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© 2016 AACE.

Original Article


Hafsa Majid, MBBS, FCPS1; Aysha Habib Khan*, MBBS, FCPS, FCPP, IFCAP1;
Maria Riaz, MBBS1; Hussain Karimi, MBBS2; Jamsheer Talati, MBBS, FRCS3

From: 1 Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine.
Aga Khan University, Stadium Road, P.O. Box 3500. Karachi 74800, Pakistan; 2 Sindh
Medical College, Dow University of Health Sciences, Karachi 74200, Pakistan; 3 Department
of Surgery, Aga Khan University, Stadium Road, P.O. Box 3500. Karachi 74800, Pakistan.

Running Title: Identifying PTH Disorders

Correspondence address: Aysha Habib Khan, MBBS, FCPS, FCPP, IFCAP
Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine.
Aga Khan University, Stadium Road, P.O. Box 3500.
Karachi 74800, Pakistan.

© 2016 AACE.

To determine the utility of bone health screening panel in identifying disorders of
parathyroid gland secretions.
A retrospective analysis of biochemical parameters in bone health screening panel (BHSP)
was conducted. The low and high cut offs were applied to determine hypo functioning and
hyper functioning conditions related to parathyroid hormone. Clinical phenotypes of
parathyroid gland abnormalities were made by using combination of levels of calcium,
vitamin D and iPTH. PTH nomogram defined by Harvey et al was applied to calculate max
expected PTH for existing level of 25OHD. Medical records of patients were reviewed for
clinical validation of biochemical findings.
Sixty eight percent subjects showed abnormal PTH secretion. Primary hyper and hypo
parathyroidism was detected in 1% (n=5) and 0.4% (n=2) respectively. Normocalcemic
hyperparathyroidism and hypercalcemia with inappropriately high normal PTH was
identified in 8.5% (n=37) and 2% (n=10) respectively. All subjects with primary and
normocalcemic hyperparathyroidism had higher measured PTH than calculated maxPTH
using PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism
was present in 18% (n=88) and 39% (n=194) subjects respectively. High prevalence of bone
pains, renal stones and low BMD were identified in patients with abnormal PTH secretion.
Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. BHSP
helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately
high PTH.

© 2016 AACE.

newer phenotypes of PHP have evolved. which are frequent in general population (1-3) and contribute to morbidity and decrease quality of life (4-7). in which increased or decreased parathyroid glandular activity is an adjustment to another pathophysiological process (e. NCHP = normocalcemic hyperparathyroidism. 25 hydroxy vitamin D (25OHD) and plasma iPTH concentrations. 25OHD = Vitamin D. in which parathyroid glandular activity is intrinsically abnormal (e. SD = standard deviation. They are DOI:10. Another phenotype is of inappropriately normal iPTH in the setting of hypercalcemia (hypercalcemia with inappropriately normal iPTH). There is wide variability in clinical presentation.ABBREVIATIONS: MBD = Metabolic bone diseases. Measurement of serum calcium. although readily available. a significant proportion of subjects do not demonstrate secondary hyperparathyroidism (sHPT) despite VDD. or a physiologic adjustment to another pathophysiological events that lead either to hypercalcemia or hypocalcaemia.4158/EP161206. BACKGROUND: Parathyroid glands are instrumental in bone and mineral homeostasis. chronic renal failure (CRF)). which is characterized by normal serum calcium and high intact parathyroid hormone (iPTH) levels in the absence of VDD and CRF. . when used individually are of limited value in assessing MBD. hypoparathyroidism) and secondary. this has been labelled as functional hypoparathyroidism. In addition. primary hyperparathyroidism (PHP).g. PTH = plasma parathyroid hormone. AKUH = Aga Khan University Hospital. BHSP = bone health screening panel. This includes normocalcemic hyperparathyroidism (NCHP). Recently. vitamin D deficiency (VDD). SPSS = Statistical Package of Social Sciences. PHP = primary hyperparathyroidism.OR © 2016 AACE. sHPTH = secondary hyperparathyroidism. Disorders of secretion are primary. Most subjects are identified only while investigated for another disorder. VDD = vitamin D deficiency.g. and non-specific in symptoms are a diagnostic challenge. Simultaneous testing with markers relevant to MBD improves diagnostic yield as interpretation can be made together with clinical history and examination. Disorders of PTH secretion are an important cause of metabolic bone diseases (MBD). Biochemical assessment of bone health is important for diagnosis.

