Glands In Hyperparathyroidism Research Articles

Head-to-Head Comparison of Tc-99m-sestamibi SPECT/CT and C-11-L-Methionin PET/CT in Parathyroid Scanning Before Operation for Primary Hyperparathyroidism.

The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands. The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism (PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons were made for differences in sensitivity and positive predictive value (PPV). Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1-79)) were enrolled into the study. The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methionine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for methionine PET PET/CT (-0.11, 95% confidence interval (95% CI): -0.29 to 0.08; -0.05, 95% CI: -0.14 to 0.04, respectively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64 (95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1). Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localization of hyperfunctioning parathyroid glands prior to surgery.

Pathological uptake with 18-Fluorocholine versus 99mTc-MIBI in the location of the parathyroid glands in hyperparathyroidism. Systematic review and meta-analysis

Introduction: The location of the pathological parathyroid glands in hyperparathyroidism is usually carried out by means of 99mTc-sestamibi scintigraphy, which increases its precision by adding the ultrasound examination. The non-localization of the parathyroid glands increases the difficulties for surgical removal. To increase the detection of pathological glands, other radioactive tracers are used, such as methionine, fluorocholine or 18F-flurpiridaz. Objective: To establish if PET / CT with 18-Fluorocholine in patients with hyperparathyroidism increases the number of uptakes compared to the 99mTc-sestamibi scan. Method: Systematic review and meta-analysis. Two subgroups were analyzed. Subgroup 1: trials comparing both techniques as an initial exploration. Thirteen studies including 1131 examinations were selected (596 PET / CT with 18-Fluorocholine vs. 535 scintigraphy with 99mTc-sestamibi). Meta-analysis was performed following the random effects model and the odds ratio was calculated. Subgroup 2: studies that include 18-Fluorocholine as a rescue examination in patients with a previous negative study with a 99mTc-sestamibi scan. 17 articles including 412 examinations with 359 patients in which there was at least one uptake were selected. Meta-analysis of the prevalence of the number of patients in whom there was at least one uptake was performed using the random effects model. Results: Subgroup 1: The number of patients in which at least one uptake occurs is significantly higher with the 18-Fluorocholine examinations (OR 4.264, 95% CI 2.400-7.577). The prevalence of uptake with 18-Fluorocholine is 0.91 [0.86, 0.95] and with sestamibi 0.68 [0.56, 0.80]. Subgroup 2: the prevalence of uptake among patients with previous negative MIBI studies was 0.90 [0.87, 0.94]. The probability of detection of both techniques in this group reaches 0.98. Publication bias in the meta-analyzes is low. Discussion: 18-Fluorocholine protocols provide higher precision, clearer images, with faster acquisition as well as being readily available for most PET / CT centers. Conclusion: The PET / CT study with 18-Fluorocholine can be recommended as a study for the location of pathological parathyroid glands after studies with negative MIBI.

Comparison between MIBI-based radiopharmaceuticals for parathyroid scintigraphy: quantitative evaluation and correlation with clinical-laboratory parameters.

Parathyroid scintigraphy is mandatory for the identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT). The use of 99mTc-methoxy-isobutyl-isonitrile (MIBI) as radiopharmaceutical for parathyroid scintigraphy is considered the most valid and useful considering its uptake mechanism. Several MIBI-based radiopharmaceuticals are commercially available (i.e., MediMIBI, TechneMIBI, Stamicis). They seem to have similar physico-chemical characteristics and the choice between them is based on commercial criteria, even though some differences in qualitative scintigraphic results have been appreciated. Aims of the study were: first, to compare the scintigraphic quantitative data of MediMIBI, TechneMIBI, and Stamicis, particularly in the view of a personalized medicine approach; second, to investigate the potential effect of clinical-laboratory data on image quality using one of these radiopharmaceuticals. Patients with diagnosis of HPT, who underwent a parathyroid scintigraphy using one of the three MIBI-based radiopharmaceuticals between December 2018 and October 2020, have been retrospectively identified. Parameters derived from regions of interest (ROIs) drawn on three different sites were obtained: a reasonable parathyroid lesion detected, an area in the lateral neck considered as the background, and the hepatic dome as the site of MIBI physiological uptake. Laboratory and clinical data, such as serum calcium, PTH, vitamin D, and creatinine levels, as well as possible drug-mediated interferences were considered. Among 250 patients included, 83 (33.2%) had the parathyroid scintigraphy using MediMIBI, 84 (33.6%) using TechneMIBI and 83 (33.2%) using Stamicis. The ROIs on the parathyroid uptake at early images, on the background, and on the hepatic dome were statistically different among the three groups (p < 0.05). No significant differences were found in the remaining semi-quantitative parameters among the three groups, not even considering clinical-laboratory data. Some differences in semi-quantitative parameters emerged among MIBI-based radiopharmaceuticals for parathyroid scintigraphy. This might justify the different qualitative scintigraphic results obtained using one or another of the cited radiopharmaceuticals.

