Normal Serum Calcium Research Articles

Occult Renal Calcifications in Patients with Normocalcemic Primary Hyperparathyroidism and Their Association with the Parathyroid Hormone-Vitamin D Axis.

Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated serum levels of parathyroid hormone (PTH) with persistently normal serum calcium concentrations after excluding secondary causes of hyperparathyroidism. Urolithiasis and/or nephrocalcinosis may occur in hypercalcemic PHPT, but little is known about these complications in NPHPT. Objectives. To identify occult urolithiasis and nephrocalcinosis in asymptomatic patients with NPHPT and evaluate biochemical markers as risk predictors for the development of renal calcification (RC). Methods. Cross-sectional analysis of 34 patients with no history of urolithiasis and/or nephrocalcinosis. The diagnosis of NPHPT was as follows: elevated serum PTH (reference range: 15–65 pg/mL), normal albumin-corrected serum calcium, normal urinary calcium excretion, serum 25(OH)D >30 ng/mL, eGFR (CKD-EPI) > 60 mL/min/1.73 m2, without intestinal disease, and not on medications such as thiazide diuretics, lithium, bisphosphonates, or denosumab. Patients were categorized according to the presence or absence of RC identified by renal imaging. Their clinical and biochemical characteristics were then compared. Results. The patients had a mean age of 67.97 ± 10.45 years, predominantly postmenopausal women (88.2%); serum PTH, 119.67 ± 64.44 pg/mL; 25(OH)D, 39.00 ± 8.88 ng/dL; 1.25(OH))2D, 74.53 ± 26.37 pg/mL; corrected serum calcium, 9.34 ± 0.62 mg/dL; and 24-hour urinary calcium, 134.87 ± 79.68 mg/day. RC was identified in 26.5% of the patients. There was no difference in anthropometric and clinical parameters, renal function, 25(OH)D, and urinary pH in patients with or without RC. Patients with RC had higher PTH values (176.22 vs. 99.32 pg/mL, P = 0.001), 1.25(OH) 2D (96.83 vs. 62.36 pg/mL, P = 0.005), and 24-hour urinary calcium (181.9 vs. 117.94 mg/day, P = 0.037). Conclusion. Occult renal calcifications are common in NPHPT and are associated with increased serum PTH, 1.25(OH))2D, and 24 h urinary calcium.

Evaluation of the Early Results of Percutaneous Ethanol Ablation in Patients with Primary Hyperparathyroidism

Abstract Percutaneous ethanol ablation (PEA) is an alternative non-surgical method for the treatment of patients with primary hyperparathyroidism (PHPT), suitable in cases with comorbidities and high surgical risk. The aim of the present study was to evaluate the results of PEA in patients with PHPT at the early stages of follow-up. Materials and methods: The study included 35 patients (30 women and 5 men, mean age 59.7 ± 12.4 years) with biochemical and hormonal data of PHPT and localized parathyroid adenoma (PTA) by ultrasound, nuclear scan, FNB with cytology and evaluation of PTH in the needle washout. All patients were at high surgical risk or refused surgical treatment. PEA was applied and changes in the PTA volume and calcium-phosphate metabolism were monitored at the third (M3) and sixth (M6) months after the procedure. Results: Normocalcaemia was achieved in 26 patients (74.3%) at M3 and persisted at M6 in 22 of them. A second course of PEA was administered in 11 patients with persistent hypercalcaemia at M3 and M6, respectively. Compared to the baseline, the mean PTA volume decreased significantly by 53% at M3 and 67% at M6 (p < 0.001). Side effects including local pain, edema and dysphonia were observed in 5 patients (14.3%). Conclusion: PEA is an efficient and safe treatment modality for the management of PHPT. A significant reduction in PTA volume and a normalization of serum calcium and PTH levels were observed at the early stages of follow-up.

