Hyperparathyroidism treatment

A class of allosteric activators of the Ca2+-sensing receptor that sensitizes the receptor to extracellular calcium and acts only in the presence but not in the absence of calcium. Calcimimetics can be used to treat various forms of hyperparathyroidism, although they are only approved for use in patients with end stage renal disease receiving dialysis treatment. 

Primary hyperparathyroidism occurs as a result of hyperplasia or the occurrence of adenoma. Secondary hyperparathyroidism may result from renal failure because of the associated phosphate retention, resistance to the metabolic actions of PTH, or impaired vitamin D metabolism. The last-mentioned factor is primarily responsible for the development of osteomalacia. Muscle symptoms are much more common in patients with osteomalacia than in primary hyperparathyroidism. Muscle biopsy has revealed disseminated atrophy, sometimes confined to type 2 fibers, but in other cases involving both fiber types. Clinical features of osteomalacic myopathy are proximal limb weakness and associated bone pain the condition responds well to treatment with vitamin D. 

What treatment would you recommend for secondary hyperparathyroidism ... 

Determine if the patient requires medical intervention to prevent the development of or treatment for secondary hyperparathyroidism. 

Zemplar (paricalcitol) injection is a synthetically manufactured selective vitamin D receptor activator (SVDRA) indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) stage 5. The U.S. Food Drug Administration (FDA) approved a capsule form of Zemplar for development to satisfy a need for an oral formulation. The objective of study M04-693 was to assess the bioequivalencies of several dosage strengths of paricalcitol capsules under fasting conditions. 

Paricalcitol is a synthetically manufactured analogue of calcitriol. It is indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease. Cinacalcet, a drug that acts as a calcimimetic, can be added if the effects on PTH levels are isufficient. 

Thiazides inhibit NaCI reabsorption from the luminal side of epithelial cells in the DCT by blocking the Na+/Q transporter (NCC). In contrast to the situation in the TAL, in which loop diuretics inhibit Ca2+ reabsorption, thiazides actually enhance Ca2+ reabsorption. This enhancement has been postulated to result from effects in both the proximal and distal convoluted tubules. In the proximal tubule, thiazide-induced volume depletion leads to enhanced Na+ and passive Ca2+ reabsorption. In the DCT, lowering of intracellular Na+ by thiazide-induced blockade of Na+ entry enhances Na+/Ca2+ exchange in the basolateral membrane (Figure 15-4), and increases overall reabsorption of Ca2+. Although thiazides rarely cause hypercalcemia as the result of this enhanced reabsorption, they can unmask hypercalcemia due to other causes (eg, hyperparathyroidism, carcinoma, sarcoidosis). Thiazides are useful in the treatment of kidney stones caused by hypercalciuria. 

Cinacalcet is the first representative of a new class of drugs that activates the calcium sensing receptor (CaR). CaR is widely distributed but has its greatest concentration in the parathyroid gland. Cinacalcet blocks PTH secretion by this mechanism and is approved for the treatment of secondary hyperparathyroidism in chronic kidney disease and for the treatment of parathyroid carcinoma. 

This rather common disease, if associated with symptoms and significant hypercalcemia, is best treated surgically. Oral phosphate and bisphosphonates have been tried but cannot be recommended. Asymptomatic patients with mild disease often do not get worse and may be left untreated. The calcimimetic agent cinacalcet, discussed previously, has been approved for secondary hyperparathyroidism and is in clinical trials for the treatment of primary hyperparathyroidism. If such drugs prove efficacious, medical management of this disease will need to be reconsidered. 

In contrast to the hypocalcemia that is more often associated with chronic kidney disease, some patients may become hypercalcemic from two other possible causes (in addition to overzealous treatment with calcium). The most common cause of hypercalcemia is the development of severe secondary (sometimes referred to as tertiary) hyperparathyroidism. In such cases, the PTH level in blood is very high. Serum alkaline phosphatase levels also tend to be high. Treatment often requires parathyroidectomy. 

