Parathyroid gland

Medical Presentation

1. Parathyroid G land Noel Christian Group:6

2. Parathyroid Gland Parathyroid glands are small endocrine glands in the neck of humans that produce parathyroid hormone. Humans usually have four parathyroid glands, variably located on the back of the thyroid gland. Parathyroid hormone and calcitonin have key roles in regulating the amount of calcium in the blood and within the bones.

3. Parathyroid glands share a similar blood supply, venous drainage, and lymphatic drainage to the thyroid glands. Parathyroid glands are derived from the epithelial lining of the third and fourth pharyngeal pouches, with the superior glands arising from the fourth pouch, and the inferior glands arising from the higher third pouch . Hyperparathyroidism and hypoparathyroidism, characterized by alterations in the blood calcium levels and bone metabolism, are states of either surplus or deficient parathyroid function.

4. Structure The parathyroid glands are two pairs of glands usually positioned behind the left and right lobes of the thyroid. Each gland is a yellowish-brown flat ovoid that resembles a lentil seed, usually about 6 mm long and 3 to 4 mm wide, and 1 to 2 mm anteroposteriorly .

5. There are typically four parathyroid glands. The two parathyroid glands on each side which are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands. Healthy parathyroid glands generally weigh about 30 mg in men and 35 mg in women. These glands are not visible or able to be felt during examination of the neck .

6. Blood S upply The blood supply, drainage, and lymphatic drainage of the parathyroid glands correspond to the thyroid overlying gland. The superior parathyroid glands receive their blood from the inferior thyroid arteries. The inferior parathyroid glands receive a variable blood supply, from either the ascending branch of the inferior thyroid arteries or the thyroid ima artery. The inferior thyroid artery arises from the subclavian arteries

7. Each parathyroid vein drains into the superior, middle and inferior thyroid veins. The superior and middle thyroid veins drain into the internal jugular vein, and the inferior thyroid vein drains into the brachiocephalic vein.

8. Lymphatic D rainage Lymphatic vessels from the parathyroid glands drain into deep cervical lymph nodes and paratracheal lymph nodes.

9. Histology The parathyroid glands are named for their proximity to the thyroid — and serve a completely different role than the thyroid gland. The parathyroid glands are quite easily recognizable from the thyroid as they have densely packed cells, in contrast with the follicular structure of the thyroid .

10. Two unique types of cells are present in the parathyroid gland : Chief cells: which synthesize and release parathyroid hormone. These cells are small, and appear dark when loaded with parathyroid hormone, and clear when the hormone has been secreted, or in their resting state . Oxyphil cells: which are lighter in appearance and increase in number with age , have an unknown function.

11. High magnification micrograph. H&E stain. The small, dark cells are chief cells , which are responsible for secreting parathyroid hormone. Intermediate magnifica tion micrograph. H&E stain. The white round structures are fat cells. Adipose tissue comprises 25–40% of normal parathyroid gland tissue.

12. High magnification micrograph. H&E stain. The cells with orange/pink staining cytoplasm are oxyphil cells

13. Function The major function of the parathyroid glands is to maintain the body's calcium and phosphate levels within a very narrow range, so that the nervous and muscular systems can function properly. The parathyroid glands do this by secreting parathyroid hormone (PTH).

14. Parathyroid hormone (PTH), also called parathormone or parathyrin , is a hormone secreted by the parathyroid glands that is important in bone remodeling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time. PTH is secreted in response to low blood serum calcium (Ca2+) levels . Regulation Of Calcium

15. IN BONES :- PTH indirectly stimulates osteoclast activity within bone marrow, in an effort to release more (Ca2 +) into the blood to elevate serum (Ca2 +) levels. The bones act as a (metaphorical) "bank of calcium" from which the body can make "withdrawals" as needed to keep the amount of calcium in the blood at appropriate levels despite the ever-present challenges of metabolism, stress, and nutritional variations .

16. While PTH acts to increase the concentration of ionic calcium (Ca2+) in the blood, calcitonin, a hormone produced by the parafollicular cells (C cells) of the thyroid gland, acts to decrease ionic calcium concentration. PTH essentially acts to increase the concentration of calcium in the blood by acting upon the parathyroid hormone 1 receptor, which is present at high levels in bone and kidney, and the parathyroid hormone 2 receptor, which is present at high levels in the central nervous system, pancreas, testis, and placenta.

17. IN KIDNEYS :- Approximately 250 mmol of calcium ions are filtered into the glomerular filtrate per day. Most of this (245 mmol /d) is reabsorbed from the tubular fluid, leaving about 5 mmol /d to be excreted in the urine. This reabsorption occurs throughout the tubule (most, 60-70%, of it in the proximal tubule), except in the thin segment of the loop of Henle. Circulating parathyroid hormone only influences the reabsorption that occurs in the distal tubules and the renal collecting ducts.

