Treatment Of Primary Hyperparathyroidism Research Articles

Complex management decisions in a woman with concurrent primary hyperparathyroidism and metastatic papillary thyroid carcinoma, both presenting during pregnancy.

SummaryA 40-year-old woman was hospitalised at 25-week gestation following a diagnosis of severe symptomatic hypercalcaemia (adjusted serum calcium 3.02 mmol/L). A diagnosis of primary hyperparathyroidism (PHP) was made on the basis of elevated parathyroid hormone (PTH) 11.2 pmol/L (reference range 1.5–6.9) and exclusion of familial hypocalciuric hypercalcaemia. Ultrasound examination of the neck did not convincingly demonstrate an abnormal or enlarged parathyroid gland and parathyroid scintigraphy was not performed due to maternal choice relating to perceived radiation risk to the foetus. At neck exploration during the 28th week of pregnancy a right lower pole parathyroid lesion was excised together with two abnormal lymph nodes (largest 1.6 cm). Histology confirmed a parathyroid adenoma and also papillary thyroid carcinoma deposits in the two resected lymph nodes. Post-operatively, levels of adjusted serum calcium normalised and pregnancy progressed uneventfully to term. Total thyroidectomy was performed 2 weeks after delivery revealing two small foci of papillary micro-carcinoma (largest 2.3 mm, one in each thyroid lobe) with no evidence of further metastatic tumour in lymph nodes removed during functional neck dissection. Radioiodine remnant ablation (RRA) was performed 2 months post thyroidectomy to allow for breast involution. The patient remains in full clinical and biochemical remission 9 years later. We present and review the difficult management decisions faced in relation to the investigation and treatment of PHP in pregnancy, further complicated by incidentally discovered locally metastatic pT1aN1aM0 papillary thyroid carcinoma.Learning points:PHP may have serious consequences during pregnancy and usually requires surgical management during pregnancy to reduce the risk of maternal and foetal complications. The indications for and optimal timing of surgical management are discussed.Localisation by parathyroid scintigraphy is controversial during pregnancy: modified dose regimes may be considered in preference as an alternative to unguided neck exploration.Breastfeeding is contraindicated for 6–8 weeks before radioactive-iodine remnant ablation (RRA) to prevent increased breast uptake. Breastfeeding is further contra-indicated until after a subsequent pregnancy.Incidentally discovered differentiated thyroid carcinoma (DTC) in cervical lymph nodes in some cases may be managed expectantly because in one quarter of thyroidectomies the primary tumour remains occult.

Major Gaps in Diagnosis and Treatment of Primary Hyperparathyroidism

Most cases of primary hyperparathyroidism are diagnosed when hypercalcemia is noted incidentally on chemistry panels ordered for other reasons. To shed

Transoral Endoscopic Parathyroidectomy Vestibular Approach (TOEPVA)—Choosing the Right Patient

Parathyroidectomy is the surgical treatment for primary hyperparathyroidism. A single parathyroid adenoma is the most common cause of primary hyperparathyroidism (PHPT) making it amenable to a focused surgery whereby the putative hyperfunctional parathyroid gland is excised. Parathyroid surgery, like thyroid surgery, is typically performed through a cervical incision usually measuring 4–5 cm. Though most surgical scars heal well over time, the presence of a scar may affect a patient’s quality of life (Goldfarb and Casillas, Thyroid. 26(7):923–32, 2016; Choi et al., Ann Dermatol. 26(6):693–9, 2014). Surgeons may perceive scars differently and more favorably than patients. Variables such as scar length do not always correlate with patient satisfaction (Arora et al., Int J Surg. 25:38–43, 2016; Toll et al., Eur Arch Otorhinolaryngol. 269(1):309–13, 2012; Linos et al., Surgery 153(3):400–7, 2013). Remote access approach to the parathyroid: Remote access approaches such as transoral and axillo-bilateral-breast approaches have been proposed to access the suspected hyperfunctional parathyroid gland similar to the thyroid to avoid a scar in the neck (He et al., J Laparoendosc Adv Surg Tech. 25(4):311–3, 2015). Transoral endoscopic thyroidectomy vestibular approach (TOETVA) for thyroidectomy introduced by Anuwong is gaining popularity as a remote access approach with feasibility demonstrated by several groups (Dionigi et al., J Endocrinol Invest. 40(11):1259–63, 2017; Russell et al., Thyroid. 28(7):825–829, 2018; Anuwong et al., Surg Endosc. 32(1):456–65, 2018). Focused parathyroid surgery may also be completed via this approach (TOEPVA) (Sasanakietkul et al., Surg Endosc. 31(9):3755–63, 2017).

