Sarah Vanderlinde and Per-Lennart Westesson, MD, PhD, DDS
Clinical
Presentation: The patient is a 34-year-old female with a history of migraine headaches who presents for evaluation for an intracranial abnormality.
Radiological Findings:MR imaging of the head show symmetrical and diffuse thickening of the skull and bony structures of the jaw.
Differential Diagnosis: The differential diagnosis for diffuse thickening or hyperostosis of the skull and jaw bones in this patient would include chronic, severe anemia, hyperparathyroidism, Paget’s disease of bone, acromegaly, osteopetrosis, chronic dilantin ingestion and several rare genetic diseases such as Camurati-Engelmann’s disease, frontometaphyseal dysplasia and craniodiaphysial dysplasia.
Diagnosis: Idiopathic skull thickening
Discussion: Chronic, severe anemia such as iron-deficiency, sickle cell, spherocytosis and most often, thalassemia major can result in hyperplasia of the red marrow in response to the anemia. This can be seen on plain radiographs, CT or MRI often as the “hair-on-end” sign produced by alternating opaque,thickened trabeculae and areas of radiolucent marrow hyperplasia. There is also widening of the diploic space and thinning of the outer table of the skull. The marrow hyperplasia is often reversed following treatment of the anemia.
Hyperparathyroidism most commonly leads to demineralization of cortical bone, reflecting the "catabolic bone activity" of PTH, with relative preservation, or thickening, of trabecular bone, reflecting its "anabolic activity." Osteitis fibrosa cystica (brown tumors) is an indication of severe disease, which occurs through increased osteoclastic resorption of calcified bone and subsequent replacement by fibrous tissue. Untreated disease can result in disorganized bone destruction and replacement with fibrous tissue causing thickening of bony structures, though they are mechanically weak.
Paget’s disease of bone, or osteitis deformans, can cause bone thickening as a result of increased bone turnover and disordered bone remodeling. The resulting structurally disorganized mosaic of bone (woven bone) is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. Radiographs and MRI can demonstrate both osteolysis and excessive bone formation. New bone formation and sclerosis causes thickening of the cortex and coarse trabeculae. Skull radiographs may reveal osteoporosis circumscripta, a lytic lesion seen in the early stages of Paget's disease.
Acromegaly is caused by an unregulated increase in growth hormone usually caused by a pituitary adenoma. Enlargement of facial bones and thickening of the skull can be seen and are among the pathologic effects of increased production of insulin-like growth factor-1 (IGF-1) from the liver, stimulated by growth hormone.
Osteopetrosis is the result of failure of osteoclast bone resorption leading to thickened, sclerotic, weak bones. On imaging, the entire skull is thickened and dense, especially at the base. Sinuses are small and underpneumatized and vertebrae are extremely radiodense.
Chronic dilantin ingestion, usually over several years, can result in skull thickening by means of widening of the diploic space. The mechanism of this is not known.
Several rare genetic diseases can cause hyperostosis of the skull including Camurati-Engelmann’s disease, frontometaphyseal dysplasia (FMD) and craniodiaphysial dysplasia (CDD). Engelmann’s disease is autosomal dominant and causes gross thickening of the cortex of bones beginning in the femur or tibia and eventually involving all bones. Onset is before 30 years of age and is usually before 10 years. FMD is an X-linked disorder which causes cranial hyperostosis, prominent supraorbital ridges and flared metaphyses. CDD has variable expression and causes generalized hyperostosis and sclerosis, especially of the skull and facial bones with progressive calvarial thickening. There are less than 20 reported cases of CDD in the literature.
References:
Goswami P, Sarma PK, Sethi S, Hazarika S. Extensive skeletal manifestations in a case of primary hyperparathyroidism caused by parathyroid adenoma. Ind J Radiol Imag 2002 12:2:267-270. [Link]
Hahn YH. Increased skull thickness. Collaborative Hypertext of Radiology. 2 February 1995. [CHORUS]
Hollar MA. The hair-on-end sign. Radiology. 2001 Nov;221(2):347-8. [Medline]
