Elevated bone turnover markers predict bone mineral density accrual in adolescents with 21-hydroxylase deficiency.

CONTEXT: Prognostic biomarkers for monitoring bone health in adolescents with 21-hydroxylase deficiency (21OHD) are needed. OBJECTIVES: To assess associations between concentrations of baseline bone turnover markers (BTMs) including osteocalcin (OC) and type-I collagen C-terminal telopeptide (CTX) and changes in lumbar spine bone mineral density (LSBMD) in adolescents with classic 21OHD. DESIGNS AND PATIENTS: A retrospective-prospective study of 33 adolescents with classic 21OHD who had baseline data for LSBMD, bone age (BA), and BTM concentrations. METHODS: BTM concentrations were converted into z-scores according to BA. We measured LSBMD at the follow-up study visit and calculated the annual percentage change in LSBMD (%∆LSBMD). RESULTS: At baseline, participants (55% female, 79% Tanner 5) had mean (±SD) age of 14.6 ± 3.6 years, BA 16.7 ± 2.9 years, and average glucocorticoid (GC) dose 17.3 ± 5.6 mg/m2 /day of hydrocortisone equivalent. The mean follow-up duration was 14.4 ± 5.6 months. Median (Q1-Q3) %∆LSBMD was 3.6% (0-8.5)/year. %∆LSBMD was similar among genders or 21OHD subtypes. Prednisolone versus hydrocortisone replacement resulted in lower %∆LSBMD (p = .004). %∆LSBMD was increased across tertiles of CTX z-score (p = .014). %∆LSBMD correlated negatively with GC dose (p = .01) and positively with CTX and OC z-scores (p < .01). In regression analyses, only CTX z-score positively associated with %∆LSBMD (p = .003), adjusting for sex, BA, body mass index, testosterone, 25-hydroxyvitamin D, and GC type and dose. CONCLUSIONS: Higher GC dose and the use of prednisolone were associated with decreased LSBMD accrual in adolescents with 21OHD. CTX z-score independently associated with LSBMD accrual, suggesting its potential for prognostic bone biomarker.

Bone Mineral Density and Dickkopf-1 in Adolescents with Non-Deletional Hemoglobin H Disease.

BACKGROUND: Low bone mineral density (BMD) is prevalent in individuals with ß-thalassemia and is associated with increased circulating dickkopf-1 concentration. These data are limited in α-thalassemia. Therefore, we aimed to determine the prevalence of low BMD and the association between BMD and serum dickkopf-1 in adolescents with non-deletional hemoglobin H disease, a form of α-thalassemia whose severity is comparable to ß-thalassemia intermedia. METHODOLOGY: The lumbar spine and total body BMD were measured and converted into height-adjusted z-scores. Low BMD was defined as BMD z-score ≤ -2. Participant blood was drawn for measurement of dickkopf-1 and bone turnover marker concentrations. RESULTS: Thirty-seven participants with non-deletional hemoglobin H disease (59% female, mean age 14.6 ± 3.2 years, 86% Tanner stage ≥2, 95% regularly transfused, 16% taking prednisolone) were included. Over one year prior to the study, mean average pretransfusion hemoglobin, ferritin and 25-hydroxyvitamin D concentrations were 8.8 ± 1.0 g/dL, and 958 ± 513 and 26 ± 6 ng/mL, respectively. When participants taking prednisolone were excluded, the prevalence of low BMD at the lumbar spine and total body was 42% and 17%, respectively. BMD at both sites was correlated positively with body mass index z-score, and negatively with dickkopf-1 (all p-values <0.05). There were no correlations among dickkopf-1, 25-hydroxyvitamin D, osteocalcin and C-telopeptide of type-I collagen. Multiple regression analysis showed dickkopf-1 inversely associated with total body BMD z-score adjusting for sex, bone age, body mass index, pre-transfusion hemoglobin, 25-hydroxyvitamin D, history of delayed puberty, type of iron chelator and prednisolone use (p-value = 0.009). CONCLUSIONS: We demonstrated a high prevalence of low BMD in adolescents with non-deletional hemoglobin H disease. Moreover, dickkopf-1 inversely associated with total body BMD suggesting it may serve as a bone biomarker in this patient population.

Single Photon Emission Computed Tomography without and with Hybrid Computed Tomography in Mandibular Condylar Hyperplasia.

