A Prospective Study of Commonly Utilized Regimens of Vitamin d Replacement and Maintenance Therapy in Adults

Objective: To determine which vitamin D dose, formulation, and schedule most effectively and safely achieves a 25-hydroxyvitamin D (25&lsqb;OH]D) level of >30 ng/mL (75 nmol/L).Methods: In this prospective study, 100 subjects from the NY Harbor HCS Brooklyn Campus, ages 25 to 85 years, with 25(OH)D <30 ng/mL (<75 nmol/L), were randomized into four groups: cholecalciferol (D3) 2,000 international units (IU) daily; D3 3,000 IU daily; ergocalciferol (D2) 50,000 IU weekly; and D2 50,000 IU twice weekly. All were supplemented with 500 mg calcium carbonate daily. 25(OH)D, parathyroid hormone (PTH), urinary calcium, urinary creatinine, and other variables were measured during 7 visits over 12 months.Results: All groups achieved a mean vitamin D level >30 ng/mL (>75 nmol/L) by visit 4 (5 months). Those receiving 50,000 IU D2 twice weekly displayed the most rapid and robust response, with 25(OH)D reaching >30 ng/mL (>75 nmol/L) after only 1 month and plateauing at 60 ng/mL (150 nmol/L) by 7 months. Although no statistically significant difference was seen in mean 25(OH)D levels between groups 1 through 3, subjects on 50,000 IU D2 weekly more consistently showed higher mean levels than either groups 1 or 2. No episodes of significant hypercalcemia occurred. There was a negative correlation in mean PTH levels and mean vitamin D levels in group 4 and all groups combined.Conclusion: All four schedules of vitamin D replacement were effective in safely achieving and maintaining 25(OH)D >30 ng/mL (>75 nmol/L). D2 50,000 IU twice weekly provided the most rapid attainment and highest mean levels of vitamin D.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; BUN = blood urea nitrogen; Ca/Cr = calcium/creatinine; D2 = ergocalciferol; D3 = cholecalciferol; IU = international units; PTH = parathyroid hormone     

Evaluation of Vitamin D Repletion Regimens to Correct Vitamin D Status in Adults

ObjectiveTo determine the efficacy and safety of commonly prescribed regimens for the treatment of vitamin D insufficiency.MethodsWe performed a retrospective analysis of 306 consecutive patients who were prescribed ergocalciferol (vitamin D₂) for correction of vitamin D insufficiency at the Atlanta Veterans Affairs Medical Center between February 2003 and May 2006. Serum levels of parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and calcium were compared before and after treatment with ergocalciferol. Patients who did not have a 25-OHD determination (n = 41) were excluded from analysis. Vitamin D deficiency, insufficiency, and sufficiency were defined as a serum 25-OHD level of < 20 ng/mL, 21 to 29 ng/mL, and > 30 ng/mL, respectively.ResultsWe identified 36 discrete prescribing regimens. The 3 most common regimens were ergocalciferol 50,000 IU once weekly for 4 weeks followed by 50,000 IU once monthly for 5 months (n = 48); ergocalciferol 50,000 IU once monthly for 6 months (n = 80); and ergocalciferol 50,000 IU 3 times weekly for 6 weeks (n = 27). Each of these 3 treatments significantly increased serum 25-OHD (P < .01), but vitamin D sufficiency was achieved in only 38%, 42%, and 82% of study subjects, respectively. Regimens with > 600,000 IU of ergocalciferol given for a mean of 60 ± 40 days achieved sufficiency in 64% of cases, without vitamin D toxicity.ConclusionIn this study, regimens that contained at least 600,000 IU of ergocalciferol appeared to be the most effective in achieving vitamin D sufficiency. Guidelines for the treatment of vitamin D insufficiency in healthy adults should be developed. (Endocr Pract. 2009;15:95-103)     

