Systemic Diseases

Fatima Jadu

Disease Mechanism

This chapter addresses diseases that alter the normal form and function of bone and normal formation of teeth. These diseases produce abnormalities through a disturbance in the balanced serum concentrations of calcium and phosphate and/or through abnormal functioning osteoblasts, osteocytes, and osteoclasts (Fig. 25-1). These factors are essential for the normal development of the initial skeleton and for the continued bone remodeling that occurs thereafter—approximately 5% to 10% of total bone volume in an adult skeleton is replaced per year. For instance, a disease that causes a decrease in serum calcium alters the calcium and phosphate balanced levels, resulting in abnormal bone and tooth formation. A low serum calcium concentration can also result in the mobilization of calcium from bone, depleting the calcium content of bone. The reduced calcium level in bone results in bone with low density in the diagnostic image. Bone remodeling is also altered by the mobilization of calcium from bone resulting in an abnormal trabecular pattern in the diagnostic image. Dental anomalies such as enamel or dentin hypoplasia or hypocalcification are other possible consequences of a reduced serum calcium level. Other diseases can affect changes to bone and teeth through altered serum levels of phosphate or through abnormal numbers and function of osteoblasts, osteocytes, and osteoclasts.

FIGURE 25-1 This figure shows the activity of vitamin D, parathyroid hormone (PTH), and glucocorticosteroids in bone and other tissues and outlines their roles in maintaining normal serum levels of calcium (Ca²⁺) and phosphate (Pi) and bone metabolism. Bone metabolism entails the balanced process of osteoblastic bone formation and osteoclastic bone resorption. *Solid arrows* indicate a promotion effect, and *dashed arrows* indicate an inhibitory effect. Vitamin D, either ingested or produced in the skin, undergoes a series of hydroxylations, first in the liver and then in the kidneys, to the active form of 1,25(OH)₂D *(black arrows)*. 1,25(OH)₂D can increase serum Ca²⁺ and Pi by promoting their absorption in the intestine and tipping the balance of bone metabolism in favor of resorption, releasing Ca²⁺ and Pi from the bone to the serum *(solid blue arrows)*. This promotion of bone resorption is accomplished through the expression of receptor activator of nuclear factor kappa B ligand (RANKL) by osteoblasts, which interacts with a receptor activator of nuclear factor-kappa B (RANK) receptor on preosteoclasts differentiating these cells into active osteoclasts that resorb the bone *(lower right inset box)*. 1,25(OH)₂D can also inhibit the last hydroxylation of its precursor 25(OH)D within the kidneys and can inhibit the parathyroid glands from producing PTH *(dashed blue arrows)*. PTH can increase serum Ca²⁺ by directly increasing bone resorption through promoting the expression of RANKL and the differentiation of osteoclasts. PTH also increases serum Ca²⁺ by increasing reabsorption of Ca²⁺ in the kidneys and promoting the hydroxylation of vitamin D to its active form in the kidneys *(orange arrows)*. However, elevated serum Ca²⁺ can reduce production of PTH by the parathyroid glands *(dashed black arrow)*. Glucocorticosteroids initially increase bone resorption through increased osteoblastic expression of RANKL, increasing osteoclast differentiation, and can prolong the life span of the osteoclast. Later, glucocorticosteroids reduce bone formation by limiting differentiation and inducing apoptosis of osteoblasts.

Diagnostic Imaging Features

Because systemic disorders affect the entire body, the changes manifested in the appearance of the jaws in diagnostic images are usually generalized and often nonspecific, making it difficult to identify the diseases based on imaging characteristics alone (Table 25-1). The general changes that can be seen in the jaws include the following:

1. Change in size and shape of the bone

2. Change in the number, size, and orientation of trabeculae

3. Altered thickness and density of cortical structures

4. Increase or decrease in overall bone density

Changes in the first three elements can result in a decrease or increase in bone density.

TABLE 25-1

Changes in Bone Observed in Systemic Disease*

	BONES
			TRABECULAE
Systemic Disease	Density	Size of Jaws	Increase	Decrease	Granular
Hyperparathyroidism	Decrease	No	Yes	Yes	Yes
Hypoparathyroidism	Rare increase	No	No	No	No
Hyperpituitarism	No	Large	No	No	No
Hypopituitarism	No	Small	No	No	No
Hyperthyroidism	Decrease	No	No	No	No
Hypothyroidism	No	Small	No	No	No
Cushing’s syndrome	Decrease	No	No	Yes	Yes
Osteoporosis	Decrease	No	No	Yes	No
Rickets	Decrease	No	No	Yes	No
Osteomalacia	Rare decrease	No	No	Rare decrease	No
Hypophosphatasia	Decrease	No	No	Yes	No
Renal osteodystrophy	Decrease; rare increase	Large	Rare	Yes	Yes
Hypophosphatemia	Decrease	No	No	Yes	Yes
Osteopetrosis	Increase	Large
Sickle cell anemia	Decrease	Large maxilla
Thalassemia	Decrease	Large maxilla

*This table summarizes the major imaging changes to bone with endocrine and metabolic bone diseases. It does not include all the possible variable appearances.

