Serum intact parathyroid hormone as a predictor of hypocalcaemia after total thyroidectomy

BACKGROUND: Hypocalcaemia from hypoparathyroidism is a complication of total thyroidectomy. The aim of the present study was to determine whether an early postoperative level of serum parathyroid hormone (PTH) after total thyroidectomy predicts the development of significant hypocalcaemia and the need for treatment. METHODS: Patients undergoing total thyroidectomy had their serum level of intact PTH checked 1 h after removal of the thyroid gland. Serum calcium level was checked on the following morning. Oral calcium and/or calcitriol was commenced if the patient developed hypocalcaemic symptoms, or if the corrected serum calcium level was <2.0 mmol/L. RESULTS: Seventy-nine patients were included in the present study. Thirteen patients had symptoms of hypocalcaemia on postoperative days 1 or 2 and 66 patients remained asymptomatic. The postoperative intact PTH, day 1 calcium and day 2 calcium was 0.32 +/- 0.60 pmol/L, 2.01 +/- 0.11 mmol/L, and 2.02 +/- 0.16 mmol/L, respectively, for the symptomatic group and 1.98 +/- 1.25, 2.21 +/- 0.13, and 2.19 +/- 0.14, respectively, for the asymptomatic group. Calcium support was given to 25 patients, of whom 14 also required calcitriol. CONCLUSION: Serum PTH 1-h after total thyroidectomy is a reliable predictor of hypocalcaemia and can allow safe early discharge of patients from hospital.     

Early postoperative PTH levels as a predictor of hypocalcaemia and facilitating safe early discharge after total thyroidectomy

OBJECTIVE: Hypocalcaemia after total or completion thyroidectomy has traditionally required 48 hours or longer inpatient monitoring of serum calcium levels. The use of parathyroid hormone (PTH) levels to predict postoperative hypocalcaemia is well established. This study aimed to measure the impact of a management plan based on postoperative PTH on achieving safe early discharge after thyroidectomy. METHODS: A prospective cohort study of 76 patients undergoing total or completion thyroidectomy was performed. Serum PTH level was measured 4-12 hours postoperatively and used to stratify patients into three groups: normal PTH (> 12 pg/mL), undetectable PTH (< 3 pg/mL) and intermediate PTH (4-11 pg/mL). A subgroup analysis was performed on a cohort of patients after a change in the management philosophy aiming for day 1 discharge based on the postoperative PTH. RESULTS: Seventy-five percent of eligible patients were successfully discharged on day 1 with no complications or readmissions; 21% of patients had intermediate or undetectable PTH levels and were monitored for 48 hours. No patient required intravenous calcium and no patient suffered permanent hypoparathyroidism. CONCLUSION: A single PTH measurement at 4-12 hours postoperatively allows for accurate prediction of patients at risk of hypocalcaemia. Patients with a normal postoperative PTH level can be safely discharged on the first postoperative day.     

Role of cyclase activating parathyroid hormone (1-84 PTH) measurements during parathyroid surgery: potential improvement of intraoperative PTH assay

