Increased PTH Levels Research Articles

12324 Clinical Features And PHEX Variants Of Adults With X-Linked Hypophosphatemia

Abstract Disclosure: L.P. Valadares: None. D.R. Carvalho: None. F.S. Lopes: None. R.S. Oliveira: None. L.G. Castro: None. X-linked hypophosphatemia (XLH), caused by loss-of-function PHEX mutations, is a lifelong renal phosphate-wasting disorder and the main cause of inherited hypophosphatemia. In adults, chronic hypophosphatemia leads to impaired bone mineralization and persistent osteomalacia. Short stature, lower limb deformities and musculoskeletal chronic pain can significantly impact the daily lives of affected individuals. This study aimed to describe the clinical and molecular profiles of 23 adults with genetically proven XLH who are being followed at a tertiary medical center in Brazil. We conducted a retrospective analysis of their medical records. The median age at diagnosis was 3.0 years (IQR 2.0-8.0) and the mean age at first visit at the adult care unit was 30.5 years (±12.7). Their mean final height was 144.2 cm (±10.5), with a mean body mass index (BMI) of 28.1 kg/m2 (±4.9). Nine patients were overweight, and seven were obese. Sixteen patients had a positive family history of rickets, and nine had offspring with XLH. Among the 14 different PHEX mutations that were identified, six had not been previously reported. Hypophosphatemia was observed in 21 patients at presentation at the adult care unit, increased serum alkaline phosphatase levels in 19, and 12 showed increased PTH levels. Chronic bone and muscular pain were reported by sixteen patients, eighteen had lower limb deformities, and six had a history of fractures and/or pseudofractures. Seventeen patients underwent orthopedic surgeries, with an average of 3.8 surgical interventions per patient. Nephrolithiasis and/or nephrocalcinosis were observed in nine patients, but none had glomerular filtration rate below 60 mL/min adjusted to 1.73 m2 of body surface. Three patients were on conventional treatment (phosphate and calcitriol) upon presentation at the adult care unit, five patients had never received XLH-specific treatment, and fifteen discontinued conventional therapy after completing skeletal growth, with a mean therapy duration of 12.1 years (±3.5). Out of the 20 patients without treatment, 16 were initiated on pharmacological therapy based on symptoms and signs of persistent osteomalacia. Eleven started combined phosphate and calcitriol supplementation, while five received calcitriol monotherapy. This cohort underscores that adults with XLH experience significant musculoskeletal morbidity throughout their lives, and require long-term follow-up, including assessment of energy metabolism. Importantly, most of them benefits from maintaining pharmacological treatment in adulthood. Presentation: 6/2/2024

O-13 Parathyroid carcinoma - a rare and challenging entity

Abstract Background Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of all cases of primary hyperparathyroidism (HPT). This entity affects both men and women equally and is usually diagnosed in the fourth or fifth decade of life. It can occur sporadically or be associated with genetic syndromes such as hyperparathyroidism-jaw tumor syndrome. Its clinical presentation can overlap with that of primary HPT, with hypercalcemia that can lead to a range of symptoms, such as fatigue, weakness, bone pain, kidney stones, and gastrointestinal disorders. Distinguished by its rarity and clinical challenges, this condition requires a high level of suspicion and its initial surgical approach correlates with long-term prognosis. Clinical Case This is the case of a male patient, 39 years old, Caucasian, with a previous history of hypertension diagnosed 5 months earlier, deep vein thrombosis (DVT) diagnosed 2 months earlier, and active tobacco use. Additional study performed after the DVT episode found severe hypercalcemia (14.3 mg/dL, N 8.6-10.0), hypophosphatemia (2.2 mg/dL, N 2.5-4.5), and renal dysfunction (Creatinine 1.43 mg/dL). The patient was asymptomatic and was admitted to the Internal Medicine department, to correct the hypercalcemia and further investigation. Increased PTH levels (1555 pg/mL, N 15-65) were found, and a cervical ultrasound revealed, on the left thyroid lobe, a bilobed nodule, mainly solid, hypoechogenic, with irregular margins and macrocalcifications, with 34×22 mm. Full body CT showed osteolytic lesions on several ribs and both iliacs and kidney stones. A bone scintigraphy was also done, showing a diffuse fixation on the axial and appendicular skeleton, compatible with diffuse osteomedullary infiltration. Due to these findings, the collaboration of the Endocrinology department was requested. Based on the PTH levels and the characteristics of the cervical mass, suspicion arose regarding a potential case of parathyroid carcinoma. Subsequently, a parathyroid scintigraphy using Sestamibi was conducted, whose report revealed an intense hyperfixation at a nodular formation projecting on the lower two-thirds of the thyroid left lobe, without unequivocal identification of its origin - thyroid nodule vs. parathyroid tissue. Based on intraoperative findings and clinical suspicion, en bloc resection of the tumor along with the thyroid lobe and unilateral neck exploration was performed by the Surgery department, with the pathological assessment confirming the malignancy diagnosis. The patient was referred to an oncologic tertiary center, for follow-up and genetic testing. Conclusion We want to shed light on this rare entity and the importance of multidisciplinary critical thinking, alongside imaging. Markedly elevated PTH and/or calcium levels on a patient with a cervical mass should arouse suspicion of a parathyroid carcinoma, which must not be biopsied and warrants a more extensive surgery to ensure the best possible prognosis.

