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Parathyroid gland


Primary hyperparathyroidism

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 16 February 2013, last major update January 2013
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.


● Autonomous, spontaneous overproduction of parathyroid hormone / parathormone / PTH by parathyroid tissue, with no evidence of prior parathyroid stimulation by renal or intestinal disease
● Important cause of hypercalcemia (0.3-5.0 cases/1000 adults)
● Higher incidence in women; usually age 50+
● Associated with irradiation in some; may be associated with sarcoidosis
● Rarely presents with bone disease (Am J Clin Pathol 1993;100:697)
● Normocalcemic primary hyperparathyroidism also occurs

Symptoms (due to increased serum PTH and calcium): bones, stones, groans, moans

Bone disease:
● Osteoporosis (from osteoclast prominence and remodeling), with later deformities and fractures
● Osteitis fibrosa cystica (also called brown tumors, Recklinghausen’s disease [not neurofibromatosis]): thin cortex, marrow with increased fibrous tissue, hemorrhage and cysts; often in jaw

● Renal calcium stones in 20%
● Also nephrocalcinosis (calcification of renal interstitium and tubules)
● Renal stones cause hypertension, are important cause of death
● Renal abnormalities may progress after treatment

Groans from GI distress:
● Nausea, peptic ulcers (associated with high serum gastrin that decreases after surgical excision), constipation, pancreatitis, gallstones

Moans from CNS disturbance:
● Depression, lethargy, seizures

● Also weakness, fatigue, calcifications of aortic and mitral valves; metastatic calcification in stomach, lungs, myocardium, blood vessels


● Adenoma (85%), hyperplasia (15%), carcinoma (~1%)

Clinical features

● Often asymptomatic (no skeletal or renal lesions)
● Detected via screening studies for serum calcium
● To diagnose, PTH level must be elevated inappropriately to level of serum calcium
● Associated with low serum phosphorus, high urinary calcium and phosphorus, high serum alkaline phosphatase


● Surgical excision of enlarged gland plus one additional gland for diagnostic purposes
● Use selective venous catheterization to localize abnormal gland preoperatively
● Also total parathyroidectomy with autotransplantation of parathyroid tissue into forearm muscle, but may get recurrence of hyperparathyroidism, and hyperplastic gland may infiltrate the skeletal muscle and look malignant

Gross description

● Solid and cystic areas, brown due to hemosiderin

Micro description

● Osteoblastic and osteoclastic activity, cysts, hemosiderin-laden macrophages
● Pale, vacuolated cells arranged in a trabecular pattern are also seen in non PTH-mediated hypercalcemia (Am J Surg Pathol 1985;9:43)

Micro images

Gland composed mainly of chief cells with a rim of normal parathyroid tissue, no stromal fat

Chief cell hyperplasia and oncocytic cells

Cytology description

● FNA shows organoid or trabecular architecture of cellular tissue fragments with epithelial cells arranged around capillary cores and frequent microacini
● Cells have round, fairly uniform nuclei 6 to 8 microns
● Larger oxyphil cells may show considerable anisonucleosis
● No features of thyroid tissue such as hemosiderin-laden macrophages, abundant colloid, paravacuolar granules (Hum Pathol 1995;26:338)

Positive stains

● Cyclin D1 (61%, Mod Pathol 1999;12:412)

Electron microscopy description

● Ribosomal-lamellar complexes and groups of centrioles is suggestive of adenoma
● Examination of normal appearing glands can detect chief cell activity associated with hyperplasia (Hum Pathol 1986;17:1036)

Molecular / cytogenetics description

● ~ 40% monoclonal
● 95% sporadic; also associated with MEN 1 and MEN 2/2A syndromes (usually chief cell hyperplasia)
● PRAD1 / cyclin D1 (parathyroid adenoma 1) protein: inversion of gene on #11 puts PRAD1 next to 5’-PTH gene regulatory sequences which are constitutively active; seen in 10% of adenomas
● MEN 1: loss of 11q13 tumor suppressor gene usually found; also noted in 20% of sporadic adenomas
● MEN 2/2A: may see chief cell hyperplasia and medullary carcinoma at the same time

Differential diagnosis

● Familial hypocalciuric hypercalcemia: young patients with family history, autosomal dominant, usually mild parathyroid hyperplasia (Hum Pathol 1981;12:229)
Giant cell reparative granuloma: similar histology and both in jaw, so use laboratory findings to differentiate
● Giant cell tumor: evenly spaced giant cells, plump stromal cells, less osteoblastic activity
● Medullary carcinoma of thyroid if intrathyroidal tissue: PTH negative, calcitonin positive (Am J Surg Pathol 1983;7:535)
● Also hyperthyroidism, myeloma, sarcoidosis, vitamin A or vitamin D intoxication
● Tumor related hypercalcemia: has PTH-related protein, more common in squamous cell carcinomas, renal cell carcinoma, ovarian clear cell carcinoma, rarely leukemia (Am J Clin Pathol 1981;75:149), Kaposi’s sarcoma (Am J Clin Pathol 1976;66:998)

End of Parathyroid gland > Hyperparathyroidism > Primary hyperparathyroidism

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