Elevated Serum Parathyroid Hormone Levels Research Articles

Neonatal Severe Hyperparathyroidism: A Case Report

Background: Neonatal severe hyperparathyroidism is an extremely rare condition that presents in the first few months of life. Recognition at the early stage followed by prompt surgical intervention are of vital importance for survival. Hypotonia, respiratory distress, lethargy and delay in growth and development occur in association with the elevated serum parathormone levels and hypercalcemia. Definitive therapy involves total parathyroidectomy. Case Description: We are presenting a case with Neonatal severe hyperparathyroidism, who underwent total parathyroidectomy. The patient had been followed up with medical therapy until. Parathormone levels rapidly declined following total parathyroidectomy and the patient was discharged with full recovery. Literature Review: Sestamibi scintigraphy might fail to show an ectopic parathyroid gland. In such conditions, on table confirmation of parathyroid glands by frozen section and Intraoperative parathormone monitoring is vital at this point. Persistently elevated parathormone levels might suggest a remnant parathyroid tissue at the surgical site or an ectopic parathyroid gland that should be excised. Clinical Relavance: Neonatal severe hyperparathyroidism is a life-threatening disease. In the present case surgery performed at the early is life-saving due to the failure of medical therapy to control the disease.

C-Cell Hyperplasia and Cystic Papillary Thyroid Carcinoma in a Patient with Type 1B Pseudohypoparathyroidism and Hypercalcitoninaemia: Case Report and Review of the Literature.

Hypercalcitoninaemia has been described in patients with pseudohypoparathyroidism (PHP) type 1A and 1B. Elevated calcitonin levels are thought to result from impaired Gsα receptor signaling, leading to multiple hormone resistance. Evidence on the risk of medullary thyroid carcinoma (MTC) or C-cell hyperplasia in PHP patients with hypercalcitoninaemia is lacking. A 43-year-old Caucasian man was referred to our endocrinology clinic for chronic hypocalcemia associated with elevated serum parathormone levels and a single cystic thyroid nodule. The patient did not show skeletal deformities, and screening for concomitant hormone resistances was negative, except for the presence of elevated serum calcitonin levels. The workup led to a molecular diagnosis of sporadic PHP1B. Fine needle aspiration of the thyroid nodule was not diagnostic. The calcium stimulation test yielded an abnormal calcitonin response. Given the scarcity of data on the risk of thyroid malignancy in PHP and calcium stimulation test results, total thyroidectomy was performed. Histological examination revealed cystic papillary thyroid cancer in a background of diffuse C-cell hyperplasia. To our knowledge, we are the first to describe a rare form of thyroid cancer combined with C-cell hyperplasia in a patient with PHP and hypercalcitoninaemia. In the present case, a mere receptor resistance might not fully explain the elevated calcitonin levels, suggesting that hypercalcitoninaemia should be carefully evaluated in PHP patients, especially in the case of concomitant thyroid nodules. Further studies on larger cohorts are needed to elucidate this topic.

흉선에서 발생한 이소성 부갑상선 선종 1예

Primary hyperparathyroidism (PHPT) is a common endocrine disorder with elevated serum parathyroid hormone levels. In most cases, the disease involves a single parathyroid adenoma, followed by parathyroid hyperplasia. Parathyroid glands are rare, but can be present in a variety of locations because it migrates long distance during fetal period. Therefore, the incidence of ectopic parathyroid adenoma is rare and it is not easy to diagnose ectopic parathyroid adenomas and to specify the location before surgery. Recently, we diagnosed ectopic parathyroid adenoma at the thymus and treated successfully. So, we report this case with literature review.