Hypocalcemia – a Diagnostic Challenge

Objective − The authors aimed to describe a case of a rare etiology of hypocalcemia in a child, and highlight the importance of clinical suspicion for prompt diagnosis of calcium disturbances.Case Report − The 5-year-old male child did not have any symptoms up to 4 days prior to presentation, but fever and a rash, followed by acute onset of seizures prompted presentation to the pediatric emergency department. Clinical records revealed that he had been found to have left hand lesions, global developmental delay, and height below the 3th percentile in a previous assessment. The combination of severe hypocalcemia, hyperphosphatemia, increased PTH levels, and identification of a mutation on a GNAS genetic test, confirmed the diagnosis of type Ia pseudohypoparathyroidism (PHP Ia).Conclusion − In this case report, the combination of clinical and biochemical findings led to the diagnosis. Hence, it is important to consider the many possible etiologies of seizures and hypocalcemia, taking into account the clues provided by clinical history and physical examination.

Bone Metabolism Effects of Medical Therapy in Advanced Renal Cell Carcinoma.

The medical therapy of advanced renal cell carcinoma (RCC) is based on the use of targeted therapies, such as tyrosine kinase inhibitors (TKI) and immune-checkpoint inhibitors (ICI). These therapies are characterized by multiple endocrine adverse events, but the effect on the bone is still less known. Relatively few case reports or small case series have been specifically focused on TKI and ICI effects on bone metabolism. However, the importance to consider these possible side effects is easily intuitable because the bone is one of the most frequent metastatic sites of RCC. Among TKI used in RCC, sunitinib and sorafenib can cause hypophosphatemia with increased PTH levels and low-normal serum calcium levels. Considering ICI, nivolumab and ipilimumab, which can be used in association in a combination strategy, are associated with an increased risk of hypocalcemia, mediated by an autoimmune mechanism targeted on the calcium-sensing receptor. A fearsome complication, reported for TKI and rarely for ICI, is osteonecrosis of the jaw. Awareness of these possible side effects makes a clinical evaluation of RCC patients on anticancer therapy mandatory, especially if associated with antiresorptive therapy such as bisphosphonates and denosumab, which can further increase the risk of these complications.

Vitamin D and Parathyroid Hormone during Growth Hormone Treatment.

Background. There is some controversy concerning a potential interaction between vitamin D and PTH and the GH/IGF-1 axis. The goal of this study is to assess vitamin D and PTH status in children with GH deficiency at diagnostic and during treatment with rhGH. Methods. Longitudinal and descriptive study in 110 patients, aged 3.3–9.1 years, with GH deficiency (GHD group) treated with rhGH. At diagnosis and after 12, 24, 36, and 48 months of treatment, a clinical (height, weight, and bone age) and laboratory (phosphorus, calcium, calcidiol, PTH, IGF-1) evaluation was performed. Concurrently, 377 healthy children, aged 3.8–9.7 years, were enrolled and constituted a control group. Vitamin D status was stated in accordance to the U.S. Endocrine Society criteria. Results. No significant differences were found in the prevalence of vitamin D deficiency among control (11.43%) and GHD (13.6%) groups at the moment of diagnosis, remaining without significant changes at 12 (12.9%), 24 (14.6%), 36 (13.1%), and 48 months (13.3%) of treatment. There were not any significant differences in serum levels of calcium, phosphorus, and calcidiol, but a steady increase (p < 0.001) in PTH was detected. Conclusions. Prepubertal patients with GH deficient do not appear to have a higher risk of vitamin D deficiency than healthy subjects, and with treatment with rhGH, no changes in the organic content of vitamin D were observed although a significant increase in PTH levels was detected.

