DOI: 10.1148/rg.253045042
RadioGraphics 2005;25:829-834
© RSNA, 2005
Best Cases from the AFIP
Primary Hyperparathyroidism Due to Parathyroid Adenoma1
Douglas K. McDonald, MD,
Linda Parman, MD and
V. O. Speights, Jr, DO
1 From the Departments of Radiology (D.K.M., L.P.) and Pathology (V.O.S.), Scott & White Memorial Hospital, 2401 S 31st St, Temple, TX 76508. Received March 15, 2004; revision requested April 7 and received June 4; accepted June 7. All authors have no financial relationships to disclose.
Address correspondence to D.K.M. (e-mail: dmcdo65166{at}yahoo.com).
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History
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A 23-year-old black man presented with a 2-day history of right upper quadrant pain and pleuritic right-sided chest pain. With the exception of nonobstructing right renal calculi discovered 4–5 months earlier, the patient reported no significant medical history. A review of systems revealed recent fatigue, weight loss, and slight burning with urination, but the results were otherwise unremarkable. Results of physical examination were notable for fullness within the region of the inferior pole of the right lobe of the thyroid gland, right chest wall pain at palpation, and prominent clubbing of the fingers (Fig 1).
Subsequent laboratory analysis demonstrated a markedly elevated alkaline phosphatase level of 1,709 IU/L (normal range, 30–115 IU/L), which prompted further investigation. Further investigation revealed hypercalcemia with a serum calcium level of 14.8 mg/dL (3.7 mmol/L) (normal range, 8.4–10.3 mg/dL [2.1–2.6 mmol/L]); a low serum phosphorus level of 2.3 mg/dL (0.74 mmol/L) (normal range, 2.4–4.2 mg/dL [0.77–1.36 mmol/L]); and an elevated parathyroid hormone level of 1,485 pg/mL (156 pmol/L) (normal range, 10–65 pg/mL [1.1–6.8 pmol/L]). Urinalysis demonstrated 2+ hematuria, but the results were otherwise unremarkable. After evaluation of the imaging findings detailed in the next section, the diagnosis of primary hyperparathyroidism resulting from a solitary right parathyroid adenoma was made.
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Imaging Findings
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The initial chest radiograph demonstrated leftward deviation of the trachea at the level of the cervicothoracic junction by the subsequently discovered right parathyroid adenoma. In addition, there was an abnormal appearance of the distal lower ribs, where multiple lytic lesions were noted (Fig 2), as well as resorption of the clavicular heads (Fig 3). Abdominal radiographs showed multiple calcific opacities overlying the renal outlines bilaterally, significant widening of the pubic symphysis and sacroiliac joints, and a well-defined lytic lesion of the right iliac wing.
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Figure 2. Posteroanterior radiograph shows leftward deviation of the trachea (black arrowhead). There is resorption of the distal aspects and heads of the clavicles (white arrows) and subligamentous resorption at the origins of the coracoclavicular ligaments (black arrow). An expansile lytic lesion of the anterolateral right 10th rib (white arrowhead) corresponds to one of many osteoclastomas seen at computed tomography (CT).
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Figure 3. Magnified view of Figure 2 shows resorption of the clavicular head (white arrow) and subligamentous resorption at the insertion of the coracoclavicular ligament (black arrow).
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Abdominal ultrasound (US) demonstrated renal calculi, a finding verified at CT of the abdomen. CT of the chest, abdomen, and pelvis also revealed a low-attenuation mass in the lower pole of the right lobe of the thyroid gland and multiple well-defined lytic lesions involving the ribs, L2 vertebral body, left hemisacrum, and iliac wings (Fig 4). Radiographs of the hands demonstrated osteopenia, resorption of the terminal tufts of the first through fifth digits, intracortical tunneling involving the metacarpals, subperiosteal resorption along the shafts of multiple phalanges and the fifth metacarpals, and erosions of the ulnar styloid process bilaterally (Fig 5).