OR23-01 The Nonredundant Role Of Beta-Amyloid In Mediating Tonic PTH Secretion In Physiological And Pathological States

Abstract Disclosure: C. Tu: None. Z. Cheng: None. K.A. Pena: None. N. Szeto: None. J.A. Sosa: None. J. Vilardaga: None. J. Koh: None. W. Chang: None. Understanding the mechanisms driving parathyroid hormone (PTH) hypersecretion in primary hyperparathyroidism (PHPT) is essential for better management of this common endocrinopathy. Prior studies showed that reduced Ca2+-sensing receptor (CaSR) expression and the subsequent increases in heterodimerization of the CaSR with the type B γ-aminobutyric acid receptor 1 (GABAB1R) are causally linked to PTH hypersecretion in PHPT mouse models (Nat Metab 2:243-255). We further showed that expression of the putative GABAB1R ligands, amyloid precursor protein (APP) and its proteolytic product, β-amyloid (Aβ1-42), is significantly upregulated in adenomas of PHPT patients associated with vitamin D insufficiency/deficiency when compared to normal donor controls. The current study aims to delineate the actions of Aβ1-42 in promoting tonic PTH secretion and its interactions with vitamin D receptor (VDR) signaling in parathyroid glands (PTGs) in basal and PHPT states. We show that Aβ1-42 (200 nM) stimulated tonic PTH secretion in cultures of normal human PTGs without shifting the calcium/PTH secretion setpoint (Ca2+-setpoint). In contrast, conditional knockout (KO) of the App gene in the parathyroid cell (PTC) of PTCAppΔflox/Δflox mice significantly reduced serum PTH levels (KO: 64±13 pg/ml vs Control: 109±12 pg/ml; p<0.05, n=8) despite hypocalcemia, indicating hypoparathyroidism. In PTGs cultured from the PTCAppΔflox/Δflox mice, supplementation of Aβ1-42 dose-dependently (EC50=5.6 nM, p<0.001) increased PTH secretion without altering the Ca2+-setpoint. However, the stimulatory effects of Aβ1-42 on tonic PTH secretion were completely abrogated in the PTGs with concurrent deletions of App, Casr and Gabbr1 genes, supporting a direct action of Aβ1-42 on CaSR and/or GABAB1R. The latter notion is further supported by the ability of Aβ1-42 to stimulate cAMP production in cells co-expressing CaSR and GABAB1R. PTC-specific deletion of the Vdr gene in the PTCVdrΔflox/Δflox mice led to elevated serum PTH levels in vivo and increased tonic PTH secretion with unaffected Ca2+-setpoint in PTGs in vitro. Concurrent ablation of the App gene completely normalized serum PTH levels in the PTCVdrΔflox/Δflox mice and prevented PTH hypersecretion in their PTGs in culture. These findings support a critical role of the APP-derived Aβ1-42 in mediating tonic PTH secretion in the normal physiological state and suggest a new mechanism driving PTH hypersecretion in PHPT due to vitamin D deficiency. Presentation: Saturday, June 17, 2023

A case of right parathyroid adenoma and its management

A 33 year old female patient presented with history of body and joint pain with easy fatiguability unable to perform her routine daily activities since 2 months. She also gave history of recurrent urinary tract infections, pain abdomen, loss of appetite and loss of weight. Examination of neck showed no palpable mass. Laboratory data revealed elevated serum calcium levels and parathyroid hormone levels. Contrast enhanced computed tomography of neck showed well-defined soft tissue density lesion measuring 2.6×1.9×1.6 cm in the postero inferior aspect of right lobe of thyroid suggestive of right parathyroid adenoma. Parathyroid imaging (SPECT) 99mTc-MIBI showed focal increased tracer uptake in relation to inferior aspect of right lobe of thyroid gland. NCCT KUB showed bilateral non obstructive renal calculi with medullary nephrocalcinosis. Patient underwent surgical resection under general anesthesia and histopathology confirmed parathyroid adenoma. Following surgery, parathyroid hormone and calcium levels gradually returned to normal levels. Parathyroid adenoma shows excellent prognosis with complete surgical resection.

Serum Calcium, 25-Hydroxyvitamin D, and Parathyroid Hormone Levels in Relation to Aneurysmal Subarachnoid Hemorrhage.