SUMMARY BACKGROUND DATA: Quick intraoperative parathyroid hormone assays are widely used as a guide to the adequacy of resection during parathyroid surgery. However, some authors have reported a 15% error rate of these assays because of the presence of false-positive and false-negative results. Recently the authors have found that most commercial intact PTH (iPTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH) and that the proportional levels of non-(1-84) PTH in patients were variable in a much wider range, accounting mostly for 20% to 60% of the immunoreactivity in samples obtained from hyperparathyroid patients. A cyclase activating PTH (CAP) measured by a novel immunoradiometric assay was shown to measure specifically 1-84 PTH. Using a CAP assay, the authors studied the rate of decline of CAP after parathyroidectomy and compared it with iPTH as measured by the Nichols intact PTH immunoradiometric assay. METHODS: This study comprised 29 patients with primary hyperparathyroidism (pHPT) caused by a single adenoma and 7 patients with secondary hyperparathyroidism (secondary HPT) who underwent parathyroidectomy. Blood samples were drawn after anesthesia, before excision of one enlarged parathyroid gland in pHPT and of the last gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value. RESULTS: The percentage of 7-84 PTH in iPTH in plasma samples was 27.5 +/- 14.4% in pHPT and 39.6 +/- 15.1% in secondary HPT. In pHPT patients the plasma CAP and iPTH value decreased to 23.4 +/- 10.8 and 32.0 +/- 11.3% of the preexcision level at 5 minutes, 10.6 +/- 7.7 and 21.1 +/- 8.8% at 10 minutes, and 8.5 +/- 4.9 and 16.1 +/- 6.8% at 15 minutes after removal of the enlarged gland, respectively. At 5 minutes, CAP levels of all 29 pHPT patients had decreased to less than 40% of the preparathyroidectomy level; however, 7 (24%) patients still had an iPTH level of more than 40%. In secondary HPT patients, CAP and iPTH values had dropped to 43.3 +/- 20.2 and 66.1 +/- 19.7% at 5 minutes, 28.6 +/- 16.6 and 53.6 +/- 18.1% at 10 minutes, and 14.2 +/- 9.0 and 41.0 +/- 12.9% at 15 minutes after removal of the last enlarged gland, respectively. At 10 minutes, CAP levels of all seven secondary HPT patients had decreased to less than 50% of the preexcision level; however, three (43%) patients still had an iPTH level of more than 50%. In pHPT and secondary HPT, the 7-84 PTH level had dropped to 57.4 +/- 85.9 and 62.1 +/- 84.9%, respectively, of the preexcision value 15 minutes after removal of the enlarged gland or glands. CONCLUSIONS: The percentage of 7-84 PTH in iPTH in plasma samples varies substantially between patients with HPT. In both pHPT and secondary HPT, the plasma CAP value decreased more rapidly than iPTH after parathyroidectomy, depending on the amount of 7-84 PTH in circulation. These results suggest that the CAP assay may be a more useful adjunct to parathyroidectomy than the currently used iPTH assay.     

Parathyroid hormone levels 1 hour after thyroidectomy: an early predictor of postoperative hypocalcemia

Background

Parathyroid dysfunction leading to symptomatic hypocalcemia is not uncommon following a total or completion thyroidectomy and is often associated with significant patient morbidity and a prolonged hospital stay. A simple, reliable indicator to identify patients at risk would permit earlier pharmacologic prophylaxis to avoid these adverse outcomes. We examined the role of intact parathormone (PTH) levels 1 hour after surgery as a predictor of post-thyroidectomy hypocalcemia.

Methods

We prospectively reviewed the cases of consecutive patients undergoing total or completion thyroidectomy. Ionized calcium (Ca²⁺) and intact PTH levels were measured preoperatively and at 1-, 6- and 24-hour intervals postoperatively. The specificity, sensitivity, negative and positive predictive values of the 1-hour PTH serum levels (PTH-1) in predicting 24-hour post-thyroidectomy hypocalcemia and eucalcemia were determined.

Results

We reviewed the cases of 149 patients. Biochemical hypocalcaemia (Ca²⁺ < 1.1 mmol/L) developed in 38 of 149 (25.7%) patients 24 hours after thyroidectomy. The sensitivity, specificity, positive and negative predictive values of a low PTH-1 were 89%, 100%, 97% and 100%, respectively.

Conclusion

We found that PTH-1 levels were predictive of symptomatic hypocalcemia 24 hours after thyroidectomy. Routine use of this assay should be considered, as it could prompt the early administration of calcitriol in patients at risk of hypocalcemia and allow for the safe and timely discharge of patients expected to remain eucalcemic.     

