Increased Serum Calcitonin in Sporadic Primary Hyperparathyroidism is an Uncommon Occurrence

Objective: To evaluate calcitonin (CT) levels in sporadic primary hyperparathyroidism (PHPT), which has to date rarely been considered.Methods: We evaluated serum CT levels in 290 consecutive patients with sporadic PHPT at diagnosis.Results: Mild elevations in CT levels (hyperCT) were found in 25 patients (8.6%), with no correlation among the demographic, clinical, and biochemical findings. In addition, no differences were found between patients with and without hyperCT. Follow-up data were available for 19/25 patients, but CT values were only available for 10. CT normalized in all surgically cured patients regardless of the extent of the surgery (parathyroidectomy [PTX] only in 8 and associated with partial or total thyroidectomy for benign nodular goiters in 7).Conclusion: hyperCT is an uncommon feature of sporadic PHPT and not related to biochemical or clinical features of the disease. In addition, hyperCT is reversible after PTX, regardless of whether concomitant thyroidectomies have been conducted.Abbreviations: CT = calcitonin; eGFR = estimated glomerular filtration rate; hyperCT = hypercalcitoninemia; MEN = multiple endocrine neoplasm; MTC = medullary thyroid carcinoma; PHPT = primary hyperparathyroidism; PPI = proton pump inhibitor; PTH = parathyroid hormone; PTX = parathyroidectomy     

HRPT2- (CDC73) Related Hereditary Hyperparathyroidism: A Case Series From Western India

Objective: To describe a case series of HRPT2- (CDC73) related hereditary primary hyperparathyroidism (PHPT) from western India.Methods: We present a case series of 4 families (7 patients) with PHPT caused by CDC73 gene mutations.Results: The mean age of presentation of the 4 index cases was 27.25 ± 9.8 years. Two family members were identified through biochemical screening (Cases 1b and 2b), while 1 mutation-positive family member did not manifest any features of PHPT or hyperparathyroidism jaw tumor syndrome (HPT-JT) syndrome (Case 2c). Biochemistry showed increased serum calcium (mean: 13.21 ± 1.24 mg/dL), low serum phosphorus (mean: 1.78 ± 0.44 mg/dL), and high parathyroid hormone (PTH, mean: 936 ± 586.9 pg/mL).All patients had a uniglandular presentation and underwent single adenoma excision initially except Cases 2a and 2b, who underwent subtotal parathyroidectomy at baseline. Two cases experienced PHPT recurrence (Cases 3 and 4), while 1 remained uncured due to parathyroid carcinoma (Case 1a). Other associated syndromic features like ossifying jaw fibromas were present in 2 patients, renal cysts in 3 patients, and uterine involvement in 2 patients. Two families had novel germline CDC73 mutations (Families 1 and 3), while the other 2 had reported mutations. Family 2 had familial isolated PHPT without any other features of HPT-JT syndrome.Conclusion: Our findings reaffirm the need for genetic analysis of patients with PHPT, especially those with younger age of disease onset; recurrent disease; and associated features like polycystic kidneys, endometrial involvement, ossifying jaw tumors, or parathyroid carcinoma.Abbreviations: FIHP = familial isolated hyperparathyroidism HPT-JT = hyperparathyroidism jaw tumor syndrome PHPT = primary hyperparathyroidism PTH = parathyroid hormone ⁹⁹Tc = ⁹⁹Technetium     

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     

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     

Increased Serum Calcium is not Common in Hospitalized Patients with Primary Hyperparathyroidism: A Retrospective,Observational Study