Metabolic Bone Disease of Prematurity.

Metabolic Bone Disease of Prematurity.

EP.TH.30Effect of One Anastomosis Gastric Bypass on Haematinics, Vitamin D, and Parathyroid Hormone Levels: A comparison between 150 cm and 200 cm Bilio-Pancreatic Limb

Abstract Introduction There is little data on the effect of One Anastomosis Gastric Bypass (OAGB) on Haematinics, Vitamins D, and Parathyroid Hormone levels. It is further unclear if an OAGB with a Bilio-Pancreatic Limb (BPL) of 150 cm (OAGB-150) would deliver better outcomes than that with a BPL of 200 cm (OAGB-200). Methods We investigated our records to obtain information on patients who underwent an OAGB-200 or OAGB-150 until 31st July 2018 in our unit. Results A total of 405 patients underwent either an OAGB-200 (n = 234) or OAGB-150 (n = 171). The mean age was 46±10.98 years and 276 (67.3%) were females. The mean preoperative weight and the Body Mass Index (BMI) were 139±29.96 kg and 49±8.14 kg/m2 respectively. With OAGB-200 there was a significant increase in anaemia rates at 1 and 2-years compared to preoperative levels with a significant fall in haemoglobin levels. After OAGB-150 there was a significant fall in haemoglobin levels at 1 and 2-years but the increase in anaemia rate was only significant at 2-years. There was a significant increase in PTH levels and the number of abnormal values at 1 and 2-years with OAGB-200. With OAGB-150, PTH changes were significant at 2 years only. Conclusion Both OAGB-200 and OAGB-150 are associated with a significant increase in anaemia and secondary hyperparathyroidism. Our findings should prompt the evaluation of supplementation protocols with higher dosages than we recommend for iron, folate, and calcium. Consideration should also be given to evaluating shorter BPL lengths than 150 cm with OAGB.

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.

Salvia officinalis Extract and 17β-Estradiol Suppresses Ovariectomy Induced Osteoporosis in Female Rats.

&lt;b&gt;Background and Objective:&lt;/b&gt; Osteoporosis is a progressive metabolic disorder characterized by an impaired bone formation that leads to increased morbidity and mortality.&lt;i&gt; Salvia officinalis &lt;/i&gt;is a source of phytoestrogens that could help mitigate the risk of osteoporotic rat fracture by exerting sex hormones. Therefore, the present study was designed to investigate the curative effect of &lt;i&gt;Salvia officinalis &lt;/i&gt;Extract&lt;i&gt; &lt;/i&gt;(SOE) and&lt;i&gt; &lt;/i&gt;17β-estradiol (E&lt;sub&gt;2&lt;/sub&gt;) and their combination&lt;i&gt; &lt;/i&gt;on bone loss in female rats with ovariectomy-induced estrogen deficiency &lt;b&gt;Materials and Methods:&lt;/b&gt; Forty adult female albino rats were divided into five groups, which included Sham control (Sham), ovariectomy (OVX), OVX+SOE, OVX+E&lt;sub&gt;2&lt;/sub&gt; and OVX +SOE+E&lt;sub&gt;2&lt;/sub&gt;.&lt;i&gt; &lt;/i&gt;SOE (10 mL kg&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt;) and E&lt;sub&gt;2&lt;/sub&gt; (30 μg kg&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt;) had been daily gavaged in the OVX+SOE, OVX+E&lt;sub&gt;2&lt;/sub&gt; and OVX+SOE+E&lt;sub&gt;2&lt;/sub&gt;, respectively for 6-weeks. &lt;b&gt;Results:&lt;/b&gt; The model of ovariectomy resulted in osteoporosis as demonstrated by the decreased serum Ca, P, vitamin D, E&lt;sub&gt;2&lt;/sub&gt; level associated with a significant increase in PTH levels in comparison to the sham control group. Besides, OVX to rats caused up-regulation in the levels of CTX-1, P1NP, BALP, OC and RANKL comparable to the sham control group. Moreover, SOE and E&lt;sub&gt;2&lt;/sub&gt; significantly modulated the calciotropic parameters and improved all bone turnover markers as well as RANKL as compared to the OVX group. However, Histopathological and immunohistochemical results showed defective mineralization with the destruction of the bone matrix and increased TNF-α expression from the OVX group relative to the treated groups. &lt;b&gt;Conclusion:&lt;/b&gt; These results suggest that both SOE and E&lt;sub&gt;2&lt;/sub&gt; or their combined administration are efficient inhibitors against ovariectomy-induced bone loss in female rats.

