Elevated Intact Parathyroid Hormone Research Articles

Factores de progresión en pacientes con ERC-3 KDOQI (estudio PROGRESER)

IntroductionThe PROGRESER study is a multicentre, prospective, observational, 3-year follow-up study of a cohort of patients with stage3 chronic kidney disease (CKD) from different nephrology departments of hospitals in the Spanish healthcare system. The primary study objective was to analyse risk factors for CKD progression, identifying possible differences between patients with and without diabetes mellitus (DM). The secondary objective was to analyse the factors associated with hospitalizations and mortality. Patients and methodsA total of 462 patients (342 men and 120 women; mean age 66.5±11.5 years) were recruited from 25 participating sites in Spain. Clinical, epidemiological and analytical data were recorder in an electronic register each six months. Biological samples were obtained and frozen for a biobank record at baseline and at 18 and 36 months. ResultsThe initial mean glomerular filtration rate estimated by MDRD and after that reestimated by CKD-EPI was 43.9±7.9mL/min/1.73m2; and 29±6,8mL/min/1,73m2 at 3years. 27.3% of patients had microalbuminuria and 22.5% had macroalbuminuria. Two-thirds of the patients (66.2%) presented renal damage progression according to the study criteria (decrease of more than 15% in eGFR over the baseline value). 38.7% presented a reduction in eGFR ≥30%; 20.3% had a reduction in eGFR ≥40%; 10.4% had a reduction ≥50% and 6.9% had a reduction ≥57%. Of the 199 diabetics, 134 (67.3%) suffered renal damage progression. Of the 263 non-diabetics, 172 (65.3%) presented progression (P=.456). 27.3% of patients had microalbuminuria and 22.5% proteinuria. The study found that CKD progression to a higher stage was not greater in diabetic compared to non-diabetic patients. Multivariate analysis revealed that the presence of arterial hypertension bordered on significance as a progression factor in non-diabetic patients (P=.07), and that, in diabetic patients, lower calcium levels and elevated intact parathyroid hormone levels at baseline were associated with progression. ConclusionIn our study we have not found new factors for progression of renal damage, different from the yet well known traditional factors. DM per se was not a differential factor for progression in relation with non DM patients. Progression of renal damage in patients with CKD-3 KDOQI may be interpreted in a multifactorial context. The search for new biomarkers, different from traditional ones, is necessary to establish new therapeutic strategies to prevent the progression of CKD.

Depressive Disorder in Primary Hyperparathyroidism and Effects of Surgery in Elderly Patients: Case Series

Background: Patients with primary hyperparathyroidism (PHPT) often present nonspecific symptoms such as major depressive disorder and psychosis. Calcium plays a role in the pathogenesis of psychiatric symptoms by determining changes in monoamine metabolism in the central nervous system, thereby modifying neurotransmission and resulting in mood and cognitive alterations. Case series: This report presents a case series of 3 patients; 70-year-old, 78 year- old and 94 year-old women with PHPT and severe depression symptoms and its response to parathyroidectomy. The patients were a poor historian. Results of preoperative laboratory tests showed an increased serum calcium level (11.15mg/dL, 10.9 mg/dL and 11.4 mg/dL- reference range 8.4-10.2 mg/dL). A repeat serum calcium test confirmed hypercalcemia with concurrent elevated intact parathyroid hormone level. Two patients were undergone at parathyroidectomy. A 94 year-old patient refuse surgical approach and was efficacy treated with a single dose of zoledronic acid. Therefore, the patients underwent parathyroidectomy two months after procedure had a clinical improvement on depressive symptoms. There was any recurrent laryngeal nerve injury or recurrent PHTP. Conclusion: The presence of a long-standing depressive disorder unresponsive to medical therapy may suggest an organic disorder such as chronic hypercalcemia which may be secondary to PHPT. Surgical intervention in these selected cases can assist medical therapy in the improvement of depressive symptoms.

Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

Hypercalcemia is highlyprevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-uptime, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64]mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40]pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipientsin our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