.OR © 2016 AACE. phosphorus. For this reason we introduced a biochemical testing panel (comprising of serum 25OHD. There are not many studies on simultaneous testing with multiple biochemical tests for correctly assessing bone minerals status. diagnose and monitor MBD in clinical practice has been developed in laboratories.4158/EP161206. variably utilizing combination of blood tests to screen.also economical both in terms of time and money for the patients and physician. Bone Health Screening Panel (BHSP). albumin and iPTH) to screen for bone and mineral disorders at the Clinical Laboratories. Aga Khan University Hospital in January 2011. These panels facilitate in answering the potential clinical questions that a physician seeks when investigating MBD. magnesium. alkaline phosphatase. which can be missed on routine health screening. DOI:10. calcium. creatinine. So this audit was conducted to determine the utility of BHSP in identifying disorders of parathyroid gland secretion.

Aga Khan University (AKU) for assessing the diagnostic utility of BHSP. Processing and Analysis of Samples in Bone Health Screening Panel: Venous blood samples were collected after overnight fast (10-12 hours) to standardize sample collection and to avoid changes due to diurnal variation and diet. Grouping of Subjects into Hyper and Hypo-functioning States: Subjects were grouped into hyper and hypo-functioning states based on the upper and lower cut-offs of the analytes used in BHSP. Patients were referred by physicians for biochemical evaluation of bone health status. Corrected calcium was measured using the formula [measured Ca + 0. II. USA) three times a year. US). Serum 25OHD was determined by electrochemiluminescence immunoassay method on Liaison auto analyzer (Diasorin the Diagnostic Specialist. Department of Pathology and Laboratory Medicine. Serum corrected calcium was used instead of serum total calcium if low albumin (<4mg/dl) was found.OR © 2016 AACE. alkaline phosphatase. This panel was introduced for patient testing at AKUH Clinical Laboratories in 2011. Data Analysis: I. NY. Classification of Subjects into Groups of PTH Disorders: Clinical phenotypes of PTH disorders were grouped based on upper and lower cutoff of calcium and iPTH after excluding VDD (<20ng/ml) as follows: DOI:10. Most patients were outside referrals. About 10 ml of venous blood was collected into a gel top vacutainer and an EDTA tube. for which only biochemical data were available only. . creatinine. Manufacturer provided controls were run with each batch of all analytes for internal quality control.albumin)]. The reference ranges used for all analytes are shown in table 1. phosphorus. Calcium.MATERIALS AND METHODS: Data Collection: A retrospective analysis was conducted at Section of Clinical Chemistry. while 111 patients were registered at the Aga Khan University Hospital Karachi for clinical consultation. Laboratory data of patients tested for this panel from 1st January 2011 till December 31st 2013 was retrieved from integrated laboratory management systems. Italy). US) and plasma iPTH was performed on Immulite 2000 (Siemens Healthcare Diagnostics Inc. albumin were performed on Advia 1800 Chemistry analyzer (Siemens Healthcare Diagnostics Inc. magnesium.4158/EP161206.08 × (4 . External proficiency was assured by simultaneously analyzing samples from College of American Pathologist (CAP. NY.

