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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2015  |  Volume : 26  |  Issue : 6  |  Page : 1199-1204
Kinetics of parathyroid hormone after parathyroidectomy in chronic hemodialysis patients


1 Service de Néphrologie-Dialyse-Transplantation Rénale, CHU Ibn Sina, Rabat, Maroc
2 Service d'Anatomie Pathologique. Hopital d'Enfants, Rabat, Maroc
3 Univérsité Mohammed V Rabat, Faculté de Médecine et de Pharmacie Rabat, Maroc Hôpital Ibn Sina, Service de Chirurgie "A", Rabat, Maroc
4 Univérsité Mohammed V Rabat, Faculté de Médecine et de Pharmacie Rabat, Maroc Hôpital Ibn Sina, Service de Chirurgie "A"; Université Internationale des Sciences de la Santé, Faculté de Médecine Abulcasis, Rabat, Maroc

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Date of Web Publication30-Oct-2015
 

   Abstract 

Secondary hyperparathyroidism is a common complication in chronic renal failure. The treatment in some cases requires parathyroidectomy. The kinetics of the parathyroid hormone (PTH) levels after surgery helps to evaluate the efficacy of parathyroidectomy. Prospective analysis was made of the kinetics of intact PTH (iPTH) after parathyroidectomy in 10 chronic hemodialysis (HD) patients who had secondary hyperparathyroidism. We determined the levels of iPTH before surgery and its evolution after parathyroidectomy at regular intervals: Day 0, D7, D15, D30 and D90. The mean age of our patients was 40 ± 13 years, with a sex ratio of 1. The mean duration on HD was 122 ± 63 months. The duration of secondary hyperparathyroidism varied from one year to 12 years. All patients had received medical treatment for hyperparathyroidism. The indications for parathyroidectomy included resistance to medical treatment in seven cases, development of brown tumors in two cases and soft tissue calcifications in one case. All patients had radiographic evidence of hyperparathyroidism. The parathyroidectomy was sub-total in all patients, 6/8 in four cases and 7/8 in six cases. The mean iPTH level was 2341 ± 1946 pg/mL before surgery. A sharp drop in this level was noticed on D0, with a median of 92 pg/mL and, thereafter, the levels were 79 pg/mL on D7, 25 pg/mL on D15 and 36 pg/mL after 1 month. At 3 months post-surgery, the mean iPTH level was 302 pg/mL. Histological examination of the resected gland showed parathyroid hyperplasia in all patients. In our series, the efficacy of sub-total parathyroidectomy was satisfactory with rapid normalization of PTH, which is consistent with the literature data. Sub-total parathyroidectomy still has a place in the treatment of secondary hyperparathyroidism in chronic renal failure. Its indications should be limited to cases resistant to medical treatment and, in particular, in cases with occurrence of complications.

How to cite this article:
Skalli Z, Elouazzani H, Alhamany Z, Mattous M, Benamar L, Bayahia R, Belkouchi M, El Malki H, Ouzeddoun N. Kinetics of parathyroid hormone after parathyroidectomy in chronic hemodialysis patients. Saudi J Kidney Dis Transpl 2015;26:1199-204

How to cite this URL:
Skalli Z, Elouazzani H, Alhamany Z, Mattous M, Benamar L, Bayahia R, Belkouchi M, El Malki H, Ouzeddoun N. Kinetics of parathyroid hormone after parathyroidectomy in chronic hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Nov 29];26:1199-204. Available from: https://www.sjkdt.org/text.asp?2015/26/6/1199/168622

   Introduction Top


Secondary hyperparathyroidism is a common complication in chronic kidney disease, with variable frequency ranging from 30% to 50%. [1] The secretion of parathyroid hormone (PTH) is stimulated essentially by hypocalcemia, secondary to the decrease in renal synthesis of calcitriol required for intestinal absorption of calcium. The primary management of secondary hyperparathyroidism is medical treatment with calcium, vitamin D, phosphate binders or calcimimetic agents. However, some cases are resistant to medical treatment and develop severe bone complications requiring parathyroidectomy. The levels of intact PTH (iPTH) after surgery are used to evaluate the efficacy of parathyroidectomy. The aim of this work is to follow the kinetics of iPTH after sub-total parathyroidectomy in order to evaluate the effectiveness of this surgery and to detect the occurrence of post-operative complications.