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Figure 4a. (a) CT image shows a 7-mm-diameter calculus in the collecting system of the mid right kidney (black arrow). There is diffuse mottled osteosclerosis of the visualized bones. A healed fracture of the posterior right 12th rib (white arrow) and expansile lytic lesions of the anterior ribs (arrowheads) are seen. (b) CT image shows subchondral resorption on the iliac side of the sacroiliac joints; subsequent collapse due to weight bearing produced apparent joint widening (black arrows). There are lytic lesions of the right iliac crest (white arrow) and left hemisacrum (arrowhead) with violation of the left first sacral foramen.
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Figure 4b. (a) CT image shows a 7-mm-diameter calculus in the collecting system of the mid right kidney (black arrow). There is diffuse mottled osteosclerosis of the visualized bones. A healed fracture of the posterior right 12th rib (white arrow) and expansile lytic lesions of the anterior ribs (arrowheads) are seen. (b) CT image shows subchondral resorption on the iliac side of the sacroiliac joints; subsequent collapse due to weight bearing produced apparent joint widening (black arrows). There are lytic lesions of the right iliac crest (white arrow) and left hemisacrum (arrowhead) with violation of the left first sacral foramen.
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Figure 5a. Magnified views from a posteroanterior radiograph of the right hand. (a) Diffuse osteopenia is seen, as well as erosions at the radial and ulnar styloid processes (black arrows) and the distal aspect of the scaphoid (white arrow). Subperiosteal resorption and intracortical tunneling are noted at the ulnar aspect of the fifth metacarpal (arrowheads). (b) There is diffuse osteopenia with subperiosteal resorption, particularly at the radial shafts of the second and third middle phalanges (solid arrows). Prominent acro-osteolysis (arrowheads) and intracortical tunneling involving multiple phalanges (open arrows) are noted.
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Figure 5b. Magnified views from a posteroanterior radiograph of the right hand. (a) Diffuse osteopenia is seen, as well as erosions at the radial and ulnar styloid processes (black arrows) and the distal aspect of the scaphoid (white arrow). Subperiosteal resorption and intracortical tunneling are noted at the ulnar aspect of the fifth metacarpal (arrowheads). (b) There is diffuse osteopenia with subperiosteal resorption, particularly at the radial shafts of the second and third middle phalanges (solid arrows). Prominent acro-osteolysis (arrowheads) and intracortical tunneling involving multiple phalanges (open arrows) are noted.
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Thyroid US showed a heterogeneous, partially cystic mass within the inferior aspect of the right thyroid lobe (Fig 6). Radionuclide imaging demonstrated a photopenic focus within the lower pole of the right thyroid lobe on technetium 99m (99mTc) pertechnetate images and a focus of increased uptake in this region after administration of 99mTc-sestamibi. At subtraction imaging, this finding was confirmed as preferential 99mTc-sestamibi activity in this region, consistent with a parathyroid adenoma (Fig 7).
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Figure 7. Dual-tracer (subtraction) scintigraphy. Top left: Scintigram obtained after injection of 99mTc-sestamibi (which is taken up by both thyroid and parathyroid tissue) shows asymmetric increased activity at the lateral aspect of the lower right thyroid lobe (arrow). Bottom left: Scintigram obtained after injection of 99mTc-pertechnetate (which is preferentially taken up by the thyroid) shows a relatively photopenic focus in the same region (arrow). Right: Subtracted image shows differential 99mTc-sestamibi activity at the same location (arrowheads). This finding was shown to represent a parathyroid adenoma.
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Pathologic Evaluation
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Gross pathologic evaluation of the surgically resected mass within the lower pole of the right lobe of the thyroid gland showed an 11-g, 3 x 2.5 x 2-cm spheroidal fragment of tan-red tissue with a smooth and glistening external surface. When it was bisected, the parenchyma was noted to be composed of solid dark tan tissue with up to 0.4-cm hyperemic foci and several subcentimeter cysts (Fig 8). A portion of the specimen submitted for frozen sectioning revealed hypercellular parathyroid tissue (Fig 9). The microscopic diagnosis was parathyroid adenoma.
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Figure 8. Photograph of the resected parathyroid adenoma shows a spheroidal fragment of tan-red tissue. The parenchyma is composed of solid dark tan tissue with multiple hyperemic foci and several subcentimeter cysts. (Scale is in centimeters.)
