Hyperparathyroid Disease PDF

Hyperparathyroid Definition ○ Hyperparathyroid (HPTH) disease is an endocrine disorder with multiple etiologies and is characterized primarily by excessive secretion of parathyroid hormone (PTH) from one or more parathyroid glands: Hypercalce...

Hyperparathyroid Definition ○ Hyperparathyroid (HPTH) disease is an endocrine disorder with multiple etiologies and is characterized primarily by excessive secretion of parathyroid hormone (PTH) from one or more parathyroid glands: Hypercalcemia Hypophosphatemia (i.e., low conc of serum phosphate) Increased excretion of both calcium and phosphate by the kidneys Demineralization of bone Pathologic fractures A host of complications associated with high concentrations of serum and urinary calcium result from elevated PTH levels ○ Primary HPTH disease: Most often caused by the secretion of PTH from a tumor in one of the parathyroid glands ○ Secondary HPTH disease: Caused by an increase in serum PTH secondary to chronic disease state, such as chronic renal failure, that leads to a decrease in serum calcium levels and parathyroid cell hyperplasia Patients with vasopressin receptor damage secondary to hyperkalemia (levels at 12.5 MG per deciliter or greater), may lead to polydipsia, polyuria and fatigue PRevalence ○ Primary HPTH disease is becoming an increasingly diagnosed disorder with an incidence of 0.1–0.2%. ○ It can be seen at any age but is more frequent in persons older than 40 years of age and is two to three times more common in women than in men. ○ Patients with abnormal parathyroid function which shows laboratory findings of a Decreased PTH level and Increased Calcium level may be secondary to Lung Cancer. ○ Hyperparathyroidism is rare in children. ○ The overall incidence of new cases is approximately 0.03% annually. ○ Dehydration secondary to diuretic use, demineralization of bone, hypertension managed with hydrochlorothiazide and parathyroid adenoma are likely to result in calcium oxalate stones. ○ Chronic renal failure is the least likely to result in the development of calcium oxalate stones ○ Technically speaking, secondary HPTH disease is not a disease state but rather a potential complication of a number of chronic disease states, such as chronic renal failure and intestinal malabsorption  Significance ○ Primary HPTH disease is one of the most common causes of hypercalcemia and should be considered in any person with an elevated serum calcium concentration ○ The significance of HPTH disease lies in a variety of potential complications of the skeletal and urinary systems, some of which can be life-threatening, and in signs and symptoms of hypercalcemia ○ Skeletal manifestations consist of: significant demineralization of bone, bone pain pathologic fractures. ○ Urinary tract manifestations are characterized by: painful, calcium-containing renal stones that can ultimately result in kidney failure. ○ Hypercalcemia causes a multitude of bothersome clinical signs and symptoms that include the following: nausea vomiting abdominal pain due to pancreatitis susceptibility to peptic ulcer disease anorexia with weight loss Constipation fatigue pruritus (i.e., itching) paresthesias (i.e., abnormal sensations such as burning, prickling, or tingling) depression excessive somnolence (i.e., inclination to sleep) calcification of tissues (e.g., skin, corneas, and blood vessels) Causes and risk factors: ○ Primary HPTH disease: Usually the result of a non-cancerous tumor (i.e., adenoma) or hyperplasia of the parathyroid glands. Less commonly, the condition is caused by parathyroid cancer (i.e., carcinoma) that is well-differentiated and thus retains its ability to produce and secrete PTH. Adenoma causes approximately 80% of all primary HPTH disease; hyperplasia, 20%; and carcinoma, 0.5%. Approximately 5% of parathyroid adenomas or hyperplasia have a genetic basis, run in families, and may be part of a syndrome known as multiple endocrine neoplasia (MEN) in which tumors in other glands (e.g., pituitary, thyroid, and adrenal glands) are common. Pathophysiology  ○ Pathophysiologic mechanisms for primary and secondary HPTH disease are clearly different With primary disease, a developing parathyroid adenoma or carcinoma persistently produces and secretes an excessive amount of PTH into the bloodstream. Tumors are not responsive to normal feedback mechanisms, such as elevated serum calcium levels (i.e., they are autonomous). Subsequently, excessive concentrations of circulating PTH increase serum calcium concentrations by a triad of pathophysiologic mechanisms: PTH stimulates the activity of osteoclasts in bone, resulting in excessive resorption (i.e.,breakdown) of bone and liberation of calcium and phosphate from bone (i.e., bone becomes demineralized and fragile). PTH acts on specific cellular receptor sites in the distal convoluted tubules of kidney nephrons to increase the reabsorption of calcium from the glomerular filtrate PTH stimulates the synthesis of a biologically active form of vitamin D (i.e1,25- dihydroxyvitamin D3), a potent stimulant of gastrointestinal calcium absorption. Excessive circulating PTH and calcium predispose the patient to the production of an abnormally alkaline urine, hypercalciuria, and hyperphosphatemia—three factors that together play a critical role in the pathogenesis of calcium-containing renal stones. Hypercalcemia: stimulates hydrochloric acid secretion in the stomach leading