Analysis of variance was done and mean and SD of all analytes for five clinical groups were generated. This equation calculates subject specific expected PTH on the basis of his or her total calcium. iPTH >87pg/ml.6-10.2mg/dl. and age measured on the same day. 25OHD. Normocalcemic hyperparathyroidism (NCHP) (calcium 8.6mg/dl. DOI:10.OR © 2016 AACE. iPTH >25pg/ml). Secondary hyperparathyroidism (sHPTH) (25OHD <20ng/ml. Ethical Consideration: Study was done in accordance with Helsinki’s ethical code. iPTH 16-87pg/ml).5 × 25OHD) + (0. calcium <10.2mg/dl. 5. 6. 3. iPTH>87pg/ml). 25OHD >20ng/ml). Functional hypoparathyroidism (25OHD <20ng/ml. calcium <10. Cutoff of >25pg/ml was used for iPTH based on study of Lungren et al (5). The equation predicts a patient-specific upper limit of normal PTH with 95% confidence interval. 4. 25OHD>20ng/ml. 1. Primary hypoparathyroidism (calcium <8.2mg/dl. Exemption was sought from Institution’s Ethical Review committee (ERC number: 2894-Pat-ERC-14) Data Analysis: The statistical analysis was performed using the Statistical Package of Social Sciences (SPSS) version 19. . 25OHD>20ng/ml). iPTH >87pg/ml. in subjects identified with NCHP and hypercalcemia with inappropriately normal PTH (8). 2. Frequency was generated for gender and means with standard deviation (SD) for continuous variables. Primary hyperparathyroidism (PHP) (calcium>10.4158/EP161206.2mg/dl. Hypercalcemia with inappropriately normal iPTH (calcium>10.(0. Clinical Validation of Phenotypes of Parathyroid Gland Disorders: Medical records of subjects enrolled at AKUH for clinical consultation were reviewed for clinical correlation and validation of biochemical findings by BHSP. iPTH <16pg/ml). Biochemical validation of Hyperparathyroidism by Application of PTH Nomogram to Calculate maxPTH: PTH nomogram developed by Harvey et al [120 .25 × age)] was used to calculate maxPTH. IV.III. To maintain confidentiality coding was given to patients and their original identifications were removed.2mg/dl.(6 × calcium) .

4158/EP161206. Sixty five percent subjects were females with mean age of 44. VDD and insufficiency were the predominant abnormalities identified in 60% (n=318) and 20% (n=109) of the subjects respectively. Fourteen subjects with incomplete information were excluded and analysis to determine biochemical phenotype was performed on 534 subjects. registered at AKUH were reviewed for clinical validation (figure 1).OR © 2016 AACE. Mean iPTH levels were suggestive of sHPTH in VDD group only (mean iPTH 87 ± 127pg/ml) while mean iPTH in the insufficient (65±36ng/ml) and sufficient group (74±51ng/ml) was within the reference interval. 5 had high iPTH levels suggestive of PHP. . insufficiency and sufficiency (data not shown). with only 19. while 10 subjects had hypercalcemia with inappropriately normal iPTH. Mean levels of calcium. Overall mean iPTH in VDD was high. Distribution of Subjects into Phenotypes of Parathyroid Hormone Dysfunction: PTH disorders were classified on 497 subjects after excluding those with high creatinine. Table 2 depicts the frequency and mean blood levels in different phenotypes of parathyroid gland disorders from figure 1. Table 1 shows the mean biochemical parameters of 534 subjects grouped into hyper. Pakistan.RESULTS: General Characteristics of the Study Subjects: Five hundred and forty eight subjects were tested with BHSP from January 2011 till December 2013 at the Section of Clinical Chemistry Pathology. Department of Pathology & Laboratory Medicine. Mean iPTH was high and mean 25OHD was in insufficient range. defined in methodology section. Secondary hyperparathyroidism to VDD was present in 17. Among them.7% (n=88) while 39% (n=194) had functional hypoparathyroidism. Thirty seven subjects DOI:10. clinical details of 111 subjects. Among the twenty subjects with hypercalcemia (mean calcium 10. Magnesium deficiency was not related to functional hypoparathyroidism. calcium. alkaline phosphatase and phosphorus.and hypo-functioning states on the basis of reference interval used by the laboratory.6±0. Abnormalities of secretion were identified in 340 subjects. Figures 1 & 2 shows distribution of subjects into various phenotypes of parathyroid hormone dysfunction based on calcium. suggestive of renal pathology. phosphorus and alkaline phosphatase were within the reference interval and were not reflective of VDD.5±17 years. 25OHD and iPTH cutoffs. Mean levels of other analytes were in normal range. High creatinine was found in 7% of subjects (n=37). Aga Khan University Hospital (AKUH) in Karachi.8% of the subjects having optimal 25OHD levels. One subject had 25OHD levels greater than 150ng/ml with normal iPTH. however subjects with low and high levels were identified for each of analyte.59mg/dl).

