Parathyroid disorders

	Parathyroid disorders
Overview
Classification Hyperparathyroidism Familial hypocalciuric hypercalcemia Hypoparathyroidism Pseudohypoparathyroidism
Diagnosis
Differentiating Parathyroid Disorders

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2], Seyedmahdi Pahlavani, M.D. [3]

Synonyms and keywords:

Overview

The parathyroid glands are small endocrine glands in the neck, usually located behind the thyroid gland, which produce parathyroid hormone. These glands were first discovered in the Indian Rhinoceros by Richard Owen in 1852. The sole function of the parathyroid glands is to maintain the body's calcium level within a very narrow range, so that the nervous and muscular systems can function properly. When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated to release hormone into the blood. Parathyroid hormone (PTH, also known as parathormone) is a small protein that takes part in the control of calcium and phosphate homeostasis, as well as bone physiology. Parathyroid hormone has effects antagonistic to those of calcitonin. It increases blood calcium levels by stimulating osteoclasts to break down bone and release calcium. It also increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium uptake by the kidneys. Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). Overactivity of one or more of the parathyroid glands causes high calcium levels (hypercalcemia) and low levels of phosphorus in the blood. Hyperfunction of the parathyroid glands could be due to adenoma, hyperplasia or, rarely, carcinoma of the parathyroid glands. Hyperparathyroidism may present with symptoms of hypercalcemia, such as painful bones, kidney stones, abdominal pain, psychic moans, and fatigue. An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyoidism. Surgical therapy is preferred over medical therapy in primary hyperparathyroidism. Hypoparathyroidism is a disorder characterized by hypocalcemia due to insufficient secretion of PTH. Most common cause for hypoparathyroidism is post-surgical including thyroidectomy, parathyroidectomy, and radical neck dissection. Second most common cause for hypoparathyroidism is autoimmune including polyglandular autoimmune syndrome type 1 and isolated autoimmune hypoparathyroidism. Hypoparathyroidism should be differentiated from other causes of hypocalcemia. Causes of hypocalcemia other than hypoparathyroidism include pseudohypoparathyroidism, hypomagnesemia, hypovitaminosis D, chronic kidney disease, and relative hypocalcemia due to hypoalbuminemia. The hallmark of acute hypocalcemia due to hypoparathyroidism is tetany. A positive history of neck surgery and symptoms of hypocalcemia is suggestive of hypoparathyroidism. The most common symptoms of hypoparathyroidism include tetany, paresthesia, carpopedal spasms, and circumoral numbness. Common symptoms of hypoparathyroidism include abdominal pain, biliary colic, fatigue, muscle cramps, myoclonic jerks, new onset seizure due to hypocalcemia or worsening of seizures, and painful menstruation. Diagnosis of hypoparathyroidism is made by measurement of serum calcium (total and ionized), serum albumin (for correction), phosphate, intact parathyroid hormone (PTH), and 25-hydroxy vitamin D levels. Normal or inappropriately low serum intact parathyroid hormone (PTH) concentration in patients with subnormal serum albumin corrected total or ionized calcium concentration diagnostic of hypoparathyroidism. Pharmacologic medical therapies for hypoparathyroidism include calcium and Vitamin D3 supplementation. Severe hypocalcemia, a potentially life-threatening condition, is treated as soon as possible with intravenous calcium (e.g. as calcium gluconate).

Classification

Parathyroid disorders

Hyperparathyroidism

Familial hypocalciuric hypercalcemia

Hypoparathyroidism

Parathyroid hormone resistance diseases

Primary

Secondary

Tertiary

Post-surgical

Autoimmune

Genetic defects associated

Functional

Pseudohypoparathyroidism

Acrodysostosis

Blomstrand chondrodysplasia

Pseudohypoparathyroidism type 1

Pseudohypoparathyroidism type 2

Acrodysostosis type 1

Acrodysostosis type 2

Type 1A

Type 1B

Type 1C

Pseudopseudohypoparathyroidism

Diagnosis

Disorder		Laboratory findings
Disorder		Parathyroid hormone	Serum calcium	Serum phosphate	Other findings
Hyperparathyroidism	Primary hyperparathyroidism	↑	↑	↓/Normal	Normal/↑ calcitriol
	Secondary hyperparathyroidism	↑	↓/Normal	↑	--
	Tertiary hyperparathyroidism	↑	↑	↑	--
Familial hypocalciuric hypercalcemia		Normal/↑	Normal/↑	--	↓ Urinary calcium/creatinine clearance ratio
Hypoparathyroidism		↓	↓	↑	↓ 1,25 Dihydroxy vitamin D Normal urinary cAMP Normal urinary phosphate
Pseudohypoparathyroidism	Type 1A	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 1B	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Type 1C	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D ↓ Urinary cAMP ↓ Urinary phosphate
	Pseudopseudohypoparathyroidism	Normal	Normal	Normal	--
	Type 2	↑	↓	↑	↓ 1,25 Dihydroxy vitamin D Normal urinary cAMP ↓ Urinary phosphate
Acrodysostosis	Acrodysostosis type 1	↑	↓	↑	Multiple hormone resistance
Acrodysostosis	Acrodysostosis type 2	↑	↓	↑	Multiple hormone resistance
Blomstrand chondrodysplasia		↑	↓	↑	↓ Urinary phosphate ↑ Urinary cAMP

Differentiating Parathyroid Disorders

The main presenting features of parathyroid disorders are related to calcium secretion. Accordingly, differentiating parathyroid disorders from other diseases is mainly dependent to changes in calcium level. Following algorithms are designed to differentiate diseases according to hypercalcemia and hypocalcemia.