Evaluation of Wisconsin and CaPTHUS Indices Usefulness for Predicting Monoglandular and Multiglandular Disease in Patients with Primary Hyperparathyroidism through the Analysis of a Single-Center Experience

Background. The main challenge for treating primary hyperparathyroidism (PHPT) is to understand if it is caused by a single adenoma (80–85% of the cases) or by a multiglandular disease (15–20%), both preoperatively and intraoperatively. For this reason, some preoperative scores were proposed in the literature, to perform focused parathyroidectomy, avoiding intraoperative parathormone assay (ioPTH). The most known are the CaPTHUS test and the Wisconsin index. We applied them to our experience. Methods. A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. Only patients affected with benign PHPT and neck ultrasound performed at our institution were included. Both patients for whom preoperative imaging agreed with the localization of a single diseased parathyroid and those with only ultrasound or scintigraphy positive for parathyroid localization underwent Mini-Invasive Video-assisted parathyroidectomy. In all cases, ioPTH assay was performed. The conversion to bilateral neck exploration was decided based on the drop in ioPTH. CaPTHUS score and the Wisconsin index (Win) were applied to the series. CaPTHUS score ≥3 and Win index >1600, according to the original studies of the literature, were considered at high probability of monoglandular disease. Outcomes in these two groups were examined. Results. 236 patients were eligible for the study. The pathology resulted in multiglandular disease in 24 patients (10.2%). Among these, 18 (75.0%) obtained a CaPTHUS score ≥3, and 20 (83.3%) had a Win index>1600. Intraoperative PTH allowed to identify multiglandular disease in 16 of 18 cases with CaPTHUS ≥3 and in 18 of 20 cases with win >1600, who could have been lost, based only on the results of these 2 tests. Conclusion. Based on our experience, CaPTHUS test and Wisconsin index were not so useful in predicting multiglandular disease as ioPTH.

Feasibility of Intraoperative Parathyroid Hormone Monitoring in Minimally Invasive Surgery

Background and Objectives There has been a long debate on whether intraoperative parathyroid hormone (IOPTH) monitoring is mandatory or not in the excision of a single abnormal parathyroid gland. The aim of this study is to suggest a new criteron of IOPTH monitoring. Subjects and Method We retrospectively analyzed 31 patients who underwent parathyroidectomy from 2005 to 2019. Patients had IOPTH not measured and those with secondary hyperparathyroidism were excluded. IOPTH was measured preoperatively (EX00), at 10 minutes (EX10) and 20 minutes (EX20) after the excision and analyzed. We determined the surgery as a ‘successful excision of lesion (SEOUL)’ when it met the following criteria: criterion 1) the level of EX10 or EX20 decreased under the upper normal or under upper limit of parathyroid hormone (65 pg/mL); criterion 2) EX20 decreased below 50% of EX00 and less than 195 pg/ mL (3 times the upper normal limit); criterion 3) multiglandular disease. Results Twenty-five patients among 31 patients were included this study (M:F=8:17). Twenty- two patients were suspected of single lesion and three patients of multiple lesions on preoperative images (99mTc-sestamibi scan, neck CT, and PET-CT). IOPTH of EX00, EX10, and EX20 were 488.92±658.74, 121.36±134.73, and 92.44±111.55 pg/mL, respectively. Sixty-four percent patients (16/25) met the criterion 1. Six patients (24%) successfully excised a lesion meeting the criterion 2. Three patients had multiglandular disease, meeting the criterion 3. Conclusion Our new criteria suggest when we could stop the procedure. If the level of IOPTH does not meet the SEOUL criteria, it means that there might be more lesions.

An Unusual Presentation of Primary Hyperparathyroidism: Ectopic Parathyroid Gland and Multiglandular Disease