Elevated serum calcium (S-Ca), 25-hydroxyvitamin D (S-25OHD), and parathyroid hormone (S-PTH) levels have been associated with risk of aneurysmal subarachnoid hemorrhage (SAH) in observational studies. However, whether these associations are causal is unclear. The objective of the present study was to determine whether genetically predicted S-Ca, S-25OHD, and S-PTH levels are causally associated with aneurysmal SAH using a Mendelian randomization design. Analyses were performed using summary-level data for genetic variants associated with S-Ca, S-25OHD, and S-PTH concentrations. Summary data for aneurysmal SAH were adopted from a genome-wide association study (GWAS) on intracranial aneurysm (n = 79,429 individuals, 69% of the cases had aneurysmal SAH). The inverse variance-weighted approach was adopted as the primary analyses. For sensitivity analyses, the weighted median and MR-Egger approaches were adopted. Genetically predicted S-Ca and S-PTH levels were associated with aneurysmal SAH in the primary analyses. The odds ratios (ORs) of aneurysmal SAH were 1.96 (95% CI: 1.003-3.812; P = 0.049) and 1.495 (95% CI: 1.058-2.114; P = 0.023) for one SD increase of genetically predicted S-Ca and S-PTH levels, respectively. Genetically predicted S-25OHD concentration was not associated with aneurysmal SAH (per 1 SD increase in S-25OHD: OR = 0.92; 95% CI, 0.78-1.09; P = 0.332). Sensitivity analysis yielded similar results, and no evidence of pleiotropy was observed. Our results indicated that higher genetically predicted S-Ca and S-PTH levels may increase the risk of aneurysmal SAH.

Impact of serum vitamin D level on selected bone-related markers in obese- type 2 diabetes patients

Background: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for skeletal fractures. The causes are probably a mix of factors, including poor glycemic control, a higher risk of falling due to hypoglycemia, osteopenia, bone quality deterioration, and drug side effects related to bone fragility. Undercarboxylated osteocalcin (ucOC) is a protein generated by osteoblasts that affects insulin secretion and sensitivity. Methods: A total number of 47 obese (BMI ˃ 30) patients with confirmed type 2 diabetes were selected depending on the American Diabetes Association ADA criteria. The control participants were similar to the patients in age and gender, with a total number of 43 obese (BMI ˃ 30) and healthy subjects chosen from the general population. The selected subjects were grouped according to their serum vitamin D levels. Their blood specimen was used for assaying ucOC, parathyroid hormone (PTH), and vitamin D3 levels by specific ELISA kits, and to estimate calcium (Ca2+) levels and inorganic phosphate (PO43−) via enzymatic colorimetric methods. Results: Serum parathyroid hormone and inorganic phosphate median (IQR) values were markedly increased in patients with T2DM when compared to healthy controls, whereas serum calcium and ucOC levels were lowered significantly in diabetic patients when compared to healthy controls. This was irrespective of serum vitamin D levels. Conclusions: Elevated serum levels of PTH and PO43− values in obese type 2 diabetic patients compared to obese non-diabetic controls were accompanied by a significant decrease in ucOC and Ca2+ levels, irrespective of serum vitamin D levels. Hence, serum vitamin D3 levels had no significant impact on levels of ucOC, PTH, Ca2+, and PO43− in obese patients with type 2 diabetes.