   Patients and Methods Top


Forty-nine patients on hemodialysis (HD) were followed-up for a period of one year (December 2007 to November 2008) to identify those with secondary hyperparathyroidism requiring surgical treatment. The inclusion criteria included terminal renal failure treated by periodic HD and absence of anterior cervical surgery. Secondary hyperparathyroidism was defined by elevation of serum iPTH above 300 pg/mL in chronic HD patients. We analyzed demographic parameters (age and sex), clinical parameters (duration on HD, clinical signs of hyperparathyroidism) and laboratory parameters (serum iPTH, calcium, phosphorus, bicarbonate, alkaline phosphatase and hemoglobin). Radiological signs of osteitis fibrosa were looked for, including bone loss, changes in the skull, resorption of phalangeal tufts and brown tumor. Treatment history including use of calcium and vitamin D, phosphate binders and recombinant human erythropoietin, was noted. The indications for parathyroidectomy included resistance to medical treatment as defined by the persistence of serum iPTH levels >300 pg/mL despite proper medical treatment (adequate intake of elemental calcium and alphacalcidiol and use of phosphate binders), presence of brown tumors or soft tissue calcifications. We noted the level of iPTH before surgery and on days D0, D7, D15, D30 and D90 after parathyroidectomy. The iPTH levels were measured by immunoassay of polypeptide fragment 1-84 of iPTH; all measurements were made in the same biochemistry laboratory. We chose only one criterion to define successful parathyroidectomy: A serum iPTH level below 300 pg/mL at Day 30 after surgery.

Statistical analysis was performed using SPSS 11.5. Quantitative variables are expressed as mean ± standard deviations when they met the normal distribution and median when they were outside the normal distribution. Categorical variables are expressed as percentages. The comparison of the medians was performed by the Friedman test. Significance was set at P <0.05.


   Results Top


Among 49 chronic HD patients in the study, 31 patients (63%) had secondary hyperparathyroidism, all of whom received medical treatment initially. Sub-total parathyroidectomy was performed in 10 patients (32%). The average age of these 10 patients was 40 ± 13 years, with a sex ratio of 1. The mean duration on HD was 122 ± 63 months. Five patients (50%) had received HD for >10 years. The median iPTH level was 1730 pg/mL IQ: (1101. 2622), the median serum calcium was 92 mg/L IQ: (90. 99), the median serum phosphorus was 54 mg/L IQ: (28. 75), the median serum bicarbonate was 24 mmol/L IQ: (23.26) and the median alkaline phosphatase was 885 IU/L IQ: (304. 14). Seven patients were anemic, with a mean hemoglobin of 8.8 ± 2.7 g/dL, and needed recombinant human erythropoietin at an average weekly dose of 6000 ± 1632 IU/week. Radiological signs of osteitis fibrosa were present in all patients. There was bone demineralization in nine patients, resorption of phalangeal tufts in four patients and a worm-eaten appearance of the skull in five patients. One patient had a brown tumor in the right tibia while another had a brown tumor in the facial bone. Ultrasound revealed cervical parathyroid adenomas in two patients while the sonographic appearance of the thyroid gland was normal in all patients with clinical and biological euthyroidism. All patients were on medical treatment involving supplementation with elemental calcium, phosphorus binders and alphacalcidiol. Indications for parathyroidectomy included resistance to medical treatment in seven cases, development of brown tumors in two cases and soft tissue calcifications in one. All 10 patients underwent sub-total parathyroidectomy, which was performed by the same surgeon using the same technique; surgical resection of 7/8 th of the parathyroid glands was performed in six patients and resection of 6/8 th in four patients. Associated thymectomy was performed in five patients. Histological examination of the surgical specimen revealed parathyroid hyperplasia in all patients, while the thymic tissue was normal in all.

The kinetics of iPTH after parathyroidectomy was marked by a rapid and significant fall in its rate on Day 0, with a median of 92 pg/mL IQ: (54. 14). The levels on the other days of monitoring are given in [Figure 1]. The decrease in the serum iPTH was statistically significant (P = 0.003). The elevation of iPTH in the three months following parathyroidectomy is due to the persistence of a high residual secretion of PTH in a patient who had resection of 7/8 th of the parathyroid glands without thymectomy.
Figure 1: Kinetics of parathormone levels after parathyroidectomy with time.

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We monitored the serum calcium very diligently after surgery (two times/day) providing adequate calcium supplementation, when required, either orally and parenterally. None of the patients had severe hypocalcemia in our series [median calcium = 84 mg/L IQ: (77. 89) at one month and 85 mg/L IQ: (82. 90) at three months] [Figure 2].
Figure 2: Changes in serum calcium levels after parathyroidectomy with time.

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We also noted a rapid and significant decrease (P = 0.003) of phosphorus after parathyroidectomy with a median of 22 mg/L IQ: (16. 27) at one month and 22 mg/L IQ: (9. 25 mg/L) at three months [Figure 3]. The median plasma alkaline phosphatase was 200 IU/L IQ: (103. 26) at the end of three months. The bicarbonate levels normalized after an average period of 25 days [Figure 4].
Figure 3: Evolution of serum phosphorus levels after parathyroidectomy with time.