MANAGEMENT OF ENDOCRINE DISEASE: Unmet therapeutic, educational and scientific needs in parathyroid disorders.

PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including parathyroid cancer (PC), and hypoparathyroidism (HypoPT). The discussions and consensus statements from the first PARAT workshop (September 2018) are reviewed. PHPT has a high prevalence in Western communities, yet evidence is sparse concerning the natural history and whether morbidity and long-term outcomes are related to hypercalcemia or plasma PTH concentrations or both. Cardiovascular mortality and prevalence of low energy fractures are increased, whereas quality of life is decreased, although their reversibility by treatment of PHPT has not been convincingly demonstrated. PC is a rare cause of PHPT, with increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity and optimal treatments. For example, ~20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized care, such as different forms of immunotherapy or targeted therapy. HypoPT, a designated orphan disease, is associated with a high risk of symptoms and complications. Most cases are secondary to neck surgery. However, there is a need to better understand the relation between disease biomarkers and intellectual function and to establish the role of PTH in target tissues, as these may facilitate the appropriate use of PTH substitution therapy. Management of parathyroid disorders is challenging, and PARAT has highlighted the need for international transdisciplinary scientific and educational studies in advancing in this field.

Who Benefits from Treatment of Primary Hyperparathyroidism?

Parathyroidectomy (PTx) is the only definitive treatment for primary hyperparathyroidism (PHPT), but is commonly underutilized. Most patients are medically observed, whereas approximately 30% of patients are treated operatively. PTx is a low-risk surgical procedure and the most cost-effective treatment option. An international consensus statement was published in 1990 to guide clinicians in the management of patients with PHPT, particularly those with asymptomatic disease. Most patients with PHPT and low perioperative risk benefit from surgical treatment, regardless of whether they meet consensus criteria, due to fracture risk reduction, health-related quality-of-life improvements, and prevention or mitigation of disease progression.

Failure to Diagnose and Treat Hyperparathyroidism Among Patients with Hypercalcemia: Opportunities for Intervention at the Patient and Physician Level to Increase Surgical Referral.

Hyperparathyroidism is both underdiagnosed and undertreated, but the reasons for these deficiencies have not been described. The purpose of this study was to identify reasons for underdiagnosis and undertreatment of hyperparathyroidism that could be addressed by targeted interventions. We identified 3,200 patients with hypercalcemia (serum calcium >10.5 mg/dL) who had parathyroid hormone (PTH) levels evaluated at our institution from 2011 to 2016. We randomly sampled 60 patients and divided them into three groups based on their PTH levels. Two independent reviewers examined clinical notes and diagnostic data to identify reasons for delayed diagnosis or referral for treatment. The mean age of the patients was 61 ± 16.5 years, 68% were women, and 55% were white. Fifty percent of patients had ≥1 elevated calcium that was missed by their primary care provider. Hypercalcemia was frequently attributed to causes other than hyperparathyroidism, including diuretics (12%), calcium supplements (12%), dehydration (5%), and renal dysfunction (3%). Even when calcium and PTH were both elevated, the diagnosis was missed or delayed in 40% of patients. For 7% of patients, a nonsurgeon stated that surgery offered no benefit; 22% of patients were offered medical treatment or observation, and 8% opted not to see a surgeon. Only 20% of patients were referred for surgical evaluation, and they waited a median of 16 months before seeing a surgeon. To address common causes for delayed diagnosis and treatment of hyperparathyroidism, we must improve systems for recognizing hypercalcemia and better educate patients and providers about the consequences of untreated disease. This study identified reasons why patients experience delays in workup, diagnosis, and treatment of primary hyperparathyroidism. These data provide valuable information for developing interventions that increase rates of diagnosis and referral.