SAT215 Sagliker Syndrome In A Filipino Female With End Stage Renal Disease

Abstract Disclosure: M.R. Pajanel: None. E. Clarito: None. K. Uytiepo: None. P. De La Peña: None. This is a case of a 29-year-old Filipina, with chronic kidney disease secondary to chronic glomerulonephritis, undergoing hemodialysis for 10 years. She presented with maxillary mass, associated with other craniofacial deformities such as mandibular enlargement and widening of teeth spaces. Other associated symptoms include difficulty in swallowing solid food, difficulty in ambulation due to bone pains, and with noted shortening of stature. Workup revealed elevated intact parathyroid hormone (iPTH) 1638.8pg/mL(20x ULN), low Vitamin D, elevated ALP, but with normal levels of calcium and phosphorus. Sestamibi scan showed focal uptake and retention along medial aspect of the right thyroid bed and inferior to both thyroid beds suggestive of parathyroid adenoma or hyperplasia. Parathyroid ultrasound was consistent with findings of Sestamibi scan which also showed parathyroid nodules in the middle segment right thyroid lobe, and inferior to right thyroid lobe. Bone mineral density is below the expected range for age. Right parathyroidectomy was done and she was discharged well. She came in for follow-up with persistent elevated PTH 4765pg/ml(60x ULN), still with symptoms. Repeat imaging on ultrasound showed a parathyroid nodule posterior to the superior aspect of left thyroid 0.9 x0.5cm. Sestamibi scan confirmed a functioning parathyroid adenoma left inferior and superior thyroid bed. Left parathyroidectomy was done with a histopathologic result of left superior parathyroid consistent with parathyroid hyperplasia. On follow up, repeat intact PTH still elevated at 3677pg/mL and persistently elevated 2 months after at 3626pg/mL. Parathyroid ultrasound showed Parathyroid nodule, left, measuring 1.5x1.7x0.9 cm, inferior and posterior to the inferior border of the left thyroid gland. 99mTc-Sestamibi scan was consistent with the ultrasound in the left thyroid lobe suggestive of parathyroid adenomas or hyperplasia. Completion Parathyroidectomy was done on November 2018. Pre-operative iPTH was 4205pg/mL, which decreased to 291.3pg/mL postoperatively. She was discharged improved. On followup in 2022, she reports of decrease bone pain and now able to ambulate without difficulty. Repeat bone mineral density has improved and now within expected range for age. CONCLUSION: Sagliker syndrome is an entity described as an “uglyfying face syndrome” seen in patients with chronic kidney disease, presenting with facial deformities. Patients usually present with elevated parathyroid hormone (PTH) levels, and has been refractory to medical therapy. Surgical treatment has been the course of approach to prevent further clinical decline of patients. Identification of the syndrome is important for clinicians to know when to maximize medical management, and to identify patients who will benefit with early surgical management. The patient’s quality of life improved even 4 years post-surgery. Presentation: Saturday, June 17, 2023

Effect of active vitamin-D on left ventricular mass index: Results of a randomized controlled trial in type 2 diabetes and chronic kidney disease

Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n=19, placebo n=26). Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.

Scintigraphy Negative Ultrasound positive parathyroid adenoma in familial hypocalciuric hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) is a rare, lifelong, benign condition with an autosomal dominant pattern of inheritance. FHH is clinically distinguished by mild to moderate PTH-dependent hypercalcemia and normal to significantly reduced urinary calcium excretion despite elevated serum calcium. FHH is usually caused by a heterozygous loss-of-function mutation in the calcium-sensing receptor gene (CASR). It should be differentiated from primary hyperparathyroidism (PHPT). The reported case of a 10-year-old girl presented with symptomatic hypercalcemia, elevated intact parathyroid hormone, and a vitamin D deficiency. 99mTc-Sestamibi scan failed to detect any abnormalities, but high-resolution ultrasound (HRUS) of the neck revealed a right inferior parathyroid adenoma, which was excised with a focused parathyroidectomy. Although the patient’s calcium and iPTH levels normalized initially, they started rising within a few days. Bangladesh J. Nuclear Med. 26(1): 62-65, 2023

PSAT215 Hypercalcemic Crisis Complicating a First Trimester Pregnancy Caused by a Giant Parathyroid Adenoma Masquerading as a Thyroid Nodule