Treatment of Adult Hypophosphatasia with Teriparatide

ObjectiveTo describe the effects of 24 months of teriparatide therapy in an adult with hypophosphatasia, which thus far has no established medical treatment.MethodsA 75-year-old woman with hypophosphatasia was treated with ergocalciferol and calcium supplements for 2 years. She had sustained multiple spontaneous and low-trauma fractures since she was 10 years old. Baseline biochemical values (and reference ranges) were as follows: serum total alkaline phosphatase ranged from 14 to 17 U/L (30 to 110), bone-specific alkaline phosphatase (BSALP) was 5 U/L (14 to 43), serum phosphorus was elevated at 5.4 mg/dL (2.6 to 4.4), and pyridoxal 5′-phosphate was high at 250 ng/mL (5 to 30). At baseline, she had mild secondary hyperparathyroidism (intact parathyroid hormone, 76 pg/mL; reference range, 10 to 65), which was corrected by the calcium supplementation and vitamin D therapy. Dual-energy x-ray absorptiometry (DXA) scanning in 2003 showed L1-L4 bone mineral density (BMD) of 0.786 g/cm², T score of -3.3, and Z score of -1.7; DXA also showed femoral neck BMD of 0.740 g/cm², T score of -2.5, and Z score of -0.5. During walking, the patient sustained a low-trauma fracture in a metatarsal. Teriparatide, synthetic parathyroid hormone(1-34), in a dosage of 20 μg subcutaneously was given daily from April 2004 until June 2006.ResultsAfter about 1.5 years of teriparatide therapy, BSALP reached the lower end of the reference range at 16 U/L, and after 24 months of continuous teriparatide treatment, both serum total alkaline phosphatase and BSALP normalized at 30 U/L and 18 U/L, respectively. Pyridoxal 5′-phosphate declined from a baseline of 250 to 188 ng/mL after 17 months of treatment. Urinary N-telopeptide increased from a baseline of < 6 to 19 after 17 months and to 70 bone collagen equivalents/mmol creatinine after 24 months of anabolic therapy. Repeated DXA scanning showed a substantial improvement in lumbar spine BMD and stability in hip BMD. The patient experienced no clinical fractures or adverse events during teriparatide therapy.ConclusionIn one woman with adult hypophosphatasia, 2 years of teriparatide treatment improved bio-chemical markers of bone remodeling and increased skeletal mineralization. Teriparatide may prove to be a viable treatment for adult hypophosphatasia; thus, this intervention warrants further evaluation. (Endocr Pract. 2008;14:204-208)     

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)     

Congenital Craniopharyngioma and Hypercalcemia Induced by Parathyroid Hormone-Related Protein

ObjectiveTo report a case of congenital craniopharyngioma and parathyroid hormone-related protein (PTHrP)-associated humoral hypercalcemia.MethodsDetails of this unusual case are reviewed, from detection of fetal hydrocephalus and a brain tumor, through cesarean delivery at 36 weeks of gestation, to subsequent laboratory studies, management, and confirmation of the diagnosis.ResultsAlthough PTHrP has been well documented as a cause of humoral hypercalcemia of malignancy (HHM) in adult patients with cancer, HHM is uncommon in children. In addition, HHM has rarely been ascribed to nonmalignant tumors. To the best of our knowledge, we report the first case of a neonate with congenital craniopharyngioma and refractory hypercalcemia (peak ionized calcium level of 1.92 mmol/L; normal, 1.05 to 1.3) attributed to an elevated PTHrP value of 8.6 pmol/L (normal, less than 4.7). Intact parathyroid hormone was appropriately undetectable (less than 10 pg/mL; normal, 15 to 65). Despite calcitonin treatment, the hypercalcemia persisted. Although pamidronate infusion stabilized the serum calcium level, the baby did not survive.ConclusionThe diagnosis of craniopharyngioma was confirmed at autopsy, and immunohistochemical studies substantiated that the craniopharyngioma produced PTHrP. (Endocr Pract. 2007;13:67-71)     

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)     

Unusual Recurrence of Hypercalcemia Due to Concurrent Parathyroid Adenoma and Parathyroid Sarcoidosis with Lymph Node Involvement

ObjectiveTo describe a patient presenting with the rare findings of synchronous parathyroid adenoma and parathyroid sarcoidosis.MethodsWe describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic data of a man who developed recurrent se- vere hypercalcemia after successful parathyroidectomy.ResultsA 67-year-old man had the following initial blood test results: calcium, 11.1 mg/dL (reference range, 8.5-10.6 mg/dL); albumin 4.0 g/dL (reference range, 3.2-5.2 g/dL); intact parathyroid hormone, 166 pg/mL (refer- ence range, 10-69 pg/mL); creatinine, 1.9 mg/dL; 25-hy- droxyvitamin D, 15 ng/mL (reference range, 30-80 ng/ mL); and 1, 25-dihydroxyvitamin D, 44 pg/mL (reference range, 16-72 pg/mL). Chest x-ray was normal, and delayed images from a technetium Tc 99m sestamibi scan showed increased activity in the right lower pole of the thyroid. Two months after successful parathyroidectomy, the pa- tient was admitted to the hospital with a serum calcium concentration of 17 mg/dL. Pathologic examination of the resected gland confirmed the diagnosis of parathyroid ad- enoma, and subsequent review disclosed the presence of noncaseating granulomas within the adenoma.ConclusionsSarcoidosis with parathyroid involve- ment causing severe hypercalcemia is unique to this case.Recurrent hypercalcemia after successful resection of a parathyroid adenoma may require consideration of poten- tial causes other than the initial diagnosis. (Endocr Pract. 2010;16:463-467)     