SUN-509 A Challenging Case of Symptomatic Primary Hyperparathyroidism during Pregnancy Treated with Cinacalcet

Primary hyperparathyroidism (PHPT) during pregnancy is rare. Hypercalcemia (HCa) may be undetected due to hypoalbuminemia and increased active transport of calcium via the placenta. Undiagnosed HCa may present with life threatening maternal hypercalcemic crisis and fetal hypocalcemia. In patients with moderate and severe HCa, parathyroidectomy (PTx) is recommended during the second trimester. Cinacalcet is approved for treatment of secondary hyperparathyroidism in patients with ESRD, HCa due to parathyroid carcinoma, and in patients with severe HCa due to PHPT unable to undergo PTx. However, cinacalcet use in pregnancy is limited to a few case reports. We present a case of PHPT presenting with severe HCa and cardiomyopathy where PTx was contraindicated due to risk of cardiac decompensation. To our knowledge this is the first case of cinacalcet use in PHPT where therapeutic doses were well tolerated resulting in a safe delivery without maternal and fetal complications. A 38 year old female at 25 weeks gestation (gravida 7, para 4) presented from an outside hospital for treatment of pyelonephritis and new onset cardiomyopathy with reduced ejection fraction of 20%. The patient had a history of preeclampsia but denied a personal or family history of nephrolithiasis and calcium abnormalities. Present medication included a prenatal multivitamin. Physical exam revealed tachycardia, hypotension and no palpable neck mass. Laboratory evaluation revealed a corrected calcium 13.8 (8.7-10.7mg/dL), ionized calcium (iCa) 1.7 (0.95-1.32 mmol/L), phosphate 1.7 (2.5-4.6 mg/dL), magnesium 1.5 (1.6-2.7 mg/dL), creatinine 0.83 mg/dL. Treatment with normal saline 0.9 % was started with IV furosemide to prevent fluid overload. Further evaluation showed an elevated intact parathyroid hormone 383 (8-85 pg/mL), elevated 1,25 dihydroxyvitamin D 147 (18-78 pg/mL), normal parathyroid hormone related peptide 14 (14-27 pg/mL), fractional excretion of calcium of 1.7%, and fractional excretion of phosphate of 25% confirming the diagnosis of PHPT. A neck ultrasound showed a 2 cm left thyroid nodule; FNA biopsy confirmed a parathyroid adenoma. Evaluation for MEN 1 was negative. Due to severe cardiomyopathy, the patient was deemed a poor surgical candidate. Treatment with cinacalcet 30 mg daily was started and slowly titrated to 90 mg twice daily. On discharge, iCa had normalized to 1.26. The patient was readmitted to the hospital four days prior to delivery for discontinuation of cinacalcet and prevention of fetal parathyroid gland suppression. The patient delivered a healthy male at 37 weeks of gestation without hypocalcemia. Treatment of PHPT during pregnancy is challenging especially in those patients who are unable to undergo PTx. Cinacalcet may be a safe option to prevent maternal and fetal complications of HCa in patients with PHPT. Further studies are needed to evaluate the safety of cinacalcet in pregnancy.

