Parathyroid Hormone Related Peptide Elevations in Normocalcemic Adults

Introduction/Objective Elevated parathyroid hormone-related peptide (PTHrP) is a biomarker often associated with hypercalcemia of malignancy. However, elevations of PTHrP can be seen in non-malignant patients with normal calcium status, notably renal failure. We investigate whether a LC-MS/MS test that specifically measures a peptide in the middle region of PTHrP fragments is immune to false elevations of PTHrP. Furthermore, we examine if PTHrP/PTH ratio or renal status can be used to further characterize PTHrP elevations in a cohort of normocalcemic patients. Methods/Case Report We conducted a retrospective study on adult patients that had at least one PTHrP laboratory test (i.e., ARUP PTHrP by LC-MS/MS) within the past 10 years (01/01/2011 to 04/29/2021) at a large academic center. We further stratified this cohort by demographics and additional laboratory markers including calcium status, parathyroid hormone (PTH) (i.e., by Siemens Centaur assay (Malvern, PA)), renal status, and known malignancies. Results (if a Case Study enter NA) We identified a total of 941 patients (585 female and 356 male). 33% of patients (30% [70/233] female and 36% [84/236] male) with elevated PTHrP were normocalcemic (i.e., did not have an elevation in calcium, ionized calcium, or diagnosis of hypercalcemia). 95% (21/22) of normocalcemic males and 100% (17/17) of normocalcemic females with an elevated PTHrP and elevated PTH had a PTHrP/PTH ratio below the normal sex specific reference ranges of 1.07 and 1.86, respectively. A subset of normocalcemic patients with elevated PTHrP had an estimated glomerular filtration rate (eGFR) recorded. Of these patients, 100% (58/58) of females and 94% (65/59) of males had an eGFR below 90 mL/min/1.73 m2 had an eGFR less than 30 mL/min/1.73 m2. and 50% (29/58) of females and 38% (26/69) of males Conclusion Our study supports the hypothesis that elevated PTHrP in the setting of normal calcium may occur due to renal insufficiency.

​Boron Supplementation to Calcium Inadequate Diet Influences Mineral Content of Serum, Tissue and Antioxidant Status in White Leghorn Layers

Background: Boron (B), a novel micronutrient is known to influence utilization of macrominerals. Present study was conducted in layer birds to study the effect of B supplementation to inadequate calcium (Ca) diet on mineral content in serum, tissue and antioxidant status. Methods: A total of 80 commrcial White Leghorn layers, 25 weeks old with a uniform body weight were randomly assigned to one of the 4 groups of 20 hens in each dietary group viz., Normal calcium (NC), inadequate/low calcium (LC), Normal calcium with 40 ppm B (NCB) and inadequate/low calcium with 40 ppm B (LCB). Dietary level of calcium was maintained at 100 and 90% of the requirement and sodium borate was used as B source. At the end of feeding trial, blood and tissue samples were collected for estimating mineral and biochemical parameters. Result: Boron supplementation did not significantly alter the serum mineral content, serum alkaline phosphatase and total antioxidant activity but significantly (P less than 0.025) increased the superoxide dismutase activity in layers fed inadequate Ca diet. Boron supplementation to both diets significantly (P less than 0.03) increased phosphorus (P) content in bone and muscle, and magnesium (Mg) content in muscle (P less than 0.019). Boron supplementation to Ca inadequate diet significantly (P less than 0.006) enhanced the P and Mg content in liver. Content of B was significantly (P less than 0.01) higher in serum, bone and liver of hens supplemented 40 ppm of B. Implication of this study is amelioration of abiotic stress due to inadequate Ca intake with B supplementation. It is concluded that 40 ppm B supplementation positively influenced the Ca, P and Mg utilization and serum SOD activity.

The Interplay between Calcium and Strontium in Chinese Cabbage under Normal and Low Calcium Conditions

The structure and chemical properties of strontium and calcium are similar. To study the interplay between calcium and strontium in plants, different concentrations of SrCl2 (0, 1, 4, and 10 mmol·L−1) were added to the Hoagland nutrient solution with 4 mmol·L−1 Ca2+ (normal level Ca2+) or 0.4 mmol·L−1 Ca2+ (low-level Ca2+), which were used to cultivate Chinese cabbage seedlings. Under the low-level calcium condition, strontium not only did not promote the growth of Chinese cabbage but showed more severe toxicity compared with that under the normal calcium condition. Under normal calcium condition, although the growth of Chinese cabbage was significantly inhibited by 4 mmol·L−1 strontium, strontium did not show significant toxicity. However, under the low-level calcium condition, 1 mmol·L−1 strontium caused a significant decline of plant biomass and photosynthetic activity. Sr2+ showed a competitive inhibitory effect on the absorption of Ca2+, and strontium was more easily absorbed by Chinese cabbage. Under the low-level calcium condition, strontium aggravated the inhibition of calcium absorption. The inhibitory effect of strontium on plant growth was significantly related to the calcium content in Chinese cabbage. Strontium cannot replace the function of calcium in plants under calcium-deficient conditions.