Abstract Background Primary hyperparathyroidism (PHP) during pregnancy is rare with a reported incidence of 1%, although the true incidence is unknown. It is associated with increased morbidity and mortality for both mother and fetus. Most reported cases of PHP during pregnancy are due to small adenomas causing mild hyperparathyroidism. Surgical management is recommended if the calcium level is &amp;gt;11mg/dL (2.75mmol/L) or the patient has symptomatic hypercalcemia. It is generally recommended that surgery be performed in the second trimester due to the risk of miscarriage in the first trimester, and preterm labor in the third trimester. Case A 29-year-old woman presented to our emergency department at 10 weeks’ gestation with nausea and vomiting. She also reported constipation and fatigue. On examination, she was euvolemic, awake and alert, with no neurological symptoms or signs. The suspected diagnosis was hyperemesis gravidarum until her laboratory evaluation revealed marked hypercalcemia [15.6mg/d (3.9mmol/L)]. Further labs revealed hypophosphatemia [1.2mg/dL (0.39mmol/L)], hypokalemia [3.3mEq/L], hypomagnesemia [1.4mEq/L], low 25-hydroxy vitamin D [16.2ng/mL (40.44pmol/L)], and elevated intact parathyroid hormone (iPTH) [573pg/mL], 1,25-dihydroxy vitamin D [251.1pg/mL (626.75pmol/L)], and 24 hour urinary calcium [448mg/24 hours (11.2mmol/24 hours]. On cardiac evaluation, her QTc was normal. The patient was given intravenous hydration with normal saline, which reduced the calcium to 13.6mg/dL (3.4mmol/L) after 48 hours. She remained symptomatic and severely hypercalcemic, so calcitonin 4 IU/kg every 12 hours was added, while a neck ultrasound was performed to localize the parathyroid adenoma. Her calcium level decreased to 10.7mg/dL (2.7mmol/L) after calcitonin, but rapidly rebounded to 13.3mg/dL (3.3mmol/L) along with hypophosphatemia and hypokalemia. Intravenous potassium phosphate was initiated and her calcium decreased to 11.8mg/dL (2.95mmol/L). The neck ultrasound did not identify a parathyroid adenoma, but identified a 2.5×1.5×3.3 cm right mixed cystic/ solid thyroid nodule. An MRI of the neck revealed two right thyroid nodules. The decision was made to perform a neck dissection given the persistent severe hypercalcemia after a multidisciplinary team evaluation, and extensive discussion with the patient. The surgical exploration of the right neck identified a giant parathyroid adenoma that weighed 11.3g. The intraoperative PTH levels reduced from 804pg/mL to 60.7pg/mL. Her calcium normalized immediately postoperatively and she was discharged home without complication. At the time of last follow up, she was 18 weeks’ gestation and a fetal ultrasound was normal. Discussion This case had three unusual features: PHP causing severe hypercalcemia during pregnancy; a giant parathyroid adenoma; and parathyroid adenoma masquerading as a thyroid nodule on imaging. This case highlights the importance of a multidisciplinary team approach in optimizing the care of such complicated patients, along with the need for definitive surgical intervention. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Abstract #1185089: Recognition of The Oral Calcium Loading Test in the Setting of Normocalcemic Hypercalcemia: A case series report

Context: Normocalcemic hyperparathyroidism is characterized by the persistence of normal serum calcium levels and elevated intact parathyroid hormone (PTH) values, after the exclusion of other secondary hyperparathyroidism causes. Patients with this condition can present with progressive complications, such as the conversion to primary hyperparathyroidism, as well as the development of osteoporosis and nephrolithiasis. The diagnosis can be challenging due to a vast number of issues including the differentiation between normocalcemic hypercalcemia and primary hyperparathyroidism, since both have similar biochemical findings.

Albuminuria Independently Determines Intact Parathyroid Hormone in Diabetic Nephropathy with Micro-albuminuria

Background: Diabetes mellitus (DM) is a well-recognised cause of end-stage renal disease (ESRD) through diabetic nephropathy (DN). Elevated intact parathyroid hormone (intact PTH) in DN represents a serious metabolic threat. Objective: We aimedto detect determinants of intact PTH changes during micro-albuminuria stage of DN. Patients and Methods: An observational study included 294 patients with type 2 diabetes mellitus (T2D) divided into 2 groups. Case group; 220 patients of DN with micro-albuminuria versus control group; 74 patients without albuminuria. Participants were subjected to history taking, clinical examination and laboratory assessment of glycosylated haemoglobin (HBA1c), serum creatinine, blood urea nitrogen (BUN), urine albumin creatinine ratio (urine ACR), estimated glomerular filtration rate (eGFR), 25(OH) vitamin D, intact PTH, serum ionized calcium, phosphorus and magnesium. Results: Among 220 patients of mean age 48.7 years and 57.7% male, albuminuria was significantly higher (P<0.001). We found non-significant difference between the study groups in estimated glomerular filtration rate (eGFR) and serum creatinine (P=0.375 and 0.294) respectively. Meanwhile, intact PTH was significantly elevated (P<0.001) in case group. Intact PTH was positively correlated with urine ACR, HBA1c, BUN, and serum creatinine and inversely correlated with eGFR. However, urine ACR was the only independent determinant of intact PTH in diabetic patients with micro-albuminuria (OR: 1.177; 95% CI: 1.074-1.290, P= 0.001). Conclusion: Interestingly, urine albumin creatinine ratio was the only independent determinant of intact PTH in diabetic patients with micro-albuminuria.