Because many parameters in the production of a diagnostic image influence the density of the image, it may be difficult to detect genuine changes in the density of bone. Systemic conditions that result in a decrease in bone density do not affect mature teeth; the image of the teeth may stand out with normal density against a generally radiolucent jaw. In severe cases, the teeth may appear to lack any bony support. Also, cortical structures appear thin, are less defined, and occasionally disappear. A true increase in bone density may be detected by a loss of contrast of the inferior cortex of the mandible as the radiopacity of the cancellous bone approaches that of cortical bone. Often the radiolucent outline of the inferior alveolar nerve canal appears more distinct in contrast to the surrounding radiopaque dense bone.

Some systemic diseases that occur during tooth formation may result in dental alterations. Lamina dura is part of the bone structure of the alveolar process, but because it is usually examined in conjunction with the periodontal membrane space and roots of teeth, it is included with the description of the dental structures (Table 25-2). Changes to teeth and associated structures include the following:

1. Accelerated or delayed eruption

2. Hypoplasia

3. Hypocalcification

4. Loss of a distinct lamina dura

TABLE 25-2

Effects on Teeth and Associated Structures*

Systemic Disease	Hypocalcification	Hypoplasia	Large Pulp Chamber	Loss of Lamina Dura	Loss of Teeth	Eruption
Hyperparathyroidism	No	No	No	Yes	Rare	No
Hypoparathyroidism	No	Yes	No	No	No	Delayed
Hyperpituitarism	No	No	No	No	No	Supereruption
Hypopituitarism	No	No	No	No	No	Delayed
Hypothyroidism	No	No	No	No	Yes	Early
Hyperthyroidism	No	No	No	Thin	Yes	Delayed
Cushing’s syndrome	No	No	No	Partial	No	Premature
Osteoporosis	No	No	No	Thin	No	No
Rickets	Yes, enamel	Yes, enamel	No	Thin	No	Delayed
Osteomalacia	No	No	No	Thin	No	No
Hypophosphatasia	Yes	Yes	Yes	Yes	Yes	Delayed
Renal osteodystrophy	Yes	Yes	No	Yes	No	No
Hypophosphatemia	Yes	Yes	Yes	Yes	Yes	No
Osteopetrosis	Yes	Rare	No	Thick	Yes	Delayed

*This table summarizes the major imaging changes that can occur to teeth and associated structures with endocrine and metabolic bone diseases. It does not include all the possible variable appearances.

The teeth and their supporting structures often exhibit no detectable changes associated with systemic diseases. However, the first symptoms of a disease occasionally may manifest as a dental problem.

Endocrine Disorders

Hyperparathyroidism

Disease Mechanism

Hyperparathyroidism is an endocrine abnormality in which there is an excess of circulating parathyroid hormone (PTH). An excess of serum PTH increases bone remodeling but tips the balance of osteoblastic and osteoclastic activity in favor of osteoclastic resorption, which mobilizes calcium from the skeleton. This activity can alter the normal morphology of bone trabeculae into irregularly shaped, small trabeculae, which can result in a granular bone pattern in the diagnostic images. In addition, PTH increases renal tubular reabsorption of calcium and renal production of the active vitamin D metabolite 1,25(OH)₂D. The net result of these functions is an increase in serum calcium levels (see Fig. 25-1).

Primary hyperparathyroidism usually results from a benign tumor (adenoma) of one of the four parathyroid glands (80% to 85%), resulting in the production of excess PTH. The condition is often sporadic, but it may be part of a hereditary syndrome, such as hyperparathyroidism–jaw tumor syndrome, which involves tumors of parathyroid glands, jaws, and kidneys. Less frequently, individuals may have hyperplastic parathyroid glands that secrete excess PTH (10% to 15%). The incidence of primary hyperparathyroidism is about 0.1%.

Secondary hyperparathyroidism results from a compensatory increase in the output of PTH in response to hypocalcemia. The underlying hypocalcemia may result from inadequate dietary intake or poor intestinal absorption of vitamin D or from deficient metabolism of vitamin D in the liver or kidneys. This condition produces clinical and imaging features similar to primary hyperparathyroidism.