Objective: Serum calcium levels often decrease during acute illness in patients with an intact calcium-regulating system. However, the dynamics of serum calcium levels in hospitalized patients with primary hyperparathyroidism (PHPT) have not yet been described.Methods: Clinical and laboratory data were retrospectively retrieved from the electronic medical records of patients with PHPT before, during, and after hospitalization for various reasons (excluding parathyroid surgery).Results: There were 99 nonselected patients with asymptomatic, hypercalcemic PHPT, hospitalized for various reasons; 42% were admitted for apparent infectious or septic conditions, and 58% were admitted for noninfectious conditions. Total serum calcium increased >0.5 mg/dL in 7.4% of the patients: 10.9% and 2.5% of the patients with noninfectious and infectious conditions, respectively. In 65.7% of the patients, the mean total serum calcium (TsCa), but not albumin-corrected calcium (corrCa), decreased significantly during hospitalization, down to below the upper limit of the reference range. Although prehospitalization TsCa and corrCa were similar in patients with infectious and noninfectious conditions, during hospitalization, TsCa was lower in patients with infectious conditions (P = .02). Both TsCa and albumin returned to prehospitalization levels after recovery.Conclusion: TsCa increases in a minority of hospitalized PHPT patients. In the majority of hospitalized patients with PHPT, TsCa, but not corrCa, decreases to within the normal reference range, more so in patients with infectious conditions, obscuring the major characteristic of PHPT. Therefore, it is prudent to follow calcium and corrCa during hospitalization in patients with PHPT.Abbreviations: corrCa = albumin-corrected serum calcium; IQR = interquartile range; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TsCa = total serum calcium     

Unknown and Already Known Thyroid Abnormalities in Primary Hyperparathyroidism

Objective: Primary hyperparathyroidism (PHPT) and thyroid diseases are highly prevalent in the general population, but the putative link between the 2 conditions remains unclear.Methods: A monocentric consecutive series of 434 patients with PHPT was retrospectively evaluated by lab and ultrasonography to look for thyroid abnormalities. Patients were classified in 3 groups: without thyroid abnormalities (group 1, n = 171), with thyroid diseases not previously known (group 2a, n = 69), and thyroid diseases previously known (group 2b, n = 194).Results: In terms of thyroid disease, no significant difference was found between groups 2a and 2b, except for the significantly larger number of patients with toxic nodular goiter in group 2b. PHPT was more frequently symptomatic in group 2a than in group 2b, despite no differences in serum calcium, creatinine, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25OHD) levels.Conclusion: A total of 60% of PHPT patients had a thyroid disease that was unknown prior to PHPT diagnosis in almost one-third of cases. The newly diagnosed and previously known thyroid diseases were similar, both mostly affecting postmenopausal females.Abbreviations: Ab = antibody; aPHPT = asymptomatic PHPT; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; Tg = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone; US = ultrasound     

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     

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.     

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)     

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)     

Radiologic Manifestation of Bone Involvement in Primary Hyperparathyroidism: Prevalence and Clinical Significance in a Southern European Series

Objective: Clinically overt symptomatic bone disease in primary hyperparathyroidism (PHPT) is rarely seen today, and osteoporosis is the dominant finding. Subperiosteal bone resorption in the fingers and skull mottling are typical bone PHPT findings, the contemporary prevalence of which is unknown. We evaluated these mild lesions and investigated the impact of their occurrence on PHPT clinical management.Methods: We evaluated retrospectively a monocentric series of 363 PHPT patients classified in Group 1 (n = 100) or Group 2 (n = 263) according to the presence or absence of bone involvement, respectively. Patients belonging to Group 1, in turn, were subdivided into Group 1A, with severe and symptomatic lesions (n = 48), and Group 1B, with milder signs of osteitis fibrosa cystica (OFC) without brown tumors or fractures (n = 52).Results: Serum total and ionized calcium, parathyroid hormone, osteocalcin, alkaline phosphatase, and its bone fraction levels were higher in Group 1 than in Group 2, while no gender or age differences were observed between the groups. Osteoporosis prevalence was similar in Group 1B and Group 2 patients but lower than in Group 1A. Mild OFC findings did not modify the surgical indication in any patient of Group 1B.Conclusion: Minor radiologic signs of OFC are not uncommon in the modern PHPT phenotype and occur in patients with more active disease. These signs could identify PHPT patients in an earlier stage of typical bone involvement. However, these features do not seem to upgrade either the clinical classification of asymptomatic PHPT patients or the propensity toward surgical choice.     

