What is Parathyroid Gland?
Parathyroid gland is so named because it is present adjacent to thyroid.The name “Parathyroid” is made up of two words namely ‘Para’ and ‘Thyroid’. The meaning of ‘Para’ is along side or adjacent to.
Before knowing the exact location of parathyroid, one should know about the terms Anterior and Posterior. These are two used in anatomy to describe front for former and back for latter.
Parathyroid gland is present on the posterior or back side of thyroid gland. It is present in the form of small lobules which are present on the upper and lower border of thyroid gland.
Parathyroid Gland History
The branch of medicine which deals with endocrine glands and hormones is endocrinology. It is one of the branches of medicine which have very slowly evolved. Parathyroid glands and diseases affecting those are the last ones to be discovered.
In the late nineteenth century, parathyroid glands were identified in humans by Ivar Sandstrom. You can also read this great book written by Ivar Sandstrom about Glandulae Parathyreoideae.
There are a few discoveries which show that diseases affecting the parathyroid gland dates back to the Pharaonic period.
Anthropologists have found head of femur bone in Dakhleh Oasis in Egypt of an adult female showing a particular type of ‘tunneling’ resorption which is peculiar to hyperparathyroidism. Further analysis of the bone showed that they aged between 36BCE to 400BCE.
Discovery of Parathyroid Glands
The small size of parathyroid glands and location behind and/or within the thyroid gland is a possible reason for its late discovery.
The first description of parathyroid glands is attributed to Richard Owen in 1850, but those did not describe the function and a proper name for these glands.
He served as the Conservator of the Hunterian collection of the Royal College of Surgeons. It was at this position he dissected a body of Indian rhinoceros. Later on he published a paper in the journal of Zoological Society, named ‘Transactions’.
He described the then parathyroid glands as “a small compact yellow glandular body, attached to the thyroid where the veins emerge.” His work on Rhinoceros is still preserved in the Museum of Royal College of Surgeons.
The anatomic remark on parathyroid glands being present or not in humans has been made by Robert Remark in 1855 and Rudolf Virchow in 1863.
The whole credit of identification, description and naming of parathyroid glands goes to Ivar Sandstrom. He made this discovery in three years of his post graduation. He dissected around 50 human cadavers and other mammals like cats, dogs, rabbits etc.
His work went unnoticed for many years as the German publishers refused to publish his findings on parathyroid gland.
Another finding of parathyroid gland was done by E.C Baber in 1881which was published in English. But unfortunately, these findings also went unseen for quite sometime.
The first physiological or functional importance of parathyroid was attempted by Eugene Gley from France. He performed a series of experiments where he removed the thyroid gland to show the effect on body. Such experiments ensued seizures in body.
For such seizures the term “Tetany” was coined by Lucien Corvisart in the year 1852. In support of these findings another scientists Giuilo Vassale and Francesco Generalli performed an important experiment by just removing the upper and lower pair of parathyroid glands. The removal resulted in the death of experimental animals due to seizures.
Then question arised why there were seizures in absence of parathyroid glands. The investigators tried to find the answer by finding the exact role of parathyroid glands. Therefore, the role of Calcium metabolism came into picture.
Establishment of Calcium Connection with Parathyroid Glands
Many medical practitioners from old times have come across bone diseases. On the other hand, they have also faced the hyperactive parathyroid glands in most of the patients suffering from bone diseases. But none of them came up with exact relation between a hyperactive parathyroid gland and bone diseases.
Another question which arised was whether the bone disease causes a hyperactive parathyroid gland or a hyperactive gland produces the bone disease. This became the question of debate over many years.
The first person to connect the hyperactivity of parathyroid glands to bone disease was a Viennese physician Z. Schlagenhaufer.
In the year 1915, when he was treating a patient of Osteitis Fibrosa Cystica (a bone disease where there is excess of parathyroid hormone, which disturbs the calcium metabolism therefore causing weakening of bones), he came across one enlarged parathyroid gland in the patient. This made him think that the bone disease may be because of enlarged parathyroid gland.
To prove this, a surgery was performed to remove the enlarged parathyroid gland. After the removal, there was radical improvement in the bone disease.
Till this time period, the role of calcium in an important physiological function of muscle contraction was established. A scientist named Jacques Loeb in 1900, proved this important function of calcium in muscle contraction.
A breakthrough in the connection of calcium with parathyroid gland function was made by Canadian Pathologist W.G.MacCallum and a Swiss Chemist Carl Veogtlin in the year 1908 and 1917.
These two investigators showed that after the removal of parathyroid glands, “Tetany” developed in the experimental animals. The tetany was accompanied by reduction of levels of calcium in blood.
This final clarification one the connection of calcium with parathyroid glands took another couple of years. Hence, it was proved that the levels of calcium in blood are maintained by the parathyroid glands and their respective hormones.
Definition of Parathyroid
Parathyroid can be defined as “a pea sized endocrine gland which has the function of regulating the levels of calcium in blood.”
