Brown tumour mimicking skeletal metastasis

Brown tumours of bone are highly vascular osteolytic lesions that depict a reparative cellular process instead of a neoplastic process in hyperparathyroidism (HPT) patients. These tumours have the potential to be aggressive and destructive. We report a case of a 30-year-old woman who presented with left thigh and lower back pain. The radiological evaluation showed multiple bony lesions in the pelvis and the spine, which mimicked multiple metastatic tumours. However, on biochemistry evaluation, serum calcium, alkaline phosphatase, and parathyroid hormone were all high, while serum phosphate was low, indicating primary HPT (PHPT), which was confirmed by parathyroid scintigraphy showing left parathyroid adenoma. Hence, the bony lesions were diagnosed as brown tumours secondary to PHPT. The patient underwent parathyroidectomy and developed severe hungry bone syndrome requiring parenteral calcium infusion along with oral calcium and active vitamin D supplementation. The clinical symptoms of bone pain improved after surgery.

Hypocalcemia in Setting of Malignancy of Unknown Origin: A Case Report

Background: Hypercalcemia is a common finding well-recognized in up to 30% of cases of malignancy, associated with poor prognosis and advanced disease state. Hypocalcemia, while uncommon, can also be found in cases of malignancy facilitated by its own unique mechanism and etiologies. We present a case of severe hypocalcemia in the setting of malignancy of unknown origin. Clinical Case: 72-year-old female with a history of metastatic carcinoma of unknown origin, followed actively by Oncology, presented acutely with shortness of breath, chest pain, stiff hands and clenched fist. Patient had reported a 20 lbs weight loss over three months with a “knot” in the epigastric area affecting appetite and interfering with eating. Prior CT showed diffuse adenopathy with diffuse permeative bone destruction highly suspicious for malignancy. Follow up PET-CT showed mixed lytic lesion and sclerotic changes throughout the entire skeleton from the skull to mid thighs compatible with osseous metastatic. Initial tests show severe hypocalcemia with appropriately PTH elevation and normal vitamin D25 (calcium 5.5 mg/dL, albumin 3.9 g/dL, phosphorus (PO4) 2.3 mg/dL, magnesium (Mg) 1.5 mg/dL, PTH 243 pg/mL, vitamin D25 31.44 ng/mL). Further workup shows normal creatinine levels (0.88 mmol/L) and elevated alkaline phosphatase (1140 IU/L). Physical exam revealed bilaterally clenched fist and positive Chvostek sign. After two doses of 2 grams calcium gluconate, calcium had improved up to 7.2 mg/dL (corrected 7.76 mg/dL, albumin 3.3 g/dL) with plans to replete Mg and PO4. Patient was started on Calcium-Vitamin-D 500-200 mg-units (Oscal) two tabs trice daily. However, calcium continues to drop the next day with levels at 5.7 mg/dL (corrected 6.42 mg/dL, albumin 3.1 g/dL). A calcium infusion of 10 grams was then given over 16 hours. Calcitriol 0.25 mg twice daily was started. 24-hour urine study showed low calcium excretion (<0.8 mg/dL), normal Mg excretion (6.5 mg/dL) with an adequate creatinine collected (0.6 grams) showing no deficiencies in kidney resorption. Prior to discharge, patient’s calcium had stabilized (corrected 8.2 mg/dL, albumin 3.4 g/dL) and her associated symptoms had resolved. She was discharged on Oscal 2 tabs 4 times daily and Calcitriol 1 mcg twice daily. Conclusion: Given these biochemical results and imaging evidence of bone metastases, this case highlights the uncommon findings of hypocalcemia in the setting of malignancy. With the combination of low 24-hour urine calcium, elevated PTH, normal vitamin D25, low PO4, normal kidney function and increased alkaline phosphatase, these findings most likely indicate hypocalcemia secondary to osteoblastic bone metastasis, resulting from deposition of calcium in osteoblastic lesions. References: Schattner A, Dubin I, Huber R, Gelber M. Hypocalcaemia of malignancy. Neth J Med. 2016 Jul;74(6):231–9. PMID: 27571720

