Home Medicine Correlation between iPTH levels on the first postoperative day after total thyroidectomy and permanent hypoparathyroidism: our experience
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Correlation between iPTH levels on the first postoperative day after total thyroidectomy and permanent hypoparathyroidism: our experience

  • Gian Luigi Canu EMAIL logo , Fabio Medas , Alessandro Longheu , Francesco Boi , Giovanni Docimo , Enrico Erdas and Pietro Giorgio Calò
Published/Copyright: June 7, 2019
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Open Medicine
From the journal Open Medicine Volume 14 Issue 1

Abstract

Permanent hypoparathyroidism is the most common long-term complication after thyroidectomy. We evaluated whether iPTH concentrations on the first postoperative day may be a good predictor of this complication.

Patients undergoing thyroidectomy in our Unit between January 2017 and February 2018 who developed postsurgical hypoparathyroidism were analysed. According to iPTH values on the first postoperative day and on the basis of the detection threshold of the iPTH test used, patients were divided into 2 groups: Group A (iPTH < 6.3 pg/mL, undetectable), Group B (iPTH ≥ 6.3 pg/mL).

Seventy-five patients were included in this study: 64 in Group A and 11 in Group B. Permanent hypoparathyroidism occurred in 14 (21.88%) patients in Group A, while none developed this complication in Group B. When iPTH was < 6.3 pg/mL, the sensitivity for the prediction of permanent hypoparathyroidism was 100%, the specificity was 18.03%, the positive predictive value was 21.88% and the negative predictive value was 100%.

No patient with iPTH ≥ 6.3 pg/mL on the first postoperative day developed permanent hypoparathyroidism. On the other hand, iPTH concentrations < 6.3 pg/mL have not proved to be a strong predictor of this condition. However, this cut-off value can be useful to identify patients at risk of developing this complication.

Keywords: Permanent hypoparathyroidism; Total thyroidectomy; Intact parathyroid hormone; Undetectable iPTH

1 Introduction

Total thyroidectomy (TT) is the most widely surgical procedure performed in endocrine surgery, for both benign and malignant thyroid diseases.

Hypoparathyroidism (HPP) is a common complication after TT [1, 2, 3, 4, 5, 6, 7, 8, 9]. This condition is characterized by decreased values of circulating parathyroid hormone leading to hypocalcemia and slightly higher phosphate levels.

Hypocalcemia can cause symptoms ranging from numbness of the face and hands to tetany, convulsions and suffocation (caused by laryngeal and diaphragmatic spasms). Moreover, manifestations of chronic hypocalcemia include some severe conditions, such as nephrocalcinosis, kidney stones, chronic kidney disease, myocardial dysfunction, basal ganglia calcifications, cataracts and dental abnormalities [10, 11, 12, 13, 14, 15].

In case of HPP, the main purpose of treatment is to maintain normal blood calcium levels. Medical therapy of hypocalcemia consists in the administration of calcium and vitamin D [16].

Although HPP after TT reverses spontaneously within a few months in most cases, in a few patients, it can persist for more than 1 year [4]. In this case this condition has to be considered permanent and, to avoid the subtle but potentially lethal complications of chronic hypocalcemia, long-term therapy and careful follow-up are mandatory. However, long-term calcium supplementation can also cause side effects, such as gastrointestinal reactions, myocardial infarction and urinary calculi [17].

The incidence of transient and permanent hypoparathyroidism is 6.9–46% and 0-10% respectively [2, 5, 18].

Costs to society in terms of increased postoperative stay, sick leave, medical treatments and surveillance, with periodic laboratory testing, are considerable. Moreover, permanent HPP is an important cause of medical litigation.

Currently, there are no reliable immediate postoperative biochemical parameters which allow the identification of those patients with postsurgical HPP who will develop permanent HPP [19]. In order to ensure patients the best follow-up, it would be very useful to be able to predict the risk of permanent HPP at an early stage after surgery. To date, there is still no consensus about the correlation between postoperative intact parathyroid hormone (iPTH) values and the development of this condition [20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34]. The aim of the present study was to investigate this topic. In particular, we evaluated whether iPTH concentrations on the first postoperative may be a good predictor of permanent HPP.

