High PTH Levels Research Articles

Cortical bone density by quantitative computed tomography mirrors disorders of bone structure in bone biopsy of non-dialysis CKD patients

Bone biopsy is still the gold standard tool to evaluate either trabecular or cortical bone, though the quantitative computed tomography of the vertebrae (QCT), a non-invasive technique, could be useful to evaluate bone structure in patients with chronic kidney disease (CKD). Cortical bone microstructure derangements have been associated with poor outcomes in the general population. An association between trabecular bone density, assessed by QCT, and bone volume and microarchitecture by histomorphometry, has been previously documented. This relationship has not yet been fully evaluated in cortical bone in the CKD scenario. The aim of this study was to evaluate the relationship among vertebrae density measured by QCT, structural histomorphometric parameters of cortical bone and biochemical and hormonal data in 50 CKD stage 2-5ND patients. This was a post hoc analysis of a cross-sectional study where cortical porosity and cortical thickness were analyzed in undecalcified bone samples from the iliac crest. The cortical bone density was obtained by QCT from the thoracic vertebrae. The patients were 52 ± 10 years, 68% men, 30% diabetes and the estimated glomerular filtration rate 34 ± 16 mL/min/1.73 m2. Cortical porosity was 4.6% (3.6; 6.6) and cortical thickness was 578.4 ± 151.8 μm, while cortical bone density was 149.2 ± 58.3 HU. Cortical density correlated with cortical thickness (p = 0.001) but not with cortical porosity (p = 0.30). Higher porosity was associated with older age (p = 0.02), higher levels of PTH (p = 0.04) and lower renal function (p = 0.03), while smaller thickness was associated with higher levels of PTH (p = 0.02). Lower density was associated with older age (p = 0.02) and higher levels of PTH (p = 0.01). In conclusion, cortical bone density measured by QCT was able to mirror the cortical thickness of bone biopsy in pre-dialysis CKD patients. In addition, PTH action on cortical bone can be already seen in this population.

Standard Biliopancreatic Limb (50cm) Roux-en-Y Gastric Bypass Versus Long Biliopancreatic Limb (100cm) Roux-en-Y Gastric Bypass in Patients with Body Mass Index 40-50kg/m2: a Randomized Prospective Study.

Roux-en-Y gastric bypass (RYGB) is a widely performed procedure worldwide especially with the presence of associated medical conditions. Patients with body mass index (BMI) 40-50kg/m2 are at more risk of weight regain and relapse of comorbidities. There is a controversy on the optimum alimentary (AL) and biliopancreatic (BPL) limb lengths to be used in RYGB to achieve weight loss and remission of comorbidities without causing nutritional deficiencies in those patients. hundred-and-fifty patients with BMI between 40 and 50kg/m2 were divided equally into 2 groups undergoing standard RYGB (S-RYGB) with AL:150cm and BPL: 50cm and long biliopancreatic RYGB (L-RYGB) with AL: 100cm and BPL: 100cm. BMI, % of total weight loss (%TWL), effect on diabetes (DM), hypertension (HTN), dyslipidemia, and nutritional statuses were recorded at 1, 2, and 3years. Only 64/75 patients in S-RYGB and 57/75 patients in L-RYGB completed the study. L-RYGB had faster weight loss, higher %TWL, and less BMI than S-RYGB with the maintenance of achieved weight. L-RYGB had better control of DM and dyslipidemia than S-RYGB. There were no significant differences in nutritional status between S-RYGB and L-RYGB rather than lower levels of calcium and Hb and higher levels of PTH in L-RYGB yet they remain within the normal range. The application of L-RYGB helps in achieving faster weight loss for a longer period with better remission of associated comorbidities as DM, HTN, and dyslipidemia in patients with BMI 40-50kg/m2 but with effects on the nutritional status.

