Severe Symptomatic Hypocalcemia Research Articles

8157 Hypercalcemia To Hypocalcemia In Three Days: The Importance Of Asking The Questions

Abstract Disclosure: P. Kachhadia: None. K. Patel: None. S. Khan: None. A. Abu Limon: None. S. Aldasouqi: None. F. Akanbi: None. Z. Ul Abideen: None. Introduction: Severe hypercalcemia needing inpatient hospitalization requires very thorough history taking in order to determine etiology and treatment plan. Causes differ drastically, and misdiagnosis or mistreatment can be life threatening. Here, we present a case of symptomatic hypercalcemia secondary to milk-alkali syndrome that was treated promptly after admission with IV zoledronic acid, leading to severe symptomatic hypocalcemia and prolonged hospitalization. Case presentation: Patient is a 68 year old female with a PMH of breast cancer, osteoporosis and hiatal hernia who presented to the emergency department for fatigue, constipation and lightheadedness. On evaluation, she was found to have a creatinine of 1.54 (0.6-1.1 mg/dL), eGFR 36 (>90 mL/min/1.73 m²), Ca 18.48 (8.6-10.2 mg/dL), albumin 4.7 (3.4-5.4 g/dL), Mg1.4 (1.7-2.2 mg/dL), 25-OHD 18 (30-100), 1,25-Dihydroxy Vitamin D 7.4 (18-78 pg/mL), PTH 11.2 (15-65 pg/mL), phosphorus level 2.4 (2.5-4.5mg/dL), TSH 2.01 (0.4-4.0 mIU/L). SPEP and PTHrP were unremarkable. Due to history of prior breast cancer, imaging was done and CT showed new possible RUL pancoast tumor with RUL spiculated opacity. Patient was started on IV fluids and subsequently received IV zoledronic acid due to concern for severe hypercalcemia secondary to malignancy. By day 3 of treatment, patient's calcium decreased severely, down to a corrected calcium level of 6.4 (8.6-10.2 mg/dL). It was upon further investigation and discussion with the patient that we discovered the patient had received subcutaneous denosumab for her osteoporosis three weeks prior to admission. In addition, she was taking six tums daily (total 1 month duration) for symptoms of dyspepsia secondary her hiatal hernia. The patient’s severe hypocalcemia was treated with high dose oral calcium carbonate and vitamin D along with IV calcium gluconate. Magnesium was replaced daily. Through daily replacement, patient was kept in the hospital for a total of 10 days duration before her calcium levels were deemed safe for return home. Discussion: Hypercalcemia is a common cause of hospitalization worldwide. Testing should be comprehensive and history taking should be thorough to help navigate treatment plans. Bisphosphonates are indicated for hypercalcemia of malignancy, and its use otherwise may be the cause of severe hypocalcemia if not used in the right setting. In our case, the patient’s hypocalcemia was multifactorial from prior denosumab use and then subsequent zoledronic acid use. Additional risk factors included low vitamin D counts and disruption of high amounts of over the counter tums after being admitted to the hospital. Anchoring bias also led clinicians to believe that the hypercalcemia was secondary to malignancy. Consequently, this led to a prolonged 10 day hospitalization for persistently low calcium levels. Presentation: 6/1/2024

Too Much of a Good Thing: Severe Hypercalcemia Presenting with Lethargy and Kidney Failure.

We present a case of a 58-year-old man with a history of laryngo-pharyngectomy including bilateral thyroidectomy due to hypopharyngeal cancer presenting with lethargy, acute kidney failure, and hypercalcemia. Milk alkali syndrome was diagnosed given the history of high-dose calcium / vitamin D supplementation after ruling out other causes of hypercalcemia. After initial treatment with normal saline, furosemide and denosumab, the patient developed severe symptomatic hypocalcemia as a rare adverse effect of denosumab.

A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family.