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Figure 9. Photomicrograph (original magnification, x40; hematoxylineosin stain) of the surgical specimen shows hypercellular parathyroid tissue with a surrounding thick fibrous capsule (arrows), findings consistent with a parathyroid adenoma.
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Discussion
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A product of the chief cells of the four parathyroid glands, parathyroid hormone (PTH) is a key modulator of calcium homeostasis. Complex in its metabolic function, PTH helps maintain the serum calcium level by mobilizing calcium at the bone surface, stimulating osteoclast-mediated bone resorption (1). PTH also promotes renal hydroxylation of 25-hydroxy–vitamin D, which, in addition to being instrumental in intestinal absorption of calcium, binds to intranuclear receptors within bone, producing mediators of calcium mobilization and mineralization of organic matrix (2). Other effects of PTH include promotion of renal tubular reabsorption of calcium and lowering of serum phosphate level by inducing phosphaturia (3).
Excessive production of PTH, termed hyperparathyroidism, is classified as primary, secondary, or tertiary in form. Primary hyperparathyroidism, due to autonomous hypersecretion of PTH, usually occurs in the setting of a parathyroid adenoma (80%) but can also be seen with parathyroid gland hyperplasia (15%–20%) or carcinoma (<0.5%) (4). Secondary hyperparathyroidism results from stimulation of the parathyroid glands as a response to hypocalcemia or due to apparent insensitivity of the parathyroid glands to elevated serum calcium levels and dysregulation of the normal negative feedback loop (pseudohypoparathyroidism). The most common cause of secondary hyperparathyroidism is renal failure, which results in phosphate retention, hypocalcemia, and 1,25(OH)2D3 deficiency, leading to a compensatory increase in the production of PTH (3). Tertiary hyperparathyroidism is seen in cases of secondary hyperparathyroidism in which the parathyroid glands continue to function autonomously despite correction of the initial cause, resulting in hypersecretion of PTH in the setting of normal calcium levels (5).
Although most patients with primary hyperparathyroidism today are asymptomatic due to the widespread availability of laboratory screening for hypercalcemia and earlier detection, the clinical presentation is variable (6). Previously encountered overt symptoms including dementia, depression, peptic ulcer disease, pancreatitis, constipation, renal calculi, and diffuse bone and joint pain are no longer common. Patients now often complain of mild subjective symptoms such as weakness and easy fatigability (7).
The classic imaging features of advanced primary hyperparathyroidism are also less frequently seen today. Generalized osteopenia is the most common imaging finding in primary hyperparathyroidism. Only very rarely encountered in primary hyperparathyroidism, diffuse or localized osteosclerosis is a more common finding in secondary hyperparathyroidism. When involving the spine, sclerosis can produce a striped appearance, the so-called "rugger jersey" spine (4).
Subperiosteal bone resorption is a common finding of advanced hyperparathyroidism, most often seen involving the hands and the feet. Although classically most pronounced at the radial aspects of the second and third middle phalanges, subperiosteal resorption can also be seen involving the medial aspects of the metaphyses of the long bones as well as the ribs and lamina dura of the teeth. Terminal tuft resorption can also be seen, and hyperparathyroidism should be considered in the differential diagnosis for acro-osteolysis (2). As in our case, the digits may appear spatulous or clubbed, presumably due to soft-tissue collapse resulting from marked terminal tuft erosion (8).
Other areas of bone resorption are seen at sites of high bone surface area and include subchondral locations, often best appreciated at the sacroiliac, acromioclavicular, sternoclavicular, and temporomandibular joints, the symphysis pubis, and the patella. Resorption of subligamentous and subtendinous bone occurs most often at the femoral trochanters, the ischial tuberosities, the calcaneal insertions of the plantar aponeurosis and Achilles tendon, the inferior margin of the distal clavicle, and the tuberosities of the humerus (4). Intracortical, endosteal, and trabecular bone resorption can also be present. Brown tumors, also known as osteoclastomas, are eccentrically located and often expansile lesions resulting from amassing osteoclasts and fibrous tissue. Chondrocalcinosis is a nonspecific finding that has a higher prevalence in primary rather than secondary hyperparathyroidism (2). Although also having a higher prevalence in primary hyperparathyroidism, brown tumors are more frequently encountered in the setting of secondary hyperparathyroidism due to the greater prevalence of this condition (2). Soft-tissue calcification and periostitis are among the radiographic findings more commonly seen in secondary hyperparathyroidism (2).