NCHP and hypercalcemia with inappropriately normal PTH to identify subject specific upper limit of PTH on the basis of age. PHP and hypercalcemia with inappropriately normal iPTH levels was identified in 7. respectively. 6 had osteoporosis and 6 subjects had osteopenia identified on DXA scanning. History of having renal stone was identified in one subject. 3 on Sestamibi scan of parathyroid glands and 1 on ultrasound neck. All subjects with PHP and NCHP had higher PTH levels than calculated maxPTH.75 only. as shown in table 3. More than half of these subjects (n=42) had pain either in joints or generalized. phosphorous.OR © 2016 AACE. Four subjects. VDD with sHPTH and functional hypoparathyroidism were identified in 22 and 42 subjects. Statistically significant differences were seen in calcium. A subject each of NCHP and hypercalcemia with inappropriately normal PTH had renal stones. Three subjects with NCHP reviewed. Clinical Validation of Biochemical Phenotypes Tested for BHSP: Clinical charts of 111 subjects were reviewed. Identification of Primary Hyperparathyroidism using maxPTH Nomogram: The maxPTH nomogram was applied in subjects grouped in PHP. were diagnosed with osteopenia based on low bone density on DXA scan. . 6 had PTH < maxPTH showing normal PTH response to hypercalcemia and 2 had PTH = maxPTH. 2 and 3 subjects respectively. Bone pain and myalgias present in 66% (n=73) of subjects. Thirty two per cent (n=35) subjects did not show any abnormality in the biochemical parameters. DOI:10. Symptoms of generalized myalgia’s and bone pains were predictive of underlying PHP/NCHP. were the major indications for screening with BHSP. distribution is shown in table 3.75±4. Proximal myopathy was present in 7 subjects.4158/EP161206. while in only 2 subjects PTH > maxPTH but the mean difference in PTH and maxPTH was 16. NCHP. 6 subjects had fractures.were identified with NCHP and primary hypoparathyroidism was observed in 2 subjects only. 25OHD and iPTH levels among the different phenotypes while significant difference was not found in alkaline phosphatase and magnesium levels (table 2). calcium and 25OHD. one each in PHP and hypercalcemia with inappropriately normal PTH and two in NCHP. were identified with parathyroid adenoma. In subjects of hypercalcemia with inappropriately normal PTH.

Phenotypes of PHP classified on biochemical cutoffs were validated by maxPTH nomogram and further correlated with clinical presentation. 3). This was later used by Sahota et al and Amouzougan et al to describe subjects presenting with hypovitaminosis D but with normal PTH levels (11. circadian variation as a cause of blunted response of iPTH was also ruled out (15).4158/EP161206. This pattern of PTH response has been frequently observed in our patients (personal observation) and also reported in previous studies from our Centre in healthy volunteers and in community dwelling females (2. The most common MBD in our subjects is VDD either with sHPTH or functional hypoparathyroidism. DOI:10. rather just vitamin D deficiency without secondarily increased PTH secretion but with robust calcium absorption (12). In this dataset only 15 subjects with functional hypothyroidism had hypocalcemia while the rest had normal calcium levels. With increased recognition of these phenotypes. The first recognition of ‘functional hypoparathroidism’ as a distinct entity was described by RK Rude in 1976 (10).DISCUSSION: Our data demonstrates that BHSP helps identify parathyroid gland dysfunction.OR © 2016 AACE. According to guidelines by Endocrine Society on PHP. This also has implication for management of VDD. Awareness of biochemical phenotypes of PHP may facilitate earlier diagnosis. The same findings have been reported from India in a retrospective review of laboratory database (14). As all the samples were collected in fasting state therefore. This approach enhanced the diagnostic accuracy in subjects with atypical biochemical findings. which is considered an important factor for functional hypoparathyroidism. did not relate with the blunted response of parathyroid gland in VDD in subjects studied in present dataset. . 12). Similar to the findings reported by Subramanian et al magnesium deficiency. However. we anticipate the prevalence of hyperparathyroidism to increase beyond what is currently reported in literature in our population. where every symptom of bone pain is currently linked to vitamin D deficiency. repeat measurement of iPTH and calcium is required for confirmation of PHP (9). Since ours was a retrospective analysis. While understanding this entity one should bear in mind that functional hypoparathyroidism is not a type of primary hypoparathyroidism at all (which presents with hypocalcemia and hypoparathyroidism). we used a multidimensional nomogram to estimate maxPTH for differentiating between normal and disease phenotypes. there is debate to recognize it as a distinct entity as vitamin D is not directly regulating PTH secretion rather it is affected by calcium and phosphorus levels (13).

