Parathyroid hormone excess

Check parathyroid hormone (PTH), vitamin D and precursors, magnesium, and phosphate levels ° Pharmacological causes of decreased ionized calcium may include excess infusions of citrate, EDTA, lactate, fluoride poisoning, foscarnet, cinacalcet, bisphosphates, or unrelated increase in serum phosphate or decrease in serum magnesium levels... 

Vitamin D is really a small family of closely related molecnles that prevent the bone disease rickets in children and osteomalacia in adnlts. In both cases, inadeqnate mineralization of bone results in bone deformation and weakness. Calcinm, Ca +, homeostasis is one goal of vitamin D activity, a goal it shares with parathyroid hormone and calcitonin. Calcium is intimately involved in bone mineralization and distnrbances of calcium levels in the blood can resnlt in inadeqnate bone mineralization or excessive calcification of other tissues. 

Osteomalacia is the condition in which bone becomes demineralised due to deficiency of vitamin D. In this condition parathyroid hormone (PTH) acts on the bone to maintain serum calcium, resulting in demineralisation. Serum calcium is usually normal or slightly low alkaline phosphatase levels are high, reflecting excessive osteoblast activity, and serum phosphate falls as an effect of PTH on the kidney. The same condition in children results in defects in long bone formation, and is termed rickets. 

Hyperparathyroidism Increased parathyroid hormone secretion, usually caused by parathyroid tumors leads to excessive bone resorption and hypercalcemia Usually treated surgically by partial or complete resection of the parathyroid gland... 

The fact that vitamin D3 toxicity results from primarily uncontrolled intestinal calcium absorption suggests that it is dietary calcium and not vitamin D3 that exacerbates the hypervitaminosis D3 toxicity effect [119]. This was tested by the interaction of excess vitamin D3 and calcium restriction [113]. Rats fed a calcium-deficient diet and given 25,000 IU of vitamin D3 three dmes/week for 2.5 weeks did not succumb to overt hypervitaminosis D3. Simple calcium restriction increased intestinal but not renal 24-OHase activity, presumably because of the absence of parathyroid hormone regulation in the intestine [113]. Coupled with vitamin D3, excess intestinal 24-OHase increased several fold more. However, when dietary calcium was adequate, vitamin D3 excess increased intestinal 24-OHase activity only slightly because of a suppressive mechanism regulated in part by increased blood calcitonin [120],... 

Q7 Calcium is present in both intracellular fluid (ICF) and ECF, but the concentration in the ECF is twice as high as that in the ICF. Calcium is found in both ionized and bound forms, and Ca2+ homeostasis is mainly controlled by parathyroid hormone, which increases absorption of calcium in the intestine and reabsorption in the nephron. Calcitonin also affects ECF calcium concentration by promoting renal excretion when there is an excess of calcium in the body. The normal kidney filters and reabsorbs most of the filtered calcium however, in renal disease this is reduced and blood calcium decreases. Calcium and phosphate imbalance can occur in patients with renal failure, leading to osteomalacia (defective mineralization of bone). Osteomalacia is mainly due to reduced production of 1,25-dihydroxycholecalciferol, an active form of vitamin D metabolized in the kidney. Deficiency of 1,25-dihydroxycholecalciferol reduces the absorption of calcium salts by the intestine. 

In the kidneys, parathyroid hormone increases 1 -hydroxylation of calcidiol and reduces 24-hydroxylation. This is not the result of de novo enzyme synthesis, but an effect on the activity of the preformed enzymes, mediated by cAMP-dependent protein kinases. In turn, calcitriol has a direct role in the control of parathyroid hormone, acting to repress expression of the gene. In chronic renal failure, there is reduced synthesis of calcitriol, leading to the development of secondary hyperparathyroidism that results in excess mobilization of bone mineral, hypercalcemia, hypercalciuria, hyperphosphaturia, and the development of calcium phosphate renal stones. 

The second most common adverse effect of foscarnet is symptomatic hjrpocalcemia, which may be responsible for the cardiac dysrhythmias and seizures that occur after acute overdose or excessively rapid infusion of foscarnet. Foscarnet stimulates the release of parathyroid hormone, which raised concerns about long-term administration (8). However, in a study of seven patients receiving a 14-day foscarnet induction regimen, there were no changes in calcium or phosphate metabolism (9). 

When the secretion of parathyroid hormone is excessive, the physiologic effects of this peptide on the gut, the skeleton, and the kidney tubules are enhanced. The percentage of dietary calcium absorbed into the circulation is increased, calcium ions are released from bone and enter the blood more rapidly, and the renal tubules reabsorb more calcium than usual from the luminal urine, all leading to hypercalcemia. Chronic hypercalcemia is associated with vague generalized musculoskeletal pain, fatigue, and eventually, slowed mentation. 

B. Hyperparathyroidism is the likely cause of all of the patient s symptoms. Increased parathyroid hormone leads to bone demineralization, increased calcium uptake from the intestine, increased blood levels of calcium, decreased calcium ion excretion by the kidney, and increased phosphate excretion in the urine. Increased blood calcium levels caused renal stones, while bone demineralization progressed to osteopenia. The patient s intake of calcium and vitamin D are not excessive. Calcitonin acts to decrease bone demineralization. Muscle weakness and depression reflect the widespread role of calcium ion in many physiologic processes. 

