Treatment of hypokalemia with amiloride unmasked hypercalcemia and hyperparathyroidism: A case report.

Colonic pseudo-obstruction, also called Ogilvie's syndrome, occurs due to impaired intestinal propulsion, and may be caused by electrolyte imbalances such as hypokalemia and some endocrine disorders such as hyperparathyroidism. Secretory diarrhea due to intestinal pseudo-obstruction can cause hypokalemia. Diuretics such as amiloride can be used to treat hypokalemia, however in this case, treatment with amiloride induced hypercalcemia and unmasked hyperparathyroidism. A 73-year-old female with a history of hypertension and parathyroid adenoma presented with recurrent colonic pseudo-obstruction and chronic hypokalemia. Her hypokalemia was treated with amiloride, causing hypercalcemia of 14.4 mg/dL, elevated PTH, and altered mental status. Amiloride was subsequently discontinued with improvement in her symptoms, and her hyperparathyroidism was treated with cinacalcet. To our knowledge, this is the first report of amiloride unmasking hyperparathyroidism and inducing hypercalcemia.

Neuroendocrine tumors in a patient with multiple endocrine neoplasia type 1 syndrome: A case report and review of the literature.

RATIONALE: Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine neoplasia 1 syndrome (MEN-1). As its main pathogenic factor involves genetic mutations, it can cause a variety of different clinical symptoms. However, cases with negative genetic testing results and multiple nonfunctional malignant neuroendocrine tumors (NETs) with metastasis are relatively rare. PATIENT CONCERNS: A 33-year-old man was admitted to the hospital for hyperparathyroidism. Imaging examination revealed multiple nodules in the parathyroid gland, pancreas, thymus, and adrenal gland, and multiple metastases to the lung, liver, thoracolumbar, as well as mediastinal lymph nodes. DIAGNOSES: After multidisciplinary consultation, this patient was diagnosed with MEN-1 syndrome with various original tumors and multiple systemic metastases. INTERVENTIONS: The patient underwent parathyroid tumor resection and metastasis biopsy. OUTCOMES: The patient received denosumab and sorafenib treatment. LESSONS: As an autosomal dominant hereditary disease, MEN-1 patients present with parathyroid hyperplasia, pancreatic and intestinal tumors, pituitary tumors, and so on, which are caused by genetic mutations. These patients would have hyperparathyroidism, hypoglycemia, gastric ulcer, and gastrointestinal diseases. However, some patients with MEN-1 syndrome cannot be diagnosed by genetic testing and simultaneously present with multiple nonfunctional NETs with systemic metastasis. This increases the difficulty of diagnosis and the subsequent treatment.

A Diagnostic Journey.

We describe the case of a patient who came with features suggestive of diabetic ketoacidosis. On further evaluation of DKA, we found that it was caused by acute pancreatitis. This acute pancreatitis was found to be caused by hypercalcemia, which was in turn due to primary hyperparathyroidism. Imaging studies done for hyperparathyroidism revealed a thyroid nodule which later turned out to be malignant. This patient was also incidentally found to have hypertrophic obstructive cardiomyopathy.

A two-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family: clinical presentations, pathological characteristics and genetic analysis: a case report.

BACKGROUND: Hyperparathyroidism-Jaw Tumor (HPT-JT) is caused by inactivating germline mutations of CDC73. This hereditary disease can present with a range of symptoms. Jaw ossifying fibroma (OF) is one of the most important clinical presentations, affecting 30% of HPT-JT patients. However, OF is easily confused with other fibro-osseous lesions (FOLs) of the jaw. The correct diagnosis of HPT-JT is a real challenge and must be confirmed by genetic testing. CASE PRESENTATION: A female proband and her father suffered from multiple and recurrent FOLs in the jaw. Considering well demarcated margin and heterogeneous calcified substance lying in a variable density of fibrous stroma, we reached the diagnosis of jaw OF through radiologic and microscopic analyses. Additionally, the proband presented with chronic anemia resulting from menorrhagia, as well as renal mixed epithelial and stromal tumor (MEST). Two patients both presented with no evidence of Hyperparathyroidism (HPT). A germline start codon mutation (c.1A > G) of CDC73 was identified in them. Copy number loss at the CDC73 gene locus was verified in the jaw tumor sample of the proband. CONCLUSION: Regardless of whether HPT manifestations are present, patients with heritable jaw OF may be at risk for HPT-JT. Genetic testing should be adopted to confirm the diagnosis. Early recognition of HPT-JT helps to better develop tailored treatment plans and surveillance programs.