Objective: Bone scintigraphy (BS) has been the mainstay in evaluating patients with mandibular condylar hyperplasia (CH). Both planar BS and single photon emission computed tomography (SPECT) have been used to determine cessation of condylar hyperactivity before corrective surgery. The present study aimed to examine the utility of the relatively new single photon emission computed tomography/computed tomography (SPECT/CT) technique for evaluation of CH. Material and Method: Sixty-one mandibular Tc-99m methylene diphosphonate bone SPECT/CT studies were reviewed. Images were analyzed without and with fusion with anatomical CT. Condylar uptake were quantified and differences in uptake between the right and left condyles were determined by both maximum uptake and average uptake in the region of interes (ROI). Differences exceeding 10 percentage points indicated condylar hyperactivity. Results: SPECT and SPECT/CT showed positivity in 34 and 31 examinations, respectively. Agreement between the two modalities was high, but was not perfect. SPECT was found to be more reproducible than SPECT/CT. Quantification using maximum ROI counts was more reproducible than using average ROI counts. Conclusion: No evidence was found to indicate superiority of SPECT/CT over simple SPECT for evaluation of condylar hyperactivity in CH, as demonstrated by the lower intra-modality reproducibility and a trend towards lower sensitivity for detection of hyperactive condyles. Utilization of SPECT alone would further benefit in terms of reduction of patient radiation exposure which is a concern, especially in younger patients such as those with CH. When using quantification, maximum ROI counts should be used over average ROI counts.

Thai National Guideline for Nuclear Medicine Investigations in Epilepsy.

Epilepsy is a disorder of the brain, which is characterized by recurrent epileptic seizures. These patients are generally treated with antiepileptic drugs. However, more than 30% of the patients become medically intractable and undergo a series of investigations to define candidates for epilepsy surgery. Nuclear Medicine studies using Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) radiopharmaceuticals are among the investigations used for this purpose. Since available guidelines for the investigation of surgical candidates are not up-to-date, The Nuclear Medicine Society of Thailand, The Neurological Society of Thailand, The Royal College of Neurological Surgeons of Thailand, and The Thai Medical Physicist Society has collaborated to develop this Thai national guideline for Nuclear Medicine study in epilepsy. The guideline focuses on the use of brain perfusion SPECT and F-18 fluorodeoxyglucose PET (FDG-PET), the mainly used methods in day-to-day practice. This guideline aims for effective use of Nuclear Medicine investigations by referring physicians e.g. epileptologists and neurologists, radiologists, nuclear medicine physicians, medical physicists, nuclear medicine technologists and technicians.

An impact of microscopic positive margin on incomplete response after I-131 treatment in differentiated thyroid cancer.

OBJECTIVE: To find an impact of microscopic positive margin on incomplete response after initial I-131 therapy in differentiated thyroid cancer. METHODS: We retrospectively recruited patients with differentiated thyroid cancer who underwent total thyroidectomy and received the first dose of radioiodine during January 2014-February 2018. Patients with grossly incomplete tumor resection or distant metastasis at the time of radioiodine therapy were excluded. Thyroid specimens were re-evaluated by one pathologist who was blinded to clinical information to determine microscopic margin status. Treatment response was evaluated at 6-12 months after therapy and was categorized according to the 2015 American Thyroid Association guidelines. Univariable and multivariable analyses were used to find an association between microscopic positive margin and incomplete response. RESULTS: A total of 101 patients (78 females; mean age 50.3 years) were enrolled. Ninety-four patients (93.1%) had papillary thyroid carcinoma. Microscopic positive margin was found in 27 patients (26.7%). After the median follow-up time of 10.3 months, incomplete response was observed in 13 patients (48.5%) and 17 patients (23.0%) with positive and negative margins, respectively. Multivariable analysis showed a significant association between microscopic positive margin and incomplete response after adjusting for tumor size, ETE, and cervical lymph node metastasis with adjusted odds ratio of 3.04 (95% CI 1.05-8.75, p value = 0.04). Moreover, after adding pre-ablative Tg as a covariate in 69 patients with negative TgAb, positive margin had a trend toward being associated with incomplete response with adjusted odds ratio of 3.43 (95% CI 0.73-16.07, p value = 0.118). CONCLUSIONS: Microscopic positive margin was found to be significantly associated with incomplete response after I-131 therapy in patients with differentiated thyroid cancer after adjusting for tumor size, ETE, and cervical lymph node metastasis and also had a trend toward being associated with incomplete response after adjusting for pre-ablative Tg.