Effect of One Anastomosis Gastric Bypass on Haematinics, Vitamin D and Parathyroid Hormone Levels: a Comparison Between 150 and 200 cm Bilio-Pancreatic Limbs.

There is little data on the effect of one anastomosis gastric bypass (OAGB) on haematinics, vitamin D and parathyroid hormone levels. It is further unclear if an OAGB with a bilio-pancreatic limb (BPL) of 150 cm (OAGB-150) would deliver better outcomes than that with a BPL of 200 cm (OAGB-200). We investigated our records to obtain information on patients who underwent an OAGB-200 or OAGB-150 until 31st July 2018 in our unit. A total of 405 patients underwent either an OAGB-200 (n = 234) or OAGB-150 (n = 171). The mean age was 46 ± 10.98 years and 276 (68.1%) were females. The mean preoperative weight and the body mass index (BMI) were 139 ± 29.96 kg and 49 ± 8.14 kg/m2 respectively. With OAGB-200, there was a significant increase in anaemia rates at 1 and 2 years compared to preoperative levels with a significant fall in haemoglobin levels. After OAGB-150, there was a significant fall in haemoglobin levels at 1 and 2 years but the increase in anaemia rate was only significant at 2 years. There was a significant increase in PTH levels and the number of abnormal values at 1 and 2 years with OAGB-200. With OAGB-150, PTH changes were significant at 2 years only. We found that both OAGB-200 and OAGB-150 are associated with a significant increase in anaemia and secondary hyperparathyroidism. Our findings should prompt the evaluation of supplementation protocols with higher dosages than we recommend for iron, folate and calcium. Consideration should also be given to evaluating shorter BPL lengths than 150 cm with OAGB.

Secondary hyperparathyroidism in patients with chronic kidney disease: A case control study

Secondary hyperparathyroidism is a major complication of Chronic kidney disease resulting from disturbances in the regulation of Parathyroid hormone, calcium, phosphorus and vitamin D. Adding to the burden of CKD elevated Parathyroid hormone levels are responsible for the long-term consequences like renal osteodystrophy, vascular calcifications and also contributes to cardiovascular morbidity and mortality among end-stage renal disease patients. Hence, this study was conducted to correlate the levels of PTH in patients with CKD in comparison to normal healthy controls.: 54 patients diagnosed as CKD and 46 healthy controls are included in the study. Serum levels of Urea, creatinine &amp; PTH measured in both cases and controls. Statistically significant increase in PTH levels were observed in cases as compared to controls (p&amp;#60;0.001). An increase in PTH levels is seen as the disease progressed. Thus, periodic measurement of PTH is recommended in all patients with CKD in order to reduce complications.