[Hypercalcemia - Diagnosis and Management]. / Hyperkalzämie ­ Diagnose, Abklärung und Therapie.

Hypercalcemia - Diagnosis and Management Abstract. The diagnostic workup of hypercalcemia requires a thorough patient history, a focused clinical examination as well as a step-by-step laboratory diagnostic approach. In order to detect the exact aetiology of hypercalcemia an accurate measurement of serum calcium in correlation with the parathyroid hormone level is therefore essential. Primary hyperparathyroidism and malignancy-related hypercalcemia are responsible for about 90% of all hypercalcemia cases. Therefore, these two pathologies should always be considered in the diagnostic approach. The therapeutic procedure is based on the aetiology and severity of the hypercalcemia.

Manifestations of hyperparathyroidism in the jaws: Concepts, mechanisms, and clinical aspects.

Hyperparathyroidism is one of the most common endocrine disorders worldwide. In countries where routine biochemical screening is not common, symptomatic hyperparathyroidism predominates. Its manifestations include skeletal alterations, calcification of soft tissues, kidney stones, and functional alterations in other systems. Notably, jaw alterations can be the first clinical sign of hyperparathyroidism, including brown tumor, renal osteodystrophy, osteitis fibrosa, and leontiasis ossea, and knowing such conditions is of core importance for the multidisciplinary diagnosis and management of hyperparathyroidism. We aimed to perform a concise review, systematizing the concepts and mechanisms underlying hyperparathyroidism and associated gnathic alterations. In addition, a detailed description of the clinical aspects of the jaw manifestations is presented.

Diagnosis and localization of parathyroid adenomas using 16-slice SPECT/CT: A clinicopathological correlation.

INTRODUCTION: This study aimed to evaluate a new 16-slice SPECT/CT scanner at Auckland City Hospital for its use in the detection and localization of parathyroid adenomas in patients with primary, secondary and tertiary hyperparathyroidism. The secondary outcome was to compare findings from SPECT/CT with ultrasound and operative findings. METHODS: One hundred patients who underwent a SPECT/CT scan for primary/secondary/tertiary hyperparathyroidism were included in this study. Of these patients, 45 received surgery. SPECT/CT and ultrasound findings were collated for each patient, and of those who received surgery, operative and pathological findings were compared with those on SPECT/CT. RESULTS: The sensitivity of diagnosis and localization was 86.5% (95% CI: 71.2-95.5%). Specificity was 25.0% (95% CI: 3.2-65.1%). Comparison between SPECT/CT and ultrasound findings demonstrated a kappa coefficient of 0.203 (95% CI: -0.036 to 0.442), correlating with fair agreement. These figures are in line with other published series. CONCLUSION: The SPECT/CT scanner (and associated reporters) at Auckland City Hospital demonstrates high sensitivity in the detection and localization of parathyroid adenomas and is an effective first-line investigation in patients with primary/secondary/tertiary hyperparathyroidism.

Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients.

BACKGROUND: Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS: A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS: Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION: Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

A neonate with late-onset hypocalcemia due to unrecognized maternal hyperparathyroidism and a systematic overview of similar cases.

Objective: Neonatal seizures are alarming manifestations of an underlying significant disorder demanding immediate attention and intervention. Hypocalcemia, although rare, must be considered in the differential diagnosis of neonatal seizures. Method: We present an unusual case of a 10-day-old infant with unexplained symptomatic hypocalcemia, experiencing multiple episodes of focal tonic-clonic seizures, born by an entirely asymptomatic mother. Moreover, we conducted a systematic search in PubMed and Scopus databases to present a clinical overview of all similar cases. Result: Maternal laboratory investigation revealed markedly increased calcium levels with concomitant high parathyroid hormone levels due to a parathyroid adenoma, undiagnosed during antenatal checkup. Conclusion: This is one of the few cases in the literature where neonatal symptomatology led to the diagnosis of undiagnosed maternal hyperparathyroidism. Early detection and appropriate management of neonatal hypocalcemia could eliminate serious maternal and fetal morbidity.

Osteitis fibrosa cystica mimicking bone tumor, a case report.

