Non-Neoplastic Lesions of the Parathyroid Glands

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General Considerations

There are a variable number of glands (2 to 10), but usually four are present, symmetrically arranged within the upper and lower poles of the bilateral thyroid gland. Approximately 5% of people have more than four glands. The glands are usually soft, pliable, and measure < 0.5 cm (5 mm), with a combined weight of approximately 120 to 140 mg. It is agreed that no single gland should be more than 60 mg, although the lower glands are often slightly larger than the upper glands. Embryologically, the upper pair arise from the fourth branchial pouch, whereas the lower pair arise from the third branchial pouch. Notably, glands can be found anywhere along the normal route of migration, resulting in glands embedded within the thymus, pericardium, esophagus, and mediastinum.

The parathyroid gland is composed of four cell types:

• The chief cell (6 to 8 µm), a small polygonal cell with central round nucleus and abundant cytoplasmic secretory granules, is the basic functional cell involved in parathyroid hormone (parathormone, PTH) secretion.

• The oxyphilic or oncocytic cell (12 µm) is slightly larger than chief cells, with abundant granular cytoplasm, ultrastructurally shown to be packed with mitochondria. These cells increase in number as the patient ages and tend to occur in nodules.

• The water-clear cell (quite rare) has well-defined cell borders and abundant clear cytoplasm due to excessive glycogen.

• Adipocytes, which also increase with age, compose up to 60% of the cellular mass. A general rule of thumb: 50% parenchymal fat at 50 years of age. There also tends to be more stromal fat at the poles of the gland(s).

The cellular components are arranged in cords, sheets, and pseudoglandular or pseudoacinar patterns. Age, sex, body fat, and other factors affect normal parathyroid gland cellularity.

In short, the principal function of the parathyroid glands is calcium homeostasis, briefly discussed here (spatial constraints limit this discussion). Calcium homeostasis is maintained within narrow limits (approximately 8 to 10 mg/dL) by the balance between variables increasing serum calcium (dietary intake, intestinal absorption, and bone resorption) and those decreasing serum calcium (bone accretion and urinary/fluid excretion). Nearly 99% of calcium is stored in the skeletal system, and osteoclastic resorption is most important. The three most important hormones are PTH, calcitonin (secreted by thyroid C cells), and vitamin D.

PTH is a polypeptide hormone (84 amino acid residues; the n-terminal is active, whereas the c-terminal is assayed) that increases blood calcium levels by stimulating osteoclastic resorption of bone and decreasing urinary excretion of calcium, while increasing renal phosphate excretion. This results in hypophosphatemia and can cause metabolic acidosis due to inhibition of HCO ₃ . The half-life of PTH is 20 to 30 minutes. Abnormal or decreased function of the parathyroid glands results in disorders of calcium metabolism, characterized by too little (e.g., osteomalacia, pseudo hypoparathyroidism) or too much (e.g., milk-alkali syndrome, calcinosis) calcium. PTH also stimulates production of 1,25 dihydroxy-cholecalciferol (calcitriol), the hormonally active form of vitamin D, which increases the uptake of calcium from the gut, decreases urinary excretion of calcium, and increases the release of calcium from bone.

Parathyroid non-neoplastic disorders include aplasia, cysts, parathyroiditis, and hyperplasia. The discussion will be limited to hyperplasia.

Hyperparathyroidism is a state of elevated serum PTH as a result of excessive secretion. It is separated into primary, secondary, and tertiary, with primary hyperparathyroidism caused most commonly by adenoma (80%), hyperplasia (15%), and carcinoma (5%). The inappropriately increased PTH is due to an intrinsic abnormality in the gland(s) rather than a known stimulus for PTH secretion. Most hyperplasia results from secondary hyperparathyroidism, in which there is an increase in parathyroid parenchymal cell mass within multiple glands in response to a known clinical stimulus for increased secretion of PTH, such as chronic renal failure, malabsorption, and abnormalities of vitamin D metabolism. It is usually characterized by hypocalcemia and hyperphosphatemia. Similarly, tertiary hyperparathyroidism is generally characterized by four-gland hyperplasia in a state of autonomous hypersecretion.

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Primary Chief Cell Hyperplasia

Primary chief cell hyperplasia is a non-neoplastic absolute increase in the parenchymal cell mass within multiple parathyroid glands without a known clinical stimulus for increased PTH secretion. There is an annual incidence of approximately 4 per 100,000 persons per year in the United States.

Radiographic Features

^99m Tc sestamibi imaging is the preferred technique for detecting the topographic location of parathyroid tissue ( Fig. 26.1 ), although limited in detecting hyperplasia, with greater clinical utility for detecting adenoma or carcinoma. In general, radiographic studies are primarily used in the setting of recurrent disease after failed surgery. Single-photon emission computed tomography (SPECT) with the use of ^99m Tc sestamibi as the radiotracer, especially when combined with computed tomography, can help with preoperative localization. Unusual locations of (ectopic) parathyroid tissue may be identified with magnetic resonance imaging using gadolinium and fat-suppression techniques. However, hyperplasia does not enhance as much with gadolinium as does an adenoma. Ultrasound (US), when used by an experienced investigator, can be a good alternative if scintigraphic studies are inconclusive. Furthermore, US may be used to guide fine needle aspiration (FNA) or guide retrograde venous sampling to determine PTH levels.