Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHPT): A Useful Tool?

Primary Hyperparathyroidism (PHPT) often leads to bone loss, even in its asymptomatic presentations. Trabecular Bone Score (TBS) is a method to assess the trabecular bone structure of the spine. This study aimed to evaluate TBS measurements combined with Dual X-ray Absorptiometry (DXA) values in the search for more accurate bone fragility risk assessment among PHPT patients. From 2017 to 2019, patients diagnosed with PHPT (n = 64), before surgery, were invited to participate in this study. Bone mineral density (BMD) by DXA at the lumbar spine, total hip, femoral neck, distal third radius, and TBS were determined in patients and controls (n = 63). The vertebral fracture was defined using the Genant method in vertebral images by DXA and vertebral fracture assessment (VFA). Patients and controls did not differ in age, sex, menopausal status, or body mass index (BMI). The PHPT patients presented significantly lower BMD values than the controls in all sites evaluated. The TBS measurements were also statistically lower in PHPT patients than controls (mean TBS PHPT = 1.233 vs TBS controls = 1.280, p = 0.044). Osteoporosis was observed in 50% of PHPT patients and 26.6% of controls (p = 0.02). However, lumbar spine T-Score < -2.5 was observed only in 21.8% of PHPT patients. Vertebral fractures were detected in nine individuals (14%) from the PHPT group and four (6.3%) in the controls (p = 0.24). The TBS area under the curve (AUC) was higher than DXA AUC in all sites, for vertebral fracture assessment. The TBS AUC was significant in the PHPT group (0.75, 95% CI 0.62 - 0.88, p = 0.02) and not significant in the DXA analysis. The ROC curve showed that TBS values < 1.187 are associated with a significantly higher risk of vertebral fracture among PHPT patients (p = 0.02). The TBS used as a complement to DXA measurements is a useful tool which may better assess fragility risk among PHPT patients.

Alert for the high prevalence of vitamin D deficiency in adolescents in a large Brazilian sample.

OBJECTIVE: To estimate the prevalence of vitamin D deficiency and severe deficiency in children and adolescents, in a large Brazilian sample. METHODOLOGY: Results of 413,988 25(OH)D measurements in children and adolescents aged 0 to 18 years collected between 01/2014 and 10/2018 were obtained from the database of a Clinical Laboratory. In this population, 25 hydroxyvitamin D concentrations below 20 ng/mL are considered deficient, and below 12 ng/mL as severe deficiency. All measurements were performed by immunoassay and the results were distributed by gender, age group, seasonality, and latitude. RESULTS: The mean of 25(OH)D levels was 29.2 ng/mL with a standard deviation of 9.2 ng/mL. Of the total samples, 0.8% had a concentration < 12 ng/mL, and 12.5% of the samples had a concentration < 20 ng/mL, with a higher prevalence in females. Children under 2 years of age had the lowest prevalence. The effects of latitude and seasonality were quite evident. In samples of female adolescents from the southern region in winter, 36% of vitamin D deficiency and 5% of severe deficiency were found. CONCLUSION: In this large number of measurements of 25(OH)D in children and adolescents, 12.5% had a deficiency and 0.8% had severe deficiency. A greater deficiency was observed among adolescents, especially females, which raises questions about the need for supplementation during this period of life.

Levels of bioavailable, and free forms of 25(OH)D after supplementation with vitamin D3 in primary hyperparathyroidism.

The 25 hydroxyvitamin D [25(OH)D] is the major metabolite for ascertaining vitamin D status, which circulates bound to a specific carrier (vitamin D-binding protein - VDBP). A portion that circulates unbound vary according to the VDBP genotype. This study evaluates the behavior of different forms of 25(OH)D, before and after supplementation with 14,000 IU of vitamin D3, weekly for 12 weeks, in individuals with primary hyperparathyroidism and controls. Fifty-six patients with active primary hyperparathyroidism (PHPT) and 64 paired controls (CTRL), not taking vitamin D3 for the last three months, were enrolled. The genetic isotypes of VDBP were determined to calculate bioavailable and free 25(OH)D. A p < 0.05 was considered significant. There were no statistical differences in free, bioavailable, and total 25(OH)D levels between PHPT and CTRL groups at baseline. The distribution of VDBP haplotypes 1s/1s, 1f/1f, 1s/1f, 2/2, 1s/2, and 1f/2 was similar between groups. After supplementation, all three forms of 25(OH)D proportionally increased within each group, although the percentage increment was lower in the PHPT group (p < 0.05). Total 25(OH)D is better correlated with PTH in the PHPT group than bioavailable and free 25(OH)D (r = -0.41; p < 0.05). The concentrations of total, free, and bioavailable 25(OH)D were similar in both PHPT and CTRL groups, and all forms increased proportionally after supplementation, although this increment percentage was higher in the CTRL group, with a subsequent reduction of PTH and AP. Total 25(OH)D correlated better with PTH than other forms, suggesting no advantages in measuring free or bioavailable 25(OH)D in these situations.