There are a few standard definitions of this endocrine gland.
- As given by the National Cancer Institute “One of four pea-sized glands found on the surface of thyroid. The hormone secreted by these glands increases the level of calcium in blood.”
- Definition of parathyroid gland as given by the Merriam Webster Dictionary “Any of usually four small endocrine glands that adjacent to or embedded in the thyroid gland and produce parathyroid hormone.”
- An explanatory working definition of parathyroid gland “A pea-sized paired endocrine gland which is located within or adjacent to thyroid gland. It produces a hormone called parathyroid hormone or parathormone. This hormone has an important function in increasing the levels of calcium in blood.”
Parathyroid Gland Location and Functions
Development of Parathyroid Gland
The branch of medicine which deals with the development of an embryo is termed as embryology. The basic plan of development of a human embryo is that the soft structures of the body are developed from structures termed as the Pharyngeal Pouches.
The Pharyngeal pouches are drawn into hollow spaces and these will eventually developed into soft structures of the body.
The parathyroid gland develops from these structures namely-
The number of parathyroid glands varies from one specie to another. In humans the parathyroid gland develops from the third and fourth pharyngeal pouch.
The development of parathyroid glands has been linked to the development of thymus. Both these organs develop from different regions of the same pharyngeal pouch.
There are a few events which take place during the development of parathyroid gland:
- The initial structure for parathyroid forms in the dorsal-anterior(term dorsal is used for the surfaces close to the brain) region of the pharyngeal pouch. This forms a primitive structure of parathyroid gland.
- The ventral (term ventral is used for the surfaces away from the brain) region of the same pharyngeal pouch forms the nidus for thymus gland.
- Eventually these two structures are separated from the rounding off by a group of cells which are the neural crest cells ( a group of cells peculiar for the vertebrates and they arise from the ectoderm cell layer in developing embryo).
- Finally, the thymus will descend down and simultaneously the parathyroid gland will also drag down because of the physical forces exerted by the descending thymus.
Anatomy of Parathyroid Gland
As discussed above the parathyroid glands are paired and present within or adjacent to the thyroid gland, within a covering of the thyroid gland called the False Capsule.
Now the parathyroid gland pairs are situated on the superior and inferior borders of thyroid. The superior parathyroid gland pair is also called the Parathyroid IV, because it develops from the fourth pharyngeal pouch.
Whereas, the inferior parathyroid gland pair is called Parathyroid III , as it develops from the third pharyngeal pouch. The parathyroid glands are found to be bilobed (5%) or sometimes multilobed (1%).
Structural Features of Parathyroid Gland
- Shape of Parathyroid Gland: It is oval in shape mostly in form of small globules. In simple terms, it resembles a pea.
- Color of Parathyroid Gland: It varies from yellow to reddish brown in color.
- Dimensions of Parathyroid Gland: The dimensions of this gland are 6x4x2 mm, with longest axis which measures about 5mm.
- Weight of Parathyroid Gland: The weight of the gland varies in both the genders-
- Males: It weighs around 0.45 gms in an adult male.
- Females:5 gms in an adult female.
Where is the Parathyroid Located?
- Superior Parathyroid Gland: The superior parathyroid gland is constant in position and lies in the middle of the posterior border of thyroid gland. But sometimes it may also be found at a much higher level.
- Position of Inferior Parathyroid Gland: The position of these set of parathyroid glands is variable and they may lie:
- Inside the thyroid capsule, below the thyroid artery, close to the lower pole of thyroid lobe.
- Outside and behind the thyroid capsule just above the inferior thyroid artery.
- Inside the substance of thyroid lobe close to the posterior border. This is situated ventral to the recurrent laryngeal nerve.
Blood Supply of Parathyroid Glands
Arteries Supplying the Parathyroid Glands
The parathyroid glands have a rich arterial blood supply from these two sources:
- The Inferior Thyroid Artery: It is the branch of the thyrocervical trunk which arises from the subclavian artery.
- The junction between Superior and Inferior Thyroid Arteries. The Superior Thyroid artery is the first branch of carotid artery.
- Venous Drainage of Parathyroid Glands
The venous drainage of parathyroid gland is associated with that of thyroid gland. The thyroid gland is drained by the Superior, Middle and Inferior thyroid veins.
Lymphatic Drainage of Parathyroid Glands
The lymphatic drainage also follows that of the thyroid gland. Therefore to know the lymphatic drainage of parathyroid it is essential to know the lymphatic drainage of thyroid gland.
The lymphatic drainage has been divided that from the upper part and from the lower part.
- Nerve Supply of Parathyroid Glands
- The vasomotor (nerves which help in the constriction or dilatation of blood vessels) nerves are derived from the middle and superior cervical ganglia.
- The secretory function of the gland is controlled by the levels of calcium in blood.