2 Methods

This is a retrospective study on patients who underwent thyroidectomy in our Unit of General and Endocrine Surgery (University of Cagliari) between January 2017 and February 2018.

Only patients with postsurgical HPP after TT were considered. Among these, those simultaneously submitted to lateral and/or central neck dissection were included in this study, while those who simultaneously underwent parathyroidectomy or parathyroid autotransplantation were excluded.

All operations were performed under general anaesthesia. Lateral and/or central neck dissection was performed in patients with preoperative or intraoperative suspicion of lymph node metastases. Recurrent laryngeal nerves and parathyroid glands were systematically searched and identified. Intraoperative nerve monitoring (IONM) was routinely used in order to facilitate nerve identification and to confirm its functional integrity. Haemostasis was mainly achieved by means of energy-based devices. One or two closed suction drains were placed below the strap muscles and removed when the secretion volume was less than 20 ml over 24 hours. The cervical linea alba and platysma were sutured with absorbable sutures and skin was closed by a continuous intradermal suture.

Demographic data (sex, age), information on surgical procedure (extent of surgery) and histopathological findings were recorded.

Serum calcium and iPTH levels were assayed preoperatively and on the first and second postoperative days. Postsurgical HPP was defined as iPTH < 10 pg/mL on the second postoperative day (normal range = 10-65 pg/mL). All patients with postsurgical HPP, even if asymptomatic, received treatment with calcium carbonate (1–3 g/day) and calcitriol (0.5–1.5 μg /day). In case of severe hypocalcemia, intravenous calcium gluconate was used.

According to iPTH values on the first postoperative day and on the basis of the detection threshold of the iPTH test used, patients were divided into 2 groups: those with iPTH < 6.3 pg/mL (undetectable) were included in Group A, those with iPTH ≥ 6.3 pg/mL in Group B.

Permanent HPP was defined as iPTH concentrations below the normal range for more than 12 months.

Intact parathyroid hormone was measured with ADVIA Centaur® XPT Immunoassay Systems (Siemens Healthcare Diagnostics, Inc.).

Statistical analyses were performed with MedCalc® 18.0.2. Fisher exact test was used for categorical variables and t-test for continuous variables. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. P values < 0.05 were considered statistically significant.

Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors' institutional review board or equivalent committee.

Informed consent: Informed consent has been obtained from all individuals included in this study.

3 Results

A total of 75 patients were included in this study. There were 16 (21.33%) males and 59 (78.67%) females, with a mean age of 49.25 ± 16.77 years old. Sixty-six (88%) patients underwent total thyroidectomy, 4 (5.33%) total thyroidectomy with ipsilateral central neck dissection, 3 (4%) total thyroidectomy with central neck dissection

Table 1

Demographic data, information on surgical procedure and histopathological findings.

Total (n = 75) Group A (n = 64) Group B (n = 11) P value
Sex
- Male 16 (21.33%) 15 (23.44%) 1 (9.09%) NS
- Female 59 (78.67%) 49 (76.56%) 10 (99.91%)
Age (mean ± SD) 49.25 ± 16.77 47.91 ± 16.99 57.09 ± 13.55 NS
Extent of surgery
- TT 66 (88%) 56 (87.50%) 10 (90.91%) NS
- TT + ICND 4 (5.33%) 3 (4.69%) 1 (9.09%) NS
- TT + CND 3 (4%) 3 (4.69%) 0 NS
- TT + CND + LND 2 (2.67%) 2 (3.12%) 0 NS
Thyroid weight 58.44 ± 61.08 59.14 ± 63.79 54.36 ± 44.11 NS
(mean ± SD)
Histological diagnosis
- Benign disease 43 (57.33%) 36 (56.25%) 7 (63.64%) NS
- Malignancy 32 (42.67%) 28 (43.75%) 4 (36.36%)

  1. TT, total thyroidectomy; ICND, ipsilateral central neck dissection; CND, central neck dissection; LND, lateral neck dissection

Table 2

Patients who developed permanent HPP.