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)     

Unusual Manifestation of Parathyroid Carcinoma in the Setting of Papillary Thyroid Cancer

ObjectiveTo describe a rare manifestation of parathyroid carcinoma in association with papillary thyroid carcinoma.MethodsWe describe the clinical history, findings on physical examination, results of laboratory studies, imaging findings, and histopathologic features of a woman with 2 previously palpable thyroid nodules and mild hypercalcemia.ResultsA 79-year-old woman presented to our endocrinology clinic for reevaluation of 2 thyroid nodules and long-standing hyperparathyroidism. She initially had undergone assessment 6 years previously, at which time an intact parathyroid hormone level was 89 pg/mL (reference range, 10 to 69) and the serum calcium concentration was 10.4 mg/dL (reference range, 8.2 to 10.2) in conjunction with normal alkaline phosphatase, creatinine, and 25-hydroxyvitamin D levels. Subsequently, she was found to have multifocal papillary thyroid cancer in the right thyroid lobe and a 5-cm parathyroid carcinoma in the left side.ConclusionSynchronous parathyroid and thyroid carcinomas are extremely rare. To our knowledge, our current case is the first documented patient with parathyroid carcinoma who had a clinical presentation consistent with longstanding mild adenoma in addition to synchronous papillary thyroid carcinoma. (Endocr Pract. 2010;16:664-668)     

Asymptomatic Primary Hyperparathyroidism Exists in North India: Retrospective Data from 2 Tertiary Care Centers

Objective: Primary hyperparathyroidism (PHPT) has evolved into an asymptomatic disease in the west. In contrast, classic symptoms of PHPT have been reported to be common in the east. Here we describe clinical and biochemical profiles of patients diagnosed with PHPT between 2009 and 2012.Methods: This was a retrospective study conducted at 2 tertiary care centers in north India. All patients who underwent evaluation and surgery for primary hyperparathyroidism (PHPT) from January 2009 to December 2012 were included.Results: A total of 50 patients were studied between 2009 and 2012. Among them 31 (62%) were symptomatic and 19 (38%) were asymptomatic. The mean age (SD) was 48.3 (15.8) years, and the female to male ratio was 1.9:1. None of the patients had brown tumors or bone deformities. The asymptomatic group had significantly lower median adenoma weight (0.57 vs. 3.4 g, P<.05), a higher mean age (57.3 vs. 42.8 years, P<.05), and a lower median intact parathyroid hormone (iPTH) level (254.5 vs. 295 pg/mL, P<.05) compared to the symptomatic group. Adenoma weight was positively correlated with baseline serum calcium, iPTH, and alkaline phosphatase (ALP) levels.Conclusion: The asymptomatic form of PHPT was found in a significant percentage of north Indian patients in this study. Asymptomatic PHPT patients were older in age and had lower parathyroid adenoma weights and iPTH levels compared to symptomatic PHPT patients. Positive correlations were found between parathyroid adenoma weight and serum calcium, iPTH, and ALP levels.Abbreviations: ALP = alkaline phosphatase iPTH = intact parathyroid hormone MIBI = 2-methoxyisobutylisonitrile 25(OH)D = 25-hydroxyvitamin D3 PHPT = primary hyperparathyroidism PTH = parathyroid hormone     

Splenic Sarcoidosis without Focal Nodularity: A Case of 1,25-Dihydroxyvitamin D-Mediated Hypercalcemia Localized with FDG PET/CT

ObjectiveTo report an uncommon cause of 1,25-dihydroxyvitamin D (1,25[OH]₂D)-mediated hypercalcemia associated with splenic sarcoidosis and illustrate the evaluation and potential role of fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in such patients.MethodsWe present detailed clinical features, laboratory results, imaging results, and pathology results for this rare entity, discuss evaluation and management options, and review previous literature.ResultsA 65-year-old male presented with symptomatic hypercalcemia, with a serum calcium level of 14.1 mg/dL 3 months after being initiated on ergocalciferol for vitamin D deficiency. He was found to have a suppressed parathyroid hormone level, normal 25-hydroxyvitamin D (25[OH]D) level, and elevated 1,25(OH)₂D level. Extensive evaluation did not yield a definitive diagnosis. Hiscalcium levels normalized and symptoms resolved on prednisone then recurred when prednisone was discontinued. FDG PET/CT showed intense uptake in the spleen. Splenectomy was performed, which resulted in resolution of hypercalcemia and yielded a diagnosis of splenic sarcoidosis.Conclusion:Splenic sarcoidosis causing hypercalcemia has been rarely reported. Our case is unique in that the spleen lacked typical focal nodularity on cross-sectional CT imaging, which is expected in sarcoid involvement of the spleen. Our case adds to an emerging literature documenting the potential value of FDG PET/CT in localizing otherwise occult 1,25(OH)₂D-mediated hypercalcemia. (Endocr Pract. 2014;20:e28-e33)     