Cells in Parathyroid Gland
The parathyroid glands are composed of two main types of cells. They are the Chief cells and the Oxyphil Cells. A third type which may sometimes be seen in a section of parathyroid glands under a microscope are the Water Cells or Clear Cells.
- 6-8 microns in size
- Polygonal in shape
- Cytoplasm contains granules of the Parathyroid Hormone.
- Nucleus is round and placed in the center
- Around 80% of chief cells have fat globules within the cell.
- This group of cells is most sensitive to changes in calcium.
- Larger than chief cells
- 12 microns in size
- Contain abundant number of mitochondria in the cytoplasm
- These cells appear during puberty
- With increasing age the number of these cells also increases
- These are the chief cells which appear empty or clear under the microscope.
Physiology of Parathyroid Gland
- Functions of Parathyroid Gland
The functions of the parathyroid gland are maintained by the hormone produced by the gland. The secretion is in the form of a hormone which is the Parathyroid Hormone (PTH).
Parathyroid Hormone/ Parathormone (PTH)
- Chemical Structure of Parathyroid Hormone
- The chemical nature of parathyroid hormone is polypeptide and it is secreted in the inactive preprohormone form.
- It is synthesized on the ribosomes as a polypeptide chain of 110 amino acids.
- This chain is first cleaved to the prohormone form containing 90 amino acids.
- Later on the chain is further cleaved to 84 amino acid chain by the golgi apparatus and endoplasmic reticulum. This is the active hormone, which is packed in the cytoplasm in the form of secretory granules.
- The final hormone has a molecular weight of 9500 kDa.
Normal Parathyroid Hormone Range
The normal parathyroid range varies from 10 – 65pg/mL. This range is applicable to all the age groups. The levels are investigated in the blood samples.
Parathyroid Hormone Test
The tests of choice for intact parathyroid hormone are Immunoradiometric or Immunochemiluminicence assays.
Immunoradiometric Assay for Parathyroid Hormone
Commercial immunoradiometric essay kits are available for measurement of parathyroid hormone in blood.The technique of Immunoradiometric Essay was first described by Miles and Hales in 1968.
Principle – This technique is based on the principles of antigen and antibody reaction but the antibodies are labeled with radioisotopes.
Labeling of antibodies is done with the help of radioactive iodine isotopes. I125 and I131
Immunochemiluminicence Assay for Parathyroid Hormone
This evaluation of parathyroid hormone is a type of reaction which will show luminescence (light) when a chemical reaction between an antigen and an antibody takes place.
What is Parathyroid Hormone Related Protein (PTHrp)??
Parathyroid hormone related protein is composed of 139 to 173 amino acids, which is structurally similar to parathyroid hormone. Parathyroid hormone related protein was first isolated in patient who had a tumor and high levels of blood calcium.
It was postulated 5 years ago that certain tumors are capable of increasing the levels of calcium in blood. Later, PTHrp was isolated from these tumors and the condition was called Malignancy Associated Hypercalceamia.
The cancers commonly associated with Hypercalceamia are of Breast, Lungs and Multiple Myeloma.
Hypercalceamia in patient suffering from cancer was first time isolated in the 1920s. The function of PTHrp is very much similar to parathyroid hormone.Till now multiple genes have been found and PTHrp has been cloned.
Functions of Parathyroid Hormone
- The major function of the parathyroid hormone is maintain the levels of calcium and phosphate levels in blood.
- There are various mechanisms by which this hormone increases the levels of calcium and phosphate in blood. These are:
- Parathyroid Hormone increases calcium and phosphate absorption from the bones.
- Parathyroid Hormone decreases calcium excretion and increases phosphate excretion by the kidneys
- Parathormone increases absorption of calcium and phosphate in the intestines.
- Parathyroid Hormone Increases Calcium and Phosphate Absorption from Bones
- The action of parathyroid hormone on bone depends on the levels of calcium in blood. Parathormone performs the removal of calcium form bone(called as Osteolysis) when blood calcium levels are low (called as Hypocalcaemia) .
- Similarly when there is increase in the levels of blood calcium (Hypercalceamia) this hormone will act in addition of calcium to the bone ( the Osteoblastic activity).
- Osteolysis – Bones are composed of certain types of cells out of which one particular type will form the bone (the Osteoblasts) while other will degrade the bone structure(the Osteoclasts).
- The cells involved in the osteolytic activity are the Osteoclasts. Along with these cells, the parathyroid hormone, there are a few other molecules like Prostaglandins, Tumor Necrosis Factors, RANK and RANK-L.
- These molecules are helpful in performing the act of osteolysis on bone and these are activated in cases where there is reduction in levels of blood calcium.
- Osteoblastic Pathway – This pathway takes place in cases where there is increase in levels of blood calcium.
- The cells taking part here are the Osteoblast cells.
- In this pathway there are a different set of molecules which become active when the signal of increased blood calcium level is received.
