Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

OBJECTIVE: Preoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual-isotope subtraction scintigraphy with 99m Tc-MIBI/123 Iodide using SPECT/CT and planar pinhole imaging (Di-SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11 C-Choline PET/CT (faster with a lower radiation dose) is non-inferior to Di-SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies. DESIGN: This is a prospective, GCP-controlled cohort study. PATIENTS AND MEASUREMENTS: One hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard. RESULTS: Among the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%-88%) and 87% (95% CI: 79%-92%) for Choline PET and Di-SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases. CONCLUSION: Choline PET and Di-SPECT performed equally well and are both appropriate as first-line imaging modalities for preoperative imaging of PHPT. When the first-line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

Number of cells in parathyroid tissue in primary hyperparathyroidism cases and its relationship with serum calcium value.

BACKGROUND: The relationship between serum calcium (Ca) level to serum parathyroid hormone (PTH), phosphorus (P) levels and tissue properties of the parathyroid gland is unknown in primary hyperparathyroidism cases. Revealing this relationship may be useful for understanding the etiopathogenesis of primary hyperparathyroidism and determining the time of treatment. METHODS: Ninety patients (71 females, 19 males, age range; 27-73 years, average age; 46) who underwent single gland excision with the diagnosis of primary hyperparathyroidism were studied. The patients were divided into 2 groups as serum Ca level <12 and serum Ca level ≥12. Age and sex of the patients, mean cell number of the gland, mean volume of the gland, serum levels of PTH, P, and histopathologic type of hyperplasia were evaluated. RESULTS: The mean cell number per cubic centimeter is 22.9 (10-220 range) million in all glands. Serum Ca level was <12 in 82 (91.1%) of the patients, and ≥12 in 8 (8.9%) cases. Mean cell number of the gland, mean volume of the gland, existence of cystic hyperplasia of the gland, serum levels of PTH and P were statistically significant between the 2 groups (P < .001, P < .001, P < .05, P < .001, P < .05 respectively). CONCLUSION: In primary hyperparathyroidism cases serum Ca level is not related to age and sex but directly related to proportionals to the cell number and volume of the gland and serum levels of PTH, inversely related to cystic hyperplasia and serum levels of P. Early surgical intervention should be planned since the serum Ca level will be high in large adenomas with a noncystic radiological appearance.

Failure to Diagnose and Treat Hyperparathyroidism Among Patients with Hypercalcemia: Opportunities for Intervention at the Patient and Physician Level to Increase Surgical Referral.

BACKGROUND: Hyperparathyroidism is both underdiagnosed and undertreated, but the reasons for these deficiencies have not been described. The purpose of this study was to identify reasons for underdiagnosis and undertreatment of hyperparathyroidism that could be addressed by targeted interventions. MATERIALS AND METHODS: We identified 3,200 patients with hypercalcemia (serum calcium >10.5 mg/dL) who had parathyroid hormone (PTH) levels evaluated at our institution from 2011 to 2016. We randomly sampled 60 patients and divided them into three groups based on their PTH levels. Two independent reviewers examined clinical notes and diagnostic data to identify reasons for delayed diagnosis or referral for treatment. RESULTS: The mean age of the patients was 61 ± 16.5 years, 68% were women, and 55% were white. Fifty percent of patients had ≥1 elevated calcium that was missed by their primary care provider. Hypercalcemia was frequently attributed to causes other than hyperparathyroidism, including diuretics (12%), calcium supplements (12%), dehydration (5%), and renal dysfunction (3%). Even when calcium and PTH were both elevated, the diagnosis was missed or delayed in 40% of patients. For 7% of patients, a nonsurgeon stated that surgery offered no benefit; 22% of patients were offered medical treatment or observation, and 8% opted not to see a surgeon. Only 20% of patients were referred for surgical evaluation, and they waited a median of 16 months before seeing a surgeon. CONCLUSION: To address common causes for delayed diagnosis and treatment of hyperparathyroidism, we must improve systems for recognizing hypercalcemia and better educate patients and providers about the consequences of untreated disease. IMPLICATIONS FOR PRACTICE: This study identified reasons why patients experience delays in workup, diagnosis, and treatment of primary hyperparathyroidism. These data provide valuable information for developing interventions that increase rates of diagnosis and referral.

