Parathyroid Glands: Diseases and Types

Parathyroid Glands Normal Structure

Anatomy The parathyroid glands are usually 4 in number: the superior pair is derived from the 4th branchial pouch and the inferior pair from the 3rd branchial pouch of the primitive foregut.

Both pairs are usually embedded in the posterior aspect of the thyroid substance but separated from it by a connective tissue capsule.

In the adults, each gland is an oval, yellowish-brown, flattened body, weighing 35-45 mg. There may, however, be variations in the number, location and size of parathyroid glands.

Read And Learn More: Systemic Pathology Notes

Histology Microscopically, parathyroid glands are composed of solid sheets and cords of parenchymal cells and a variable amount of stromal fat. The parenchymal cells are of 3 types: chief cells, oxyphil cells and water-clear cells.

The chief cells are the most numerous and are the major source of parathyroid hormone. The latter two types of cells appear to be derived from the chief cells and have sparse secretory granules but are potentially capable of secreting parathyroid hormone.

Parathyroid Hormone Functions: The major function of the parathyroid hormone, in conjunction with calcitonin and vitamin D, is to regulate serum calcium levels and the metabolism of bone. Parathyroid hormone tends to elevate serum calcium levels and reduce serum phosphate levels.

Secretion of parathyroid hormone takes place in response to the serum level of calcium by a feedback mechanism—lowered serum calcium stimulates the secretion of parathyroid hormone, while elevated serum calcium causes decreased secretion of the hormone.

The role of the parathyroid hormone in regulating calcium metabolism in the body is at the following 3 levels:

1. Parathyroid hormone stimulates osteoclastic activity and results in the resorption of bone and the release of calcium. Calcitonin released by C-cells, on the other hand, opposes parathyroid hormone by preventing the resorption of bone and lowering serum calcium levels.
2. Parathyroid hormone acts directly on renal tubular epithelial cells and increases renal reabsorption of calcium and inhibits reabsorption of phosphate; calcitonin enhances renal excretion of phosphate.
3. Parathyroid hormone increases renal production of the most active metabolite of vitamin D, i.e. 1, 25-dihydro cholecalciferol, which in turn increases calcium absorption from the small intestine.

The major parathyroid disorders are its functional disorders (hyper- and hypoparathyroidism) and neoplasms.

Parathyroid Gland

Hyperparathyroidism:

Hyperfunction of the parathyroid glands occurs due to excessive production of parathyroid hormone. It is classified into 3 types primary, secondary and tertiary.

1. Primary hyperparathyroidism occurs from the oversecretion of parathyroid hormone due to disease of the parathyroid glands.
2. Secondary hyperparathyroidism is caused by diseases in other parts of the body.
3. Tertiary hyperparathyroidism develops from secondary hyperplasia after the removal of the cause of secondary hyperplasia.

Primary Hyperparathyroidism:

Primary hyperparathyroidism is not uncommon and occurs more commonly with increasing age. It is especially likely to occur in women near the time of menopause.

Aetiology: Common causes of primary hyperparathyroidism are as follows:

1. Most commonly, parathyroid adenomas are in approximately 80% of cases.
2. Carcinoma of the parathyroid glands in 2-3% of patients.
3. Primary hyperplasia in about 15% of cases (usually chief cell hyperplasia).

Also included above are the familial cases of multiple endocrine neoplasias (MEN) syndromes where parathyroid adenoma or primary hyperplasia is one of the components.

Primary Hyperparathyroidism Clinical Features: The patients with primary hyperparathyroidism have the following characteristic biochemical abnormalities:

1. Elevated levels of parathyroid hormone
2. Hypercalcaemia
3. Hypophosphataemia
4. Hypercalciuria

Clinical presentation of individuals with primary hyperparathyroidism may be in a variety of ways:

1. Most commonly, nephrolithiasis and/or nephrocalcinosis. These dysfunctions result from excessive excretion of calcium in the urine due to hypercalcaemia induced by increased parathyroid hormone levels.
2. Metastatic calcification, especially in the blood vessels, kidneys, lungs, stomach, eyes and
   other tissues.
3. Generalised osteitis fibrosa cystica due to osteoclastic resorption of bone and its replacement
   by connective tissue.
4. Neuropsychiatric disturbances such as depression, anxiety, psychosis and coma.
5. Hypertension is found in about half the cases.
6. Other changes such as pancreatitis, cholelithiasis and peptic ulcers due to hypercalcaemia and high parathyroid hormone level are less constant features.

Secondary Hyperparathyroidism

Secondary hyperparathyroidism occurs due to increased parathyroid hormone elaboration secondary to a disease elsewhere in the body. Hypocalcaemia stimulates compensatory hyperplasia of the parathyroid glands and causes secondary hyperparathyroidism.

Secondary hyperparathyroidism Etiology Though any condition that causes hypocalcaemia stimulates the excessive secretion of parathyroid hormone, the important causes of secondary hyperparathyroidism are as under:

1. Chronic renal insufficiency results in the retention of phosphate and impaired intestinal absorption of calcium.
2. Vitamin D deficiency and consequent rickets and osteomalacia may cause parathyroid hyperfunction.
3. Intestinal malabsorption syndromes cause a deficiency of calcium and vitamin D.