- Parathyroid Hormone Decreases Calcium Excretion and Increases Phosphate Excretion by the Kidneys
- The parathyroid hormone plays an important role in increasing the levels of calcium in blood by acting on three organs: the bones, kidney and the intestines.
- In kidneys this hormone acts by promoting the re absorption of calcium and hence reduces the level of calcium in urine.
- Secondly, parathyroid hormone acts as a very important factor in promoting the formation of Vitamin D, in kidneys.
- Parathormone Increases Absorption of Calcium and Phosphate in the Intestines
- The effect of Parathyroid hormone on intestines is indirect.
- It increases the level of calcium in blood by promoting formation of Vitamin D (Calcitriol) in the kidneys.
- Calcitriol in turn promotes the formation of calcium absorbing proteins in the intestinal cells, hence increasing the calcium absorption.
The parathyroid gland functions may get disturbed in cases where there is an overactive gland. The hyperactivity of parathyroid gland is reflected in the levels of calcium in blood.
Parathyroid Hormone and Vitamin D
In recent years the requirement of Vitamin D for maintenance of bone health has gained a lot of interest.There is an inverse relationship between the levels of Vitamin D and Parathyroid hormone.
Calcium metabolism in the body is maintained by three factors –
- Parathyroid Hormone
- Vitamin D
Among these three, parathyroid hormone and Vitamin D are known to increase the level of blood calcium where as Calcitonin, which is a hormone secreted by the C-cells of Thyroid Gland is known to reduce the blood calcium levels.
As Vitamin D increases the absorption of calcium from intestines, the rising calcium level after reaching to an optimum limit puts an inhibitory influence on the parathyroid hormone.
Parathyroid Diseases and Disorders
For descriptive purpose the disorders affecting the parathyroid glands can be divided in the various categories as discussed in the next para.
Diseases affecting the release of Parathyroid Hormone
Hyperparathyroidism/ Overactive Parathyroid Gland:
An uncommon disease which increases due to the increased activity of parathyroid glands and manifests itself as hypercalceamia.
- Types of Hyperparathyroidism
Primary Hyperparathyroidism (Osteitis Fibrosa Cystica) – This type of hyperactivity of parathyroid gland is because of underlying Benign Tumor (Adenoma).
Any Reactive Hyperplasia (an increase in size of any organ due to increase in number of cells), can also produce this type of hyperparathyroidism.
Causes of Primary Hyperparathyroidism
- Exact cause is unknown
- Genetic – It can occur as a part of a syndrome called Multiple Endocrine Neoplasia (MEN I & MEN IA).
- Ionising Radiation
- Declining kidney function with increasing age.
Clinical Features of Primary Hyperparathyroidism
- Common in females.
- Female/Male ratio 4:1.
- This disease affects 1 in 1000 individuals
- Most common feature of presentation is Hypercalceamia of unknown cause(50% cases).
- Kidney Stones (25% cases).
Effect of Hyperparathyroidism
Effect of Hyperparathyroidism on Bones
Increasing levels of parathyroid hormone, cause excessive destruction of the skeleton. This makes the bones brittle and easily breakable.
Effect of Hyperparathyroidism on Kidneys
Increase in the levels of Calcium in blood causes more amount of calcium to be reabsorbed by the kidneys and therefore the patient is more prone to have kidney stones.
Effect of Hyperparathyroidism on Abdomen –
- Calcium causes increased production of a hormone in stomach called the Gastrin. This hormone produces large amounts of acid which can produce ulcers in stomach.
- Calcium can also cause inflammation in pancreas, thus producing pain.
- Increase in blood calcium can also produce gall bladder stones.
- Psychological Effects –
- Hypercalceamia can also result in depression, anxiety, sometimes psychosis (mental disorder).
- In severe cases even coma may ensue.
This type of hyperparathyroidism occurs due to long standing kidney failure (Chronic Renal Failure). It occurs because of inability of kidneys to reabsorb calcium. As a result of which the calcium passes in urine and thereby there is increase in levels of phosphate.
It is a type of hyperparathyroidism is seen in patients undergoing kidney transplant for long standing kidney failure. These patients may also have problems similar to those seen in primary type of hyperparathyroidism.
Treatment of Hyperparathyroidism
Medical Management of Hyperparathyroidism
In severe cases, where there are very high levels of blood calcium, the treatment plan followed is-
- Infusion of intravenous fluids like saline
- Prescription of drugs like Bisphosphonates, these are known to reduce the destruction of bone.
- Administration of Calcitonin, a hormone which is important in reducing the blood calcium levels.
- A group of steroid hormones, Glucocorticoids, is given orally as it an anti-tumor agent.
- Patients who have kidney disease producing hypercalceamia, Dialysis is performed within 24-48 hours.
What is Hypercalceamia and Non – Parathyroid Hypercalceamia
The normal range of calcium in blood is 9-11 mg/dL. A fluctuation above this normal range is termed as Hypercalceamia.
