MLTTP (case study) Bakur Ahmed Wedaa Ali 57752 Monday 28/1/2013 Hyperparathyroidism MLTTP (case study) Bakur Ahmed Wedaa Ali 57752 Monday 28/1/2013

Low circulating serum calcium (Ca2+) concentrations stimulate the parathyroid glands to secrete parathyroid hormone (PTH), which mobilizes calcium from bones by osteoclastic stimulation. PTH also stimulates the kidneys to reabsorb calcium and to convert 25-hydroxyvitamin D3 (produced in the liver) to the active form, 1,25-dihydroxyvitamin D3, which stimulates gastrointestinal calcium absorption. High serum calcium concentrations have a negative feedback effect on PTH secretion.

How Many People Get Hyperparathyroidism? The incidence of parathyroid disease (hyperparathyroidism) is 1 in 800 people. This rate is much higher in women over 50 where the rate is 1 in 250 or so. All of you will know somebody with hyperparathyroidism.  Unfortunately, it is our opinion that about 70% of patients with hyperparathyroidism do not know they have it... they have high calcium levels but their doctors don't know what this means and so the high calcium is ignored. Often, when something bad happens (kidney stones, bad osteoporosis, severe depression), then the doctors pay attention to the high calcium. Hyperparathyroidism occurs in women more often than men (almost exactly 75% women, 25% men), and the average age is about 59 years old--but people of any age can get it. Young people do get parathyroid disease, but this is rare.

How much Parathyroidsm is Bad? Since everybody has 4 parathyroid glands, we could potentially get tumors in all four glands this is almost impossible, however. It is usually just one, and occasionally two. In January, 2011 there was published of data on 10,000 patients that operated on and cured for hyperparathyroidism. In 2012, published another article on 15,500 patients in the Journal of the American College of Surgeons.  * 83.5 % = one enlarged, overactive gland (termed a single adenoma) * 15 % = two or three large glands (termed multiple adenomas)...(this group is over-reported) * 1.5 % = four enlarged, overactive glands (termed four-gland hyperplasia) (this group is over-reported)<<<1 % = cancer of the parathyroid (very, very, very, very, very, very, very RARE.)

Symptoms Back pain Blurred vision (because of cataracts) Bone pain or tenderness Decreased height Depression Fatigue Fractures of long bones Increased urine output Increased thirst Itchy skin Joint pain Loss of appetite Nausea Muscle weakness and pain Personality changes Stupor and possibly coma Upper abdominal pain

Primary Hyperparathyroidism Etiology In approximately 85% of cases, primary hyperparathyroidism is caused by a single adenoma. In 15% of cases, multiple glands are involved (ie, either multiple adenomas or hyperplasia). Rarely, primary hyperparathyroidism is caused by parathyroid carcinoma. The etiology of adenomas or hyperplasia remains unknown in most cases. Familial cases can occur either as part of the multiple endocrine neoplasia syndromes (MEN 1 or MEN 2a), hyperparathyroid-jaw tumor (HPT-JT) syndrome, or familial isolated hyperparathyroidism (FIHPT). Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism also belong to this category.

Pathophysiology Due to adenomas, the normal feedback on PTH production by extracellular Ca seems to be lost, resulting in a change in the set point. However, this is not the case in primary hyperparathyroidism from parathyroid hyperplasia. An increase in the cell numbers is probably the cause. The chronic excessive resorption of calcium from bone caused by excessive PTH can result in osteopenia. In severe cases, this may result in osteitis fibrosa cystica. In addition, the chronically increased excretion of calcium in the urine can predispose to the formation of renal stones. The other symptoms of hyperparathyroidism are due to the hypercalcemia itself and are not specific to hyperparathyroidism. These can include muscle weakness, fatigue, volume depletion, nausea and vomiting, and in severe cases, coma and death. Neuropsychiatric manifestations are particularly common and may include depression, confusion, or subtle deficits that are often characterized poorly and may not be noted by the patient. Increased calcium can increase gastric acid secretion, and persons with hyperparathyroidism may have a higher prevalence of peptic ulcer disease. Rare cases of pancreatitis have also been attributed to hypercalcemia.

Secondary Hyperparathyroidism Secondary hyperparathyroidism is the overproduction of parathyroid hormone secondary to a chronic abnormal stimulus for its production. Typically, this is due to Chronic renal failure. Another common cause is Vitamin D deficiency. A study by Bleskestad found that more than 50% of patients who undergo kidney transplantation have elevated levels of intact PTH more than 1 year after transplantation. If these elevated levels are associated with mortality, it may have a major impact on future guidelines.

Pathophysiology Chronic overproduction of parathyroid hormone in patients with renal failure contributes to the spectrum of bone disease observed in patients on dialysis (eg, osteitis fibrosa cystica and mixed uremic osteodystrophy). Nonskeletal consequences include cardiovascular calcification, soft tissue calcification, endocrine disturbances, compromised immune system, neurobehavioral changes, and altered erythropoiesis. Symptoms are mainly due to the vitamin deficiency (eg, osteomalacia with increased fracture risk, myopathy [rarely]). In advanced cases of secondary hyperparathyroidism, some patients may have bone pain.

Tertiary Hyperparathyroidism Tertiary disease is characterized by the development of autonomous hypersecretion of parathyroid hormone causing hypercalcemia. The etiology is unknown but may be due to monoclonal expansion of parathyroid cells (nodule formation within hyperplastic glands). A change may occur in the set point of the calcium-sensing mechanism to hypercalcemic levels. Four-gland involvement occurs in most patients. The clinical manifestations of tertiary hyperparathyroidism include persistent hyperparathyroidism after renal transplantation or new hypercalcemia in the setting of chronic secondary hyperparathyroidism.

Pathophysiology Tertiary hyperparathyroidism is observed most commonly in patients with chronic secondary hyperparathyroidism and often after renal transplantation. The hypertrophied parathyroid glands fail to return to normal and continue to oversecrete parathyroid hormone, despite serum calcium levels that are within the reference range or even elevated. In these cases, the hypertrophied glands become autonomic and cause hypercalcemia, even after withdrawal of calcium and calcitriol therapy. They also may become resistant to calcimimetic treatment.[31, 32] This type of tertiary disease is particularly dangerous because the phosphate level is often elevated. If the calcium value multiplied by the phosphate value yields a high product, diffuse calcinosis may occur.

Quaternary and Quintary Quaternary and quintary are rare conditions that may be observed after surgical removal of primary hyperparathyroidism, when it has led to renal damage that now again causes a form of secondary (quaternary) hyperparathyroidism that may itself result in autonomy (quintary) hyperparathyroidism. Additionally, quaternary hyperparathyroidism may ensue from hungry bone syndrome after parathyroidectomy

What is a parathyroid crisis? A parathyroid crisis occurs in patients with severe hypercalcaemia. Parathyroid hormone (PTH) levels are 5-10 times higher than normal and calcium levels are severely high (4 millimoles per litre or above.) The patients are confused and have kidney symptoms (such as kidney stones) and bone symptoms (such as pain). In addition they are usually grossly dehydrated (due to poor kidney function). This collection of symptoms can be completely debilitating

Related Disorders Familial benign (hypocalciuric) hypercalcemia (FHH) is caused by a loss-of-function mutation of one allele of the gene for the calcium-sensing receptor (CaR). Hypercalcemia of malignancy usually caused by tumor release of a hormone called parathyroid hormone -related peptide Calciphylaxis (rare) also known as uremic gangrene syndrome, is a rare disorder observed in patients with renal failure and secondary or tertiary hyperparathyroidism.