scholarly journals Bilateral Basal Ganglia Calcification; An Unusual Initial Presentation of Pseudohypoparathyroidism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A184-A185
Author(s):  
Ahmad Zare ◽  
Sara Choudhry
Keyword(s):  
Vitamin D ◽  
Basal Ganglia ◽  
Serum Calcium ◽  
Initial Presentation ◽  
Active Vitamin ◽  
Adequate Treatment ◽  
Basal Ganglia Calcification ◽  
Active Vitamin D ◽  
Calcium Phosphorus ◽  
History Of

Abstract Physiological intracranial calcification occurs in about 0.3–1.5% of cases. Hypoparathyroidism and pseudohypoparathyroidism are the most common causes of pathological basal ganglia calcification. A 21-year-old female who was initially evaluated by neurology team for headache and diplopia, underwent MRI of brain which revealed Calcifications involving the bilateral basal ganglia, thalami, dentate nuclei as well as juxtacortical frontal lobes. She reported Fatigue and muscle pain, usually in her arms especially after playing sports which had been going on for many years. She had no history of fractures, seizures, psychiatric disorders, developmental delay or obvious cognitive impairments. She denied any family history of calcium disorders or autoimmune diseases. As she had been generally healthy in her whole life, she never had any lab testing done. On examination, Height 5’1”, Chvostek’s sign was positive. Fundoscopy was normal. she had no dysmorphic features or shortened 4th metacarpal. Investigations revealed serum calcium less than 5.0 mg (N 8.3 - 10.1 mg/dl), PTH 205.1 pg/ml (N 18.4 - 80.1 pg/ml), phosphate 7.1 mg (N 2.5 - 5 mg), Vitamin-D 36.2 ng/ml (N 30.0 - 100.0 pg/ml),magnesium 2.0 m (N 1.6 - 2.6 mg/dl) with normal albumin, alkaline phosphatase and renal function test. She was diagnosed with pseudohypoparathyroidism and started on calcium and active vitamin D supplement and was referred for genetic testing study. She reported significant improvement in myalgia after a few weeks of starting calcium and active vitamin D supplementations and repeat lab testing showed improved hypocalcemia and hyperphosphatemia. This case illustrates unusual presentation of PTH resistance with basal ganglia calcification as initial presentation prompting further workup. She likely has pseudohypoparathyroidism type 1b. Since adequate treatment of hypoparathyroidism may lead to marked clinical improvement, determination of serum calcium, phosphorus, and parathyroid hormone is mandatory in all individuals with calcification of the basal ganglia to rule out hypoparathyroidism.

scholarly journals Disease Burden of Patients Living With Hypoparathyroidism: Results From the Voices of Hypopara Survey

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A260-A261
Author(s):  
Deborah Murphy ◽  
Bob Sanders ◽  
Loretta Gulley ◽  
Ami Knoefler ◽  
Alden Smith ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Disease Burden ◽  
Vitamin D Supplementation ◽  
Urgent Care ◽  
Monitoring Device ◽  
Active Vitamin ◽  
The Past ◽  
Active Vitamin D ◽  
At Home

Abstract Background: Hypoparathyroidism (HP) is a rare disease that is characterized by insufficient levels of parathyroid hormone, resulting in hypocalcemia, hyperphosphatemia and hypercalciuria. Standard of care (SoC) consists of calcium and active vitamin D supplementation. Some patients may suffer from “calcium crashes”, sudden hypocalcemia symptoms that can be severe enough to require a visit to the emergency room (ER) or urgent care. Conversely, chronic use of SoC supplements can also increase risk of hypercalciuria and renal failure. The HypoPARAthyroidism Association (HPA), a nonprofit organization dedicated to improving the lives of hypoparathyroid patients, developed the “Voices of Hypopara” survey to capture the journey of patients with HP in the US. Methods: The online survey was distributed to all HPA members (approximately 1,000) in May 2020. Questions focused on evaluating patients’ experiences including diagnosis, treatment, quality of care, and impact on daily living. Results: The survey was completed by 146 HPA members (89% female; mean age 51). Most participants reported they are currently taking SoC (calcium 91%; active vitamin D 77%). However, over half felt that this did not optimally address their disease and 29% were extremely concerned about hypocalcemia despite supplementation. Many (69%) felt that taking SoC was moderately to extremely burdensome. More than two-thirds (69%) of respondents reported a “calcium crash” in the past year; of these, 43% reported calcium crashes monthly or weekly. Almost half (42%) of all participants required a visit to an ER/urgent care in the last year as a result of HP symptoms; of these, 56% believed that the staff was inexperienced with management of a calcium crash. More than 60% of participants checked serum calcium levels at least every couple of months at a physician’s office or lab in the past year, with 36% checking monthly or more frequently; the majority of respondents (70%) said the reason was due to symptoms of hypocalcemia. Participants viewed an at-home device for measuring serum calcium, phosphate, and magnesium levels as one key approach to manage their HP symptoms (47% ranked as “most preferred”), followed by more effective medications as the second most preferred option (23%). Almost all (99%) responded that they would use an at-home monitoring device and would test frequently. Conclusions: Results from this survey underscore the high disease burden of patients with HP, highlighting sudden hypocalcemic episodes as a key morbidity despite treatment with calcium and active vitamin D supplementation, and sub-optimal management by clinicians as an impediment to optimal treatment. These findings reinforce the need for more frequent, easily accessible, and real-time serum calcium level monitoring device, more efficacious therapies, and greater disease understanding among health care workers to best manage patients with HP.

