parathyroid-2017 (2).ppt

PARATHYROID 1 GLANDS FUNCTION& DISORDER 4/12/2021  PARATHYROID GLANDS  The parathyroid glands, located in the neck, that control the body’s calcium level. Each gland is about the size of a grain rice  The f...

PARATHYROID 1 GLANDS FUNCTION& DISORDER 4/12/2021  PARATHYROID GLANDS  The parathyroid glands, located in the neck, that control the body’s calcium level. Each gland is about the size of a grain rice  The four glands normally lie in close to the upper and lower poles of each thyroid lobe  10% of individuals have only two or three glands. 2   In the adult, the parathyroid is a yellow- brown, ovoid encapsulated nodule weighing approximately 35 to 40 mg.  Most of the gland is composed of chief cells.  They contain secretory granules of parathyroid hormone (PTH).  Oxyphil cells and transitional oxyphils are found throughout the normal parathyroid, either singly or in small clusters.(have no known function). 3 4 5  Parathyroid Hormone 6  Synthesized in chief cells as large precursor – pre-proparathyroid hormone  Cleaved intracellularly into proparathyroid hormone then to final 84 AA PTH  PTH then metabolized by liver into hormonally active N-term and inactive C-term   The activity of the parathyroid glands is controlled by the level of free (ionized) calcium in the bloodstream rather than by trophic hormones secreted by the hypothalamus and pituitary. 7   The metabolic functions of PTH in supporting serum calcium levels can be summarized as follows:  PTH activates osteoclasts ((‫مة‬5‫هاد‬, thereby mobilizing calcium from bone.  It increases the renal tubular reabsorption of calcium, thereby conserving free calcium.  It increases the conversion of vitamin D to its active dihydroxy form in the kidneys.  It increases urinary phosphate excretion, thereby lowering serum phosphate levels.  It augments((‫زيد‬55‫ي‬gastrointestinal calcium absorption. 8  PTH function 9 10 11 12  Calcitonin 13  A peptide hormone produced by the parafollicular, or C, cells of the thyroid gland  Lowers blood calcium levels.  Antagonist to parathyroid hormone (PTH) 14  Calcitonin 15  Calcitonin targets the skeleton, where it:  Inhibits osteoclast activity (and thus bone resorption) and release of calcium from the bone matrix  Stimulates calcium uptake and incorporation into the bone matrix  Regulated by a humoral (calcium ion concentration in the blood) negative feedback mechanism 16  Hyperparathyroidism 17  PRIMARY HYPERPARATHYROIDISM  Primary hyperparathyroidism is one of the most common endocrine disorders, and it is an important cause of hypercalcemia.  The frequency of the various parathyroid lesions underlying the hyperfunction is as follows:  Adenoma: 75% to 80%  Primary hyperplasia (diffuse or nodular): 10% to 15%  Parathyroid carcinoma: less than 5%   Primary hyperparathyroidism is usually a disease of adults and is more common in women than in men by a ratio of nearly 3:1.  In more than 95% of cases, the disorder is caused by sporadic((5‫تقطع‬5‫ م‬parathyroid adenomas or sporadic hyperplasia : 18  Hyperparathyroidism 19  Primary Hyperparathyroidism  Normal feedback of Ca disturbed, causing increased production of PTH  Secondary Hyperparathyroidism  Defect in mineral homeostasis leading to a compensatory increase in parathyroid gland function  Clinical Presentation 20 Nephrolithiasis (deposition of Ca2 in parenchymal of the kidney) Bone Disease Peptic Ulcer Disease Psychiatric disorders Muscle weakness Constipation Polyuria Pancreatitis Myalgia (muscle pain) (( ‫ ا>>لم عضلي‬- Arthralgia (joint pain).  Cardinal features of hyperparathyroidism. With routine evaluation of calcium levels in most patients, primary hyperparathyroidism is often detected at a clinically silent stage. Hypercalcemia from any other cause can also give rise to the same symptoms. 21 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 20 February 2006 11:38 PM) © 2005 Elsevier 22 Biochemical tests  Hypercalcemia  Hypophosphataemia  Raised PTH  Raised serum alkaline phosphatase  Laboratory Diagnosis 23  Elevated Serum Ca and PTH  Must measure Ionized Ca  50% will have hypophosphatemia Elevated Alkaline Phosphatase in 10- 40%  Hyperchloremic metabolic acidosis  Low Mg in 5-10%  High Urinary Ca in almost all cases  Primary hyperparathyroidism is the most common cause of hyper-calcemia overall.  