Total Group A Group B P value
(n = 75) (n = 64) (n = 11)
Permanent 14 (18.67%) 14 (21.88%) 0 NS
hypoparathyroidism

and 2 (2.67%) total thyroidectomy with central and lateral neck dissection. Mean thyroid weight was 58.44 ± 61.08 g. Histopathological diagnosis was benign disease in 43 (57.33%) patients and malignancy in 32 (42.67%).

Of the 75 patients, 64 were included in Group A and 11 in Group B.

In Group A, there were 15 (23.44%) males and 49 (76.56%) females, with a mean age of 47.91 ± 16.99 years old. Fifty-six (87.50%) patients underwent total thyroidectomy, 3 (4.69%) total thyroidectomy with ipsilateral central neck dissection, 3 (4.69%) total thyroidectomy with central neck dissection and 2 (3.12%) total thyroidectomy with central and lateral neck dissection. Mean thyroid weight was 59.14 ± 63.79 g. Histopathological diagnosis was benign disease in 36 (56.25%) patients and malignancy in 28 (43.75%).

In Group B, there were 1 (9.09%) male and 10 (99.91%) females, with a mean age of 57.09 ± 13.55 years old. Ten (90.91%) patients underwent total thyroidectomy and 1 (9.09%) total thyroidectomy with ipsilateral central neck dissection. Mean thyroid weight was 54.36 ± 44.11 g. Histopathological

Table 3

Correlation between iPTH levels < 6.3 pg/mL on the first postoperative day and the development of permanent HPP.

Sensitivity 100%
Specificity 18.03%
PPV 21.88%
NPV 100%

  1. PPV, positive predictive value; NPV, negative predictive value

diagnosis was benign disease in 7 (63.64%) patients and malignancy in 4 (36.36%).

Demographic data, extent of surgery and histopathological findings were comparable between the 2 groups.

Permanent HPP occurred in 14 (21.88%) patients in Group A, while none developed this complication in Group B (this difference was not statistically significant).

When iPTH levels were < 6.3 pg/mL on the first postoperative day the sensitivity for the prediction of permanent HPP was 100%, the specificity was 18.03%, the PPV was 21.88% and the NPV was 100%.

4 Discussion

Despite progress in surgical technique and even in the most experienced hands, postsurgical HPP remains a challenging problem. Permanent HPP is the most common long-term complication after TT [1, 2, 3, 4, 5, 6, 7, 8, 9].

During surgery parathyroid glands can be damaged due to various mechanisms: thermal or mechanical stress, vascular injury (interrupted blood flow or impaired venous efflux) and involuntary removal [7, 31, 35, 36, 37].

Some factors have been associated with an increased risk of developing postsurgical HPP, such as female gender, thyroid cancer, Graves’ disease, autoimmune thyroiditis and central neck dissection [1, 31, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45,].

To date, there is still no consensus about the usefulness of postoperative iPTH levels to predict permanent HPP [20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34]. We evaluated whether iPTH values on the first postoperative day may be a good predictor of this complication. In the literature, we found some similar studies.

Almquist M. et al [29] stated that iPTH levels measured on the first postoperative day are associated with the risk of permanent HPP. In their experience, of 10 patients with permanent HPP, 8 had iPTH < 6.6 pg/mL and 2 had iPTH between 6.6 and 15 pg/mL. However, among the patients with iPTH values < 6.6 pg/mL the rate of this complication was only 19.2%.

In the study of Julián M.T. et al [30], iPTH concentrations ≤ 5.8 pg/mL on postoperative day 1 had 100% sensitivity, 81.5% specificity and 30% positive predictive value for permanent HPP. Conversely, iPTH levels > 5.8 pg/mL were correlated with normal parathyroid function in the long term.

In the experience of Wang J.B. et al [31], iPTH concentrations < 7 pg/mL on postoperative day 1 had sensitivity and negative predictive value of 100% for permanent HPP, but poor specificity and positive predictive value (70.19% and 8.63% respectively).