scholarly journals Leukaemic Secretion of Calcitriol: A Novel Mechanism of Hypercalcaemia in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5098-5098
Author(s):  
Joshua Misha Lewis Casan ◽  
Sarah Ghotb ◽  
Sue Morgan ◽  
Stephen B Ting
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Rare Complication ◽  
Kidney Injury ◽  
Active Vitamin ◽  
Normal Range ◽  
Lymphoid Malignancies ◽  
Active Vitamin D ◽  
Upper Limit

Abstract Introduction: Whilst relatively common in lymphoid malignancies, hypercalcaemia is an extremely rare complication of acute myeloid leukaemia (AML). Previous case reports have described ectopic parathyroid hormone secretion, leukaemic bony invasion and the release of boneresorptivemediators as causes of hypercalcaemia in AML (GewirtzAM et al. Br JHaematology1983;31(12):1590,ZidarBL, et al.NEJM.1976;295:692). We describe a case of severe hypercalcaemia with acute kidney injury (AKI) accompanying a new diagnosis of AML, subsequently demonstrated to be secondary to leukaemic blast production of active vitamin D (calcitriol) with gross over-expression of vitamin D related genes. This represents a novel pathogenic mechanism causing hypercalcaemia in a myeloid malignancy. Case Report: AA, a 68 year old male presenting with fatigue and found to have circulating blasts was subsequently diagnosed with acutemyelomonocyticleukaemia(78% blasts on bone marrow biopsy). Additionally, he had marked hypercalcaemia (calcium 3.3mmol/L, normal range 2.1-2.6mmol/L) and AKI (creatinine 263umol/L, normal range 60-110umol/L). Given the rarity of AML-associated hypercalcaemia, extensive investigations were undertaken to elucidate the cause. In search of a second concurrent malignancy, AA underwent computed tomography and positron emission tomography scanning, with subsequent biopsy of FDG avid vocal cord nodules; but only benign pathology could be demonstrated. Parathyroid hormone (PTH) levels were appropriately suppressed (0.9pmol/L, normal range 1.6-6.9pmol/L) and levels of PTH-related peptide and serum ACE were normal (<2pmol/L, and 37units/L, normal range 20-70units/L, respectively). Inactive vitamin D, (calcidiol or 25(OH)D3) levels were also normal (88nmol/L, normal range 50-250nmol/L). However, the active vitamin D (calcitriol or 1,25(OH)2D3) level was grossly elevated beyond the upper limit of assay (>500pmol/L, upper limit of normal: 190pmol/L). Both the hypercalcaemia and kidney injury proved refractory to multiple therapeutic strategies including aggressive hydration with an average of over 2.5L of crystalloid per day, as well as intravenouspamidronate. However, as depicted in Figure 1, there was a precipitous response following the initiation of chemotherapy (idarubicinandcytarabine, 7+3 regimen). Within several days, AA's serum calcium levels returned to normal levels, and his kidney function followed a similar pattern of improvement shortly thereafter. The rapid resolution of serum calcium levels also mirrored peripheral blast clearance, and repeat testing of calcitriol levels showed progressive improvement towards a normal concentration. AA achieved complete remission following induction chemotherapy and remains leukaemia free after consolidation chemotherapy and current maintenanceazacitidine. His hypercalcaemia has not recurred and his renal function remains normal. Having excluded other causes of hypercalcaemia and given the dramatic response to chemotherapy, we hypothesised that AA's AML blasts were secreting calcitriol. Accordingly, quantitative PCR was performed on AA's stored leukaemic cells for genes essential to vitamin D metabolism: the vitamin-D receptor (VDR), CYP24A1, and CYP27B1 (1-α-hydroxylase). RNA was extracted from AML cells using the QIAGEN RNeasykit. cDNAwas synthesised from 400ng of RNA using the Roche First Strand cDNASynthesis Kit. Gene expression was assessed by quantitative real-time PCR, relative to the housekeeping gene GAPDH. AA's leukaemia cells demonstrated markedly elevated expression of these vitamin-D related genes compared to healthy control CD34+ cells and four other independent primary AML cells (Figure 2, labelled AML 1-4), which were selected for absence of patient hypercalcaemia from our institution's tissue bank (Figure 2). Conclusion: Hypercalcaemia secondary to secretion of calcitriol can be a manifestation of lymphoid malignancies, however our case is the first documented occurrence of this phenomenon in a myeloid cancer. The PCR studies demonstrated striking overexpression of vitamin D related genes in leukaemia cells, resulting in the patient's hypercalcaemia and AKI. This finding represents a novel mechanism for a rare complication in AML. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Standards of care for hypoparathyroidism in adults: a Canadian and International Consensus