Recurrent Nephrolithiasis in a Patient With Hypercalcemia and Normal to Mildly Elevated Parathyroid Hormone

A 42-year-old man was referred to our stone clinic for recurrent episodes of symptomatic nephrolithiasis. Spontaneous stone passages occurred at the ages of 25, 40, and 42 years with one need for endoscopic stone removal. Calculi were composed of 100% calcium oxalate monohydrate. The patient had not taken any medication or supplements. Increased fluid intake was the only intervention for stone prevention. Metabolic work-up at presentation revealed mild hypercalcemia and normal to mildly elevated intact parathyroid hormone, even after repletion with oral 25-hydroxyvitamin D.

Mineral and bone disorder biomarkers and inflammation indexes in patients with end stage renal disease.

Chronic kidney disease (CKD) is an independent risk factor for bone and mineral metabolism disorder. Bone and mineral metabolism disorder develop gradually with the progression of renal failure. Various abnormalities include elevated fibroblast growth factor-23, decreased levels of 1,25-Dihydroxy Vitamin D (1,25-(OH)2D), and secondary hyperparathyroidism. This study aimed to evaluate the biomarkers and inflammation indexes of CKD-mineral and bone disorder (MBD), and to examine the associations of serum alkaline phosphatase (ALP) levels with serum C-reactive protein (CRP) levels and leukocyte count, in patients with end-stage renal disease (ESRD). ESRD patients who were yet to initiate dialysis were enrolled as the study subjects. All CKD patients who were discharged from our hospital between January 1, 2013, and December 31, 2017, were screened. Based on quartiles of serum ALP, all subjects were categorized into four subgroups. The clinical characteristics of patients in the four subgroups were investigated. The prevalence of hypocalcemia, hyperphosphatemia, elevated intact parathyroid hormone (iPTH), and elevated CRP level was calculated in the four subgroups. The association between serum ALP and inflammation indexes was examined using regression analysis. Based on the inclusion criteria and exclusion criteria, 256 cases with ESRD were included in our study. The overall prevalence of hypocalcemia and hyperphosphatemia was 57.81% and 89.84%, respectively. Of the patients with ESRD, 174 (68.75%) had an elevated iPTH level >2 times of the upper limit of normal value), and 40 (15.63%) had an elevated iPTH level >9 times of the upper limit of normal value Discrepancies between serum ALP and iPTH levels were found in 29 patients. In the adjusted model, log-transformed CRP, log-transformed iPTH, and leukocyte count were significantly associated with log-transformed ALP. Hypocalcemia, hyperphosphatemia, and increased levels of iPTH and CRP were found to be extremely common in ESRD patients. Discrepancies between serum ALP and iPTH were also observed. Our results also indicate that serum ALP level is associated with the levels of iPTH and CRP, as well as leukocyte count.

Three Rare Concurrent Complications of Tertiary Hyperparathyroidism: Maxillary Brown Tumor, Uremic Leontiasis Ossea, and Hungry Bone Syndrome.

A 48-year-old woman in her 40’s with end-stage renal disease and tertiary hyperparathyroidism (HPT) presented for a rapidly progressive maxillary tumor. Initial workup was notable for elevated intact parathyroid hormone (PTH) and diffuse thickening of skull and facial bones on computed tomography, and maxillary tumor biopsy with multinucleated giant cells. She underwent subtotal parathyroidectomy (with removal of a parathyroid adenoma and 2 hyperplastic glands) and partial resection of maxillary brown tumor. The patient’s post-operative course was complicated by hungry bone syndrome, with hypocalcemia refractory to aggressive calcium repletion. Teriparatide (recombinant PTH) was utilized with rapid resolution of hypocalcemia. To our knowledge, this is the first case of maxillary brown tumor in tertiary HPT to be reported in the USA. This case also supports teriparatide as a novel therapeutic for hungry bone syndrome refractory to aggressive calcium repletion.