ODP117 Pseudohypoparathyroidism Type IB: A Rare Cause of Hypocalcemia

Abstract Introduction Pseudohypoparathyroidism (PHP) describes disorders of hypoparathyroidism that are the result of resistance of target tissues to the actions of parathyroid hormone (PTH). Studies have estimated the prevalence of PHP to be 0.34 in 100,000 in Japan and 1.1 in 100,000 in Denmark. The first biochemical abnormalities to become apparent are elevated serum levels of PTH and elevated serum levels of phosphorus, followed by hypocalcaemia. We present a patient diagnosed with PHP Type 1B (PHP1B), which was presented to us many years after her initial diagnosis, with other major comorbidities now present. Case description This patient is an 81 year old female presenting to the clinic to discuss her previously diagnosed PHP1B. Her past medical history revealed she began having symptoms of intermittent muscle cramping at the age of 22, followed by carpopedal spasms and periorbital paresthesia a year later. She has also had a physical examination significant for a positive Trousseau sign, but no phenotypical signs of Albright hereditary Osteodystrophy (AHO). Lab evidence from 1977 was recovered showing urinary cyclic AMP level <20 nmol/mg after administration of PTH, consistent with PHP1B. The family history in her parents and children has revealed no similar genetic history so far. Other comorbidities she has developed since her diagnosis are hypokalemia, hypothyroidism, osteoporosis with a femur fracture, obesity, chronic kidney disease and nephrolithiasis. She has been continuing treatment throughout her life with calcium, calcitriol and vitamin D supplementation for hypocalcemia. She has been mostly eucalcemic since then, and complains of occasional carpopedal spasms and perioral numbness. Discussion PHP1B is isolated resistance to PTH in the kidney and normal PTH response in bone without features of AHO. PHP1A and 1C have PTH resistance in bone, and both express AHO. These various forms of PHP are due to defects in the GNAS gene that lead to decreased expression of the alpha-subunit of G protein (Gsa). In the absence of molecular analysis, the clinical and biochemical overlap between PHP and related disorders can lead to challenges in diagnostic classification. There are 2 types of PHP1B cases- autosomal dominant (AD) and sporadic. However, the majority of Patients with PHP1B do not have mutations within the GNAS but they have methylation and imprinting defects that result in absence of maternal Gsa. To emphasize, epimutation study rather than sequencing of the coding region in GNAS should be performed for genetic investigation, which has now become standard practice. Although there is no difference in clinical presentation between AD PHP1B and sporadic PHP1B, their differentiation early during the disease onset can help providers give patients more reliable genetic and reproductive counseling and provide optimal medical management of complications such as hypocalcemia. Presentation: No date and time listed

Normocalcemic non-renal hyperparathyroidism

Parathyroid hormone (PTH) is produced by the parathyroid glands, which are the main regulators of calcium and phosphorus metabolism. Hyperparathyroidism is a clinical condition associated with an increase in serum PTH content. The state of parathyroid glands depends very much on the amount of vitaminD, magnesium and boron in the blood because, according to official data, substantiated by a number of scientific studies, the majority of the world population (80%) has a lack/deficiency of vitamin D. This fact explains the high prevalence of thyroid diseases (hyperplasia, adenoma, hyperparathyroidism) and associated pathology. Previous studies have shown that a deficiency/lack of vitaminD was found in 85–94% of Ukraine population. A deficiency/lack of vitamin D compensatorily stimulates an increase in PTH synthesis. Doctors very rarely determine the level of PTH, which prolongs the progression of hyperparathyroidism, and they detect it only with severe associated changes in other systems. Hyperparathyroidism occurs when one or more of the parathyroid glands become hyperactive, gradually leading to elevated serum parathyroid hormone levels and hypercalcemia. The diagnostic criteria for hyperparathyroid conditions are very vague, which is confusing and leads to unnecessary surgeries instead of simple vitamin D and boron therapy. Normocalcemic primary hyperparathyroidism is a diagnosis of exclusion, and it can be considered only after careful assessment of the causes of secondary hyperparathyroidism, including that associated with a lack of vitamin D. The most common form of hyperparathyroidism is normocalcemic non-renal hyperparathyroidism. Prophylactic use of vitamin D in the correct individualized doses (25(OH)D range of 100–150 nmol/l or 40–60 ng/ml) should reduce the risk of parathyroid pathology but only 10% of the population receives such therapy, others do not know that it is useful. The only way to eliminate the gradual progression of parathyroid disorders is to administer individual prophylactic or therapeutic doses of vitaminD.

Vitamin D Deficiency Mimicking Pseudohypoparathyroidism Type II in an Adolescent Boy: A Case Report

