Calciphylaxis in A Morbidly Obese Woman with Rheumatoid Arthritis Presenting with Severe Weight Loss and Vitamin D Deficiency

ObjectiveTo present an unusual case of calciphylaxis in an obese patient with inactive rheumatoid arthritis and normal renal function.MethodsWe describe a 46-year-old morbidly obese Caucasian woman who had previously weighed 200 kg and presented with painful leg ulcers following a rapid weight loss of 102 kg in 1 year.ResultsThe subject was admitted with a 6-week history of painful leg ulcers that progressed to her thighs. Vasculitis and active rheumatoid arthritis were excluded clinically and biochemically. A skin biopsy confirmed calciphylaxis in the context of normal renal function. Serum 25-hydroxyvitamin D was low at 14 ng/mL (reference range, 20 to 200 ng/mL), with an elevated serum parathyroid hormone level of 241 pg/mL (reference range, 10 to 65 pg/mL), but normal serum calcium and phosphorus levels. The skin lesions persisted despite local wound care, daily hyperbaric oxygen, and parenteral sodium thiosulfate therapies. After normalizing the serum vitamin D level through oral supplementation, she responded well to pamidronate infusion with complete healing of the ulcers and regained 13% of her premorbid weight.ConclusionThis is the first case of calciphylaxis preceded by weight loss of greater than 100 kg in a patient with hypovitaminosis D who responded to pamidronate therapy. (Endocr Pract. 2011;17:e104-e108)     

Decreased Calcitriol Requirement During Pregnancy and Lactation With A Window of Increased Requirement Immediately Post Partum

ObjectiveTo describe the changes in calcium and cal- citriol requirements during pregnancy and lactation in a pa- tient with hypoparathyroidism due to autosomal dominant hypocalcemia.MethodsWe summarize the clinical presentation and treatment of the patient and review the pertinent literature.ResultsCalcitriol requirements disappeared during pregnancy in a 34-yearold woman with autosomal dominant hypoparathyroidism secondary to an activating mutation in the calciumsensing receptor gene. Within hours after delivery, her serum calcium concentration dropped to 4.7 mg/dL (albumin, 3.2 g/dL), and she required intravenous calcium and reinstitution of calcitriol. When lactation began a few days later, her calcitriol requirement again disappeared. As has occasionally been described in the literature, this patient with hypoparathyroidism required no calcitriol during late pregnancy and lactation to maintain a normal serum calcium level.ConclusionsTo our knowledge, this is the first reported case documenting a period of time between pregnancy and lactation when calcitriol requirements reappeared, likely due to a parathyroid hormone-related protein “window” between delivery, when placental production of parathyroid hormone-related protein stops, and lactation, when mammary gland production begins. (Endocr Pract. 2010:16:459-462)     

Unusual Case of Calciphylaxis Associated with Primary Hyperparathyroidism Without Coexistent Renal Failure

ObjectiveTo report a case of calciphylaxis in a patient with primary hyperparathyroidism without coexistent renal failure.MethodsThe clinical, laboratory, and radiographic details of this case are reviewed, and the pathogenesis of calciphylaxis and the associated prognosis are discussed.ResultsA 52-year-old woman had progressive fatigue, cachexia, severe osteoporosis, and necrotizing skin lesions. Her serum calcium level was 16 mg/dL, serum phosphorus level was 2.13 mg/dL, and parathyroid hormone level was 2,257 pg/mL (reference range, 15 to 65). On physical examination, gangrenous skin lesions with black crusts were noted on her legs, abdomen, and gluteal region. A mass lesion was detected in the parathyroid region by both ultrasonography and a parathyroid scan. The patient underwent a bilateral neck exploration, and a parathyroid adenoma measuring 3.5 by 1.5 by 1.2 cm was found on pathologic examination. After the operation, biochemical findings normalized, and the skin lesions progressively improved.ConclusionSevere primary hyperparathyroidism may be a factor leading to calciphylaxis, even in the absence of renal failure and a high calcium-phosphate product. This potentially life-threatening condition should not be left untreated if the levels of serum calcium and parathyroid hormone are severely elevated. (Endocr Pract. 2008;14:368-372)     