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Figure 4: Evolution of serum alkaline phosphatase levels after parathyroidectomy with time.

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The mean hemoglobin level increased from 8.8 ± 2.7 g/dL before parathyroidectomy to an average of 11 ± 1 g/dL on Day 90, with a net reduction in weekly requirement of recombinant human erythropoietin (6000 ± 1632 IU/ week before surgery to 4250 ± 500 IU/week at one month). The increase in hemoglobin was statistically significant (P = 0.021) as well as reduction of the need for erythropoietin (P = 0.018).


   Discussion Top


Secondary hyperparathyroidism is a common problem in the management of end-stage renal disease, with a prevalence ranging from 30% to 50% according to various authors. [1],[2],[3],[4] This prevalence increases with the duration on HD. In our series, the prevalence of secondary hyperparathyroidism was 63%, with an average duration on HD being 122 ± 63 months. Indeed, the serum PTH increases as the glomerular filtration rate falls below 60 mL/min. [2],[4] Several factors contribute to its maintenance in patients on dialysis, but hyperphosphatemia and hypocalcemia remain the most important. [2],[3] After sub-total parathyroidectomy, the levels of iPTH showed a rapid and significant fall in all patients (median iPTH, 1730 pg/mL initially and 36 pg/mL at one month of evolution), with rapid normalization of other parameters as well:

  1. Phosphorus-calcium balance [initial serum calcium = 92 mg/L IQ: (90. 99), serum calcium levels at one month = 84 mg/L IQ: (77. 89) with P = 0.047; initial phosphorus = 54 mg/L IQ: (28. 75), phosphate at one month = 22 mg/L IQ: (16.27), P = 0.008].
  2. The level of serum bicarbonate [initial level = 24 mmol/L IQ: (23. 26), level at one month = 27 mmol/L IQ: (25. 28), P = 0.095].
  3. The level of alkaline phosphatase [initial level = 885 IU/L IQ: (304. 14), level at one month = 200 IU/L IQ: (200. 26), P = 0.043].


These very satisfactory results show the effectiveness of sub-total parathyroidectomy in the treatment of refractory secondary hyperparathyroidism. [1] Indeed, after failure of medical resources, the best treatment of this pathology is the excision of the glandular cells that secrete PTH, either by injecting percutaneous alcohol or by surgical parathyroidectomy. [1],[2],[5] Chemical parathyroidectomy involves injection of alcohol (ethanol) into the parathyroid glands with ultrasound localization. This technique was not used in our practice. [5] The effectiveness of this technique is highly variable according to the authors. [5],[6] In addition, it comes with a risk of transient or permanent damage to the recurrent laryngeal nerve. [5] There are two surgical approaches: Sub-total parathyroidectomy or total parathyroidectomy with or without grafting. The transplant is performed most frequently in the forearm. [1] We did not use this last technique given the significant risk of permanent hypoparathyroidism post-surgery and the lack of cryopreservation with liquid nitrogen in our facility. [1],[2],[3]

Sub-total parathyroidectomy is the technique most frequently recommended. It requires careful intra-operative surgical exploration to identify the four parathyroid glands. This involves surgical resection of a maximum portion of the parathyroid tissue, leaving a residual tissue to ensure a residual secretion of PTH. This often entails resection of 7/8 th of the parathyroid tissue. This removal exposes the risk of leaving behind a very low volume of parathyroid tissue, particularly if surgical exploration showed that the parathyroid glands are very small. In such situations, resection of 6/8 th of the parathyroid tissue and leaving the entire small gland in order to ensure a sufficient residual secretion of PTH is indicated. We performed resection of 6/8 th of the parathyroid glands in four patients in whom surgical exploration revealed the presence of very small parathyroid glands.

The effectiveness of surgical resection is accepted by most authors. [1],[4],[7] The success rate of the procedure is about 95%. However, a second operation may be needed in about 1% of cases. [7] In our study, the efficacy of sub-total parathyroidectomy was satisfactory. Most of our patients had an iPTH in the therapeutic range of 150-300 pg/mL 8 for one month, with the exception of one patient whose serum iPTH was 500 pg/mL. This patient probably had a fifth ectopic parathyroid gland in the thymus. Ectopic thymic parathyroid tissue is frequently encountered in 13-30% of the cases. [8],[9]

The immediate medical complication of parathyroidectomy is hypocalcemia and needs to be managed by frequent daily monitoring of serum calcium and calcium supplementation, when necessary. [10],[11],[12] This is the "hungry bone syndrome," characterized by a high calcium binding to bone following the fall in serum PTH. [2],[3],[4] In our series, most patients exhibited a fall in serum calcium within 24-h following surgery. We were able to prevent the occurrence of severe hypocalcemia in all patients with careful monitoring of serum calcium several times a day in addition to adequate calcium supplementation. Other complications can occur, in particular, the post-surgical adynamic bone disease that is reported by many authors and is a real therapeutic problem. [2],[3] The adynamic bone disease is defined by inadequate secretion of iPTH below 100 pg/ mL. [3],[13] No cases of post-operative adynamic bone disease were noted in our series, thanks to the persistence of a sufficient residual secretion of PTH.