SAT-349 Cinacalcet Resistant Tertiary Hyperparathyroidism with One Large Parathyroid Gland

Tertiary hyperparathyroidism is thought to develop after long term secondary hyperparathyroidism, such as CKD on dialysis. In This case, all parathyroid glands are significantly enlarged.We report a case of an 84-year-old female with a past medical history of ESRD on HD and recurrent nephrolithiasis who was found to have an enlarged multinodular goiter with the dominant mass in the lower pole of the right gland measuring about 4.7 cm on thyroid ultrasound. Blood work was done which showed elevated intact PTH levels at 2720 pg/mL (12–88). Her calcium level was normal at that time at 10.5 mg/dL (8.6–10.8) with an albumin of 4.2 g/dL (3.5–5.7), and a phosphorus of 5.7 mg/dL (2.5–4.5). Patient had a DEXA scan which showed severe osteoporosis in the lumbar spine, left hip, and right forearm. Patient had increased PTH levels despite being on Cinacalcet. She had a nuclear medicine parathyroid scan with SPECT CT which showed increased uptake along the right inferior thyroid concerning for a large right lower parathyroid adenoma or functional thyroid nodule. FNA of the nodule was done and showed colloid nodule but PTH wash showed elevated PTH at 7634 pg/mL. She was referred for right lower parathyroidectomy and Cinacalcet was discontinued prior to surgery. She had right and left inferior parathyroidectomy and 4 gland exploration. Pathology showed the right inferior parathyroid gland to be markedly hyper-cellular, weighing 36 grams consistent with hyperplasia and the left inferior parathyroid gland to be slightly hyper-cellular parathyroid gland consistent with hyperplasia. No evidence of malignancy was noted on pathology. Prior to surgery her calcium level of 10.6 mg/dL which went down to 9.6 mg/dL post-operatively. Patient then developed severe hypocalcemia and hungry bone syndrome following the surgery requiring a calcium drip for 3 days post-operatively. Was changed to oral calcium but required large amounts of calcium gluconate and calcitriol supplementation and an extended hospital stay of 13 days. However, throughout the hospital stay, PTH levels continued trending back up to 239 which may represent either increased activity from remaining parathyroid glands or residual parathyroid adenoma with incomplete resection. Post-operative US neck showed Post-surgical collection in the lower pole of the right gland measuring 4.8 cm compatible with recent resection.In conclusion, tertiary hyperparathyroidism can develop due to one enlarged parathyroid gland or an adenoma, which can be resistant to cinacalcet.

Purification and characterization of positive allosteric regulatory peptides of calcium sensing receptor (CaSR) from desalted duck egg white

HPLC-ESI-MS/MS, molecular docking simulation and in situ single-pass intestinal perfusion (SPIP) study were used to identify, select, and confirm the binding affinities between peptides identified from desalted duck egg white peptides (DPs) and calcium sensing receptor (CaSR), respectively. F3 fraction from DPs possessed superior calcium binding activity (P < 0.05), and 16 peptides enriched aromatic amino acids and other 33 peptides were identified. FAE, FNE, INSW, FDPE and NFE presented well binding affinities with CaSR in molecular docking. Additionally, SPIP results showed that NFE and INSW significantly reduced the increased PTH levels by 45.8% and 48.8%, respectively (P < 0.05), and increased calcium percent absorption, calcium absorption rate constant (Ka) and calcium effective permeability (Peff) (P < 0.05), as well as up-regulated mRNA levels of CaSR (P < 0.05). Moreover, NFE and INSW could interact with the VFT domain of CaSR, which exhibited the potential activities in regulation of CaSR.

Refractory hypercalcemia due to an ectopic mediastinal parathyroid gland in a hemodialysis patient: a case report

BackgroundHypercalcemia crisis is a complex disorder rarely induced by tertiary hyperparathyroidism, which clinically presents as nonsuppressible parathyroid hyperplasia with persistent increased PTH levels and hypercalcemia. It is one of the major risk factors of morbidity and mortality in end-stage renal disease. Parathyroidectomy should be in consideration in dialysis patients with severe hyperparathyroidism who are refractory to medical therapy. The implications and consequences of it, however, are not fully understood.Case presentationWe present a case of a 70 year-old man disturbed by gastrointestinal manifestations due to hypercalcaemic crisis. The patient had longstanding hypercalcaemia and hyperparathyrodism refractory to calcimimetics, calcitonin, hormone and haemodialysis. A ectopic parathyroid gland in anterior mediastinum was found and elucidated by Tc-99 m scan.Futhermore, a video-assisted thoracoscopic parathyroidectomy was performed. Histologically, the tumour consisted of densely arranged chief cells immunohistochemically positive for PTH antigens. Consequently, calcium and parathormone were declining stably without any complications.ConclusionsOn account of refractory hypercalcemia and hyperparathyroidism, radionuclide scanning is useful in the diagnosis of ectopic parathyroid gland. it is of great significance for multidisciplinary therapy combing anesthesia, surgical, endocrinology and nephrology staff.

