Teaching Case

A 34-year-old female with prior history of X-linked hypophosphatemic rickets (XLHR), treated with high phosphate doses, is admitted to our hospital's endocrinology ward with intense diffuse skeletal pain. Laboratory findings revealed increased PTH levels and normal levels of serum calcium.

A skeletal survey was performed following the laboratory findings.
As a consequence of XLHR, short stature and multiple deformations are apparent, especially in the lower limbs (Figure 1). Rachitic rosary and healed looser zones are also visible (Figures 1 and 2).
Multiple expansive and lytic lesions are seen, especially in the right humerus and radius, producing no cortical interruption nor periosteal reaction - “brown tumours” (Figures 2 and 3). Bone reabsorption is apparent in several bones, most notably in the radial aspects of the middle phalanges (Figure 3e). Two other hallmark signs of hyperparathyroidism are observed: “salt-and-pepper” (Figure 4) and “rugger-jersey spine” (Figure 5).
The radiological findings were consistent with the diagnosis of hyperparathyroidism. A cervical ultrasonography was performed to screen for nodules, revealing a solid, hypoechoic nodule, inferior to the right lobe of thyroid, suggestive of a parathyroid adenoma (Figure 6). The diagnosis was histologically confirmed.

XLHR is a rare disorder characterized by alterations in the normal renal metabolism of phosphate due to reduced tubular reabsorption (with phosphaturia and hypophosphatemia) and lack of normal elevation of 1, 25(OH)2 vitamin D, the normal physiological response. This metabolic change leads to slow growth, rickets and osteomalacia[1, 2].

Hyperparathyroidism usually occurs in XLHR patients secondary to treatment with high phosphate doses. If left untreated, the continuous parathyroid stimulation can trigger autonomous parathyroid function, leading to a more unusual complication: tertiary hyperparathyroidism. These cases usually present with elevated levels of PTH and normal levels of serum calcium[1, 3, 4].
Symptoms often correlate with the level PTH and include generalized pain, decreased bone density and fractures, pruritus, nephrolithiasis, peptic ulcers, pancreatitis, soft tissue or vascular calcifications, muscle weakness and mental status alterations[4].

XLHR children exhibit the “classic” radiographic findings associated with of rickets: short stature, epiphyseal irregularities, genum varum and "rachitic rosary”[1, 2]. Adults usually present with diaphyseal long bone bowing (especially in lower extremities) and Looser zones (sclerotic, usually symmetrical insufficiency fractures). Enthesopathy and degenerative arthrosis are also common features in these patients, usually after the late second or third decades of life. Other findings include iliac wing flaring, endosteal hyperostosis, spondylosis and decreased vertebral density[5]. Radiographs are useful to screen painful locations for calcified enthesopathy and stress fractures[1].

Skeletal manifestations of hyperparathyroidism are numerous and well documented as primary hyperthyroidism is a relatively common condition. Bone reabsorption is a prominent feature of this disease and radiologists should be aware of the locations where it is most prevalent, such as the radial aspect of the second and third middle phalanges (a pathognomonic finding). In the skull, bone loss can manifest as the well-known “salt-and-pepper” sign. Other findings include “rugger-jersey spine”, soft tissue calcifications and insufficiency fractures[4, 7].
Indubitably, the most exuberant findings in our case were brown tumours. These lytic lesions are usually eccentric and well-defined, but are sometimes expansile, mimicking malignancy. They are the consequence of increased osteoclastic bone resorption and destruction in the cortical bone, and are usually found in ribs, long bones and pelvis. Calcification, sclerosis and size reduction of brown tumours is seen with adequate treatment of hyperparathyroidism, and can be used to assess therapeutic responsiveness[6].

In patients with XLHR secondary hyperparathyroidism can be managed medically, with phosphate cessation, but once tertiary hyperparathyroidism is detected surgical intervention is usually required[1, 3, 4].

Written informed patient consent for publication has been obtained.