0 mg/dl or 2.1% (109 out of total 5202) post-menopausal women with hyperparathyroidism. one of them was identified with parathyroid adenoma on Sestamibi scan and renal stone. Reevaluation of 99 women with NCHP eight years after screening identified 48 women who developed PHP (5). Lundgren et al revisited PHP in menopausal women with serum calcium in the upper normal range (≥10. NCHP can be easily missed if only serum calcium or PTH is performed or both are performed but on separate occasions (12-15).5mmol/l) 8 years after (2002) population based screening in 19911992 in Sweden. followed by the development of frank hypercalcemia in some cases. in which PTH levels are elevated first but serum calcium remains normal. The term “Normohormonal primary hyperparathyroidism” has been used (NHPHP) for the phenotype (19). showed higher measured iPTH levels than calculated maxPTH using PTH nomogram of Harvey et al (8) indicating altered secretion.4158/EP161206. The measured iPTH was lower than the calculated maxPTH in 8 subjects. Hence it is important to understand that NCHP not an indolent condition. Two patients had high measured iPTH and on chart review. He identified 2. osteopenia. Patients were easily missed but with increasing awareness more patients are now being diagnosed and referred for surgical evaluation (18). indicating normal response of PTH to hypercalcemia.5%) in this study. Based on this and similar findings. . Simultaneous screening with multiple biochemical markers including creatinine and 25OHD is required to diagnose this condition (17). In 2013 NCHP was reported for the first time among community-dwelling individuals by screening of unselected. Subjects grouped as NCHP. Recently a systematic analysis of the largest cohort of hypercalcemia with inappropriately normal PTH has been published. non-referral populations from subjects enrolled in Osteoporosis in Men & Dallas Heart Study (16). and 66% of them exhibited normocalcemia (4). NCHP is considered as a subclinical condition. myalgias. Positive localization provides more evidence in support DOI:10. Although NCHP has long been recognized as a phenotype of PHP. with follow-up and monitoring by biochemical testing at multiple time points.OR © 2016 AACE. An ultrasound examination and a Sestamibi scan should be performed.NCHP is recognized as the next frequent PTH abnormality (8. Hypercalcemia with inappropriately normal iPTH was observed in 10 subjects. The literature on this manifestation of PHP is scant and consists of mainly case reports. and osteoporosis were identified on chart reviews in NCHP. High prevalence of bone pains. little is known about its epidemiology or natural history. Malignancy should be excluded as the cause of hypercalcemia. Patient’s overall health should be critically reviewed for presence of consequences of PHP.

