Hyperparathyroidism

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

The view that nucleating sites are an essential Induction factor in stone formation has led to a number of efforts to decrease their presence. Thus, oral cellulose phosphate has been utilized to decrease the brushite (CaHP0 2H20) activity in urine. Allopurinol (26), administered apparently with some success, reduces the hyperuricosurla observed concomitantly with some oxalate stone formation. 

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A common cause of PTH-dependent hypercalcemia results from benign, or occasionally malignant, enlargement of one or more parathyroid glands, a condition known as primary hyperparathyroidism (PHPT). Although many patients with PHPT present in an asymptomatic state that does not require medical intervention, some are afflicted with excess bone loss, kidney stones, or other complications. If patients are... 

Block GA, Martin KJ, de Francisco AL et al (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350 1516-1525... 

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. 

Prepro-opiomelanocortin Primary Hemostasis Primary Hyperparathyroidism Prodrug... 

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. 

Insulin is a powerful anabolic hormone but it is unlikely that insulin deficiency causes skeletal muscle atrophy by direct action on muscle fibers (as opposed to neurogenic atrophy) except in chronic untreated cases. There is however a close parallel between the catabolic states induced by glucocorticoid excess and by insulin deficiency. Moreover, impaired insulin action is implicated in other endocrine myopathies as a contributory cause of muscle wasting. Both acromegaly and thyrotoxicosis are associated with insulin resistance due to a postreceptor defect, and secondary hyperparathyroidism due to hypophosphatemia also gives rise to insulin insensitivity. 

Hyperparathyroidism Excess parathormone causes bone resorption. 

A. E. Sizemore, G. W. Arnaud, C. D. "Etiology of Hyperparathyroidism and Bone Disease During Chronic Hemodialysis. III. Evaluation of Parathyroid Suppressability". J. Clin. Invest. (1973), 52, 173-180. 

Riggs, B. L. Arnaud, C. D. Reynolds, J. C. Smith, L. H. "Immunologic Differentiation of Primary Hyperparathyroidism From Hyperparathyroidism Due to Nonparathyroid Cancer". 

Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism". J. Clin. Invest. (1974), 175-181. 

It has been shown that in postmenopausal women habitually high intakes of dietary isoflavones are associated with higher bone mineral density (BMD) values at both the spine and hip region (Mei et al, 2001). It is conceivable that an isoflavone-rich diet may help to reverse the state of secondary hyperparathyroidism associated with estrogen withdrawal and hence lower the rate of bone turnover in postmenopausal women, thus reducing the risk of osteoporosis (Valtuena et al, 2003). Phytoestrogens could be used as natural SERMs (Brzezinski and Debi, 1999) and some studies (Setchell, 2001 and refs therein) support such an idea since the molecular targets of... 

The management of secondary hyperparathyroidism involves correction of serum calcium and phosphorus levels, and decreasing parathyroid hormone secretion. 

What signs are consistent with secondary hyperparathyroidism ... 

As kidney function continues to decline and the GFR falls less than 60 mL/minute/1.73 m2, phosphorus excretion continues to decrease and calcitriol production decreases, causing PTH levels to begin to rise significantly, leading to secondary hyperparathyroidism (sHPT). The excessive production of PTH leads to hyperplasia of the parathyroid glands, which decreases the sensitivity of the parathyroid glands to serum calcium levels and calcitriol feedback, further promoting sHPT. 

FIGURE 23-5. Pathogenesis of secondary hyperparathyroidism and renal osteodystrophy in patients with CKD. 

Clinical Presentation of Secondary Hyperparathyroidism and Renal Osteodystrophy ... 

The cause of pruritus is unknown, although several mechanisms have been proposed. Vitamin A is known to accumulate in the skin and serum of patients with CKD, but a definite correlation with pruritus has not been established. Histamine may also play a role in the development of pruritus, which may be linked to mast cell proliferation in patients receiving hemodialysis. Hyperparathyroidism has also been suggested as a contributor to pruritus, despite the fact that serum PTH levels do not correlate with itching. Accumulation of divalent ions, specifically magnesium and aluminum, may also play a role in pruritus in patients with CKD. Other theories that have been proposed include inadequate dialysis, dry skin, peripheral neuropathy, and opiate accumulation.43... 

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

Renal osteodystrophy Altered bone turnover that results from sustained metabolic conditions that occur in chronic kidney disease, including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. 

Secondary hyperparathyroidism Increased secretion of parathyroid hormone from the parathyroid glands caused by hyperphosphatemia, hypocalcemia, and vitamin D deficiency that result from decreased kidney function. It can lead to bone disease (renal osteodystrophy). 

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