Thyroid & parathyroid

Parathyroid nonmalignant


Last author update: 1 January 2013
Last staff update: 20 January 2021

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PubMed Search: Primary hyperparathyroidism[TI] pathology free full text[sb]

Monika Roychowdhury, M.D.
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Cite this page: Roychowdhury M. Hyperparathyroidism. website. Accessed April 15th, 2024.
Definition / general
  • 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
  • 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

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, von Recklinghausen 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

  • Rare and life threatening condition of vascular calcification, first described in 1962, that causes ischemic damage to skin (usually lower extremity) and other organs (G Ital Nefrol 2012;29:674, Hum Pathol 1995;26:1055)
  • Also known as calcific uremic arteriopathy (CUA), calcifying panniculitis, vascular calcification-cutaneous necrosis syndrome
  • Affects 1 - 4% of dialysis patients; associated with primary, secondary or tertiary hyperparathyroidism
  • 60 - 80% mortality
  • Diagnosis: bilateral, symmetrical, superficial skin lesions with persistence of dorsal pulses; confirm with biopsy
  • Treatment: parathyroidectomy

Secondary hyperparathyroidism
  • Hyperparathyroidism due primarily to non-PTH disease
  • Bone changes usually less severe than primary hyperparathyroidism
  • Dialysis patients may have discrete, punched out bone lesions with minimal resorption or osteoblast activity (Am J Surg Pathol 1987;11:205)
  • Due to hypocalcemia, which causes elevated PTH levels; causes of hypocalcemia are renal failure (phosphorus retention directly depresses serium calcium levels), inadequate calcium intake, steatorrhea (failure to absorb vitamin D), vitamin D deficiency or resistance; note:
  • ~60% monoclonal

Tertiary hyperparathyroidism
  • Autonomous parathyroid hyperplasia / adenoma arising from secondary hyperparathyroidism
  • Often detected after hemodialysis or transplantation corrects the renal disease
  • May have 10-40x increase in parathyroid mass
  • Treatment: surgical excision
  • Micro description: marked hyperplasia, with predominance of chief cells and abundance of oxyphil cells (Hum Pathol 1985;16:772)
Case reports
  • 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
Clinical images

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Gross description
  • Solid and cystic areas, brown due to hemosiderin
Microscopic (histologic) 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)
Microscopic (histologic) images

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

Chief cell hyperplasia and oncocytic cells

Calciphylaxis: ischaemic skin changes

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
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
  • MEN1: 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
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