Parathyroid imaging with 18F-fluorocholine PET/CT as a first-line imaging modality in primary hyperparathyroidism: a retrospective cohort study

Background18F-fluorocholine (FCH) PET/CT is a promising technique for visualizing hyperfunctioning parathyroid glands in hyperparathyroidism. It is still under debate whether to use this technique as a first-line imaging modality or to use it when conventional techniques such as 99mTc-sestamibi scintigraphy or ultrasonography are inconclusive. This study evaluates FCH PET/CT as a first-line modality.MethodsPatients with primary hyperparathyroidism, referred between June 2015 and December 2018 for FCH PET/CT as a first-line imaging method, were included in this study. Baseline characteristics, clinical data, scan results, and type of treatment were recorded. The rate of correct detection was calculated on a per patient-based and a per lesion-based analysis. The reference standard comprised histopathological results, intraoperative response to parathyroidectomy, and clinical follow-up.ResultsTwo hundred and seventy-one patients were included, of which 139 patients underwent parathyroidectomy, 48 were treated with calcimimetics, and 84 patients received further follow-up without active treatment. In the surgically treated group, a single adenoma was suspected in 127 scans, double adenoma in three scans, and one scan showed evidence of three hyperfunctioning glands. In eight scans, no lesions were visualized. A total of 154 parathyroid glands were surgically removed. The rate of correct detection was calculated at 96% and 90%, on a per patient-based and per lesion-based analysis, respectively.ConclusionThis retrospective study in a large cohort shows high detection rates of FCH PET/CT in primary hyperparathyroidism, which is in accordance to literature. The use of FCH PET/CT as a first-line imaging modality in preoperative planning of parathyroid surgery may therefore be a suitable choice.

Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis.

Hyperparathyroidism (HPT) is a common endocrine disorder caused by hyperfunctioning parathyroid glands (HP). The correct detection and localization of HP is challenging but crucial, as it may guide surgical treatment, particularly in patients with primary HPT. There is a growing body of data regarding the role of radiolabelled choline positron emission tomography (PET) in this setting. Therefore, we performed a systematic review and meta-analysis of the diagnostic performance of this method in detecting HP in patients with HPT. This systematic review and meta-analysis was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE and Cochrane Library databases for studies published through May 2018 was performed using the following search algorithm: (a) "choline" or "fluorocholine" or "F-choline" or "C-choline" or "FCH" or "CH" or "FECH" or "FMCH" and (b) "PET" or "positron emission tomography" and (c) "parathyroid" or "hyperparathyroidism". The diagnostic performance of radiolabelled choline PET was expressed as sensitivity and positive predictive value (PPV) on a per-patient and per-lesion basis and as detection rate (DR) on a per-patient basis, with pooled proportion and 95% confidence interval (95% CI) obtained using a random-effects model. Eighteen studies were included in the systematic review. Fourteen articles (517 patients) were selected for the meta-analysis. The meta-analysis provided the following results on a per-patient analysis analysis: sensitivity 95% (95% CI: 92-97%), PPV 97% (95% CI: 95-98%) and DR 91% (95% CI: 87-94%). On a per-lesion analysis, pooled sensitivity and PPV were 92% (95% CI: 88-96) and 92% (95% CI: 89-95%), respectively. No significant heterogeneity was found among the selected studies. Radiolabelled choline PET demonstrated excellent diagnostic performance in detecting HP in patients with HPT. Large multicentre studies and cost-effectiveness analyses are needed to better define the role of this imaging method in this setting.