2019 ◽  
Vol 180 (3) ◽  
pp. P1-P22 ◽  
Author(s):  
Aliya A Khan ◽  
Christian A Koch ◽  
Stan Van Uum ◽  
Jean Patrice Baillargeon ◽  
Jens Bollerslev ◽  
...  
Keyword(s):  
Vitamin D ◽  
Patient Education ◽  
Serum Calcium ◽  
Standards Of Care ◽  
Close Monitoring ◽  
Active Vitamin ◽  
Vitamin D Analogs ◽  
Diagnosis And Management ◽  
Active Vitamin D

Purpose: To provide practice recommendations for the diagnosis and management of hypoparathyroidism in adults. Methods: Key questions pertaining to the diagnosis and management of hypoparathyroidism were addressed following a literature review. We searched PubMed, MEDLINE, EMBASE and Cochrane databases from January 2000 to March 2018 using keywords ‘hypoparathyroidism, diagnosis, treatment, calcium, PTH, calcidiol, calcitriol, hydrochlorothiazide and pregnancy’. Only English language papers involving humans were included. We excluded letters, reviews and editorials. The quality of evidence was evaluated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. These standards of care for hypoparathyroidism have been endorsed by the Canadian Society of Endocrinology and Metabolism. Results: Hypoparathyroidism is a rare disease characterized by hypocalcemia, hyperphosphatemia and a low or inappropriately normal serum parathyroid hormone level (PTH). The majority of cases are post-surgical (75%) with nonsurgical causes accounting for the remaining 25% of cases. A careful review is required to determine the etiology of the hypoparathyroidism in individuals with nonsurgical disease. Hypoparathyroidism is associated with significant morbidity and poor quality of life. Treatment requires close monitoring as well as patient education. Conventional therapy with calcium supplements and active vitamin D analogs is effective in improving serum calcium as well as in controlling the symptoms of hypocalcemia. PTH replacement is of value in lowering the doses of calcium and active vitamin D analogs required and may be of value in lowering long-term complications of hypoparathyroidism. This manuscript addresses acute and chronic management of hypoparathyroidism in adults. Main conclusions: Hypoparathyroidism requires careful evaluation and pharmacologic intervention in order to improve serum calcium and control the symptoms of hypocalcemia. Frequent laboratory monitoring of the biochemical profile and patient education is essential to achieving optimal control of serum calcium.

scholarly journals Hypoparathyroidism and pseudohypoparathyroidism

2006 ◽  
Vol 50 (4) ◽  
pp. 664-673 ◽  
Author(s):  
Sergio S. Maeda ◽  
Erika M. Fortes ◽  
Ulisses M. Oliveira ◽  
Victoria C.Z. Borba ◽  
Marise Lazaretti-Castro
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Basal Ganglia ◽  
Calcium Supplementation ◽  
Free Calcium ◽  
Principal Function ◽  
Active Vitamin ◽  
Basal Ganglia Calcification ◽  
Oral Calcium ◽  
Glomerular Filtrate

The principal function of the parathyroid hormone (PTH) is maintenance of calcium plasmatic levels, withdrawing the calcium from bone tissue, reabsorbing it from the glomerular filtrate, and indirectly increasing its intestinal absorption by stimulating active vitamin D (calcitriol) production. Additionally, the PTH prompts an increase in urinary excretion of phosphorus and bicarbonate, seeking a larger quantity of free calcium available in circulation. Two mechanisms may alter its function, limiting its control on calcium: insufficient PTH production by the parathyroids (hypoparathyroidism), or a resistance against its action in target tissues (pseudohypoparathyroidism). In both cases, there are significantly reduced levels of plasmatic calcium associated with hyperphosphatemia. Clinical cases are characterized by nervous hyperexcitability, with paresthesia, cramps, tetany, hyperreflexia, convulsions, and tetanic crisis. Abnormalities such as cataracts and basal ganglia calcification are also typical of these diseases. Treatment consists of oral calcium supplementation associated with increased doses of vitamin D derivatives.

