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 [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     

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     

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)     

Effect of Post-Surgical Rai Therapy on Parathyroid Function in Patients with Differentiated Thyroid Cancer

Objective: Radiotherapy with radioactive iodine (RAI) has become a common treatment for postsurgical differentiated thyroid carcinoma (DTC). The objective of this study was to determine the effect of RAI therapy following surgery on the function of the parathyroid glands in DTC patients.Methods: A total of 81 DTC patients who received RAI therapy after surgery were enrolled in the study. The size of the residual thyroid was detected by technetium-99m (^99mTc)-pertechnetate thyroid scan (^99mTc thyroid scan) before RAI therapy. The iodine uptake ability of residual thyroid was evaluated by iodine-131 (¹³¹I) whole-body scan (WBS). All patients were treated with an activity of 3.7 GBq (100 mCi) ¹³¹I. Parathyroid hormone (PTH), serum calcium, phosphorus, and magnesium were evaluated at 1 day before treatment, and at 1 month and 3 months after treatment.Results: The results show that there was no statistically significant difference in blood PTH level observed (P>.05) between 3 time points (pre-treatment, 1 month post-treatment and 3 months post-treatment). The serum calcium and phosphorus did not change significantly (P>.05), but serum magnesium level was elevated after treatment (P<.05). There were no significant differences between PTH changes and sex, age, scores of ^99mTc thyroid scan, scores of ¹³¹I WBS, Tumor (T) stage, and Node (N) stage.Conclusion: RAI therapy following surgery did not significantly affect parathyroid function in DTC patients.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid carcinoma; FT3 = free triiodothyronine; FT4 = free thyroxine; 131I = iodine-131; PTH = parathyroid hormone; RAI = radioiodine; 99mTc = Technetium-99m; TG = thyroglobulin; TNM = Tumor Node Metastasis; TSH = thyroid-stimulating hormone; WBS = whole-body scan     

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     

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     

Pre-Operative Localization of Parathyroid Adenoma: Performance of 4D Mri Parathyroid Protocol

Objective: Accurate pre-operative image localization is critical in the selection of minimally invasive parathyroidectomy as a surgical treatment approach in patients with primary hyperparathyroidism (PHPT). Sestamibi scan, ultrasound, computed tomography, and conventional magnetic resonance imaging (MRI) has varying accuracy in localizing parathyroid adenoma (PTA). Our group has previously shown that four-dimensional (4D) MRI is more accurate than conventional imaging in identifying single adenomas. In this study, we set out to determine if it is possible to accurately localize the quadrant of the adenoma using 4D MRI.Methods: We analyzed and matched the quadrants of PTA identified by pre-operative 4D-MRI with the operative findings during parathyroidectomy for PHPT at our institution during the study period. All resections were confirmed to be successful with an adequate decrease in intraoperative parathyroid hormone as defined by the Miami criterion.Results: A total of 26 patients with PHPT underwent pre-operative localization with the 4D MRI parathyroid protocol. Fourteen patients had true single-gland adenoma (SGA) and 12 patients had multi-gland disease (MGD). 4D MRI accurately identified all the SGA. Using this method, we were also able to localize the adenoma in the correct quadrant in 14 of the 18 patients with SGA. All 3 double adenomas were accurately identified using 4D MRI; however, MGD was only accurately identified 67% of the time. The 4D MRI had an overall 85% accuracy in distinguishing SGA from MGD.Conclusion: 4D MRI accurately identified single and double adenomas in their respective quadrants. However, accuracy was lower with MGD.Abbreviations: BNE = bilateral neck exploration; CT = computed tomography; IOPTH = intra-operative parathyroid hormone; MGD = multi-gland disease; MIBI = sestamibi; MIP = minimally invasive parathyroidectomy; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PTA = parathyroid adenoma; PTH = parathyroid hormone; SGA = single-gland adenoma; SPECT = single photon emission computed tomography; 4D = four-dimensional     

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     

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     

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)     

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)     

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)     

The Detection of Preoperative Parathyroid Lesions: The Success of Ultrasonography,Technetium-99m Methoxyisobutylisonitrile Parathyroid Scintigraphy,and Single-Photon Emission Computed Tomography–Computed Tomography

