to high intact parathyroid hormone (median
64 [IQR, 43–123] pg/mL, normal range, 15–65 pg/mL). The serum
FGF23 was elevated (median 241 [IQR, 194–3750] pg/mL). The clinical
signs, imaging studies, low serum phosphate levels, and elevated serum
FGF23 levels all pointed TIO.
To determine the localization of the primary tumor, systemic venous
sampling of FGF23 was performed in five patients. FGF23 levels were
highest in the internal jugular vein in two patients, the external
jugular vein, subclavian vein, and superior vena cava in one patient
each (Table 1). In all patients, MRI revealed a tumor in the head and
neck region. Somatostatin receptor scintigraphy was performed, which
enabled tumor visualization in all four available patients. FDG-PET/CT
revealed mild uptake (SUV max median 5.7, IQR 5.1–6.2) in the suspected
tumor.