Introduction :

Fibrous dysplasia may involve one (monostotic) or multiple (polyostotic) bones. Although any bone can be affected, it occurs most commonly in the proximal femur, tibia, ribs, and skull. In its polyostotic form, fibrous dysplasia may be associated with extra skeletal anomalies. Along with café-au-lait spots and precocious puberty, polyostotic fibrous dysplasia completes the triad that defines McCune-Albright syndrome. We report one such case.

Clinical Profile:

A 20 year old woman came with complaints of fracture of the right forearm following trivial trauma four years back. She also had fractures of the right forearm and the right leg three years back, without any significant trauma. She had multiple bone pains for last two months.

She had no history of any renal or pancreatic disease. She had no complaints of galactorrhoea or early menarche.

Biochemical investigations : 

ALP > 1400, PTH – 720 pg/ml. Calcium and phosphate levels were normal.

Radiological findings:

1. Skeletal Survey (radiograph of the skull, dorso-lumbar spine and both upper and lower extremities)

There was reduction in bone density with multiple lytic lesions in the long bones. There were areas of sclerosis in the metaphysis of the long bones.

DL spine showed reduced bone density with endplate sclerosis suggestive of rugger jersey spine.

Multiple lytic lesions were seen in the scapula, ribs, clavicle multiple vertebral bodies, pelvic bones and metacarpals on both the sides.

There was subperiosteal resorption on the radial aspect of head of second proximal phalanx.

Skull radiograph showed widening of the diploic spaces with multiple well defined, variable sized sclerotic lesions.

2. USG neck – there was a well-defined heterogeneously hypoechoic lesion posterior to the right lobe of the thyroid.

3. CT Parathyroid protocol – Arterially hyper enhancing lesion posterior to the right lobe of the thyroid, suggestive of parathyroid adenoma

Figure 1A, 1B, 1C, 1D, 1E - The shafts of the long bones show groundglass opacities with expansion of the mandibular and thinning of the cortex.

Fig 2  A and 2 B : 2A , 2B , 2C , 2D, 2E -There is severe osteoporosis.

Ground glass opacities are seen within the vertebral bodies. There is a relative osteosclerosis of the vertebral endplates. Similar changes are seen in the bones of the pelvis on both sides.. 

Fig 3- There is subperiosteal resorption on the radial aspect of head of second proximal phalanx.

Fig 4 The diploic spaces are widened and replaced with bone and soft groundglass opacities. There are multiple circumscribed areas of osteosclerosis throughout the skull.

Fig 5 The sonogram of the neck shows a well-defined heterogeneously hypoechoic lesion posterior to the right lobe of the thyroid.

Fig 6 A , 6B – Well defined hypodense lesion posterior to the right lobe of thyroid

Fig7A , 7B – There is arterial phase hyperenhancement of the lesion 

FIG 8A, 8B, 8C – The lesion shows enhancement lower than the thyroid gland in both arterial and venous phase suggestive of type B enhancement curve

Radiological diagnosis:  

Fibrous dysplasia ; Primary hyperparathyroidism : McCune-Albright syndrome

Further management: The patient is planned for resection of the parathyroid adenoma.

Discussion

Fibrous dysplasia of bone is a sporadic genetic condition caused by activating missense mutations in the G-protein alpha subunit (GNAS1) gene on the long arm of chromosome 20 that encodes the alpha subunit of the stimulatory G protein-coupled receptor (Gsα). (1)

These postzygotic mutations substitute an arginine with a cysteine, histidine, or serine residue at position 201. The activating mutations selectively inhibit guanosine triphosphatase (GTPase) activity, resulting in constitutive activation of 5’ adenosine monophosphate (AMP)-protein kinase A intracellular signal transduction pathways. Osteoblastic cells expressing mutant Gsα undergo increased proliferation and do not mature properly, leading to overproduction of disorganized fibrous bone. (2,3)

Fibrous dysplasia may involve one (monostotic) or multiple (polyostotic) bones. Although any bone can be affected, it occurs most commonly in the proximal femur, tibia, ribs, and skull. (4)

In its polyostotic form, fibrous dysplasia may be associated with extra skeletal anomalies. Along with café-au-lait spots and precocious puberty, polyostotic fibrous dysplasia completes the triad that defines McCune-Albright syndrome. Other endocrinopathies may also be present, including acromegaly, hyperthyroidism, and rarely, hyperparathyroidism (5). Association with hyperparathyoidism is thought by some to be simply coincidental (6). When polyostic fibrous dysplasia occurs in association with soft tissue myxomas, it is known as Mazabraud syndrome (7).