Malignancy is the most common cause of symptomatic hypercalcemia.  Primary hyperparathyroidism and malignancy account for nearly 90% of cases of hypercalcemia.  Secondary and tertiary hyperparathyroidism are most commonly associated with progressive renal failure. 24  SECONDARY HYPERPARATHYROIDISM 25  Secondary hyperparathyroidism is caused by any condition associated with a chronic depression in the serum calcium level because low serum calcium leads to compensatory overactivity of the parathyroid glands.  Renal failure is by far the most common cause of secondary hyperparathyroidism, although a number of other diseases, including inadequate dietary intake of calcium, steatorrhea, and vitamin D deficiency, may also cause this disorder. 26  In a minority of patients, parathyroid activity may become autonomous((‫ه‬5‫ت‬5‫زا‬555‫ستقلب‬5‫ م‬and excessive, with resultant hypercalcemia, a process that is sometimes termed tertiary hyperparathyroidism. Parathyroidectomy may be necessary to control the (treatment) hyperparathyroidism in such patients.  Hypoparathyroidism  Hypoparathyroidism is far less common than is hyperparathyroidism. There are many possible causes of deficient PTH secretion resulting in hypoparathyroidism:  Surgically induced hypoparathyroidism occurs with inadvertent removal of all the parathyroid glands during thyroidectomy, excision of the parathyroid glands in the mistaken 27  Congenital absence of all glands, as in certain developmental abnormalities, such as thymic aplasia and cardiac defects (22q11.2 syndrome) most common congenital heart defect.  Familial hypoparathyroidism: is often associated with chronic mucocutaneous (immune disorder of T-cells) candidiasis and primary adrenal insufficiency.  Idiopathic hypoparathyroidism most likely represents an autoimmune disease with isolated atrophy of the glands. 28  The major clinical manifestations of hypoparathyroidism are referable to hypocalcemia and are related to the severity and chronicity of the hypocalcemia.  The hallmark ((‫يزة‬5‫م‬, ‫مة‬55‫ س‬of hypocalcemia is tetany, which is characterized by neuromuscular irritability  Mental status changes can include emotional instability, anxiety and depression, confusional states,, and frank psychosis. 29   Ocular ‫صرى‬555‫ب‬ ( ) disease results in calcification of the lens leading to cataract((‫ عتمة‬formation.  Cardiovascular manifestations include a conduction defect, (CD).  Dental abnormalities occur when hypocalcemia is present during early development. 30  Pseudohypoparathyroidi 31 sm  Pseudohypoparathyroidism (Pseudo mean -not actual but have appearance) is a heritable (genetic) disorder resulting in a lack of responsiveness to PTH in the target tissue.  PTH binds its receptor but cannot activate the second messenger, cAMP, and thus there is no response.  This is an example of a hormone resistance syndrome.  Treatment is with calcium and vitamin D. 32   Parathyroid carcinomas  lesions that are difficult to distinguish from adenomas, or they may be clearly invasive neoplasms (have potential to spread to the lymph node or other areas of the body).  These tumors enlarge one parathyroid gland and consist of gray-white, irregular masses that sometimes exceed 10 gm in weight. 33   The cells of parathyroid carcinomas are usually uniform and resemble normal parathyroid cells.  diagnosis of carcinoma based on cytological examination test. 34  Hypercalcemia of malignancy is due to increased bone resorption ((‫تصاص‬5‫م‬5‫ ا‬and subsequent release of calcium in blood stream.  There are two major mechanisms by which this can occur:  (1) osteolytic metastases (break down too much of the bone) and local release of cytokines (it depends on other modules factors).  (2) release of PTH-related protein (PTHrP). (acting as endocrine hormone). 35   PTH-related protein: The most frequent cause of hypercalcemia in nonmetastatic solid tumors- particularly squamous cell cancers  PTHrP-induced hypercalcemia. 36 37 THANK