The Importance of Vitamin D in Long-Term Care Residents

The Importance of Vitamin D in Long-Term Care Residents

Calcinosis Cutis of the Nasal Dorsum

Summary:Calcinosis cutis is a common dermatological problem in patients with systemic sclerosis, dermatomyositis, and systemic lupus erythematous; however, it is rare to occur outside of these diseases. It represents a multidisciplinary problem that involves primary care physicians, dermatologists, and surgeons. The pathophysiology is defined by deposition of calcium salts in the subcutaneous tissue as hydroxyapatite, but the underlying mechanism has yet to be determined. The most common locations of lesions are the scalp, scrotum, extremities, and joints. Rarely does calcinosis cutis occur on the face. We present a unique case of idiopathic calcinosis cutis that occurred in a healthy patient with normal serum calcium and phosphate levels on the nasal dorsum, which was managed surgically. The histology of the calcinosis showed normal morphology, dominated by large deposits of calcium and normal surrounding tissues. This case represents a rare but clinically relevant presentation of idiopathic calcinosis cutis in an otherwise healthy individual.

Risk factors influencing cure of ultrasound-guided microwave ablation for primary hyperparathyroidism

Objective To evaluate the potential risk factors influencing cure rate of ultrasound-guided microwave ablation (MWA) for primary hyperparathyroidism (PHPT). Materials and methods Seventy five patients (25 males and 50 females; mean age, 56.80 ± 12.34; age range, 26–85) with PHPT undergoing MWA under ultrasound guidance were enrolled between May 2017 and December 2020. The cure rate and complications were evaluated after treatment. The potential factors influencing cure rate of ultrasound-guided MWA for PHPT were analyzed by univariate and multivariate binary logistic regression. Results Fifty six of 75 patients had normal PTH and serum calcium levels after at least 6 months after one session MWA, and the cure rate was 74.7% (56/75). 6 uncured patients received the second session MWA during follow-up, and the cure rate achieved 81.3% (61/75) after the second session MWA. Voice changes occurred in 4 patients (5.33%) and recovered within 3 months after ablation without special treatment. Nodule volume was the independent risk factor associated with cure in PHPT patients undergoing MWA, whether after one session (p = 0.0224; odds ratio, 0.67) or the second session MWA (p = 0.0408; odds ratio, 0.74). The cutoff value for nodule volume in predicting the cure was 0.96 cm3 (one session: sensitivity, 76.8%; specificity, 73.7%; the second session: sensitivity, 72.1%; specificity, 71.4%). Conclusion In conclusion, parathyroid nodule volume was the independent risk factor associated with cure in PHPT patients undergoing MWA.

The efficacy and safety of cinacalcet in primary hyperparathyroidism: a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Cinacalcet, a positive allosteric modulator of the calcium sensing receptor (CaSR) reduces parathyroid hormone (PTH) secretion by increasing the sensitivity of the CaSR on parathyroid cells. We conducted a systematic review and meta-analysis on the safety and efficacy of cinacalcet in Primary Hyperparathyroidism (PHPT). MEDLINE, Embase, BIOSIS, and the Cochrane Library were searched for published articles (from database inception to Sept 2020). All double-blind RCTs and cohort studies that reported data on the efficacy and safety of cinacalcet therapy in individuals ≥ 18 with PHPT were included. Random effect meta-analysis was performed to estimate the efficacy of cinacalcet in lowering serum calcium and PTH levels compared with placebo. 4 RCTs (177 participants) and 17 cohort studies (763 participants) were eligible for final analysis. Pooled results from the RCTs suggest that, when compared to placebo and administered for up to 28weeks, cinacalcet normalizes serum calcium (≤ 10.3mg/dl) in patients with PHPT [RR 20 (95% CI 6.04 - 68.52, I2 = 0%, pheterogeneity < 0·00001)]. Serum PTH levels decreased significantly after 2weeks and up to 28weeks after treatment with cinacalcet. In the pooled analysis of the 17 cohort studies, serum calcium levels normalized in 76% (95% CI 66% to 86%; I2 = 92%, pheterogeneity < 0·00001) of patients regardless of the duration of treatment. In most studies, PTH levels decreased by 13% to 55%. No RCT reported on BMD as a primary or secondary outcome, and no improvement in BMD was noted in the 2 non-randomized studies that reported densitometric findings. No significant difference in urinary calcium was noted with cinacalcet therapy in either the RCTs or non-randomized studies. There was no significant difference in overall adverse events (AE) (RD 0.01, 95% CI -0.07 to 0.26) compared to placebo noted in the RCTs. In the non-randomized studies, pooled weighted AE rate was 45% (95% CI 32 to 59%). Risk of bias was low in 2/4 RCTs and 6/17cohort studies; risk was intermediate in 2/4 RCTs and 8/17 cohort studies, and risk was high in 3/17 cohort studies. In PHPT, cinacalcet lowers serum calcium and PTH with greater effects on calcium than on PTH in the short term. In the doses reported, the drug is safe with tolerable side effects. These findings can help inform targeted medical therapy of PHPT in those for whom lowering the serum calcium is indicated and for whom parathyroidectomy is not an option.