Thymus carcinoid producing parathyroid hormone (PTH)-related protein: Report of a case

We report herein the rare case of a thymus carcinoid producing parathyroid hormone (PTH)-related protein (PTHrP) found in a 43-year-old Japanese man who presented with a 19-month history of dyspnea. The diagnosis of a carcinoid was established by light microscopic, electron microscopic, and immunohistochemical examinations. The tumor was considered to be thymic in origin because of its anatomic location, the presence of feeders to the tumor (derived from the internal thoracic arteries), and the fact that no other tumors from which it could have originated were found. After an excisional biopsy, which revealed PTH-related immunoreactivity in the tumor cells, 60 Gy of irradiation was delivered, resulting in a 48% reduction in the size of the tumor. Flow cytometry showed a diploid DNA pattern, with 94% of the cells in the GI phase, 4% in the S phase, 2% in the G2+M phase, and a G2+M/Gl ratio of 1.95. The primary cell culture showed some cells adopted in a cord-like pattern. To our knowledge, this is the first report of a carcinoid tumor in which positive staining for PTHrP by immunohistochemical methods was demonstrated.     

Early post-operative serum albumin level predicts survival after curative nephrectomy for kidney cancer: a retrospective study

Background

Previous studies have shown that albumin-related systemic inflammation is associated with the long-term prognosis of cancer, but the clinical significance of an early (≤ 7?days) post-operative serum albumin level has not been well-documented as a prognostic factor in patients with renal cell cancer.

Methods

We retrospectively included patients hospitalized for kidney cancer from January 2009 to May 2014. First, the receiver operating characteristic analysis was used to define the best cut-off of an early post-operative serum albumin level in determining the prognosis, from which survival analysis was performed.

Results

A total of 329 patients were included. The median duration of follow-up was 54.8?months. Patients with an early post-operative serum albumin level?<?32?g/L had a significantly shorter median recurrence-free survival (RFS; 49.1 versus 56.5?months, P?=?0.001) and median overall survival (OS; 52.2 versus 57.0?months, P?=?0.049) than patients with an early post-operative serum albumin level?≥?32?g/L. After adjusting for age, BMI, tumor stage, post-operative hemoglobin concentration, and pre-operative albumin, globulin, and hemoglobin levels, multivariate Cox regression showed that an early post-operative serum albumin level?<?32?g/L was an independent prognostic factor associated with a decreased RFS (HR?=?3.60; 95% CI,1.05–12.42 [months], P?=?0.042) and decreased OS (HR?=?9.95; 95% CI, 1.81–54.80 [months], P?=?0.008).

Conclusion

An early post-operative serum albumin level?<?32?g/L is an independent prognostic factor leading to an unfavorable RFS and OS. Prospective trials and further studies involving additional patients are warranted.

     

Intact parathyroid hormone measurement 1 hour after thyroid surgery identifies individuals at high risk for the development of symptomatic hypocalcemia

Background

There is currently no consensus regarding the utilization of intact parathyroid hormone (iPTH) for predicting postthyroid surgery hypocalcemia. The objective of this study was to determine a threshold value for the 1-hour postoperative iPTH level that can identify those patients at significantly increased risk for the development of symptomatic hypocalcemia.

Methods

A prospective study of 21 individuals undergoing either total or completion thyroid operations was performed. One-hour postoperative iPTH levels were drawn along with ionized calcium at 6 hours postoperatively and at 7 am the following morning. Symptoms of hypocalcemia were recorded.

Results

Of the 21 patients recruited into the study cohort, there were 18 individuals that developed hypocalcemia (4 symptomatic and 14 asymptomatic) and 3 that remained normocalcemic. The mean iPTH level 1 hour postoperatively was significantly different when comparing the normocalcemic, asymptomatic hypocalcemic, and symptomatic hypocalcemic patient groups (6.50 pmol/L versus 3.76 pmol/L versus 0.7 pmol/L, respectively; P = .007). An iPTH level ≤2.5 pmol/L was 100% sensitive for predicting which individuals would go on to develop symptomatic hypocalcemia.

Conclusions

This study suggests that a 1-hour postoperative iPTH level ≤2.5 pmol/L can identify those individuals at risk for developing symptomatic hypocalcemia. Therefore, we recommend early calcium supplementation for these patients to decrease their postoperative morbidity from symptomatic hypocalcemia.     

Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34)

Intermittently administered parathyroid hormone (PTH) is a potent bone anabolic agent. We aimed to determine the impact of long-term treatment with PTH on bone structure, dynamics, and mineralization. We ovariectomized (ovx) 1-year-old rats with the exception of a baseline and a sham-operated group. Twelve weeks later, a 36 week treatment with PTH analog SDZ PTS 893 (12.5, 25, 50, 100 microg/kg), human PTH(1-34) (25, 50, 100 microg/kg), or vehicle (ovx, sham) was initiated. Bone dynamics, structure, and mineralization were evaluated in the lumbar spine and in the femoral diaphysis. Cancellous bone turnover was elevated 12 weeks postovariectomy in estrogen-deficient, vehicle-treated animals, but returned to the level of the sham group by 48 weeks. The animals experienced substantial cancellous bone loss associated with a reduction of trabecular number and presented with a partly rod-like trabecular network. After 36 weeks of treatment with SDZ PTS 893 or human PTH(1-34), cancellous bone formation rates and turnover were raised in all treated groups compared with age-matched controls. The mineral apposition rate was increasing with dose. This amplified matrix synthesis led to trabecular thickening, but not to an increase in trabecular number, resulting in a crude, plate-like cancellous network with a high bone volume fraction. Fluorochrome label-based cortical bone dynamics demonstrated that a thick ring of new bone was formed at the endocortex by activation of modeling drifts during treatment. Treatment-induced cortical bone formation was increased with dose at the subperiosteal and endocortical envelopes, but substantially higher at the latter. Intracortical bone turnover was elevated near the endocortex. Bone mineralization was undisturbed in all compartments. The average degree of mineralization was lowered slightly, reflecting the increased portion of new bone formed during treatment. In summary, the main anabolic effect was mediated for both peptides by an increase in bone apposition with dose, persisting throughout treatment that lasted more than one third of the lifespan of the rats, and direct activation of bone-forming surfaces. As a result, a substantial amount of new bone, maintained at elevated turnover and adequate mineralization levels, formed predominantly at compartments exposed to bone marrow.     

Hip fracture type: Important role of parathyroid hormone (PTH) response to hypovitaminosis D

ObjectiveTo investigate whether clinical and laboratory characteristics, including serum 25-hydroxyvitamin D (25(OH) D), PTH and parameters of mineral and bone metabolism, differ by hip fracture (HF) type.Patients and methodsWe studied prospectively 761 consecutively admitted older patients (mean age 82.3 + 8.8(SD) years; 74.9% women) with low trauma non-pathological HF. A detailed clinical examination was performed, haematologic, renal, liver and thyroid function tests, serum 25(OH)D, PTH, calcium, phosphate, magnesium, C-reactive protein (CRP) and cardiac troponin I (cTnI) measured. In a subset of 294 patients' markers of bone formation (serum osteocalcin, OC; bone specific alkaline phosphatase, BAP) and bone resorption (urinary deoxypyridinoline, DPD/Cr; N-terminal cross-linked telopeptide of type 1 collagen, NTx/Cr; both corrected to urinary creatinine, Cr) were also measured.ResultsIn the trochanteric compared to the cervical group, females were older than males and the prevalence of Parkinson's disease, mean haemoglobin and albumin levels were lower. Incidence and degree of myocardial injury (cTnl rise) and inflammatory reaction (CRP elevation) as well as length of hospital stay, need of institutionalisation or in-hospital mortality were similar in both groups. Hypovitaminosis D (25(OH)D < 50 mmol/L) was present in 77.8% of patients with cervical and in 82.1% with trochanteric HF, elevated PTH (> 6.8 pmol/L) in 30.2% and 41.3%, respectively. The associations between 25(OH)D, PTH, and parameters of mineral metabolism and bone turnover were site-specific. In multivariate analyses, PTH (both as a continuous or categorical variable) response to hypovitaminosis D was a strong independent predictor of HF type. Coexistence of vitamin D deficiency (25(OH) D< 25 nmol/L) and elevated PTH predicts trochanteric HF while blunted PTH response predicts cervical HF (OR = 3.5; 95% CI 1.5–80; p = 0.005). PTH response and phosphate status (above or below median level) correctly discriminated HF type in 73.8% of patients with vitamin D deficiency.ConclusionsHF type is significantly associated with PTH response to hypovitaminosis D and impaired phosphate homeostasis. We detected only minor differences between two main HF types with regard to a wide range of clinical and routine laboratory variables as well as short-term outcomes.     