Idiopathic Hypoparathyroidism Presenting with Severe Hypocalcemia and Asymptomatic Basal Ganglia Calcification Followed by acute Intracerebral Bleed

ObjectiveTo report a case of idiopathic hypoparathyroidism presenting with severe hypocalcemia and intracerebral calcifications that resulted in a spontaneous intracerebral bleed.MethodsWe present the clinical, laboratory, and radiologic findings in a woman with idiopathic hypoparathyroidism who developed spontaneous intracerebral bleed in the setting of chronic intracerebral calcifications.ResultsA 37-year-old woman presented with vague symptoms of hypocalcemia. Clinical evaluation revealed brisk deep tendon Reflexes and positive Chvostek’s and Trousseau’s signs. The serum calcium level was 3.7 mg/ dL (reference range, 8.0 to 10.6 mg/dL) and the phosphorus level was 8.2 mg/dL (reference range, 2.3 to 5.0 mg/dL). Serum intact parathyroid hormone was undetectable. Computed tomography of the head showed extensive bilateral symmetrical calcification of basal ganglia and dentate nucleus in the cerebellum and centrum semiovale. Fluid and electrolytes were replaced appropriately, and calcium and calcitriol were prescribed. While in the hospital, the patient developed an acute intracerebral bleed confirmed by computed tomography. The patient recovered without neurologic sequelae and was discharged from the hospital on calcium supplementation and calcitriol. Repeated computed tomography of the head 3 years later demonstrated complete resolution of the bleed.ConclusionThis case suggests that patients with severe hypoparathyroidism and intracerebral calcification may be at risk for spontaneous intracerebral bleed and should be monitored accordingly. (Endocr Pract. 2007; 13:487-492     

Proton Pump Inhibitor-Induced Hypocalcemic Seizure in A Patient with Hypoparathyroidism

ObjectiveTo report a case of proton pump inhibitor-induced hypocalcemic seizure in a patient with hypoparathyroidism.MethodsWe describe the clinical history, physical examination findings, and laboratory values of the patient and briefly review the relevant literature.ResultsA 48-year-old woman with a history of postsurgical hypoparathyroidism who was taking calcium carbonate, 1500 mg 3 times daily, and cholecalciferol, 1200 IU daily, presented with a generalized seizure in the setting of hypocalcemia 12 days after initiating therapy with the proton pump inhibitor lansoprazole. Physical examination revealed a positive Chvostek sign. Electrocardiogram was notable for a prolonged QT_c interval of 576 milliseconds. Laboratory data were notable for the following values: total serum calcium, 5.3 mg/dL; ionized calcium, 2.51 mg/dL; and intact parathyroid hormone, 5.8 pg/mL. The patient’s condition responded to therapy with intravenous calcium gluconate, oral calcium carbonate, and calcitriol. As an outpatient she remained asymptomatic off lansoprazole, treated with calcium carbonate and calcitriol.ConclusionsCaution should be exercised in prescribing proton pump inhibitors to patients with a history of hypoparathyroidism treated with calcium carbonate supplementation because severe hypocalcemia is a potential adverse effect. (Endocr Pract. 2011;17:104-107)     

Recombinant Human Parathyroid Hormone Therapy (1-34) In an Adult Patient with a Gain-of-Function Mutation in the Calcium-Sensing Receptor-a Case Report

ObjectiveTo describe a case of hypocalcemia in a patient with a gain-of-function mutation in the calcium-sensing receptor that was undetected until adulthood and successfully treated with recombinant parathyroid hormone.MethodsThe clinical findings, laboratory data, and a review of the pertinent literature are presented.ResultsA 55-year-old woman was hospitalized and seen by the endocrinology consult service for hypocalcemia that was refractory to repeated doses of intravenous calcium gluconate. She expressed concern about chronic leg muscle cramps and paresthesias of the lips and fingertips. In addition, she had no history of neck surgery, neck irradiation, or any autoimmune disease. She was a well-appearing female with no dysmorphic features or skin changes. Laboratory tests revealed hypocalcemia, hyperphosphatemia, hypomagnesemia, and hypovitamino-sis D. Her parathyroid hormone concentration (PTH) was low at 14.2 pg/mL. Her PTH and calcium concentrations remained low despite repletion of magnesium and treatment with calcitriol and oral calcium replacement. A 24-hour collection for urinary calcium showed inappropriate hypercalciuria. Medical records showed her hypocalcemia to be chronic. Additionally, several family members had also complained of muscle cramps. A congenital cause of her hypoparathyroidism was considered, and genetic testing confirmed heterozygosity for a gain-of-function mutation in the calcium-sensing receptor gene associated with autosomal dominant familial isolated hypoparathyroidism (ADH). Treatment with subcutaneous recombinant human parathyroid hormone teriparatide (rhPTH [1-34]) 20 mcg twice daily for three days normalized her calcium and phosphorus concentrations.ConclusionrhPTH (1-34) is an effective treatment for patients with hypoparathyroidism due to gain-of-function mutations in the calcium-sensing receptor. ADH can be insidious in presentation and the diagnosis can be missed unless there is a high index of suspicion. (Endocr Pract. 2013;19:e24-e28)     

