Mrs AG, a 40-year-old Filipino woman, presented with a two-month history of musculoskeletal chest wall pain without evidence of fracture on plain film. She had no history of trauma. A persistently elevated plasma alkaline phosphatase (ALP) was noted. Increased uptake in the right seventh rib, fourth thoracic vertebrae and the tibial shafts bilaterally was seen on a technetium-99m(99mTc) bone scintiscan. It was thought that she may have sustained injuries she did not recollect and no follow-up was arranged. Symptoms progressed over 12 months and she represented with pain. Repeat whole-body 99mTc bone scintigraphy demonstrated new areas of increased uptake.
A bone biopsy demonstrated osteomalacia. Plasma phosphate was noted to be low at 0.58 mmol/L (reference range [RR] 0.7-1.5mmol/L) and had been low at symptom onset (Table 1). She had low tubular reabsorption of phosphate (0.34mmol/L (RR 0.8 -1.35mmol/L)). TIO was suspected. Plasma FGF23 concentration was elevated at 113 RU/mL (RR 3-4RU/mL). Phosphate and calcitriol replacement were commenced.
Mrs AG underwent three MRI scans, two CT scans and an octreotide scintiscan over a six-year period before a 14mm lesion in the anterosuperior left femoral head was identified on 68Ga-DOTATATE PET/CT. In retrospect this lesion, though small and not reported, could be seen on MRI at the time TIO was first suspected.
Mrs AG opted for RFA as an alternative to surgery. CT-guided biopsy was performed at the time (Fig. 1). Histology confirmed PMT with positive immunohistochemical staining for FGF23. By two months all symptoms had resolved and plasma phosphate remained normal without supplementation. Seven years following RFA, Mrs AG remained symptom-free with no biochemical evidence of relapse.
Mrs PJ, a 36-year-old Māori woman, presented with worsening low back pain for one year and bilateral proximal muscle weakness for four months. Spinal MRI demonstrated superior endplate insufficiency fractures of multiple vertebral bodies. With knowledge of the previous case, the reviewing radiologist noted hypophosphataemia (0.24mmol/L) and referred to an endocrinologist. Adjusted plasma calcium was 2.15mmol/L, and ALP 198U/L (Table 1). Phosphate and calcitriol replacement were commenced.
MRI demonstrated a 21mm suspicious lesion in the left acetabulum. 68Ga-DOTATATE PET/CT demonstrated increased uptake in the left acetabulum corresponding to the lesion seen on MRI.
Planned RFA was deferred when Mrs PJ became pregnant. Phosphate and vitamin D supplementation were continued during pregnancy. CT-guided RFA was performed four months post-partum. Biopsy performed at the time of the RFA confirmed PMT, with FGF23 immunohistochemical staining strongly positive.
Plasma phosphate normalised for two months without supplementation, before beginning to fall. Repeat 68Ga-DOTATATE PET/CT showed the original lesion had reduced uptake compared to initial imaging but was still present. RFA was repeated 21 months following the first intervention. Plasma phosphate was normal without supplementation one month following ablation (1.27mmol/L) and at five years (1.19mmol/L).
Mrs AY a 60-year-old Chinese woman, was referred to Endocrinology on the basis of a 12-month history of back and leg pain, and a raised ALP (407 U/L). She had a past history of treated hypertension. 99mTc bone scintigraphy showed abnormal multifocal uptake in several ribs, thoracic and lumbar vertebrae, left sacroiliac joint, left acetabulum, bilateral tibial plateau and left maxilla. Hypophosphataemia was noted (plasma phosphate 0.57 mmol/L). TIO was suspected.
A whole-body MRI turbo STIR study was performed. A solitary 18x17x38mm lesion in the intertrochanteric region of the left femur was identified. This area demonstrated increased uptake on 68Ga-DOTATATE PET/CT. RFA was performed. Biopsies taken at the time of the procedure did not contain tumour elements.
One month following the procedure her plasma phosphate was elevated at 1.82 mmol/L and phosphate supplementation was stopped. Phosphate remained normal one month later (1.14mmol/L).
One year following RFA plasma phosphate had dropped to 0.61 mmol/L. Her plasma phosphate then temporarily normalised but within six months had fallen again and she had persisting symptoms. A repeat 68Ga-DOTATATE PET/CT demonstrated reduced but persistent uptake in the left proximal femur (Fig. 2). Biopsy and RFA were repeated. Again, no tumour was seen on histology. Seventeen months later, and four years after the first RFA, plasma phosphate was 1.09 mmol/L off supplementation.