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     

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)     

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     

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)     

Serum Monocyte Chemokine Protein-1 Levels Before and After Parathyroidectomy in Patients with Primary Hyperparathyroidism

ObjectiveTo investigate the effects of parathyroidectomy on serum monocyte chemokine protein-1 (MCP- 1) levels in patients with primary hyperparathyroidism (PHPT).MethodsForty-three PHPT patients, age 56 ± 12 years, underwent minimally invasive parathyroidectomy. Serum samples were collected at 0 and 15 to 20 minutes after parathyroid adenoma removal. Serum samples were stored at -70°C until time of assay.ResultsIn 40 PHPT patients with a single adenoma, MCP-1 levels decreased from 342 ± 103 to 250 ± 77 pg/ mL (P < .001) 15 to 20 minutes after parathyroid adenoma removal. MCP-1 levels were positively correlated with intact parathyroid hormone (PTH) levels (R = 0.47; P < .01). In 3 PHPT patients with double parathyroid adenoma, MCP-1 levels did not decrease after removal of the first adenoma but decreased 15 to 20 minutes after second adenoma removal.ConclusionOur results provide evidence that the decrease in serum intact PTH due to minimally invasive parathyroidectomy results in an immediate decrease in serum MCP-1 levels. (Endocr Pract. 2014;20:1165-1169)     

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     

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     

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     

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     

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     

Greater Than Age-Predicted Functional Deficits In Older Patients with Primary Hyperparathyroidism

ObjectiveTo compare the functional capacity of “asymptomatic” patients with primary hyperparathyroidism (PHPT) with normative values of healthy age-matched subjects.MethodsEighteen asymptomatic patients with PHPT met the study inclusion criteria: age > 55 years, serum calcium concentration elevated ≤ 1 mg/dL above normal, inappropriate elevation of parathyroid hormone (PTH) level, and no objective symptoms of PHPT. Functional capacity was assessed by (1) a 6-minute walk test, (2) time to complete 2 sit-to-stand maneuvers, (3) gait velocity, and (4) forward reach. Serum calcium, 25-hydroxyvitamin D, and PTH levels were measured by standard laboratory assays. Functional outcomes of the study patients were compared with age-matched normative values (unpaired t test) and correlated with these biomarkers. Because these patients often have weakness, fatigue, and malaise, we hypothesized that their functional capacity would be compromised relative to that of healthy, age-matched persons.ResultsThe mean age of the patients was 65.6 years, and the mean serum calcium, PTH, and 25-hydroxyvitamin D levels (and standard deviations) were 10.36 ± 0.37 mg/dL, 122.22 ± 39.54 pg/mL, and 44.4 ± 14.27 ng/mL, respectively. Relative to normative values of healthy, agematched subjects, these patients had comparable 6-minute walk distances but required a 37% longer time to complete a repeated sit-to-stand maneuver (P < .05), demonstrated a 52% slower gait speed (P < .001), and had a greater forward reach (P = .05).ConclusionOur findings suggest that older asymptomatic patients with PHPT may have significant functional deficits that can affect their safety and quality of life. Therefore, their functional capacity should be routinely evaluated, and identified deficits should be treated with appropriate interventions. (Endocr Pract. 2012;18: 450-455)     

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)     

Safety of Vitamin D Replacement in Patients with Primary Hyperparathyroidism and Concomitant Vitamin D Deficiency

ObjectiveTo evaluate the safety of vitamin D replacement in patients with vitamin D deficiency and primary hyperparathyroidism.MethodsRetrospective chart review of 35 patients from our endocrine clinic, age 22 to 89 years, diagnosed with primary hyperparathyroidism and vitamin D deficiency, and treated with either 1,000 to 2,000 international units (IU) of vitamin D daily or 50,000 IU of vitamin D weekly for 5 months. Data were collected before and after treatment on serum calcium, 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), phosphorus, alkaline phosphatase, nephrolithiasis, fractures, and osteoporosis.Results25-OH D increased significantly, from a baseline of 14.65 ± 6.57 ng/mL to 42.17 ± 12.98 ng/ mL after weekly treatment with 50,000 IU of vitamin D (P<.0001), and from 22.42 ± 5.47 ng/mL to 33.33 ± 6.39 ng/mL following daily treatment with 1,000 to 2,000 IU of vitamin D (P<.0001). Pre- and posttreatment unadjusted serum calcium remained stable in the high-dose group (10.80 ± 0.43 mg/dL vs. 10.72 ± 0.67 mg/dL; P = .47), but decreased slightly in the low-dose group (10.76 ± 0.58 mg/dL vs. 10.11 ± 0.54 mg/dL; P = .0007). After adjusting for age, sex, vitamin D, and PTH levels, the small calcium difference in the low-dose group became statistically insignificant. Treatment with either high or low doses of vitamin D did not significantly change iPTH levels. Creatinine remained stable in all patients, and no new cases of nephrolithiasis were reported.ConclusionReplacing vitamin D in mild primary hyperparathyroidism is safe, effective, and does not increase calcium to dangerous levels. (Endocr Pract. 2013;19:420-425)     

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     

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     

Increased Bone Turnover in Type 2 Diabetes Patients Randomized to Bariatric Surgery Versus Medical Therapy at 5 Years

Objective: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial.Methods: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index &lsqb;BMI], 36.5 ± 3.6 kg/m²) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% &lsqb;78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed.Results: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB (P<.001) and 61.1 ± 90% in SG (P<.001) compared to 29.8 ± 93% in IMT (P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB (P<.001) and 71 ± 69% in SG (P<.001) compared to 43.8 ± 121.1% in IMT (P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients (P<.001). Increase in CTX correlated with decreased BMI in SG patients (P = .039).Conclusion: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients.Abbreviations: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione     