Recurrent Bilateral Lower Motor Neuron Type of Facial Palsy with Hearing Impairment: Hyperphosphatemic Familial Tumoral Calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg 2 /mL 2 ) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

Normocalcemic primary hyperparathyroidism: 99mTc SestaMibi SPECT/CT results compare with hypercalcemic hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (nPHPT) is defined by an inappropriately increased serum PTH with normal serum calcium. Information about the diagnostic yield of parathyroid SPECT/CT scan and ultrasonography in nHPPT is limited and not conclusive. To evaluate the positivity rate of 99m Tc-Sestamibi SPECT/CT scan in nPHTP compared with classical hypercalcemic PHPT (cPHPT). We retrospectively studied 125 patients with 99m Tc-Sestamibi SPECT/CT scans. Subjects were divided into 2 groups: cPHPT (n = 93) and nPHPT (n = 32). The detection rate of 99m Tc-Sestamibi SPECT/CT in cPHPT was 86,02% (80/93) and 59.37%, in nPHPT (19/32), p = .003. No significant differences were seen between the SPECT/CT scan and ultrasonography (p = .28) and the agreement was higher in cPHPT than in nPHPT, p = .03. Sensitivity of 99m Tc-Sestamibi-SPECT/CT was 98% on a per-patient basis (PPV 96%) and 91% on a per-lesion basis (PPV 88%). Glandular size was smaller in nPHPT (mean value 6.8 mm) and it was related only with PTH value. Localization rate of parathyroid hyperfunctioning tissue with 99m Tc-Sestamibi SPECT/CT is lower in nPHPT and it is related to a smaller glandular size. However, our study suggests that the positivity rate and sensitivity are nonnegligible by adding SPECT/CT. The reduction in the detection rate in nPHPT could benefit techniques with higher resolution such as 18 F-Choline PET/CT when the clinical context justifies it.

Tumor-Induced Osteomalacia With Normal Fibroblast Growth Factor-23 (FGF23) and Idiopathic Hypercalciuria

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome characterized by low serum phosphate, phosphaturia, inappropriately low/normal levels of serum calcitriol, and normal or elevated levels of fibroblast growth factor-23 (FGF23). Finding this mesenchymal tumor is challenging since it is usually benign, small, slow-growing, and is localized in the appendicular skeleton. We report a 58-year-old male patient who arrived at the endocrinology outpatient clinic due to slowly progressive low back pain and generalized weakness since the age of 48. On physical examination, only a reduced range of motion was noted. Laboratory tests revealed hypophosphatemia with normal parathyroid hormone (PTH) levels, normal serum calcium, high 24-hour urine calcium, normal 1,25-dihydroxyvitaminD levels, low renal threshold phosphate concentration (TmPO4/GFR), and high FGF23. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) reported a hypermetabolic extramedullary lesion in the C1-C2 vertebral bodies measuring 1.5 x 1.1 cm. Two months after the 18F-FDG PET/CT, complete excision of the cervical tumor was performed. The pathology ward reported a histiocytic mesenchymal neoplasm with accumulations of multinucleated giant cells compatible with phosphaturic mesenchymal tumor. After surgery, the patient’s hypophosphatemia was completely resolved. With this, the diagnosis of TIO was confirmed. The patient remains asymptomatic, with normal phosphate levels at one year of follow-up. Hypophosphatemia due to renal losses in an adult patient is a challenging diagnosis and one must consider TIO, autosomal dominant hypophosphatemic rickets, fibrous dysplasia, and even Fanconi syndrome. FGF23 can be extremely useful during the diagnostic approach since acquired dependent hypophosphatemia (FGF23 ≥ 30 RU/mL) highly suggests TIO. In this case report, we want to highlight the paramount importance of adequate tumor screening in adult patients with acquired FGF23-dependent hypophosphatemia. TIO is a reversible cause of hypophosphatemia with potentially disabling consequences if left untreated. These manifestations are non-specific (bone pain and muscle weakness), while others are progressive and severely disabling (bone deformities and multiple fractures). In this case report, we want to highlight the paramount importance of adequate tumor screening in adult patients with acquired hypophosphatemia, and the crucial lead that phosphate and vitamin D regulating hormones (FGF23) have for suspecting TIO.