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     

Impact Of Ethnic Background On Clinical Characteristics And Cardiovascular Risk Factors Among Patients With Primary Hyperparathyroidism

Objective: To compare initial laboratory values and cardiovascular risk factors (CRF) among patients with primary hyperparathyroidism (PHPT) of different ethnic backgrounds.Methods: In this retrospective study, we reviewed 500 charts of PHPT patients who presented at Robert Wood Johnson University Hospital from January 2000 to December 2013. Among these patients were 46 African Americans (AA), 31 Asians (A), 19 Hispanics (H), and 404 Caucasians (C). The following characteristics were compared between the groups: age; body mass index (BMI); levels of serum calcium, intact parathyroid hormone (iPTH), 25-OH vitamin D, and 24-hour urine calcium; and parathyroid adenoma weight. Presence of CRF including BMI, diabetes mellitus, hypertension, and hyperlipidemia were also recorded for comparison. Associations of adenoma weight and several other parameters were also assessed.Results: Among different ethnic groups, AA patients with PHPT had higher iPTH levels compared to the A and C groups (P<.05), while 25-OHD levels were lower in the AA compared to the A and C groups (P<.05). Adenoma weight was significantly greater in AA than in C and A PHPT patients (P<.01). Adenoma weight was positively correlated with iPTH levels (r = 0.493, P <.001) and serum calcium levels (r = 0.255, P<.01). The group BMIs were C: 29.5 ± 6.9, AA: 33.8 ± 10, A: 24.7 ± 3.3, and H: 30.2 ± 6.6. AA patients had a lower rate of renal stones (9%) compared to other groups (21–29%, P<.05).Conclusion: The results of our study indicate that AA patients with PHPT presented with a more severe PHPT profile but had lower 24-hour urine calcium and fewer renal stones. AA patients with PHPT also had higher prevalence of CRF when compared to A and C.Abbreviations:A = AsianAA = African AmericanC = CaucasianCRF = cardiovascular risk factorsH = HispaniciPTH = intact parathyroid hormonePHPT = primary hyperparathyroidismPTH = parathyroid hormone     

KDIGO Categories of Glomerular Filtration Rate and Parathyroid Hormone Secretion in Primary Hyperparathyroidism

Objective: The recent Fourth Workshop on the Management of Asymptomatic primary hyperparathyroidism (PHPT) maintained the threshold of 60 mL/min for decreased renal function, below which surgery is recommended. This study investigated the relationship between different stages of renal insufficiency and parathyroid hormone (PTH) levels in an updated case series of PHPT patients.Methods: This was a retrospective, cross-sectional study involving 379 consecutive PHPT patients. Biochemical evaluation included total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D₃ (25[OH]D₃) levels in the fasting state. Glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.Results: Mean CKD-EPI estimated GFR was 81.9 ± 20.3 mL/min/1.73 m², and median GFR was 84.0 mL/min/1.73 m² (interquartile range, 26.8 mL/min/1.73 m²). The patients were divided into 5 groups according to the Kidney Disease: Improving Global Outcomes 2012 guidelines: group 1 with normal or increased GFR (>90 mL/min/1.73 m²); group 2 with mild GFR decrease (60 to 89 mL/min/1.73 m²); group 3a with mild to moderate GFR decrease (45 to 59 mL/min/1.73 m²); group 3b with moderate to severe GFR decrease (30 to 44 mL/min/1.73 m²); and group 4 with severe GFR decrease (<30 mL/min/1.73 m²). Among the 5 groups of patients, serum calcium levels were different (P = .025), whereas 25(OH)D₃ levels were not (P = .36). PTH levels were comparable across groups 1 through 3a, but they were significantly higher in groups 3b and 4 (P<.0001).Conclusion: In our series of PHPT patients, PTH levels did not rise as a result of renal impairment until GFR decreased below 45 mL/min/1.73 m².Abbreviations: 25(OH)D₃ = 25-hydroxyvitamin D₃ CKD-EPI = Chronic Kidney Disease-Epidemiology Collaboration GFR = glomerular filtration rate K/DOQI = National Kidney Foundation Disease Outcomes Quality Initiative KDIGO = Kidney Disease: Improving Global Outcomes MDRD = Modification of Diet in Renal Disease PHPT = primary hyperparathyroidism PTH = parathyroid hormone     