to abdominal pain and peptic ulcer disease causes decreased peristalsis of the gastrointestinal tract leading to constipation stimulates the vomiting center in the brain causes neuro pathophysiologic changes leading to psychiatric illnesses, such as depression Muscular weakness and muscle pain (myalgia) in HPTH disease have been linked to degenerative changes in muscles and nerves and to excessive levels of PTH Diagnosis: clinical manifestations and lab tests ○ Both primary and secondary HPTH disease is characterized by a significant elevation in the serum concentration of PTH. ○ The size of a parathyroid adenoma is directly related to the serum PTH concentration. ○ An immunoradiometric assay (known as IRMA) is both specific and sensitive and recognizes the PTH molecule at two sites with two different antibodies. ○ The clinical hallmark of primary disease is hypercalcemia (serum calcium 10.5 mg/dL).  ○ Hypercalcemia often results in a susceptibility to developing calcium-containing kidney stones, constipation, nausea, vomiting, anorexia, weight loss, and various neuropsychiatric conditions. ○ With primary disease, urinary calcium and phosphate levels are often elevated and serum phosphate is typically low. ○ With secondary disease, serum calcium is typically normal or low and serum phosphate is high ○ Both primary and secondary disease may cause bone x-ray changes (i.e., cystic bone lesions), but these are not required for a definitive diagnosis. ○ Serum alkaline phosphatase concentrations are high when bone disease is present. ○ If a parathyroid tumor is suspected, imaging tests are advisable. ○ Scintigraphy is a diagnostic procedure that consists of administering a radionuclide with an affinity for a particular tissue of interest followed by recording the distribution of radioactivity with a special type of camera. Appropriate therapy ○ Depending on the patient’s specific condition, treatment for HPTH disease can be: Surgical Non-pharmacologic pharmacologic. ○ Patients with mild, asymptomatic disease are advised to keep active, avoid immobilization, and drink plenty of fluids. ○ They should also avoid thiazide diuretics, large doses of vitamin D, and calcium-containing antacids and supplements—all of which contribute to high serum calcium levels. ○ Surgical removal of the parathyroid glands (i.e., parathyroidectomy) is recommended for symptomatic HPTH disease characterized by kidney stones or bone disease and for asymptomatic patients when serum calcium levels are 11.5 mg/dL and urinary calcium excretion is 50 mg/24 hr. ○ Surgical excision of a parathyroid adenoma is usually curative. ○ Parathyroid hyperplasia, commonly seen with chronic renal failure, is best treated with a subtotal parathyroidectomy (three and one-half glands are usually removed). ○ Parathyroid carcinomas often are resected and the patient subsequently treated with radiation. ○ Within hours after surgery, serum PTH concentrations often fall below normal, causing paresthesias and tetany when hypocalcemia is severe. ○ Once hypercalcemia has resolved, liquid or chewable calcium carbonate is given orally to reduce the probability of developing hypocalcemia. ○ Symptomatic hypocalcemia is treated with larger doses of calcium and occasionally calcitriol (a vitamin D analog).  Hyperparathyroid disease: ○ Hyperthyroidism, caused by the release of stored thyroid hormones during surgery is a common complication ○ Short-term treatment with propranolol may be required for several days. ○ Propranolol is a β-adrenergic blocking drug that prevents the adverse cardiac effects associated with high circulating levels of thyroid hormones ○ Hypercalcemia is treated with high fluid intake. ○ Severe hypercalcemia requires hospitalization and intensive hydration with intravenous saline. ○ Bisphosphonates (pamidronate, zoledronate) are potent inhibitors of bone resorption and are used to temporarily treat hypercalcemia associated with HPTH disease. ○ When given intravenously, these drugs cause a gradual decline in serum calcium within several days that may last for months. ○ However, bisphosphonates are not effective in treating hypercalcemia when given orally. ○ Cinacalcet hydrochloride helps to control HPTH disease by binding to calcium-sensing g receptors in the parathyroid glands, increasing sensitivity to serum calcium levels, and decreasing PTH secretion ○ For patients with vitamin D deficiency, careful vitamin D replacement may be beneficial. ○ Bone disease caused by secondary hyperparathyroidism associated with renal failure is best prevented by avoiding hyperphosphatemia. ○ Oral doxercalciferol or intravenous paricalcitol are also options for dialysis patients. Serious complications and prognosis ○ The most serious complications associated with HPTH disease are: renal failure from calcium containing kidney stones pathologic fractures from bone disease Hypercalcemia induced pancreatitis, which increases the mortality rate. High serum calcium concentrations can also promote hypertension and its numerous serious complications (e.g., heart attack stroke, loss of vision, kidney failure, and heart failure). At least 5% of all kidney stones are associated with this condition and approximately 20% of patients with HPTH disease have kidney stones. ○ Mild, asymptomatic HPTH disease may be monitored and treated medically without compromising survival. ○ Surgical removal of parathyroid adenomas generally results in a permanent cure.