Analysis of the cause and management of persistent laboratory abnormalities occurring after the surgical treatment of primary hyperparathyroidism.

PurposeThe surgical success rate for primary hyperparathyroidism (PHPT) is currently 95%–98%. However, 3%–24% of patients show persistently elevated (Pe) parathyroid hormone (PTH) levels after parathyroidectomy (PTX). This single-center retrospective study aimed to compare the outcomes of patients with normal PTH and PePTH levels after successful PTX and to identify the factors associated with PePTH.MethodsThe normal group, defined as patients with normal serum calcium and PTH levels immediately after PTX, was compared with the PePTH group (patients with normal or low serum calcium and increased serum PTH levels up to 6 months postoperatively) to determine the causes of disease in the PePTH group.ResultsThere were no significant differences in age, sex, or preoperative estimated glomerular filtration rate between the normal PTH group (333 of 364, 91.5%) and the PePTH group (31 of 364, 8.5%). However, there were significant differences in preoperative 25-hydroxyvitamin D (17.9 and 11.8 ng/mL, respectively; P = 0.003) and PTH levels (125.5 and 212.4 pg/mL, respectively; P < 0.001) between the 2 groups. Among the 31 cases of the PePTH group, 18 were attributed to vitamin D deficiency.ConclusionPreoperative vitamin D deficiency is a predictive factor for PePTH. Therefore, preoperative administration of vitamin D supplements may reduce the probability of postoperative disease persistence. Patients with temporary laboratory abnormalities within 6 months after successful PTX should be monitored, and appropriate vitamin D and calcium supplementation may reduce the effort and cost of various examinations or reoperations.

Tumor-induced osteomalacia: Easing the diagnosis with fibroblast growth factor 23

Tumor-induced osteomalacia (TIO), is a rare paraneoplastic syndrome resulting in bone pain, muscle weakness, and recurrent fractures. Hypophosphatemia, hyperphosphaturia, low 1, 25 dihydroxyVitamin D, and normal serum calcium are noted. It is mostly caused by fibroblast growth factor 23 (FGF23) secreting tumors. Apart from testing for FGF23, additional imaging modalities are required to identify the causative lesion. Prompt remission follows successful lesion excision. This case report highlights the importance of FGF 23 in the diagnosis of TIO.

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

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

IS CONFIRMATION OF PARATHYROID TISSUE BY FROZEN SECTION SUPERIOR TO LOCALIZATION OF SOLITARY PARATHYROID ADENOMA USING INTRAOPERATIVE GAMMA PROBE SURVEY? A RETROSPECTIVE COHORT STUDY.

In the surgical treatment of primary hyperparathyroidism, intraoperative localization of the diseased glands is an essential issue. We aimed to evaluate the impact of the intraoperative frozen section during radio-guided focused parathyroidectomy and compare its efficiency with intraoperative gamma probe survey and measurement of intraoperative quick parathyroid hormone. All consecutive patients underwent radio-guided focused parathyroidectomy for primary hyperparathyroidism due to solitary parathyroid adenoma. The outcomes of parathyroidectomy were evaluated by serum levels of calcium and parathyroid hormone. The primary outcome was the surgical cure diagnosed by normal serum calcium levels in the sixth postoperative month. A total of 55 patients with a mean age of 54.3±12.2 years were evaluated. The diagnostic accuracy of the preoperative localization tests was calculated as 92.7%. The intraoperative gamma probe survey impacted the operative plans of four patients (7.3%) by localizing the diseased gland in other positions. The accuracy of intraoperative quick parathyroid hormone and frozen section analysis was 100% for both. In all patients, serum calcium and PTH levels dropped to normal in the sixth postoperative month. There were no cases of the persistent or recurrent disease during the follow-up period. The results of the intraoperative gamma probe survey, intraoperative quick parathyroid hormone, and frozen section were concordant with the final pathology in all cases. In four patients (7.3%), intraoperative gamma probe survey impacted the operative plans. The intraoperative gamma probe survey may be used as the sole intraoperative method to locate the correct position of the solitary parathyroid adenoma.

