**4. Embryology and anatomy of the parathyroid glands**

Embryologically, the parathyroid glands have an endodermal origin, usually four glands, and rarely may be in number of three, five, or more glands. They develop through the proliferation of the dorsal part of the branchial pharyngeal pouches. Both parathyroid glands migrate to the posterior portion of the thyroid gland, since the lower ones are able to migrate to the thymus or upper mediastinum [4, 12, 16].

### **4.1 Inferior parathyroid glands**

The inferior parathyroid glands originate from the dorsal portion of the third branchial pouch. This branchial pouch differs around the 5th to the 6th week of gestation, when the ventral portion gives rise to the thymus. Around the 7th week of pregnancy, both the thymus and the lower parathyroid loosen the connection with the pharynx, occurring medial and caudal migration of the thymus, bringing together the inferior parathyroid, when, finally, it separates from the thymus. Usually the inferior parathyroid glands are found outside the capsule of the thyroid gland and have a more variable location [17]. Caudal migration close to the thymus explains the lower localization of the inferior parathyroid glands (derived from the third branchial pouch) than the superior parathyroid glands (derived from the fourth branchial pouch). During this process, debris from the parathyroid tissue that can form supernumerary glands may detach. The arterial supply of the inferior parathyroid glands is from the branches of the inferior thyroid artery [17–19].

#### **4.2 Superior parathyroid glands**

The superior parathyroid glands originate from the dorsal portion of the fourth branchial pouch. In the 7th week of pregnancy, they lose their relationship with the

**73**

*Parathyroid Glands and Hyperparathyroidism: A General Overview*

pharynx and adhere to the thyroid gland, which is migrating caudally and medially. This migration occurs to a lesser extent than the migration of the thymus and inferior parathyroid glands, and therefore their locations are more predictable. Superior parathyroid glands are usually located more posteriorly and medially than inferior parathyroid glands, often located on the dorsal surface and outside the

*Anatomical location of the parathyroid glands, posterior view (modified by F. netter, atlas of human* 

These glands are closely related to the inferior thyroid artery and its intersection with the recurrent laryngeal nerve, although many anatomical variations may occur. The superior parathyroid glands have arterial supply from the branches of the inferior thyroid artery and posterior branches of the superior thyroid artery. The inferior thyroid artery generates branches to supply the parathyroid glands

Parathyroid appears in the body as two superior and two inferior glands in approximately 85–90% of the population. In addition, in 10% of the population, they appear as supernumerary, with 5 or more glands, with reports of up to 10

PTH, in these cases, is produced through a stimulus of the parathyroid due to an intrinsic pathology of this gland. In 85% of the cases, a parathyroid adenoma forms, generating an increase in PTH production. However, hyperplasia of the

*DOI: http://dx.doi.org/10.5772/intechopen.92785*

thyroid capsule [4, 17–19].

**Figure 3.**

*anatomy).*

before irrigating the thyroid lobes.

**5. Clinical presentations**

**5.1 Primary HPT**

parathyroid glands in a single patient [19].

**Figure 3** shows the locations of the parathyroid glands.

HPT can be divided into primary, secondary, or tertiary.

*Parathyroid Glands and Hyperparathyroidism: A General Overview DOI: http://dx.doi.org/10.5772/intechopen.92785*

**Figure 3.**

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

vitamin D (calcitriol) [12, 14, 15].

**3.3 Effect of PTH on the intestine**

num [4, 12, 16].

**4.1 Inferior parathyroid glands**

**4.2 Superior parathyroid glands**

hydroxyproline (markers of osteolysis) [11–13].

serum calcium from the resorption of bowel lumen [11].

**4. Embryology and anatomy of the parathyroid glands**

**3.2 Effect of PTH on bones**

alkalinization, resulting from decreased bicarbonate reabsorption in the proximal renal tubules; inhibition of sodium reabsorption in the proximal tubules, with increased clearance of free water and greater urinary flow; and increased activity of vitamin D1 alpha-hydroxylase, with greater production of the active form of

PTH produces both anabolic and catabolic effects, depending on the phases of action. In the early phase, there is a mobilization of calcium from the bones, entering equilibrium with the extracellular fluids. In the late phase, there is an increase in the synthesis of bone enzymes, such as lysosomal enzymes, which promotes bone resorption and remodeling. PTH also inhibits osteoclasts and stimulates bone resorption, leading to an increase in serum alkaline phosphatase and urinary

PTH has no direct action on the intestine. Its effect is due to an increase in the synthesis of calcitriol (activate form of vitamin D) in the kidneys, through the stimulation of the enzyme α1-hydroxylase. Calcitriol has an effect on increasing

