Review
Laboratory screening for hyperparathyroidism

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Abstract

Introduction

The clinical syndrome produced by excess parathyroid hormone (PTH) is referred to as hyperparathyroidism (HPT). Autonomous growth of PTH producing cells is defined as primary hyperparathyroidism (pHPT). In its classic form pHPT is characterized by painful bones, kidney stones, abdominal groans, psychic moans, fatigue overtones and hypercalcemia. Chronic stimulation of the parathyroid glands secondary to low circulating calcium level results in secondary hyperparathyroidism (sHPT). Tertiary hyperparathyroidism (tHPT) results from prolonged secondary hyperparathyroidism when the glands take on an autonomous function manifested by hypercalcemia and high PTH levels despite resolution of the original stimulus.

Review

The paper reviews the physiologic regulation of PTH secretion and types and forms of HPT. Calcium homeostasis is discussed, emphasizing interactions of PTH, PO4 and vitamin D that can lead to HPT. In addition, the paper reviews the contribution of serum calcium, chloride, phosphorus and PTH levels to the diagnosis of HPT, the role of urinary calcium in the diagnosis of familial benign hypocalciuric hypercalcemia (FBHH), and the role of alkaline phosphatase and bone mass measurements as markers of severity of hyperparathyroid bone disease.

Conclusions

It is concluded that the diagnosis of hyperparathyroidism can be made with a very high confidence rate by documenting an increased serum PTH level with an increased ionized or total calcium level in pHPT, increased serum PTH level with low or normal calcium level and an underlying renal failure or vitamin D deficiency in sHPT. Early management of HPT is important because many of the nonspecific complains, or classic symptoms, or metabolic conditions often improve after proper control of hyperparathyroidism.

Introduction

Since its first description in 1925, hyperparathyroidism (HPT) is being more diagnosed especially in developed countries. This might be explained, at least partially, by the newly discovered advanced diagnostic tools which allow early detection of hypercalcemia. Severe forms of HPT with bone disease and renal stones are rarely seen these days [1], [2]. Most patients with HPT present today with nonspecific general complaints associated with mild skeletal complications and mild to moderate degrees of hypercalcemia as the case with pHPT [3]. Moreover, the severity of sHPT and tHPT has dramatically declined because of the effective prophylactic measures taken by patients liable for these disorders such as patients with chronic renal failure or malabsorption syndromes [4], [5]. The shift from the classic presentation of HPT occurred during the 1970s when automated serum calcium measurements became liberally and widely utilized [6]. The changing face of hyperparathyroidism was coupled with a marked increase in its incidence [7], [8], [9]. Today, hyperparathyroidism in developed countries is usually associated with less dramatic laboratory changes and smaller parathyroid tumors, in developing countries, however, the old version of the disease is still being encountered [10], [11].

Section snippets

Pathophysiology and forms of HPT

The parathyroid glands are composed of two cellular components; the chief cells and oxyphil cells, and a stroma that is largely made up of fat cells. The chief cell produces most of the parathyroid hormone (PTH), which is an 84-amino-acid single-chain peptide [12]. Its molecular weight is about 9500 with a plasma half-life of 3–4 min. Smaller compounds with as few as 34 amino acids adjacent to the N-terminus of the molecule have also been isolated from the parathyroid gland exhibit full

Calcium–PTH–Vit D–calcitonin interaction

The skeleton, the largest calcium reservoir, contains more than 99% of the total body calcium. This reservoir is readily available for homeostatic needs [36]. Hypocalcemia and hypercalcemia are life-threatening conditions. Therefore, extracellular Ca concentration must be controlled in a narrow range (8.1–10.5 mg/dl). Three calciotropic hormones (PTH, calcitonin and vitamin D) targeting three organs (bone, kidney and intestine) work in coherence to achieve this goal. Acutely, slight changes

Clinical diagnosis

Primary hyperparathyroidism (pHPT) is the most common form of hyperparathyroidism. It is the third most common endocrine disorder, after diabetes mellitus and thyroid disease. In its classic form (which is becoming less common); symptomatic hyperparathyroidism patients have manifestations secondary to high serum calcium and PTH levels such as overt bone disease, kidney stones, and nonspecific gastrointestinal, cardiovascular, and neuromuscular dysfunction [3], [6], [42]. Currently, asymptomatic

Summary

Hyperparathyroidism is a common and potentially serious disorder. Primary hyperparathyroidism (pHPT) is the most common cause of hypercalcemia in outpatients' clinics and is usually mild, asymptomatic, and sustained for years. PTH measurement in the serum is the most direct and sensitive measure of parathyroid function. Diagnosis of pHPT has improved substantially since the introduction of sensitive and specific assays for intact 84-amino-acid peptide. The sensitivity for the diagnosis of

Acknowledgments

This work was supported by the Faculty of Medicine/University of Jordan. We thank Ms. Sana Al Tamemi for her help with the graphs.

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