Effects of ghrelin, GH-releasing peptide-6 (GHRP-6) and GHRH on GH, ACTH and cortisol release in hyperthyroidism before and after treatment.

In thyrotoxicosis GH responses to stimuli are diminished and the hypothalamic-pituitary-adrenal axis is hyperactive. There are no data on ghrelin or GHRP-6-induced GH, ACTH and cortisol release in treated hyperthyroidism. We, therefore, evaluated these responses in 10 thyrotoxic patients before treatment and in 7 of them after treatment. GHRH-induced GH release was also studied. Peak GH (µg/L; mean ± SE) values after ghrelin (22.6 ± 3.9), GHRP-6 (13.8 ± 2.3) and GHRH (4.9 ± 0.9) were lower in hyperthyroidism before treatment compared to controls (ghrelin: 67.6 ± 19.3; GHRP-6: 25.4 ± 2.7; GHRH: 12.2 ± 2.8) and did not change after 6 months of euthyroidism (ghrelin: 32.7 ± 4.7; GHRP-6: 15.6 ± 3.6; GHRH: 7.4 ± 2.3), although GH responses to all peptides increased in ~50% of the patients. In thyrotoxicosis before treatment ACTH response to ghrelin was two fold higher (107.4 ± 26.3) than those of controls (54.9 ± 10.3), although not significantly. ACTH response to GHRP-6 was similar in both groups (hyperthyroid: 44.7 ± 9.0; controls: 31.3 ± 7.9). There was a trend to a decreased ACTH response to ghrelin after 3 months of euthyroidism (35.6 ± 5.3; P = 0.052), but after 6 months this decrease was non-significant (50.7 ± 14.0). After 3 months ACTH response to GHRP-6 decreased significantly (20.4 ± 4.2), with no further changes. In hyperthyroidism before treatment, peak cortisol (µg/dL) responses to ghrelin (18.2 ± 1.2) and GHRP-6 (15.9 ± 1.4) were comparable to controls (ghrelin: 16.4 ± 1.6; GHRP-6: 13.5 ± 0.9) and no changes were seen after treatment. Our results suggest that the pathways of GH release after ghrelin/GHRP-6 and GHRH are similarly affected by thyroid hormone excess and hypothalamic mechanisms of ACTH release modulated by ghrelin/GHSs may be activated in this situation.

The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.

OBJECTIVES: The routine screening for macroprolactin of all hyperprolactinemic patients may avoid unnecessary imaging procedures and medication prescription. The study described the frequency and types of tests requested after a diagnosis of high serum prolactin concentration, and assessed whether the diagnosis of macroprolactinemia resulted in lower downstream utilization and costs compared with hyperprolactinemic patients. METHODS: A cost analysis was conducted using a decision tree to model the health-care utilization of the two groups. The database of the Fleury Medicina e Saúde provided the tests and medication of patients with a prolactin value >or=30 microg/L for a period of 6 months. RESULTS: Six hundred fifty-four of 1793 patients (36.5%) had hyperprolactinemia because of macroprolactin. The average number of tests per individual was higher (P = 0.001) in the patients with true hyperprolactinemia (3.07) than in patients with macroprolactinemia (2.51).The average cost in the hyperprolactinemic group (R$425 or euro 162) was significantly higher (P < 0.001) than the macroprolactinemic group (R$340 or euro 130), an incremental cost 25% higher. CONCLUSION: The macroprolactin screening did not completely avoid inappropriate clinical investigation or associated health-care costs. Our results demonstrate the importance of proper medical education and knowledge diffusion of the meaning of macroprolactinemia.

Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

OBJECTIVE: To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. SUBJECTS AND METHODS: 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. RESULTS: One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. CONCLUSION: PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

False diagnosis of recurrent thyroid carcinoma: the importance of testing for heterophile antibodies

SUMMARY Thyroglobulin (Tg) levels are important to predict recurrence in differentiated thyroid cancer patients. However, false-positive results can hence the request of unnecessary tests and treatments. We reported two cases of interference in thyroglobulin measurement and the workup to investigate them. Both patients achieved an excellent response to therapy after total thyroidectomy and one patient had also received radioiodine treatment. During the follow-up, Tg levels increased and there was no evidence of recurrent disease in the imaging studies. The Tg levels by the Access platform were positive but the results by Elecsys platform and LC-MS/MS were undetectable, leading to the hypothesis of heterophile antibodies (HAbs) interference. The possibility of HAbs interference must be considered when the Tg levels do not fit in the clinical picture. The measurement of Tg by another immunoassay or by LC-MS/MS may be useful in these situations.

Simultaneous quantitation of seven endogenous C-21 adrenal steroids by liquid chromatography tandem mass spectrometry in human serum.

Quantitation of endogenous steroids is important in the diagnosis of several endocrine disorders. In this study we present a new method for simultaneous quantitation of cortisol, cortisone, 11-desoxycortisol, 21-desoxycortisol, corticosterone, 17-hydroxyprogesterone and 11-desoxycorticosterone in human serum by on-line extraction and LC-MS/MS. Analytes extraction was performed on-line using a 2-position and 6-port valve equipped with a monolithic silica cartridge. After chromatographic separation of all analytes, detection was performed in the multiple reaction monitoring mode using positive atmospheric pressure chemical ionization mode. Total imprecision of the assay ranged from 5.5 to 15.5%. Comparison with immunoassays yielded coefficients of 0.893 for cortisol, 0.848 for 11-desoxycortisol and 0.924 for 17-hydroxyprogesterone. The sensitivity of this method provides meaningful data for patients within normal and elevated range and it may be useful for the diagnosis of a variety of adrenal dysfunctions.

Parathyroid responsiveness during hypocalcemia after total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism. / Responsividade paratireoideana à hipocalcemia após paratireoidectomia total com autoimplante em portadores de hiperparatireoidismo associado à doença renal crônica.

INTRODUCTION: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management. OBJECTIVE: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT. METHODS: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery. RESULTS: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693). CONCLUSION: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels.

Experience with a third-generation parathyroid hormone assay (BIO-PTH) in the diagnosis of primary hyperparathyroidism in a Brazilian population.

OBJECTIVE: To evaluate the usefulness of a third-generation PTH assay in the diagnosis of primary hyperparathyroidism (PHPT). SUBJECTS AND METHODS: Forty-one PHPT patients (4 men and 37 women) with 61.2 ± 10.9 (mean ± SD) years, were studied and had PTH levels measured with two different methods using the same immunochemiluminescent assay plataform (Elecsys 2010 System, Roche). We compared a second-generation assay (I-PTH) with a third-generation PTH assay (Bio-PTH). Two populations of 423 and 120 healthy adults with serum 25OHD levels above 25 ng/mL were used to define normal values in the I-PTH and Bio-PTH assays respectively. RESULTS: Normal PTH values based in the healthy adults population were 24.2-78.0 pg/mL for the I-PTH assay and 19.9-58.5 pg/mL for Bio-PTH assay. In PHPT patients, PTH values ranged from 67 to 553 pg/mL (median: 168 pg/mL) using the I-PTH assay and from 55 to 328 pg/mL (median: 111 pg/mL) using the Bio-PTH assay. Results obtained with the Bio-PTH assay were significantly lower (p < 0.0001, Wilcoxon). In general I-PTH and Bio-PTH showed highly significant correlation (r = 0.952, p < 0.0001). Passing-Bablok analysis gave a regression equation of Bio PTH = 13.44 + 0.59 x intact PTH. PHPT patients had 25OHD levels ranging from 4 to 36 ng/mL (mean 16.2 ng/mL); 35 subjects (85.3%) had values bellow 25 ng/mL. CONCLUSION: Our results demonstrate that both second and third generation PTH methods are strongly correlated in PHPT patients and control subjects. Lower results with Bio-PTH tests are expected in function of the assay specificity determined by the amino-terminal antibody used.