Primary Hyperparathyroidism: Comparing Between Solid and Cystic Adenomas and the Efficacy of Ultrasound and Single-Photon Emission Computed Tomography in their Diagnosis

Objective: Primary hyperparathyroidism (PHPT) is a disorder that results from abnormal functioning of the parathyroid glands. The purpose of this study was to compare cystic and solid adenomas by analyzing different variables associated with PHPT and parathyroid adenomas (age, calcium, phosphorus, and parathyroid hormone &lsqb;PTH] levels, adenoma volume) while comparing the efficacy of ultrasound and single-photon emission computed tomography in differentiating between both types of adenoma.Methods: From 152 patients diagnosed with PHPT between January 2013 and 2014, only 109 patients who had positive ultrasonographic findings for single parathyroid adenoma were included in the study.Results: A total of 26 patients had cystic adenomas and 83 patients had solid adenomas. Sestamibi (MIBI) was negative in 50% of the cystic adenoma group and 27.7% of the solid adenoma group, with an overall technetium-MIBI efficacy of 67%. Age, phosphorus level, and adenoma volume were significantly higher in patients with cystic adenomas (P = .001, P = .02, and P = .02, respectively), whereas calcium and PTH levels were significantly higher in patients with solid adenomas (P = .02, P = .038, respectively). MIBI had a significant correlation with PTH levels (P = .031) and adenoma volume (P = .05) only in patients with solid adenomas. No significant correlation was found between sex and type of parathyroid adenoma.Conclusion: The current study is the first to compare age, PTH levels, and adenoma volume between cystic and solid adenoma patients, providing more information for the poorly understood pathology of cystic adenomas. Our findings showed that age and calcium and PTH levels are significantly higher in patients with solid adenomas, whereas adenoma volume and phosphorus levels are significantly higher in patients with cystic adenomas.Abbreviations: BMD = bone mineral density GFR = glomerular filtration rate iPTH = intact parathyroid hormone MIBI = sestamibi PHPT = primary hyperparathyroidism PTH = parathyroid hormone SPECT = single-photon emission computed tomography Tc = technetium US = ultrasound     

Associations of Serum Ionized Calcium,Phosphate, and Pth Levels with Parathyroid Scan in Primary Hyperparathyroidism

Objective: To evaluate the relationship between various biochemical parameters in patients with primary hyperparathyroidism (PHPT) with positive and negative technetium-99 sestamibi (Tc) parathyroid scans performed with single-photon emission computed tomography/computed tomography (SPECT/CT).Methods: This retrospective analysis was used to develop a logistic probability model. It included 218 patients with PHPT. The main outcome measures were serum total calcium, ionized calcium, intact parathyroid hormone (PTH), albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-h urinary calcium levels, and parathyroid adenoma weight.Results: Individually, using cut-off levels of 6.0 mg/dL for ionized calcium, 3.0 mg/dL for phosphate, and 90 pg/mL for intact PTH, we found that 91.3% (P = .005), 70.7% (P = .004) and 87.90% (P = .023) of the patients had a positive Tc scan with their corresponding strengths of associations in the parentheses. Similar significant associations were sustained in multivariate setting for serum ionized calcium (P = .015), phosphate (P = .016), and intact PTH (P = .028). A logistic probability model was designed to predict the probability of being positive for Tc scan given a set of covariates.Conclusion: There are significant associations between the levels of serum ionized calcium, phosphate, intact PTH, and Tc scan positivity. Further studies with larger patient populations are needed.Abbreviations: BMI = body mass index; CT = computed tomography; CV = coefficient variation; DXA = dual-energy x-ray absorptiometry; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PPV = positive predictive value; PTH = parathyroid hormone; SPECT = single-photon emission computed tomography; Tc = technetium-99 sestamibi     