SUN-494 Multiple Ectopic Parathyroid Foci: An Unexpected Finding Leading to Primary Hyperparathyroidism

Background: A patient with severe hypercalcemia and extremely elevated PTH levels found to have multiple foci of ectopic parathyroid tissue. Clinical Case: A 60-year-old female with a history of hypothyroidism and hypertension was transferred from another facility for evaluation for a parathyroidectomy. Vital signs were within normal limits. Initial evaluation revealed a corrected calcium of 8.2 mg/d, albumin level of 2.4 g/dL (n 3.2 - 4.6 g/dL). Creatinine was within normal limits. PTH level of 908 pg/dL (n 9.0 - 77.0 pg/dL), 25-vitamin D level of 15 ng/mL. The patient was recently admitted to another facility for septic shock secondary to UTI. She was found to have bilateral renal stones, for which she underwent ureteral stent placement. Further workup revealed severe hypercalcemia of 20.0 mg/dL and a PTH level >2,500 pg/dL. She was treated with IV fluids, bisphosphonates, calcitonin and cacimimetics. She was discharged with the plan for an outpatient parathyroidectomy. Prior to the parathyroidectomy, the patient was readmitted for acute respiratory failure. A parathyroid NM scan was performed and revealed no persistent uptake to suggest a parathyroid adenoma. She was subsequently transferred and admitted to our facility.During the admission, ENT and endocrinology were consulted. A NM scan was repeated, which showed a questionable right lower pole thyroid focus concerning for a parathyroid adenoma. 4D CT scan had concordant findings. Due to the exceedingly elevated PTH level, there was concern for parathyroid carcinoma. Patient underwent right thyroid lobectomy, parathyroidectomy with four-gland exploration, right central neck dissection, and reimplantation of ½ left super parathyroid to the left sternocleidomastoid. After the surgery, calcium and vitamin D supplementation were initiated. Her calcium levels remained stable throughout the hospital course. Operative parathyroid pathology revealed normal parathyroid glands with no malignancy, in addition to 12 foci of ectopic parathyroid glands. Conclusion: Treatment of primary hyperparathyroidism with parathyroidectomy is efficacious in 80-97% of initial explorations. The ability to locate ectopic glands are linked to the failure or success rates. Although ectopic parathyroid glands are common (15%), multiple ectopic glands, as in this case, are rarely reported.

OR30-2 Efficacy and Safety of Percutaneous Ethanol Ablation of Parathyroid Adenoma

Introduction: Parathyroidectomy is the standard of care for the treatment of primary hyperparathyroidism (PHP). Patients who are not surgical candidates have limited options of treatment. Percutaneous ethanol injection (PEI) for the treatment of parathyroid adenoma was first introduced in the 1980s. Main safety and efficacy data about PEI of parathyroid adenoma comes from the mayo clinic review publication of the treatment of recurrent primary hyperparathyroidism in patient with MEN1. There is no large review of the treatment of PHP. In our practice, we localize the parathyroid adenoma with ultrasound in preparation for surgery. In addition, non-surgical patients who meet the criteria for treatment of hyperparathyroidism get offered the PEI as an option of treatment. All patients who were treated with PEI had FNA from the parathyroid adenoma and PTH level was measured on the aspirate to confirm the diagnosis. Study design: This is a retrospective longitudinal cohort study of calcium and PTH level in patient with PHP after PEI treatment. All patients with PHP who received PEI treatment between 2013 and 2017 electronic chart was reviewed and data was collected about calcium, PTH level before treatment and after treatment up to one year, also side effect and complication of the procedure was collected. Patient who we do not have the 6 months data we assumed treatment failure Result: Baseline characteristic 60 patients, age 34 to 95, 49 female and 11 male, PTH average 136, calcium average 11.2 Normal calcium was achieved in 39 patients (65%) at 1 week after the PEI and 36 patients (58%) at 6 months, also at 6 months the 26 patients who continued to have elevated calcium 17 of them (65%) had improvement in calcium level after the treatment and it was below 11.2. At one year we did not have lab result for all patients, out of the 36 patients who had normal calcium at 6 months we have the result of 29 patients and they continue to have normal calcium Complications from the procedure: pain in the injection site for a few minutes after injection, 4 patients (6%) had hoarseness that resolved in two weeks in 3 patients and one patient had hoarseness that persisted after one year Conclusion: This is the largest cohort of PHP patients treated with PEI and it showed 58% normalization of calcium after treatment. The main significant complication was recurrent nerve injury which was temporary in most cases