Profound Hypocalcemia Following Thyroidectomy for Graves’ Disease

Introduction: While transient parathyroid insufficiency is not an uncommon complication of thyroidectomy, severe and prolonged hypocalcemia attributed to a combination of post-surgical hypoparathyroidism, hungry bone syndrome (HBS) and hypovitaminosis D is unusual. Clinical Case: A 17-year-old female from a remote community in Australia with Graves’ disease, complicated by exophthalmos and atrial flutter, underwent total thyroidectomy due to challenges with medication adherence leading to persistent thyrotoxicosis. FT4 was >150 pmol/L (normal 10–20 pmol/L) almost two years after diagnosis. Pre-operatively, she received Lugol’s iodine, carbimazole and beta-blockade. The operation was uncomplicated and three parathyroid glands were preserved. Within six hours of thyroidectomy, she developed symptomatic hypocalcemia with corrected calcium 1.9 mmol/L (7.6 mg/dL) (normal 2.2–2.65 mmol/L). PTH level was 0.8 pmol/L (normal 1.4–9.0 pmol/L). Magnesium and phosphate levels were initially normal but hyperphosphatemia developed the following day. 25-OH vitamin D was low (29 nmol/L, normal 50–150 nmol/L) and was corrected with high dose cholecalciferol. Despite use of continuous intravenous calcium gluconate in addition to oral calcium carbonate, as well as both intravenous and oral calcitriol and magnesium, urinary calcium excretion remained undetectable. Teriparatide 20 mcg BD was commenced on post-operative day 14 with no demonstrable improvement in serum calcium. Less than 48 hours after cessation of parenteral calcium on day 18 post-operation, corrected calcium and ionised calcium declined to 1.47 mmol/L (5.9 mg/dL) and 0.46 mmol/L (normal 1.15–1.33 mmol/L) respectively, prompting recommencement of calcium infusion. Her remarkably high requirement for calcium replacement with negligible urinary calcium excretion for at least one month in spite of parenteral calcium infusion for a total of three weeks’ duration is highly suggestive of HBS which became evident due to post-surgical hypoparathyroidism. She had elevated ALP (618 U/L, normal 35–140 U/L) and increased bone resorption marker (N-telopeptide/creatinine 262 nmol BCE/mmol, normal <100 nmol BCE/mmol), with osteopenia at lumbar spine (Z-score -1.7) and femur (Z-score -1.3). Additionally, vitamin D deficiency is likely to have contributed to the severity of hypocalcemia. 60 days after surgery, she was still requiring calcium carbonate 2500 mg QID (4 g/day elemental calcium) and calcitriol 1 mcg TDS. Her phosphate level had normalised and ALP gradually declined to 241 U/L. Clinical Lesson: This case highlights the importance of attaining euthyroid status as early as possible pre-operatively to allow near-complete reversal of thyrotoxicosis-induced osteodystrophy, as indicated by normalisation of serum ALP, and ensuring vitamin D levels are replete prior to thyroidectomy for Graves’ disease.

Comparison between regional citrate anticoagulation and heparin for intermittent hemodialysis in ICU patients: a propensity score-matched cohort study

