Endocrine Pathophysiology › Parathyroid Gland

Hypoparathyroidism & Calcium Imbalances

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Hypoparathyroidism & Calcium Imbalances

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Overview

Parathyroid hormone increases ECF calcium levels.

Regulated by calcium and vitamin D.

Parathyroid hormone protects against hypocalcemia by causing calcium release from the bones and reabsorption from the kidneys.

Calcium is a vital mineral that participates in various cellular processes, including muscle contraction, nerve conduction, bone and tooth formation, and blood clotting (for a full review of parathyroid hormone and calcium physiology, please see the tutorial on Parathyroid Hormone & Calcium Homeostasis).

Physiology Review:

Both calcium and phosphate are stored within the hydroxyapatite crystals of bone, and calcium can be retained or excreted in renal and digestive systems, depending on the body's needs.

A typical reference blood calcium range is 2.2-2.6 mmol/L (8.6-10.3 mg/dL).

Parathyroid gland location: posterior aspect of the thyroid gland.

Other key organs that engage in calcium homeostasis: Kidneys, small intestine, particularly the duodenum and, bone.

In response to reduced extracellular calcium concentration, the parathyroid glands secrete parathyroid hormone (PTH).

Effects of parathyroid hormone on the bones and kidneys:

  • Prolonged exposure to parathyroid hormone promotes resorption of old bone, and, therefore, the release of calcium and phosphate into extracellular fluid (episodic, transient binding of parathyroid hormone causes an increase in new bone synthesis).
  • In the kidneys, parathyroid hormone works directly and indirectly to raise extracellular calcium levels:

Parathyroid hormone increases calcium reabsorption in the distal convoluted tubule of the nephrons.

It also stimulates activation of Vitamin D (activated form = 1,25(OH)2-VD).

  • Vitamin D acts on the nephron to increase reabsorption of calcium and phosphate.
  • In the small intestine, Vitamin D increases calcium and phosphate reabsorption.
  • In the bones, Vitamin D works with parathyroid hormone to facilitate skeletal remodeling, which requires both synthesis and resorption of bone.

Thus, the total effect of parathyroid hormone is to elevate extracellular calcium levels.

If Vitamin D levels are high, parathyroid hormone secretion is inhibited.

Hypoparathyroidism

Hypoparathyroidism is most often the result of surgical removal or damage to the parathyroid glands.
Other causes include autoimmune destruction (i.e., Autoimmune polyglandular syndrome type 1), congenital lack of functioning parathyroid glands, and very low magnesium levels.

Low parathyroid hormone leads to low levels of calcium and high levels of phosphate.

Neuromuscular effects:

  • Muscle weakness
  • Paresthesia (tingling or burning, especially in the feet, hands, and around the mouth)
  • Cramping
  • Tetany
  • Laryngospasms, bronchospasms, and stridor are also associated with hypoparathyroidism.

Two key signs of tetany in hypoparathyroidism, and in hypocalcemia more generally, include:
Chvostek sign, in which tapping the facial nerve (in the parotid gland/masseter muscle area) produces facial muscle spasms.
Trousseau's sign, in which a carpopedal spasm is seen after a few minutes of wearing an inflated blood pressure cuff (20 mmHg above systolic pressure).
In the spasm, the patient will have flexed wrist, thumb, and metacarpophalangeal but hyperextended fingers.

Psychiatric effects:
Irritability and confusion.

Cardiovascular effects:
Include prolonged QT interval or heart failure.

Ocular:
Cataracts

Treatments
Activated Vitamin D and calcium supplements, possibly magnesium supplements.

Patients are often recommended diets high in calcium (consume more green leafy vegetables, legumes, fortified cereals) and low in phosphorous (so, consume less meat, soft drinks, and dairy products, which are high in phosphorus).

Pseudohypoparathyroidism
Patients present with signs and symptoms associated with hypoparathyroidism but normal or elevated levels of parathyroid hormone – these patients have hormone resistance in the target organs.
This is very rare.

Calcium Imbalances - Additional Causes

Hypercalcemia:

Disorders that cause excessive bone resorption (and therefore calcium release): Cancers, Paget disease, hyperthyroidism, Familial hypocalciuric hypercalcemia, Vitamin D toxicity, etc.

Disorders that cause excessive gastrointestinal calcium absorption:
Sarcoidosis, other granulomatous diseases.

Drugs that increase extracellular calcium, including lithium and thiazide diuretics.

Hypocalcemia:

Vitamin D deficiency or resistance (including antiseizure drugs that alter vitamin D metabolism)

Magnesium imbalances.

Board Review

Hypoparathyroidism

Getting ready for boards? Review these concise, bulleted high yield reviews for your exam.

USMLE & COMLEX-USA

Nurse Practitioner (NP)

Physician Assistant (PA)

Internal Medicine (ABIM)

References

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  • Franca Gois, Pedro Henrique, Martin Wolley, Dwarakanathan Ranganathan, and Antonio Carlos Seguro. "Vitamin D Deficiency in Chronic Kidney Disease: Recent Evidence and Controversies." International Journal of Environmental Research and Public Health 15, no. 8 (August 2018): 1773. https://doi.org/10.3390/ijerph15081773.
  • Gafni, Rachel I., and Michael T. Collins. "Hypoparathyroidism." Edited by Caren G. Solomon. New England Journal of Medicine 380, no. 18 (May 2, 2019): 1738–47. https://doi.org/10.1056/NEJMcp1800213.
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Textbooks:

  • Gardner, David. Greenspan's Basic and Clinical Endocrinology, Tenth Edition. McGraw-Hill Education, 2017.
    Hammer, Gary D., and Stephen J. McPhee, eds. Pathophysiology of Disease: An Introduction to Clinical Medicine. Eighth edition. New York: McGraw-Hill Education, 2019.
  • Holt, Elizabeth H, Beatrice Lupsa, Grace S Lee, Hanan Bassyouni, Harry E Peery, and H. Maurice Goodman. Goodman's Basic Medical Endocrinology, 2022. https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20170018724.
  • Jameson, J. Larry, ed. Harrison's Principles of Internal Medicine. Twentieth edition. New York: McGraw-Hill Education, 2018.
  • Kumar, V, AK Abbas, JC Aster, and JA Perkins. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders, 2015.
  • McPhee, Stephen J, Gary D Hammer, and Yeong Kwok. Pathophysiology of Disease: An Introduction to Clinical Medicine, 8e. New York, N.Y.: McGraw-Hill Education LLC., 2019. https://accessmedicine.mhmedical.com/cases.aspx?gboscontainerID=216.