Mathematical model for preoperative differential diagnosis for the parathyroid neoplasms

Background and objectivePreoperative diagnosis of parathyroid carcinoma (PC) is critical for the determination of the scope of surgical intervention. Nowadays, specific diagnostic markers for differentiation of PC and benign tumors are unknown, and less than half of patients with PC undergo necessary en bloc surgery. The aim of this study was to develop the instrument for preoperative diagnosis of PC. MethodsA multi-center retrospective study included 242 patients with primary hyperparathyroidism: 50 patients with PC, 30 with аtypical adenoma (AA), and 162 with adenoma of the parathyroid glands. ResultsPatients with PC and AA had higher levels of PTH, ionized and albumin-corrected calcium, ALP, volume and the largest diameter of neoplasm, and the higher frequency of GFR decrease less than 60 ml/min/1.73 m2 compared to patients with adenoma. The frequency of low-energy fractures was higher in the carcinoma group versus the adenoma group (32% vs 8%). Heterogeneous structure and indefinite contour of glands detected by US were more typical for PC than for AA and adenomas. The mathematical model was developed using CatBoost gradient boosting algorithm for the noninvasive preoperative differential diagnosis of PC, AA, and adenoma. ConclusionsModel can predict adenoma with PPV 100% and PC with PPV 81–92%. Using model clinicians could plan extended en bloc resection for PC and selective parathyroidectomy for adenoma. If AA is predicted, he has to make a decision on the choice of the necessary volume of PTE based on his experience, because AA are the zone of uncertainty.

Еffectiveness of long-term cinacalcet administration in hemodialysis patients with secondary hyperparathyroidism: A prospective, historically controlled study

Abstract. Our study aimed to determine the long-term effects of cinacalcet in hemodialysis patients with secondary hyperparathyroidism.
 Materials and methods. The study was conducted in 2 phases. At Phase 1, a retrospective analysis of data from 238 outpatient cards of patients treated with hemodialysis on the Kyiv City Center of Nephrology and Dialysis in 2015-2018 was conducted. According to the inclusion and exclusion criteria, data from 93 patients who made up the historical observation group were selected for further analysis In Phase 2, a prospective cohort study lasting 18 months was conducted. The study included 82 hemodialysis patients treated on the Kyiv City Center of Nephrology and Dialysis in the period from 2019 to 2021. These patients were the main observation group. Patients of the main group were prescribed cinacalcet for the correction of secondary hyperparathyroidism. The primary endpoint of the study was death from any cause, surrogates - deaths from cardiovascular events, fractures, parathyroidectomy.
 Results. At the end of the follow-up period, the target PTH level was in 48 (64.9%) of the 74 survived patients (main group). In another 22 (29.7%) patients the PTH level was ≥40% lower than the initial level. There were no significant changes in PTH levels in 4 (5.4%) patients. At the end of treatment, the level of PTH in the main group was 398 (385; 521.4) pg/ml (p <0.001). The dose of cinacalcet was 60 (30; 90) mg/day.
 At patients of the historical group in 18 months observation, the target PTH level was reached in 8 (10.4%) of the 77 survived patients, in 10 (12.9%) patients the PTH level decreased by more than 40% compared to baseline, and in 59 (76, 7%) of patients, there were no significant changes in PTH levels. At the end of treatment, the level of PTH in the historical group was 859.7 (568; 928.9) pg/ml (p> 0.05).
 32 (23%) patients reported at least one adverse event (AE) associated with cinacalcet. The stated AEs in most cases were mild and did not require discontinuation of the drug. During the observation period in the historical group, the overall mortality rate was more than 1.7 times higher than in the main group, but this difference was not statistically significant (RR 1.76, 95% CI: 0.796 - 3.905). The cardiovascular mortality in the historical group was more than 2.4 times higher than in the main group, but this difference was not statistically significant (RR 2.47, 95% CI: 0.929 - 6.558). In the main group, 4 cases of fractures were recorded (4.9%). The frequency of fractures in the historical group was 2.4 times higher than in the main group, but this difference was not statistically significant (RR 2.425, 95% CI: 0.803 - 7.32). The difference in the frequency of parathyroidectomies was statistically significant in the historical group and was almost 3.3 times higher than in the main group (RR 3.306, 95% CI: 1.143 – 9.565).
 Conclusions. The obtained data showed the high efficiency of cinacalcet in the correction of high PTH levels, as well as a beneficial effect on important clinical consequences.