Glucocorticoid sensitivity in young healthy individuals: in vitro and in vivo studies.

CONTEXT: Interindividual variation and tissue specificity of glucocorticoid (GC) sensitivity may occur in healthy subjects. OBJECTIVE AND PARTICIPANTS: The objective of this study was to evaluate the GC sensitivity in 40 healthy young subjects (21 women and 19 men; 22-42 yr old). DESIGN: We measured salivary and plasma cortisol levels before and after the administration of 0.25, 0.5, and 1 mg dexamethasone (DEX), given at 2300 h. We also evaluated the pattern of DEX-mediated inhibition of concanavalin A-stimulated peripheral blood mononuclear cell proliferation using different DEX doses, the number of binding sites, and the affinity of the GC receptor (Kd). RESULTS: The increasing DEX doses resulted in a dose-dependent decrease in cortisol levels. The majority of the subjects (70%) suppressed cortisol with DEX doses lower than 0.5 mg, and two did not suppress even with 1 mg DEX. The binding capacity was 4.1 +/- 0.3 fmol/mg protein, and the Kd was 8.1 +/- 1.3 nm. Four individuals presented with elevated Kd. Peripheral blood mononuclear cell proliferation was inhibited by DEX in a dose-dependent pattern. The median IC50 value was 7.1 x 10(-7) mol/liter. We found 77.5% (31 of 40) concordance among all three tests; 29 subjects showed all parameters between the 10th and 90th percentiles (P10-P90), one above P90, and one below P10. These two subjects could be classified as more GC resistant or sensitive, respectively. No concordance between in vivo and in vitro tests in two subjects suggested a tissue-specific sensitivity. CONCLUSIONS: This is the first report that, taking advantage of three bioassays performed on the same subject, demonstrated a considerable interindividual variability and tissue-specific GC sensitivity in a young healthy population.

Determination of cortisol and cortisone in human saliva by a liquid chromatography-tandem mass spectrometry method.

OBJECTIVE: Salivary cortisol measurement plays an important role in the evaluation of adrenal function. Its high correlation with free serum cortisol, the easy of sampling and the limited presence of interfering steroids, generated multiple recent studies of its application, in special in the screening of adrenal hyperfunction. In this paper we present our experience in the development of a high pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for salivary cortisol and cortisone measurement. MATERIALS AND METHODS: For this study we used 181 saliva samples from our routine diagnostic laboratory. The HPLC-MS/MS method was based on a Waters Quattro Premier tandem mass spectrometer with an electrospray probe. After derivatization with hydroxylamine transitions monitored included cortisol and cortisone. An in-house radioimmunoassay (RIA) was used for salivary cortisol results comparison. RESULTS: Functional sensitivity was 24 ng/dL for cortisol and linearity from 24 to 1929 ng/dL. Saliva cortisol values obtained in the 181 samples presented a median of 52 ng/dL with 5-95% percentile of 24 and 374 ng/dL. With the RIA the results were 86, 25 and 436 ng/dL, respectively, with values for RIA being significantly higher (P<0.0001) and high correlation (r=0.8312, P<0.0001). Cortisone measured in 159 samples showed a median of 278 ng/dL, with 5-95% percentile of 100 and 1,133 ng/dL. Correlation with cortisol values was significant (r=0.820, P<0.0001). CONCLUSION: We conclude that the HPLC-MS/MS method compares favorably with the RIA for salivary cortisol measurement, with the additional possibility of concomitant cortisone measurement and the evaluation of 11ßHSD2 activity.

Autotransplant tissue selection criteria with or without stereomicroscopy in parathyroidectomy for treatment of renal hyperparathyroidism.