Limited clinical utility of intraoperative frozen section during parathyroidectomy for treatment of primary hyperparathyroidism

BackgroundThis study's objective was to evaluate the utility of intraoperative frozen section (IFS) performed during parathyroidectomy for treatment of primary hyperparathyroidism (PHP), and to identify patients for whom it is most helpful. MethodsA retrospective chart review was carried out for all patients who underwent parathyroidectomy for treatment of PHP between January 2013 and June 2018. Results262 patients made up the final study population. Overall, IFS provided information that influenced the operative plan in 46 patients (17.6%). IFS altered the operative plan in 10.2% of cases that were correctly preoperatively localized, and in 41.5% of cases that were either incorrectly or not preoperatively localized. ConclusionsIFS did not provide information that influenced the operative plan during parathyroidectomy for treatment of PHP for the majority of patients. Patients that present with normal PTH and hypercalcemia, or those who do not localize preoperatively, are most likely to benefit from IFS.

Is day surgery for minimally‐invasive parathyroidectomy a feasible option?

AimThe aim of the present study was to explore the safety of day surgery for minimally‐invasive parathyroidectomy (MIP) in the treatment of primary hyperparathyroidism (PHPT). Patients and MethodsThe records of all patients who underwent minimally‐invasive parathyroidectomies for PHPT from January 2001 to December 2017 at our centre were reviewed. Patients who underwent bilateral neck exploration, reoperation and concomitant procedures, such as hemithyroidectomy, were excluded. Patients were placed into two groups: group 1 included day surgery cases, and group 2 included patients who were admitted 1 day before the operation and discharged >1 day after the operation. Patient demographics and clinical outcomes were compared between the two groups.ResultsOverall, 194 patients were included: 42 in group 1 and 152 in group 2. There was no statistically‐significant difference between the mean age (P = 0.094), percentage of female patients (P = 0.072), American Society of Anesthesiologists score (P = 0.659) and preoperative and postoperative blood calcium level (P = 0.252 and P = 0.097, respectively) between the two groups. There was also no statistically‐significant difference between the two groups in terms of outcomes, such as bleeding/haematoma (P = 0.598), wound infection (P = 0.328), recurrent laryngeal nerve injury (P = 0.234), postoperative hypocalcaemia (P = 0.082), recurrent/persistent disease (P = 0.328), revisit to the Accident and Emergency Department within 30 days of discharge (P = 0.446), unplanned readmission (P = 0.359) and death (P = 0.598).ConclusionsOverall, we believe that our data indicate that day surgery is a feasible and safe option for patients undergoing MIP for PHPT.

Hungry bone syndrome: biochemical and clinical risk factors

Primary hyperparathyroidismremains the first cause of hypercalcaemia. Parathyroid surgery is the most efficient treatment of primary hyperparathyroidism, however surgery entails risk of development of a Hungry Bone Syndrome (HBS) – rapid, profound, and prolonged hypocalcaemia. The risk factors of HBS are significantly elevated calcium and PTH concentration in plasma, large tumor mass, previously diagnosed osteoporosis and age over 61 years old before surgery. Pre-surgery supplementation of vitamin D3 and long-term therapy with bisphosphonate allows for more efficient control of hypocalcemia and bone metabolism after surgery.

Сравнительные аспекты диагностики и лечения первичного гиперпаратиреоза

Сравнительные аспекты диагностики и лечения первичного гиперпаратиреоза

Comparison of ultrasound-guided percutaneous microwave ablation and parathyroidectomy for primary hyperparathyroidism