Tominaga et al [7] reported the largest series of surgical parathyroidectomy in ESRD patients. In their report of 782 surgical patients, nodular hyperplasia was noted in 85% of the patients. Nodular parathyroid hyperplasia is almost always associated with lack of response to treatment with alphacalcidiol. This hyperplasia was found in all patients in our series. In the series of Tominaga et al, [7] the four parathyroid glands were identified in 98.5% of patients and the most common weight of the glands was 200-500 mg. Hyperparathyroidism may persist despite surgery in 3% of patients, and the recurrence rate after surgery was 10% at three years, 20% at five years and 30% at seven years. [7]

In our study, we assessed the short-term efficacy of sub-total parathyroidectomy for the treatment of secondary hyperparathyroidism in chronic HD patients. Longer follow-up of the evolution of these patients is needed to judge the effectiveness of this intervention over time.

Conflict of interest: None declared.

 
   References Top

1.
Guevara N, Castillo L, Santini J, et al. Parathyroid glands surgery. Medico Surgical Encyclopedia Surgical Techniques. Head and neck. 2006. p. 46-465.  Back to cited text no. 1
    
2.
Maitra S, Stanley S. The Treatment of Secondary Hyperparathyroidism on Renal insufficiency Patients Terminal. Nephrology Rounds Vol. 2, 2001.  Back to cited text no. 2
    
3.
Lafage-Proust MH. Renal osteodystrophy. Medico-Surgical Encyclopaedia. head and neck. 2008. [14-275-A-10].  Back to cited text no. 3
    
4.
Bardin T, Martine C. Renal osteodystrophy. Medico-Surgical Encyclopaedia. head and neck. 1996. [14-027-L-10].  Back to cited text no. 4
    
5.
Kakuta T, Fukagawa M, Fujisaki T, et al. Prognosis of parathyroid function after successful percutaneous ethanol injection therapy guided by color Doppler flow mapping in chronic dialysis patients. Am J Kidney Dis 1999;33:1091-9.  Back to cited text no. 5
    
6.
Fletcher S, Kanagasundaram NS, Rayner HC, et al. Assessment of ultrasound guided percutaneous ethanol injection and parathyroidectomy in patients with tertiary hyperparathyroidism. Nephrol Dial Transplant 1998;13:3111-7.  Back to cited text no. 6
    
7.
Tominaga Y. Surgical management of secondary hyperparathyroidism in uremia. Am J Med Sci 1999;317:390-7.  Back to cited text no. 7
    
8.
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42 4 Suppl 3:S1-201.  Back to cited text no. 8
    
9.
Pattou FN, Pellissier LC, Noël C, Wambergue F, Huglo DG, Proye CA. Supernumerary parathyroid glands: Frequency and surgical significance in treatment of renal hyperparathyroidism. World J Surg 2000;24:1330-4.  Back to cited text no. 9
    
10.
Schömig M, Ritz E. Management of disturbed calcium metabolism in uraemic patients: 2. Indications for parathyroidectomy. Nephrol Dial Transplant 2000;15 Suppl 5:25-9.  Back to cited text no. 10
    
11.
Bieglmayer C, Kaczirek K, Prager G, Niederle B. Parathyroid hormone monitoring during total parathyroidectomy for renal hyperparathyroidism: Pilot study of the impact of renal function and assay specificity. Clin Chem 2006;52:1112-9.  Back to cited text no. 11
    
12.
Cannata-Andía JB, Fernández-Martín JL, Zoccali C, et al. Current management of secondary hyperparathyroidism: A multicenter observational study (COSMOS). J Nephrol 2008;21:290-8.  Back to cited text no. 12
    
13.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKDMBD). Kidney Int 2009;76 Suppl 113:S1-130.  Back to cited text no. 13
    

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Correspondence Address:
Z Skalli
Service de Néphrologie - Dialyse - Transplantation Rénale, CHU Ibn Sina, Rabat
Maroc
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DOI: 10.4103/1319-2442.168622

PMID: 26586059

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