Biochemical and Hematological Parameters in a Group of Chronic Kidney Disease Patients in Albania

Chronic kidney disease is a serious, life threating health problem. It is also known as chronic kidney failure, as it is a process of irreversible loss of nephrons, which at the end stage leads to kidney failure. There are many different reasons that lead to kidney failure, such as: hypertension, diabetes, polycystic kidney disease, glomerulonephritis, parathyroid glands dysfunction, etc. The aim of this study was to evaluate the biochemical and hematological profile in a group of chronic kidney patients in Albania. A group of 247 chronic kidney disease patients is included in this study (170 adult males and 77 adult females). A group of biochemical parameters, such as urea, CRP, albuminemia, HbA1C, creatinine, ALT, AST, calcium, phosphate, CaxP product, sodium, potassium and hematological parameters, such as hemoglobin, red blood cells, white blood cells and PTH, where measured and compared to the findings from the control group. Results were analyzed statistically using SPSS 20 program for windows. From data analysis, we found a reduced count of red blood cells and hemoglobin, statistically significant change, compared to the control group (p0.05). High levels of PTH, serum urea, creatinine and hyperphosphatemia, accompanied by hypocalcemia, were found statistically significant compared to the control group (p0.05). From our observations, hypertension, diabetes and kidney stones were the main causes leading to chronic kidney disease. Evaluation of these parameters, results to be significant in the differentiation and management of the health state of these patients.

Assessment of 4DCT imaging findings of parathyroid adenomas in correlation withbiochemical and histopathological findings.

To assess polar vessel presence and enhancement 4DCT imaging and their relation with biochemical and histopathological features. Patients with primary hyperparathyroidism and preoperative 4DCT imaging were screened retrospectively and those with histopathologically proven diagnosis of PA were included. Biochemical findings, densitometric measurements (HUprecontrast, HUarterial, HUvenous, HUwash-in, HUwash-out, HUretained) and CTvolume of PA on 4DCT, presence of a polar vessel (PV), and histopathological features were recorded. Correlations between serum PTH, calcium levels and densitometric measurements of PA on 4DCT were investigated. Differences between subgroups created according to PV presence were also evaluated. Thirty-nine patients were enrolled (F/M = 32/7, median age = 57, interquartile range = 50-62years). In all patients, serum PTH levels positively correlated with CTvolume (r = 0.398, p = 0.012) but negatively correlated with HUarterial (r = - 0.366; p = 0.022), HUvenous (r = - 0.452; p = 0.004) and HUretained (r = - 0.421; p = 0.008). In PV (-) PAs, PTH levels were positively correlated with CTvolume (r = 0.608, p ≤ 0.002) and negatively with HUarterial (r = - 0.449, p ≤ 0.028), HUvenous (r = - 0.560, p = 0.004), HUwash-in (r = - 0.460, p = 0.024), and HUretained (r = - 0.539, p = 0.007). No correlation between PTH levels and densitometric measurements was found in PV (+) PAs. HUwash-in and HUwash-out were significantly higher in PV (+) PAs compared to PV (-) PAs (p = 0.021 and p = 0.033, respectively). Histopathologic features revealed no difference according to the presence of PV. PTH levels might have an association with imaging findings of PAs, especially when categorized with respect to PV presence. PTH levels were negatively correlated with degree of enhancement in PV (-) PAs. Therefore, radiologists should be aware that in patients with high serum PTH levels and without a discernible PV, PA might be difficult to localize.

RETRACTED ARTICLE: Middle east pain syndrome is a pollution-induced new disease mimicking rheumatoid arthritis