HDR syndrome is an autosomal dominant disorder characterized by hypoparathyroidism (H), deafness (D), and renal dysplasia (R) caused by genetic variants of the GATA3 gene. We present the case of a 38-year-old Japanese man with HDR syndrome who exhibited hypoparathyroidism, sensorineural deafness, renal dysfunction, severe symptomatic hypocalcemia with Chvostek's and Trousseau's signs, and QT prolongation on electrocardiography. He had a family history of deafness and hypocalcemia. Genetic testing revealed a novel GATA3 gene variant at exon 2 (c.48delC), which induces a frameshift resulting in termination at codon 178, causing HDR syndrome. We summarized 45 Japanese cases of HDR syndrome with regard to the mode of onset (familial or sporadic) and the age at diagnosis. In addition, we summarized all previous cases of HDR syndrome with GATA3 gene variants. Mapping of previously reported genetic variants in HDR syndrome revealed that most missense variants were observed at exons 4 and 5 regions in the GATA3 gene. These two regions contain zinc finger domains, demonstrating their functional importance in GATA3 transcription. This review of literature provides a useful reference for diagnosing HDR syndrome and predicting the related future manifestations.

FRI595 Two Cases Of Severe Symptomatic Hypocalcemia Secondary To Vitamin D Deficiency Diagnosed Within The Same Week

Abstract Disclosure: F.I. Cooper: None. U. Jonsdottir: None. G. Guadalupe Rios: None. N. Vyas: None. S. Gurnurkar: None. Background: Vitamin D is a fat-soluble vitamin that plays a significant role in intestinal calcium absorption. Humans acquire vitamin D through sun exposure and diet, though few foods naturally contain vitamin D in the amount needed to prevent deficiency. Vitamin D deficiency can result in nutritional rickets, which may present with impaired growth, weakened bones, dental abnormalities, and fractures secondary to decreased calcium absorption. Hypocalcemia can lead to a wide variety of clinical manifestations from mild symptoms such as irritability, tremors, and muscle cramps to life threatening seizures and arrhythmias. Case: This case series describes two children presenting to our pediatric emergency department within the same week with severe hypocalcemia secondary to profound vitamin D deficiency. The first was a 2-year-old female with prior medical history of 29-week prematurity who presented with a first time generalized tonic clonic seizure. She had a limited diet that consisted mostly of non-fortified almond milk. As an infant, she was on breast milk but did not receive vitamin D supplementation. On presentation, she was noted to have exam findings and radiographic evidence of rickets. The second was a 13-year-old male with history of non-verbal autism presenting with one month of diarrhea, agitation, and progressive leg pain. The patient was described as a picky eater and spent minimal time outdoors. Both children were found to have severe hypocalcemia (6.6 mg/dL and 4.8 mg/dL, respectively) in the setting of vitamin D deficiency (vitamin D-25 6.8 ng/dL and 4.9 ng/dL, respectively). They were successfully treated acutely with intravenous calcium gluconate bolus (one dose of 495 mg and three 2,000 mg) and oral calcium, with normalization of ionized calcium levels and improvement of symptoms. They were treated long-term with oral calcium, calcitriol, and vitamin D supplementation. Conclusion: Vitamin D deficiency should be considered in severe symptomatic hypocalcemia in children. Vitamin D supplementation is necessary in all breast-fed babies and a large proportion of other children not meeting vitamin D requirements through diet and sun exposure. Presentation: Friday, June 16, 2023