Hyperparathyroidism refers to excess parathyroid hormone in the body. It can be primary, secondary, or tertiary. Primary hyperparathyroidism can be caused by parathyroid adenoma ,parathyroid hyperplasia or parathyroid carcinoma. Secondary hyperparathyroidism is caused by chronic hypocalcaemia resulting from renal osteodystrophy, malnutrition, vitamin D deficiency which leads to parathyroid hyperplasia. Tertiary hyperparathyroidism results from autonomous parathyroid adenoma caused by the chronic overstimulation of hyperplastic glands in renal insufficiency.

Fibrous dysplasia and skeletal lesions caused by hyperparathyroidism share a common pathogenesis; both are generated by the intracellular downstream effect of activation of the parathyroid hormone (PTH) G protein-coupled receptor of osteogenic cells. In hyperparathyroidism, these receptors are overstimulated by excessive amounts of PTH, whereas they are constitutively active due to Gsα mutations in patients with fibrous dysplasia (8).

The resulting activation of AMP-protein kinase A signaling leads to an increase in osteoclastogenesis and subsequent bone resorption in both fibrous dysplasia and hyperparathyroidism (9).

While there is evidence to suggest that mutant cells in fibrous dysplastic lesions are more sensitive to PTH, interestingly, elevated serum PTH does not seem to impact unaffected bone in fibrous dysplasia patients. (10)

The spectrum of bone lesions of fibrous dysplasia can be classified into three primary bony patterns: cystic, sclerotic and mixed. A typical FD lesion in the axial skeleton appear as an area of radiolucent ground glass matrix, which is usually smooth and homogeneous, not centrally located within medullary bone. Craniofacial FD typically demonstrates dense and sclerotic lesions. The lesions usually cause cortical thinning due to enlarged fibro-osseous masses within the bone. The periosteal reaction is not usually present unless it is associated with a pathological fracture. Although endosteal scalloping may be present, a smooth outer cortical contour is always maintained. The lesion may undergo expansile remodelling secondary to the enlarging mass of fibro-osseous tissue. A thick layer of sclerotic bone is known as a rind sign. Small islands of cartilage, which later ossify and are seen as dense punctate or flocculent calcifications within FD lesions, can also be seen. This combination of enchondromas within an FD lesion, referred to as fibro cartilaginous dysplasia, is most frequently seen in the proximal femur. (11)

Radiological features of hyperparathyroidism includes subperiosteal bone resorption, subchondral resorption, subligamentous resorption, salt and pepper skull , browns tumor, acro osteolysis, rugger jersey spine and osteopenia. Subperiosteal bone resorption results from increased bone turnover due to the unregulated effects of parathyroid hormone on bone calcium homeostasis (12). Elevated PTH levels lead to upregulation of nuclear factor-κβ ligand (RANKL), which interacts with its respective RANK receptor on osteoclast progenitor cells, leading to resorption via the indirect growth of bone-remodelling osteoclasts (13, 14). The osseous changes most commonly occur at the proximal and middle phalanges at the radial margins of the second and third fingers (15). Salt-and-pepper skull is another characteristic finding of HPT resulting from diffuse, lytic foci interspersed between regular bone in the calvarium giving a granular skull appearance (16). Lytic lesions are due to localized bone loss. The lytic lesions associated with HPT also called brown tumours. Osteolytic aggregate of cyst-like entities seen in long-standing hyperparathyroidism termed Osteitis fibrosa cystica. The most common sites of brown tumors include the pelvis, mandibles, ribs, long bones, and hands and vertebrae. (17)

In our case, there is widening of diploic spaces with multiple sclerotic lesions in skull , multiple lytic lesions were seen in the scapula, ribs, clavicle multiple vertebral bodies, pelvic bones and metacarpals , few of them shows ground glass matrix. All these features suggestive of fibrous dysplasia. Along with that there is reduction in bone density, rugger jersey spine , multiple browns tumors and parathyroid  adenoma suggestive of coexistent primary hyperparathyroidism.

There are few case reports shows coexistence of fibrous dysplasia and primary hyperparathyroidism. Ehrig and Wilson described two patients with monostotic fibrous dysplasia and primary hyperparathyroidism. (18) Rosen and Palmer reviewed 350 cases of hyperparathyroidism seen over 20 years at the University of Toronto. They noted 5 patients with facial bone lesions; histology revealed fibrous dysplasia in 2 cases and nonossifying fibromas in the other 3 (19). Adina F. et al described 10 patients shows coexistence of fibrous dysplasia and primary hyperparathyroidism. Most of them have polyostotic fibrous dysplasia. (1)

Although coexistence of these two conditions reported, there is no syndromic association or genetic condition responsible for coexistence found yet. So, all these cases are considered coincidental. 

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