Polymorphisms of CASR gene increase the risk of primary hyperparathyroidism.

OBJECTIVE: To evaluate correlations between polymorphisms of calcium-sensing receptor (CASR) gene [A986S (rs1081725), R990G (rs1042636) and Q1011E (rs1801726)] and the risk of primary hyperparathyroidism (PHPT) among human population. METHODS: Relevant studies were retrieved from online databases using computer-based search strategies, which were then supplemented by manual search strategies. Case-control studies related to our topic were identified based on strict inclusion and exclusion criteria. Statistical analyses were conducted using the Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA). RESULTS: We retrieved 202 studies from online databases and other sources initially and eventually enrolled six studies into our meta-analysis. These six studies contained a sum of 693 PHPT patients and 1252 healthy controls. Our meta-analysis results showed that single nucleotide polymorphisms (SNPs) of CASR gene A986S (rs1081725) and R990G (rs1042636), but not Q1011E (rs1801726), may increase the risk of PHPT [A986S (rs1081725): allele model: P = 0.013; dominant model: P = 0.044; R990G (rs1042636): allele model: P = 0.023; dominant model: P = 0.026)]. Subgroup analyses based on ethnicity showed that among Asians, A986S (rs1081725) increased the PHPT risk (P = 0.04) under the allele model, but not under the dominant model. Among Caucasians, there was no association between gene frequencies and PHPT under both the allele and dominant model. In Asians, no significant association was observed between R990G (rs1042636) and PHPT risk, but in Caucasians, R990G (rs1042636) significantly increased the incidence of PHPT [R990G (rs1042636): allele model: P = 0.015; dominant model: P = 0.009)]. CONCLUSION: Our results indicate that SNPs of CASR gene A986S (rs1081725) and R990G (rs1042636) may increase the risk of PHPT, and the polymorphisms can potentially be used as important biological markers for early diagnosis of PHPT.

The effectiveness of low-dose versus high-dose 99mTc MIBI protocols for radioguided surgery in patients with primary hyperparathyroidism.

OBJECTIVE: The aim of this study was to compare the efficacy of low-dose and high-dose (99m)Tc methoxy isobutyl isonitrile (MIBI) protocols in intraoperative localization of parathyroid adenomas by means of a gamma probe in patients with primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: The study included 62 patients with PHPT who were divided into two groups. Group 1 consisted of 32 patients who were injected with a low dose (1 mCi) of (99m)Tc MIBI in the surgical suite 10 min before incision. Group 2 included 30 patients who were intravenously administered a high dose (15 mCi) of (99m)Tc MIBI 2 h before surgery. With the aid of a gamma probe, intraoperative localization of parathyroid adenomas was performed in both groups of patients who underwent minimally invasive parathyroidectomy. All lesions thought to be parathyroid adenomas were excised and subsequently evaluated histopathologically. RESULTS: All parathyroid adenomas in both groups were localized and excised by means of an intraoperative gamma probe. The sensitivity, specificity, and accuracy of low-dose and high-dose (99m)Tc MIBI protocols in the intraoperative localization of adenomas in patients with PHPT were 100%. CONCLUSION: In the light of these findings, we conclude that low-dose (99m)Tc MIBI may be preferred to intraoperative identification of parathyroid adenomas by means of a gamma probe in PHPT patients because it appears to be as effective as high-dose (99m)Tc MIBI. Moreover, the low-dose protocol does not have the disadvantages of high-dose protocol.

[The study of an animal model in rabbits with the early primary hyperparathyroidism].