SAT223 Persistent Hypocalcemia After Thyroidectomy

Abstract Disclosure: R. Subramani: None. F. Manas: None. A. Kauser: None. S. Yavuz: None. Introduction: Hypocalcemia is one of the serious complications after total thyroidectomy with a reported incidence of 27.4% (transient)and 12.1% (permanent) probably related to iatrogenic parathyroidectomy. Here we report a case of hypocalcemia after thyroidectomy in the setting of normal parathyroid hormone levels. Summary: A 42-year-old female with medical history of multinodular goiter s/p thyroidectomy 2019 on thyroid hormone replacement presented with hypocalcemia since 2021. During the first-year post thyroidectomy, patient was doing well until she acquired COVID-19 in 2020 and started developing symptoms of paresthesia, and muscle spasms. Other parameters such as phosphorus, and 25 OH vitamin D were normal. Despite being on a high-dose calcium supplement 1200 mg every hour for 10 times daily and calcitriol 0.75 mg twice daily, her calcium levels were persistently low ranging between 7.1 to 8 mg/dl and normal albumin levels of 3.9 and 4.3, but parathyroid level (PTH) remained normal (27.7-37.5). The patient was also symptomatic. She was later switched to liquid calcium 1000 mg 6 times daily for better absorption. It is noted that she had recurrent symptomatic hypocalcemia episodes requiring multiple emergency room (ER) visits during times of stress such as viral illness. The patient was treated with a trial of teriparatide, after which her symptoms improved and there were no further ER visits. Her calcium level increased from 7.4 to 8.4 and calcium supplement requirement reduced to 1200 mg daily. During recent outpatient visit, the patient had hypocalcemia episodes after missing teriparatide doses as expected. Conclusion: Despite our patient had normal PTH levels, the parathyroids glands did not respond appropriately to hypocalcemia. Promberger et al studied a case of eight patients with hypocalcemia with normal PTH following thyroidectomy. All these patients had normal PTH levels during post-op period, but persistently low and ionized calcium levels 12 months after surgery. This suggests during persistent hypocalcemia normal parathyroid levels may indicate an inadequate PTH response. In our case, developing hypocalcemia long after surgery and relation to COVID-19 infection may suggest autoimmune phenomenon as developing PTH-antibodies or receptor malfunction, theory yet to be investigated. In cases of severe symptomatic hypocalcemia requiring significant amount of calcium supplement PTH analogs are very effective treatment. Presentation: Saturday, June 17, 2023

Gastrointestinal manifestations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patient: major effect on treatment and prognosis.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in autoimmune regulator (AIRE) gene. The three clinical components of this syndrome are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations.We report a case of a 17-year-old Caucasian female patient diagnosed with APECED who presented with acute abdominal pain. Her medical history revealed chronic digestive discomfort without bowel movement disorders. The patient needed a significant increase in doses of calcium supplementation and hydrocortisone which appeared to be partially inefficient. Investigation with esophagogastroduodenoscopy and biopsy showed autoimmune atrophic gastritis. The patient eventually needed increasing doses of treatment received in order to achieve desired clinical and biological therapeutic goals. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in the autoimmune regulator (AIRE) gene. The three clinical components of this syndrome that appear in early childhood are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations like atrophic gastritis. They can be caused by many abnormalities including atrophic gastritis and the modification of intestinal biofilm and microbiota. Early diagnosis and treatment of gastrointestinal manifestations associated with APECED prevent multiple life-threatening consequences like acute adrenal crisis and severe symptomatic hypocalcemia.

Severe Symptomatic Hypocalcaemia Associated with Zoledronic Acid in a Patient of Ca Prostate: Case Report and Literature Review

Zoledronic acid is a parenteral long acting bisphosphonate that has been used widely in the management of osteoporosis, bone metastasis and malignancy induced hypocalcaemia. Zoledronic acid is well tolerated but rarely severe hypocalcaemia and nephrotoxicity may occur. Here we report a case of 62 year male patient of metastatic Ca prostate who had severe hypocalcaemia after receiving intravenous zoledronic acid and docetaxel. Patient was hospitalized and managed with intravenous calcium supplementation and remained admitted for several days. Post recovery he was again started on zoledronic acid therapy and chemotherapy.