C. The major action of vitamin D is to increase absorption of calcium from the small intestine. Deficiency of the vitamin leads to low blood calcium levels, stimulation of parathyroid hormone secretion, and acting synergistically, promotion of bone demineralization. Renal excretion of calcium is decreased by hypocalcemia but elevated parathyroid hormone levels promote renal excretion of phosphate, to prevent excessive accumulation of this product of bone demineralization. Although lack of exercise decreases bone density, it does not lead to rickets if vitamin D is sufficient. 

Calcium Absorption. In animals, excess strontium indirectly suppresses the activation of vitamin D3 in the kidney, which severely reduces the expression of calbindin D mRNA and the translation of calbindin D protein in the duodenum (Armbrecht et al. 1979, 1998 Omdahl and DeLuca 1972). As a result, duodenal absorption of calcium is reduced. The reported inverse correlation between the amount of strontium that is absorbed and the levels of parathyroid hormone (Vezzoli et al. 1998) suggest that changes in parathyroid hormone levels mediate this effect. While there are no data on strontium-binding to the calcium receptor of the parathyroid gland, it is likely that strontium binds in place of calcium, mimicking calcium and thereby suppressing parathyroid hormone levels. A reduction in parathyroid hormone levels will decrease the level of 1-hydroxylase available to activate vitamin D3. 

Calcitonin is also involved in calcinm homeostasis by inhibiting bone resorption and by preventing excess increases in the serum calcium concentration throngh its monitoring of parathyroid hormone s actions (see Figure 75). 

A subset of patients with hypercalcaemia related to a malignancy show no evidence of excess parathyroid hormone production or osseous metastases. PG have been implicated in the pathogenesis of malignancy-related hypercalcaemia, since PG enhance bone resorption, and are necessary for the synthesis of osteoclastic activating factor. Some patients with renal cell carcinoma and concomitant hypercalcaemia have been shown to have elevated renal PG levels which can be suppressed with indomethacin. 

High serum levels of chloride (hyperchloremia), that is levels of 109 mEq/L (109 mmol/L) or higher, can result from dehydration and other conditions, including renal disease and excess parathyroid hormone (PTH). Hyperchloremia also results from metabolic acidosis owing to the loss of base and respiratory alkalosis that occurs with hyperventilation. 

Pathological intracellular calcifications can also occur in conditions associated with hypercalcaemia [26] - excess levels of calcium in the blood, caused, e.g. by hyperparathyroidism (excess secretion of parathyroid hormone by overactive parathyroid glands which normally regulate calcium levels tightly) or malignancy [27]. Intramitochondrial cdcifications often precede necrosis, and fusion or rupture of calcified mitochondria results in calcareous masses in the cytoplasm or outside of the cell. Much progress has been made in the ultramicroscopic identification and systematic classification of these calcifications [28]. 

Excessive amounts of parathyroid hormones can cause focal pancreatic necrosis. It is not known whether pancreatitis precedes hyperparathyroidism or vice versa, but it has been suggested that the pancreatitis leads to steatorrhea with hypocalcemia and secondary hyperparathyroidism. 

A functional parathyroid adenoma would produce excess parathyroid hormone (PTH). PTH stimulates osteodasiic activity and increases renal tubular calcium resorption, leading to hypercalcemia by increasing bone turnover. Vitamin D is metabolized to the active 1,25 dihydroxy form, which interacts with parathyroid hormone to prodiKe hypercalcemia. Impaired renal tubular function in chronic renal disease Oncluding cadmium toxicosis)... 

Excess phosphorus in the blood serum, which may result (1) when the kidneys do not excrete phosphorus adequately, or (2) from hypoparathyroidism, which causes an insufficient secretion of parathyroid hormone. When serum phosphorus rises, serum calcium falls, causing tetany. 

Little is known about the biochemical mechanism of vitamin D action. It promotes the absorption of Ca++-ions in the gastro-intestinal tract and influences the metabolism of bone tissue. Deficiency of vitamin D results in the clinical syndrome rachitis (also in animal experiments), characterized by a softenii (inadequate calcification) of the bones. Excessive administration of vitamin D produces a hyper-vitaminosis, during which calcium is again mobilized out of the bone structure this hypervitaminosis resembles the action of the parathyroid hormone. 

Q6 The cause of excessive PTH secretion maybe primary, secondary, or tertiary. In primary hyperparathyroidism one or more glands show exaggerated functions, do not respond to the normal feedback via serum calcium and secrete PTH autonomously. However, the most common cause (80% of the cases) is a benign tumour of parathyroid tissue in one of the glands. Secondary hyperparathyroidism is due to the development of hypocalcaemia. There is an increase in the level of PTH however, the kidneys, which are major target organs for this hormone, fail to respond and therefore the level of calcium remains low. In tertiary hyperparathyroidism, which occurs in chronic renal failure, the hyperplastic parathyroid cells lose their sensitivity to circulating calcium levels. This leads to autonomous secretion of PTH. 

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