OBJECTIVE: to study the biochemistry of blood and feature of pathology of an animal model in rabbits with the early primary hyperparathyroidism(PHPT). METHODS: 60 rabbits were divided into six groups of 10 each and fed a control diet (Ca:P, 1:0.7) or a high-phosphate diet (Ca:P, 1:7) for 1-, 2- or 3-month intervals. Compared with the control animals, serum PTH levels, serum calcium levels and serum phosphorus levels were determined. The parathyroid and kidneys of all animals were performed by the histologic examination. RESULTS: compared with the control animals, serum parathyroid hormone (PTH) levels were elevated at 1-, 2-, 3-month intervals in experimental group (t = -7.665, t = -16.033, t = 12.877 respective, P < 0.05), whereas serum calcium levels were decreased at all three time intervals (t = 6.184, t = 9.329, t = 13.842, respective, P < 0.05), but serum phosphorus levels did not change (t = 0.611, t = 1.041, t = 1.941, respective, P > 0.05). Parathyroid histopathologic studies demonstrated no change at 1 month whereas six of ten experimental animals showed mild hyperplasia at 2 months and nine of ten showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2- and 3-month in the experimental groups. CONCLUSION: the high-phosphate diet successfully induced an animal model in rabbits with the early primary hyperparathyroidism, which has a better stability and reproducibility.

Normocalcemic, subclinical, asymptomatic primary hyperparathyroidism in patients with goiter or papillary thyroid cancer--preliminary report. Normocalcemic primary hyperparathyroidism and thyroid pathology.

UNLABELLED: The aim of the prospective study was the evaluation of primary, subclinical, normocalcemic hyperparathyroidism (PHPT) incidence in patients, operated on because of non-toxic (NTG), toxic (TG) goiter and papillary thyroid cancer (PTC). MATERIAL AND METHODS: The study was performed in the group of 196 patients operated on NTG (115 patients), TG (43 patients) and PTC (38 patients). All patients had never been operated because of goiter. No patient had clinical symptoms of PHPT. Calcium concentration (Ca), phosphorus concentration (P) and alkaline phosphatase activity (ALP) in blood serum were measured in all patients a day before operation. When those parameters were out of range, parathormone concentration (PTH) in blood serum was measured. In the case of elevated PTH concentration PHPT was diagnosed. Furthermore, in order to exclude renal failure and insufficiency tests for creatinine and urea concentrations in blood serum and urinalysis were performed. RESULTS: There was no case of increased Ca concentration among 158 patients with benign goiter. The values of at least one measured parameters (P or ALP) were abnormal in 47 out of 158 patients with benign goiter (29.7%). Increased PTH concentration (mean 101.5 pg/ml) was in 16 of 47 patients (10.1% of 158 patients). Normocalcemic PHPT was diagnosed in 12 (10.4%) NTG patients and 4 (9.3%) TG patients. In patients with PTC hypercalcemia was not affirmed. In 7 (18.42%) cases of 38 PTC patients P concentration and ALP activity were abnormal. Increased PTH concentration (84.85 pg/ml) was found in one female with PTC with normal values of P and ALP. Incidence of PHPT was observed in 2.63% of PTC patients. CONCLUSIONS: 1. There was no significant difference of PHPT incidence between various type of goiter. 2. In our study coexistence of PTC and normocalcemic, asymptomatic PHPT is rare.

[65-year old female patient with persistent hypercalcemia]. / 65-jährige Patientin mit persistierender Hyperkalzämie.

A 65-year old patient presented with newly diagnosed hypercalcemia and elevated parathyroid hormone levels. Exploration of parathyroid glands was performed under the diagnosis of primary hyperparathyroidism and was combined with thyreoidectomy due to concomittant multinodular goiter. However, no parathyroid adenoma was identified despite careful exploration. Therefore, the operation was terminated and an ectopic adenoma was suspected. A (99m)Tc-sestamibi scintigraphy with SPECT, neck ultrasound, neck CT scan with contrast media and selective venous sampling were performed for further localization of the adenoma. A single adenoma localized in the submandibular area of the left jaw was suspected and confirmed during surgical reexploration. Postoperatively, parathyroid hormone levels were below detection level and the patient required short-term calcium supplementation for symptomatic hypocalcemia.