Very low or undetectable intact parathyroid hormone levels in patients with surgically verified parathyroid adenomas

Abstract

When the clinical suspicion is high, the diagnosis of primary hyperparathyroidism should be pursued despite suppressed or low-normal serum intact PTH levels after carefully excluding other causes of hypercalcaemia. Further research on various intact PTH molecular species secreted by parathyroid adenomas or post-translational changes in the intact PTH molecule that might interfere with in vitro measurements should be undertaken to understand the precise reason(s) for such anomalous findings.

Intraoperative parathyroid hormone (PTH) testing in patients with primary hyperparathyroidism and PTH levels in the normal range

“…The first authors to propose potential etiopathogenetic mechanisms were Hollenberg and Arnold [15] in 1991. Theories have included the pulsatile secretion of PTH, the secretion of abnormal PTH altering its measurement but not its function, the presence of unmeasured active PTH fragments, the presence of a circulating antibodies interfering with the assay, the presence of another mediator of hypercalcemia (PTH-related peptide), and the increased peripheral tissue sensitivity to normal PTH [2,8,10,14,16,17,25]. Potential mechanisms to consider are also discrepancies between different types of equipment, methods of dosing and sampling as well as early diagnosis [14].…”

“…Primary hyperparathyroidism (PHP) is the third most common endocrine disorder in the United States and the second most common cause of hypercalcemia [1][2][3][4][5][6][7].…”

“…The literature on this condition is poor and consists mainly of clinical cases [3,4,[12][13][14][15][16]. An incidence of 5 to 33% has been documented in the literature [2,10,12,13,17] but no etiologic explanation has been given [10]. In 1987, parathyroid-hormone-related peptide (PTHrp) has been isolated as a causative factor of malignant hypercalcemia [10].…”

Novel Use of Calcimimetic Activity to Diagnose Primary Hyperparathyroidism in a Patient With Persistently Low-Normal Parathyroid Hormone Level

“…PTH is unequivocally elevated in the majority of cases, though 5%-10% of patients have PTH levels in the laboratory reference range [4,5]. There are well-documented case reports of patients with PHPT and PTH levels that are low or low normal, and an uncharacteristically low PTH level may delay recognition of PHPT as parathyroid-independent etiologies of hypercalcemia such as malignancy typically suppress PTH to less than 20 pg/mL [6][7][8][9][10].…”

Metabolic bone disease: Newer perspectives

“…In such situation, it is difficult to take a decision to go ahead for surgery. [2] The localization of adenoma in PHPT is of importance in our scenario, where expert parathyroid surgeons are not easily available. Ultrasonography has a reasonably good sensitivity of 70% with positive predictive value of 100% and is a useful and inexpensive tool in establishing the etiology of PHPT.…”