Background: Vitamin D deficiency in children is common and usually characterized by hypocalcemia, hypophosphatemia, and elevated serum parathyroid hormone level. However, vitamin D deficiency can be associated with parathyroid hormone resistance in the kidneys which may cause hyperphosphatemia instead, mimicking thus pseudohypoparathyroidism type II. The exact pathogenesis for parathyroid hormone resistance remains unclear, and the distinction between the two conditions remains difficult. We describe the case of an adolescent who presented with seizures and was found to have biochemical features consistent with pseudohypoparathyroidism, likely related to vitamin D deficiency. Case Report: A 13-year-old previously healthy adolescent presented with seizures. He experienced back pain during the previous month prior to the presentation. He did not have features of Albright hereditary osteodystrophy. His laboratory studies were significant for hypocalcemia, hyperphosphatemia, elevated serum alkaline phosphatase level, elevated parathyroid hormone level, and a deficient vitamin D level. Magnetic resonance imaging of the spine revealed multiple compression fractures. The child was treated with intravenous calcium and vitamin D administration with rapid improvement and his seizures resolved. Conclusion: Hypocalcemia from vitamin D deficiency can mimic pseudohypoparathyroidism type II. The principles of treatment for hypocalcemia in both conditions are similar and patients require timely intervention with close follow-up to ensure the resolution of symptoms. Patients with resolution of symptoms after adequate treatment may not require further evaluation for other types of pseudohypoparathyroidism.

A Randomized Controlled Dose-Escalation Study of LY06006, a Recombinant Humanized Monoclonal Antibody to RANKL, in Chinese Healthy Adults.

Background: This study was conducted to explore the safety, tolerance, pharmacokinetics, pharmacodynamics, and immunogenicity of LY06006, a recombinant humanized monoclonal antibody to RANKL, when administrated subcutaneously in Chinese healthy adults. Research design and methods: This was a randomized, double-blinded, placebo-controlled, single ascending dose study performed in 32 healthy Chinese adults, who were randomly assigned to receive a single injection dose of 18, 60, 120 mg study drug or placebo with a follow-up of 140–252 days. Results: No deaths or drug-related serious adverse events occurred. LY06006 was rapidly absorbed in the 60 mg group with a Tmax range of 120–480 h and serum LY06006 concentrations decreased slowly 11–13 days after dosing with a long mean (SD) half-life of 389.58 (63.44) h. The most frequent AEs were elevated serum parathyroid hormone (PTH) level (83.3%), hypocalcemia (54.2%), and hypophosphatemia (45.8%). None of the 32 subjects tested positive for anti-drug antibody during the trial. Conclusion: Single-dose subcutaneous administration of LY06006 was safe and well-tolerated in healthy Chinese adults. Cmax showed linear pharmacokinetic characteristics in the dose range of 18–120 mg based on dose-exposure proportionality analysis.

Thoracoscopic removal of a posterior mediastinal parathyroid adenoma

Ectopic Parathyroid Adenomas (EPA) can occur in many anatomical locations and the most frequent one was the mediastinum region. Traditionally, the adenoma resection has been performed through conventional thoracotomy or sternotomy. Recently, a few cases of thoracoscopic excision of mediastinal adenoma were reported. We report here the case of a successful exclusive thoracoscopic removal of a mediastinal parathyroid adenoma. A 58-year-old female patient presented with bilateral renal stones and fatigue. Biology results showed elevated serum calcium and parathyroid hormone levels. The diagnosis of primary hyperparathyroidism caused by solitary EPA in lateralesophageal region was confirmed by imaging tools. The patient underwent successful thoracoscopic resection. He was discharged on the 2rd postoperative day. Keywords: primary hyperparathyroidism; parathyroid adenoma; mediastinum; thoracoscopic excision.

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

BackgroundNormocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients.MethodsA total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122).ResultsNPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions.ConclusionWe found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Increased thyroid malignancy in patients with primary hyperparathyroidism.