P1406A CASE-CONTROL STUDY ON RISK FACTORS OF CALCIPHYLAXIS: DATA FROM CHINESE HEMODIALYSIS PATIENTS

Abstract Background and Aims Calciphylaxis (CUA) is a rare but potentially fatal disease that is commonly occurred in dialysis patients. Since there is no data based on Chinese population, the study is aimed to investigate risk factors of CUA in Chinese hemodialysis patients. Method We retrospectively evaluated medical records of 20 hemodialysis patients who were newly diagnosed with CUA by skin biopsy admitted to Zhongda Hospital Southeast University from Oct.2017 to Dec.2018. Non-CUA dialysis patients with the same age and duration of dialysis were randomly selected as controls (Ratio=1:2). Results Most of CUA patients were male (80%) and elderly (55%), while 50% had a body mass index higher than 24. The mean time interval since start of dialysis to CUA diagnosis was 114.65±81.32 months, and the median time from appearance of skin lesion to diagnosis was 6 (2, 15) months. The incidence of hyperparathyroidism was higher in patients with CUA (80% vs 62.5%), but the differences of duration of elevated serum intact parathyroid hormone (iPTH) and its highest value were not significant compared with the controls. Warfarin therapy had no significant difference between two groups (15% vs 5%). Univariate logistic regression analysis indicated that male (OR 3.619, 95%CI 1.027-12.748), each 1 point increase in score of use of vitamin D and its analogues (OR 1.505, 1.029-2.201), each 1 mmol/L increase in corrected serum calcium level (OR 24.486, 1.570-381.873), each 1 mmol/L increase in serum phosphate level (OR 5.382, 1.767-16.389), each 1 pg/mL increase in iPTH level (OR 1.002, 1.000-1.003), each 1 g/L decline in serum albumin level (OR 1.181, 1.041-1.340), each 1 IU/L increase in serum alkaline phosphatase (ALP) level (OR 1.005, 1.000-1.009) and each 1 mg/L increase in hypersensitive c-reactive protein level (OR 1.029, 1.000-1.059) were significantly associated with CUA. Serum phosphate, albumin and ALP were still significant risk factors after multivariate analysis. Conclusion This is the first report of risk factors of CUA based on Chinese population. The results show that high levels of serum phosphate and ALP, low level of serum albumin are independent risk factors of CUA in Chinese hemodialysis patients. Unlike previous research from western countries, warfarin therapy didn’t show an increased risk in this study, propably because of the low exposure rate of it in China.

SAT-344 Venous Thromboembolism Caused by Primary Hyperparathyroidism

Background. Primary hyperparathyroidism (PHPT) is often overlooked as a potential etiology of hypercoagulability and thrombosis. We present a case in which PHPT was the only identifiable risk factor for an episode of venous thromboembolism (VTE). Case. A 64 year old female with no chronic health problems presented to the emergency department for evaluation of dyspnea and right lower extremity pain. Symptoms had steadily increased in severity over approximately one week. The patient denied any long distance travel, sustained immobility, or tobacco use, and she was not taking any prescription or over-the-counter medications. Examination was notable for right distal lower extremity pain to palpation, but no swelling or erythema was observed. Elevated D-dimer (4.00 mg/mL, < 0.50) and hypercalcemia (12.7 mg/dL, 8.8–10.5) were discovered on initial laboratory testing, and an ECG showed sinus tachycardia. CT angiography of the chest revealed extensive, bilateral pulmonary emboli, and lower extremity venous Doppler studies confirmed a right lower extremity deep venous thrombus (DVT). Unequivocally elevated intact parathyroid hormone (PTH) level (235 pg/mL, 12–88) confirmed a diagnosis of PHPT, and an apparent left lower parathyroid adenoma was identified by both Tc99m parathyroid scintigraphy and neck ultrasonography. After hydration, serum calcium remained in the range of 11.5–12.0 mg/dL. The patient was discharged home on the direct factor Xa inhibitor rivaroxaban (Xarelto™) with a plan for six months of anticoagulation before parathyroidectomy. Conclusions. The skeletal, neuromuscular, cardiovascular, and neuropsychiatric manifestations of PHPT are well described, but little is published regarding PHPT and VTE. In a multivariate analysis of participants in the fourth and fifth Tromsø surveys controlled for age, sex, and BMI, simultaneous elevations of PTH and serum calcium were associated with a nearly 80% increased risk of VTE. PHPT has been linked to several changes that predispose to a hypercoagulable state and thrombosis including dehydration, vasoconstriction, increased platelet count and levels of coagulation factors VII and X, elevated tissue plasminogen activator inhibitor-1 and D-dimer levels, and diminished tissue factor pathway inhibitor levels. Unfortunately, risk of VTE is not addressed in series documenting long-term outcomes for patients undergoing parathyroidectomy for management of PHPT. However, in cases of VTE where PHPT is diagnosed, parathyroidectomy should be considered to potentially improve hypercoagulability and reduce the risk of subsequent VTE.

Thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1: one case report and literature review

Objective To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1(MEN1) through analyzing the clinical diagnosis and treatment process, as well as outcomes in one case of this disorder. Methods The clinical manifestations, biochemical and hormone levels, imaging presentations, medical and surgical treatments, and post-operational pathologic findings in the process of diagnosis and treatment of a patient with thyrotropin-secreting adenoma in MEN1 were analyzed. The next generation sequencing followed by Sanger method was used for analyzing MEN1 and related genes. The results were evaluated with online PolyPhen2 and PROVEAN for variation hazard. Results One 19-year old male patient was diagnosed with hyperthyroidism due to thyrotoxicosis and high level of thyroid hormones(THs) with measurable TSH(2.78 mIU/L) and negative thyrotropin receptor antibody(TRAb). Meanwhile, primary hyperparathyroidism was suggested by hypercalcemia, hypophosphatemia, and elevated intact parathyroid hormone(PTH) level, all the parameters were returned to normal after surgical resection of the mass which was below the left thyroid lobe indicated by ultrasound and 99mTc scan. Thyrotoxicosis remained in spite of one year treatment with antithyroid drug, thyrotropinoma was then suspected, and subsequent MRI scan found a macroadenoma at right pituitary. TSH and THs returned to normal 1 month after transsphenoidal removal of the adenoma. As expected, immunohistochemical staining revealed TSH positive. In addition, a pancreatic mass was found by both CT and MRI scan, which was considered as a silent neuroendocrine tumor. Gene analysis revealed a missense mutation of MEN1 as c. 415C>T and p. His139Tyr(H139Y), which was predicted highly hazard. Only five cases of thyrotropinoma in MEN1 were previously reported. Conclusion Thyrotropinoma should be cautiously identified from hyperthyroidism to avoid misdiagnosis and mistreatment, and it should keep in mind that thyrotropinoma may be associated with MEN1 though it would be very rare. Key words: Thyrotropinoma; Multiple endocrine neoplasia type 1; Hyperthyroidism; Hyperparathyroidism; MEN1 gene; Silent pancreatic neuroendocrine tumor

A patient with extensive cerebral calcification due to pseudohypoparathyroidism: a case report

BackgroundPseudohypoparathyroidism(PHP) is a heterogeneous group of disorders due to impaired activation of c AMP dependant pathways following binding of parathyroid hormone (PTH) to its receptor. In PHP end organ resistance to PTH results in hypocalcaemia, hyperphosphataemia and high PTH levels.Case presentationA 59 year old male presented with a history of progressive impairment of speech and unsteadiness of gait for 1 week and acute onset altered behavior for 1 day and one episode of generalized seizure. His muscle power was grade four according to MRC (medical research council) scale in all limbs and Chovstek’s and Trousseau’s signs were positive. Urgent non contrast computed tomography scan of the brain revealed extensive bilateral cerebral and cerebellar calcifications. A markedly low ionized calcium level of 0.5 mmol/l, an elevated phosphate level of 9.5 mg/dl (reference range: 2.7–4.5 mg/dl) and an elevated intact PTH of 76.3 pg/l were noted. His renal functions were normal. His hypocalcemia was accentuated by the presence of hypomagnesaemia. His 25 hydroxy vitamin D level was only marginally low which could not account for severe hypocalcaemia. A diagnosis of pseudohypoparathyroidism without phenotypic defects, was made due to hypocalcaemia and increased parathyroid hormone levels with cerebral calcifications. The patient was treated initially with parenteral calcium which was later converted to oral calcium supplements. His coexisting Vitamin D deficiency was corrected with 1αcholecalciferol escalating doses. His hypomagnesaemia was corrected with magnesium sulphate parenteral infusions initially and later with oral preparations. With treatment there was a significant clinical and biochemical response.ConclusionPseudohypoparathyroidism can present for the first time in elderly resulting in extensive cerebral calcifications. Identification and early correction of the deficit will result in both symptomatic and biochemical response.

Population-level associations of achievement of targets for bone-mineral markers with survival in haemodialysis patients with mildly elevated intact-PTH levels: a case-cohort study

Achieving calcium, phosphorus, and intact parathyroid hormone (PTH) targets helps improve dialysis population outcomes. We aimed to assess the population-level associations of achievement of those targets with survival using population-attributable-fractions (PAFs). We conducted a case-cohort study using data from 8229 haemodialysis patients with mildly elevated intact PTH, treated at 86 dialysis facilities in Japan. We examined associations among calcium, phosphorus, intact PTH, and mortality over 3 years. We estimated PAFs for achieving the targets of calcium, phosphorus, and intact PTH from the adjusted hazard ratios by Cox regression models. Proportions within the recommended range were 55.8%, 63.3%, and 39.1% for calcium (8.4–10.0 mg/dL), phosphorus (3.5–6.0 mg/dL) and intact PTH (60–240 pg/mL), respectively. The mortality rate was 5.7 per 100 person-years. Mortality was independently associated with non-achievement of targets. Regarding the population-level impact, statistically significant PAFs were found for achieving the combination of calcium and phosphorus (8.8%; 95% CI, 1.1–16.0). Further, PAF for combined calcium, phosphorus, and intact PTH was the largest (16.8%; 95% CI, 5.6–30.4). In conclusion, there might be additive and substantial population-level associations between survival and the achievement of calcium, phosphorus, and intact-PTH targets in the haemodialysis population with mildly elevated intact PTH.