The causes of Hypercalceamia can either be Parathyroid related or non-parathyroid related.
|Parathyroid Related Hypercalceamia||Non – parathyroid Hypercalceamia|
|Primary HyperparathyroidismSecondary Hyperparathyroidism
|Malignancy – Secretion of Parathyroid like substance from a few tumors. For exam PTHrp.
Bacterial Granulomatous Diseases – Tuberculosis
Non – Parathyroid Endocrine Disease – Increased thyroid hormone (T4), Tumor of Adrenal Gland (Pheocromocytoma), Diseases affecting the adrenal gland.
Medications – Milk-alkali syndrome, Thiazides, Vitamin A/D toxicity, Thiazides etc.
It is a disease of the parathyroid gland in which there is reduced parathyroid hormone in the blood circulation.
- Causes of Hyperparathyroidism
- Surgical removal of parathyroid glands
- Immune mediated destruction of parathyroid glands (Autoimmunity)
- Defects of calcium absorption at cellular level.
- A congenital absence of parathyroid glands (Di George Syndrome)
- Clinical Presentation
- Hypoparathyroidism leads to reduced calcium levels in blood and the symptoms arise due to this deficiency.
- Hypoparathyroidism can be symptomatic or asymptomatic.
- When produces symptoms it causes –
- Numbness around the lips
- Muscle spasms (sudden contraction of muscles causing pain)
- Seizures (abnormal electrical activity in brain causing unconsciousness)
- Tetany ( intermittent muscle spasm because of parathyroid gland hypofunction).
What is Tetany and How Does It Happen Due to Hypofunction of Parathyroid Gland??
Tetany is a disorder which occurs because of hypocalcaemia. In this disorder, there is increase in the excitation of the neuromuscular junction which produces extreme contraction in the muscles.
The symptoms of this condition vary from mild to life threatening. In mild cases, the muscles around the mouth, small muscles of the wrist and feet are affected. Also tingling sensation of the hand and feet is common.
In severe cases, the muscles of the larynx, generalized muscle involvement is noted. In these cases, the muscles of heart may also be affected producing a life threatening condition.
Clinical Signs to Detect Tetany
- Trousseau Sign – It is a sign in which the Tetany is diagnosed during a period of latency. This means the patient will not have any other symptom.
- This sign is very uncomfortable and painful.
- To check this sign the blood pressure cuff is tied to the patient’s arm and inflated till 20 mm of Hg.
- This inflation blocks the blood supply to hand for about 3-5 minutes.
- A positive Trousseau sign, shows spasm in the muscles of the hand and wrist.
- Chevostek Sign
This is another characteristic sign which helps in the diagnosis of Tetany.
- This sign is performed to detect the abnormal function of Facial Nerve. This nerve controls the muscular activity of face.
- To perform this test, a tap is given at the corner of jaw.
- A positive Chevostek sign will give immediate contraction of facial musculature.
Treatment of Hypoparathyroidism
- Diet Management –Foods rich in calcium are given, this includes dairy products, nuts, green leafy vegetables, fortified fruit juices etc
- Food articles rich in phosphates should be avoided, for example carbonated drinks.
- Oral calcium supplements.
- Vitamin D supplements like
- Administration of Synthetically available Parathyroid Hormone.
Diseases Affecting Structure of Parathyroid Gland
Tumors of Parathyroid Gland – The tumors of parathyroid gland can be either benign or malignant.
Sometimes the variation in levels of calcium can also present as an enlargement or a growth. One such example is Secondary hyperparathyroidism can present itself as an enlargement called as the Brown Tumor.
Brown tumor is a reactive response of the body towards the increasing levels of calcium in blood. This enlargement never turns cancerous. Moreover, this can involve any bone in the body.
Benign Tumors of Parathyroid Gland
- Hyperplasia of Parathyroid Glands – Before knowing about parathyroid gland hyperplasia, one should understand what is hyperplasia.
- Definition of Hyperplasia – According to National Cancer Institute, the increase in number of cells in organ is called hyperplasia. This is considered to be initial stage of cancer.
- According to the Meriam Webster dictionary, Hyperplasia is defined as an abnormal or unusual increase in the elements composing a part.
- In case of parathyroid glands, the cells undergoing hyperplasia are the chief cells. Sometimes, water/clear cells may also show hyperplasia.
- Parathyroid gland hyperplasia involves all four parathyroid glands.
- The levels of blood calcium are >11.7mg/dl.
- Approximately, 15% cases of primary hyperparathyroidism are caused by hyperplasia.
- Hyperplasia of parathyroid glands may sometimes be associated with Multiple Endocrine Neoplasia syndrome (MEN). Thus, showing a genetic association.
- Hyperplastic changes make the parathyroid gland to weigh around 3-5 gms.
- Parathyroid Adenoma – It is a benign tumor of the parathyroid gland, which arises from the chief cells of the gland.
- Clinical Presentation of Adenoma of Parathyroid Gland –
- Commonly seen in females
- Incidence rate is around 30 – 90%.