BACKGROUND: We report a case of osteitis fibrosa cystica, a rare benign resorptive bone lesion caused by hyperparathyroidism, that presented on imaging as an aggressive bone tumor. CASE PRESENTATION: The patient is a 51-year-old male complaining of severe sustained pain of the right hip region. Imaging studies were suspicious for a malignant tumor of the right iliac bone. Biopsy under CT guidance was performed and showed remodeled bone trabeculae with numerous osteoclasts, excluding bone tumor and raising the possibility of osteitis fibrosa cystica. Complementary tests disclosed elevated blood level of parathyroid hormone and a partially cystic enlarged left inferior parathyroid gland consistent with adenoma. After parathyroidectomy, the clinical symptoms were relieved and the radiological findings were significantly improved, which confirmed the diagnosis. CONCLUSIONS: Metabolic diseases-associated bone lesions should always be considered in the differential diagnosis of bone tumors, to avoid unnecessary surgeries and treatments.

Anesthetic considerations in hyperparathyroid crisis: A case report.

INTRODUCTION: Hyperparathyroid crisis is a rare and potentially life-threatening complication of severe calcium intoxication. Parathyroidectomy is the only curative method for hyperparathyroid crisis. Several case reports and case series have been published on the medical and surgical treatments for hyperparathyroid crisis, however, few reports have focused on the associated perioperative anesthetic management. PATIENT CONCERNS: A 48-year-old Chinese woman presented with a 2-week history of nausea and vomiting and complained of mental status alteration including confusion and agitation in the 24 hours prior to her admission. She denied any history of past illness. Laboratory tests showed severe hypercalcemia crisis with a serum calcium level of 5.21 mmol/L and a serum intact parathyroid hormone level of > 5000 pg/mL. DIAGNOSIS: The diagnosis was hyperparathyroid crisis, acute kidney injury, acute liver injury, rhabdomyolysis, infection, and shock. INTERVENTIONS: She underwent initial management with aggressive intravenous fluid resuscitation, loop diuretic treatment, vitamin D supplement, intravenous bisphosphonates, and calcitonin therapy. However, her condition worsened, and she was transferred to the operating theater for a parathyroidectomy under general anesthesia. She was under general anesthesia and monitored with electrocardiogram, pulse oxygen saturation, continuous arterial blood pressure, central venous pressure and nasopharyngeal temperature. Cardiac output and stroke volume variation were monitored from the FloTrac system. After liberal fluid rehydration, circulatory support, cooling treatment and calcium supplement after tumor removal, her unstable vital signs gradually improved. OUTCOMES: After meticulous anesthetic management by the anesthesiologist and complete tumor resection by the surgeon, she survived this fatal disease. The patients was discharged on postoperative day 37 without any sequelae. LESSONS: Patients with hyperparathyroid crisis should undergo a thorough preoperative evaluation. Difficult airway, fluid depletion, multiple organ dysfunction, hypercoagulability, and concomitant diseases are the primary challenges in anesthetic management. After tumor removal, the serum calcium level should be monitored closely and calcium should be supplemented in a timely manner to prevent serious complications.

Intra-operative parathyroid hormone evaluation is superior to frozen section analysis in parathyroid surgery.

BACKGROUND: Surgery is currently the only treatment option for patients with primary hyperparathyroidism (PHPT). Recently, minimally invasive parathyroidectomy (MIP) has begun to replace traditional bilateral neck exploration (BNE). OBJECTIVE: The aim of this study is to compare the results of parathyroidectomies performed in our hospital over the past decade that were guided by intra-operative parathyroid hormone (IOPTH) sampling or frozen section (FS) analysis. MATERIAL AND METHODS: Data on 697 patients who underwent parathyroidectomies in the Department of Endocrine Surgery, Dokuz Eylul University between January 2005 and 2018 were included in this study. Patients with malignancies other than thyroid papillary microcarcinoma and parathyroid cancer were excluded from the study. RESULTS: The concomitant use of neck ultrasound (US) and technetium 99m Sestamibi (99mTc MIBI) scintigraphy successfully localized the hyperfunctioning parathyroid glands in nearly 96% of cases. As compared with the IOPTH group, the operation time was longer in the FS group (p < 0.001), and the need for postoperative calcium (Ca) supplementation was higher (p < 0.001). The duration of hospitalization (days) was significantly higher in the FS group (4.2 ± 3.4 vs. 2.6 ± 1.9) as compared with that in the IOPTH group (p < 0.001). In addition, the recurrence rate in the FS group was significantly higher than that in the IPOTH group (p = 0.002). CONCLUSION: IOPTH sampling is a safe and effective method when performed by experienced surgeons and with appropriate preoperative screening. This study emphasizes that IOPTH sampling. We believe that the success in parathyroid surgery is due to three factors: correct indication, accurate localization and experienced surgeon.