Musculoskeletal pains are sometimes misdiagnosed in some diseases, like rheumatoid and psoriatic arthritis, erosive OA, etc. Secondary hyperparathyroidism was not considered a differential diagnosis for RA, despite the fact that it can cause arthralgia or arthritis. Also, fibromyalgia is a psychosomatic condition marked by widespread pain and tenderness. This study included 400 patients attended certain outpatient clinics of Rheumatology in Egypt and Saudi Arabia, who were not fulfilling criteria for RA diagnosis. Criteria for classification of fibromyalgia syndrome were applied to all patients. We did lab tests and radiological imaging modalities for diagnosis or exclusion of suspected diseases were applied. All patients were fulfilling both old and new criteria of fibromyalgia syndrome, and not fulfilling any RA criteria, and had vitamin D3 deficiency or insufficiency. 75% of patients had abnormally high levels of PTH, without parathyroid gland pathology. Radiology showed subperiosteal and subchondral resorption of mainly thumbs, subchondral osteopenia of proximal and middle phalanges, mild subperiosteal resorption along the radial aspect of the middle phalanx and mild tuft erosions, besides changes in the carpus closely resembling those of rheumatoid arthritis, of ulnar styloid resorption, radiocarpal and scapho-trapezoid joint arthritis. Of special interest, the presence of tuft spur-like excrescences.

Familial hypocalciuric hypercalcemia: grey zones of the differential diagnosis from primary hyperparathyroidism: a case report

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant inherited disorder due to inactivating mutations in the calcium-sensing receptor (CaSR), less commonly in the G-protein subunit α11 (GNA11) or the adaptor-related protein complex 2, sigma 1 subunit (AP2S1) genes. It is characterized by mild to moderate hypercalcemia, hypocalciuria, and inappropriately normal or high PTH levels. The disorder is usually asymptomatic, and bone or renal involvement is rare. Adequate differential diagnosis between primary hyperparathyroidism and FHH is important to avoid unnecessary surgery. We report the case of a male patient with FHH showing biochemical heterogeneity to highlight the difficulties of differential diagnosis

Musculoskeletal Disorders and Associated Factors Among Patients with Chronic Kidney Disease Attending at Saint Paul Hospital, Addis Ababa, Ethiopia.

BackgroundMusculoskeletal disorders contributed from chronic kidney disease are increasing worldwide. Musculoskeletal disorders had a significant health burden and are leading causes of co-morbidities, disability and low productivity, which potentially affect individual’s functional status and quality of life.PurposeThe aim of this study was to assess the prevalence of musculoskeletal disorders and its associated factors among patients with chronic kidney attending in Saint Paul Hospital, Addis Ababa, Ethiopia.Patients and MethodsAn institution-based cross-sectional study was conducted on 302 enrolled study participants through systematic random sampling techniques. Face-to-face interview, physical examination and chart reviews were used to collect data using semi-structured questionnaire adapted from a standard Nordic Musculoskeletal Questionnaire and other literatures. Data were entered into Epi Info version 7 and exported to SPSS version 23 for analysis. Bivariate logistic regression analysis was employed with a p-value less than 0.25. Finally, those variables having a p-value less than 0.05 with 95% CI in multivariate analysis were taken as statistically significant.ResultsThe prevalence of musculoskeletal disorders among CKD individuals was found to be 58.6% (95% CI; 53.0, 64.1). Being female (AOR = 0.49; 95% CI 0.26, 0.94), age between 40 and 49 (AOR = 3.34; 95% CI 1.07, 10.44), stage III (AOR = 0.24; 95% CI 0.06, 0.89) and stage IV (AOR = 0.24; 95% CI 0.06, 0.89) chronic kidney disease, having HTN (AOR = 7.47; 95% CI 3.47, 16.06), parathyroid hormone level ≥100 pg/mL (AOR = 0.43; 95% CI 0.21, 0.87), calcium level <8.4 mg/dl (AOR = 5.89; 95% CI 2.66, 13.56) and serum 25 hydroxy vitamin D level <20 ng/mL (AOR = 3.91; 95% CI 1.32, 11.56) were significantly associated with musculoskeletal disorders.ConclusionMSDs were shown to be moderately common in CKD patients. Female gender, age between 40 and 49 yrs, stage III and stage IV CKD, hypertension, higher PTH level, lower calcium level and lower vitamin D level were statistically significant in their association with musculoskeletal disorders.

The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease.

Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.