Long-term voice quality outcomes after total thyroidectomy: a prospective multicenter study

Background

Postthyroidectomy voice disorders can occur without any recurrent laryngeal nerve injury, and probably are the most frequent complication after thyroidectomy. We report the long-term voice quality outcomes after total thyroidectomy without vocal cord palsy using a simple self-assessment tool: the voice handicap index self-questionnaire.

Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34)

BACKGROUND: Recombinant human parathyroid hormone (PTH [1-34]; teriparatide) is a new treatment for postmenopausal osteoporosis that can be systemically administered for the primary purpose of increasing bone formation. Because several studies have described the enhancement of fracture-healing and osteointegration in animals after use of PTH, we sought to critically analyze this skeletal effect. METHODS: Two hundred and seventy male Sprague-Dawley rats underwent standard, closed femoral fractures and were divided into three groups that were administered daily subcutaneous injections of 5 or 30 mug/kg of PTH (1-34) or vehicle (control). The dosing was administered for up to thirty-five days. Groups were further divided into three subgroups and were killed on day 21, 35, or 84 after the fracture. The bones were subjected to mechanical torsion testing, histomorphometric analysis, or microquantitative computed tomography. RESULTS: By day 21, calluses from the group treated with 30 mug of PTH showed significant increases over the controls with respect to torsional strength, stiffness, bone mineral content, bone mineral density, and cartilage volume. By day 35, both groups treated with PTH showed significant increases in bone mineral content and density and total osseous tissue volume, and they demonstrated significant decreases in void space and cartilage volume (p < 0.05). Torsional strength was significantly increased at this time-point in the group treated with 30 mug of PTH (p < 0.05). While dosing was discontinued on day 35, analyses performed after eighty-four days in the group treated with 30 mug of PTH showed sustained increases over the controls with respect to torsional strength and bone mineral density. No change was noted in osteoclast density at the time-points measured, suggesting that treatment with PTH enhanced bone formation but did not induce bone resorption. CONCLUSIONS: These data show that daily systemic administration of PTH (1-34) enhances fracture-healing by increasing bone mineral content and density and strength, and it produces a sustained anabolic effect throughout the remodeling phase of fracture-healing.     

Early effect of parathyroid hormone (1-34) on implant fixation.

Intermittent systemic administration of parathyroid hormone increases bone formation by stimulating osteoblastic activity. The current study determined how parathyroid hormone (1-34) administration influences the bony fixation of stainless steel screws with time. A screw was implanted in the left tibia and a metal rod was implanted in the right tibia in 30 adult male rats that then were injected three times a week with human parathyroid hormone (1-34) at 60 microg/kg/injection (n = 15) or saline (n = 15). The animals were euthanized after 1, 2, or 4 weeks of treatment. Eight additional rats received only the screw and were euthanized immediately after implantation. No significant effects of parathyroid hormone on body weight change or ash weight of the femurs were seen. The degree of fixation was assessed by measuring pullout strength of the screws. The mean pullout strength immediately after implantation was 12 N. The pullout strength of the group injected with saline was 33 N after 1 week, 23 N after 2 weeks, and 41 N after 4 weeks. The pullout strength of the group injected with parathyroid hormone increased to 43 N after 1 week, 58 N after 2 weeks, and 100 N after 4 weeks. The increase at 2 and 4 weeks was statistically significant. Strength reflects the mechanical properties of the bone within the screw threads. The contralateral tibia with its metal rod was used for blinded histologic assessment. Parathyroid hormone increased the fraction of the metal surface having contract with bone without an intervening soft tissue layer from 45% to 69% after 1 week. The current results suggest that intermittent parathyroid hormone treatment can enhance early implant fixation by enhancing the density of the surrounding bone and by increasing the implant bone contact.     