Spinal Stenosis Caused by Calcinosis in a Patient With Systemic Sclerosis

Calcinosis or dystrophic soft-tissue calcification occurs in damaged/devitalized tissues in the presence of normal calcium/ phosphorus metabolism.1 It is a known complication of connective tissues diseases, especially juvenile dermatomyositis and systemic sclerosis (SSc), and may be localized or widespread.2

Case Report: Severe Hypocalcemic Episodes Due to Autoimmune Enteropathy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic disorder, associated with endocrine deficiencies and non-endocrine involvement. Gastrointestinal (GI) manifestations appear in approximately 25% of patients and are the presenting symptom in about 10% of them. Limited awareness among pediatricians of autoimmune enteropathy (AIE) caused by destruction of the gut endocrine cells in APECED patients delays diagnosis and appropriate therapy. We describe an 18-year-old female presenting at the age of 6.10 years with hypoparathyroidism, oral candidiasis and vitiligo. The clinical diagnosis of APECED was confirmed by sequencing the autoimmune regulator-encoding (AIRE) gene. Several characteristics of the disease—Hashimoto’s thyroiditis, Addison’s disease, diabetes mellitus type 1 and primary ovarian insufficiency—developed over the years. She had recurrent episodes of severe intractable hypocalcemia. Extensive GI investigations for possible malabsorption, including laboratory analyses, imaging and endoscopy with biopsies were unremarkable. Revision of the biopsies and chromogranin A (CgA) immunostaining demonstrated complete loss of enteroendocrine cells in the duodenum and small intestine, confirming the diagnosis of AIE. Management of hypocalcemia was challenging. Only intravenous calcitriol maintained calcium in the normal range. Between hypocalcemic episodes, the proband maintained normal calcium levels, suggesting a fluctuating disease course. Repeated intestinal biopsy revealed positive intestinal CgA immunostaining. The attribution of severe hypocalcemic episodes to AIE emphasizes the need for increased awareness of this unique presentation of APECED. The fluctuating disease course and repeated intestinal biopsy showing positive CgA immunostaining support a reversible effect of GI involvement. CgA immunostaining is indicated in patients with APECED for whom all other investigations have failed to reveal an explanation for the malabsorption.

Pulmonary alveolar microlithiasis: Blizzard of lung

Pulmonary alveolar microlithiasis (PAM) is a rare inherited disorder in which patients present with either nonspecific signs and symptoms or are asymptomatic. Clinical-radiological dissociation is a commonly seen feature of the disease. Majority of cases are diagnosed in second and third decade of life, although presentation in paediatric and elderly population is also reported. Pathognomonic radiological findings, with normal calcium and phosphate levels can confirm the diagnosis without the need of further investigations in large number of cases. A high index of suspicion and knowledge of the disease is of paramount importance as it has a wide range of presentation and variable course thus posing a diagnostic challenge. We present two cases of this rare disease in elderly females with distinct presentations although with similar and characteristic radiological findings along with a brief review of literature of the disease.

18F-Fluorocholine-PET/CT for Localizing Hyperfunctioning Parathyroid Glands and Optimizing Surgical Treatment in Patients With Hyperparathyroidism

PurposeHyperparathyroidism (HPT) is a common disorder. Cure can only be achieved by removal of all diseased glands. Exact localization of hyperfunctioning glands is of importance to prevent extensive surgical exploration. The number of false negative/inconclusive results in standard imaging techniques is high. We aimed to evaluate the diagnostic accuracy of 18F-Fluorocholine-PET/CT (FCH-PET/CT) and its sensitivity in patients with primary, secondary/tertiary and familial HPT with negative and/or discordant findings in ultrasound and/or 99mTc-sestamibi scintigraphy/SPECT/CT.Methods96 patients with HPT and negative/equivocal conventional imaging were referred for FCH-PET/CT. 69 patients who have undergone surgery and histopathologic workup were analyzed in this retrospective single institution study. 60 patients suffered from primary HPT, 4 from secondary or tertiary HPT and 5 from familial HPT. Sensitivities, positive predictive values, and accuracies were calculated.ResultsAll patients showed normalized serum calcium levels in the postoperative period. The follow-up rate was 97%. 58 of 60 patients with primary HPT and 4 of 4 patients with secondary/tertiary HPT showed normal calcium- and PTH-levels after 6 months and were cured. 4 of 5 patients with familial HPT were cured. Sensitivity/positive predictive value (PPV) per lesion for primary HPT was 87.5/98.3%, for secondary/tertiary HPT 75/100% and for familial HPT 14.6/100%, respectively. Sensitivity/PPV per patient was 91.5/98.2% for primary HPT, 100/100% for secondary/tertiary HPT and 50/100% for familial HPT, respectively.ConclusionDiagnostic accuracy of 18F-Fluorocholine-PET/CT for patients with pHPT is excellent. 18F-Fluorocholine-PET/CT is a valuable tool for endocrine surgeons to optimize the surgical treatment of patients with hyperparathyroidism.