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)     

Vitamin D Deficiency Does Not Affect The Likelihood Of Presurgical Localization In Asymptomatic Primary Hyperparathyroidism

Objective: Vitamin D deficiency (VDD) was previously associated with larger adenoma size in primary hyperparathyroidism (PHPT), but this topic was not addressed in patients with the mild/asymptomatic form of the disease (aPHPT).Methods: We retrospectively retrieved from our series of patients affected by PHPT, 96 consecutive subjects with aPHPT in whom 25-hydroxyvitamin D (25OHD) levels had been assayed and compared those results with localizing imaging studies.Results: Twenty-five of 96 patients had VDD (25OHD <20 ng/mL), but positive ultrasound and scintigraphic studies were not different between patients with and without VDD (52.3% versus 55.7% and 42.9% versus 52.4%, respectively). Upon logistic regression analysis, after adjusting for different variables, including the presence of goiter, VDD was not an independent predictor of localization by imaging studies.Conclusion: VDD does not affect the likelihood of positive pre-operative imaging in aPHPT and the consequent surgical decisions.Abbreviations:25OHD = 25-hydroxyvitamin DaPHPT = asymptomatic primary hyperparathyroidismMIBI = Tc99m sestamibiPHPT = primary hyperparathyroidismPTH = parathyroid hormoneUS = ultrasoundVDD = vitamin D deficiency     

Does Baseline PTH Influence Recovery of Bone Mineral Density,Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism

Objective: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery.Methods: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery.Results: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638 ± 0.093 versus 0.698 ± 0.041 g/cm²; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH.Conclusion: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score     

Vitamin D-Binding Protein Levels in Female Patients with Primary Hyperparathyroidism

ObjectiveTo determine whether low levels of vitamin D-binding protein (DBP) are related to 25-hydroxyvitamin D (25[OH]D) deficiency in female patients with primary hyperparathyroidism (PHPT).MethodsTwenty-five female patients with PHPT (serum calcium level >10.2 mg/dL and intact parathyroid hormone (iPTH) level >66 pg/mL) and 25 healthy age- and body mass index-matched female control subjects were xaminod. Serum calcium and iPTH levels were determined by commercial laboratories. Levels of 25(OH)D and 1,25-dihydroxyvitamin D (1,25[OH]₂D) were determined by radioimmunoassay, and DBP level was determined by enzyme-linked immunosorbent assay.ResultsSerum iPTH and calcium levels were higher in PHPT patients than control subjects (P<.001). Levels of 25(OH)D, albumin, and DBP were lower in the serum of PHPT patients than control subjects (P<.01). There were no significant differences in 1,25(OH)₂D and free 25(OH) D levels between PHPT patients and control subjects. DBP level was inversely correlated with calcium (r = -0.47; P<.01) and iPTH (r = −0.31; P<.05) levels. The 25(OH)D level correlated positively with both DBP (r = 0.28; P <.05) and albumin (r = 0.44; P<.05) levels.ConclusionsBoth serum 25(OH)D and DBP levels were lower in female patients with PHPT compared with control subjects. We suggest that a low DBP level contributes to the low 25(OH)D level observed in female PHPT patients. The etiology of the decrease in DBP and its relationship to calcium, 25(OH)D, and PTH levels require further investigation. (Endocr Pract. 2013;19:609-613)