MON-LB085 Blurred Vision and Hypocalcemia after Denosumab Injection in a Patient with Tertiary Hyperparathyroidism

Background: Denosumab is a human monoclonal antibody that targets the receptor activator of nuclear factor kappa B ligand (RANKL). It inhibits osteoclast-mediated bone resorption by binding to receptor. Denosumab prevents skeletal-related events (SREs) from osteoporosis and bone metastasis. However, there has been arising concern about hypocalcemia that is more vulnerable for patients with renal impairment due to elevated total osteoblast mass, coexisting calcitriol deficiency, inhibition by fibroblast growth factor 23. Clinical Case: A 66-year-old woman with ESRD on HD was transferred our endocrinology clinic for hypercalcemia and elevated intact parathyroid hormone(PTH); corrected calcium, 10.8 mg/dL(normal range: 8.5-10.2) and PTH, 164 pg/mL(8.00-72.00). I thought she had tertiary hyperparathyroidism(HPT). It is observed in patients with chronic secondary HPT who have been on dialysis therapy for years. I planned to examine sestamibi scan and neck ultrasonography to localize hypertrophied parathyroid glands. And then, I prescribed denosumab and a combined oral calcium/vitamin D supplement for her because she had persistent hypercalcemia and no medication for osteoporosis(DEXA T score is -3.8, -3.1 and -3.7 in L1-4, right femoral total, and neck respectively). After two weeks, she presented to our hospital for blurred vision of left eye. Papilledema and inferior visual field defect of left eye were observed in ophthalmology examination. Furthermore she had been receiving multiple dose of calcium and calcitriol injection during dialysis due to severe hypocalcemia at local dialysis center. Laboratory finding of dialysis clinic revealed corrected calcium decreased to 6.6 mg/dL(8.5-10.2) and PTH extremely increased to 3066 pg/mL(8.00-72.00). After rechecking her blood, laboratory work up showed corrected calcium, 7.7 mg/dL(8.5-10.2); 25(OH)vitamin D, 16.26 ng/mL(30-80); PTH, 1739 pg/mL(8.00-72.00). I examined sestamibi scan and neck USG. The results of sestamibi scan indicated hyperfunctioning parathyroid adenoma/hyperplasia in upper pole level of right thyroid gland and lower pole level of left thyroid gland that were matched with hypoechoic nodules of neck USG. We considered surgical interventions, total parathyroidectomy with autotransplantation or subtotal parathyroidectomy paying attention to postoperative complications such as hungry bone syndrome. Conclusion: Denosumab is an effective, tolerable anti-resorptive agent that has no nephrotoxicity, however, the risk of hypocalcemia is increasing, especially patients with chronic kidney disease. Hypocalcemia is a potentially life-threatening biochemical disorder that cause papilledema leading to the loss of vision. Therefore we should be aware of importance of monitoring calcium levels and renal function before and during denosumab therapy. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-509 A Challenging Case of Symptomatic Primary Hyperparathyroidism during Pregnancy Treated with Cinacalcet