INTRODUCTION: Several methods have been proposed to improve operative success in renal hyperparathyroidism. OBJECTIVE: To evaluate stereomicroscopy in parathyroid tissue selection for total parathyroidectomy with autotransplantation in secondary (SHPT)/tertiary (THPT) hyperparathyroidism. METHODS: 118 renal patients underwent surgery from April of 2000 to October 2009. They were divided into two groups: G1, 66 patients operated from April of 2000 to May of 2005, with tissue selection based on macroscopic observation; G2, 52 patients operated from March of 2008 to October 2009 with stereomicroscopy for tissue selection searching for the presence of adipose cells. All surgeries were performed by the same surgeon. Patients presented SHPT (dialysis treatment) or THPT (renal-grafted). Follow-up was 12-36 months. Intra-operative parathyroid hormone (PTH) was measured in 100/118 (84.7%) patients. RESULTS: Data are presented as means. G1 included 66 patients (38 SHPT, 24 females/14 males; 40.0 years of age; 28 THPT, 14 females/14 males; 44 years of age). G2 included 52 patients (29 SHPT, 11 females/18 males; 50.7 years of age; 23 THPT, 13 females/10 males, 44.4 years of age). SHPT patients from G2 presented preoperative serum calcium higher than those of SHPT patients in G1 (p<0.05), suggesting a more severe disease. Definitive hypoparathyroidism was found in seven of 118 patients (5.9%). Graft-dependent recurrence occurred in four patients, two in each group. All occurred in dialysis patients. CONCLUSION: Stereomicroscopy in SHPT/THPT surgical treatment may be a useful tool to standardize parathyroid tissue selection.

Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

ABSTRACT Objective To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. Subjects and methods 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. Results One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. Conclusion PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

Intraoperative PTH cutoff definition to predict successful parathyroidectomy in secondary and tertiary hyperparathyroidism.

UNLABELLED: In order to improve success rates in surgery of renal hyperparathyroidism, we evaluated intraoperative PTH (IOPTH) measurement utility. METHOD: 86 patients underwent total parathyroidectomy with intramuscular presternal autotransplantation from 04/2000 to 10/2009 and were followed for 26.5 months on average (prospective cohort). Patients were divided in secondary (SHPT) and tertiary hyperparathyroidism (THPT). SHPT group was composed by patients under dialysis treatment, THPT group included renal grafted ones. IOPTH (Elecsys-PTH-Immunoassay/Roche) was measured at anesthesia induction (IOPTH-0') and 20 minutes (IOPTH-20') after parathyroidectomy. RESULTS: 80.2% (69/86) presented with 80% decrease or more in the IOPTH-20' and all were cured. In 11/86 patients (12.7%), a lower IOPTH-20' drop (70-79%) was observed, and 2 of them (18.1%) failed to cure. 6/86 (6.9%) patients presented IO-PTH-20' decrease of less than 70%: two were cured, in three a supernumerary/ectopic parathyroid was found and removed, and in one of these six patients, surgery was finished after 4-gland excision and the patient failure to cure. CONCLUSION: IOPTH-20' decrease of 80% or more compared to IOPTH-0' predicts cure in all renal patients throughout follow-up. A decay of less than 70% points to missed or hyperfunctioning supernumerary gland and is predictive of surgical failure in 66.6%. A marginal IOPTH drop of 70-79% leaves the decision whether or not surgery should be continued up to the experienced surgeon.

Parathyroid carcinoma and hungry bone syndrome.

We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.

Parathyroid hormone: an early predictor of symptomatic hypocalcemia after total thyroidectomy.

OBJECTIVE: The purpose of this study was to evaluate if the measurement of peri-operative parathyroid hormone (PTH) is able to identify patients with increased risk of developing symptoms of hypocalcemia. SUBJECTS AND METHODS: Forty patients who underwent total thyroidectomy were studied prospectively. Ionized serum calcium and PTH were measured after induction of anesthesia, one hour (PTH1) and one day after surgery (PTH24). Patients were evaluated for symptoms of hypocalcemia and treated with calcium and vitamin D supplementation as necessary. RESULTS: Symptomatic hypocalcemia developed in 16 patients. Symptomatic patients had significant lower PTH1 and greater drops in PTH levels. The selection of 12.1 ng/L as PTH1 level cutoff level divided patients with and without symptoms with 93.7% sensitivity and 91.6% specificity. The selection of 73.5% as the cutoff value for PTH decrease resulted in 91.6% sensitivity and 87.5% specificity. CONCLUSION: PTH1 levels and the drop in PTH levels are reliable predictors of developing symptomatic hypocalcemia after total thyroidectomy.