SAT-347 Diagnosis of Autosomal Dominant Hypocalcemia Type 1 Following the Initiation of Imatinib for Treatment of Chronic Myeloid Leukemia

Background: Autosomal Dominant Hypocalcemia Type 1 is an underdiagnosed condition due to the vast majority of patients being asymptomatic and having mild hypocalcemia. Imatinib has been associated with hypophosphatemia and hypocalcemia. Clinical Case: 69-year-old man who had a long history of asymptomatic mild hypocalcemia, calcium level of 7.9 mg/dL (8.4 – 10.2 mg/dL) diagnosed with chronic myeloid leukemia and developed symptoms of hypocalcemia within 2 months of treatment with imatinib. After the initiation of imatinib, his calcium reduced to 6.8 mg/dL (8.4 – 10.2 mg/dL) with a corresponding ionized calcium of 0.98 mmol/L (1.12–1.32 mmol/L) within 2 months. He developed tetany. With the reduced calcium level his PTH was unexpectedly low-normal at 34 pg/mL (16–62 pg/mL). He also had a higher than expected urinary calcium of 342 mg/24 hours. The PTH and 24-hour urinary calcium levels raised concern for an underlying diagnosis of autosomal dominant hypocalcemia type 1. His phosphorous was normal at 3.3 mg/dL (2.6–4.9 mg/dL). He never had hypophosphatemia, which is common with imatinib.After two doses of IV calcium and initiation of oral calcium replacement, 1000 mg BID, his level continued to be reduced with symptoms. Given his symptoms, laboratory results, and continued hypocalcemia he underwent genetic testing. Results of his genetic testing showed a p.Thr151Met mutation in the CASR gene consistent with autosomal dominant hypocalcemia type 1. With this diagnosis, there is concern for nephrolithiasis with over treatment. His symptoms resolved with treatment with calcium 1000mg TID, calcitriol 0.25 mg BID and vitamin D3 2000 IU daily. He has not developed nephrolithiasis and his urinary calcium increased to 424mg/24 hours. A thiazide diuretic is being considered to decrease urinary calcium excretion.He continues on imatinib with an excellent response to therapy. It is likely that the trigger for symptomatic severe hypocalcemia was initiation of imatinib superimposed on the hypocalcemia type 1. Possible mechanisms for this are decreased intestinal absorption, increased urinary loss, or decreased dissolution from bone. 1 These mechanisms are also associated with hypophosphatemia, which our patient did not have. Another possible cause could be an immune mediated destruction of the parathyroid gland, a rare finding seen with other tyrosine kinase inhibitors.2 Conclusion: This is the first reported case of imatinib triggering severe symptomatic hypocalcemia leading to the diagnosis of underlying autosomal dominant hypocalcemia type 1.

SAT-355 Severe Symptomatic Hypocalcemia Related to Cinacalcet Administration Introduction