BackgroundMultiple studies have reported the increased incidence of thyroid cancer in patients with primary hyperparathyroidism (PHPT). However, the underlying risk factors of concomitant thyroid cancer in patients with PHPT remain unknown. The primary aim of this study was to examine the records of patients with PHPT to identify characteristics that correlated with the presence of coexisting thyroid nodules, and which may have an implication for the prediction of thyroid cancer.MethodsMedical records of consecutive patients with PHPT (n = 318) were reviewed from January 2010 to September 2020 in two tertiary medical centers in China. Patient clinicopathological and biological data were collected and analyzed.ResultsOf a total of 318 patients with PHPT, 105 (33.0%) patients had thyroid nodules and 26 (8.2%) patients were concomitant with thyroid cancer. A total of 38 thyroid nodules taken from 26 patients were pathologically assessed to be well-differentiated papillary thyroid carcinoma (PTC), with 81% being papillary thyroid microcarcinoma (PTMC). In 79% (30/38) of these cancers, thyroid nodules were considered suspicious following preoperative ultrasound. Multinomial logistic regression analysis revealed that female gender was associated with increased risk of thyroid nodules (OR = 2.13, 95% CI: 1.13–3.99, P = 0.019), while lower log-transformed parathyroid hormone levels were an independent predictor of thyroid cancer in patients with PHPT (OR = 0.50, 95% CI: 0.26–0.93, P = 0.028).ConclusionIn conclusion, we observed a relatively high prevalence of thyroid cancer in our cohort of Chinese patients with PHPT. Evaluation of thyroid nodules by preoperative ultrasound may be advisable in patients with PHPT, particularly for females and patients with modestly elevated serum parathyroid hormone levels.

The elevated serum parathyroid hormone level is associated with the occurrence of atrial fibrillation in patients with advanced heart failure.

The elevated serum parathyroid hormone level is associated with the occurrence of atrial fibrillation in patients with advanced heart failure.

Utility of blood tests in screening for metabolic disorders in kidney stone disease.

To determine the clinical utility of blood tests as a screening tool for metabolic abnormalities in patients with kidney stone disease. Clinical and biochemical data from 709 patients attending the Oxford University Hospitals NHS Foundation Trust for assessment and treatment of kidney stones were prospectively collected between April 2011 and February 2017. Data were analysed to determine the utility of serum calcium, parathyroid hormone (PTH), urate, chloride, bicarbonate, potassium and phosphate assays in screening for primary hyperparathyroidism, normocalcaemic hyperparathyroidism, hyperuricosuria, distal renal tubular acidosis (dRTA) and hypercalciuria. An elevated serum calcium level was detected in 2.3% of patients. Further investigations prompted by this finding resulted in a diagnosis of primary hyperparathyroidism in 0.2% of men and 4.6% of women for whom serum calcium was recorded. An elevated serum PTH level in the absence of hypercalcaemia was detected in 15.1% of patients. Of these patients, 74.6% were vitamin D-insufficient; no patients were diagnosed with normocalcaemic hyperparathyroidism. Hyperuricosuria was present in 21.6% of patients and hypercalciuria in 47.1%. Hyperuricaemia was not associated with hyperuricosuria, nor was hypophosphataemia associated with hypercalciuria. No patient was highlighted as being at risk of dRTA using serum chloride and bicarbonate as screening tests. This study indicates that individuals presenting with renal calculi should undergo metabolic screening with a serum calcium measurement alone. Use of additional blood tests to screen for metabolic disorders is not cost-effective and may provide false reassurance that metabolic abnormalities are not present. A full metabolic assessment with 24-h urine collection should be undertaken in recurrent stone formers and in those at high risk of future stone disease to identify potentially treatable metabolic abnormalities.

Calcific uraemic arteriolopathy

A 52-year-old man with end-stage renal disease (ESRD) undergoing haemodialysis presented with systemic non-healing and painful skin ulceration (figure 1A,B). Two years previously, he was diagnosed with giant cell arteritis...

Abdominal Pain in a Patient with Hypercalcemia.

### Case Answer A 56-year-old woman with a medical history of hypertension, diabetes, and obesity presented to the emergency room with abdominal pain. She was on losartan/hydrochlorothiazide and dapagliflogin. Computed-tomography imaging of her abdomen revealed bilateral medullary nephrocalcinosis with a few calyceal tip stones (Figure 1A). She did not have any prior history of kidney stones or a family history of kidney stones. Serum chemistry was remarkable for hypercalcemia at 11 mg/dl, serum phosphorous of 2.9 mg, elevated serum parathyroid hormone level of 74 pg/ml, and normal serum creatinine of 0.82 mg/dl. Her 25-hydroxyvitamin D level was normal at 52 ng/ml (normal, 51–80 ng/ml). The rest of her laboratory results were normal. She underwent a 24-hour urine supersaturation study that showed …

Heterophile antibody interference associated with natural killer cell therapy.

