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Year : 2018  |  Volume : 6  |  Issue : 4  |  Page : 122-125

Correlations between parathyroid hormone level, adenoma size, and serum calcium level in patients with primary hyperparathyroidism

Department of Surgery, College of Medicine, Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia

Date of Web Publication13-Dec-2018

Correspondence Address:
Dr. Jubran Al Faifi
Assistant Professor of Surgery, Department of Surgery, College of Medicine, Imam Muhammad Ibn Saud Islamic University, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ssj.ssj_79_17

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Aim: The main goal of this study is to determine the association of preoperative parathyroid hormone (PTH) levels with parathyroid gland adenoma sizes and serum calcium levels in patients with primary hyperparathyroidism caused by single-gland adenoma.
Methods: We included all patients with single parathyroid gland adenoma who were admitted to and underwent parathyroidectomy at Security Forces Hospital in Riyadh during a period of 10 years from January 1, 2000 to October 30, 2011. PTH level and serum corrected calcium were recorded 1 day before surgery. Adenoma size was recorded from pathology reports for all patients.
Results: In 35 cases of parathyroid adenoma including 12 males (34.3%) and 23 females (65.7%) with an average age of 48.94 years (±13.52), the average PTH level 1 day preoperatively was 769.94 pg/mL (±793.27), the average largest dimension (LD) of parathyroid adenoma was 2.18 cm (±1.38), and the average calcium level 1 day preoperatively was 2.71 mmol/L (±0.3). The mean PTH level in males was 1098.5 pg/mL compared to 598.5 pg/mL in females (P = 0.068), mean LD of parathyroid adenoma in males was 2.34 cm versus 2.09 cm in females (P = 0.72), and mean calcium level in males was 2.70 mmol/L compared to 2.72 mmol/L in females (P = 0.46). A positive correlation was found between PTH level and adenoma size, with a correlation coefficient of 0.29 (P = 0.095). The correlation between PTH level and calcium level was negative, with a correlation coefficient of −0.033 (P = 0.85). Negative correlation was also found between adenoma size and calcium level, with a correlation coefficient of −0.033 (P = 0.85).
Conclusion: Based on the findings of this study, preoperative PTH level or serum calcium level cannot be used to predict adenoma size. Further prospective studies with larger sample sizes are recommended.

Keywords: Adenoma, calcium, hormone level, hyperparathyroidism, parathyroid gland

How to cite this article:
Al Faifi J. Correlations between parathyroid hormone level, adenoma size, and serum calcium level in patients with primary hyperparathyroidism. Saudi Surg J 2018;6:122-5

How to cite this URL:
Al Faifi J. Correlations between parathyroid hormone level, adenoma size, and serum calcium level in patients with primary hyperparathyroidism. Saudi Surg J [serial online] 2018 [cited 2019 Jun 25];6:122-5. Available from: http://www.saudisurgj.org/text.asp?2018/6/4/122/247420

  Introduction Top

Hyperparathyroidism is a disease known since ancient times, being mentioned in literature sources from 7000 years ago.[1] It is classified as primary, secondary, or tertiary hyperparathyroidism based on the etiology of disturbances in thyroid gland function. Primary hyperparathyroidism (PHP) is a common disorder of the gland which affects all age groups with a peak in the sixth decade of life.[2] Female-to-male incidence ratio has been found to be 3:1 in several epidemiological studies.[1],[2] PHP is defined based on an elevation in serum-ionized calcium in the setting of inappropriate elevation in parathyroid hormone (PTH) with or without clinical symptoms.[1],[2],[3]

Parathyroid adenoma is known as the single most common cause of PHP, accounting for up to 90% of cases. It can originate in any of the four glands but is more common in the lower glands.[3] Studies have shown that parathyroid adenomas are monoclonal proliferations and that these tumors arise from neoplastic proliferations of a single abnormal cell.[1],[2],[3] Multiple parathyroid adenomas have been reported in 2%–4% of cases and approximately 15% of patients with PHP diagnosed histologically with hyperplasia show involvement of all four parathyroid glands.[4] PHP can also present as a manifestation of multiple endocrine neoplasia syndromes Type I and Type II.[4],[5]