ObjectiveWe aimed to find and compare the efficacy of ultrasonography (US), technetium-99m methoxyisobutylisonitrile parathyroid scintigraphy (MIBI-S), and single-photon emission computed tomography–computed tomography (SPECT-CT) in detecting the localization of parathyroid adenomas in patients with primary hyperparathyroidism.MethodsIn total, 348 patients were included in this study. Preoperative parathyroid imaging with US, MIBI-S, and SPECT-CT was evaluated and compared with operative findings. The results of the imaging methods were compared with pathology and operation reports.ResultsIn 318 patients (91.3%), one of the imaging methods was able to localize the lesion correctly. US detected the localization of the parathyroid lesions correctly in 268 patients (77%), whereas SPECT-CT and MIBI-S were correct in 254 (73%) and 209 (60%) patients, respectively. There was a statistically significant relationship between the parathyroid hormone (PTH) level and 3 imaging methods’ success rates (P < .05). The PTH cut-off value, which best determined the correct localization, was 152.5 pg/mL for US, 143 pg/mL for MIBI-S, and 143 pg/mL for SPECT-CT. It was observed that the correct localization rate for parathyroid lesions increased with higher PTH levels.ConclusionIn our study population, US was more successful, in most cases, than other imaging methods in localizing parathyroid lesions but SPECT-CT was more accurate in localizing mediastinal lesions. In addition, it was found that preoperative PTH levels affect the accuracy of imaging methods.     

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     

The Clinical Presentation of Primary Hyperparathyroidism: A Southern European Perspective Over the Last 2 Decades

Objective: The clinical presentation of primary hyperparathyroidism (PHPT) has changed widely in developed countries in the last few decades. We evaluated its variations in our series over a 20-year period (i.e., 1997–2016).Methods: A retrospective survey was conducted in our series of 364 well-characterized consecutive patients, arbitrarily divided into 4 consecutive 5-year periods at diagnosis.Results: In the overall series, only estimated glomerular function (eGFR) and urinary calcium (UCa) showed a significant upward trend (P = .032 and .039, respectively), whereas demographic and clinical characteristics were stable. The UCa upward trend was also confirmed for the subgroup of symptomatic patients (P = .013). No difference was observed in the demographic, clinical, or biochemical characteristics of asymptomatic patients or in the fraction of patients meeting surgical criteria.Conclusion: The clinical presentation of PHPT was stable over 20 years in our large series.Abbreviations: Ca = calcium; eGFR = estimated glomerular filtration rate; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; UCa = urinary calcium     

Imaging Localization and Surgical Approach in the Management of Ectopic Parathyroid Adenomas

Objective: (1) Review the anatomy and epidemiology of ectopic parathyroid adenomas (EPAs), (2) summarize the role of relevant imaging modalities in the localization of EPAs, and (3) characterize surgical approaches for various ectopic locations.Methods: Literature review of published English-language articles from 1995 through August 2017.Results: Summary of the literature indicates that the prevalence of EPA is approximately 20% in unexplored patients with primary hyperparathyroidism, but it is as high as 66% in re-operative patients. EPAs may be located anywhere from the carotid bifurcation to the aorto-pulmonary window. Ultrasound has limited accuracy in identifying EPAs except near the thyroid and thyrothymic ligament and requires expert experience from the user. Among dual-phase ^99mTc sestamibi scintigraphy techniques, hybrid imaging with both single-photon emission computed tomography (SPECT) and computed tomography (CT) (SPECT/CT) is superior to planar scintigraphy or SPECT alone at localizing EPAs. Four-dimensional computed tomography (4DCT) precisely delineates important anatomic relationships and is highly sensitive in localizing EPAs. Although 4DCT requires radiation, intravenous iodinated contrast, and reader experience, it is well-equipped to detect lesions at various ectopic sites and guide the surgical approach. EPAs frequently require alternative surgical approaches. Re-operative parathyroidectomy may be attempted in patients having previously undergone bilateral neck exploration by an experienced surgeon once the lesion is colocalized by 2 repeat imaging modalities. Removal of nonlocalized disease requires a careful and systematic exploration of superior and inferior gland locations.Conclusion: EPAs pose challenges during both localization and surgical removal. High-volume experience and multidisciplinary care are necessary for optimal outcomes.Abbreviations: CT = computed tomography; 4DCT = 4-dimensional CT; EPA = ectopic parathyroid adenoma; EPG = ectopic parathyroid gland; PHPT = primary hyperparathyroidism; RLN = recurrent laryngeal nerve; SPECT = single-photon emission computed tomography; TE = tracheo-esophageal     

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)     

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     

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.