Identifying Parathyroid Hormone Disorders and Their Phenotypes Through a Bone Health Screening Panel

It's Not Simple Vitamin D Deficiency!

Hafsa Majid, MBBS, FCPS; Aysha Habib Khan, MBBS, FCPS, FCPP, IFCAP; Maria Riaz, MBBS; Hussain Karimi, MBBS; Jamsheer Talati, MBBS, FRCS

Disclosures

Endocr Pract. 2016;22(7):814-821. 

In This Article

Abstract and Introduction

Abstract

Objectives: To determine the utility of bone health screening panels in identifying disorders of parathyroid gland secretions.

Methods: A retrospective analysis of biochemical parameters in a bone health screening panel (BHSP) was conducted. Low and high cutoffs were applied to determine hypofunctioning and hyperfunctioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were determined using a combination of levels of calcium, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH). A PTH nomogram was applied to calculate the maximum expected PTH for existing levels of 25-hydroxyvitamin D. Medical records of patients were reviewed for clinical validation of biochemical findings.

Results: Sixty-eight percent of subjects showed abnormal PTH secretion. Primary hyper- and hypoparathyroidism were detected in 1% (n = 5) and 0.4% (n = 2) of subjects, respectively. Normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high-normal PTH were identified in 8.5% (n = 37) and 2% (n = 10) of subjects, respectively. All subjects with primary and normocalcemic hyperparathyroidism had higher measured PTH than calculated maximum PTH using the PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism were present in 18% (n = 88) and 39% (n = 194) of subjects, respectively. High prevalence of bone pains, renal stones, and low bone mineral density were identified in patients with abnormal PTH secretion.

Conclusion: Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. A BHSP helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high PTH.

Introduction

The parathyroid glands are instrumental in bone and mineral homeostasis. Disorders of secretion can be primary, in which parathyroid glandular activity is intrinsically abnormal (e.g., primary hyperparathyroidism [PHPT] and hypoparathyroidism) or secondary, in which increased or decreased parathyroid glandular activity is an adjustment to another pathophysiologic process (e.g., vitamin D deficiency [VDD] or chronic renal failure [CRF]) or a physiologic adjustment to another pathophysiologic event that leads either to hypercalcemia or hypocalcaemia.

Recently, newer phenotypes of PHPT have evolved. This includes normocalcemic hyperparathyroidism (NCHPT), which is characterized by normal serum calcium and high intact parathyroid hormone (iPTH) levels in the absence of VDD and CRF. Another phenotype is of inappropriately normal iPTH in the setting of hypercalcemia (hypercalcemia with inappropriately normal iPTH). In addition, a significant proportion of subjects do not demonstrate secondary hyperparathyroidism (SHPT) despite VDD; this has been labeled as functional hypoparathyroidism.

Disorders of parathyroid hormone (PTH) secretion are an important cause of metabolic bone diseases (MBDs), which are frequent in the general population[1–3] and contribute to morbidity and decreased quality of life.[4–7] Biochemical assessment of bone health is important for diagnosis. There is wide variability in clinical presentation; and nonspecific symptoms present a diagnostic challenge. Most subjects are identified only while investigated for another disorder.

Measurement of serum calcium, 25-hydroxyvitamin D (25OHD), and plasma iPTH concentrations, although readily available, are of limited value in assessing MBD when used individually. Simultaneous testing with markers relevant to MBD improves diagnostic yield, as interpretation can be made together with clinical history and examination. They are also economical both in terms of time and money for both patients and physicians. Bone health screening panels (BHSPs) variably utilize combinations of blood tests to screen, diagnose, and monitor MBDs in clinical practice. These panels facilitate answering the potential clinical questions that a physician asks when investigating MBDs.

For this reason, we introduced a biochemical testing panel (including serum 25OHD, calcium, phosphorus, magnesium, alkaline phosphatase, creatinine, albumin, and iPTH) to screen for bone and mineral disorders at the Clinical Laboratories, Aga Khan University Hospital (AKUH) in January 2011. This audit was therefore conducted to determine the utility of the BHSP in identifying disorders of parathyroid gland secretion. There are few studies of simultaneous testing with multiple biochemical tests for correctly assessing bone minerals status, which can be missed on routine health screening.

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