The majority of PHP cases are asymptomatic initially and present with abnormal serum calcium levels in routine laboratory investigations for other clinical presentations.[6] In addition to hypercalcemia, PTH is abnormally elevated.[7] Abnormal laboratory findings mandate clinical workup to identify the cause, which includes radiological evaluation and localization of abnormally functioning parathyroid gland.[8] Almost all clinical guidelines agree on preoperative means to localize the hyperfunctioning gland, which includes neck ultrasound scan, neck computed tomography scan, neck magnetic resonance imaging, or sestamibi parathyroid scintigraphy.[7],[8],[9] Neck exploration is indicated when preoperative localization methods fail to localize the abnormal gland.[8],[9] Recently, intraoperative PTH monitoring has been found to be helpful in localizing the abnormal gland and minimizing the rate of reoperation.[7],[8],[9],[10]

In general, surgical intervention to remove the hyperfunctioning parathyroid gland is the gold standard for treating patients with PHP.[10] Surgical approaches are variable and all of them are aimed at removing the abnormal glands and minimizing the rate of reoperation.[10],[11] Intraoperative PTH monitoring with preoperative localization studies has enabled a success rate of minimally invasive parathyroidectomy in PHP as high as 98%, which also minimizes the rate of reoperation.[11],[12],[13]

The main goal of this study was to determine the association of preoperative PTH levels with parathyroid gland adenoma size and serum calcium level in patients with PHP caused by adenoma.

  Methods Top

This was a retrospective study in which all included cases were reviewed to obtain all the data required.

Inclusion criteria included all patients who were admitted to the Security Forces Hospital in Riyadh, Saudi Arabia, and diagnosed with PHP caused by single parathyroid gland adenoma and who underwent parathyroidectomy during a 10-year period from January 1, 2000 to December 31, 2010.

All cases of hyperplasia, carcinoma, and multiple adenomas were excluded from the study.

For all patients, data were collected from medical records to include medical record number, sex, age, date of surgery, preoperative corrected serum calcium level (normal range 2.20–2.55 mmol/L), preoperative intact PTH level (normal range 11–55 pg/mL), and the largest dimension (LD) of adenoma in centimeters as per the histopathology report.

All data were collected and prepared for analysis. The software SPSS Software (Statistical Package for the Social Sciences) version 18.0 by IBM, Armonk, New York 10504-1722, United States was used for data entry and analysis.

  Results Top

Thirty-five patients in total were included in our review. The sample included 12 males (34.3%) and 23 females (65.7%) as shown in [Table 1], with an average age of 48.9 years. [Table 2] shows the average levels of PTH and corrected calcium level 1 day before surgery. It shows also the average LD in centimeters of adenoma as reported in the histopathology report postoperatively.
Table 1: Patients distribution according to their gender

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Table 2: Mean values of variables among all included patients

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Comparison between males and females with respect to levels of PTH and serum calcium as shown in [Table 3] did not reveal statistically significant differences. Preoperative PTH levels were higher in males while serum calcium levels were higher in females. Adenoma size also did not show any significant differences between males and females and neither did PTH and corrected serum calcium levels.
Table 3: Comparison between males and females: Mann-Whitney U Test

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A positive correlation was found between PTH level and adenoma size [Table 4], with no statistical significance, while the correlation between PTH level and calcium level was unexpectedly negative, with no statistical significance. Further, a negative correlation was found between adenoma size and calcium level as well, with no statistical significance either.
Table 4: Correlation between PTH and serum calcium levels and adenoma sizes: Spearman's rho correlation coefficients

