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)     

Calcium,Parathyroid Hormone,and Vitamin D in Patients with Primary Hyperparathyroidism: Normograms Developed from 10000 Cases

ObjectiveTo better define the typical and atypical biochemical profiles of patients with surgically proven primary hyperparathyroidism.MethodsIn this single-center, prospectively conducted study of consecutive patients with surgically proven primary hyperparathyroidism over a 7-year period, we analyzed serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations.ResultsA total of 10 000 patients were included, and more than 210 000 calcium, parathyroid hormone, and 25-hydroxyvitamin D values were evaluated. Both calcium and parathyroid hormone levels demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/mL. The average highest calcium and parathyroid hormone concentrations were 11.4 ± 0.7 mg/dL and 115.3 ± 50 pg/mL, respectively. At least 1 calcium value of 11.0 mg/dL was seen in 87% of patients, but only 21% had 1 or more calcium value above 11.5 mg/dL. Only 7% had a single serum calcium level reaching 12.0 mg/dL. Normocalcemic hyperparathyroidism was seen in just under 3% of patients who had identical findings at surgery. An average parathyroid hormone concentration less than 65 pg/mL was seen in 16%, with 10% of patients who had no high parathyroid hormone values. The average 25-hydroxyvitamin D concentration was 22.4 ± 9 ng/mL, with levels decreasing as calcium levels increased (P < .001); 36% had 25-hydroxyvitamin D levels below 20 ng/mL.ConclusionsPatients with PHPT present with a number of distinct biochemical profiles, but as a group, they present with a near-normal Gaussian distribution of both calcium and parathyroid hormone levels. Either serum calcium or parathyroid hormone remained normal in 13% of patients, yet the findings at surgery are similar to those of patients with elevated calcium or parathyroid hormone. Low 25-hydroxyvitamin D is an expected finding in patients with PHPT, decreasing as serum calcium levels increase. (Endocr Pract. 2011;17:384-394)     

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry

ObjectiveTo describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM).MethodsWe conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index–matched patients with PHPT without T2DM (in 1:2 ratio).ResultsOf the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06).ConclusionThe prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.     

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)     

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)     

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     

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     

A Retrospective Study of Ultrasonography in the Investigation of Primary Hyperparathyroidism: A New Perspective for Ultrasound Echogenicity Features of Parathyroid Nodules

ObjectiveTo identify and understand parathyroid lesions of patients with primary hyperparathyroidism (PHPT) more accurately under ultrasound.MethodsThis retrospective study involved 423 adult patients with PHPT with a single parathyroid nodule and positive parathyroid ultrasonography between 2018 and 2019. The clinical characteristics of the study patients and histopathologic sections were reviewed.ResultsAccording to the main grayscale echogenicity features of parathyroid nodules, 423 cases were divided into groups: iso-hyperechogenicity solid (61/423), hypoechogenicity solid (304/423), and mixed-echogenicity cyst-solid (58/423) groups. Comparison among the 3 groups showed that the iso-hyperechogenicity group included more asymptomatic patients with PHPT and fewer patients with severe symptoms like bone fractures (P < .05). The mixed-echogenicity group showed higher median serum parathyroid hormone (PTH) and serum calcium levels and larger lesion sizes (P < .05), and the iso-hyperechogenicity group showed the lowest median serum PTH level. No difference in lesion size was noted between the 2 solid groups, but the median serum PTH level in the hypoechogenicity group was higher than that in the iso-hyperechogenicity group (P < .05). According to histopathology, the hypoechogenic area of the samples may contain more functional components (chief cells), whereas the iso-hyperechogenic area has more nonfunctional components (eg, lipocytes and connective tissues).ConclusionThe PHPT nodules distinguished by ultrasound echogenicity features showed different histopathologic components, reflected by different clinical characteristics of the patients with PHPT.     

Bone Marrow Uptake in Parathyroid Scintigraphy is A Consequence of Extremely High Parathyroid Hormone Levels