Clinical Features

Primary hyperparathyroidism affects females two to three times more commonly than males. The condition occurs mainly in adults 30 to 60 years old. Clinical manifestations of the disease cover a broad range, but most patients have renal calculi, peptic ulcers, cognitive impairment, or bone and joint pain. These clinical symptoms are mainly related to hypercalcemia. Gradual loosening, drifting, and loss of teeth may occur. The combination of hypercalcemia and an elevated serum level of PTH is diagnostic of primary hyperparathyroidism. Because of daily fluctuations, the serum calcium level should be tested at different intervals. The serum alkaline phosphatase level, a reliable indicator of bone turnover, may also be elevated in hyperparathyroidism.

Imaging Features

Only about one in five patients with hyperparathyroidism has observable bone changes.

General Features.

The major manifestations of hyperparathyroidism are as follows:

1. The earliest and most reliable changes of hyperparathyroidism are subtle erosions of bone from the subperiosteal surfaces of the phalanges of the hands.

2. Demineralization of the skeleton results in an unusual radiolucent appearance (generalized osteopenia).

3. Osteitis fibrosa cystica is seen in advanced cases as localized regions of bone loss produced by osteoclastic activity resulting in a loss of all apparent bone structure.

4. In about 10% of cases, brown tumors occur late in the disease. These lesions are called brown tumors because the gross specimen has a brown or reddish brown color. In diagnostic images, these tumors appear radiolucent.

5. The increased levels of serum calcium result in precipitation of the mineral in the soft tissues forming punctate or nodular calcifications in the joints and kidneys.

6. In prominent hyperparathyroidism, the entire calvaria has a granular appearance classically known as the “salt and pepper” skull. This appearance is caused by loss of the central (diploic) trabeculae and thinning of the cortical tables (Fig. 25-2).

FIGURE 25-2 Axial **(A)** and sagittal **(B)** MDCT images with bone algorithm of a case of secondary hyperparathyroidism. Note the lack of normal cortical bone at the inner and outer tables of the skull, internal granular bone pattern, and generalized lack of defined outer cortical boundary of the osseous structures.

Jaws.

Demineralization and thinning of cortical boundaries often occur in the jaws, including the inferior border of the mandible, the cortical boundaries of the mandibular canal, and the cortical outlines of the maxillary sinuses. The density of the jaws is decreased, resulting in a radiolucent appearance that contrasts with the normal density of the teeth (Fig. 25-3). The elevated rate of bone remodeling can cause an abnormal bone pattern secondary to replacement of normal trabeculae by numerous, small, randomly oriented trabeculae, resulting in a ground-glass appearance in the diagnostic image.

FIGURE 25-3 A, Panoramic image. The loss of bone in hyperparathyroidism results in the radiopaque teeth standing out in contrast to the radiolucent jaws. B, Periapical film of a different case demonstrates the loss of a distinct lamina dura and the granular texture of the bone pattern. (B, Courtesy H. G. Poyton, DDS, Toronto, Ontario, Canada.)

Brown tumors of hyperparathyroidism may appear in any bone but are frequently found in the facial bones and jaws, particularly in cases of long-standing disease. These lesions may be multiple within a single bone. They have variably defined margins and may produce cortical expansion. If solitary, the tumor may resemble a central giant cell granuloma or an aneurysmal bone cyst (Fig. 25-4). The histologic appearance of a brown tumor is identical to giant cell granuloma. If a giant cell granuloma occurs later than the second decade, the patient should be screened for an increase in serum calcium, PTH, and alkaline phosphatase levels.

FIGURE 25-4 Axial **(A)** and coronal **(B)** MDCT images with bone algorithm of a case of secondary hyperparathyroidism with a brown tumor involving the maxilla. This tumor has features of a central giant cell granuloma with a granular expanded cortex of the maxilla and very subtle and ill-defined internal septa.

Teeth and Associated Structures.

Occasionally, periapical images reveal loss of the lamina dura in patients (about 10%) with hyperparathyroidism. Depending on the duration and severity of the disease, loss of the lamina dura may occur around one tooth or all the remaining teeth (Fig. 25-5). The loss may be either complete or partial around a particular tooth. The result of lamina dura loss may give the root a tapered appearance because of loss of image contrast. Although PTH mobilizes minerals from the skeleton, mature teeth are immune to this systemic demineralizing process.

FIGURE 25-5 Hyperparathyroidism. A and B, Granular bone pattern that was characteristic in all intraoral films. Note the loss of a distinct lamina dura and floor of the maxillary antrum. C, This view of the same case reveals a brown tumor related to the apical region of the second and third molars.