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  Discussion Top

Correlations between biochemical assay parameters and parathyroid adenoma size have been investigated in several studies with variable and conflicting results. Hamidi et al., in 2006, reviewed 71 patients with a mean age of 42.6 years, to identify correlations of preoperative serum calcium, phosphate, and intact PTH levels with parathyroid adenoma mass, and they concluded that PTH level is not a reliable guide for surgeons to estimate adenoma mass.[14] In the same study, PTH was found to be an approximate guide for estimating adenoma mass, with heavy adenomas secreting relatively less PTH than light adenomas, while no association was found with preoperative serum calcium and/or phosphate levels.[14]

In contrast, a positive association was found earlier in 2002 by Bindlish et al., when they retrospectively studied 63 patients with single-gland adenoma and concluded that preoperative serum calcium and PTH levels may be able to predict adenoma mass and volume in PHP caused by a single adenoma.[15]

Earlier in 1985, Rutledge et al. reviewed 92 patients with a mean age of 56 years and found a weak correlation between serum calcium level and size of enlarged parathyroid glands, serum calcium, and parathyroid hormone levels, with a statistically significant association between the hormone levels and size of enlarged glands.[16]

Four years later, Saadeh et al., in 1989, reviewed 24 patients with a mean age of 54.3 years and found that the commercial assays for parathyroid hormone were less sensitive in patients with small tumors and that sensitivity increased with larger tumors.[17]

Correlation between biochemical variables and adenoma mass was assessed in 2007 in a retrospective data analysis study by Randhawa et al. when they analyzed data from 77 patients with PHP with a mean age of 59 years and found that biochemical markers cannot accurately predict adenoma size.[18]

Our results were consistent in general with all the above-mentioned studies. The mean age of our patients reflects the mean age PTH of diagnosis of PHP in Saudi Arabia, which is lesser compared to that reported in western populations.

Regarding correlation with adenoma size, our results showed no significant correlation between preoperative serum calcium and adenoma size, although statistical analysis showed a negative relation which may be explained by Vitamin D deficiency correlating with enlargement of the parathyroid gland.[19] In Saudi Arabia, Vitamin D deficiency is considered prevalent, affecting approximately 30% of Saudi adult females.[20],[21] In our study, females represented 65% of the sample and we presumed that Vitamin D supplements may affect the results.

Comparison between males and females with respect to biochemical and clinical variables found no statistical significance, which may be explained by our small sample size and ratio of males to females. Randhawa et al. concluded that sex had no correlation with biochemical and clinical variables in patients with PHP.[18]