MO725DAPT ALLEVIATES CKD-RELATED CAC BY MODULATING PTH-INDUCED ENDOTHELIAL-TO-OSTEOBLAST TRANSITION VIA NOTCH1 PATHWAY ACTIVATION

Abstract Background and Aims Coronary artery calcification (CAC)-induced myocardial infarction (MI) is an important cause of death in patients with chronic kidney disease (CKD). However, effective treatment for CAC is lacked at present. Previous studies have shown that endothelial cells (ECs) participated in vascular calcification through endothelial-to-osteoblast transition. DAPT, N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester, could inhibit the activity of γ-secretase and block the activation of the Notch1 pathway. In this study, we investigated the function of DAPT in alleviating the CAC process by blocking endothelial-to-osteoblast transition via inhibition of the Notch1 pathway. Method We administered 5/6 subtotal nephrectomy and a 10-week high-phosphate diet (P, 2.0%) to construct a rat model of CKD. DAPT and AAV-129-5p was administered orally and injected abdominally to rats respectively in the treatment groups at the beginning of the high-phosphate diet. In vivo, it was performed to detect the expression levels of EndMT and Notch1 pathway markers in the coronary arteries. In vitro, the effect of high PTH levels on the endothelial-to-osteoblast transition and the role of the miR-129-5p/Notch1 signaling pathway were studied in human coronary artery endothelial cells (HCAECs). Results In vivo, endothelial-to-osteoblast transition accompanied with the Notch1 pathway activation was found in HCAECs upon stimulation of PTH, characteristic with up-regulated endothelial markers (CD31, CD34) and down-regulated mesenchymal markers (CD44, CD10, α-SMA, FSP1) and ostoblast markers (Runx2, Osterix). miR-129-5p was responsible for regulating Notch1; γ-secretase was time-dependently and concentration-dependently activated by PTH, which further affected the transcription of downstream regulators (HES1, HEY1). DAPT arrested HCAECs migration through decreasing γ-secretase activity, thus inhibiting endothelial-to-osteoblast transition. In vivo data showed that serum γ-secretase activity decreased in rats intraperitoneally injected with DAPT (10mg/kg) once a week after 5/6 nephrectomy. DAPT intervention or overexpression of mir-129-5p inhibited coronary endothelial-to-osteoblast transition by blocking the activation of the Notch1 pathway. Notably, DAPT retarded CAC and MI without obvious negative effects on rats heart function. Conclusion DAPT is a promising agent for protecting against PTH-induced endothelial-to-osteoblast transition via inhibiting the Notch1 pathway in HCAECs, thus alleviating CAC.

The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery

Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities. The study is focused on the predictive role of PTH with the indices of hepatic steatosis/NAFLD and NASH based on liver biopsy, elastography, and sonography in morbidly obese patients. Ninety patients with BMI between 35 and 40 kg/m2 with more than two comorbidities who referred to Imam Reza outpatient clinic from December 2016 to September 2017 were recruited and underwent initial assessments, including demographic profiles, psychological assessment, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least two weeks before liver biopsy. The histological analysis of the liver was performed using biopsy samples which obtained from left hepatic lobe during bariatric surgery under direct surgeon observation using a 16-gauge Tru-cut needle. The study was approved by the ethical committee (IR.MUMS.fm.REC.1396.312). The level of PTH was significantly high in patients with positive histology for hepatic fibrosis, steatosis, and NASH/NAFLD compared to patients with negative histology (p = 0.005, p = 0.009, and p = 0.013, respectively). Also, patients with liver fibrosis confirmed by elastography had significantly higher serum PTH concentration than patients without fibrosis (p = 0.011). PTH was also positively correlated with hepatic fibrosis, NASH, and steatosis (p = 0.007, p = 0.012, p = 0.023, respectively). High levels of PTH was significantly associated with histological indices of (hepatic fibrosis, steatosis, NAFLD and NASH) and elasticity indices. Therefore, it is imperative to assess for high levels of PTH in the morbidly obese population pre-and post-bariatric surgery. However, for a more robust and comprehensive assessment, a randomized controlled trial is needed. The study was conducted in accordance with the practice guidance in the diagnosis and management of NAFLD from the American association for the study of liver disease (AASLD) 2018. Evidence obtained from well-designed cohort or case-control analytic studies.