18. A more important effect of PTH on the kidney is , its inhibition of the reabsorption of phosphate from the tubular fluid, resulting in a decrease in the plasma phosphate concentration, which increases the amount of calcium that is ionized. A third important effect of PTH on the kidney is its stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine.

19. IN INTESTINES :- via kidney, PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D . This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin .

20. Regulation Of Phosphate PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine.   PTH enhances the uptake of phosphate from the intestine and bones into the blood . IN BONES :- slightly more calcium than phosphate is released from the breakdown of bone . IN INTESTINES :- absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. The absorption of phosphate is not as dependent on vitamin D as is that of calcium .

21. Regulation Of PTH   Secretion of parathyroid hormone is determined chiefly by  serum ionized calcium concentration through  negative feedback . Parathyroid cells express calcium-sensing receptors on the cell surface. PTH is secreted when [Ca2+] is decreased (Calcitonin is secreted when serum calcium levels are elevated ). High concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C.

22. This hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to liberate intracellular messengers IP3 and diacylglycerol (DAG). Ultimately , these two messengers result in a release of calcium from intracellular stores into the cytoplasmic space. Hence a high extracellular calcium concentration leads to an increase in the cytoplasmic calcium concentration. In contrast, high cytoplasmic calcium concentration inhibits the fusion of vesicles containing granules of preformed PTH with the membrane of the parathyroid cell, and thus inhibits release of PTH.

23. Stimulators: Decreased serum [Ca2+]. Mild decreases in serum [Mg2+]. An increase in serum phosphate (increased phosphate causes it to complex with serum calcium, forming calcium phosphate, which reduces stimulation of Ca-sensitive receptors ( CaSr ) that do not sense calcium phosphate, triggering an increase in PTH). Adrenaline Histamine Inhibitors Increased serum [Ca2+]. Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia).[26] Calcitriol

24. Clinical significance Parathyroid disease is conventionally divided into states where the parathyroid is overactive (hyperparathyroidism), and states where the parathyroid is under- or hypoactive (hypoparathyroidism). Both states are characterized by their symptoms, which relate to the excess or deficiency of parathyroid hormone in the blood.

25. Hyperparathyroidism Hyperparathyroidism is an increased parathyroid hormone (PTH) levels in the blood. This occurs either from the parathyroid glands inappropriately making too much PTH (primary hyperparathyroidism) or other events triggering increased production by the parathyroid glands (secondary hyperparathyroidism ). Most people with primary disease have no symptoms at the time of diagnosis.

26. In those with symptoms the most common is kidney stones with other potential symptoms including weakness, depression, bone pains, confusion, and increased urination . Both types increase the risk of weak bones .

27. Primary hyperparathyroidism in 80% of cases is due to a single benign tumor known as a parathyroid adenoma with most of the rest of the cases due to a multiple benign tumors. Rarely it may be due to parathyroid cancer. Secondary hyperparathyroidism typically occurs due to vitamin D deficiency, chronic kidney disease, or other causes of low blood calcium . Diagnosis of primary disease is by finding a high blood calcium and high PTH levels .

28. Primary hyperparathyroidism may be cured by removing the adenoma or overactive parathyroid glands. In those without symptoms, mildly increased blood calcium levels, normal kidneys, and normal bone density monitoring may be all that is required . The medication cinacalcet may also be used to decrease PTH levels. In those with very high blood calcium levels treatment may include large amounts of intravenous normal saline. Low vitamin D levels should be corrected .

29. Primary hyperparathyroidism is the most common form. In the developed world between one and four per thousand people are affected. It occurs three times more often in women than men and is typically diagnosed between the ages of 50 and 60. The disease was first described in the 1700s and in the late 1800s was determined to be related to the parathyroid. Surgery as a treatment was first carried out in 1925.

30. Signs A nd S ymptoms Symptoms depend on whether the hyperparathyroidism is the result of parathyroid overactivity or secondary . In primary hyperparathyroidism about 75% of people have no symptoms. The problem is often picked up during blood work for other reasons via a raised calcium . Many other people only have non-specific symptoms.

31. Common manifestations of hypercalcemia include weakness and fatigue, depression, bone pain, muscle soreness ( myalgias ), decreased appetite, feelings of nausea and vomiting, constipation, polyuria, polydipsia, cognitive impairment, kidney stones and osteoporosis. A history of acquired racquet nails ( brachyonychia ) may be indicative of bone resorption. Parathyroid adenomas are very rarely detectable on clinical examination. Surgical removal of a parathyroid tumor eliminates the symptoms in most patients.

32. In secondary hyperparathyroidism the parathyroid gland is behaving normally; clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia and renal osteodystrophy.

33. Cause Radiation exposure increases the risk of primary hyperparathyroidism . A number of genetic conditions including multiple endocrine neoplasia syndromes also increase the risk.

