Vitamins hypoparathyroidism

One of the major problems In the treatment of patients with vitamin D compounds (l.e., patients with hypoparathyroidism) has been the unpredictable development of hypercalcemia and the syndrome of vitamin D Intoxication. Although this problem may become less serious when some of the faster-acting metabolites and analogues of metabolites of vitamin D become available for clinical use. It Is likely that monitoring of serum levels of... 

Causes of hypocalcemia include hypoparathyroidism, hypomagnesemia, alcoholism, hyperphosphatemia, blood product infusion (due to chelation by the citrate buffers), chronic renal failure, vitamin D deficiency, acute pancreatitis, alkalosis, and hypoalbuminemia. Medications that cause hypocalcemia include phosphate replacement products, loop diuretics, phenytoin (Dilantin, available as generic), pheno-barbital (available as generic), corticosteroids, aminoglycoside antibiotics, and acetazolamide (available as generic).34,39,42... 

Reduction in the serum 1,25-dihydroxyvitamin D concentration has been reported as an indicator of increased lead absorption or lead levels in the blood (Rosen et al. 1980). Lead inhibits the formation of this active metabolite of vitamin D, which occurs in bone mineral metabolism (EPA 1986a Landrigan 1989). Children with PbB concentrations of 12-120 pg/dL lead showed decreased serum 1,25-dihydroxyvitamin D concentrations comparable to those found in patients with hypoparathyroidism, uremia, and metabolic bone disease (Mahaffey et al. 1982 Rosen et al. 1980). This biomarker is clearly not specific for lead exposure and several diseases can influence this measurement. 

Cholestyramine, colestipol, orlistat, or mineral oil decrease vitamin D absorption Might induce hypercalcemia with thiazide diuretics in hypoparathyroid patients... 

Hypocalcemia results from altered effects of parathyroid hormone and vitamin D on the bone, gut, and kidney. The primary causes are postoperative hypoparathyroidism and vitamin D deficiency. 

Oral calcium supplementation (e.g., 1 to 3 g/day of elemental calcium) is indicated for chronic hypocalcemia due to hypoparathyroidism and vitamin D deficiency. If serum calcium does not normalize, a vitamin D preparation should be added. 

Oral As a dietary supplement when calcium intake may be inadequate. Conditions that may be associated with calcium deficiency include the following Vitamin D deficiency, sprue, pregnancy and lactation, achlorhydria, chronic diarrhea, hypoparathyroidism, steatorrhea, menopause, renal failure, pancreatitis, hyperphosphatemia, and alkalosis. Some diuretics and anticonvulsants may precipitate hypocalcemia, which may validate calcium replacement therapy. Calcium salt therapy should not preclude the use of other corrective measures intended to treat the underlying cause of calcium depletion. 

Calcitriol (Rocaltrol, Calcnex) [Antihypocalcemic/Vitamin D Analog] Uses Reduction of i PTH levels, -iTca on dialysis Action 1,25-Dihydroxycholecalcifool (vit D analog) Dose Adul. Renal failure 0.25 mcg/d PO, t 0.25 mcg/d q4-6wk PRN 0.5 meg 3 x/wk IV, t PRN Hypoparathyroidism ... 

Vitamin D preparations are also used to treat hypoparathyroidism, but they require even larger doses, often up to 2.5 mg (100,000 units) daily to increase the serum calcium back to normal. As in vitamin D deficiency, the dose must be carefully monitored. 

The active forms of the D vitamins are la,25-dihydroxy-vitamin Dj and 25-hydroxy-vitamin Dj. They are formed by enzymatic hydroxylation in the liver microsomes and then in the kidney mitochondria by a ferredoxin flavoprotein and cytochrome P-450. The 1,25-dihydroxy vitamin is then transported to the bone, intestine, and other target organs (kidneys, parathyroid gland). Consequently, it can be considered a hormone since it is produced in one organ but used elsewhere. It mobilizes calcium and phosphate and also influences the absorption of these ions in the intestine, thus promoting bone mineralization. The hormone is also active in relieving hypoparathyroidism and postmenopausal osteoporosis, which, for example, results in the brittle bones of elderly women. 

It is indicated in osteoporosis, hypoparathyroidism, hyperparathyroidism (with bone disease), renal osteodystrophy, nutritional and malabsorptive rickets, hypophosphataemic vitamin D resistant rickets and osteomalacia. 

The main features of hypocalcemia are neuromuscular—tetany, paresthesias, laryngospasm, muscle cramps, and convulsions. The major causes of hypocalcemia in the adult are hypoparathyroidism, vitamin D deficiency, chronic kidney disease, and malabsorption. Neonatal hypocalcemia is a common disorder that usually resolves without therapy. The roles of PTH, vitamin D, and calcitonin in the neonatal syndrome are under active investigation. Large infusions of citrated blood can produce hypocalcemia by the formation of citrate-calcium complexes. Calcium and vitamin D (or its metabolites) form the mainstay of treatment of hypocalcemia. 

Hypoparathyroidism Lack of parathyroid hormone causes hypocalcemia and hyperphosphatemia. These patients may be treated with any form of vitamin D, together with parathyroid hor mone. 

