Parathyroid hormone adverse effects

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Reviews of parathyroid hormone have suggested that it is generally well tolerated (4,5,6). The adverse effects of parathyroid hormone that have been reported in clinical trials are mild and include transient bone pain, nausea, dizziness and local irritation at the injection site (7). Hypercalcemia, which is common, is usually mild and asymptomatic. Adverse effects, including hypercalcemia, appear to be dose related in the therapeutic range. 

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). 

In two placebo-controUed trials, 90% of dialysis patients with moderate to severe secondary hyperparathyroidism who received doxercalciferol for 16-24 weeks had about a 70% reduction in parathyroid hormone concentrations. The most frequently reported adverse effects include edema, headache, and malaise. 

Adverse effects of oral calcium and vitamin D supplementation include hypercalcemia and hypercalciuria, especially in the hy-poparathyroid patient, in whom the renal calcium-sparing effect of parathyroid hormone is absent. Hypercalciuria may increase the risk of calcium stone formation and nephrolithiasis in susceptible patients. One maneuver to help prevent calcium stones is to maintain the calcinm at a low normal concentration. Monitoring 24-hour urine collections for total calcium concentrations (goal <300 mg/24 h) may also minimize the occurrence of hypercalciuria. The addition of thiazide dinretics for patients at risk for stone formation may result in a reduc-tionof both urinary calcium excretion and vitamin D requirements." ... 

Teriparatide contains the first 34 amino acids in human parathyroid hormone and represents a novel approach to osteoporosis treatment. Although hyperparathyroidism leads to bone loss (see Fig. 88-3), therapeutic doses (for shorter periods of time) conversely improve BMD and rednce fractnre risk. Parathyroid hormone is currently the only approved osteoporosis medication that works by stimulating bone formation. Becanse of adverse effects and cost concerns, teriparatide is reserved for treating those at high risk of osteoporosis-related fracture who cannot or will not take or have failed bisphosphonate therapy. 

The ability of the renal cells to make 1.25 dihydroxycholecalciferol fulls as the renal tubular damage progresses. Calcium absorption is reduced and there is a tendency towards hypocalcaemia. Parathyroid hormone is stimulated in an attempt to restore plasma ealcium to normal, and high circulating PTH may have adverse effects on bone if this is allowed to continue (Fig. 2). Secondary hyperparathyroidism causes the changes in bone which are characteristic of renal osteodystrophy. 

Tumorigenidty Osteosarcoma is postulated as a potential adverse reaction to parathyroid hormone analogues, based on animal studies, and another case has been reported in a 67-year-old man who took teriparatide 20 micrograms/day subcutaneously for 2 months, 7 years after a course of radiotherapy for recurrent prostate cancer [65 ]. However, the osteosarcoma occurred within the field of previous radiotherapy and the time course suggested that the osteosarcoma may have been present before teriparatide administration. The authors noted that 430 000 patients have been treated with teriparatide for osteoporosis and that there have been only two reported cases of osteosarcoma, which is consistent with the expected population incidence of 4-5 per million. However, the effect of teriparatide on the growth of an undiagnosed osteosarcoma is unknown, and so teriparatide should be used with caution in patients who have had previous radiotherapy. 

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