Treatment with active vitamin D (alphacalcidol) in patients with mild primary hyperparathyroidism

1989 ◽  
Vol 120 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Lars Lind ◽  
Bo Wengle ◽  
Ole Helmer Sørensen ◽  
Leif Wide ◽  
Göran Åkerström ◽  
...  
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Controlled Study ◽  
High Dose ◽  
Active Vitamin ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Active Vitamin D ◽  
Mild Primary Hyperparathyroidism

Abstract. The parathyroid gland possesses receptors for 1,25-dihydroxyvitamin D3, the active metabolite of the vitamin D system, and in vitro experiments have shown that 1,25-dihydroxyvitamin D3 can inhibit the secretion of PTH. In this study 31 subjects who had displayed persistent mild hypercalcemia for 14 years and presumably had mild primary hyperparathyroidism (HPT) were challenged with 1.0 μg alphacalcidol (1α-(OH)-vitamin D3) over 6 months in a double-blind, placebo-controlled study. Before initiation of therapy, the hyperparathyroid subjects showed lower serum levels of 1,25-dihydroxyvitamin D in relation to PTH or calcium when compared with age- and sex-matched controls. Treatment induced a slight rise in serum calcium (0.05 mmol/l), but no significant decrease of the PTH levels. Eighteen of the subjects thereafter entered an open study with a higher dose of alphacalcidol (2.0 μg) over 1 year. Although this high dose induced a marked rise in serum calcium (0.17 mmol/l), there was only a transient reduction of the PTH levels. Thus, during long-term condition there was an escape from the suppressive action of the elevated calcium concentrations and no evidence of a specific inhibition of PTH secretion by a small oral dose of active vitamin D.

2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial

2016 ◽  
Vol 45 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Ravi Thadhani ◽  
Julia B. Zella ◽  
Danielle C. Knutson ◽  
William J. Blaser ◽  
Lori A. Plum ◽  
...  
Keyword(s):  
Vitamin D ◽  
Single Agent ◽  
Hemodialysis Patients ◽  
Double Blind Study ◽  
Dialysis Patients ◽  
Active Vitamin ◽  
Double Blind ◽  
Active Vitamin D ◽  
Vitamin D Analog ◽  
Calcium Phosphorus

Background: Vitamin D analogs and calcimimetics are used to manage secondary hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic women, and hemodialysis patients. The safety and effectiveness of DP001 suppressing PTH in dialysis patients previously managed with active vitamin D with or without a calcimimetic are presented. Methods: A multicenter, randomized, double-blind study compared DP001 to placebo in hemodialysis patients with serum-intact PTH (iPTH) ≥300 pg/ml. The primary efficacy endpoint was the proportion of patients achieving 2 consecutive ≥30% decreases in iPTH levels during the 12 weeks of treatment. Calcium, phosphorus, calcium × phosphorus product and safety were also evaluated. The responses to DP001 were compared in patients previously treated with both active vitamin D and a calcimimetic to those previously on active vitamin D alone. Results: Sixty-two patients were randomized (n = 34 DP001; n = 28 placebo). At week 12, 78% of all DP001-treated patients and 7% of all placebo-treated patients achieved the primary endpoint (p < 0.0001); iPTH fell 45% in the DP001 group and increased 37% in the placebo group. No patient exceeded the safety threshold of 2 consecutively corrected serum calcium levels ≥11.0 mg/dl. Patients previously on cinacalcet plus active vitamin D also responded to DP001 (n = 10) resulting in a 55% decrease in iPTH, while those on placebo (n = 9) increased by 70%. Conclusion: DP001 safely and effectively suppressed iPTH in hemodialysis patients with SHPT that were previously managed with active vitamin D alone or with a calcimimetic (www.clinicaltrials.gov, NCT01922843).

scholarly journals Hypoparathyroidism in Pregnancy and Lactation: Current Approach to Diagnosis and Management