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目的 探讨甲状腺手术病人甲状旁腺素（PTH）测定与术后低钙血症发生率的关系，总结术后低钙血症的预防和治疗经验。方法 2004年1月至2007年8月对南京医科大学附属无锡市第二人民医院收治的592例甲状腺病人分别于术前．术中切除标本后10min、术后第1、2天测血清门H值，术前、术后第1、2、3天动态监测血清钙离子变化。结果 甲状腺手术后出现低钙血症86例，术中切除标本10min后PTH≤15ng／L（14．19％）及术后第1天≤10ng／L（8．28％）者低钙血症发生率与〉15ng／L（0．34％）、〉10ng／L（6．25％）者相比差异有统计学意义；将切除后10min PTH下降〉75％做为预测术后低钙血症的指标。其敏感性、特异度分别为100％、94．51％。结论 术中切除标本后10min门H下降〉75％时可做为预测术后低钙血症的指标；甲状腺手术后3d内血钙变化最显著；一侧甲状腺全切除＋对侧次全切除及切除范围更大的病人，应常规行术中门H测定，并据情况适当补充钙剂，可以防止低钙症状的发生。     

Early prediction of hypocalcemia after thyroidectomy using parathyroid hormone: an analysis of pooled individual patient data from nine observational studies

BACKGROUND: Monitoring for hypocalcemia after thyroidectomy, using only symptoms and serum calcium levels, can delay the discharge of patients who will remain normocalcemic and can delay the treatment of hypocalcemic patients. STUDY DESIGN: We conducted a systematic search for articles describing use of parathyroid hormone (PTH) assay, checked within hours of completing thyroidectomy, to predict postoperative symptomatic hypocalcemia. Studies were excluded if all patients were treated with postoperative calcium, or if early PTH values were used to alter management of the patient. Individual patient data (perioperative PTH and calcium levels, development of hypocalcemia) were obtained for 457 patients from the corresponding authors of 9 studies and pooled to yield the following results. RESULTS: PTH, checked at three time periods after removal of the thyroid gland (0 to 20 minutes, 1 to 2 hours, and 6 hours), was substantially lower in patients who became hypocalcemic compared with those who remained normocalcemic. The accuracy of PTH in determining hypocalcemia increased with time and was excellent when checked 1 to 6 hours postoperatively. A single PTH threshold (65% decrease compared with preoperative level), checked 6 hours after completing thyroidectomy, had a sensitivity of 96.4% and specificity of 91.4% in detecting postoperative hypocalcemia. CONCLUSIONS: PTH assay, when checked 1 to 6 hours after thyroidectomy, has excellent accuracy in determining which patients will become symptomatically hypocalcemic. Routine use of this assay should be considered because it may allow earlier discharge of the normocalcemic patient and earlier identification of patients requiring treatment of postthyroidectomy hypocalcemia.     

A novel homozygous mutation in the parathyroid hormone gene (PTH) in a girl with isolated hypoparathyroidism

CASE REPORT: A female patient with consanguineous parents presented with severe symptomatic hypocalcemia (1.62mmol/l) at the age of 4months. Treatment with oral 1,25-(OH)2-vitamin D and calcium carbonate was started and serum calcium concentrations were stabilized at the lower end of the normal range. Subsequently she developed normally and had no evidence for additional abnormalities. Over the next 6years of observation, serum levels of PTH were always low but detectable (5.3-2.5pg/ml; normal: 15-65pg/ml) resulting in the diagnosis of isolated hypoparathyroidism. Disturbances in the vitamin-D metabolism, autoimmune polyendocrine syndrome (APS), chromosomal anomalies or mutations in the calcium-sensing receptor gene (CaSR) were excluded. Nucleotide sequence analysis of PTH revealed the presence of a homozygous point mutation (c.68C>A) in exon 2 that introduces a premature termination codon (p.Ser23X in the Pre- sequence of PTH) resulting in a non-functional PTH-precursor. CONCLUSION: A novel, homozygous PTH mutations was identified, which is obviously a very rare cause of isolated hypoparathyroidism (IHP). Although activating CaSR mutations are the most common cause of hypoparathyroidism, analysis of the PTH gene should be considered in those IHP patients in whom a CaSR has been excluded, particularly if the parents are likely to be consanguineous.