BACKGROUND: Cinacalcet, a class of drug used to treat secondary hyperparathyroidism due to end-stage renal disease, is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. This drug acts as a calcimimetic agent by allosteric activation of the calcium-sensing receptor that is expressed in various tissues. Common side effects of cinacalcet include nausea, vomiting, diarrhea and weakness. Although mild hypocalcemia is a common side effect, severe hypocalcemia is rare. Case Presentation: A 61-year-old man was evaluated for treatment of type I diabetes mellitus. He reported several months of progressive fatigue, muscle weakness, and paresthesia of his hands and feet. He was prescribed cinacalcet for a parathyroid disorder since 2014 and his previous physician increased the dose of cinacalcet about 2 months ago from 60mg daily to 120mg daily. Since that time his paresthesias have been more severe. Physical examination: normal vital signs, Chvostek’s and Trousseau’s signs were positive. Rest of the examination was normal. Laboratory: corrected serum calcium (Ca) of 6.7 mg/dL (ref 8.6–10.0), down from 7.6 mg/dL 2 months earlier. Additional laboratory: Ionized Ca 3.4 mg/dL (ref 4.5–5.6), PTH 68 pg/mL (ref 15–65), 25-OH vitamin D 37 ng/mL (ref 29–100), phosphorus 4.9 mg/dL (ref 2.5–4.5) and calculated GFR 97 mL/min. Cinacalcet was stopped. The patient was treated with calcium intravenously in the ICU resulting in normal serum calcium levels after 36 hours of treatment and complete resolution of symptoms. He was discharged on oral calcitriol and calcium supplementation, which was discontinued within 1 week of discharge.Discussion:In vast majority of cases hypocalcemia associated with cinacalcet therapy are mild and self-limited. Generally hypocalcemia develops within 16 weeks of starting therapy and resolves spontaneously within 2 weeks. This case is unusual in that the hypocalcemia occurred years after starting therapy and the patient experienced severe symptoms, undiagnosed for a prolonged period of time and required admission for close monitoring. Additionally, this patient was without the most common risk factor for cinacalcet-associated hypocalcemia which was secondary hyperparathyroidism, and he had normal renal function. The marked decrease in serum Ca levels may be related to his low baseline serum Ca levels and due to the recent increase in cinacalcet dose. However this has not always verified based on retrospective studies. Interestingly the cinacalcet dose was increased in up to 14% of patients with severe hypocalcemia (<7.5 mg/dL) and even in this population severe symptomatic hypocalcemia symptoms were rare. In conclusion, clinicians should closely monitor patients on calcimimetic drugs for hypocalcemic symptoms although mild asymptomatic hypocalcemia may resolve without intervention.

The Case | Severe symptomatic hypocalcemia in a patient with sickle cell disease

The Case | Severe symptomatic hypocalcemia in a patient with sickle cell disease

286 Severe Symptomatic Hypocalcemia Following Denosumab Administration

286 Severe Symptomatic Hypocalcemia Following Denosumab Administration

Severe Hypocalcemia After the Administration of Zoledronic Acid for Osteoporotic Fracture

Zoledronic acid is a potent intravenous bisphosphonate used in the treatment of osteoporosis and malignancy-induced hypercalcemia or bone metastasis. Although zoledronic acid generally seems to be safe and well-tolerated, rare but life-threatening nephrotoxicity or hypocalcemia may occur. The majority of cases of hypocalcemia with zoledronic acid have been seen in patients with underlying malignancy and are asymptomatic or mild. Vitamin D deficiency, renal failure, hypoparathyroidism, and hypomagnesemia have been reported as risk factors for hypocalcemia. Here, the author reports a case of severe symptomatic hypocalcemia following the administration of zoledronic acid for the treatment of osteoporotic fracture. This patient also had underlying but unrecognized vitamin D deficiency and chronic kidney disease. Following the administration of calcium and vitamin D, her symptoms improved and calcium levels returned to normal within several days. To avoid serious hypocalcemia with zoledronic acid, calcium and vitamin D status and renal function should be assessed and corrected if appropriate. J Med Cases. 2016;7(10):441-444 doi: http://dx.doi.org/10.14740/jmc2646w

SAT0479 Early Findings from Prolia® Post-Marketing Safety Surveillance for Atypical Femoral Fracture, Osteonecrosis of the Jaw, Severe Symptomatic Hypocalcemia, and Anaphylaxis

BackgroundProlia has marketing authorization in the EU, US, Canada, Japan, and over 40 countries or administrative districts worldwide for the treatment of postmenopausal women with osteoporosis at high/increased risk for...