Management

After successful surgical removal of the causative parathyroid adenoma, almost all changes revert to normal. The only exception may be the site of a brown tumor, which often heals with bone that is more sclerotic than normal. Many people with this disease are being diagnosed earlier, resulting in fewer severe cases.

Hypoparathyroidism and Pseudohypoparathyroidism

Disease Mechanism

Hypoparathyroidism is an uncommon condition in which insufficient secretion of PTH occurs. Several causes exist, but the most common is damage or removal of the parathyroid glands during thyroid surgery. In pseudohypoparathyroidism, there is a defect in the response of the target tissue cells to normal levels of PTH. In both cases, the result is low serum levels of calcium.

Clinical Features

There are a variety of clinical manifestations. Most often, manifestations include sharp flexion (tetany) of the wrist and ankle joints (carpopedal spasm). Some patients have sensory abnormalities consisting of paresthesia of the hands, feet, or the area around the mouth. Neurologic changes may include anxiety and depression, epilepsy, parkinsonism, and chorea. Chronic forms may produce a reduction in intellectual capacity. Some patients show no changes. Patients with pseudohypoparathyroidism often have early closure of certain bony epiphyses and manifest short stature or extremity disproportions.

Imaging Features

The principal change is calcification of the basal ganglia. On skull images, this calcification appears flocculent and paired within the cerebral hemispheres on the posteroanterior view. Imaging of the jaws may reveal dental enamel hypoplasia, external root resorption, delayed eruption, or root dilaceration (Fig. 25-6).

FIGURE 25-6 Pseudohypoparathyroidism-induced dental anomalies. (Courtesy Dr. S. Bricker, San Antonio, TX.)

Management

These conditions are managed with orally administered supplemental calcium and vitamin D.

Hyperpituitarism

Synonyms

Synonyms for hyperpituitarism include acromegaly and gigantism.

Disease Mechanism

Hyperpituitarism results from hyperfunction of the anterior lobe of the pituitary gland, which increases the production of growth hormone. An excess of growth hormone causes overgrowth of all tissues in the body still capable of growth. The usual cause of this problem is a benign functioning tumor of the somatotrophs (growth hormone–secreting cells) in the anterior lobe of the pituitary gland.

Clinical Features

Hyperpituitarism in children involves generalized overgrowth of most hard and soft tissues, a condition termed gigantism. Active growth occurs in bones in which the epiphyses have not united with the bone shafts. Throughout adolescence, generalized skeletal growth is excessive and may be prolonged. Affected individuals ultimately may attain heights of 7 to 8 feet or more, but they exhibit remarkably normal proportions. The eyes and other parts of the central nervous system do not enlarge except in rare cases in which the condition manifests in infancy.

Adult hyperpituitarism, called acromegaly, has an insidious clinical course, quite different from the clinical profile seen in the childhood disease. In adults, the clinical effects of a pituitary adenoma develop quite slowly because many types of tissues have lost the capacity for growth. This is true of much of the skeleton; however, an excess of growth hormone can stimulate the mandible and the phalanges of the hand. Mandibular condylar growth may be very prominent. Also, the supraorbital ridges and the underlying frontal sinus may be enlarged. Excess growth hormone in adults may also produce hypertrophy of some soft tissues. The lips, tongue, nose, and soft tissues of the hands and feet typically overgrow in adults with acromegaly, sometimes to a striking degree.

Imaging Features

General Features.

The pituitary tumor responsible for hyperpituitarism often produces enlargement (“ballooning”) of the sella turcica (see Fig. 25-7, B). In some examples, the sella may not expand at all. Skull images characteristically reveal enlargement of the paranasal sinuses (especially the frontal sinus). These air sinuses are more prominent in acromegaly than in pituitary gigantism because sinus growth in gigantism tends to be more in step with the generalized enlargement of the facial bones. Hyperpituitarism in adults also produces diffuse thickening of the outer table of the skull.

Jaws.

Hyperpituitarism causes enlargement of the jaws, most notably the mandible (Fig. 25-7, A). The increase in the length of the dental arches results in spacing of the teeth. In acromegaly, the angle between the ramus and body of the mandible may increase. This increase, in combination with the flaring of the anterior teeth caused by enlargement of the tongue (macroglossia), may result in development of an anterior open bite. The sign of incisor flaring is a helpful point of differentiation between acromegalic prognathism and inherited prognathism. In acromegaly, the most profound growth occurs in the condyle and ramus, often resulting in a class III skeleta/>

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Tags: Oral Radiology Principles and Interpretation

Jan 12, 2015 | Posted by mrzezo in Oral and Maxillofacial Radiology | Comments Off

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25. Systemic Diseases

Systemic Diseases

Disease Mechanism

Diagnostic Imaging Features