2021 ◽  
Vol 10 (7) ◽  
pp. 1378
Author(s):  
Dalal S. Ali ◽  
Karel Dandurand ◽  
Aliya A. Khan
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Calcium Absorption ◽  
Case Reports ◽  
Case Series ◽  
Close Monitoring ◽  
Active Vitamin ◽  
Diagnosis And Management ◽  
Active Vitamin D ◽  
Pregnancy And Lactation

Background: Hypoparathyroidism is an uncommon endocrine disorder. During pregnancy, multiple changes occur in the calcium-regulating hormones, which may affect the requirements of calcium and active vitamin D during pregnancy in patients with hypoparathyroidism. Close monitoring of serum calcium during pregnancy and lactation is ideal in order to optimize maternal and fetal outcomes. In this review, we describe calcium homeostasis during pregnancy in euparathyroid individuals and also review the diagnosis and management of hypoparathyroidism during pregnancy and lactation. Methods: We searched the MEDLINE, CINAHL, EMBASE, and Google scholar databases from 1 January 1990 to 31 December 2020. Case reports, case series, book chapters, and clinical guidelines were included in this review. Conclusions: During pregnancy, rises in 1,25-dihydroxyvitamin D (1,25-(OH)2-D3) and PTH-related peptide result in suppression of PTH and enhanced calcium absorption from the bowel. In individuals with hypoparathyroidism, the requirements for calcium and active vitamin D may decrease. Close monitoring of serum calcium is advised in women with hypoparathyroidism with adjustment of the doses of calcium and active vitamin D to ensure that serum calcium is maintained in the low-normal to mid-normal reference range. Hyper- and hypocalcemia should be avoided in order to reduce the maternal and fetal complications of hypoparathyroidism during pregnancy and lactation. Standard of care therapy consisting of elemental calcium, active vitamin D, and vitamin D is safe during pregnancy.

scholarly journals Primary Hypoparathyroidism and Chronic Kidney Disease: Is It Always Related to Treatment?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A214-A215
Author(s):  
Todor Zlatanski ◽  
Nicole Simon
Keyword(s):  
Vitamin D ◽  
Basal Ganglia ◽  
Critical Role ◽  
Phosphate Binders ◽  
Close Monitoring ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Qt Interval Prolongation ◽  
Ectopic Mineralization ◽  
Chronic Hypoparathyroidism

Abstract Background: Anterior neck surgery is the leading cause of acquired hypoparathyroidism. Renal failure is the most common complication of treatment for hypoparathyroidism with active vitamin D and calcium supplements. However, the contribution of hypoparathyroidism to development of CKD in the absence of treatment is not well studied. Clinical Case: A 70-year old woman was brought to ED after she was found on the floor at home. Medical history was significant only for a partial thyroidectomy over 20 years prior, without reported post-operative complications. She was not taking any medications. Pertinent physical findings included altered mental status, hand tremors, involuntary contractions of left arm, and ashen skin. Laboratory tests upon presentation were significant for profoundly low albumin-corrected calcium of 3.68 mg/dL (n 8.6–10.2 mg/dL); low PTH 9.9 pg/dL (n 15–65 pg/dL); elevated phosphorous 8.5 mg/dL (n 2.7–4.5 mg/dL), elevated BUN 36 mg/dL (n 8–22 mg/dL), creatinine 2.76 mg/dL (n 0.5–1.3 mg/dL) and elevated CK of 4787 U/L (n 10–225 U/L). EKG showed QT interval prolongation. Head CT revealed periventricular and basal ganglia calcifications. Renal US was normal. The patient was treated with IV and PO calcium acetate and active vitamin D with resolution of the symptoms while calcium level improved. Post hospital follow-ups were significant for persistent hyperphosphatemia, which gradually improved with calcium and non-calcium phosphate binders as well as active vitamin D. Although this patient presented with acute hypocalcemia, she had chronic hypoparathyroidism as evidenced by basal ganglia calcifications. In the absence of other medical conditions, including negative PTH antibodies, or treatment for chronic hypoparathyrodism, the most likely cause of the CKD was chronic hypoparathyroidism itself. Conclusion: Post-surgical hypoparathyroidism may develop many years after surgery and can be asymptomatic. It is essential to diagnose this condition early to avoid late complications of the disease. The kidneys are particularly affected. Conventional treatment with calcium and vitamin D analogues is associated with ectopic mineralization and can lead to CKD. Untreated hypoparathyroidism on the other hand, can also lead to CKD, posing therapeutic challenges on finding the most appropriate and balanced treatment regimen in order to prevent further renal complications. Close monitoring and optimizing therapy plays critical role in preserving renal function of patients with hypoparathyroidism.

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