This BHSP can be performed for routine health screenings or as a preliminary screening tool for identifying PTH related disorders for those at high risk of MBDs. such as elderly. internists. rheumatoid arthritis and other connective tissue disorders. thyroid disorders. bone malignancies. especially in when the world is facing epidemic of VDD. It can be helpful for at least yearly screening of high risk population for MBDs (20-25). Whilst plasma iPTH can identify abnormal levels. inflammatory bowels disease. full characterization of the type of hyperparathyroidism requires evaluation of the other parameters included in the BHSP. The patient should also be counseled regarding the possibility that the parathyroid glands may be found to be normal at surgery. patients should be extensively counseled regarding the potential benefit of halting the progression of the disease with surgery.of the diagnosis. DOI:10. CONCLUSION: Parathyroid hormone related disorders are not rare and have potential impact on bone health. . changes due to pre-analytical variables are eliminated. Paget’s diseases.OR © 2016 AACE. At the same time. BHSP provides early diagnosis and facilitates management of such diseases. It is therefore desirable to popularize this Test Panel’s use amongst physicians especially geriatricians. thalassemia. endocrinologists. multiple myeloma. in parts of the world with extant VDD. metastatic cancers. postmenopausal women. orthopedic surgeons and rheumatologists. risks of surgery. and the alternative of observation. patients with CKD.4158/EP161206. rheumatological diseases. By collecting samples for all analytes at the same time.

AHK: Conception and design of study.COMPETING INTERESTS: All authors have no competing interests. acquisition of data. DOI:10. HK: Acquisition of data and manuscript review.OR © 2016 AACE. Review and revising manuscript critically for intellectual content MR: Conception and design of study. . analysis and manuscript writing. JT: Review and revising manuscript critically for intellectual content All authors read and approved the final manuscript. AUTHORS’ CONTRIBUTIONS: HM: Design of study. acquisition of data and manuscript review.4158/EP161206.

Vanderschueren D. Lundgren E. vitamin D-based. 7. 6. 2012. Lindstedt G. Ghani F. Pakistan. Prevalence of vitamin D deficiency and its correlates: results of a community-based study conducted in Karachi. Iqbal R. Akerstrom G. et al. Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women. Khan AH. A new. World J Surg. Hagstrom EG.7:275-82. 2011. Eggertsen R. 2012. Bone health status of premenopausal healthy adult females in Pakistani females. Rastad J. Eur J Endocrinol. Lundin J. 2. Primary hyperparathyroidism revisited in menopausal women with serum calcium in the upper normal range at population-based screening 8 years ago. 2002. Naureen G. Scand J Prim Health Care.151:297-304.OR © 2016 AACE. Johansson E. multidimensional nomogram for the diagnosis of primary hyperparathyroidism. Lundgren E. Primary hyperparathyroidism: diagnosis and management in the older individual. Nystrom E. Ljunghall S.REFERENCES: 1. 4. Gupta M. . Harvey A. 2005.10:192-7. Thrufjell E. Hu M. Iqbal R.26:931-6. 1992. 5. Arch Osteoporos. Arch Osteoporos. Dar FJ. Khan AH. 3. Endocr Pract. Lundberg PA. Fahim F. Pelemans W. Dar FJ. et al. 1997.7:93-9. Siddiqui I. Bouillon R. J Pak Med Assoc. Surgery. Screening of an elderly population in primary care for primary hyperparathyroidism. Boonen S. 8. DOI:10.4158/EP161206. 2004.18:124-31.55:500-2. Ahmed FN.121:287-94. The magnitude of low bone mineral [corrected] density in middle and old age women.

2009. Chopin F. 11. 2014. Reiss E. J Clin Invest. 13. 1976.OR © 2016 AACE. Functional hypoparathyroidism in postmenopausal women with fragility fracture. Hosking DJ. Joint Bone Spine.4158/EP161206. Oldham SB. DOI:10. Kannan S. Tyler FH. Indian J Endocrinol Metab. Clin Endocrinol (Oxf). Hypovitaminosis D and ‘functional hypoparathyroidism’—the NoNoF (Nottingham Neck of Femur) study. Sahota O. 2011. .51:2040-6. Singer FR.9. Thomas T.18:821-5. Mahadevan S. Khan AA. Jubiz W. Age and ageing. Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Circadian rhythm in serum parathyroid hormone concentration in human subjects: correlation with serum calcium. 15. Potts Jr JT. Rude RK. 2012. albumin. 10. Joint Bone Spine.5:209-24.94:335-9. 12. Bilezikian JP.79:170-5. et al. 2001. Laporte S. Velayutham P.30:467-72. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. Gaynor K. Secondary hyperparathyroidism does not develop in patients with low 25(OH)D3 levels: review of parathyroid hormone regulation. Laroche M. author reply 30. The Journal of Clinical Endocrinology & Metabolism. 14. Vico L. Harwood RH. phosphate. Canterbury JM.79:529. and growth hormone levels. Estimation of magnesium in patients with functional hypoparathyroidism. Amouzougan A. 1972.

