Thyroid & parathyroid
Parathyroid nonmalignant
Hyperparathyroidism
Author: Monika Roychowdhury, M.D.
Last author update: 1 January 2013
Last staff update: 20 January 2021
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: Primary hyperparathyroidism[TI] pathology free full text[sb]
Table of Contents
Definition / general | Etiology | Clinical features | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosisCite this page: Roychowdhury M. Hyperparathyroidism. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/parathyroidprimarypth.html. Accessed April 24th, 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
Etiology
- 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
Stones:
- 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
Calciphylaxis
- 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
- 69 year old woman with primary hyperparathyroidism due to parathyroid adenoma (Arch Pathol Lab Med 2001;125:1351)
- 70 year old man with end stage renal failure secondary to IgA nephropathy (J Med Case Rep 2009;3:9297)
Treatment
- 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
Images hosted on other servers:
Calciphylaxis
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
Images hosted on other servers:
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
- 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
- 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
- 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
- Also hyperthyroidism, myeloma, sarcoidosis, vitamin A or vitamin D intoxication
- Medullary carcinoma of thyroid if intrathyroidal tissue: PTH-, calcitonin+ (Am J Surg Pathol 1983;7:535)
- 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 sarcoma (Am J Clin Pathol 1976;66:998)