Kim H. et al [32] stated that the safest cut-off value of iPTH on the first postoperative day for the prediction of permanent HPP is 9.65 pg/mL (70.9% sensitivity and 100% specificity). None of the patients with iPTH > 9.65 pg/mL developed this complication.

In the study of Wang W. et al [33], iPTH levels ≤ 3.14 pg/mL on postoperative day 1 had 100% sensitivity for the prediction of permanent HPP, 95% specificity, 66.67% positive predictive value and 100% negative predictive value. Therefore, these researchers stated that iPTH levels > 3.14 pg/mL are great in assessing the absence of this complication.

Calvo Espino P. et al [34] found that a cut-off value of iPTH on the first postoperative day of 5 pg/mL has 95% sensitivity, 77% specificity, 21.6% positive predictive value and 99.6% negative predictive value for the prediction of permanent HPP. Therefore, they stated that this iPTH level, because of its high negative predictive value, is a useful predictor of permanent HPP.

In our study, we included only patients with postsurgical HPP, diagnosed on the basis of iPTH concentrations on the second postoperative day. According to our experience and that of other researchers, we consider iPTH values on postoperative day 2, rather than on postoperative day 1, more accurate in assessing the true functional state of parathyroid glands after TT. Among the patients considered, iPTH levels on the first postoperative day have been analysed. When iPTH concentrations were < 6.3 pg/ mL, the sensitivity and the negative predictive value for permanent HPP were high (both 100%), but the specificity and the positive predictive value were poor, 18.03% and 21.88% respectively. It is important to underline that no patient with iPTH values ≥ 6.3 pg/mL developed this complication. As already explained above, in our study, the cut-off value was established on the basis of the detection threshold of the iPTH test used. Among the 2 groups obtained in this way, no statistically significant difference was found in terms of demographic data, extent of surgery and histopathological findings.

In light of the results obtained by our and the other studies analysed, to date, a cut-off value of iPTH on the first postoperative day accurate enough for the prediction of permanent HPP has not yet been identified. Thus, further larger and possibly multicenter studies are needed to better investigate this topic.

5 Conclusions

No patient with iPTH levels ≥ 6.3 pg/mL on the first postoperative day after TT developed permanent HPP. On the other hand, iPTH concentrations < 6.3 pg/mL have not proved to be a strong predictor of this condition (PPV, 21.88%; specificity, 18.03%). However, this cut-off value can be useful to identify patients at risk of developing this complication (sensitivity, 100%), who require a careful follow-up.

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  1. Conflict of interest: Authors state no conflict of interest.

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Received: 2019-02-26
Accepted: 2019-04-24
Published Online: 2019-06-07