Low Free (But Not Total) 25-Hydroxyvitamin D Levels in Subjects with Normocalcemic Hyperparathyroidism

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated PTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25&lsqb;OH]D) in NPHPT subjects and healthy controls.Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL, total 25(OH)D 30 to 40 ng/mL, and intact PTH (iPTH) ≥66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay.Results: Mean age of NPHPT subjects was 59.9 ± 5.4 years, and mean BMI was 28.4 ± 2.3 kg/m², which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 ± 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 ± 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 ± 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 ± 1.3 pg/mL; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P<.05) but did not correlate with levels of total 25(OH)D (r = -0.14; P>.10).Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CV = coefficient of variation; DBP = vitamin D–binding protein; iPTH = intact parathyroid hormone; NPHPT = normocalcemic primary hyperparathyroidism     

Primary Hyperparathyroidism is Associated With subclinical Peripheral Neural Alterations

ObjectiveSome case reports have suggested primary hyperparathyroidism (PHPT) and peripheral polyneuropathy (PPN) are associated; however, there are no reports of studies examining this possible relationship. The aim of this study was to evaluate peripheral nerve conduction in subjects with PHPT.MethodsThe study involved 17 patients with PHPT. Mean patient age was 60.5 ± 12.9 years, serum calcium concentration was 11.5 ± 1.0 mg/dL, and the serum parathyroid hormone (PTH) level was 315 ± 569 pg/dL. The control group comprised 17 individuals without PHPT. The mean age of controls was 60.8 ± 12.5 years and the serum calcium concentration was 9.8 ± 0.3 mg/dL. Motor and sensory nerve conduction was assessed by electroneurography (ENG).ResultsThe following ENG parameters differed significantly between the PHPT and control groups: right (R) sural sensory nerve action potential conduction velocity (52.7 ± 6.3 m/s versus 58.0 ± 8.0 m/s; P = .041); R median compound muscle action potential (CMAP) amplitude (7.4 ± 1.6 mV versus 8.9 ± 1.7 mV; P = .002); R median CMAP latency (4.3 ± 1.2 ms versus 3.6 ± 0.6 ms; P = .032); R tibial CMAP latency (4.2 ± 1.1 ms versus 3.3 ± 0.4 ms; P = .001). The neurological examination was normal in all patients.ConclusionOur data demonstrate an association between PHPT and peripheral neurological alterations, consistent with subclinical sensory-motor PPN. (Endocr Pract. 2013;19:219-225)     

Short-Term Decline in Prolactin Concentrations Can Predict Future Prolactin Normalization,Tumor Shrinkage,and Time to Remission in Men with Macroprolactinomas

Objective: To identify early follow-up measures that will predict the dynamics of prolactin (PRL) decrease and adenoma shrinkage in men harboring macroprolactinomas.Methods: A single-center historical prospective study including a consecutive group of 71 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (PRL >7 times the upper limit of normal &lsqb;ULN]) treated medically with cabergoline. Comparisons of PRL normalization rates were performed according to PRL levels achieved at 6 months, maximal adenoma shrinkage during follow-up, and other patient characteristics. Correlations were analyzed to identify characteristics of PRL suppression dynamics.Results: PRL levels after 6 months of treatment correlated positively with current PRL levels (r = 0.74; P<.001), with time to PRL normalization (r = 0.75; P<.001), and with adenoma diameter following treatment (r = 0.38; P = .01). Adenoma shrinkage depicted by first magnetic resonance imaging on treatment correlated with maximal adenoma shrinkage during follow-up (r = 0.56; P = .006). Five patients had nadir PRL levels ≥3 times the ULN (51 ng/mL) and showed slower response to cabergoline treatment, with consistently higher PRL levels compared with responding patients throughout follow-up (mean 6-month PRL levels, 519 ± 403 ng/mL versus 59 ± 118 ng/mL; P<.001).Conclusion: Six-month PRL level might serve as a surrogate marker for PRL normalization and adenoma shrinkage dynamics among men harboring macroprolactinomas.Abbreviations: CAB = cabergoline MRI = magnetic resonance imaging PRL = prolactin RMC = Rabin Medical Centre ULN = upper limit of normal     

Parathyroid Function after Total Thyroidectomy: A Randomized Clinical Trial Concerning the Influence of the Surgical Technique

Objective: Thyroidectomy impairs parathyroid function, even if it does not necessarily lead to postoperative clinical hypocalcemia. This study was prospective and evaluated the parathyroid hormone (PTH) function in nonclinically symptomatic patients after total thyroidectomy performed by two different techniques.Methods: Prospective randomized clinical trial including 269 patients undergoing classic or harmonic scalpel total thyroidectomy. Pre-operatively and at 48 hours, biochemical analysis was performed. Simultaneously, a sodium bicarbonate test (SBT) was performed.Results: Calcium and PTH were altered for both groups (P<.001). During SBT at 3 minutes after infusion, PTH rose and reached its maximum for both groups (P<.001) and then decreased at 5 minutes (P<.001 and P = .004) and at 10 minutes (P = .006 and P = .043) before returning to baseline levels. At 5 and 10 minutes of the SBT, some differences were observed between the groups. The difference in clinically obvious parathyroid dysfunction between groups was not significant, but there was a difference in the peak PTH levels after bicarbonate stimulation. Similarly, total secretion during the test, as well as total secretion for the first 10 minutes, was practically the same for the two groups. Additionally, partial subclinical postoperative hypoparathyroidism was clearly more common in the harmonic scalpel thyroidectomy group (P<.001).Conclusion: SBT demonstrated more impairment in the harmonic scalpel group, as parathyroid function was altered after thyroidectomy.Abbreviations:HSTT = harmonic scalpel total thyroidectomyPTH = parathyroid hormoneSBIT = sodium bicarbonate infusion test