ObjectiveWe retrospectively evaluated patients with end-stage renal disease (ESRD) who were referred to our department for parathyroid scintigraphy. The aim of this study was to investigate the causes of bone marrow uptake observed on parathyroid scintigraphy.MethodsWe included 18 ESRD patients (10 F, 8 M; mean, 52 ± 13 years old; range, 45-59) in the study. The disease duration of the patients was mean 7.7 ± 4.7 years. The patients’ mean plasma calcium and parathormone (PTH) levels were 9.7 ± 1.4 mg/dL and 1,553.3 ± 691.7 pg/mL, respectively. Dual-phase technetium-99m 2-methoxyisobutyl-isonitrile (Tc-99m MIBI) parathyroid imaging and, if necessary, additional Tc-99m pertechnetate scintigraphy were performed. Quantification of the planar early phase parathyroid images was performed for various regions (sternum, humerus, ribs) with the same size rectangular region of interest (ROI, 176 × 176 pixels). Average counts were compared with paired samples Student’s t tests, and P <.05 was considered statistically significant.ResultsTc-99m MIBI parathyroid imaging revealed parathyroid hyperplasia, adenoma, and ectopic adenoma in 7, 3, and 2 patients, respectively. The other 7 patients had normal scintigraphy results with regard to parathyroid pathologies. Bone marrow uptake in the sternum, ribs, and humerus was observed in 6 patients. The difference between the average quantitative value obtained from the ROIs drawn on the sternum and humerus was also statistically significant compared to patients without bone marrow uptake (P<.05). All 6 patients’ exhibited extremely high PTH levels (>2,000 pg/mL; mean, 2,413.7 ± 150 pg/mL) compared to the other 12 patients (mean, 1,342.8 ± 249 pg/mL).ConclusionOur results show that bone marrow uptake on parathyroid scintigraphy is a consequence of extremely high PTH levels in ESRD patients; no further analysis is required. (Endocr Pract. 2013;19:202-205)     

Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients

ObjectiveCalcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration.MethodsTwo thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H).ResultsThere were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm³, DA = 1.43 cm³, and H = 1.27 cm³; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001).ConclusionThis is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.     

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)     

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)     

Role of Imaging Tests for Preoperative Location of Pathologic Parathyroid Tissue in Patients with Primary Hyperparathyroidism

Objective: Primary hyperparathyroidism (PHPT) can be cured by parathyroidectomy, and the preoperative location of enlarged pathologic parathyroid glands is determined by imaging studies, especially cervical ultrasonography and scintigraphy scanning. The aim of this retrospective study was to evaluate the use of preoperative cervical ultrasonography and/or parathyroid scintigraphy in locating pathologic parathyroid tissue in a group of patients with PHPT followed in the same endocrine center.Methods: We examined the records of 61 patients who had undergone parathyroidectomy for PHPT following ^99mTc-sestamibi scintigraphy scan and/or cervical ultrasonography. Scintigraphic and ultrasonographic findings were compared to histopathologic results of the surgical specimens.Results: Ultrasonography detected enlarged parathyroid glands in 87% (48/55) of patients with PHPT and ^99mTc-sestamibi scintigraphy in 79% (37/47) of the cases. Ultrasonography was able to correctly predict the surgical findings in 75% (41/55) of patients and scintigraphy in 72% (34/47). Of 7 patients who had negative ultrasonography, scintigraphy correctly predicted the surgical results in 2 (29%). Of 10 patients who had negative scintigraphy, ultrasonography correctly predicted the surgical results in 4 (40%). When we analyzed only patients with solitary eutopic parathyroid adenomas, the predictive positive values of ultrasonography and scintigraphy were 90% and 86%, respectively.Conclusion: Cervical ultrasonography had a higher likelihood of a correct positive test and a greater predictive positive value for solitary adenoma compared to ^99mTc-sestamibi and should be used as the first diagnostic tool for preoperative localization of affected parathyroid glands in PHPT.Abbreviations:Ca = calciumIEDE = Instituto Estadual de Diabetes e Endocrinologia Luiz CapriglionePHPT = primary hyperparathyroidismPTH = parathyroid hormone     

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)     

Effects of Successful Parathyroidectomy on Metabolic Cardiovascular Risk Factors In Patients With Severe Primary Hyperparathyroidism

ObjectiveTo evaluate the effect of parathyroidectomy on metabolic abnormalities associated with cardiovascular disease in patients with primary hyperparathyroidism (PHPT).MethodsThirty-four patients with PHPT (aged 51.0 ± 11.8 years, mean ± standard deviation) underwent assessment before and 1 year after successful parathyroidectomy. A control group of 42 normocalcemic healthy subjects, matched for age and body mass index, was also examined at baseline. We measured serum lipids, glucose, insulin, uric acid, calcium, parathyroid hormone, C-reactive protein, and bone density. Insulin resistance index was evaluated by homeostasis model assessment, and the presence of metabolic syndrome was determined. Because of multiple tests, the level of statistical significance was set at .01.ResultsAfter parathyroidectomy, there was a decrease in diastolic blood pressure (P < .02) and in serum concentrations of uric acid (P < .04) and insulin (P < .009). No difference was observed in rates of metabolic syndrome in patients before and 1 year after parathyroidectomy (23.5% versus 17.6%; P > .46). Insulin resistance index values were also unchanged from before to after parathyroidectomy (1.3 ± 0.9 and 1.1 ± 0.9, respectively; P > .68). A substantial increase in spine bone density (5%; P < .05) was notedpostoperatively. Multivariate logistic regression analysis, after adjustment for age and body mass index, revealed that parathyroidectomy did not lead to a significant decrease in likelihood of cardiovascular risk—odds ratio (OR), 1.82; 95% confidence interval (CI), 0.53 to 6.21 (P > .34) for the metabolic syndrome and OR, 0.82; 95% CI, 0.17 to 3.88 (P > .8) for the insulin resistance index.ConclusionIn this study, surgical treatment had no beneficial effect on cardiovascular risk, as assessed by the metabolic syndrome and insulin resistance markers in patients with PHPT 1 year after parathyroidectomy.(Endocr Pract. 2011;17:584-590)     