FIBROBLAST GROWTH FACTOR 23 AS EARLY MARKER OF MINERAL AND BONE DISORDER IN PATIENTS WITH CHRONIC KIDNEY DISEASE

The aim: to study the state of regulation of mineral metabolism in CKD by evaluating the serum concentration of c-terminal FGF-23, PTH, Ca, P, and to investigate the relationship between FGF-23 and PTH in CKD.&#x0D; Materials and methods. The study involved 106 people with CKD, 47women (44%) and 59men (56%) aged (49.6 ± 13.9) years. The C-terminal FGF-23 fragment was determined using a set of reagents for the enzyme immunoassay «Biomedica». The glomerular filtration rate (GFR) was calculated using the CKD EPI formula (KDIGO 2012).&#x0D; Results. A progressive increase in PTH levels was observed in parallel with the development of renal insufficiency in patients with CKD. Beginning with the CKD stage III, a significant increase above the norm (p &lt;0.05) in the level of PTH ((85.79 ± 29.3) pg / ml) was observed. A progressive increase in the serum concentration of the c-terminal fragment of FGF-23 in patients with CKD was observed along with the GFR decrease. Statistically significant (p &lt;0.05) increase in the concentration of FGF-23 was observed in CKD stage II ((1.29 ± 0.08) pmol / L) compared with CKD I ((0.76 ± 0.07) pmol / L). A strong negative association was found between FGF-23 and GFR (r = -0.87, p &lt;0.05) in CKD. The existence of a strong direct association (r = 0.84, p &lt;0.05) between the level of PTH and FGF-23 in CKD was established.&#x0D; Conclusions. Growth of the level of FGF-23 outstrips the increase in PTH in the time interval by 1 stage of CKD. C-terminal FGF-23 can be used as an early marker of the development of mineral disturbances in patients with CKD.

The shift from high to low turnover bone disease after parathyroidectomy is associated with the progression of vascular calcification in hemodialysis patients: A 12-month follow-up study.

Parathyroidectomy (PTX) may cause low levels of PTH, leading to an excessive reduction of bone turnover, which is associated with poor outcomes in dialysis patients, including vascular calcification (VC). We aimed to prospectively investigate the impact of PTX on bone remodeling and its potential consequence on the progression of VC in hemodialysis patients. In this prospective study, 19 hemodialysis patients with severe secondary hyperparathyroidism (sHPT) were evaluated. All patients underwent laboratorial tests and coronary tomography at baseline and, 6 and 12 months after PTX; bone biopsy was performed at baseline and 12-month. At baseline, all patients had increased PTH levels up to 2500 pg/mL and high turnover bone disease in their bone biopsies. Fourteen (74%) patients had VC. During the follow-up, there was a significant decrease of PTH at 6 and 12-month. At 12-month, 90% of the patients evolved to low turnover bone disease. During the period of the hungry bone syndrome (first 6 months), no change of coronary calcium score was observed. However, calcium score increased significantly thereafter (12th month). There was an association between VC progression and the severity of low turnover bone disease. In conclusion, the shift from high to low turnover bone disease after PTX occurs in parallel to VC progression, contributing to the understanding of the complex pathophysiology involving mineral metabolism and cardiovascular disease in hemodialysis patients.

The pitfall of treating low bone turnover: Effects on cortical porosity

Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46±13years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)] and correlated with PTH (p=0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p=0.015) and the delta of PTH (p=0.03); it was also higher among non-white patients than in white patients (p=0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r2=0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.