One in a billion: a patient with Marfan syndrome and familial hypocalciuric hypercalcaemia.

SummaryMarfan syndrome is an autosomal dominant multisystem disorder that has an estimated incidence of 1 in 5000. It is caused by mutations in the FBN1 gene, which encodes the extracellular matrix protein type 1 fibrillin. Familial hypocalciuric hypercalcaemia (FHH), also inherited in an autosomal dominant pattern, is a rare benign disorder characterised by hypercalcaemia, hypocalciuria and relative hyperparathyroidism with normal or high plasma PTH levels, with an estimated incidence of between 1 in 10 000 to 1 in 100 000. We report a unique case of a 26-year-old man referred for investigation of hypercalcaemia, who also had clinical features of Marfan syndrome but no previous genetic investigations. Calculated fractional urinary excretion of calcium was low (0.0005) following correction of vitamin D deficiency, raising the possibility of FHH. Genetic testing for Marfan syndrome and FHH, via a hyperparathyroidism multiplex gene panel test, revealed a novel truncating variant in the FBN1 gene (c.8481T>G; p.(Tyr2827Ter)), consistent with Marfan syndrome; and a pathogenic truncating variant in the CaSR gene (c.741dupT; p.[Asp248Ter]), which confirmed the diagnosis of FHH. The patient’s mother was subsequently found to have mild hypercalcaemia (adjusted calcium 2.76 mmol/L) and is also heterozygous for the same CaSR mutation. Genetic testing of his father confirmed the presence of the same FBN1 gene mutation. This case illustrates the importance of making robust diagnoses in the era of modern genomic medicine, confirming FHH as the cause of hypercalcaemia means that no treatment is warranted and the patient can be reassured.Learning pointsFamilial hypocalciuric hypercalcaemia (FHH) should always be excluded during the investigation of hypercalcaemia by measuring urinary calcium: creatinine clearance ratio.Diagnosing FHH is important as the condition is benign and misdiagnosing patients with primary hyperparathyroidism could potentially lead to unnecessary morbidity from parathyroid surgery.Genetic testing is increasingly available for a variety of inherited conditions including Marfan syndrome and FHH. Patients who present with clinical features suggestive of a particular genetic condition should undergo prompt, appropriate confirmatory testing wherever possible.Taking a thorough family history is vital when assessing patients presenting with endocrine conditions, as this could prompt cascade testing and appropriate genetic counselling where necessary.

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.

Falsely Positive Parathyroid Scan in a Patient With Medullary Thyroid Cancer

Background: Technitium 99m sestamibi is a very useful method for preoperative localization in hyperparathyroidism. It have some limitations including false positivity due to thyroid pathology. We present a patient with positive Technitium 99m sestamibi uptake by a medullary thyroid cancer Case Presentation: A 67-year-old female referred to the endocrine clinic for evaluation of medullary thyroid cancer diagnosed by fine needle aspiration of left side thyroid nodule. TSH level was normal with high normal serum calcium and high PTH levels. No family history of medullary thyroid cancer, hyperparathyroidism or pheochromocytoma. Her plasma metanephrines were normal. Preoperative evaluation included a parathyroid scan with oral I-123 and Intravenous Technitium 99m sestamibi. I-123 scan showed a cold nodule in the left thyroid lobe and the subtraction images demonstrated persistent uptake of Technitium 99M sestamibi which was reported by the radiologist as a parathyroid adenoma. Repeated serum calcium was normal and intraoperative evaluation of parathyroid glands demonstrated no abnormal enlargement confirming that parathyroid scan was falsely positive secondary to medullary thyroid cancer. Conclusion: This case highlights the importance of careful interpretation of nuclear parathyroid scan results. False positive results have been reported with both benign and malignant thyroid disease including medullary thyroid cancer.