253:585-91. Taher AT. Musallam KM. Svara F. et al. 18.48:425-32. Haidar R. Campenni A. Ruggeri RM. 2009.35 Suppl 1:3-6. 19. Ann Surg. et al. Maalouf NM. 2010. Agnew JE. Wang PY. Cusano NE. 22. et al. Tuck SM. J Ren Care.150:1102-12. Lin Z. 17. Gonzalez EA.98:2734-41.103:911-5. Br J Haematol. 23. The superiority of minimally invasive parathyroidectomy based on 1650 consecutive patients with primary hyperparathyroidism. 21. 2011.19:486-92.4158/EP161206. J Bone Miner Metab. DOI:10. Udelsman R. Ross LV. .18:875-85. Chronic kidney disease-mineral and bone disorder (CKD-MBD): a new term for a complex approach. 2012. Bone disease and skeletal complications in patients with beta thalassemia major. Hamada Y. [Chronic kidney disease (CKD) and bone. 2010. 2009. Jensen CE. 24. The mechanisms of chronic kidney disease--mineral and bone disorder (CKD-MBD)]. 20. Donovan P. Normocalcemic hyperparathyroidism and hypoparathyroidism in two community-based nonreferral populations. The phenotype of primary hyperparathyroidism with normal parathyroid hormone levels: how low can parathyroid hormone go? Surgery. 2013. Metabolic bone disease in chronic kidney disease. J Am Soc Nephrol. Fukagawa M.16.30:367-72.OR © 2016 AACE. Wallace LB. High prevalence of low bone mass in thalassaemia major. 2007. Parathyroid carcinoma presenting as normocalcemic hyperparathyroidism. J Clin Endocrinol Metab. Clin Calcium. Martin KJ. Bone. 1998. Parikh RT. et al. Sindoni A.

DOI:10. 2006. Christiansen C. . Karsdal MA. Leeming DJ. Biochemical approach to the detection and monitoring of metastatic bone disease: What do we know and what questions need answers? Cancer Metastasis Rev.4158/EP161206.OR © 2016 AACE.25:659-68. Tanko LB.25.

Figure 1: Consort Diagram Showing the Selection and Distribution of Subjects Tested for BHSP at AKUH Clinical Laboratories. BHSP performed January 2011 to December 2013 n = 548 Data Collection and Analysis Incomplete BHSP data excluded n = 14 Subjects with Complete BHSP data n = 534 High Creatinine excluded n = 37 Subjects with Normal Creatinine n = 497 Medical records review Classification of Parathyroid Disorders No Parathyroid Pathology detected n = 161 Groups of Parathyroid Hormone Disorders n=336 Hypercalcemia with Inappropriately normal PTH n=10 Primary Hypoparathyroidism n=2 sHPTH n=88 n=22 n=3 n=2 Functional Hypoparathyroidism n=194 NCHP n=37 PHP n=5 n=7 n=0 n=42 .

2 mg/dl) and each data point is represented by a study subject tested by bone health profile .Figure 2: Distribution of Subjects Tested for BHSP into Clinical Phenotypes of Parathyroid Hormone Disorders based on Calcium and iPTH (n=340) Reference lines on X axis represent upper and lower cut off for PTH (16 & 87 ng/ml) while on Y axis are cutoffs for Ca (8.6 & 10.