An uncommon presentation of a common disease

A 24 year old woman presented to our institution with a two week history of multiple discrete, painful, nodular and indurated foci of erythema on her lower limbs against a six week background history of a constellation of more nonspecific symptoms including intermittent dry cough, malaise, migrating arthralgias, subjective fevers, anorexia and weight loss. She denied B symptoms. There were no ophthalmic, neurological or cardiovascular symptoms. Examination was significant for features of mild hyper-metabolism manifest by low grade pyrexia with accompanying diaphoresis in conjunction with bilateral lower limb predominant erythema nodosum. Laboratory studies revealed a neutrophilic leucocytosis, raised acute phase reactants/ inflammatory markers, normal serum calcium, ACE, Vitamin D, renal and liver indices. Chest radiography revealed bilateral hilar adenopathy with minimal interstitial involvement. A diagnosis of Löfgren’s syndrome was suspected, an uncommon variant of multisystem sarcoidosis. Subsequent bronchoscopy with trans-bronchial tissue biopsy revealed non-caseating granulomas. The diagnosis was confirmed and treatment instituted with non-steroidal anti-inflammatory medication.

Bone Turnover Markers in Response to Ultrasound-Guided Microwave Ablation for Primary Hyperparathyroidism.

ObjectiveTo assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT), and to investigate whether MWA can improve the bone turnover and renal function.MethodsA total of 20 consecutive PHPT patients with 21 parathyroid lesions treated with MWA in our center from May 2019 to March 2021 were recruited in this study. Serum parathyroid hormone (PTH), calcium and phosphorus levels before MWA and at 20 minutes, 4 hours, 1 day, 3 months, 6 months and 12 months after MWA were measured. Bone turnover biomarkers, renal function and lesion volume with volume reduction rate (VRR) before MWA and at the last follow-up were compared. Any complication related with MWA was evaluated. The technical and clinical success rates of MWA in the treatment of PHPT were calculated. Clinical success was defined as normal serum PTH and calcium without PHPT-associated manifestations at more than 6 months after ablation. Technical success was defined as complete ablation indicated by immediate postoperative contrast-enhanced ultrasound.ResultsThe serum PTH, calcium and phosphorus levels at their respective follow-up time points dropped significantly after MWA (P <0.05). The volume of parathyroid lesions at the final examination was significantly reduced, compared with pre-ablation volume (P <0.001), with a median VRR reaching 89%. The technical and clinical success rates were 100% and 63.6%, respectively. Substantial changes of bone turnover biomarkers were observed before and after MWA (P <0.05), but the differences in renal function were not statistically significant. No major complications were reported in all cases. Pre-MWA serum PTH, lesion volume, maximum diameter of lesion and ablation time were significantly different between patients with successful and failed MWA.ConclusionsPHPT can be effectively and safely treated by ultrasound-guided MWA, as proven by drop in serum PTH and reduction in the volume of parathyroid adenomas. Besides, MWA can impede bone remodeling to suppress hyperparathyroidism in the condition of PHPT.

Clinical Image: Calcinosis cutis universalis in a patient with polymyositis/scleroderma overlap syndrome.