Heterogeneity is a common ground in familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN19 gene mutations.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy caused by mutations in the CLDN16 or CLDN19 genes. Patients usuallydevelop hypomagnesemia, hypercalciuria, nephrocalcinosis and renal failure early in life. Patients with CLDN19 mutations may also have ocular abnormalities. Despite clinical variability, factors associated with kidney functionimpairment, especially in patients with CLDN19 mutations, have not been addressed. Retrospective multicenter study of 30 genetically confirmed FHHNC Spanish patients. We analyzed kidney function impairmentconsidering as outcomeschronic kidney disease (CKD) stage3 and annual estimated glomerular filtration rate (eGFR) decline, to identify factors associated with thedifferent phenotypes. Of thirty patients, 27 had mutations in the CLDN19 gene (20 homozygous for the p.G20D mutation) and 3 in the CLDN16. Age at diagnosis was 1.71 (0.67-6.04) years and follow-up time was 8.34 ± 4.30years. No differences in CKD stage3-free survival based on CLDN19 mutation (p.G20D homozygous vs. other mutations) or gender were found, although females seemed to progress faster than males. Patients with more pronounced eGFR decline had higher PTH levels at diagnosis than those with stablekidney function, despite similar initial eGFR. Approximately 60% of CLDN19 patients presented ocular abnormalities. Furthermore, we confirmed high phenotypic intrafamilial variability. In a contemporary cohort of FHHNC patients with CLDN19 mutations, females seemed to progress to CKD-stage3 faster than males. Increased PTH levels at baseline may indicate amore severe renal course. There was high phenotype variability among patients with CLDN19 mutations and kidney function impairment differedeven betweensiblings.

POS-090 PRIMARY HYPERPARATYHROIDISM: A NEPHROLOGIST EXPERIENCE

Primary hyperparathyroidism (PHPT) is a common endocrine disorder frequently encountered in everyday practice. It classically presents with hypercalcemia which is the hallmark of the disease in association with inappropriately normal to high levels of PTH . The clinical presentation may vary from asymptomatic to symptomatic disease with eventual complications, for instance skeletal and renal abnormalities. It may be due to a single benign parathyroid adenoma which is by far the most common cause or a multiglandular disease in the familial forms Herein is a retrospective and descriptive single-center study of PHPT observed among patients between 2010 and 2020 realized in our department of nephrology in Monastir Tunisia. 10 patients were gathered. The mean age was 58.5 years ranging from 27 to 87 years . The sex ratio was1 :1. Hypertension was found in 5 patients (50 %) : 3 females and 2 males. 1 patient was found to have diabetes. Lithiasis occured in 3 patients all of whom were women and nephrocalcinosis occured in 2 patients. There were no vascular calcifications nor pain in any patient. The average hemoglobin was 9.2 g/dl ranging from 8 to 11.3 g/dl. All patients had hypercalcemia with a mean of 3.09 mmol/l. 5 patients had hypophosphatemia (50 %). PAL was available in 5 patients all of whom had elevated levels with a mean of 190.8 UI/ml. The mean creatinine level was 196.2 umol/l. Cervical ultrasound was performed in all patients and came back normal in 6 patients (60%). In the remaining patients, it has shown bilateral or unilateral lobules. Scintigraphy was also performed in all patients and findings were consistent with those found in the 4 patients with ultrasound abnormalities but has shown anomaly in 4 of the 6 patients (66%) in whom ultrasound came back normal. One patient had developed a brown tumor. Total parathyroidectomy was performed in 6 patients and partial parathyroidectomy in 2 patients. In the post-operative follow-up, all of the patients have normalized their calcemia levels , 5 patients have normalized their kidney function (50%) and the diagnosis of acute kidney injury secondary to hypercalcemia was retained. PHPT affects women 3 to 4 times more than men but in our study they were similar. Hypercalcemia was the most important biological sign.

Bone Mineral Disease After Kidney Transplantation.