Two analogs of calcitriol—doxercalciferol and paricalcitol—are approved for the treatment of secondary hyperparathyroidism of chronic kidney disease. Their principal advantage is that they are less likely than calcitriol to induce hypercalcemia for any given reduction in PTH. Their greatest impact is in patients in whom the use of calcitriol may... 

Quarles LD Cinacalcet HCI A novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease. Kidney Int Suppl 2005 Jul(96) S24. 

The incidence of acute pancreatitis as a suspected complication of finasteride treatment has been examined in a case-control study in a Danish regional population of 490 000 over 7 years. Of 302 men aged 60 and older with incident acute pancreatitis, three had been exposed to finasteride of 2994 controls 37 had been exposed to finasteride. After adjustment for alcohol-related diseases, gallstone disease, hyperlipidemia, hypercalcemia, and hyperparathyroidism, the authors found no evidence of an increased risk of acute pancreatitis in users of finasteride (48). 

Picca S, Cappa M, Rizzoni G. Hyperparathyroidism during growth hormone treatment a role for puberty Pediatr Nephrol 2000 14(l) 56-8. 

Exacerbation of secondary hyperparathyroidism occurred in a 20-year-old renal transplant patient who also developed psoriasis during interferon alfa treatment (527). Both disorders resolved after withdrawal. 

Hyperparathyroidism was considered a possible cause of treatment-resistant manic psychosis in a patient taking lithium (663). 

In the last case the authors concluded that the hypercalcemia was due to long-term lithium treatment and cited studies showing that hyperparathyroidism occurs in 5—40% of patients taking long-term lithium, compared with a population frequency of less than 4%. The patient s chief complaint included nausea when he was exposed to food and water, and he therefore refused food and water for 2-3 days before admission. He also had acute renal insufficiency, which was thought to be due to... 

Anecdotal observations suggest that excessive use of oral phosphates may be a risk factor for the development of tertiary hyperparathyroidism in patients with X-linked hypophosphatemic rickets. Of 13 patients with X-linked hypophosphatemic rickets two developed tertiary hyperparathyroidism and 11 secondary hyperparathyroidism during treatment (939). Patients with tertiary hyperparathyroidism had on average earlier and longer treatment and higher doses of phosphates (over lOOmg/kg/day) than the 11 patients with secondary hyperparathyroidism. Those who later developed tertiary hyperparathyroidism had very high serum parathormone concentrations (over 42 pmol/1). 

Abdullah H, Bliss R, Guinea Al, Delbridge L. Pathology and outcome of surgical treatment for lithium-associated hyperparathyroidism. Br J Surg 1999 86(l) 91-3. 

Dieserud F, Brun AC, Lahne PE, Normann E. Litiumbehandling og hyperparatyreoidisme. [Lithium treatment and hyperparathyroidism.] Tidsskr Nor Laegeforen 2001 121(22) 2602-3. 

Makitie O, Kooh SW, Sochett E. Prolonged high-dose phosphate treatment a risk factor for tertiary hyperparathyroidism in X-linked hypophosphatemic rickets. Clin Endocrinol 2003 58 163-8. 

Parica Icito l/Ze m pla r/ Abbott/Treatment of secondary hyperparathyroidism associated with chronic failure... 

Calcitonin is a peptide hormone produced in the thyroid gland that serves to lower serum calcium and phosphate levels by inhibiting bone resorption. Calcitonin has been used in the treatment of a variety of diseases, such as primary hyperparathyroidism, Paget s disease, and postmenopausal osteoporosis [99,100]. Salmon calcitonin has a longer half-life than human calcitonin. Salmon calcitonin, 3.6 kDa, is available as a nasal formulation that contains only benzalkonium chloride as a preservative, without an absorption enhancer, and as a parenteral product for injection. The direct effect of benzalkonium chloride on the nasal mucosa is under... 

Torring, O., et al. 1991. Salmon calcitonin treatment by nasal spray in primary hyperparathyroidism. Bone 12 311. 

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