- Common cause of primary hyperparathyroidism.
- Blood calcium levels are more than compared to parathyroid hyperplasia and ranges about 12.5 – 13.5 mg/dl.
- Usually the patients do not feel any discomfort and hypercalceamia is detected accidentally.
- Patients may only complain of fatigue, weakness or depression.
- Another commonly documented disturbance is presence of kidney stones.
- It commonly involves lower pair of parathyroid glands.
- Surgically removed tumor specimen are kidney shaped, red-brown in color.
- Parathyroid Adenomas are a single gland disease, unlike parathyroid hyperplasia.
Parathyroid Adenoma Treatment
The treatment of parathyroid adenomas include a combined therapy of Medical and Surgical intervention. The medical management is aimed at controlling the raised levels of calcium in blood and thereby treat the effects of Hypercalceamia.
- The medical management includes the treatment similar to that of primary hyperparathyroidism.
- Surgical intervention becomes necessary in around 25% of patients.
Malignant Tumor of Parathyroid Gland (Parathyroid Gland Cancer)
A slow growing cancer which involves not only the parathyroid gland but also the surrounding structures in the neck.
Features of Parathyroid Carcinoma
- Cancer of parathyroid gland presents with profound hypercalceamia.
- It affects younger age group as compared to the patients of Parathyroid Adenomas.
- 5 – 2% of primary hyperparathyroidism are because of parathyroid carcinomas.
- Severe hypercalceamia which is often >14mg/dl.
- Occasionally, patients with normal blood calcium levels may also be seen.
- Parathyroid carcinomas are comparatively large tumors which invade the surrounding deep structures of neck like thyroid and esophagus.
- Cancer of parathyroid glad makes it weigh around 6-7 gms.
- Symptoms of parathyroid carcinoma are similar to those of primary hyperparathyroidism, but more severe.
- The major diagnostic criteria of a parathyroid gland cancer is the presence of invasion of deep neck structures by the tumor making “Tongue-like” protrusions.
Secondary Tumors Affecting Parathyroid Gland
What are Secondary Tumors / Cancers?
The secondary tumors or cancers are those which spread to other organs from the primary affected organ.For example a primary tumor of the oral cavity may produce secondary cancers in the liver, lungs or breasts etc.
Secondary Cancers affecting the Parathyroid Gland
Primary tumors of the adjacent neck structures or any distant organ can produce secondary cancers in the parathyroid glands.This formation of secondary cancer can occur by spreading of cancer cells by the means of –
- If the tumor is situated in close approximation of the gland (Local Invasion).
- Spread of tumor cells by means of blood vessels.
- Tumors cells may spread by means of lymphatic channels.
Features of Secondary Cancers affecting Parathyroid Glands
- Usually it does not produce any symptoms.
- Common complaints can be pain in neck, hoarseness in voice, difficulty in swallowing.
- Sometimes the patient may present with low blood calcium levels.
- Though these kind of secondary tumors are rare in parathyroid glands, but few cancers which may affect are –
Investigations For Parathyroid Gland Disorder
A final diagnosis cannot be made without the laboratory investigations.
Laboratory Investigations for Hyperparathyroidism
- Blood Calcium and Phosphate
- Calcium Creatinine Clearance Ratio
- Blood Parathyroid Hormones
- Levels of Alkaline Phosphatase
- X-ray of Bones
- Bone density test
- Levels of Vitamin D in blood
Blood Calcium and Phosphate
- In patients with suspected hyperparathyroidism, atleast three fasting samples of blood should be taken.
- A blood calcium level above 10.4 mg/dl is alarming.
- The tests for blood calcium is done for its ionic form and for the bound form in which it is bound to the serum protein albumin.
- The main pre-requisite for measuring ionic calcium is that the blood sample should be fresh and collected after overnight fasting.
- About 45% of blood calcium is bound to albumin.
- In cases where there is increased levels of albumin in blood there will be low blood calcium giving a false negative result.
- Blood phosphate levels are also important in detection of hyperparathyroidism.
- The level of phosphate in blood is low.
Calcium Creatinine Clearance Ratio
It is an important test to rule out a genetic disease which is Familial Hypercalciuric Hypercalceamia. In order to distinguish this disease from hyperparathyroidism, the Calcium Creatinine Clearance Ratio should be < 0.1.
Blood Parathyroid Hormone Levels
The normal range of parathyroid hormone in blood is around 10-65 ng/ml. Once the high levels of calcium in blood have been confirmed, the next step should be to check for high levels of parathyroid hormone.
Almost all the patients with a raised blood calcium have high levels of parathyroid hormone. But sometimes the patients may also present with normal or suppressed levels of the hormone.
Evaluation of parathyroid hormone in blood is expensive and requires a very sophisticated set up. Parathyroid hormone set estimation is done by help of immunoassay.
