PARATHYROID GLAND The glands were first discovered in humans by Ivar Viktor Sandstrom (1852-1889), a Swedish medical student, in 1880. It was the last major organ to be recognized in humans. The parathyroid glands are usually located on the upper and lower poles of the thyroid gland. Majority of people have four parathyroid glands but some people may have up to 12 pairs. The glands contain two types of cells. 1. Smaller parathyroid chief cells, which produce parathhormon 2. Larger oxyphil cells, whose function is unknown Parathhormon (PTH, or parathrin) is a polypeptide synthesized by the parathyroid glands. PTH takes part in the control of calcium and phosphate homeostasis, as well as bone physiology. Parathyroid hormone has effects antagonistic to those of calcitonin of thyroid gland. PTH increases blood calcium levels by stimulating osteoclasts to break down bone and release calcium. PTH also increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium conservation (reabsorption) by the kidneys. Also, PTH affects the perception of well being and absence of PTH can be associated with feeling of fatigue and anxiety. PTH elevates serum calcium and lowers serum the phosphate levels. Calcium ions are important for organisms’ normal activities and participate in: 1. Process of all tissues metabolism 2. The transmission of neuronal impulse 3. Blood coagulation 4. The 99% is stored in the bones to provide their strength 99% of the calcium stored in the bones as hydroxyapatite and 1% phosphate salts. The phosphate salts dissolve easily to provide a calcium supply in hypocalcemic condition. Derangements of calcium homeostasis lead to hypercalcemia or hypocalcemia, both of which can have important consequences for health. There are two types of calcium in the blood. 1) Bound with proteins 2) Free ionized calcium The serum level of calcium is closely regulated with a normal total calcium of 2,2-2,6 mmol/L (9-10,5mg/dL) and a normal ionized calcium of 1,1-1,4 mmol/L (4,5-5,6mg/dL). The amount of total calcium varies with the level of serum albumin, a protein to which calcium is bound. The biologic effect of calcium is determined by the amount of ionized calcium , rather than the total calcium. Ionized calcium does not vary with albumin level, and therefore it is useful to measure the ionized calcium level when the serum albumin is not within normal ranges, or when a calcium disorder is suspected despite a normal total calcium level. There is constant calcium loss with nails, hair, blood, skin, GIT, kidney, 1 Calcium levels are regulated by. 1. PTH Increases bone resorption of calcium and phosphate Increases distal renal tubular calcium reabsorption Decreases renal tubular phosphare reabsorption Increases renal production of 1,25 (OH)2 D Net effect: increases serum calcium and decreases phosphate 2. Vitamin D3 is a prohormone produced in the epidermis by reactions requiring absorption of ultraviolet radation, is reabsorbed by gut and converted to 1,25(OH)2D in the liver. 1,25 dihydrocholecalciferol or calcitriol: Increases bone resorption of calcium and phosphate Increases renal reabsorption of calcium and phosphate Increases gut absorption of calcium and phosphate Decreases parathyroid production of PTH Decreases renal production of 1,25(OH)2D Net effect : increases serum calcium and phosphate 3. Calcitonin is 32-amino-acid peptide produced primarily by parafollicular C cells of the thyroid gland. Decreases bone resorption of calcium and phosphate Decreases renal reabsorption of calcium and phosphate Decreases gut absorption of phosphate Net effect: decreases serum calcium and phosphate The parathyroid diseases 1. Hyperparathyroidism is a clinical syndrome that results from elevated parathyroid hormone (PTH) levels. 2. Pseudohypoparathyroidism is a genetic disorder with target organ resistance to PTH. 3. Hypoparathyroidism results from the decreased parathyroid hormone levels. 4. Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder manifested by hypercalcemia which results from decreased urinary calcium excretion. 5. Hypocalcemia – results from VIT D deficiency. 6. Acute hypocalcemia. 7. Latent hypocalcemia. Hyperparathyroidism (HPT) Hyperparathyroidism(HPT) is a clinical syndrome that result from elevated parathyroid hormone levels. There are three types of HPT: primary, secondary and tertiary. 2 Primary HPT : the majority of cases are parathyroid adenoma and parathyroid hyperplasia. Clinical features 1. Musculoskeletal system involvement: osteoporosis, osteopenia, cystic bone lesions,vertebral collapse, chondrocalcinosis and pseudogout, easily fatigued muscle (particularly proximal muscle groups). 2. Renal system involvement: the renal manifestations of primary hyperparathyroidism include recurrent calcium nephrolithiasis, nephrocalcinosis, impaired renal function, uremia, poliuria and polidipsia. 