Assay of Free Thyroxine and Free Triiodothyronine in Fine-Needle Aspiration of Thyroid Nodules: a Useful and Low-Cost Assessment

ObjectiveTo evaluate whether analysis of thyroid hormones in fine-needle aspiration (FNA) of thyroid nodules can provide information about the functional status and the nature of the nodules.MethodsWe studied 4 groups of patients: group 1, 17 patients with autonomous hyperfunctioning thyroid nodules; group 2, 52 patients with cold nonfunctioning thyroid nodules; group 3, 12 patients with malignant thyroid nodules; and group 4 (control group), 10 patients with nonthyroid nodular lesions (enlarged parathyroid glands or lymph nodes). The assay of thyroid hormones was performed in FNA after the washing of needles and, with patient consent, also in normal thyroid parenchyma.ResultsThe free thyroxine (FT₄) and free triiodothyronine (FT₃) values were remarkably high in group 1 (mean, 5.5 ± 0.53 ng/dL and 27.6 ± 3.1 pg/mL, respectively; P < 0.05 versus group 2 and group 4, the control group). The levels of FT₄ and FT₃ were very low in group 3 (< 0.2 ng/dL and < 1.0 pg/mL, respectively; P < 0.05 versus group 2). Thyroglobulin values in FNA specimens were much higher than the normal range in human serum, but no significant differences were found between the various groups. The control group had low levels of FT₄ and FT₃ (< 0.2 ng/dL and < 1.0 pg/mL, respectively) in conjunction with low levels of thyroglobulin, whereas parathyroid hormone levels were high in parathyroid nodules.ConclusionThese results show that assay of FT₄ and FT₃ in FNA can yield information about the functional status of thyroid nodules and, indirectly, about the nature of nodules. In this era of sophisticated new molecular markers in FNA cytology, this low-cost diagnostic method can be readily performed in every laboratory. (Endocr Pract. 2004;10:311-316)     

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     

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)     

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     

Diurnal Glucose Profiles Using Continuous Glucose Monitoring to Identify the Glucose-Lowering Characteristics of Colesevelam HCL (WELCHOL)

ObjectiveThe study's purpose was to identify the antihyperglycemic affects of colesevelam-HCl (C-HCl) by characterizing the diurnal and postprandial glucose patterns in type 2 diabetic subjects treated concomitantly with metformin, sulfonylurea, or a combination of metformin/ sulfonylurea. A secondary aim was to determine whether C-HCl significantly increased the risk of hypoglycemia.MethodsA prospective, randomized, double-blind, placebo-controlled, crossover study employing continuous glucose monitoring (CGM) with ambulatory glucose profile (AGP) analysis was undertaken. Fifteen males and 6 females, age 60 ± 8 years, treated with metformin (n = 8), sulfonylurea (n = 2), or combination (n = 11) participated.ResultsTreatment with C-HCl led to reductions in glycated hemoglobin (HbAlc) (7.5 ± 0.3 to 7.0 ± 0.4% P<.0001), LDL (90.9 ± 18.6 to 68.9 ± 15.2 mg/dL, P<.0007) and total cholesterol (169.2 ± 24.4 to 147.8 ± 21.5 mg/dL, P<.001). Significantly lower normalized diurnal (21 mg/dL/hour, P = .0006), nocturnal (19 mg/dL/hour, P = .0005), and daytime (22 mg/dL/hour, P = .0008) glucose exposure was detected immediately upon C-HCl administration. Additionally, there was a significant (P<.004) decline in postprandial glucose excursions (averaging 15% or -36 mg/dL/hour) pronounced at dinner following C-HCl administration. There was a nonsignificant increase in the incidence of hypoglycemia (0.4-1%), with no difference due to antihyperglycemic medications.ConclusionsAGP analysis of CGM visually and quantitatively showed immediate and midterm impacts of C-HCl on basal and postprandial glucose patterns. This suggests a multifactorial glucose-lowering mechanism for C-HCl affecting both meal-related and basal glucose levels. (Endocr Pract. 2013;19:275-283)