© 2019 Gian Luigi Canu et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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  11. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and susceptibility to late-onset Alzheimer’s disease
  12. microRNA-1236-3p regulates DDP resistance in lung cancer cells
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  14. The link between thyroid autoimmunity, depression and bipolar disorder
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  16. Effects of miR-107 on the Chemo-drug sensitivity of breast cancer cells
  17. Analysis of pH dose-dependent growth of sulfate-reducing bacteria
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  19. Musculoskeletal clinical and imaging manifestations in inflammatory bowel diseases
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  21. Regional hyperthermia combined with chemotherapy in advanced gastric cancer
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  24. The reliability of adjusting stepped care based on FeNO monitoring for patients with chronic persistent asthma
  25. Comparison of the clinical outcomes of two physiological ischemic training methods in patients with coronary heart disease
  26. Analysis of ticagrelor’s cardio-protective effects on patients with ST-segment elevation acute coronary syndrome accompanied with diabetes
  27. Computed tomography findings in patients with Samter’s Triad: an observational study
  28. Case Report
  29. A spinal subdural hematoma induced by guidewire-based lumbar drainage in a patient with ruptured intracranial aneurysms
  30. Research Article
  31. High expression B3GAT3 is related with poor prognosis of liver cancer
  32. Effects of light touch on balance in patients with stroke
  33. Oncoprotein LAMTOR5 activates GLUT1 via upregulating NF-κB in liver cancer
  34. Effects of budesonide combined with noninvasive ventilation on PCT, sTREM-1, chest lung compliance, humoral immune function and quality of life in patients with AECOPD complicated with type II respiratory failure
  35. Prognostic significance of lymph node ratio in ovarian cancer
  36. Case Report
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  39. Treating infertility: current affairs of cross-border reproductive care
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  46. Compare fuhrman nuclear and chromophobe tumor grade on chromophobe RCC
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  51. Loneliness in the context of quality of life of nursing home residents
  52. Biological characteristics of cervical precancerous cell proliferation
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  54. Management of complications of first instance of hepatic trauma in a liver surgery unit: Portal vein ligation as a conservative therapeutic strategy
  55. Matrix metalloproteinase 2 knockdown suppresses the proliferation of HepG2 and Huh7 cells and enhances the cisplatin effect
  56. Comparison of laparoscopy and open radical nephrectomy of renal cell cancer
  57. Case Report
  58. A severe complication of myocardial dysfunction post radiofrequency ablation treatment of huge hepatic hemangioma: a case report and literature review
  59. Solar urticaria, a disease with many dark sides: is omalizumab the right therapeutic response? Reflections from a clinical case report
  60. Research Article
  61. Binge eating disorder and related features in bariatric surgery candidates
  62. Propofol versus 4-hydroxybutyric acid in pediatric cardiac catheterizations
  63. Nasointestinal tube in mechanical ventilation patients is more advantageous
  64. The change of endotracheal tube cuff pressure during laparoscopic surgery
  65. Correlation between iPTH levels on the first postoperative day after total thyroidectomy and permanent hypoparathyroidism: our experience
  66. Case Report
  67. Primary angiosarcoma of the kidney: case report and comprehensive literature review
  68. Research Article
  69. miR-107 enhances the sensitivity of breast cancer cells to paclitaxel
  70. Incidental findings in dental radiology are concerning for family doctors
  71. Suffering from cerebral small vessel disease with and without metabolic syndrome
  72. A meta-analysis of robot assisted laparoscopic radical prostatectomy versus laparoscopic radical prostatectomy
  73. Indications and outcomes of splenectomy for hematological disorders
  74. Expression of CENPE and its prognostic role in non-small cell lung cancer
  75. Barbed suture and gastrointestinal surgery. A retrospective analysis
  76. Using post transplant 1 week Tc-99m DTPA renal scan as another method for predicting renal graft failure
  77. The pseudogene PTTG3P promotes cell migration and invasion in esophageal squamous cell carcinoma
  78. Lymph node ratio versus TNM system as prognostic factor in colorectal cancer staging. A single Center experience
  79. Review Article
  80. Minimally invasive pilonidal sinus treatment: A narrative review
  81. Research Article
  82. Anatomical workspace study of Endonasal Endoscopic Transsphenoidal Approach
  83. Hounsfield Units on Lumbar Computed Tomography for Predicting Regional Bone Mineral Density
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  86. Research Article
  87. Osteopontin and fatty acid binding protein in ifosfamide-treated rats
  88. Familial polyposis coli: the management of desmoid tumor bleeding