Primary hyperparathyroidism (PHPT) during pregnancy is rare. Hypercalcemia (HCa) may be undetected due to hypoalbuminemia and increased active transport of calcium via the placenta. Undiagnosed HCa may present with life threatening maternal hypercalcemic crisis and fetal hypocalcemia. In patients with moderate and severe HCa, parathyroidectomy (PTx) is recommended during the second trimester. Cinacalcet is approved for treatment of secondary hyperparathyroidism in patients with ESRD, HCa due to parathyroid carcinoma, and in patients with severe HCa due to PHPT unable to undergo PTx. However, cinacalcet use in pregnancy is limited to a few case reports. We present a case of PHPT presenting with severe HCa and cardiomyopathy where PTx was contraindicated due to risk of cardiac decompensation. To our knowledge this is the first case of cinacalcet use in PHPT where therapeutic doses were well tolerated resulting in a safe delivery without maternal and fetal complications. A 38 year old female at 25 weeks gestation (gravida 7, para 4) presented from an outside hospital for treatment of pyelonephritis and new onset cardiomyopathy with reduced ejection fraction of 20%. The patient had a history of preeclampsia but denied a personal or family history of nephrolithiasis and calcium abnormalities. Present medication included a prenatal multivitamin. Physical exam revealed tachycardia, hypotension and no palpable neck mass. Laboratory evaluation revealed a corrected calcium 13.8 (8.7-10.7mg/dL), ionized calcium (iCa) 1.7 (0.95-1.32 mmol/L), phosphate 1.7 (2.5-4.6 mg/dL), magnesium 1.5 (1.6-2.7 mg/dL), creatinine 0.83 mg/dL. Treatment with normal saline 0.9 % was started with IV furosemide to prevent fluid overload. Further evaluation showed an elevated intact parathyroid hormone 383 (8-85 pg/mL), elevated 1,25 dihydroxyvitamin D 147 (18-78 pg/mL), normal parathyroid hormone related peptide 14 (14-27 pg/mL), fractional excretion of calcium of 1.7%, and fractional excretion of phosphate of 25% confirming the diagnosis of PHPT. A neck ultrasound showed a 2 cm left thyroid nodule; FNA biopsy confirmed a parathyroid adenoma. Evaluation for MEN 1 was negative. Due to severe cardiomyopathy, the patient was deemed a poor surgical candidate. Treatment with cinacalcet 30 mg daily was started and slowly titrated to 90 mg twice daily. On discharge, iCa had normalized to 1.26. The patient was readmitted to the hospital four days prior to delivery for discontinuation of cinacalcet and prevention of fetal parathyroid gland suppression. The patient delivered a healthy male at 37 weeks of gestation without hypocalcemia. Treatment of PHPT during pregnancy is challenging especially in those patients who are unable to undergo PTx. Cinacalcet may be a safe option to prevent maternal and fetal complications of HCa in patients with PHPT. Further studies are needed to evaluate the safety of cinacalcet in pregnancy.

SUN-507 Parathyroid Carcinoma and Incidental Finding of Hashimoto's Thyroiditis in a Patient with End-Stage Renal Disease: A Case Report

Background: Parathyroid carcinoma is a very rare endocrine neoplasia. The incidence reported is less than 1% in primary hyperparathyroidisim (1). The presence of this rare carcinoma is even less likely in the setting of chronic kidney disease. Unfortunately, parathyroid carcinoma is difficult to differentiate clinically with parathyroid adenoma and hyperplasia pre-operatively. Clinical Case: A case of a 48-year-old male, diagnosed with end-stage renal disease secondary to IgA Nephropathy and maintained on chronic hemodialysis for 8 years, presented with progressive decreasing height and occasional bone pain. Despite compliance to hemodialysis, calcimimetics, phosphate binders, calcium and vitamin D supplementation to suppress the high PTH levels, patient remained persistently hyperparathyroid with intact PTH of 4793pg/ml (NV: 15-65 pg/ml). Other laboratory findings showed vitamin D sufficiency (Vitamin D 87 nmol/L (NV: >75 nmol/L), hypocalcemia (ionized calcium 1.08 mmol/L (NV: 1.10-1.35) and hyperphosphatemia (inorganic phosphate 2.15 mmol/L (NV: 0.01-1.45 mmol/L). With the failure of medications to suppress the high PTH levels, surgical removal of the parathyroid glands was then the next possible option. A dual phase sestamibi scan of the parathyroid revealed a single focal activity at the mid aspect of the right thyroid bed on the wash-out phase. Patient underwent total parathyroidectomy and total thyroidectomy. Intraoperative findings revealed enlarged bilateral parathyroid glands with largest measuring 2x2 cm and incidental findings of multiple nodules in bilateral thyroid glands. Final histopathology revealed parathyroid carcinoma in 3 out of 4 glands and Hashimoto’s thyroiditis with multi-nodular adenomatous goiter. Conclusion: It is a challenge to clinically differentiate parathyroid carcinoma and other causes of hyperparathyroidism among patients undergoing chronic maintenance hemodialysis due to the effect of renal insufficiency on calcium metabolism. This case highlights an unusual case of parathyroid carcinoma in a patient with ESRD and incidental finding of hashimoto’s thyroiditis, who presented with extremely elevated intact parathyroid hormone accompanied with hypocalcemia. Reference: (1) Ronald A. De Lellis, Ricardo V. Lloyd, Philipp U. Heitz, CharisEng: World Health Organization Classification of Tumors. Pathology and Genetics, Tumors of Endocrine Organs.77, 2004