Although directed US examination, CT of the neck, and magnetic resonance imaging are useful in the complete evaluation of primary hyperparathyroidism, 99mTc-sestamibi parathyroid scintigraphy is now considered the best preoperative localizing modality for the detection of parathyroid adenomas (9). As parathyroid scintigraphy can be limited by the coexistence of thyroid nodules or other metabolically active tissues such as lymph nodes, diffuse hyperplasia, or metastatic thyroid cancer, it is often correlated with CT results to yield functional and anatomic localization (5).
As most patients with primary hyperparathyroidism are asymptomatic, treatment is controversial. Given the potential unpredictable long-term complications including recurrent urolithiasis and osteoporosis, some clinicians believe that surgical management is essentially always appropriate (7). The National Institutes of Health (NIH) consensus statement in 1990 concluded that while surgical intervention is the acceptable treatment of primary hyperparathyroidism, "conscientious surveillance may be justified in patients whose calcium levels are only mildly elevated and whose renal and bone status are close to normal." NIH criteria identified for selecting patients for parathyroidectomy include the following: (a) typical parathyroid-related symptoms involving the skeletal, renal, or gastrointestinal systems; (b) a sustained elevation of serum calcium level more than 1–1.6 mg/dL (0.25–0.40 mmol/L) above the upper limits of normal; (c) a substantial decline in bone mass; (d) a decline in renal function by 30% or more; (e) nephrolithiasis or worsening of calciuria; (f) severe neuromuscular or psychological problems; or (g) unwillingness of the patient to continue under medical supervision (10).
Our patient underwent parathyroidectomy with gamma probe localization. Apart from transient hypocalcemia in the immediate postoperative period, which was treated with calcium supplements, he had an uneventful hospital course. During subsequent follow-up visits, he reported resolution of right upper quadrant pain and fatigue. Plans are to continue current management with calcium supplementation and observation.
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Footnotes
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Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
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References
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- Khan A, Bilezikian J. Primary hyperparathyroidism: pathophysiology and impact on bone. CMAJ
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- Disler DG. Metabolic bone diseases. In: Manaster BJ, Disler DG, May DA, eds. Musculoskeletal imaging. 3rd ed. St Louis, Mo: Mosby, 2002; 401–409.
- Cotran RS, Kumar V, Robbins SL. The endocrine system. In: Robbins SL, ed. Pathologic basis of disease. 5th ed. Philadelphia, Pa: Saunders, 1994; 1144–1146.
- Lenchik L, Mitchell K. Hyperparathyroidism and renal osteodystrophy. In: El-Khoury G, ed. Essentials of musculoskeletal imaging. Philadelphia, Pa: Churchill Livingstone, 2003; 295–301.
- Sosa JA, Udelsman R. New directions in the treatment of patients with primary hyperparathyroidism. Curr Probl Surg
2003; 40:803–849.[CrossRef]
- Genant HK, Hick LL, Lanzl LH, Rossmann K, Horst JV, Paloyan E. Primary hyperparathyroidism: a comprehensive study of clinical, biochemical, and radiographic manifestations. Radiology
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- Clark OH. How should patients with primary hyperparathyroidism be treated? [editorial]. J Clin Endocrinol Metab
2003; 88:3011–3014.[Free Full Text]
- Davis G, Rubin J, Bower J. Digital clubbing due to secondary hyperparathyroidism. Arch Intern Med
1990; 150:452–454.[Abstract]
- Giordano A, Rubello D, Casara D. New trends in parathyroid scintigraphy. Eur J Nucl Med
2001; 28:1409–1420.[CrossRef][Medline]
- NIH conference. Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement. Ann Intern Med
1991; 114:593–597.
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History
Imaging Findings