  89. microRNA-27a-3p down-regulation inhibits malignant biological behaviors of ovarian cancer by targeting BTG1
  90. PYCR1 is associated with papillary renal cell carcinoma progression
  91. Prediction of recurrence-associated death from localized prostate cancer with a charlson comorbidity index–reinforced machine learning model
  92. Colorectal cancer in the elderly patient: the role of neo-adjuvant therapy
  93. Association between MTHFR genetic polymorphism and Parkinson’s disease susceptibility: a meta-analysis
  94. Metformin can alleviate the symptom of patient with diabetic nephropathy through reducing the serum level of Hcy and IL-33
  95. Case Report
  96. Severe craniofacial trauma after multiple pistol shots
  97. Research Article
  98. Echocardiography evaluation of left ventricular diastolic function in elderly women with metabolic syndrome
  99. Tailored surgery in inguinal hernia repair. The role of subarachnoid anesthesia: a retrospective study
  100. The factors affecting early death in newly diagnosed APL patients
  101. Review Article
  102. Oncological outcomes and quality of life after rectal cancer surgery
  103. Research Article
  104. MiR-638 repressed vascular smooth muscle cell glycolysis by targeting LDHA
  105. microRNA-16 via Twist1 inhibits EMT induced by PM2.5 exposure in human hepatocellular carcinoma
  106. Analyzing the semantic space of the Hippocratic Oath
  107. Fournier’s gangrene and intravenous drug abuse: an unusual case report and review of the literature
  108. Evaluation of surgical site infection in mini-invasive urological surgery
  109. Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway
  110. Clinico-pathological features of colon cancer patients undergoing emergency surgery: a comparison between elderly and non-elderly patients
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  113. Research Article
  114. Protective effects of specneuzhenide on renal injury in rats with diabetic nephropathy
  115. PBF, a proto-oncogene in esophageal carcinoma
  116. Use of rituximab in NHL malt type pregnant in I° trimester for two times
  117. Cancer- and non-cancer related chronic pain: from the physiopathological basics to management
  118. Case report
  119. Non-surgical removal of dens invaginatus in maxillary lateral incisor using CBCT: Two-year follow-up case report
  120. Research Article
  121. Risk factors and drug resistance of the MDR Acinetobacter baumannii in pneumonia patients in ICU
  122. Accuracy of tumor perfusion assessment in Rat C6 gliomas model with USPIO
  123. Lemann Index for Assessment of Crohn’s Disease: Correlation with the Quality of Life, Endoscopic Disease activity, Magnetic Resonance Index of Activity and C- Reactive Protein
  124. Case report
  125. Münchausen syndrome as an unusual cause of pseudo-resistant hypertension: a case report
  126. Research Article
  127. Renal artery embolization before radical nephrectomy for complex renal tumour: which are the true advantages?
  128. Prognostic significance of CD276 in non-small cell lung cancer
  129. Potential drug-drug interactions in acute ischemic stroke patients at the Neurological Intensive Care Unit
  130. Effect of vitamin D3 on lung damage induced by cigarette smoke in mice
  131. CircRNA-UCK2 increased TET1 inhibits proliferation and invasion of prostate cancer cells via sponge miRNA-767-5p
  132. Case report
  133. Partial hydatidiform mole and coexistent live fetus: a case report and review of the literature
  134. Research Article
  135. Effect of NGR1 on the atopic dermatitis model and its mechanisms
  136. Clinical features of infertile men carrying a chromosome 9 translocation
  137. Review Article
  138. Expression and role of microRNA-663b in childhood acute lymphocytic leukemia and its mechanism
  139. Case Report
  140. Mature cystic teratoma of the pancreas: A rare cystic neoplasm
  141. Research Article
  142. Application of exercised-based pre-rehabilitation in perioperative period of patients with gastric cancer
  143. Case Report
  144. Predictive factors of intestinal necrosis in acute mesenteric ischemia
  145. Research Article
  146. Application of exercised-based pre-rehabilitation in perioperative period of patients with gastric cancer
  147. Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats
  148. MicroRNA-181a-5p regulates inflammatory response of macrophages in sepsis
  149. Intraventricular pressure in non-communicating hydrocephalus patients before endoscopic third ventriculostomy
  150. CyclinD1 is a new target gene of tumor suppressor miR-520e in breast cancer
  151. CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma
  152. Epidemiological characteristics of postoperative sepsis
  153. Association between unstable angina and CXCL17: a new potential biomarker
  154. Cardiac strains as a tool for optimization of cardiac resynchronization therapy in non-responders: a pilot study
  155. Case Report
  156. Resuscitation following a bupivacaine injection for a cervical paravertebral block
  157. Research Article
  158. CGF treatment of leg ulcers: A randomized controlled trial
  159. Surgical versus sequential hybrid treatment of carotid body tumors
https://doi.org/10.1515/med-2019-0047
Keywords for this article
Permanent hypoparathyroidism; Total thyroidectomy; Intact parathyroid hormone; Undetectable iPTH
Creative Commons
BY-NC-ND 4.0

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