Calcium Carbonate Toxicity: The Updated Milk-Alkali Syndrome; Report of 3 Cases and Review of the Literature

ObjectiveTo describe 3 patients with calcium carbonate-induced hypercalcemia and gain insights into the cause and management of the milk-alkali syndrome.MethodsWe report the clinical and laboratory data in 3 patients who presented with severe hypercalcemia (corrected serum calcium ≥ 14 mg/dL) and review the pertinent literature on milk-alkali syndrome.ResultsThe 3 patients had acute renal insufficiency, relative metabolic alkalosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations. No malignant lesion was found. Treatment included aggressive hydration and varied amounts of furosemide. The 2 patients with the higher serum calcium concentrations received pamidronate intravenously (60 and 30 mg, respectively), which caused severe hypocalcemia. Of the 3 patients, 2 were ingesting acceptable doses of elemental calcium (1 g and 2 g daily, respectively) in the form of calcium carbonate. In addition to our highlighted cases, we review the history, classification, pathophysiologic features, and treatment of milk-alkali syndrome and summarize the cases reported from early 1995 to November 2003.ConclusionMilk-alkali syndrome may be a common cause of unexplained hypercalcemia and can be precipitated by small amounts of orally ingested calcium carbonate in susceptible persons. Treatment with hydration, furosemide, and discontination of the calcium and vitamin D source is adequate. Pamidronate treatment is associated with considerable risk for hypocalcemia, even in cases of initially severe hypercalcemia. (Endocr Pract. 2005;11: 272-280)     

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)     

Coronary Artery Calcification in Patients with Primary Hyperparathyroidism in Comparison with Control Subjects from the Multi-Ethnic Study of Atherosclerosis

ObjectiveTo determine whether coronary artery calcification (CAC) is increased in patients with primary hyperparathyroidism (pHPT) because of the presence of hypercalcemia, which has been shown in vitro to promote vascular calcification.MethodsElectron beam computed tomography of the coronary arteries was performed on 20 patients with pHPT referred to our endocrinology clinic for evaluation of hypercalcemia. All patients were nonsmokers, with normal renal function, no history of diabetes, and no history of coronary artery disease. CAC in the patients with pHPT was compared with that in population-based control subjects from the Multi-Ethnic Study of Atherosclerosis (MESA). Two methods of analysis were used: (1) calculation of the odds ratio of CAC and (2) a nested case-control (1:4) study.ResultsOne patient with pHPT had a history of nephrolithiasis; the other 19 patients were asymptomatic. The mean age (± SD) of the patients with pHPT was 57.3 ± 9.1 years, the mean serum calcium concentration was 2.68 ± 0.18 mmol/L, and the mean intact parathyroid hormone level was 119 ± 76.5 pg/mL. Of the 20 patients, 14 had CAC scores of zero. The odds ratio for measurable CAC in the presence of pHPT in comparison with that in the MESA control subjects was 0.17, which was not significant. In the matched analysis, the CAC scores for the patients with pHPT did not differ significantly from those for the MESA control subjects (P = 0.25 with use of the Wilcoxon test).ConclusionWe found no evidence for a difference in CAC in patients with pHPT in comparison with the population-based control subjects in this small pilot study. (Endocr Pract. 2008;14:155-161)     

Endoscopic Ultrasound-Guided Fine-Needle Aspiration With Aspirate Assay to Diagnose Suspected Mediastinal Parathyroid Adenomas

ObjectiveTo describe our experience with mediastinal parathyroid adenomas diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) and measurement of parathyroid hormone.MethodsWe describe the clinical and pathologic findings and diagnostic techniques used in 2 study patients.ResultsPatient 1 was a 54-year-old man with persistently elevated serum calcium and parathyroid hormone concentrations despite removal of a right inferior parathyroid adenoma. An echoendoscope was used to identify the lesion and to perform FNA. The parathyroid hormone concentration measured in the aspirated material was 1800 pg/mL. Pathologic examination of the resected specimen revealed a 29.7-g parathyroid adenoma. Patient 2 was an 86-year-old woman with recurrent hyperparathyroidism. A linear array echoendoscope was used to perform FNA of the lesion in her mediastinum. The parathyroid hormone concentration measured in the aspirated specimen was 6905 pg/mL.ConclusionsPreoperative localization of recurrent or persistent hyperparathyroidism is often difficult. EUSFNA allows evaluation of masses, such as those found in the mediastinum, that are poorly evaluated by other imaging modalities. This technique may be a useful adjunct in diagnosing mediastinal parathyroid adenomas. (Endocr Pract. 2010;16:437-440)     

Parathyroid carcinoma arising from four-gland hyperplasia

ObjectiveTo report the use of immunohistochemical staining for parafibromin, APC, and galectin-3 to evaluate the malignant potential of a resected parathyroid specimen in a patient initially presenting with primary hyperparathyroidism attributable to 4-gland hyperplasia, who subsequently developed metastatic parathyroid carcinoma.MethodsWe describe a patient with primary hyperparathyroidism who underwent a 3-gland resection of hypercellular parathyroid glands, with postoperative normalization of her serum calcium and parathyroid hormone levels. She returned 4 years later with recurrent hypercalcemia and underwent partial resection of her remaining hypercellular parathyroid gland, without improvement of her hypercalcemia. Selective venous sampling localized the source as draining into her azygos vein, and metastatic parathyroid carcinoma was ultimately diagnosed.ResultsImmunohistochemical staining for parafibromin, APC, and galectin-3 suggested the malignant potential of the atypical adenoma removed during the patient’s original operation, which is believed to be the source of her metastatic disease. Access to this information by the treating surgeon may have prompted a more extensive en bloc resection or more vigilant follow-up that could have altered the patient’s clinical course.ConclusionImmunohistochemical staining for parafibromin, APC, and galectin-3 can be used to help distinguish the source of metastatic disease in patients with parathyroid carcinoma. Selective venous sampling may help localize metastatic parathyroid carcinoma when the source is otherwise not apparent. (Endocr Pract. 2011;17:e37-e42)     

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     

Synchronous Parathyroid Carcinoma,Parathyroid Adenoma,and Papillary Thyroid Carcinoma in a Patient with Severe and Long-Standing Hyperparathyroidism

ObjectiveTo describe a patient presenting with the rare constellation of synchronous parathyroid carcinoma, parathyroid adenoma, and papillary thyroid carcinoma.MethodsWe summarize the clinical presentation, diagnostic work-up, surgical management, and pathologic features of our patient and review the pertinent literature.ResultsThe patient was a 59-year-old man who presented with severe clinical manifestations of long-standing primary hyperparathyroidism, a serum calcium concentration of 14.4 mg/dL, and a parathyroid hormone level of 2,023 pg/mL. He was found to have a 3.4-cm parathyroid carcinoma on the left side and a 3.2-cm papillary carcinoma in the right thyroid lobe. In addition, a 917-mg parathyroid adenoma was found on the right side.ConclusionSynchronous parathyroid and thyroid carcinomas are extremely rare. To our knowledge, our patient is the first documented case with a parathyroid adenoma in addition to synchronous parathyroid and thyroid carcinomas. The presence of concurrent parathyroid carcinoma and parathyroid adenoma can cause diagnostic confusion and should be considered in patients presenting with severe hyperparathyroidism. Any concomitant thyroid nodules must be investigated to rule out thyroid carcinoma. (Endocr Pract. 2009;15:463-468)     

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)     

Increased Atherogenic Low-Density Lipoprotein Cholesterol in Untreated Subclinical Hypothyroidism

ObjectiveTo evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).MethodsIn a prospective, double-blind, placebo- controlled study, we enrolled 120 patients—mostly, but not exclusively, premenopausal women—with SCH. Patients were randomly assigned to either a levothyroxine- treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.ResultsIn the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 ± 0.98 mmol/L versus 4.74 ± 0.87 mmol/L (P < .0001); LDL-C, 3.30 ± 0.90 mmol/L versus 2.89 ± 0.59 mmol/L (P < .01); TG, 1.18 ± 0.71 mmol/L versus 0.95 ± 0.53 mmol/L (P < .002); and HDL-C, 1.20 ± 0.33 mmol/L versus 1.19 ± 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 ± 0.60 mmol/L to 3.11 ± 0.77 mmol/L, a change that was statistically significant (P < .001). At the end of the study, the lipid profile changes between levothyroxine- treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P < .029 and P < .0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.ConclusionIn premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated. (Endocr Pract. 2008;14:570-575)