Delayed-Onset Hypoparathyroidism in an Adolescent with Chromosome 22Q11 Deletion Syndrome

ObjectiveTo describe the first case of established chromosome 22q11 deletion syndrome with late onset presentation of hypocalcemia secondary to hypoparathyroidism.MethodsWe present the history, clinical and laboratory investigations, and management of a 17-yearold adolescent boy who presented with 3 separate seizures secondary to hypocalcemia. This patient had an established diagnosis of chromosome 22q11 deletion syndrome at the time of the seizure presentations, but had previously normal calcium levels.ResultsHypocalcemia was noted during each seizure, with corrected calcium levels ranging from 6.64 to 7.76 mg/dL (reference range, 8.52 to 10.52 mg/dL). The hypocalcemia was secondary to hypoparathyroidism, with parathyroid hormone levels < 2.75 pg/mL (reference range, 22.9 to 68.75 pg/mL). He was treated with calcitriol, 0.5 μg daily, and calcium carbonate, 2,400 mg daily, leading to normalization of serum calcium and resolution of seizures.ConclusionChromosome 22q11 deletion syndrome is a relatively common genetic disorder with a wide variety of phenotypic manifestations including cardiac abnormalities, abnormal facies, thymic dysfunction, cleft palate, and hypocalcemia. This case shows that medical practitioners should be aware that hypocalcemia can present after an established diagnosis, which has implications for the management of this disorder. (Endocr Pract. 2011;17: e123-e125)     

Heart Failure in Hypophosphatemic Rickets: Complications from High-Dose Phosphate Therapy

ObjectiveTo report a rare case of hypophosphatemic rickets (HR) leading to extensive cardiac complications.MethodsWe present the clinical course and autopsy findings of a patient with HR, treated with chronic phosphate-only therapy as a child, who subsequently developed tertiary hyperparathyroidism leading to extensive cardiac calcifications and complications. We also review the literature on the pathophysiology of calcifications from HR.ResultsA 34-year-old man was diagnosed with HR at 4 years of age after presenting with growth delay and leg bowing. Family history was negative for the disease. He was initiated on high-dose phosphate therapy (2-6 g of elemental phosphorus/day) with sporadic calcitriol use between 4-18 years of age. For 6 years he received phosphate-only therapy. Subsequently, he developed nephrocalcinosis, heart valve calcifications, severe calcific coronary artery disease, heart block, and congestive heart failure. At a young age, he required an aortic valve replacement and a biventricular pacemaker that was subsequently upgraded to an implantable cardioverter defibrillator. Autopsy showed extensive endocardial, myocardial, and coronary artery calcifications.ConclusionCardiac calcification is a known sequela of tertiary hyperparathyroidism when it occurs in patients with renal failure, but it is rarely seen in HR due to high phosphate therapy. Phosphate alone should never be used to treat HR; high doses, even with calcitriol, should be avoided. It is important to be cognizant of high-dose phosphate effects and to consider parathyroidectomy for autonomous function, if needed. This case emphasizes the importance of appropriate therapy, monitoring, and management of patients with HR. (Endocr Pract. 2013;19:e8-e11)     

An Open-Label Extension Study of Parathyroid Hormone Rhpth(1-84) in Adults with Hypoparathyroidism