The patient, a 32-year-old woman with a known history of polymyositis/scleroderma overlap, presented for a second opinion regarding subcutaneous nodules. On examination, the patient had extensive subcutaneous painful nodules over multiple areas of the body, including bilateral arms, thighs, and hands. There were no open or ulcerative lesions. Workup demonstrated normal creatine kinase, parathyroid hormone, serum calcium, and serum phosphate levels and normal bone mineral density. Electromyography showed no evidence of active myositis. A frontal projection radiograph demonstrated extensive sheetlike soft tissue calcinosis consistent with calcinosis cutis universalis. Calcinosis cutis describes the deposition of insoluble calcium salts in the cutaneous and subcutaneous tissue (1). Five subtypes of calcinosis cutis exist on the basis of the etiology: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. The dystrophic subtype results from tissue trauma or chronic inflammation due to autoimmune connective tissue disorders. Dystrophic calcinosis cutis develops in approximately 25% of patients with systemic sclerosis and 11% to 20% of patients with dermatomyositis (2, 3). Calcinosis cutis universalis, as seen in this patient, is a rare presentation. Two types of calcinosis cutis universalis exist: diffuse deposits along myofascial planes and deep intramuscular tumoral deposits, as seen in this patient (4). Although multiple treatment modalities have been trialed, no effective treatment is known (5).

Persistent hypercalcemia with similar familial Hypocalciuric hypercalcemia features: a case report and literature review

BackgroundPrimary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the most important differential diagnosis of parathyroid hormone (PTH)-dependent hypercalcemia. The clinical features of FHH and PHPT can overlap in some cases. Therefore, these two diseases must be differentiated to prevent unnecessary parathyroidectomy. Here, we present a case that was not entirely matched with any of the known differential diagnoses of hypercalcemia.Case presentationA 19-year-old girl with no history of any disease presented with persistent hypercalcemia without any specific musculoskeletal complaint. We found persistent hypercalcemia in her routine laboratory data from 3 years ago; while no data was available during the childhood period. Her dietary calcium intake was normal. She did not mention any history of renal stone, bone fracture as well as family history of hypercalcemia. Biochemical features showed normal values of serum creatinine, high normal serum calcium (range, 10.3–11.3 mg/dL; (normal range: 8.8–10.4)), and non-suppressed PTH levels (range, 37.2–58.1 pg/mL; (normal range: 10–65)). Serum 25 OH vitamin D level at the first visit was 16.1 ng/mL that treated by vitamin D supplementation. Since then, all 25 OH vitamin D levels were in the acceptable range. After correction of vitamin D deficiency during the follow-up period the calcium creatinine clearance ratio(s) (CCCR) were calculated in the range of 0.009 to 0.014 (means below 1%). The clinical and laboratory data indicate more FHH rather than PHPT. Genetic studies were negative for the common genes associated with FHH (CASR, GNA11, and AP2S1 genes) and multiple endocrine neoplasia type1 (MEN1). On the other hand, no evidence of autoimmunity was found in her to support an autoimmune FHH-like syndrome. Hence, the case did not match completely to any diagnosis of FHH and PHPT, so we decided to follow her.ConclusionWe presented a patient with FHH phenotype whose common genetic tests were negative. Further research is needed to ascertain other causes leading to similar manifestations.

Evaluation of serum macronutrients level and depression among adolescents and its association with pre-hypertension: A cross sectional study

Introduction and Aim: Serum macronutrients measurement prove to be precedent values with regard to diagnose hypertension at an earlier age. Depression in any form could be ruinous to younger generation, also could precipitate hypertension. The aim of the study is to estimate serum calcium, magnesium levels, grade depression and to establish its association with prehypertension. Materials and Methods: A cross sectional study was conducted on 68 students aged 17-19 years over a two months period. Blood samples were drawn and serum magnesium and calcium were estimated. Depression was assessed by administering KADS – 6 questionnaires. Blood Pressure was measured by auscultatory method using mercury sphygmomanometer. All parameters were presented as mean ± SD. Chi square test was used to compare proportions for the groups. Unpaired t test was used to compare the groups. ANOVA was used to compare the groups for continuous variables. Statistical analysis was done using Epi info (version 6.04d) software package. Results: More than 44% of the study participants had elevated serum calcium levels, while about 10% of them had elevated serum magnesium levels. More than half (58.8%) of the participants were pre-hypertensive. One third of the study participants were depressed of which about 10% of them had severe depression. The prevalence of prehypertension was 2.1 times higher among participants having hypercalcemia when compared to participants who have normal serum calcium levels with 95% CI of 1.38 - 3.22 which is statistically significant (p-value &lt; 0.001). The study could not establish a statistical difference between different groups with regards to serum magnesium levels and depression. Conclusion: Our study portrays the widely prevalent depression and pre-hypertension in younger generation and exhibits firm evidence on measuring serum macronutrient levels to diagnose pre-hypertension before time that can prevent the disease load and help ineffective management.

