Hyperparathyroidism Primary

Primary hyperparathyroidism is essentially a biochemical disturbance in the normal equilibrium between bone mineral and tissue fluid. It may remain undetected for many years before the development of complications [frequently, renal calculi (F2) ] lead to its discovery, by which time it may be too late for effective treatment. It threatens health and even life, and early diagnosis and treatment are therefore of prime importance. 

The responsibility for this diagnosis rests almost entirely on the clinical chemist, on whose findings and recommendation surgical exploration must be carried out. Until the hormone can be assayed easily and precisely in body fluids, the diagnosis will depend on the secondary biochemical disturbances which will now be described. 

The most important single biochemical estimation in primary hyperparathyroidism is the concentration of calcium in the plasma. Since the elevation above the normal value may be very small indeed, it is essential that every laboratory should know with the greatest possible precision the upper limit of the normal range of plasma calcium by its own particular method. In appropriate cases plasma calcium should be estimated not once but three or four times, and any abnormal values should be regarded with the greatest suspicion (M2). 

It is doubtful whether the measurement of ionic calcium in the ultrafiltrate is called for at the present time other than for research purposes. The method devised by Rose (R9) is available, but although it represents a considerable contribution to calcium research, it is slow and laborious and the results obtained with it have confirmed that it offers little or no advantage over the much easier measurement of ultrafiltrable calcium. 

The tendency to renal calculus formation in hyperparathyroidism is not simply the result of hypercalcuria, since stone formation is rare in other conditions, such as hyperthyroidism, in which urine calcium may be much higher. It is more probably connected with the tendency to an alkaline urine (F5, N12), which, when combined with a rather high urine calcium concentration, predisposes to stone formation. The cases with the highest urine calcium are not necessarily those that form stones (N16). 

---

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... 

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. 

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

Parathyroid hormone (PTH) produces CNS effects in normal subjects and neuropsychiatric symptoms are frequently encountered in patients with primary hyperparathyroidism, where EEG changes resemble those described in acute renal failure. Circulating PTH is not removed by hemodialysis. In uremic patients both EEG changes and neuropsychiatric symptoms are improved by either parathyroidectomy or medical suppression of PTH. The mechanism whereby PTH causes disturbances of CNS function is not well understood, but it has been suggested that increased PTH might facilitate the entry of Ca2+ into the cell resulting in cell death. 

The calcium value is only slightly raised hut the PTH concentration, although within the stated reference range, is inappropriately high for the stated calcium concentration. Normally, PTH and calcium concentrations are inversely related. A diagnosis of primary hyperparathyroidism was subsequently confirmed. The role of PTH is to raise plasma calcium concentration, partly, by enhancing osteoclast activity. 

Miedlich, S., Lamesch, P., Mueller, A., and Paschke, R. (2001) Frequency of the calcium-sensing receptor variant A986S in patients with primary hyperparathyroidism. Eur. J. Endocrinol. 145,421 27. 

Specific Disorders Involving the Bone Mineral-Regulating Hormones PRIMARY HYPERPARATHYROIDISM... 

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. 

Primary hyperparathyroidism was the likely explanation in this patient, rather than a direct effect of calcitonin. 

A 63-year-old woman taking long-term lithium who developed subclinical hypothyroidism and primary hyperparathyroidism (641). 

Awad SS, Miskulin J, Thompson N. Parathyroid adenomas versus four-gland hyperplasia as the cause of primary hyperparathyroidism in patients with prolonged lithium therapy World J Surg 2003 27 486-8. 

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. 

Warner et al, 2004). Moreover this study points out that there can be overlap in the clinical presentations of FHH and primary hyperparathyroidism, particularly in familial forms of the latter. 

Clinical and Genetic Features of Neonatal Severe Primary Hyperparathyroidism (NSHPT) [OMIM 239200]... 

Grantmyre, E, 1973, Roentgenographic features of primary hyperparathyroidism in infancy, J Can Assoc Radiol 24 257-260... 

Marx, S, Attie, M, Spiegel, A, Levine, M, Lasker, R and Fox, M, 1982, An association between neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia in three kindreds, N Engl J Med 306 257-284... 

Marx, SJ, Attie, MF, Stock, JL, Spiegel, AM and Levine, MA, 1981b, Maximal urine-concentrating ability familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism, J Clin Endocrinol Metab 52 736-740... 

D5. de la Piedra, C., Toural, V., and Rapado, A., Osteocalcin and urinary hydroxyproline/creatinine ratio in the differential diagnosis of primary hyperparathyroidism and hypercalcaemia of malignancy. Scand. J. Clin. Lab. Invest. 47, 587-592 (1987). 

Polymorphisms in the VDR gene may be related to bone mineral density and predispose an individual to osteoporosis [337], The use of restriction length fragment polymorphism (RFLP) analysis and other markers of VDR polymorphisms could be an additional early assessment parameter for the future risk of developing osteoporosis. Identification of the defective allele also referred to as BB or bb, depending on the laboratory from which the studies first originated, has been correlated to an increased risk of primary and secondary osteoporosis and primary hyperparathyroidism. But... 

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. 

---