Objective: Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism.Methods: This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia.Results: Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3–90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred.Conclusion: This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.Abbreviations:AE = adverse eventBMD = bone mineral densityBSAP = bone-specific alkaline phosphataseBTM = bone turnover markerCa × P product = calcium × phosphate productCTX = cross-linked C-telopeptide of type 1 collagenOCN = osteocalcin25(OH)D = 25-hydroxyvitamin DP1NP = aminoterminal propeptide of type 1 collagenPTH = parathyroid hormonerhPTH(1-84) = recombinant human parathyroid hormoneTEAE = treatment-emergent adverse eventULN = upper limit of normal     

Oncogenic Osteomalacia Cured by Removal of an Organized Hematoma

ObjectiveTo describe a patient with oncogenic osteomalacia whose symptoms were rapidly resolved after surgical removal of an organized hematoma of the hip.MethodsA case report is presented, including clinical and laboratory findings. The relevant literature is reviewed, and the current understanding of oncogenic osteomalacia is summarized.ResultsIn September 1996, a 44-year-old black woman presented with a 2-year history of bone pain, progressive muscle weakness, depression, osteomalacia, and hypophosphatemia. Her condition did not improve with use of calcitriol and phosphate replacement. During the previous year, her serum phosphorus levels were low, ranging from 1.0 to 2.2 mg/dL, and the levels of serum 1,25-dihydroxyvitamin D [1,25-(OH)₂D] were very low, ranging from < 5 to 19.4 pg/mL (normal, 15 to 60). The serum 25-hydroxyvitamin D levels were low, ranging from 8 to 14 ng/mL (normal, 9 to 52). The higher values were noted after she had received large doses of phosphate, 1,25-(OH)₂D, and vitamin D. During the previous year, her serum alkaline phosphatase levels were high, ranging from 253 to 314 U/L; serum calcium and parathyroid hormone levels were normal. The abnormalities on physical examination were obesity and a 10- by 10-cm firm, poorly demarcated mass superior to the left greater trochanter. A computed tomographic scan of this region showed a water-density fluid collection in the left buttock measuring 7.8 by 7.8 cm, consistent with a chronic hematoma. The mass was resected, and histopathologic examination revealed features of an organized hematoma with areas of myxoid changes and cartilaginous metaplasia. Postoperatively, the patient’s strength improved, and the levels of serum phosphorus and 1,25-(OH)₂D became supranormal.ConclusionThe symptoms and laboratory abnormalities of this patient with oncogenic osteomalacia promptly resolved after resection of an organized hematoma of the left hip. (Endocr Pract. 2005;11:190-193)     

Management of Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease

ObjectiveTo review approved treatment options for secondary hyperparathyroidism (SHPT) in patients with stages 3 and 4 chronic kidney disease (CKD).MethodsRecently published data on the diagnosis and treatment of SHPT in patients with CKD were critically assessed.ResultsEarly detection of SHPT is critical for effective treatment. Approximately 40% of patients with stage 3 CKD and 80% of patients with stage 4 have SHPT due to low serum 1,25-dihydroxyvitamin D levels. Appropriate treatment involves suppression of parathyroid hormone (PTH) to normal levels with active vitamin D therapy and phosphate binders. Ergocalciferol or cholecalciferol should be used to correct 25-hydroxyvitamin D levels either before or during active vitamin D therapy. Active vitamin D analogues include calcitriol, doxercalciferol, and paricalcitol. Calcitriol is effective, but has a narrow therapeutic window at higher doses because of hypercalcemia and hyperphosphatemia, which require frequent monitoring. Doxercalciferol is also effective, but has been associated with significant elevations in serum phosphorus requiring greater use of oral phosphate binders. Paricalcitol effectively suppresses PTH with minimal impact on serum calcium and phosphorus. Limited data exist on the use of cinacalcet in treating SHPT in stages 3 and 4 CKD, and it is only approved for use in patients receiving dialysis.ConclusionSHPT is an early and major complication of CKD. Treatment involves suppression of PTH to prevent metabolic bone disease, bone loss, and metabolic complications that may result in marked morbidity and mortality. Early detection of elevated PTH levels with appropriate intervention using active vitamin D therapy, even in the absence of elevated serum phosphorus and reduced serum calcium, is critical. (Endocr Pract. 2008;14:18-27)     