Subcutaneous calcinosis: Is it different between systemic sclerosis and dermatomyositis?

Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It is a manifestation of several autoimmune connective tissue diseases, most frequently with systemic sclerosis and juvenile dermatomyositis, followed by adult dermatomyositis. Autoimmune connective tissue disease-associated calcinosis is of the dystrophic subtype, which occurs at sites of damaged tissue in the setting of normal serum calcium and phosphate levels. In juvenile dermatomyositis, calcinosis is considered a marker of ongoing disease activity and possibly inadequate treatment, while in adult dermatomyositis, it is a hallmark of skin damage due to chronic rather than active disease. Calcinosis is associated with long disease duration in systemic sclerosis and dermatomyositis, anti-polymyositis/sclerosis autoantibodies in systemic sclerosis and NXP-2 and melanoma differentiation-associated gene 5 in dermatomyositis. Calcinosis in systemic sclerosis occurs most frequently in the hands, particularly the fingers, whereas in dermatomyositis, it affects mainly the trunk and extremities. The primary mineral component of calcinosis is hydroxyapatite in systemic sclerosis and carbonate apatite in dermatomyositis. Calcinosis in dermatomyositis and systemic sclerosis share some pathogenic mechanisms, but vascular hypoxia seems to play a more important role in systemic sclerosis, whereas the release of calcium from mitochondria in muscle cells damaged by myopathy may be a primary mechanism contributing to dermatomyositis-related calcinosis. Multiple treatment strategies for dermatomyositis and systemic sclerosis-related calcinosis have been used with variable results. Early aggressive treatment of underlying myositis in patients with dermatomyositis may improve long-term outcomes of calcinosis. A better understanding of the pathogenesis of calcinosis is needed to improve treatment options.

Overlapping Phenotypes Associated With CYP24A1, SLC34A1, and SLC34A3 Mutations: A Cohort Study of Patients With Hypersensitivity to Vitamin D.

Mutations in CYP24A1 (vitamin D 24-hydroxylase) and SLC34A1 (renal phosphate transporter NPT2a) cause autosomal recessive Infantile Hypercalcemia type 1 and 2, illustrating links between vitamin D and phosphate metabolism. Patients may present with hypercalciuria and alternate between chronic phases with normal serum calcium but inappropriately high 1,25-(OH)2D and appropriately low PTH, and acute phases with hypercalcemia with suppressed PTH. Mutations in SLC34A3 and SLC9A3R1 have been associated with phosphate wasting without hypercalcemia. The aims of this study were to evaluate the frequency of mutations in these genes in patients with a medical history suggestive of CYP24A1 mutation to search for a specific pattern. Using next generation sequencing, we screened for mutations in 185 patients with PTH levels < 20 pg/mL, hypercalcemia and/or hypercalciuria, and relatives. Twenty-eight (15%) patients harbored biallelic mutations in CYP24A1 (25) and SLC34A3 (3), mostly associated with renal disease (lithiasis, nephrocalcinosis) (86%). Hypophosphatemia was found in 7 patients with biallelic mutations in CYP24A1 and a normal phosphatemia was reported in 2 patients with biallelic mutations in SLC34A3. Rare variations in SLC34A1 and SLC34A3 were mostly of uncertain significance. Fifteen patients (8%) carried only one heterozygous mutation. Heterozygous relatives carrying SLC34A1 or SLC34A3 variation may present with biochemical changes in mineral metabolism. Two patients’ genotype may suggest digenism (heterozygous variations in different genes). No variation was found in SLC9A3R1. As no specific pattern can be found, patients with medical history suggestive of CYP24A1 mutation should benefit from SLC34A1 and SLC34A3 analysis.