34. Mechanism Normal parathyroid glands measure the (Ca2 +) concentration in the blood and secrete PTH accordingly: if the ionized calcium rises above normal the secretion of PTH is decreased, whereas when the Ca2+ level falls, parathyroid hormone secretion is increased . Secondary hyperparathyroidism occurs if the calcium level is abnormally low. The normal glands respond by secreting PTH at a persistently high rate. This typically occurs when the 1,25 dihydroxyvitamin D3 levels in the blood are low and there is hypocalcemia.

35. L ack of 1,25 dihydroxyvitamin D3 (Calcitriol) can result from a deficient dietary intake of vitamin D, or from a lack of exposure of the skin to sunlight, so the body cannot make its own vitamin D from cholesterol. The resulting hypovitaminosis D. Vitamin D3 (or cholecalciferol) is converted to 25-hydroxyvitamin D (or calcidiol ) by the liver, from where it is transported via the circulation to the kidneys where it is converted into the active hormone, 1,25 dihydroxyvitamin D3. Thus a third cause of secondary hyperparathyroidism is  chronic kidney disease. Here the ability to manufacture 1,25 dihydroxyvitamin D 3  is compromised, resulting in hypocalcemia.

36. Diagnosis The gold standard of diagnosis is the parathyroid immunoassay. Once an elevated Parathyroid hormone has been confirmed, goal of diagnosis is to determine whether the hyperparathyroidism is primary or secondary in origin by obtaining a serum calcium level : Serum Ca+ Phosphate ALP PTH Likely Type Increased Decreased Increased Increased Primary hyperparathyroidism Decreased Increased Increased Increased Secondary hyperparathyroidism

37. Tertiary hyperparathyroidism has a high PTH and a high serum calcium. It is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism. Blood tests (intact PTH, Calcium levels, Serum phosphate, Alkaline phosphate)

38. Treatment Primary People with primary hyperparathyroidism who are symptomatic benefit from surgery to remove the parathyroid tumor (parathyroid adenoma). Indications for surgery are as follows : Symptomatic hyperparathyroidism Asymptomatic hyperparathyroidism with any of the following: 24-hour urinary calcium > 400 mg serum calcium > 1 mg/ dL above upper limit of normal Creatinine clearance > 30% below normal for patient's age Bone density > 2.5 standard deviations for below peak People age < 50 Surgery can rarely result in hypoparathyroidism.

39. Secondary In people with secondary hyperparathyroidism, the high PTH levels are an appropriate response to low calcium and treatment must be directed at the underlying cause of this (usually vitamin D deficiency or chronic kidney failure). If this is successful PTH levels should naturally return to normal levels unless PTH secretion has become autonomous (tertiary hyperparathyroidism. Calcimimetics A  calcimimetic  (such as  cinacalcet ) is a potential therapy for some people with severe hypercalcemia and primary hyperparathyroidism who are unable to undergo parathyroidectomy and for secondary hyperparathyroidism on dialysis . In the treatment of secondary hyperparathyroidism due to chronic kidney disease on dialysis calcimimetics do not appear to affect the risk of early death.They do decrease the need for a parathyroidectomy but cause more issues with low blood calcium levels and  vomiting .

40. Hypoparathyroidism Hypoparathyroidism  is decreased function of the parathyroid glands with underproduction of parathyroid hormone. This can lead to  low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany  (involuntary muscle contraction), and several other symptoms . The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes.

41. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The treatment of hypoparathyroidism is limited by the fact that there is no exact form of the hormone that can be administered as replacement. However teriparatide , ( Forteo ) a biosimilar peptide to parathyroid hormone, may be given by injection. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease.

42. References   Illustrated Anatomy of the Head and Neck, Fehrenbach and Herring, Elsevier, 2012, p. 159 ^  Jump up to: a   b   c   Drake, Richard L.; Vogl , Wayne; Tibbitts, Adam W.M. Mitchell; illustrations by Richard; Richardson, Paul (2005). Gray's anatomy for students. Philadelphia: Elsevier/Churchill Livingstone. p. 918.  ISBN   978-0-8089-2306-0 .   Gray, Henry  (1980). Williams, Peter L; Warwick, Roger, eds.  Gray's Anatomy  (36th ed.).  Churchill Livingstone . p. 1453.  ISBN   0-443-01505-8 . Jump up ^   Colledge , Nicki R.; Walker, Brian R.; Ralston, Stuart H., eds. (2010). Davidson's principles and practice of medicine (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. p. 767.  ISBN   978-0-7020-3084-0 . Jump up^   Staren , Prinz ; Richard, A., eds. (2000). Endocrine surgery. Georgetown TX: Landes Bioscience. pp. 98–114.  ISBN   978-1-57059-574-5 .