Immunoassays are based on the principle of reaction between antigen and antibodies which can be demonstrated by the help of a color imparting substance (Chromogen).
Levels of Alkaline Phosphatase
Alkaline Phosphatase is an enzyme which increases in the body when there is increase osteolysis of bones. Therefore, alkaline Phosphatase becomes an important marker in giving a final diagnosis of hyperparathyroidism.
Although there are other bone diseases where these levels of alkaline Phosphatase are elevated. This enzyme is also used for the detection of liver diseases.
The test for Alkaline Phosphatase is comparatively less expensive, and requires blood as the testing sample.
- Bone Density Test
Bone density test/ Bone Mineral Density is an easy, fast and inexpensive procedure. This test is done in patients diagnosed with hyperparathyroidism, to evaluate future fracture risk of the brittle bones.
In hyperparathyroidism, the fracture rates are increased at all the sites in the body. A Bone Mineral Density score of < 2.5 is a situation when further investigations regarding exploration of parathyroid tumors.
- Principle of Bone Density Test – Bone density test also known as DEXA (Dual Energy X-ray Absorptiometry). This method used least amount of ionizing radiation and gives pictures of inside the body.
- The test requires least or no prior patient preparation. Commonly images of hip and backbone are taken.
- Requirements for Bone Density Test
- The patient should not be wearing any jewelry or carrying any other metallic object.
- Patient should avoid taking calcium supplements prior to the test.
- Scans such as barium meal or barium swallow should be avoided before the test as it would give false results.
- Blood Levels of Vitamin D
A deficiency of Vitamin D can also co exist with hyperparathyroidism. Vitamin D is synthesized in the body in three parts i.e, the skin which is exposed to sunlight having ample amount of Ultra Violet B rays.
The other organ of the body to synthesize Vitamin D is intestine. Here the parathyroid hormone controls the process. Lastly, kidneys are the place where final activation of Vitamin D takes place.
The tests employed for Vitamin D evaluation in blood are expensive and mostly advised in cases of –
- Patients of Hyperparathyrodism
- High risk individuals with inadequate exposure to sunlight, low oral intake, malnourished.
- Individuals with intestinal disorders which lead to impaired absorption.
- Normal Range of Vitamin D in Blood – An adequate range of Vitamin D in healthy individuals is 50-70 ng/ml.
- A deficiency state will have levels < 50 ng/ml/
- Whereas Vitamin D toxicity levels have a value > 100ng/ml.
- X-ray of Bones
Since hyperparathyroidism affects all the bones of the body, multiple x rays of the affected bones can be taken. Around less than 50% of cases are diagnosed with the help of bone manifestations detected by X-ray.
In an X-ray the bone changes in hyperparathyroidism are characteristic. The features may range from –
- Pathologic fractures
- Completely hollow decalcified bone.
- Presence of bone destructive diseases example Brown Tumor
- Presence of calcium deposits in joints
- Peculiar dental changes like loosening of teeth
- The bones commonly employed for the purpose of X-ray in hyperparathyroidism are those of hands, skull, jaws, long bones of thigh.
- Parathyroid Scan
It is a procedure which is done to located the exact site of parathyroid hyperactivity. In this process the field of nuclear medicine has an active participation.
Features of a Parathyroid Scan
- It is useful for the localization of a suspected tumor.
- Adenoma of a parathyroid gland is usually situated near or sometimes inside the thyroid gland.
- Patients taking medications for thyroid disorders should be cleared off of the medications as these can interfere with the procedure.
- The scanning takes about two days
- Patients should avoid eating or drinking 4 hours prior to the test on day 1.
- Scan is indicated in cases prior to parathyroid surgery and in patients having recurrent disease of hyperparathyroidism
- This scan is restricted for pregnant females.
- In breast feeding women, the scan requires to stop lactating 24 hours prior to the test.
- Parathyroid Scan Procedure
Day 1 – The patient is made to swallow two capsules. These capsules will be lodged in the thyroid gland within next 24 hours. The patient can continue with routine activities within 3 hours.
Day 2 – Patient will be asked to lie on the imaging table. Images of the thyroid gland will be obtained. During imaging a radioactive substance will be infused in the patient with the help of a catheter tube. After three hours a set of delayed images is taken.
- Types of Parathyroid Scan
Based on the type of material infused in the patient types of parathyroid scan are-
- Thallium-technitium Isotope Scan : In this technique, Technititum 99 is used to outline thyroid gland first. This is followed by administration of Thallium Chloride.
It is take up by both the thyroid and parathyroid glands. With the help of image subtraction and image enlargement parathyroids will appear like a hot spot.
- Sestamibi Scanning : It was invented in early 1990s. This scan uses a small protein named Sestamibi, which is administered in the patient. This protein is labeled with a radio isotope Technitium 99m which localizes the gland.
Sestamibi scanning is more superior to thallium technetium scan. This technique very effectively identifies Adenomas of parathyroid glands.