Imaging features of bone metastases from cholangiocarcinoma.

PURPOSE: Cholangiocarcinoma (CCA) is the second most common primary malignant hepatic tumor originating from bile duct epithelia. Bone metastasis is uncommon and less documented. The aim of this study was to characterize the imaging features of bone metastasis from CCA. METHODS: A retrospective descriptive imaging characteristics in 199 patients (1465 lesions) diagnosed as CCA with bone metastasis were evaluated based on plain radiography, computed tomography (CT), magnetic resonance imaging (MRI) and Tc-99 m methylene diphosphonate bone scan. RESULTS: The common vertebral metastatic sites were lumbar spines (94 [47.2 %], 95 %CI 40.1-54.4), upper thoracic spines (89 patients [44.7 %], 95 % CI 37.7-51.9), and lower thoracic spines (80 [40.2 %], 95 % CI 33.3-47.4). On plain radiograph, most of lesions had osteolytic pattern (68 %) with pedicular destruction (45.3 %) whereas on CT had mixed osteolytic and osteosclerotic destruction (40.8 %). The common non-vertebral metastatic sites were ribs and pelvis (80 patients [40.2 %], 95 % CI 33.3-47.4 and 60 [30.2 %], 95 % CI 23.9-37). On plain radiograph, in the long bones, usually had permeative destruction (58.9 %), whereas on CT showed mixed osteolytic and osteosclerotic (34.6 %). On bone scan, increased-uptake was the common pattern, found in the vertebral and non-vertebral sites (93.6 % and 92.4 %). CONCLUSIONS: Bone metastasis from CCA usually occurred in the axial skeleton. The common patterns of destruction were osteolytic or mixed osteolytic and osteosclerotic. Periosteal reaction was scant in the appendicular long bones. On bone scan commonly had increased-uptake.

Detection of Lower Limb Deep Vein Thrombosis: Comparison between Radionuclide Venography and Venous Ultrasonography.

Deep vein thrombosis (DVT) is a serious medical condition that needs prompt diagnosis and treatment. The invasive gold standard contrast venography has largely been replaced by venous ultrasonography which is currently the imaging modality of choice for DVT diagnosis. Radionuclide venography (RNV) is an alternative test for DVT, but a few studies have directly compared RNV with venous ultrasonography. This study aims to determine the agreement between RNV and venous ultrasonography for diagnosis of DVT and to determine the predictive value of different RNV findings for the prediction of DVT as detected by venous ultrasonography. Imaging results from patients who underwent both RNV and venous ultrasonography for suspected DVT no more than 1 week apart were reviewed. Results from both modalities were compared to determine inter-modality agreement. A total of 121 venous segments from 102 lower limbs of 75 patients could be compared. The prevalence of DVT as detected by venous ultrasonography was 39%. RNV and venous ultrasonography had moderate agreement (73.6% agreement, κ =0.48, P < 0.0001). The absence of radiotracer activity from a deep venous segment had a positive predictive value (PPV) of 100% for DVT. Other findings such as isolated great saphenous vein activity had a lower PPV. The negative predictive value of RNV is 97.5% with only one patient out of forty with normal RNV found to have DVT by venous ultrasonography, which suggests that DVT can virtually be excluded in patients with normal RNV.

Value of SPECT/CT in Diagnostic I-131 MIBG Scintigraphy in Patients with Neuroblastoma.

PURPOSE: Diagnostic I-131 MIBG scintigraphy is an important imaging modality for evaluation of patients with neuroblastoma (NB) especially in centers where I-123 MIBG is not available. Single photon emission computed tomography/computed tomography (SPECT/CT) could potentially improve lesion detection over planar scintigraphy, but studies regarding its usefulness as an add-on to diagnostic I-131 MIBG scintigraphy are limited. This study aimed to determine the usefulness and factors related to usefulness of SPECT/CT in diagnostic I-131 MIBG scintigraphy in NB patients. METHODS: Usefulness of SPECT/CT for lesion detection, lesion localization, resolving suspicious findings, and clarifying the nature of lesions on anatomical imaging were retrospectively reviewed in 86 diagnostic planar I-131 MIBG scintigrams with add-on SPECT/CT. RESULTS: SPECT/CT detected additional lesions in 23.2%(20/86), helped localize lesions in 21.1%(8/38), resolved suspicious findings in 85.7%(6/7), determined functional status of lesions on anatomical imaging in 94.4%(17/18), and changed diagnosis from a negative to a positive study in 19.5%(8/41). Independent predictors of SPECT/CT being useful included presence of suspicious findings on planar imaging (OR 99.08; 95% C.I. 6.99-1404.41; p = 0.001), positive findings on planar imaging (OR 4.61; 95% C.I. 1.05, 20.28; p < 0.001), and presence of structural lesions on anatomical imaging (OR 32.54; 95% C.I. 5.37-196.96; p < 0.001). CONCLUSION: SPECT/CT is a useful add-on to diagnostic planar I-131 MIBG scintigraphy. Predictors of usefulness of SPECT/CT include suspicious or positive findings on planar scintigraphy and the presence of structural lesions on anatomical imaging.