  Conclusion Top

Based on our results, preoperative serum calcium or PTH levels cannot be used to predict adenoma size in patients with PHP. Further prospective studies are recommended for verification and detailed investigation.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Baloch ZW, LiVolsi VA. Pathology of the parathyroid glands in hyperparathyroidism. Semin Diagn Pathol 2013;30:165-77.  Back to cited text no. 1
Rosen JE, Costouros NG, Lorang D, Burns AL, Alexander HR, Skarulis MC, et al. Gland size is associated with changes in gene expression profiles in sporadic parathyroid adenomas. Ann Surg Oncol 2005;12:412-6.  Back to cited text no. 2
Helme S, Lulsegged A, Sinha P. Incidental parathyroid disease during thyroid surgery: Should we remove them? ISRN Surg 2011;2011:962186.  Back to cited text no. 3
Bilezikian JP, Brandi ML, Rubin M, Silverberg SJ. Primary hyperparathyroidism: New concepts in clinical, densitometric and biochemical features. J Intern Med 2005;257:6-17.  Back to cited text no. 4
Rao DS, Honasoge M, Divine GW, Phillips ER, Lee MW, Ansari MR, et al. Effect of Vitamin D nutrition on parathyroid adenoma weight: Pathogenetic and clinical implications. J Clin Endocrinol Metab 2000;85:1054-8.  Back to cited text no. 5
Demıralay E, Altaca G, Demırhan B. Morphological evaluation of parathyroid adenomas and immunohistochemical analysis of PCNA and ki-67 proliferation markers. Turk Patoloji Derg 2011;27:215-20.  Back to cited text no. 6
Moosgaard B, Vestergaard P, Heickendorff L, Melsen F, Christiansen P, Mosekilde L, et al. Plasma 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D is associated with parathyroid adenoma secretion in primary hyperparathyroidism: A cross-sectional study. Eur J Endocrinol 2006;155:237-44.  Back to cited text no. 7
Wheeler MH. Primary hyperparathyroidism: A surgical perspective. Ann R Coll Surg Engl 1998;80:305-12.  Back to cited text no. 8
Erbil Y, Kapran Y, Işsever H, Barbaros U, Adalet I, Dizdaroğlu F, et al. The positive effect of adenoma weight and oxyphil cell content on preoperative localization with 99mTc-sestamibi scanning for primary hyperparathyroidism. Am J Surg 2008;195:34-9.  Back to cited text no. 9
Farmer PE, Kim JY. Surgery and global health: A view from beyond the OR. World J Surg 2008;32:533-6.  Back to cited text no. 10
Velázquez-Fernández D, Laurell C, Saqui-Salces M, Pantoja JP, Candanedo-Gonzalez F, Reza-Albarrán A, et al. Differential RNA expression profile by cDNA microarray in sporadic primary hyperparathyroidism (pHPT): Primary parathyroid hyperplasia versus adenoma. World J Surg 2006;30:705-13.  Back to cited text no. 11
Amin AL, Wang TS, Wade TJ, Yen TW. Normal PTH levels in primary hyperparathyroidism: Still the same disease? Ann Surg Oncol 2011;18:3437-42.  Back to cited text no. 12
Moretz WH 3rd, Watts TL, Virgin FW Jr., Chin E, Gourin CG, Terris DJ, et al. Correlation of intraoperative parathyroid hormone levels with parathyroid gland size. Laryngoscope 2007;117:1957-60.  Back to cited text no. 13
Hamidi S, Aslani A, Nakhjavani M, Pajouhi M, Hedayat A, Kamalian N, et al. Are biochemical values predictive of adenoma's weight in primary hyperparathyroidism? ANZ J Surg 2006;76:882-5.  Back to cited text no. 14
Bindlish V, Freeman JL, Witterick IJ, Asa SL. Correlation of biochemical parameters with single parathyroid adenoma weight and volume. Head Neck 2002;24:1000-3.  Back to cited text no. 15
Rutledge R, Stiegel M, Thomas CG Jr., Wild RE. The relation of serum calcium and immunoparathormone levels to parathyroid size and weight in primary hyperparathyroidism. Surgery 1985;98:1107-12.  Back to cited text no. 16
Saadeh G, Licata A, Esselstyn C, Gupta M. Relationship of parathyroid adenoma volume and biochemical function. Horm Res 1989;32:142-4.  Back to cited text no. 17
Randhawa PS, Mace AD, Nouraei SA, Stearns MP. Primary hyperparathyroidism: Do perioperative biochemical variables correlate with parathyroid adenoma weight or volume? Clin Otolaryngol 2007;32:179-84.  Back to cited text no. 18
Kirkby-Bott J, El-Khatib Z, Soudan B, Caiazzo R, Arnalsteen L, Carnaille B, et al. 25-hydroxy Vitamin D deficiency causes parathyroid incidentalomas. Langenbecks Arch Surg 2010;395:919-24.  Back to cited text no. 19
Elsammak MY, Al-Wossaibi AA, Al-Howeish A, Alsaeed J. High prevalence of Vitamin D deficiency in the sunny Eastern region of Saudi Arabia: A hospital-based study. East Mediterr Health J 2011;17:317-22.  Back to cited text no. 20
Alsuwadia AO, Farag YM, Al Sayyari AA, Mousa DH, Alhejaili FF, Al-Harbi AS, et al. Prevalence of Vitamin D deficiency in Saudi adults. Saudi Med J 2013;34:814-8.  Back to cited text no. 21


  [Table 1], [Table 2], [Table 3], [Table 4]


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