Background Regional citrate anticoagulation (RCA) is the gold standard of anticoagulation for continuous renal replacement therapy but is rarely used for intermittent hemodialysis (IHD) in ICU. Few studies assessed the safety and efficacy of RCA during IHD in ICU; however, no data are available comparing RCA to heparin anticoagulation, which are commonly used for IHD. The aim of this study was to assess the efficacy and safety of RCA compared to heparin anticoagulation during IHD. Methods This retrospective single-center cohort study included consecutive ICU patients treated with either heparin anticoagulation (unfractionated or low-molecular-weight heparin) or RCA for IHD from July to September in 2015 and 2017. RCA was performed with citrate infusion according to blood flow and calcium infusion by diffusive influx from dialysate. Using a propensity score analysis, as the primary endpoint we assessed whether RCA improved efficacy, quantified with Kt/V from the ionic dialysance, compared to heparin anticoagulation. The secondary endpoint was safety. Exploratory analyses were performed on the changes in efficacy and safety between the implementation period (2015) and at long term (2017). Results In total, 208 IHD sessions were performed in 56 patients and were compared (124 RCA and 84 heparin coagulation). There was no difference in Kt/V between RCA and heparin (0.95 ± 0.38 vs. 0.89 ± 0.32; p = 0.98). A higher number of circuit clotting (12.9% vs. 2.4%; p = 0.02) and premature interruption resulting from acute high transmembrane pressure (21% vs. 7%; p = 0.02) occurred in the RCA sessions compared to the heparin sessions. In the propensity score-matching analysis, RCA was associated with an increased risk of circuit clotting (absolute differences = 0.10, 95% CI [0.03–0.18]; p = 0.008). There was no difference in efficacy and safety between the two time periods (2015 and 2017). Conclusion RCA with calcium infusion by diffusive influx from dialysate for IHD was easy to implement with stable long-term efficacy and safety but did not improve efficacy and could be associated with an increased risk of circuit clotting compared to heparin anticoagulation in non-selected ICU patients. Randomized trials to determine the best anticoagulation for IHD in ICU patients should be conducted in a variety of settings.

The challenges of post-bariatric surgery hypocalcaemia in pre-existing hypoparathyroidism

Summary Conventional treatment of hypoparathyroidism relies on oral calcium and calcitriol. Challenges in managing post-parathyroid- and post-thyroidectomy hypocalcaemia in patients with a history of bariatric surgery and malabsorption have been described, but postoperative management of bariatric surgery in patients with established hypoparathyroidism has not. We report the case of a 46-year-old woman who underwent elective sleeve gastrectomy on a background of post-surgical hypoparathyroidism and hypothyroidism. Multiple gastric perforations necessitated an emergency Roux-en-Y gastric bypass. She was transferred to a tertiary ICU and remained nil orally for 4 days, whereupon her ionised calcium level was 0.78 mmol/L (1.11–1.28 mmol/L). Continuous intravenous calcium infusion was required. She remained nil orally for 6 months due to abdominal sepsis and the need for multiple debridements. Intravenous calcium gluconate 4.4 mmol 8 hourly was continued and intravenous calcitriol twice weekly was added. Euthyroidism was achieved with intravenous levothyroxine. Maintaining normocalcaemia was fraught with difficulties in a patient with pre-existing surgical hypoparathyroidism, where oral replacement was impossible. The challenges in managing hypoparathyroidism in the setting of impaired enteral absorption are discussed with analysis of the cost and availability of parenteral treatments. Learning points: Management of hypoparathyroidism is complicated when gastrointestinal absorption is impaired. Careful consideration should be given before bariatric surgery in patients with pre-existing hypoparathyroidism, due to potential difficulty in managing hypocalcaemia, which is exacerbated when complications occur. While oral treatment of hypoparathyroidism is cheap and relatively simple, available parenteral options can carry significant cost and necessitate a more complicated dosing schedule. International guidelines for the management of hypoparathyroidism recommend the use of PTH analogues where large doses of calcium and calcitriol are required, including in gastrointestinal disorders with malabsorption. Approval of subcutaneous recombinant PTH for hypoparathyroidism in Australia will alter future management.

Calcinosis cutis in a neonate with transient hypoparathyroidism

Calcinosis cutis is a condition, where there is deposition of calcium salts in skin and subcutaneous tissue, seen often in the middle to elderly aged population and is rare in neonates and infants. There are many aetiological factors, but in neonates and infants it is mostly seen as complication of extravasation of intravenous calcium infusion or trauma. For uncomplicated cases supportive treatment has been advocated. Authors describe a case presented with calcinosis cutis, who was treated for transient hypoparathyroidism in neonatal period.