Experience with a third-generation parathyroid hormone assay (BIO-PTH) in the diagnosis of primary hyperparathyroidism in a Brazilian population

ABSTRACT Objective To evaluate the usefulness of a third-generation PTH assay in the diagnosis of primary hyperparathyroidism (PHPT). Subjects and methods Forty-one PHPT patients (4 men and 37 women) with 61.2 ± 10.9 (mean ± SD) years, were studied and had PTH levels measured with two different methods using the same immunochemiluminescent assay plataform (Elecsys 2010 System, Roche). We compared a second-generation assay (I-PTH) with a third-generation PTH assay (Bio-PTH). Two populations of 423 and 120 healthy adults with serum 25OHD levels above 25 ng/mL were used to define normal values in the I-PTH and Bio-PTH assays respectively. Results Normal PTH values based in the healthy adults population were 24.2-78.0 pg/mL for the I-PTH assay and 19.9-58.5 pg/mL for Bio-PTH assay. In PHPT patients, PTH values ranged from 67 to 553 pg/mL (median: 168 pg/mL) using the I-PTH assay and from 55 to 328 pg/mL (median: 111 pg/mL) using the Bio-PTH assay. Results obtained with the Bio-PTH assay were significantly lower (p < 0.0001, Wilcoxon). In general I-PTH and Bio-PTH showed highly significant correlation (r = 0.952, p < 0.0001). Passing–Bablok analysis gave a regression equation of Bio PTH = 13.44 + 0.59 x intact PTH. PHPT patients had 25OHD levels ranging from 4 to 36 ng/mL (mean 16.2 ng/mL); 35 subjects (85.3%) had values bellow 25 ng/mL. Conclusion Our results demonstrate that both second and third generation PTH methods are strongly correlated in PHPT patients and control subjects. Lower results with Bio-PTH tests are expected in function of the assay specificity determined by the amino-terminal antibody used.

Responsividade paratireoideana à hipocalcemia após paratireoidectomia total com autoimplante em portadores de hiperparatireoidismo associado à doença renal crônica / Parathyroid responsiveness during hypocalcemia after total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism

Resumo Introdução: O hiperparatireoidismo é uma complicação frequente da doença renal crônica (DRC). A paratireoidectomia (PTX) total com autotransplante (AT) de tecido paratireoideano é uma opção terapêutica para os indivíduos que não respondem ao manejo clínico. Objetivo: Avaliar a resposta do tecido paratireoideano enxertado durante hipocalcemia induzida em pacientes portadores de DRC submetidos à PTX total com AT. Métodos: Dezoito pacientes portadores de hiperparatiroidismo associado à DRC foram submetidos à PTX total com AT de tecido paratireoideano selecionado por estereomicroscopia entre Abril e Outubro de 2008 em nosso serviço. Onze indivíduos (oito com transplante renal funcionante, 2 em diálise peritoneal e 1 em hemodiálise) apresentavam boa condição clínica e foram elegíveis para o teste. Induziu-se hipocalcemia por infusão de bicarbonato de sódio em 5 controles normais e nos pacientes 6-12 meses após a PTX. Resultados: A hipocalcemia determinou um aumento importante dos níveis de PTH intacto (iPTH) no grupo controle 4 minutos após a infusão de bicarbonato. Nos pacientes, houve uma redução significativa do cálcio ionizado [de 1,17 ± 0,12 para 1,09 ± 0,11 (media ± EP) mmol/L] no 4º minuto (p < 0,001) ilustrando o nadir do teste. No 10º minuto não houve elevação do cálcio ionizado comparado ao 4º minuto (p = 0,451). Os níveis de iPTH foram de 34,8 ± 18,6 para 34,1 ± 18,8 pg/mL (valor basal semelhante ao 4º minuto p = 0,087) e se mantiveram no 10º minuto (33,3 ± 19,6 pg/mL p = 0,693). Conclusão: Em pacientes portadores de DRC testados 6-12 meses depois da cirurgia, o enxerto de tecido paratireoideano revelou incapacidade de resposta à hipocalcemia induzida por bicarbonato sem mudança dos níveis de iPTH.

Abstract Introduction: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management. Objective: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT. Methods: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery. Results: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693). Conclusion: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels.