Low Urine Calcium Excretion in African American Patients with Primary Hyperparathyroidism

ObjectiveTo evaluate the prevalence of low urine calcium excretion in African American patients with primary hyperparathyroidism (PHPT), a common disorder associated with bone and renal complications, and to assess the distinction between PHPT and familial hypocalciuric hypercalcemia (FHH), a rare benign genetic disease.MethodsWe conducted a retrospective study on a cohort of 1,297 patients in whom a 24-hour urine study was performed for measurement of urine calcium and creatinine. PHPT was diagnosed if the serum calcium concentration was ≥ 10.5 mg/dL and intact parathyroid hormone (PTH) was ≥ 40 pg/mL. Patients receiving medications that affect urine calcium or with glomerular filtration rate ≤ 30 mL/min were excluded.ResultsNinety-six patients satisfied the diagnostic criteria for PHPT. The African American (n = 70) and non-African American (n = 26) patients did not differ in their mean age, body mass index, glomerular filtration rate, serum PTH, 25-hydroxyvitamin D levels, and 24-hour urine creatinine values. Median values of urine calcium/creatinine (mg/g) were 122 for African American versus 214 for non-African American patients (P = .006). Thirty-one of 70 African American patients (44%) had a urine calcium/creatinine ratio ≤ 100 mg/g, whereas only 2 of 26 non-African American patients (8%) had this value (P = .001).ConclusionThe prevalence of low urine calcium excretion among African American patients with PHPT is unexpectedly high. A threshold of 100 mg/g urine calcium/ creatinine identified 44% of such patients with PHPT as having FHH in this cohort. Therefore, other clinical criteria and laboratory variables should be used to distinguish PHPT from FHH in African American patients with PTH-dependent hypercalcemia. (Endocr Pract. 2011;17: 867-872)     

Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications

ObjectiveTo discuss the unusual occurrence of both familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism in the same patient and to explore potential mechanisms of association and issues related to clinical management.MethodsWe discuss the diagnosis, compare the clinical presentations of FHH and primary hyperparathyroidism, review the literature regarding patients who have presented with both disorders, and discuss management considerations. We also describe 2 patients who have both FHH (confirmed by genetic testing for a mutation in the gene encoding the calcium-sensing receptor [CASR]) and primary hyperparathyroidism.ResultsThe occurrence of both FHH and primary hyperparathyroidism in the same patient has been reported in a few cases, including 2 patients described here, one of whom was documented to have a novel CASR mutation. Inthose with clinical sequelae of hyperparathyroidism, parathyroidectomy has led to reduction, but not normalization, of serum calcium levels.ConclusionsThe coexistence of FHH and primary hyperparathyroidism should be considered in patients with hypercalcemia, hypophosphatemia, frankly elevated parathyroid hormone levels, and low urinary calcium excretion. Genetic testing for inactivating CASR gene mutations can confirm the diagnosis of FHH. Although surgical intervention does not resolve hypercalcemia, it may be beneficial by reducing the degree of hypercalcemia, alleviating the symptoms, and preventing potential complications of hyperparathyroidism. (Endocr Pract. 2012;18:412-417)     

Diseases associated with the extracellular calcium-sensing receptor

The human calcium-sensing receptor (CaSR) is a 1078 amino acid cell surface protein, which is predominantly expressed in the parathyroids and kidney, and is a member of the family of G protein-coupled receptors. The CaSR allows regulation of parathyroid hormone (PTH) secretion and renal tubular calcium reabsorption in response to alterations in extracellular calcium concentrations. The human CaSR gene is located on chromosome 3q21.1 and loss-of-function CaSR mutations have been reported in the hypercalcaemic disorders of familial benign (hypocalciuric) hypercalcaemia (FHH, FBH or FBHH) and neonatal severe primary hyperparathyroidism (NSHPT). However, some individuals with loss-of-function CaSR mutations remain normocalcaemic. In addition, there is genetic heterogeneity amongst the forms of FHH. Thus, the majority of FHH patients have loss-of-function CaSR mutations, and this is referred to as FHH type 1. However, in one family, the causative gene for FHH is located on 19p13, referred to as FHH type 2, and in another family it is located on 19q13, referred to as FHH type 3. Gain-of-function CaSR mutations have been shown to result in autosomal dominant hypocalcaemia with hypercalciuria (ADHH) and Bartter's syndrome type V. CaSR auto-antibodies have been found in FHH patients who did not have loss-of-function CaSR mutations, and in patients with an acquired form (i.e. autoimmune) of hypoparathyroidism. Thus, abnormalities of the CaSR are associated with three hypercalcaemic and three hypocalcaemic disorders.     

Primary Hyperparathyroidism in the Young: Comparison with Adult Primary Hyperparathyroidism

Objective: Primary hyperparathyroidism (PHPT) is relatively common among adults but rarely encountered in children and adolescents. According to the western literature, young PHPT is different from adult PHPT and is associated with more severe hypercalcemia. PHPT in the adult Indian population is different from its western counterpart. Here we present the clinical, biochemical, and surgical characteristics of young patients with PHPT treated at our tertiary care center.Methods: PHPT patients were divided into adult (≥25 years) and young (<25 years) groups. The clinical, biochemical, hormonal, and histopathologic characteristics and treatment outcomes in the groups were compared.Results: Out of 358 patients, 47 patients were young and 311 patients were adults. The mean ages of the groups were 19 ± 4 and 45 ± 12 years, respectively. The corresponding female-to-male ratios were 1.24:1 and 3.38:1 (P<.05). The nature and frequency of presenting symptoms were comparable between the 2 groups. The most common symptom in young patients with PHPT was bone pain and was not significantly different from adults (57% vs. 61%, respectively). The most common symptom in adult PHPT was fatigue, which was also not significantly different from young patients (63% vs. 53%, respectively), The serum calcium, phosphate, 25-hydroxyvitamin D levels; alkaline phosphatase Z-score; and parathyroid hormone levels were comparable between the 2 groups. Parathyroid adenoma was the most common histopathologic finding, while hyperplasia was rare in both groups.Conclusion: We observed that young PHPT is not markedly different from its adult counterpart in an Indian population.Abbreviations: ALP = alkaline phosphatase; Ca = calcium; Cr = creatinine; iPTH = intact parathyroid hormone; 25(OH)D = 25-hydroxyvitamin D; P = phosphate; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; RR = reference range; ^99mTc sestamibi = technetium sestamibi; USG = ultrasonography     

Calcium-Creatinine Clearance Ratio is not Helpful in Differentiating Primary Hyperparathyroidism from Familial Hypercalcemic Hypocalciuria: A Study of 1,000 Patients

Objective: With increasing recognition of more subtle presentations of primary hyperparathyroidism (pHPT), laboratory values are frequently seen in a range that would be expected for patients who have familial hypercalcemic hypocalciuria (FHH). Calcium-creatinine clearance ratio (CCCR) has been advocated as a diagnostic tool to differentiate between these two disorders. However, it is limited by an indeterminate range (0.01 to 0.02). The aim of this study was to assess the relevance of CCCR in a modern series of patients with surgically managed pHPT.Methods: We performed a retrospective cohort study of 1,000 patients who underwent parathyroid surgery for pHPT over 11 years. CCCR was evaluated by degree of biochemical derangement, single versus multiple gland disease, and interfering medications.Results: Patient demographics and resected histopathology were typical for a current series of patients with pHPT. In retrospect, none of the patients were suspected to have FHH postoperatively. CCCR was <0.01 for 19.0%, between 0.01 and 0.02 for 43.7%, and >0.02 in 37.3%. Distribution of CCCR for patients free from interfering medications and different histologic subtypes were the same. One-third of the cohort had mild calcium elevations, more typical for FHH. Of these, almost two-thirds had a CCCR in a range suspect for FHH (<0.02).Conclusion: To our knowledge, this is the largest series to evaluate the validity of CCCR for patients with surgically confirmed pHPT. The utility of CCCR in screening for FHH is limited, as 63% of modern patients with confirmed pHPT have low values.Abbreviations: CaSR = calcium sensing receptor; CCCR = calcium-creatinine clearance ratio; CeE = calcium excretion; FHH = familial hypercalcemic hypocalciuria; pHPT = primary hyperparathyroidism; PTH = parathyroid hormone     

Urinary Calcium Excretion in Primary Hyperparathyroidism: Relationship to 25-Hydroxyvitamin D Status

ObjectiveTo determine the prevalence of vitamin D deficiency in patients with primary hyperparathyroidism (PHPT) and evaluate the relationship between urinary calcium excretion and serum 25-hydroxyvitamin D (25-OH-D) levels in patients with PHPT.MethodsWe present a case report and a review of the medical records of patients with PHPT. Of 75 patients with PHPT substantiated by hypercalcemia and increased levels of intact parathyroid hormone (iPTH), 35 were identified with laboratory evaluation of vitamin D levels and 24-hour urinary calcium excretion. These study subjects were stratified as 25-OH-D deficient, insufficient, or replete (on the basis of serum values of < 15, 15 to 25, or > 25 ng/mL, respectively). Total 24-hour urinary calcium excretion and the fractional excretion of calcium (FECa) were analyzed as a function of 25-OH-D status.ResultsOf the 35 study subjects, 14 (40%) and 13 (37%) had 25-OH-D deficiency or insufficiency, respectively. Those patients with a 25-OH-D level < 15 ng/mL had higher serum iPTH concentrations as well as lower urinary calcium excretion and FECa. No significant correlations were found, however, between 25-OH-D status and iPTH concentrations (r = -0.21; P = 0.23), total 24-hour urinary calcium excretion (r = 0.07; P = 0.7), or FECa (r = 0.04; P = 0.8).ConclusionVitamin D deficiency (25-OH-D levels < 15 ng/mL) was common in our population of patients with PHPT. Urinary calcium excretion was not significantly altered by 25-OH-D deficiency in patients with newly recognized PHPT. Measurements of total urinary calcium excretion and FECa can be reliably used to rule out familial benign hypocalciuric hypercalcemia in the initial evaluation of PHPT, regardless of 25-OH-D status. Determining 25-OH-D concentrations best assesses the vitamin D status. (Endocr Pract. 2005;11:37-42)     

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)     

Distal Renal Tubular Acidosis Due to Primary Hyperparathyroidism

ObjectiveTo present 4 cases of distal renal tubular acidosis (RTA) in patients with primary hyperparathyroidism (PHPT) and discuss their possible etiopathogenetic correlation.MethodsWe diagnosed distal RTA in 4 patients with symptomatic primary PHPT on the basis of the baseline biochemical variables and the results of the ammonium chloride loading test. Complete resolution of distal RTA was documented after surgical cure of PHPT by removal of a parathyroid adenoma.ResultsAll our patients presented with symptomatic bone disease and metabolic myopathy. One patient presented with recurrent renal stones. Inappropriately alkaline fasting urine (pH > 5.5) in association with a normal anion gap metabolic acidosis suggested the diagnosis of distal RTA. All cases were confirmed by an ammonium chloride loading test. Three patients responded to surgical cure of PHPT by normalization of the acid-base status.ConclusionHypercalciuria in PHPT can lead to nephrocalcinosis and renal tubular dysfunction, which manifests as distal RTA. Cure of distal RTA after surgical treatment of PHPT establishes PHPT as the primary cause of distal RTA in these cases. (Endocr Pract. 2008;14: 1133-1136)     

Aldosterone Secretion in Patients With Primary Hyperparathyroidism Without Arterial Hypertension

ObjectiveThere is a direct bidirectional link between parathyroid hormone (PTH) and the renin-angiotensin-aldosterone system (RAAS), but few studies evaluated the RAAS in patients with primary hyperparathyroidism (PHPT), mainly biased from concomitant antihypertensive treatment.MethodsWe retrospectively evaluated a consecutive series of 130 normotensive patients with PHPT comparing aldosterone (ALD) levels and plasma renin activity (PRA) with the demographic, biochemical, or clinical features of PHPT.ResultsNo correlation was found between ALD and PRA, and the demographic, biochemical, and bone densitometry parameters in patients with PHPT without hypertension, with the exception of a negative correlation between age and serum PRA. Moreover, there was no significant correlation between PTH and ALD levels even in patients whose PTH level was >100 ng/L (P = .088).ConclusionIn our normotensive patients with PHPT, the ALD, PRA, and aldosterone/renin ratio were not correlated to PTH and calcium levels. In addition, they were neither related to PHPT clinical presentation nor renal function, vitamin D status, bone mass loss, or the presence of comorbidities such as diabetes and obesity. Further studies are needed to clarify the complex interplay between PTH and the RAAS in the modern PHPT presentation.     

Radioguided Parthyroidectomy is Successful in 98.7% of Selected Patients

ObjectiveTo examine an individualized approach to patients with primary hyperparathyroidism (PHPT) in an effort to identify factors that would differentiate patients who can be treated with radioguided parathyroidectomy (RP) from those that require more extensive parathyroid exploration (PE) using intraoperative parathyroid hormone (IOPTH) measurement and to compare rates of recurrent and persistent hypercalcemia.MethodsA total of 100 patients were retrospectively studied. Patients with positive single photon emission computed tomography (SPECT) scans underwent surgeon-performed sonography (SPS) followed by RP. Patients with negative or equivocal SPECT scans underwent PE utilizing SPS as a guide and IOPTH. The success rate, recurrence and persistence rates, and rate of bilateral exploration were compared.ResultsSeventy-five percent of patients with PHPT had a positive SPECT scan and underwent RP, whereas 25% of patients had a negative SPECT scan and underwent PE with IOPTH utilizing SPS as a guide. Persistent hypercalcemia was noted in 1 patient (1.3%) and recurrent hypercalcemia in 2 patients (2.6%) in the RP group, whereas no persistent hypercalcemia was noted in the group undergoing PE utilizing SPS and IOPTH. Overall, 89% of patients were cured with unilateral surgery.ConclusionPatients with positive SPECT scans may undergo RP with an expected cure rate of 98.7%. Patients with negative SPECT scans should undergo SPS followed by PE using IOPTH and can expect a cure rate near 100%. Properly selected patients may undergo RP, with low rates of persistent (1.3%) and recurrent (2.6%) hypercalcemia. (Endocr Pract. 2014;20:305-309)     

Diagnostic Fine-Needle Aspiration Biopsy of an Intrathyroidal Parathyroid Gland and Subsequent Eucalcemia in a Patient with Primary Hyperparathyroidism

ObjectiveTo present the clinical course of a patient with persistent primary hyperparathyroidism (PHPT) whose intrathyroidal parathyroid gland was diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).MethodsWe describe the clinical course and laboratory, radiographic, and microscopic findings of a patient with persistent PHPT due to an intrathyroidal cystic parathyroid gland and review the relevant literature.ResultsA 74-year-old man with PHPT (presenting serum calcium concentration, 16.2 mg/dL; intact parathyroid hormone [PTH] concentration, 341 pg/mL) had surgical excision of the right superior, right inferior, and left inferior parathyroid glands, but the left superior parathyroid gland remained unidentified. Microscopic examination revealed parathyroid hyperplasia. Technetium Tc 99m sestamibi single-photon emission computed tomography imaging showed uptake in 2 foci, 1 on each side of midline in the neck. Reoperation with attention to the left neck failed to locate another parathyroid gland. Neck ultrasonography demonstrated a complex nodule within the right lower lobe of the thyroid. Results from FNAB of the solid component were consistent with parathyroid cells, and cystic fluid PTH concentration was greater than 1800 pg/mL. Nine months later, neck ultrasonography showed a hypoechoic area located posterior to the inferior pole of the right thyroid. The patient remained eucalcemic 16 months postprocedure.ConclusionAutoinfarction of the parathyroid gland and aspiration of cystic fluid may explain resolution of hypercalcemia. Although PHPT due to functioning parathyroid cysts is rare, and PHPT due to cystic parathyroid hyperplasia has been described, this is the first case report of a patient with persistent PHPT due to a functional parathyroid cyst whose diagnosis by FNAB was followed by eucalcemia. (Endocr Pract. 2008;14:80-86)     

Primary Hyperparathyroidism During Pregnancy: A Case Series of 8 Patients

Objective: Due to a lack of typical clinical manifestations and physiologic changes in calcium metabolism during pregnancy, primary hyperparathyroidism (PHPT) during pregnancy is commonly underdiagnosed, and treatment during this unique period presents a clinical challenge. Hence, the aim of the present study was to summarize the cases of 8 pregnant patients with PHPT who were treated at our center to provide better clinical insight into this condition.Methods: Our study comprised a retrospective analysis of 8 pregnant PHPT patients and a control group of 22 age-matched, nonpregnant PHPT patients during the same period. Clinical manifestations, biochemical indices, pathologic types, therapeutic strategies, and pregnancy outcomes were compiled, and 25 patients were screened for germline mutations in the MEN1, CDC73, and CaSR genes.Results: The most-common symptoms in the pregnancy group involved the gastrointestinal tract (GIT) in 7/8 cases (87.5%), followed by urinary system involvement (50%) and joint pain (50%). In contrast, GIT symptoms in the control group were significantly less common (31.82%; P = .012). There was a trend of more-severe elevation of serum parathyroid hormone levels in the control group compared to that in the pregnancy group (P = .053). No differences were found in blood-ionized calcium, phosphate, or alkaline phosphatase levels between the two groups. In the pregnancy group, the serum albumin-corrected calcium level was reduced from 3.42 ± 0.66 mmol/L to 2.89 ± 0.46 mmol/L (P = .025) after hydration and medical treatment. Six patients, three of whom were in the second trimester of pregnancy, underwent parathyroidectomy, and 3 patients were after childbirth or had induced labor. Postoperative serum calcium levels were reduced to within the normal range. Fetal/neonatal complications were observed in 4 of 5 patients who had not received surgical treatment during pregnancy. In addition, 2 of 5 pregnant PHPT patients were found to carry MEN1 mutations, whereas no mutations were detected in any of the 20 nonpregnant patients.Conclusion: In this case series of PHPT during pregnancy, the most-common complaint of GIT symptoms may be easily confused with pregnancy reactions, which might contribute to the under- or misdiagnosis of this clinical entity. Patients who did not receive surgical treatment during pregnancy had high incidences of fetal/neonatal complications and worse pregnancy outcomes.Abbreviations: CaSR = calcium-sensing receptor; CDC73 = cell division cycle 73; GIT = gastrointestinal tract; MEN = multiple endocrine neoplasia; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; SCa = serum calcium     

Biochemical Dynamics of Untreated Primary Hyperparathyroidism: an Observational Study

Objective: The natural biochemical history of untreated primary hyperparathyroidism (PHPT) is poorly understood. The purpose of this study was to determine the extent of biochemical fluctuations in patients with PHPT.Methods: Retrospective cohort study from January 1, 1995, to December 31, 2014. Serum calcium and parathyroid hormone (PTH) levels in patients with classic (Ca >10.5 mg/dL, PTH >65 pg/mL) and nonclassic (Ca >10.5 mg/dL, PTH 40 to 65 pg/mL) PHPT were followed longitudinally at 1, 2, and 5 years. Biochemical profiles in follow-up were ranked in descending biochemical severity as classic PHPT, nonclassic PHPT, normal calcium with elevated PTH (Ca <10.5 mg/dL, PTH >65 pg/mL), possible PHPT (Ca >10.5 mg/dL, PTH 21 to 40 pg/mL), or absent PHPT (Ca >10.5 mg/dL, PTH <21 pg/mL or Ca <10.5 mg/dL, PTH <65 pg/mL).Results: Of 10,598 patients, 1,570 were treated with parathyroidectomy (n = 1,433) or medications (n = 137), and 4,367 were censored due to study closure, disenrollment, or death. In the remaining 4,661 untreated patients with 5 years of follow-up, 235 (5.0%) progressed to a state of increased biochemical severity, whereas 972 (20.8%) remained the same, and 3,454 (74.1%) regressed to milder biochemical states. In 2,522 untreated patients with classic PHPT, patients most frequently transitioned to the normal calcium with elevated PTH group (n = 1,257, 49.8%). In 2,139 untreated patients with nonclassic PHPT, patients most frequently transitioned to the absent PHPT group (n = 1,354, 63.3%).Conclusion: PHPT is a biochemically dynamic disease with significant numbers of patients exhibiting both increases and decreases in biochemical severity.Abbreviations: IQR = interquartile range; KPSC = Kaiser Permanente Southern California; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; PTx = parathyroidectomy     

Silent Renal Stones in Primary Hyperparathyroidism: Prevalence and Clinical Features

Objective(1) To evaluate the prevalence of silent nephrolithiasis in patients with primary hyperparathyroidism (PHPT) compared with controls, and (2) To characterize clinically PHPT patients with silent renal stones.MethodsWe reviewed clinical data for 141 patients with PHPT and without symptoms or history of nephrolithiasis in whom renal ultrasonography was performed at diagnosis. A total of 141 sex- and age- matched subjects with abdomen ultrasonography obtained for reasons different from urinary symptoms served as controls.ResultsSilent nephrolithiasis was more prevalent in PHPT patients than in controls (11.35% vs. 2.13%, P = .003). Among patients with PHPT, those with silent renal stones showed higher serum calcium and parathyroid hormone levels and met surgical criteria, regardless of nephrolithiasis, more frequently than those without renal stones.ConclusionThe prevalence of silent nephrolithiasis is increased in patients with PHPT as compared with controls. Moreover, it seems likely that silent renal stone disease could identify a subset of PHPT patients with more severe disease. Accordingly, we suggest ultrasonographic screening of nephrolithiasis in all PHPT patients. Further studies are needed to better characterize this clinical entity. (Endocr Pract. 2014;20:1137-1142)     

Primary Hyperparathyroidism and Vitamin D In African Americans

ObjectivesVitamin D deficiency is more common in African Americans than in the general population or other ethnicities. Vitamin D deficiency also occurs more frequently in patients with primary hyperparathyroidism (PHPT) than in the general population. Currently, the limited data on vitamin D deficiency in African Americans with primary hyperparathyroidism (PHPT) is inconsistent as to whether the vitamin D deficiency observed in PHPT is yet even more pronounced in Africans with PHPT relative to non-African Americans with PHPT.MethodsOn the basis of biochemical, radiological, and surgical (adenoma weight) parameters, African Americans have been reported to have a more severe form of PHPT than non-African Americans. However, comparative clinical manifestations of PHPT in African Americans have not been well described.ResultsCurrent guidelines recommend vitamin D repletion in mild, asymptomatic PHPT when levels of 25-hydroxyvitamin D are less than 20 ng/mL. Studies that reported vitamin D repletion with ergocalciferol or cholecalciferol in PHPT have not stratified data according to ethnicity. Discrepancies therefore exist between repleting vitamin D in African Americans who may potentially have a more severe PHPT profile, but simultaneously a more pronounced vitamin D deficiency.ConclusionEffectively designed clinical trials are necessary to evaluate the indications, efficacy, and safety of vitamin D in African Americans with PHPT. (Endocr Pract. 2012;18:947-953)     

Active Crohn Disease and Hypercalcemia Treated With Infliximab: Case Report and Literature Review

ObjectiveTo report a case of 1,25-dihydroxyvitamin D–mediated hypercalcemia caused by active Crohn disease that improved with infliximab therapy.MethodsWe present the clinical and laboratory findings and describe the clinical course of a patient who had hypercalcemia during Crohn disease exacerbations. The literature is reviewed regarding 1,25-dihydroxyvitamin D production in Crohn disease, and the 3 cases of hypercalcemia in individuals with Crohn disease reported in the literature are described.ResultsA 50-year-old man with long-standing Crohn disease treated with multiple bowel resections presented for take-down ileostomy. He was hypercalcemic and had suppressed parathyroid hormone and parathyroid hormone–related peptide levels. Histopathology of the resected ileostomy site and adjacent small bowel indicated active Crohn disease. Hypercalcemia promptly resolved after a few days of treatment with intravenous glucocorticoids. One month later, hypercalcemia recurred in the presence of an inappropriately high 1,25-dihydroxyvitamin D level and increased urinary calcium and serum angiotensin-converting enzyme levels. The serum and urinary calcium levels became normal with infliximab therapy. Three previous reports of hypercalcemia caused by active Crohn disease describe effective treatment with glucocorticoids. This is the first report of successful response to infliximab in this setting.ConclusionHypercalcemia mediated by 1,25-dihydroxyvitamin D in the setting of Crohn disease may respond to glucocorticoid-sparing immunomodulators. (Endocr Pract. 2008;14:87-92)     

1,25-Dihydroxyvitamin D-Mediated Hypercalcemia in Oleogranulomatous Mastitis (Paraffinoma), Ameliorated by Glucocorticoid Administration

ObjectiveTo report a case of oleogranulomatous mastitis (paraffinoma) in which both the hypercalcemia and the inappropriately elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were successfully reduced by administration of prednisone.MethodsWe describe the clinical, imaging, and laboratory findings in the study patient. Furthermore, we review the relevant literature regarding hypercalcemia in oleogranulomatous mastitis.ResultsA 58-year-old man with oleogranulomatous mastitis (paraffinoma)-related hypercalcemia, renal failure, and inappropriately elevated levels of 1,25(OH)2D presented to our institution. Treatment with prednisone—0.5 mg/kg of body weight or 30 mg daily—for 10 days resulted in a reduction of his serum calcium and 1,25(OH)2D levels to near-normal or normal values and a substantial improvement of his renal function. Nevertheless, the patient ultimately died 11 months later of multiple paraffinomarelated complications.ConclusionIn selected cases, treatment with glucocorticoids may offer a temporary relief from paraffinomarelated hypercalcemia until definitive treatment options are feasible. (Endocr Pract. 2010;16:102-106)     

Identifying Parathyroid Hormone Disorders and their Phenotypes through a Bone Health Screening Panel: It's not Simple Vitamin D Deficiency!

Objectives: To determine the utility of bone health screening panels in identifying disorders of parathyroid gland secretions.Methods: A retrospective analysis of biochemical parameters in a bone health screening panel (BHSP) was conducted. Low and high cutoffs were applied to determine hypofunctioning and hyperfunctioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were determined using a combination of levels of calcium, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH). A PTH nomogram was applied to calculate the maximum expected PTH for existing levels of 25-hydroxyvitamin D. Medical records of patients were reviewed for clinical validation of biochemical findings.Results: Sixty-eight percent of subjects showed abnormal PTH secretion. Primary hyper- and hypoparathyroidism were detected in 1% (n = 5) and 0.4% (n = 2) of subjects, respectively. Normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high-normal PTH were identified in 8.5% (n = 37) and 2% (n = 10) of subjects, respectively. All subjects with primary and normocalcemic hyperparathyroidism had higher measured PTH than calculated maximum PTH using the PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism were present in 18% (n = 88) and 39% (n = 194) of subjects, respectively. High prevalence of bone pains, renal stones, and low bone mineral density were identified in patients with abnormal PTH secretion.Conclusion: Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. A BHSP helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high PTH.Abbreviations:25OHD = 25-hydroxyvitamin DAKUH = Aga Khan University HospitalBHSP = bone health screening paneliPTH = intact parathyroid hormonemaxPTH = maximum parathyroid hormoneMBD = metabolic bone diseaseNCHPT = normocalcemic hyperparathyroidismPHPT = primary hyperparathyroidismPTH = parathyroid hormoneSHPT = secondary hyperparathyroidismVDD = vitamin D deficiency     

Echocardiographic Findings in Patients With Normocalcemic Primary Hyperparathyroidism Compared With Findings in Hypercalcemic Primary Hyperparathyroid Patients and Control Subjects

ObjectiveThere are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls.MethodsSeventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation.ResultsPatients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction).ConclusionIn a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.     

Characteristics of Ectopic Parathyroid Glands in 145 Cases of Primary Hyperparathyroidism

ObjectiveTo determine the prevalence of primary hyperparathyroidism (PHPT) arising from ectopic parathyroid glands, to analyze the clinical, biochemical, and anatomic characteristics of such cases, and to compare these characteristics with those found in PHPT associated with orthotopic parathyroid glands.MethodsWe conducted a retrospective study of cases of PHPT evaluated and treated at a referral center. Differences between patients with orthotopic and ectopic parathyroid glands were analyzed statistically.ResultsDuring a recent 5-year period at our institution, 145 cases of PHPT were treated operatively by 3 experienced surgeons. An ectopic parathyroid location was detected in 13 cases (9%). Of the 13 ectopic glands, 4 (31%) were at the tracheoesophageal groove, 4 (31%) were intrathymic, 2 (15%) were intrathyroidal, and 1 each was located in the aortopulmonary window, the anterior (nonthymic) mediastinum, and the submaxillary region. Patients with PHPT attributable to ectopic adenomas had significantly higher serum calcium levels (12.6 ± 0.9 mg/ dL versus 11.4 ± 1.2 mg/dL; P = .05) and larger tumors (25 ± 6.1 mm versus 19 ± 7.6 mm; P = .05) than did patients with orthotopic parathyroid glands. Moreover, hyperparathyroidism-related bone disease was significantly more frequent in patients with abnormal ectopic parathyroid glands than in those with orthotopic parathyroid glands (23% versus 1.5%, respectively; P = .04).ConclusionIn 9% of all cases of PHPT in our study, the condition was associated with ectopically located parathyroid glands. Such cases are usually characterized by larger parathyroid glands, higher serum calcium levels, and a higher frequency of severe bone disease. (Endocr Pract. 2010;16:977-981)