Selective parathyroid venous sampling in reoperative parathyroid surgery: A key localization tool when noninvasive tests are unrevealing.

BACKGROUND: Preoperative localization studies are essential for parathyroid re-exploration. When noninvasive studies do not regionalize the abnormal parathyroid gland, selective parathyroid venous sampling may be employed. We studied the utility of parathyroid venous sampling in reoperative parathyroid surgery and the factors that may affect parathyroid venous sampling results. METHODS: Patients with hyperparathyroidism and previous cervical surgery undergoing evaluation for reoperative parathyroidectomy over a 20-year period were identified. Patients with indeterminate or negative noninvasive studies underwent parathyroid venous sampling. Parathyroid hormone values were mapped with a ≥2-fold increase above peripheral signifying positive parathyroid venous sampling. These results were correlated with reoperative findings. RESULTS: Parathyroid venous sampling was positive in 113 of 140 (81%). Re-exploration occurred in 75 (66%). Parathyroid venous sampling correctly detected the region of abnormal glands in 58 (77%). With 1 gradient, 1 abnormal gland was found in 81%. With multiple gradients, 1 abnormal gland was found in 78%, most often at the site with the largest gradient. Eighty percent of patients who underwent reoperative parathyroidectomy were biochemically cured. CONCLUSION: Parathyroid venous sampling can guide parathyroid re-exploration when noninvasive localizing studies are indeterminate. Expectation of 1 versus multiple remaining glands was key in interpreting the results.

Parathyroidectomy for tertiary hyperparathyroidism after second kidney transplantation: a case report.

Successful kidney transplantation usually resolves secondary hyperparathyroidism (SHPT). However, some patients fail to normalize, and their condition is often referred to as tertiary hyperparathyroidism (THPT). Surgical consensus on the timing of post-transplant parathyroidectomy (PTX) for THPT has not been reached. Herein, we report a case of a 58-year-old post-transplant woman, considering the concrete timing of PTX for both SHPT and THPT. She initiated hemodialysis with end-stage renal disease at the age of 24, and underwent first kidney transplantation at the age of 28. When peritoneal dialysis (PD) was induced due to the worsening kidney function at the age of 50, the serum intact parathyroid hormone (iPTH) level remarkably increased (2332 pg/mL). Although cinacalcet was administered, the patient's iPTH levels were not sufficiently suppressed for seven years. Diagnostic images including ultrasound, computed tomography, and 99mTc-methoxyisobutylisonitrile scintigraphy indicated THPT as the reason for prolonged post-transplant hypercalcemia. Therefore, PTX was performed 14 months after the second transplantation. Histology showed nodular hyperplasia of all parathyroid glands, indicating autonomous secretion of parathyroid hormone. In general, patients with more severe THPT are recognized with more severe SHPT prior to transplantation during the dialysis period. We should consider a referral for surgery based on the individual risk factors. We recommend to perform parathyroidectomy earlier, before the kidney transplantation in the clinical suspicion of severe SHPT.

Establish pre-clinical diagnostic efficacy for parathyroid hormone as a point-of-surgery-testing-device (POST).

Measuring the Parathyroid hormone (PTH) levels assists in the investigation and management of patients with parathyroid disorders. Rapid PTH monitoring is a valid tool for accurate assessment intraoperatively. Rapid Electro-Analytical Device (READ) is a point-of-care device that uses impedance change between target and capture probe to assess the PTH concentration in undiluted patient plasma samples. The aim of this work focuses on evaluating the analytical performance of READ platform to Roche analyzer as a prospective clinical validation method. The coefficient of variation (CV) for intra-assay imprecision was < 5% and inter-assay imprecision CV was < 10% for high (942 pg/mL) and low (38.2 pg/mL) PTH concentration. Functional sensitivity defined at 15% CV was 1.9 pg/mL. Results obtained from READ platform correlated well (r = 0.99) with commercially available clinical laboratory method (Roche Diagnostics) to measure PTH concentrations with a turn-around time of less than 15 min. Furthermore, the mean bias of 7.6 pg/mL determined by Bland-Altman analysis, showed good agreement between the two methods. We envision such a sensing system would allow medical practitioners to facilitate targeted interventions, thereby, offering an immediate prognostic approach as the cornerstone to delivering successful treatment for patients suffering from primary hyperparathyroidism.