A case report of defective endogenous vitamin D: a new clinical entity

To report a case of defective endogenous vitamin D with excellent response to low dose calcitriol replacement therapy. We describe the patient's clinical presentation, biochemical workup, and clinical course. The patient initially presented with severe symptomatic hypocalcemia and was diagnosed with pseudohypoparathyroidism type 1b at an outside hospital and started on calcitriol 2.25 mcg twice daily with good response but calcitriol was stopped later for cost concerns which led to recurrence of symptoms, worsening hypocalcemia and increased parathormone levels. On review of her case it was noted that her 1,25 dihydroxy: vitamin D level was within normal limits even before she started taking calcitriol, which is not consistent with pseudohypoparathyroidism type 1b. Restarting low dose calcitriol (0.25 mcg twice daily) improved the patient's calcium level to 10.1 mg/dl and decreased the parathormone level to 17 pg/ml and symptoms resolved. Conditions associated with low serum calcium and high parathormone include pseudohypoparathyroidism, vitamin D deficiency and vitamin D resistance. This patient does not fit into any of the known entities causing hypocalcemia and elevated parathormone. We hypothesize that this patient had an inadequate number of vitamin D receptors that was corrected by exogenous administration of vitamin D.

Severe symptomatic hypocalcaemia following a single dose of denosumab

Severe symptomatic hypocalcaemia following a single dose of denosumab

Severe Symptomatic Hypocalcemia after Denosumab Administration in an End-Stage Renal Disease Patient on Peritoneal Dialysis with Controlled Secondary Hyperparathyroidism

Severe Symptomatic Hypocalcemia after Denosumab Administration in an End-Stage Renal Disease Patient on Peritoneal Dialysis with Controlled Secondary Hyperparathyroidism

Risk assessment for severe hypocalcemia requiring hospitalization with denosumab.

115 Background: Skeletal-related events (SRE) pose clinical risks to patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) that can be mitigated with denosumab. Hypocalcemia is a side effect, however risk factors are not well described. Methods: An IRB waiver was obtained to review medical records for all mCRPC pts receiving denosumab at MSKCC between March-August 2011 for baseline labs, calcium (ca) and vitamin D nadirs, details of hospitalizations, concurrent therapies, and comorbidities. Comparisons between groups were made using Fisher’s exact test and the Wilcox rank sum test. Results: Nine of sixty pts (15%) treated with 1-2 doses of denosumab developed severe symptomatic hypocalcemia (median nadir 6.5 mg/dL) requiring hospitalization for intravenous (IV) ca replacement. Ca/Vitamin D was recommended to all pts. Ca recovered in 17 days in those who did return to baseline levels (n=5). However, four of nine (44%) pts required repeated hospitalizations for IV ca, never recovered to baseline ca levels, and died of advanced disease within 3 months. Median vitamin D 25-OH was 22.5 ng/ml for hospitalized pts, and PTH was 198 pg/ml at ca nadir. Conclusions: Denosumab was associated with severe hypocalcemia sufficient to require hospitalizations for IV ca replacement in 15% of pts with mCRPC. PSA, Ca, Alk Phos, and current chemotherapy were associated with severe hypocalcemia requiring hospitalization for IV ca. Clinicians are cautioned regarding potential risk factors including advanced disease, vitamin D insufficiency, and possibly comorbidities affecting calcium absorption. [Table: see text]

Severe Symptomatic Hypocalcemia after Denosumab Administration in an End-Stage Renal Disease Patient on Peritoneal Dialysis with Controlled Secondary Hyperparathyroidism

We report the 1 case of severe, symptomatic hypocalcemia after denosumab (RANKL inhibitor) treatment in a peritoneal dialysis patient with secondary hyperparathyroidism and osteoporosis. A 58-year-old Caucasian female has been receiving chronic ambulatory peritoneal dialysis for four years secondary to polycystic kidney disease. Laboratory studies revealed: albumin-corrected calcium 9.0 mg/dL, phosphorus 5 mg/dL, alkaline phosphatase (ALP) 58 U/L [normal, 40-105], albumin 3.4 gm/dL [normal, 3.6-5.4] and intact parathyroid hormone (PTH) 315 pg/mL [normal, 40-72]. Marked osteoporosis was noted on the DXA scan, preventing her from renal transplantation considerations. She had failed conventional medical treatment, including per os calcium, monthly ergocalciferol (50,000 units/month), activated vitamin-D analog (doxercalciferol) and Case Study British Journal of Medicine & Medical Research, 3(4): 1398-1406, 2013 1399 renal-failure adjusted alendronate (70 mg twice a month). She was started on subcutaneous denosumab 60 mg every 6 months. After her first dose, she developed a progressive drop of calcium, phosphorus, bicarbonate and magnesium, in spite of massive escalation of doxercalciferol and calcium supplementation. Hypocalcemia nadired at 6.3 mg/dL with symptomatic tetany, requiring a brief hospitalization approximately 7 weeks after denosumab treatment. Her elevated PTH rose further transiently (647 pg/mL), along with ALP (123 U/L). Bone-mineral parameters normalized approximately 3 months after denosumab administration. The observed phenomenon resembled the phenotype of “hungry bone syndrome” observed after surgical parathyroidectomy. Conclusion: Treatment decisions based on bone densitometry results alone are not transposable between patients with or without end-stage renal disease. Denosumab may lead to critical hypocalcemia in dialysis patients and further aggravate existing secondary hyperparathyroidism.