A Patient With Hypophosphatemia,a Femoral Fracture,and Recurrent Kidney Stones: Report of a Novel Mutation in SLC34A3

ObjectiveTo determine if there was a genetic contribution to our patient’s unusual clinical presentation of nephrolithiasis and nonhealing stress fracture.MethodsWe describe a 31-year-old man who had rickets as a child and developed a femur insufficiency fracture and recurrent nephrolithiasis as an adult after moving to the United States from India. The patient’s clinical course and results from radiographic and biochemical analyses are described. Analysis of the SLC34A3 gene was performed using genomic DNA samples from the patient and his family members.ResultsBefore referral to the Yale Bone Center, the patient was treated with calcitriol, ergocalciferol, and phosphate. Changing therapy to phosphate alone led to clinical improvement. Genetic analysis revealed that the patient is a compound heterozygote for mutations in the SLC34A3 gene. On 1 allele, he has a previously described missense mutation in exon 7: c.575C > T (p.Ser192Leu). The other allele carries a novel nonsense mutation in exon 3: c.145C > T (p.Gln49X). One unaffected sibling is a carrier of the missense mutation and 1 sister with a history of flank pain is a carrier of the novel mutation.ConclusionsHereditary hypophosphatemic rickets with hypercalciuria is a rare metabolic disorder associated with mutations in SLC34A3, the gene that encodes the renal sodium phosphate cotransporter NaPi-IIc. Although hypercalciuria is a distinguishing feature of the disease, nephrolithiasis is rarely described. The patient’s atypical clinical presentation illustrates that both environmental and genetic factors potentially affect phenotypic expression of SLC34A3 mutations. (Endocr Pract. 2008;14:869-874)     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)     

Incidence,Risk Factors,and Clinical Implications of Delayed Hypoparathyroidism on Postoperative Day two Following Total Thyroidectomy for Papillary Thyroid Carcinoma

Objective: This study aimed to investigate the incidence rates, risk factors, and clinical implications of delayed hypoparathyroidism on postoperative day 2 (POD-2) after total thyroidectomy in patients with papillary thyroid carcinoma.Methods: This study included 410 patients with normal serum intact parathyroid hormone (iPTH) and calcium levels on postoperative day 1 (POD-1) who were classified into 2 groups according to the presence or absence of delayed hypoparathyroidism on POD-2.Results: Of the 410 patients, 98 experienced delayed hypoparathyroidism on POD-2 (23.9%). The significant risk factors for delayed hypoparathyroidism on POD-2 included female gender, age older than 45 years, central lymph node dissection, increased number of excised lymph nodes, and low POD-1 versus preoperative iPTH ratios. Additionally, delayed hypoparathyroidism on POD-2 was found to be a significant risk factor for hypocalcemia on POD-2 and permanent hypoparathyroidism.Conclusion: Prophylactic calcium supplementation and long-term surveillance for permanent hypoparathyroidism should be considered in patients with risk factors for delayed hypoparathyroidism on POD-2.Abbreviations: CI = confidence interval; iPTH = intact parathyroid hormone; OR = odds ratio; POD-1 = postoperative day 1; POD-2 = postoperative day 2; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic     

Research on Intra-Operative Indocyanine Green Angiography of the Parathyroid for Predicting Postoperative Hypoparathyroidism: A Noninferior Randomized Controlled Trial

Objective: A noninferiority randomized controlled trial was undertaken to clarify whether the postoperative measurements of serum calcium and parathyroid hormone and oral supplementation of calcium and calcitriol could be omitted if patients had at least one well-perfused parathyroid gland evaluated by intra-operative indocyanine green (ICG) angiography.Methods: Patients with at least one parathyroid gland well-perfused by ICG angiography (ICG score >2) were randomized to the control group or test group. For the control group, oral calcium and calcitriol were systematically supplemented. For the test group, no oral calcium or calcitriol was supplemented to the patients. Levels of serum calcium and parathyroid hormone of patients on the first and 30th postoperative day were compared between the two groups.Results: Among all 68 selected patients, 56 patients had at least one well-perfused parathyroid gland evaluated by intra-operative ICG angiography. The 56 patients were randomized to the control group or test group. There were no statistically significant differences in the levels of serum calcium and parathyroid hormone between test group and control group on the first or 30th postoperative day.Conclusion: The postoperative measurements of serum calcium and parathyroid hormone and oral supplementation of calcium and calcitriol were evaluated as redundant, if patients had at least one well-perfused parathyroid gland evaluated by intra-operative ICG angiography.Abbreviations: ICG = indocyanine green; NIR = near infrared; POD = postoperative day; PTH = parathyroid hormone; SBR = signal background ratio     