Chronic kidney disease-mineral bone disorder (CKD-MBD) after kidney transplantation is a mix of pre-existing disorders and new alterations. The final consequences are reflected fundamentally as abnormal mineral metabolism (hypercalcemia, hypophosphatemia) and bone alterations [high or low bone turnover disease (as fibrous osteitis or adynamic bone disease), an eventual compromise of bone mineralization, decrease bone mineral density and bone fractures]. The major cause of post-transplantation hypercalcemia is the persistence of severe secondary hyperparathyroidism, and treatment options include calcimimetics or parathyroidectomy. On turn, hypophosphatemia is caused by both the persistence of high blood levels of PTH and/or high blood levels of FGF23, with its correction being very difficult to achieve. The most frequent bone morphology alteration is low bone turnover disease, while high-turnover osteopathy decreases in frequency after transplantation. Although the pathogenic mechanisms of these abnormalities have not been fully clarified, the available evidence suggests that there are a number of factors that play a very important role, such as immunosuppressive treatment, persistently high levels of PTH, vitamin D deficiency and hypophosphatemia. Fracture risk is four-fold higher in transplanted patients compared to general population. The most relevant risk factors for fracture in the kidney transplant population are diabetes mellitus, female sex, advanced age (especially > 65years), dialysis vintage, high PTH levels and low phosphate levels, osteoporosis, pre-transplant stress fracture and high doses or prolonged steroids therapy. Treatment alternatives for CKD-MBD after transplantation include minimization of corticosteroids, use of calcium and vitamin D supplements, antiresorptives (bisphosphonates or Denosumab) and osteoformers (synthetic parathyroid hormone). As both mineral metabolism and bone disorders lead to increased morbidity and mortality, the presence of these changes after transplantation has to be prevented (if possible), minimized, diagnosed, and treated as soon as possible.

Lower Leg Arterial Calcifications Assessed by High-Resolution Peripheral Quantitative Computed Tomography in Hypoparathyroid and Pseudohypoparathyroid Patients.

Hypoparathyroidism (HypoPT) and pseudohypoparathyroidism (PHP) are diseases with abnormal calcium and phosphate homeostasis and low and high PTH levels, respectively. It has been hypothesized that this could dispose to vascular calcifications and thereby perhaps also cardiovascular morbidity. The aim of this study was to assess lower leg arterial calcifications (LLAC) in patients with HypoPT or PHP. Using a cross-sectional design, we measured the LLAC using a high-resolution peripheral quantitative computed tomography (HR-pQCT) scanner in 72 patients with HypoPT and 25 patients with PHP and compared them with findings in 61 controls. LLAC were found in only two (3%) of the controls. Compared to the controls, LLAC were significantly more prevalent in patients with HypoPT (N = 12, [17%], p < 0.01) and PHP (N = 4, [16%], p < 0.04). Compared to the patients without calcifications, patients with calcifications had higher plasma calcium levels and a lower eGFR, as well as they were older and more often males. Plasma phosphate levels and the calcium-phosphate product were not associated with LLAC. In conclusion, we found that HypoPT and PHP are associated with an increased prevalence of vascular calcifications.

Skeletal abnormalities in Hypoparathyroidism and in Primary Hyperparathyroidism.

Both hypoparathyroidism (HypoPT), as well as its pathological counterpart, primary hyperparathyroidism (PHPT), can lead to skeletal abnormalities. Chronic deficiency of PTH in patients with HypoPT is associated with a profound reduction in bone remodeling, with consequent increases in bone density, and abnormalities in microarchitecture and bone strength. It is still not clear whether there is an increase in fracture risk in HypoPT. While standard therapy with calcium supplements and active vitamin D does not restore bone homeostasis, treatment of HypoPT with PTH appears to correct some of those abnormalities. In PHPT, the continuous exposure to high levels of PTH causes an increase in bone remodeling, in which bone resorption prevails. In the symptomatic form of PHPT, patients can present with fragility fractures, and/or the classical radiological features of osteitis fibrosa cystica. However, even in mild PHPT, catabolic skeletal actions of PTH are evident through reduced BMD, deterioration of bone microarchitecture and increased risk of fragility fractures. Successful parathyroidectomy improves skeletal abnormalities. Medical treatment, such as bisphosphonates and denosumab, can also increase bone density in patients with PHPT who do not undergo surgery. This article reviews skeletal involvement in HypoPT and in PHPT, as assessed by bone remodeling, DXA, trabecular bone score, and quantitative computed tomography, as well as data on bone strength and fracture risk. The effects of PTH replacement on the skeleton in subjects with HypoPT, and the outcome of parathyroidectomy in patients with PHPT, are also reviewed here.