Primary hyperparathyroidism (PHPT) can be associated as a single parathyroid adenoma in approximately 85% of patients, the remaining 15% of them correspond to individuals with hyperplasia. The multiglandular parathyroid disease varies in range 7–33% and contribute a persistent PHPT. We report a case of primary hyperparathyroidism with an unusual presentation of ectopic mediastinal parathyroid. The case was of a 54-year-old female, who started her illness 3 years ago, with frequent headache, regular fatigue and muscle pain, denied losing weight. She was admitted to emergency room for a urinary infection. During the hospitalization showed bilateral nephrocalcinosis, hypercalcemic crisis. She has a background of total thyroidectomy and subtotal parathyroidectomy because a thyroid adenomatous hyperplasia and parathyroid hyperplasia with removal of a total of three parathyroid glands. She had very high PTH level. Laboratory: serum calcium: 16.8mg/dl; ionic calcium: 2.37 mmol/L; P: 1.9 (2.7–4.5g/dL); Hb: 9 g/dL; Platelets: 558 000 per microliter; Leukocytes 9 600 cells/mcL; Albumin: 4g/dl; TSH: 0.06 mU/L; fT4: 1.29 (L-T4 doses were 100 ug). Four months after parathyroid surgery, the intact PTH level dropped from 1602 ng/l to 550 (15–65 ng/L). Computed tomography and Tc-sestamibi scintigraphy - SPECT revealed a residual cervicothoracic mass in retroesophageal region (D1-D2) (Fig1 -2). The patient underwent a new surgery and the intact PTH dropped 39ng/L. Histopathology revealed characteristic features of a parathyroid adenomatous (10 gram weight) (Fig.3); additionally a retroesternal ectopic thyroid tissue. There was not reappearance of high blood calcium and parathormone levels more than 6 months after second surgery for PHPT. An unusual case of PHPT caused by a multiglandular disease parathyroid varies (four glands and a ectopic gland), reliable histopathologic adenomatous and hyperplastic parathyroid disease, and persistent primary hyperparathyroidism with very high serum intact PTH level. Reference: (1) Masi L. Primary Hyperparathyroidism. Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs. Front Horm Res. Basel, Karger, 2019, vol 51, pp 1–12. (2) Pecheva M, Mahendran K, Kadlec J, Lofthouse M1, Van Tornout F. Mediastinal giant parathyroid adenoma-a minimally invasive mediastinal surgical approach for an emergency presentation. Ann Cardiothorac Surg. 2016 Jan;5(1):70–3. (3) Cakmak H 1, Tokat AO, Karasu S, Özkan M. Adenoma paratiroideo mediastínico gigante. Tuberk Toraks. 2011; 59 (3): 263–5. (4)Thier M, Daudi S, Bergenfelz A, Almquist M. Predictors of multiglandular disease in primary hyperparathyroidism. Langenbecks Arch Surg. 2018;403(1):103–109.

Use of Preoperative Imaging in Primary Hyperparathyroidism

Context Preoperative imaging is performed routinely to guide surgical management in primary hyperparathyroidism, but the optimal imaging modalities are debated. Objective Our objectives were to evaluate which imaging modalities are associated with improved cure rate and higher concordance rates with intraoperative findings. A secondary aim was to determine whether additive imaging is associated with higher cure rate. Design, Setting, and Patients This is a retrospective cohort review of 1485 adult patients during a 14-year period (2004-2017) at an academic tertiary referral center that presented for initial parathyroidectomy for de novo primary hyperparathyroidism. Main Outcome Measures Surgical cure rate, concordance of imaging with operative findings, and imaging performance. Results The overall cure rate was 94.1% (95% confidence interval, 0.93-0.95). Cure rate was significantly improved if sestamibi/single-photon emission computed tomography (SPECT) was concordant with operative findings (95.9% vs. 92.5%, P = 0.010). Adding a third imaging modality did not improve cure rate (1 imaging type 91.8% vs. 2 imaging types 94.4% vs. 3 imaging types 87.2%, P = 0.59). Despite having a low number of cases (n = 28), 4-dimensional (4D) CT scan outperformed (higher sensitivity, specificity, positive predictive value, negative predictive value) all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas. Conclusions Preoperative ultrasound combined with sestamibi/SPECT were associated with the highest cure and concordance rates. If pathology was not found on ultrasound and sestamibi/SPECT, additional imaging did not improve the cure rate or concordance. 4D CT scan outperformed all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas, but these findings were underpowered.

Three Patients with Lithium-Associated Hyperparathyroidism: Literature Review Regarding Medical and Surgical Management

Lithium (Li) carbonate has been established as a mood stabilizer and an efficacious treatment for bipolar disorder since its discovery by Dr. John Cade in 1948. Li interacts significantly with organ systems and endocrine pathways. One of the most challenging side effects of Li to manage is its effect on the parathyroid glands. Dysregulation of parathyroid signaling due to Li results in hypercalcemia due to increased vitamin D3 generation, increased calcium absorption from the gut, and bone resorption, occasionally resulting in concomitant hypercalciuria. However, hypercalciuria is not a definitive feature for hyperparathyroidism, and normal calcium excretion might be seen in these patients. Hypercalcemia may also result from volume contraction and decreased renal clearance, which are commonly seen in these patients. Anatomically the parathyroid abnormalities can present as single or multiglandular disease. We report 3 cases where the patients developed multiple side effects of Li therapy as well as hypercalcemia due to hyperparathyroidism. The literature is reviewed with regard to medical and surgical management of Li-associated hyperparathyroidism in the context of these 3 presented cases.