Multiple Regression Analysis of Predictors of Bone Scintigraphy Positivity in Patients with Head and Neck Cancers.

PURPOSE: The value of bone scintigraphy (BS) in patients with head and neck cancers (HNCs) has been questioned, with conflicting findings regarding positivity yield with some reports recommending BS be omitted from work-up of HNC patients since it rarely yields positive results. This study aims to determine the positivity yield of BS in HNCs and to determine predictors for BS positivity to help tailor appropriate BS utilization. METHODS: BS studies of HNC patients were reviewed, the positivity yield was determined. Clinical predictors for BS positivity including age, sex, site of cancer, staging, histological grading were analyzed using univariable and multivariable logistic regression. RESULTS: Among the 259 BS studies included, 35 (13.5%), 194 (74.9%), and 30 (11.6%) were positive, negative, and equivocal for bone metastasis, respectively. After exclusion of equivocal cases, 229 were analyzed in the regression models. Independent predictors of BS positivity include site of tumor at the nasopharynx (OR 4.37, 95% C.I. 1.04-18.41, p = 0.044), age less than 45 years (OR 3.01, 95% C.I. 1.24-7.33, p = 0.015), and presence of distant metastasis to other organs (OR 3.84, 95% C.I. 1.19-12.43, p = 0.025). CONCLUSIONS: In contrast to several studies, bone metastasis as detected by BS was found in a relatively high proportion of patients with HNCs. Independent predictors of BS positivity include the age of less than 45 years, tumor site at the nasopharynx, and the presence of extraskeletal distant metastasis. BS could be useful in patients with these characteristics which enhance the pretest probability of bone metastasis.

Diagnostic accuracy of planar, SPECT, and SPECT/CT parathyroid scintigraphy protocols in patients with hyperparathyroidism.

BACKGROUND: Several parathyroid scintigraphy protocols have been used for preoperative localization of hyperfunctioning parathyroid glands in patients with hyperparathyroidism. The aim of this study is to compare the diagnostic accuracy of various parathyroid scintigraphy protocols. MATERIAL AND METHODS: A retrospective diagnostic accuracy study with histopathology as the reference standard was done. Five imaging protocols were investigated including planar dual tracer Tc-99m pertechnetate/Tc-99m sestamibi (DT), planar dual phase Tc-99m sestamibi (DP), and combined dual tracer dual phase (DTDP) protocols, as well as add-on single photon emission computed tomography (SPECT), and single photon emission computed tomography/computed tomography (SPECT/CT). RESULTS: A total of 63 patients underwent parathyroid scintigraphy and subsequent parathyroid surgery with a total of 106 excised lesions with histopathological diagnosis. On a lesion-based analysis, sensitivity and specificity (with 95% confidence interval) of protocols were as follows. DT protocol: 69.4% (53.1-82.0%) and 80.0% (49.0-94.3%); DP protocol: 78.6% (52.4-92.4%) and 33.3% (9.7-70.0%); DTDP protocol: 64.7% (47.9-78.5%) and 50.0% (18.8-81.2%); SPECT: 92.3% (66.7-98.6%) and 75.0% (30.1-95.4%); SPECT/CT: 80.0% (49.0-94.3%) and 75.0% (30.1-95.4%). All protocols had perfect sensitivity for detection of parathyroid adenoma whereas SPECT was the most sensitive method for detection of hyperplastic parathyroid glands. CONCLUSION: Planar parathyroid scintigraphy using the DT protocol has a trend towards being more accurate than DP and DTDP protocols. Additional imaging with SPECT and SPECT/CT had a trend towards being more accurate than planar imaging.