But about 50% times this technique gives wrong results so usually not preferred. This is popularly known as the MIBI scan.
- SPECT – Also known as the single proton emission computed tomography.
This scan is used along with Sestamibi technique in cases when the parathyroid tumor may be located in the mediastinum.
- Parathyroid Ultrasound
Ultrasonography of the neck region requires an experienced sonologist. During the scan, a small handled device called the Transducer, is moved back and forth near the neck. This moving of the transducer helps in obtaining the image.
- Parathyroid surgery is aimed at reducing the levels of Calcium and Parathyroid Hormone in blood. This surgery involves either partial or complete removal of parathyroid glands, which is termed as
- Parathyroidectomy involves certain issues like –
- Which patient requires surgery?
- How would be the surgery beneficial for the patient?
- How to locate the gland or the tumor to be removed?
- When is the correct time to locate the gland either before or after the surgery?
Which patient requires surgery?
This question has been a topic of debate for many years. It has been debated that whether to use non surgical treatment and the observe or to perform Parathyroidectomy so as to improve the deleterious effects of increased blood calcium.
However, after this long debate it has been finally decided to give more weight age to surgical management.
Recommendations of Parathyroid Surgery
Surgery as an option for treatment can be considered in these cases –
- Medical treatment is not responding or not desirable.
- The Calcium Creatinine Clearance Ratio is increased > 30%
- Very low bone density
- Blood calcium levels are very high.
- Excretion of Calcium in urine is increased within 24 hours.
- Patient age < 50 years.
How would be the surgery beneficial for patient?
Surgical management i.e., Parathyroidectomy has shown considerable promising results like:
- Substantial relief from muscular spasms and improved muscle tone.
- Improved mental health and resolution of symptoms like depression, anxiety or psychosis.
- Reduction in blood calcium levels
- Excretion of calcium reduced in urine.
- Decreased incidence of kidney stones.
How to locate the gland or the tumor to be removed?
Major advances in scanning procedures has made it very convenient to locate the parathyroid gland. These advance scanning techniques have also reduced the time required for surgery.The gland or the tumor to be removed can be either explored before the surgery or during the surgery.
When is the correct time to locate the gland before or during the surgery?
Localization of the parathyroid gland during the surgery, was earlier considered to be a better choice. But this procedure resulted in more trauma to the structures in the neck during surgery, hence lower results.
With the advancement in the localization techniques and Parathyroid Scans it has become easier and more acceptable to explore the gland or the tumor before the surgical procedure.Also with earlier exploration the surgical procedure is minimal making it more patient friendly.
Cost of Parathyroid Surgery
Management strategies of parathyroid disease include both medical and surgical therapies. The medical management consists of administration of multiple number of drug regimens and long term observation of the patient.
Moreover, the observation period also includes, continuous and repeated cycles of blood tests for calcium levels and parathyroid hormone. The techniques used for these estimations are very sensitive and hence expensive.
On the other hand, Surgical intervention includes removal of the source of the disease which is either Hyperplasia or a benign tumor like that of Adenoma. Advance scanning techniques have given better results.
Therefore, Surgery becomes a better option of treatment with advantages of low costs and complete ablation of the disease.
Side Effects of Parathyroid Surgery
Parathyroid Surgery is a very delicate procedure where the surgeon removes this pea sized gland with utter care. But every surgery has its complications, is the case with Parathryoidectomy.
The possible side effects of Parathyroid Surgery are –
- Neck region of the body has very important structures which are very closely placed. One such structure is the Recurrent Laryngeal Nerve, this nerve controls the movement of the vocal cords and indirectly affects breathing.
Sometimes during the surgery the nerve may get traumatized, which causes paralysis and weakness of the vocal cords. Paralysis results in a weak breathy voice and difficulty in swallowing.In patients of parathyroid Cancers, the tumor might invade the nerve and spread.
- Accidental damage to remaining parathyroid glands can cause the disturbance in calcium levels in blood and the patient might have to take calcium tablets for the rest of their lives.
- In cases where the exploration fails even after using the advanced parathyroid scans, there is requirement for an extensive surgery.
- Patient may have slow healing, prolonged pain and low response to the surgical procedure.
- A rich blood supply to the parathyroid glands makes it obvious to have large amount of blood loss during the surgery.
- Sometimes there is recurrence of the tumor in case there is inadequate removal.
- In cases, where parathyroid gland or the tumor are situated within the substance of the gland, such cases need the elaborative procedure of thyroidectomy (Removal of Thyroid Gland).
Parathyroid gland is so named because of it location adjacent to the thyroid gland. This gland has a very important role in maintaining the levels of blood Calcium and therefore functions related to it.
Disturbance in the function can be either in the form of gland be overactive or reduced activity, both the situations produce diseases which need to be taken care of immediately.
If an individual is experiences symptoms like mood swings, depression, muscle weakness, fatigue and fractures of unexplained cause, they should seek for medical help to get a timely treatment.
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