Embryologically, the parathyroid glands have an endodermal origin, usually four glands, and rarely may be in number of three, five, or more glands. They develop through the proliferation of the dorsal part of the branchial pharyngeal pouches. Both parathyroid glands migrate to the posterior portion of the thyroid gland, since the lower ones are able to migrate to the thymus or upper mediasti-

The inferior parathyroid glands originate from the dorsal portion of the third branchial pouch. This branchial pouch differs around the 5th to the 6th week of gestation, when the ventral portion gives rise to the thymus. Around the 7th week of pregnancy, both the thymus and the lower parathyroid loosen the connection with the pharynx, occurring medial and caudal migration of the thymus, bringing together the inferior parathyroid, when, finally, it separates from the thymus. Usually the inferior parathyroid glands are found outside the capsule of the thyroid gland and have a more variable location [17]. Caudal migration close to the thymus explains the lower localization of the inferior parathyroid glands (derived from the third branchial pouch) than the superior parathyroid glands (derived from the fourth branchial pouch). During this process, debris from the parathyroid tissue that can form supernumerary glands may detach. The arterial supply of the inferior parathyroid glands is from the branches of the inferior thyroid artery [17–19].

The superior parathyroid glands originate from the dorsal portion of the fourth branchial pouch. In the 7th week of pregnancy, they lose their relationship with the

**72**

*Anatomical location of the parathyroid glands, posterior view (modified by F. netter, atlas of human anatomy).*

pharynx and adhere to the thyroid gland, which is migrating caudally and medially. This migration occurs to a lesser extent than the migration of the thymus and inferior parathyroid glands, and therefore their locations are more predictable. Superior parathyroid glands are usually located more posteriorly and medially than inferior parathyroid glands, often located on the dorsal surface and outside the thyroid capsule [4, 17–19].

These glands are closely related to the inferior thyroid artery and its intersection with the recurrent laryngeal nerve, although many anatomical variations may occur. The superior parathyroid glands have arterial supply from the branches of the inferior thyroid artery and posterior branches of the superior thyroid artery. The inferior thyroid artery generates branches to supply the parathyroid glands before irrigating the thyroid lobes.

Parathyroid appears in the body as two superior and two inferior glands in approximately 85–90% of the population. In addition, in 10% of the population, they appear as supernumerary, with 5 or more glands, with reports of up to 10 parathyroid glands in a single patient [19].

**Figure 3** shows the locations of the parathyroid glands.

## **5. Clinical presentations**

HPT can be divided into primary, secondary, or tertiary.

#### **5.1 Primary HPT**

PTH, in these cases, is produced through a stimulus of the parathyroid due to an intrinsic pathology of this gland. In 85% of the cases, a parathyroid adenoma forms, generating an increase in PTH production. However, hyperplasia of the

parathyroid gland (13%) or carcinoma (1%) can occur. Parathyroid adenoma is the most common clinical presentation in primary HPT. It usually presents with only one adenoma, but it can manifest in more than one parathyroid, known as multiple adenomas [20–22]. Structural genetic mutations are associated with the etiology of the adenoma, although it can also occur after exposure to neck irradiation, treatment with lithium, or thiazide diuretics [20, 23]. The consequence is the disorderly overproduction of PTH, increasing osteoclastic activity and therefore raising calcium levels in the body. PTH also stimulates renal calcium reabsorption and acts on the activation of vitamin D, increasing intestinal calcium absorption. Most are asymptomatic; however the patient may develop clinical manifestations. The most frequent consequence of primary HPT is nephrolithiasis that develops in almost 15–20% of cases. Nevertheless, HPT is found in just 5% of patients with nephrolithiasis. Osteoporosis, fibrous osteitis, and peptic disease may be also found in these patients. Neuropsychiatric and neuromuscular disorders such as asthenia, weakness, and mild depression can be found less frequently [24]. In rare presentations, brown tumors may be formed, the etiology of which is associated with the disruption of bone turnover between osteoblastic and osteoclastic activity, resulting in benign bone tumors. Sporadic presentation is more frequent; however, family forms may be associated. The main familial manifestations are multiple endocrine neoplasia (MEN) type I, or Werner's syndrome (HPT, pancreatic tumor and pituitary tumor), and type IIA, or Sipple's syndrome (HPT, medullary thyroid carcinoma and pheochromocytoma), and are associated with the expression of the RET proto-oncogene [24, 25].

Other existing familial forms described are primary neonatal HPT, familial hypocalciuric hypercalcemia, jaw tumor HPT syndrome, and isolated familial HPT [26]. Associated with primary HPT is the parathyroid carcinoma, a rare presentation, less than 1% of cases. It is suspected when there are high levels of serum calcium and PTH and may also have a palpable cervical mass on the thyroid gland topography. HPT in patients, if not treated quickly and efficiently, can progress rapidly to complications secondary to hypercalcemia and may progress to death [20, 26, 27].