3. CNS involvement: neuropsychiatric illness, altered mental status, coma (in severe cases) 4. Gastrointestinal system involvement: pancreatitis, pancreatic calcification, or both. Peptic ulcer disease ( may be present at a higher rate ). 5. Eye involvement: keratitis and conjunctivitis. Diagnosis 1. Total calcium serum level > 2,6 mmol/l (>10,5mg %) 2. Free calcium serum level >1,3mmol/l(>5,2mg%) 3. The phosphate serum level normal or lower 2,5mol/l 4. The level of parathhormone 3 time higher than normal level 5. Increased bone turnover may be reflected in elevated levels of markers of bone formation (alkaline phosphatase) and bone resorption (urinary pyridinoline). 6. The noninvasive imaging modalities commonly used are ultrasonography, CT scanning, and MRI. Treatment Intravenous administration of isotonic saline, loop diuretics. In postmenopausal women with mild hyperparathyroidism, estrogen therapy has been advocated. Surgery that involves open surgical excision with frozen section diagnosis is the only definitive treatment for severe hyperparathyroidism. Other calcium-lowering agents, such as bisphosphonates, plicamycin, and calcitonin, are used to treat malignant causes of hypercalcemia and are not used for hyperparathyroidism. Secondary HPT occurs when the parathyroid glands become hyperplastic after long-term hyperstimulation and release of PTH. In secondary hyperparathyroidism, elevated PTH levels do not result in hypercalcemia. This has been classically attributed to an underlying state of hypocalcemia in those with chronic renal failure( CRF). Tertiary HPT refers to hypercalcemia caused by autonomous parathyroid function after long-term hyperstimulation. 3 Hypoparathyroidism There are low circulating levels of parathyroid hormone (PTH) or insensitivity to its action. Etiology 1. Surgical damage or removal of parathyroid tissue. 2. Radiation on the neck. 3. Idiopatic or autoimmune hypoparathyroidism. 4. Magnesium depletion. 5. Familial hypoparathyroidism. Clinical 1. Increased neuromuscular irritability resulting in muscle cramping(tetany) is a common feature of hypocalcemia. The classic sign of tetany is carpopedal spasm(Troussau sign ). Chvostek sign is evidence of increased irritability of the fifth cranial nerve. Other neuromuscular signs include paresthesias, laryngospasm, bronchospasm, abdominal cramping and generalized hyperreflexia. CNS disturbances include seizure equivalents, grand or petit mal seizures, syncope, impaired memory, psychosis. 2. The cardiovascular effects of hypocalcemia are usually bradydysrhythmias or prolongation of the QT interval. Rarely, severe hypocalcemia can mimic myocardial infarction. 3. Chronic manifestations include cataracts, dry skin, coarse hair, brittle nails, psoriasis, chronic pruritus and poor dentition. The diagnosis of hypoparathyroidism is supported by : 1. Hypocalcemia: both total and ionized calcium are decreased. 2. Hyperphosphatemia, hypophosphaturia and hypocalciuria. 3. Low parathyroid hormone levels. Treatment Calcium, vitamin D, milk products. 4 Pseudohypoparathyroidism (PHP) PHP is an inherited disorder of target-organ unresponsiveness to PTH. Clinical features are the same as of hypoparathyroidism, but PH are normal or elevated. The patients have short stature, round face, short neck, brachydactyly(short digits), shortened metatarsals, subcutaneous ossifications, and often reduced intelligence. Because of shortening of the metacarpal bones most often the fourth and fifth metacarpals affected digits have s dimple, instead of a knuckle, when a fist is made. They also have hypocalcemic clinical features and abnormalities of reproductive function such as oligomenorrhea in females and infertility in males. Diagnosis This disorder presents with hypocalcemia, hypophosphatemia and normal or high PTH. Familial Hypocalciuric Hypercalcemia Familial hypocalciuric hypercalcemia (FHH), also appropriately called familial benign hypercalcemia, is, in most families, a disorder of autosomal dominant inheritance caused by mutations of the calcium –sensing receptor gene found in parathyroid glands, kidney, and other organs. Serum calcium level is usually less than 12mg/dL, but can be higher. Phosphate levels are low, as in primary hyperparathyroidism. Urine calciu levels are usually low. Vitamin D Deficiency The two sources of vitamin D are the diet and cutaneous synthesis after UV irradiation. Lack of solar irradiation and decreased intake or impaired absorption of vitamin D can lead to vitamin D deficiency. Vit D deficiency may lead to decreased gut absorption of calcium and phosphate and cause hypocalcemia. There are three types of vit D deficiency: