Chemistry, toxicology & urinalysis
General chemistry
Metabolism
Parathyroid hormone


Topic Completed: 23 July 2020

Minor changes: 23 July 2020

Copyright: 2020, PathologyOutlines.com, Inc.

PubMed Search: Parathyroid hormone pathology[title]

Patricia Tsang, M.D., M.B.A.
Page views in 2020 to date: 49
Cite this page: Tsang P. Parathyroid hormone. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/chemistryPTH.html. Accessed August 8th, 2020.
Definition / general
  • Hormone secreted by parathyroid glands for maintaining blood calcium homeostasis
  • Has reciprocal effect on phosphate metabolism
  • Its release controlled by ionized calcium level with negative feedback system
  • 84 amino acids derived from cleavage of prepro parathyroid hormone (PTH); biologic activity due to 34 amino acids at amino terminus; other portions are inert but may give false positives in detection systems
  • Binding of PTH to its receptor stimulates cAMP and phosphatidylinositol diphosphate
  • Note: PTH related protein is rarely produced by benign lesions (Am J Clin Pathol 1996;105:487)
Essential features
  • Maintains serum calcium within a tight range of around 9 - 10 mg/dL
  • Mobilizes calcium from bone, increases calcium reabsorption from the kidney and stimulates calcium absorption from the gut (Compr Physiol 2016;6:561)
  • Primary hyperparathyroidism leads to elevated PTH, elevated blood calcium and reduced blood phosphate; managed most commonly by parathyroidectomy
    • Intraoperative rapid PTH assays are useful as an indicator for successful surgical removal of the PTH hypersecreting parathyroid tissue
  • Both second and third generation PTH assays measure 1-84 full length intact PTH protein
    • Third generation assays are more specific and do not target truncated protein fragments
    • While second and third generation assays tend to correlate well (correlation coefficient close to 1.0), third generation assays may generate significantly lower absolute PTH values (Metabolism 2013;62:1416)
Pathophysiology
  • PTH maintains serum calcium homeostasis by exerting the following biological effects:
    • Activates and increases the number of osteoclasts, mobilizing calcium from bone
    • Increases renal tubular reabsorption of calcium
    • Activates 1-alpha-hydroxylase, which increases conversion of inactive vitamin D to the active dihydroxy form in kidneys
      • Active form of vitamin D promotes GI calcium absorption
    • Increases urinary phosphate excretion, which reduces calcium loss
  • Reference: Front Horm Res 2018;50:1
Diagrams / tables

Images hosted on other servers:

Biologic effects of PTH and
vitamin D on calcium and
phosphate metabolism

Clinical features
  • Primary hyperparathyroidism
    • Relatively common endocrine disorder (up to 80 per 100,000) caused by overactive parathyroid glands
    • 80% single adenoma, 10 - 15% hyperplasia, 5% multiple adenomas (Nat Rev Endocrinol 2018;14:115)
    • Presents with elevated circulating PTH, hypercalcemia and hypophosphatemia
    • Can lead to osteoporosis, bone fractures, hypercalciuria and nephrolithiasis (Best Pract Res Clin Rheumatol 2020;101514)
    • Managed with parathyroidectomy that leads to rapid decline in PTH level
    • Intraoperative rapid PTH assay: certain assays enable results in less than 20 minutes (Endocr Pract 2011;17:2)
    • Short half life of PTH (2 - 5 minutes) provides sensitive indication of successful removal of hypersecreting parathyroid gland(s)
    • Serial intraoperative PTH levels for trending are a common practice
  • Secondary hyperparathyroidism
    • Common complication of chronic renal disease that can lead to reduced vitamin D production
    • Low serum calcium or elevated phosphate leads to parathyroid hyperplasia and elevated circulating PTH (Ther Apher Dial 2019;23:309)
    • Elevated PTH can result in abnormal bone turnover (renal osteodystrophy)
  • Tertiary hyperparathyroidism
    • Most common in patients with chronic secondary hyperparathyroidism who have been on dialysis for years
    • Observed in 1 - 3% of patients with renal failure (Am J Otolaryngol 2017;38:630)
    • Hypertrophied parathyroid glands oversecrete PTH in an autonomic fashion despite resolution of the underlying condition (e.g. renal transplant)
    • Resulting hypercalcemia and hyperphosphatemia can lead to diffuse calcinosis
  • Hypoparathyroidism
    • Relatively rare heterogeneous condition characterized by insufficient circulating PTH (Expert Opin Drug Saf 2017;16:617)
    • Leads to hypocalcemia and hyperphosphatemia
    • Treated by vitamin D (inactive and active) and oral calcium tablets
  • Hypercalcemia of malignancy (breast, lung, kidney, myeloma) due to:
    • Release of PTH related protein, usually in advanced disease (squamous cell carcinoma, lung cancer, hepatoma) or
    • Osteolytic metastases with local release of cytokines (IL1, TNF alpha) (multiple myeloma, breast cancer, renal cell carcinoma)
Laboratory
Board review style question #1
Which of the following sets of laboratory values is characteristic of primary hyperparathyroidism?

  1. Elevated blood PTH, elevated calcium, elevated phosphate
  2. Elevated blood PTH, reduced calcium, elevated phosphate
  3. Elevated blood PTH, elevated calcium, reduced phosphate
  4. Elevated blood PTH, reduced calcium, reduced phosphate
Board review answer #1
C. In primary hyperparathyroidism, the elevated blood PTH physiologically increases serum calcium and reciprocally reduces serum phosphate.

Reference: Parathyroid hormone

Comment Here
Board review style question #2
Which of the following describes the difference between second generation and third generation PTH assays?

  1. Second generation PTH assays detect the 1-84 intact PTH protein in addition to the N truncated 7-84 fragment, while the third generation assays detect only the 1-84 intact PTH
  2. PTH values are numerically interchangeable between second generation and third generation assays
  3. Second generation PTH assays provide faster results as compared to third generation assays for intraoperative PTH evaluation
  4. Third generation PTH assays are more comprehensive than second generation assays by detecting more circulating PTH fragments
Board review answer #2
A. Third generation PTH assays do not detect 7-84 PTH and other fragments, which second generation assays typically do.

Reference: Parathyroid hormone

Comment Here
Back to top