Purpose: To compare the clinical efficacy of ultrasound-guided percutaneous microwave ablation (MWA) and parathyroidectomy for primary hyperparathyroidism.Methods: In an observational retrospective study, we compared the outcomes in patients with primary hyperparathyroidism who underwent ultrasound-guided MWA with the outcomes in those who underwent surgical resection (SR). The primary outcome was cure rate. Secondary outcomes were the rate of complications, and the difference of the treatment parameters of two treatment methods. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics.Results: Among 108 patients who met inclusion criteria, 28 patients who underwent ultrasound-guided MWA (MWA group) and 28 who underwent SR (SR group) had similar propensity scores and were included in the analyses. There was no significant difference in the cure rate between MWA group and SR group (82.1% vs. 89.3%, p = .705). Patients who underwent MWA had significantly less estimated blood loss and shorter surgical time than those who underwent SR (p < .001). The incidence of side effects and complications was comparable between MWA group and SR group (21.4% vs. 25%, p = .752).Conclusions: MWA and SR provided comparable short-term results in terms of cure rate and complications in treatment of primary hyperparathyroidism. Ultrasound-guided percutaneous MWA is a promising and minimally invasive method for primary hyperparathyroidism.

Less-than-subtotal parathyroidectomy as treatment for primary hyperparathyroidism in multiple endocrine neoplasia- type 1: a good option?

Less-than-subtotal parathyroidectomy as treatment for primary hyperparathyroidism in multiple endocrine neoplasia- type 1: a good option?

Remote results of surgical treatment of primary hyperparathyroidism

Remote results of surgical treatment of primary hyperparathyroidism

Аспекти хірурґічного лікування первинного гіперпаратиреозу

Аспекти хірурґічного лікування первинного гіперпаратиреозу

Удосконалення та впровадження інноваційних методів операційного лікування первинного гіперпаратиреозу

Удосконалення та впровадження інноваційних методів операційного лікування первинного гіперпаратиреозу

The diagnostic value of parathyroid hormone washout in primary hyperparathyroidism patients with negative or equivocal 99 m Tc-MIBI results.

The accurate identification of hyper functioning parathyroid gland is needed for definitive surgical treatment in primary hyperparathyroidism. Ultrasonography and 99mTechnetium sestamibi scintigraphy are the two most used methods with varying sensitivities. This study aimed to assess the value of parathyroid hormone (PTH) assay in preoperative ultrasound guided fine needle aspiration (FNA)-PTH washout fluid to verify the correct localisation of lesions with negative or inconclusive scintigraphy results. We evaluated data of 28 lesions in 21 patients who underwent US-guided parathyroid fine-needle aspiration (FNA) with PTH washout, retrospectively. The PTH washout results and the reports of parathyroid surgery and imaging studies were reviewed. Of operated 28 lesions 23 had positive and 5 had negative washout results. The median FNA-PTH washout was 2315.5 pg/ ml (min-max: 12.3-6978 pg/ ml). The calculated sensitivity of FNA-PTH washout was 85.7% and the specifity was 28.6%. The positive and negative predictive values were 78.3% and 40.0%, respectively. FNA-PTH can be used to establish the nature of the lesion, discriminate parathyroid gland from thyroid lesions or cervical lymph nodes, improving the surgical outcomes. It can be used to localise parathyroid lesions preoperatively when negative or discordant ultrasound and scintigraphy findings are obtained.

Intraoperative parathyroid hormone testing in primary hyperparathyroidism surgery: time for giving up?

Intraoperative PTH testing (IOPTH) in treatment of primary hyperparathyroidism (PH) is debated. Some authors advise against IOPTH in patients with concordant preoperative imaging undergoing focused parathyroidectomy. This study aims to compare focused parathyroidectomy success rates with and without IOPTH in patients with concordant preoperative imaging. Retrospective cohort study involving 599 consecutive patients underwent surgery for PH from 2012 to 2017. Patients with discordant preoperative imaging were excluded. 426 patients underwent focused parathyroidectomy (214 patients without IOPTH and 212 with IOPTH) and were considered for the statistical analysis. In case of insufficient IOPTH decay (less than 50%), a bilateral exploration was carried out. The IOPTH group and the non-IOPTH group were similar for demographics and preoperative PTH and calcaemia. 413 patients were cured and disease persistence rates between groups were not significantly different (p > 0.05). Although further testing and randomized-controlled trials are required to validate our findings, our data show that IOPTH does not seem to improve the outcome in patients with concordant preoperative imaging undergoing focused parathyroidectomy.