Secondary Hyperparathyroidism Clinical Features: The main biochemical abnormality in secondary hyperparathyroidism is mild hypocalcaemia, in striking contrast to hypercalcaemia in primary hyperparathyroidism. Patients with secondary hyperparathyroidism have signs and symptoms of the disease which caused it.

Usually, secondary hyperparathyroidism is a beneficial compensatory mechanism, but more severe cases may be associated with renal osteodystrophy (i.e. features of varying degrees of osteitis fibrosa, osteomalacia, osteoporosis and osteosclerosis in cases of chronic renal insufficiency) and soft tissue calcification.

Parathyroid Gland

Tertiary Hyperparathyroidism:

Tertiary hyperparathyroidism is a complication of secondary hyperparathyroidism in which the hyperfunction persists in spite of the removal of the cause of secondary hyperplasia.

Possibly, a hyperplastic nodule in the parathyroid gland develops which becomes partially autonomous and continues to secrete large quantities of parathyroid hormone without regard to the needs of the body.

Hypoparathyroidism:

Deficiency or absence of parathyroid hormone secretion causes hypoparathyroidism. Hypoparathyroidism is of 3 types primary, pseudo- and pseudopseudo-hypoparathyroidism.

Primary Hypoparathyroidism

Primary hypoparathyroidism is caused by a disease of the parathyroid glands. The most common causes of primary hypoparathyroidism are surgical procedures involving the thyroid, parathyroid, or radical neck dissection for cancer.

Other causes are uncommon and include idiopathic hypoparathyroidism of autoimmune origin in children and may occur as sporadic or familial cases. These cases are generally associated with other autoimmune diseases.

Primary Hypoparathyroidism Clinical Features: The main biochemical dysfunctions in primary hypoparathyroidism are hypocalcaemia, hyperphosphataemia and hypocalciuria. The clinical manifestations of these abnormalities are as under:

1. Increased neuromuscular irritability and tetany
2. Calcification of the lens and cataract formation
3. Abnormalities in cardiac conduction
4. Disorders of the CNS due to intracranial calcification
5. Abnormalities of the teeth.

Pseudo-Hypoparathyroidism:

• In pseudo-hypoparathyroidism, the tissues fail to respond to parathyroid hormone though parathyroid glands are usually normal. It is a rare inherited condition with an autosomal dominant character.
• The patients are generally females and are characterised by signs and symptoms of hypoparathyroidism and other clinical features like short stature, short metacarpals and metatarsals, flat nose, round face and multiple exostoses.
• Since renal tubules cannot adequately respond to parathyroid hormone, there is hypercalciuria, hypocalcaemia and hyperphosphataemia.

Parathyroid Gland

Pseudopseudo-Hypoparathyroidism:

Pseudo-pseudo-hypoparathyroidism is another rare familial disorder in which all the clinical features of pseudo-hypoparathyroidism are present except that these patients have no hypocalcaemia or hyperphosphataemia and the tissues respond normally to parathyroid hormone. Pseudo-pseudo-hypoparathyroidism has been considered an incomplete form of pseudohypoparathyroidism.

Parathyroid Tumours:

Parathyroid adenoma and carcinoma are the neoplasms found in parathyroid glands, the former being much more common than the latter.

Parathyroid Adenoma:

The commonest tumour of the parathyroid glands is an adenoma. It may occur at any age and in either sex but is found more frequently in adult life. Most adenomas are first brought to attention because of excessive secretion of parathyroid hormone causing features of hyperparathyroidism as described above.

Morphologic Features Grossly, a parathyroid adenoma is a small (less than 5 cm diameter) encapsulated, yellowish-brown, ovoid nodule weighing up to 5 gm or more.

Microscopically, the majority of adenomas are predominantly composed of chief cells arranged in sheets or cords. Oxyphil cells and water-clear cells may be found intermingled in varying proportions. Usually, a rim of normal parathyroid parenchyma and fat are present external to the capsule which helps to distinguish an adenoma from diffuse hyperplasia.

Parathyroid Carcinoma:

Carcinoma of the parathyroid is rare and produces manifestations of hyperparathyroidism which is often more pronounced. Carcinoma tends to be irregular in shape and is adherent to the adjacent tissues. Most parathyroid carcinomas are well-differentiated.

It may be difficult to distinguish carcinoma of the parathyroid gland from an adenoma but local invasion of adjacent tissues and distant metastases are helpful criteria of malignancy in such cases.

Diseases of Parathyroid Gland:

• Hyperparathyroidism occurs due to excessive production of parathyroid hormone and may be primary (due to disease of the parathyroid glands), secondary (caused by diseases in other parts of the body) and tertiary (developing after removal of the cause of secondary hyperplasia).
• Hypoparathyroidism is of 3 types primary, pseudo- and pseudopseudohypoparathyroidism.
• The commonest tumour of the parathyroid glands is an adenoma; carcinoma of the parathyroid is rare and most often well-differentiated.