Loose and frequent stools and PTH levels are positively correlated post–gastric bypass surgery due to less efficient intestinal calcium absorption

BackgroundAfter Roux-en-Y gastric bypass, calcium and vitamin D deficiencies are frequently reported. In the presence of adequate vitamin D levels, calcium deficiency is caused by a lower efficacy of the intestinal calcium transport. ObjectiveTo investigate whether the use of a simple clinical score quantifying bowel habits (fecal score [FS]) correlates with the degree of secondary hyperparathyroidism that arises to compensate for calcium deficiency postsurgery. SettingLarge peripheral hospital. MethodsSeventy-five patients supplemented with calcium and vitamin D were prospectively studied before and 6 and 12 months after Roux-en-Y gastric bypass. FS, calcium (mmol/L), phosphate (mmol/L), magnesium (mmol/L), vitamin D (nmol/L), and parathyroid hormone (PTH; pmol/L) were measured in each patient. ResultsMean body mass index was 44.7±5.4 kg/m2 preoperatively and decreased to 34.3±5.0 kg/m2 at 6 months and 30.8±4.8 kg/m2 at 12 months, corresponding to a total weight loss of 23.2±5.9% and 30.9±8.3% respectively. There were no significant changes in serum calcium levels. Mean PTH levels rose from 3.5 pmol/L at baseline to 4.1 pmol/L at 6 months (P = .01) and to 4.9 pmol/L at 12 months (P<.001). Nine patients (12%) had increased PTH levels at 6 months, and 14 patients (19%) had increased PTH levels at 12 months. A significant positive correlation between FS and PTH at 12 months was found, which persisted after adjusting for vitamin D levels. ConclusionFS is positively correlated with secondary hyperparathyroidism using vitamin D–adjusted PTH levels as a biochemical marker. The present study in humans confirms the relation reported in animal studies. These results emphasize that managing stool habits are important after bariatric surgery.

Serum parathyroid hormone and calcium changes in metastatic castration resistant prostate cancer patients receiving enzalutamide in post-docetaxel setting.

349 Background: Among novel hormonal therapeutic targets for post docetaxel mCRPC, Enzalutamide is an oral androgen-receptor blocker disrupting the androgen-receptor nuclear translocation that significantly increases the OS. In this study we evaluated the potential association of both PTH and Ca levels change in pts with mCRPC after the first Enzalutamide administration. Methods: Between 01 and 05/2015, 20 mCRPC pts relapsed after 2-3 prior lines of therapy (docetaxel, cabazitaxel, abiraterone) have been treated with Enzalutamide that was orally administered at 160 mg/day as continuous dosing. Patient characteristics included: median age 67 years (range 50-84), median baseline PSA 120 ng/ml (range 6-1200), median ECOG P S: 1 (range 0-2), Gleason score ≥ 7. In addition 80% of pts had ≥ 2 metastatic sites. Pretreatment baseline and follow up data including measurement of serum Ca and PTH levels (6.5-36.8 pg/ml), ALP, PSA and QoL parameters were evaluated through all lines of therapy. Pts with bone metastasis received zoledronic acid or denosumab with Ca and vitamin D supplementation. Results: In 18/20 pts with bone disease progression we recorded increased PTH levels and, contrarily, decreased Ca levels after 1 month of Enzalutamide despite vit. D and Ca supplementation. PTH levels remained unchanged after 3 months. In 2/20 pts without bone disease progression PTH ranged normal. All pts reported PSA response ≥ 50%, with improved QoL and are still on treatment since Enzalutamide is well tolerated. We did not find PTH change in bone mCRPC pts treated with prior therapy. Conclusions: Our study showed that increase in PTH levels and reduction in Ca levels and increase in PTH levels after 1 month of Enzalutamide treatment is associated with a dramatic reduction of PSA level. These data support a relationship between PTH and Ca changes in pts treated with Enzalutamide and, thus, their changes level may be adopted in clinical practice as surrogate to reflect the drug activity. No studies have evaluated the variations in serum PTH levels following Enzalutamide treatment and whether these early changes relate to the clinical outcome.

Nonfunctioning Parathyroid Carcinoma

Parathyroid carcinoma (PC) is a rare endocrine malignancy accounting for less than 1% of cases of primary hyperparathyroidism (PHPT) [1,2]. There is an equal sex predilection, whereas adenomas are most commonly seen in females. Patients with PC are younger than those with adenoma (50 vs. 60 years) and usually present with marked hypercalcemia and/or systemic manifestations, related to either hypercalcemia or increased PTH levels.