As a brief introductory summary, vitamin D substances perform the following fundamental physiological functions (1) promote normal growth (via bone growth) (2) enhance calcium and phosphorus absorption from the intestine (3) serve to prevent rickets (4) increase tubular phosphorus reabsorpiion (5) increase citrate blood levels (6) maintain and activate alkaline phosphatase m bone (7) maintain serum calcium and phosphorus levels. A deficiency of D substances may be manifested in the form of rickets, osteomalacia, and hypoparathyroidism. Vitamin D substances are required by vertebrates, who synthesize these substances in the skin when under ultraviolet radiation, Animals requiring exogenous sources include infant vertebrates and deficient adult vertebrates, Included there are vitamin D (calciferol ergocalciferol) and vitamin D< (activated 7-dehydrocholesterol cholecalciferol). 

Disease Hypoparathyroidism Pathophysiology Decreased parathyroid hormone secretion leads to impaired bone resorption and hypocalcemia Primary Drug Treatment Calcium supplements, vitamin D... 

The principal therapeutic concern is to restore normocalcemia and normophosphatemia. Under most circumstances, vitamin D (25,000-100,000 units three times per week) and dietary calcium supplements suffice. More rapid increments in serum calcium can be achieved with calcitriol, though it is not clear that this metabolite offers a substantial advantage over vitamin D itself for long-term therapy. Many patients treated with vitamin D develop episodes of hypercalcemia. This complication is more rapidly reversible with cessation of therapy using calcitriol rather than vitamin D. This would be of importance to the patient in whom such hypercalcemic crises are common. Dihydrotachysterol and 25(OH)D have not received much study as therapy for hypoparathyroidism, though both should be effective. Whether they offer advantages over vitamin D sufficient to justify their added expense remains to be seen. 

The metabolism of phosphorus (P) is largely related to that of calcium (Ca). The Ca P ratio in the diet affects the absorption and excretion of these elements (Harper 1969). Any increase in serum phosphorus results in a decrease of serum calcium by mechanisms which are still unknown. For example, increased serum phosphorus levels and decreased serum calcium levels are seen in uremia (renal retention of phosphorus), hypoparathyroidism, hypocalcemia (decreased serum calcium levels), and hyperphosphatemia (increased serum phosphorus levels), and the reverse is seen in hypercalcemia (increased serum calcium levels) and hyperparathyroidism. Hypophosphatemia (low serum phosphorus levels) is seen in ricketts (vitamin D deficiency) (Harper 1969 Tietz 1970). 

These in vitro findings allow us to suggest that transferrin receptor-mediated uptake of Al might, besides other factors such as vitamin D, high calcium dialysate or CaC03 intake, play a role in the development of hypoparathyroidism associated with Al bone disease. The exact mechanism by which Al-transferrin suppresses iPTH secretion remains to be elucidated [253]. Hyperparathyroidism may afford the bone some protection against the toxic effects of Al [17]. 

Hypercalcemia persists for many months after the cessation of excessive intakes of vitamin D, because of the accumulation of the vitamin in adipose tissue and its slow release into the circulation. The introduction of calcitriol and 1 a -hydroxycalcidiol for the treatment of such conditions as hypoparathyroidism, renal osteodystrophy, hypophosphatemic osteomalacia, and vitamin D-dependent rickets has meant that hypercalcemia is less of a problem than when high doses of vitamin D were used in the treatment of these conditions. Because calcitriol has a short half-life in the circulation, the resultant hypercalcemia is of shorter duration than after cholecalciferol, and adjustment of the dose is easier. 

Advantages of alfacalcidol and dihydrotachysterol include a fast onset and short duration of clinical effect (days) which renders them suitable for rapid adjustment of plasma calcium, e.g. in hypoparathyroidism. Such factors are not relevant to the slower adjustment of plasma calcium (weeks) with vitamins Dg and Dg in the ordinary management of vitamin D deficiency. 

Indications for vitamin D are the prevention and cure of rickets of all kinds and osteomalacia, and the symptomatic treatment of some cases of hypoparathyroidism also psoriasis. 

The hypocalcaemia of hypoparathyroidism may require ergocalciferol in doses up to 2.5 mg (100 000 units) daily to achieve normocalcaemia but the dose is difficult to titrate and hypercalcaemia from overdose may take weeks to resolve. The synthetic vitamin D derivatives, alfacalcidol and... 

For chronic use, e.g. hypoparathyroidism, alfa-calcidol or calcitriol are needed. Dietary calcium is increased by giving calcium gluconate (an effervescent tablet is available) or lactate. Aluminium hydroxide binds phosphate in the gut causing hypo-phosphataemia, which stimulates renal formation of the most active vitamin D metabolite and usefully enhances calcium absorption. 

Hyperparathyroidism and aluminium hydroxide lead to aluminium-related bone disease however, total parathyroidectomy does not lead to failure of aluminium mobilization after renal transplantation. This man had satisfactory graft function, and the aluminium excretion that was achieved by deferoxamine suggests that the renal transplant was not the limiting factor for the mobihzation of aluminium. The most likely explanation was that he developed adynamic bone through a combination of vitamin D deficiency, hypoparathyroidism, and aluminium deposition. Vitamin D supplementation failed to prevent the osteodystrophy on its own. When aluminium chelation therapy was used, bone healing occurred and his symptoms improved. 

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