A novel homozygous mutation in the parathyroid hormone gene (PTH) in a girl with isolated hypoparathyroidism

Case reportA female patient with consanguineous parents presented with severe symptomatic hypocalcemia (1.62mmol/l) at the age of 4months. Treatment with oral 1,25-(OH)2-vitamin D and calcium carbonate was started and serum calcium concentrations were stabilized at the lower end of the normal range. Subsequently she developed normally and had no evidence for additional abnormalities. Over the next 6years of observation, serum levels of PTH were always low but detectable (5.3–2.5pg/ml; normal: 15–65pg/ml) resulting in the diagnosis of isolated hypoparathyroidism. Disturbances in the vitamin-D metabolism, autoimmune polyendocrine syndrome (APS), chromosomal anomalies or mutations in the calcium-sensing receptor gene (CaSR) were excluded. Nucleotide sequence analysis of PTH revealed the presence of a homozygous point mutation (c.68C>A) in exon 2 that introduces a premature termination codon (p.Ser23X in the Pre- sequence of PTH) resulting in a non-functional PTH-precursor. ConclusionA novel, homozygous PTH mutations was identified, which is obviously a very rare cause of isolated hypoparathyroidism (IHP). Although activating CaSR mutations are the most common cause of hypoparathyroidism, analysis of the PTH gene should be considered in those IHP patients in whom a CaSR has been excluded, particularly if the parents are likely to be consanguineous.

Severe Symptomatic Hypocalcaemia Following High-Dose Oral Ibandronate in a Patient With Prior Thyroidectomy and Metastatic Bone Disease

Ibandronate is used to treat bony metastatic disease and hypercalcaemia of malignancy. We report the first case of severe hypocalcaemia following oral ibandronate. A 65-year-old woman with widespread sclerotic bony metastases due to breast cancer was commenced on oral ibandronate (50 mg daily). The corrected calcium level decreased from 2.11 mmol / L to 1.38 mmol / L (2.1 - 2.6 mmol / L) accompanied by lower leg muscle cramps 3 weeks after initiation of ibandronate therapy. She had an inappropriately normal PTH level of 6.8 pmol / L (1 - 7 pmol/L) with normal 25-OH vitamin D level of 59 nmol / L and normal magnesium level of 0.88 mmol / L (0.7 - 1.05 mmol / L). There was a history of previous total thyroidectomy for multinodular goitre. Intermittent calcium infusion was required to maintain the corrected calcium level around 1.9 - 2 mmol / L over the next 3 weeks. The patient was discharged on calcium citrate 250 mg tds and calcitriol 0.5 mcg qid with calcium level of 1.96 mmol / L. We conclude that oral bisphosphonates are widely used but rarely associated with symptomatic severe hypocalcaemia. Possible mechanisms in this case include hypoparathyroidism and metastatic bone disease with widespread sclerosis. This case demonstrates that patients may develop symptomatic hypocalcaemia when treated with oral bisphosphonates. doi:10.4021/jem96w