0) 25 (4.9 Vitamin D (25OHD) (ng/ml) Corrected Calcium (Ca) 8.2±4.8±137.3 0.6-2.5 mg/dl Alkaline Phosphatase (ALP) 45-129 IU/l Magnesium (Mg) 1.9±5 Deficiency (<20) 318 (59.28±0.5) 11.8 103.2 g/dl Phosphorus (Phos) 2.6-1.5-4.4) 24±2.8-1.2 mg/dl Albumin (Alb) 3.6) 177±223 7.9±0.5 2.6-10.Table 1: Biochemical Characteristics of Subjects Tested with BHSP from January 2011 to December 2013 at AKUH Clinical Laboratories (n = 534) Analytes Mean ± SD Intact PTH (iPTH) 16-87 pg/ml 91.5±18.8±79.3 9.5-5.8 Optimal (>30) 7R[LFLW\•.3 mg/dl 21.6 mg/dl Creatinine (Cr) Female 0.5±0.2mg/dl Male 0.3 Insufficiency ( 20-30) 109 (20.3±0.2±0.78 4.4 3.8 Hyper/Hypofunctioning States High iPTH (>87) Low iPTH (<16) Frequency (%) Mean±SD 150 (28.

1) 49±20 High Ca (>10.5) Low Phos (<2.9) 10.6±0.7) 15 (0.4) High ALP (>129) Low ALP (<45 ) High Mg (>2.4±0.1) 19 (3.4±1 2.4 1.4 5.3 3±0.1 The data is presented as the frequency and mean levels of total.6) 3.3±0.7 2.2) 14 (2.3) 24 (4.6 ) 45.2 Male (>1.3±0.7) High Cr 8.8) 01 (0.5±2.05 5.4) 4 (0.2 228±139 39±4.4) 4 (0.5) High Phos (>4.9 (8. high and low results of all analytes.2) 20 (3.9±0.3) 7 (1. .6 ) Low Mg (<1.2) Low Alb (<3.2±0.3) 2.1±2 Female(>1.6) High Alb (>5.9) 33 (6. 106 (19.59 Low Ca (<8.5) 66 (12.3) 23 (4.

1 37±27 10.2±4.2 88 (17.9 13±1.9 4.83 0.00 0.39 3.1±0.01 0.2±0.3±0.6 3.2 37 (8.2 9±0.3 Functional Hypoparathyroidism 194 (39) 56±21 12±4.6±19 9. .3 3.6 63±2 2.6 102±72 2.2±0.6±0.2 10 (2) 43±11 32±19 10.1 p-value - 0.2±0.24 Hypoparathyroidism 2 (0.3 9. and number (percentages).27 5.7 113±110 2.4±0.5 88±49 2.3±0.4±0.2±0.2±0.00 0.2±0.4±8.22 Parathyroid Gland Abnormalities Primary Hyperparathyroidism Hypercalcemia with inappropriately normal iPTH Normocalcemic Hyperparathyroidism Secondary Hyperparathyroidism n(%) Results are presented as mean ± standard deviation.5 3.Table 2: Frequency and Mean Blood Levels of Biochemical Parameters in BHSP for Subjects categorized into Clinical Groups of Parathyroid Hormone Disorders (n=340) iPTH 25OHD Ca Phos ALP Mg pg/ml ng/ml mg/dl mg/dl IU/l mg/dl 5 (1) 97±41.11 3.7±6.6±1 101±55 2.4±0.7) 170±203 11.4) 9.00 0.7 175±210 2.7±0.4±0.5) 126±46 39.

Parathyroid Gland Abnormalities Measured PTH pg/mL Calculated maxPTH Frequency of subjects with PTH > maxPTH Primary Hyperparathyroidism 97±41.1 54±12 5 Hypercalcemia with inappropriately normal iPTH 43±11 51±11 2 Normocalcemic Hyperparathyroidism 126±46 56±12 37 Clinical Diagnosis Adenoma 1 Fracture 1 Adenoma & Renal stones 1 Adenoma 2 Osteopenia 3 Renal stones 1 The maxPTH was calculated using Harvey et al PTH nomogram {120 . . Normocalcemic Hyperparathyroidism. and Hypercalcemia with Inappropriately Normal PTH using PTH nomogram. and number (percentages). Results are presented as mean ± standard deviation.25 × age)}.5 × 25OHD) + (0.(6 × calcium) .Table 3: Maximum Estimated PTH of Patients with Primary Hyperparathyroidism.(0.