Effects of Amiodarone,Thyroid Hormones and CYP2C9 and VKORC1 Polymorphisms on Warfarin Metabolism: A Review of the Literature

ObjectiveTo review the literature regarding the interaction among amiodarone therapy, thyroid hormone levels, and warfarin metabolism.Methods73-year-old male with type 2 after describing an unusual case of amiodarone-induced thyrotoxicosis (AIT) who experienced a severe rise in international normalized ratio (INR) values after initiating warfarin therapy due to an unusual combination of excessive thyroid hormones, amiodarone therapy, and a genetic abnormality affecting warfarin metabolism.ResultsGenetic analysis revealed that the patient was CYP2C9*2 wild-type, CYP2C9*3/*3 homozygous mutant, and VKORC1*3/*3 homozygous mutant. A review of the literature revealed that both mutations can independently affect warfarin metabolism. In addition, amiodarone therapy and the presence of thyrotoxicosis per se can affect warfarin metabolism and reduce the dose needed to maintain INR in the therapeutic range. The association of the 2 genetic polymorphisms in a patient with AIT is extremely rare and strongly impairs warfarin metabolism, exposing the patient to a high risk of overtreatment.ConclusionsIn patients with AIT, warfarin therapy should be gradually introduced, starting with a very low dose, because of the significant risk of warfarin overtreatment. Whether the genetic analysis of CYP2C9 and VKORC1 polymorphisms should be routinely performed in AIT patients remains conjectural. (Endocr Pract. 2013; 19:1043-1049)     

Familial adult onset X-linked hypophosphataemic osteomalacia (report of a family; clinical and experimental studies)

From four patients (a great-grandmother, grandmother, her daughter and her grandson) suffering from a very severe form of familial X-linked hypophosphataemic osteomalacia (XLH), belonging to a 23-number-kindred of five generations, the youngest patient a 24-year-old man with an adult onset XLH was treated with phosphate and calcitriol for two years. Phosphate was given in increasing doses (500-6000 mg elemental phosphate) by mouth for a relatively short-term period and calcitriol in high doses per os combined with intermittent intravenous administration. Long-term treatment consisted of daily three grams of phosphate and 1.25 micrograms calcitriol by mouth combined with daily 2 micrograms calcitriol intravenously for one week every month. Dramatic clinical improvement occurred accompanied with definite radiological and scintigraphical changes. Serum phosphate increased from 0.525 +/- 0.478 mmol/l to 1.054 +/- 0.041 mmol/l (p < 0.001) in response to 3000 mg phosphate. A close correlation (r = 0.69) was found between serum phosphate and urinary phosphate excretions (p < 0.001) and an inverse correlation (r = -0.31) was found between serum phosphate and tubular reabsorption of phosphate (p < 0.01). Serum and urinary calcium values, parathormone as well as renal functions did not change. Administration of high doses of phosphate seemed to be an effective and probably safe form of treatment in XLH provided that development of hyperparathyroidism is prevented by the coadministration of high doses of calcitriol.     

Chemotherapy-Induced Hypocalcemia

ObjectiveTo present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy.MethodsWe present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality.ResultsIn a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature.ConclusionThe severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication. (Endocr Pract. 2010;16:284-290)     

Calciphylaxis in Man

A patient with renal failure developed widespread calcification in the thighs after the injection of iron-dextran (Imferon). This is considered as an example of calciphylaxis, a process in which calcium is laid down in parts of the body following the administration of a “challenger.” Iron-dextran is a known challenger, and should be used with caution in uraemic subjects, who may be sensitized by high serum parathyroid hormone levels. Contributing factors may have been a high calcium/phosphate product, steroids, and the patient''s immobility.