The adoptive transfer of ex vivo-expanded natural killer (NK) cells has recently been employed as an alternative cancer treatment in certain institutions. However, the safety profiles of this strategy remain uncharacterized. We evaluated three patients who exhibited elevated serum parathyroid hormone (PTH) levels without the relevant clinical manifestations and had a history of autologous NK cell therapy. The serum PTH concentration was measured using a second-generation PTH assay, and the serum thyroglobulin concentration was measured using a second-generation thyroglobulin assay. Subsequently, the PTH or thyroglobulin concentration obtained using heterophile-blocking tube (HBT) for a secondary confirmation assay was measured and compared with the result of the initial assay. The three patients had falsely elevated serum PTH and thyroglobulin levels owing to heterophile antibody interference associated with NK cell therapy that persisted for at least up to 12 months after the treatment and was confirmed by normalization of hormone levels after HBT treatment. We propose that certain types of mouse monoclonal antibodies used to stimulate NK cells can induce heterophile antibodies. Abnormal laboratory test results in individuals administered NK cell therapy without the relevant clinical manifestations must be examined in the context of heterophile antibody interference to avoid misdiagnosis and unnecessary testing.

Diagnosis and Management of Primary Hyperparathyroidism Across the Veterans Affairs Health Care System

Untreated primary hyperparathyroidism impairs quality of life and incurs substantial costs. Parathyroidectomy is a low-risk, high-success, definitive intervention. To determine the appropriateness of diagnostic evaluation for primary hyperparathyroidism in patients with hypercalcemia and the use of parathyroidectomy for the treatment of primary hyperparathyroidism across the Veterans Affairs (VA) health care system. A retrospective cohort study of veterans with hypercalcemia and primary hyperparathyroidism was conducted from January 1, 2000, through September 30, 2015, using the VA Corporate Data Warehouse, a national electronic health record-based repository. The study included 371 370 veterans with chronic hypercalcemia and 47 158 veterans with biochemical evidence of primary hyperparathyroidism diagnosed by hypercalcemia, elevated serum parathyroid hormone levels, and near-normal serum creatinine levels. Statistical analysis was performed from April 21, 2017, to April 10, 2019. The proportion of veterans with hypercalcemia who have parathyroid hormone levels evaluated, the proportion of veterans with hyperparathyroidism who are treated surgically, and the factors associated with parathyroidectomy using generalized linear latent and mixed model regression. Of 371 370 patients with chronic hypercalcemia, 86 887 (23.4%) received further testing with parathyroid hormone level. Of 47 158 patients meeting diagnostic criteria for primary hyperparathyroidism (42 737 men [90.6%] and 4421 women [9.4%]; mean [SD] age, 67.3 [11.8] years), 6048 (12.8%) underwent parathyroidectomy. Of 5793 patients with primary hyperparathyroidism presenting with a serum calcium level more than 1 mg/dL above the upper limit of normal, 1501 (25.9%) underwent parathyroidectomy. There was a decreasing trend in the use of parathyroidectomy over time. Factors positively associated with parathyroidectomy were nephrolithiasis (odds ratio [OR], 2.23; 95% CI, 1.90-2.61) and non-Hispanic white race/ethnicity (OR, 1.31; 95% CI, 1.17-1.46), while age (OR, 0.95; 95% CI, 0.95-0.96), Elixhauser Comorbidity Index score (OR, 0.76; 95% CI, 0.72-0.80), decreased estimated glomerular filtration rate (OR, 0.52; 95% CI, 0.45-0.60), and diagnosis of osteoporosis (OR, 0.65; 95% CI, 0.52-0.80) were inversely related to surgery. From this study's findings, parathyroid hormone level is infrequently tested in patients with hypercalcemia, suggesting underdiagnosis of primary hyperparathyroidism. Patients meeting diagnostic criteria for primary hyperparathyroidism are undertreated with recommended parathyroidectomy. Similar gaps have previously been observed in non-VA care of primary hyperparathyroidism, suggesting the need for a systematic evaluation of barriers to diagnosis and treatment that informs intervention design.