The role of 99mTc-MIBI SPECT-CT in reoperation therapy of persistent hyperparathyroidism patients.

To compare the role of 99mTc-MIBI SPECT-CT image and US in reoperation of persistent secondary hyperparathyroidism patients. A total of 8 persistent secondary hyperparathyroidism patients underwent parathyroidectomy. The sensitivity and accuracy of US and 99mTc-MIBI images before operation were determined. 9 of 14 surgical resection tissues from 8 persistent secondary hyperparathyroidism patients were confirmed to parathyroid hyperplasia. The results showed that the sensitivities were 77.8% and 100%, respectively, for US and 99mTc-MIBI SPECT-CT images. And the accuracies of US and 99mTc-MIBI dual time planar image and SPECT-CT were 50%, 78.6%, respectively. There was significantly difference between two procedures (P=0.021). The superior and inferior localization of glands were both detected by the ultrasound and scintigraphy. Two ectopic parathyroidism nodules were found by 99mTc-MIBI SPECT-CT imaging, while US provided no consistent findings. There was no significantly difference between two procedures (P=0.3). Although two cases of them were not confirmed by pathology, the iPTH of them (800 and 1429 respectively) were much higher than other four cases (<400) pg/ml. PTX is a safe and effective treatment for the patients with persistent SHPT. 99mTc-MIBI planar and SPECT-CT imaging may provide more helps for clinician’s localization the hyperparathyroidism glands accurately.

Pathology of the parathyroid glands in hyperparathyroidism

This paper reviews the embryology, histology and pathology of the human parathyroid glands. It emphasizes those pathologic lesions which are found in the setting of clinical hyperparathyroidism. Also discussed are certain molecular features of hyperfunctioning parathyroid glands. The difficulties encountered in parathyroid FNA are reviewed and illustrated.

副甲状腺の画像診断の進歩MIBI シンチグラフィ，CTを中心に

副甲状腺の画像診断の進歩MIBI シンチグラフィ，CTを中心に

Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1

To evaluate frequency, anatomic presentation, and quantities of supernumerary parathyroids glands in patients with primary hyperparathyroidism (HPT1) associated with multiple endocrine neoplasia type 1 (MEN1), as well as the importance of thymectomy, and the benefits of localizing examinations for those glands. Forty-one patients with hyperparathyroidism associated with MEN1 who underwent parathyroidectomy between 1997 and 2007 were retrospectively studied. The location and number of supernumerary parathyroids were reviewed, as well as whether cervical ultrasound and parathyroid SESTAMIBI scan (MIBI) were useful diagnostic tools. In five patients (12.2%) a supernumerary gland was identified. In three of these cases (40%), the glands were near the thyroid gland and were found during the procedure. None of the imaging examinations were able to detect supernumerary parathyroids. In one case, only the pathologic examination could find a microscopic fifth gland in the thymus. In the last case, the supernumerary gland was resected through a sternotomy after a recurrence of hyperparathyroidism, ten years after the initial four-gland parathyroidectomy without thymectomy. MIBI was capable of detecting this gland, but only in the recurrent setting. Cervical ultrasound did not detect any supernumerary glands. The frequency of supernumerary parathyroid gland in the HPT1/MEN1 patients studied (12.2%) was significant. Surgeons should be aware of the need to search for supernumerary glands during neck exploration, besides the thymus. Imaging examinations were not useful in the pre-surgical location of these glands, and one case presented a recurrence of hyperparathyroidism.

Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1

To evaluate frequency, anatomic presentation, and quantities of supernumerary parathyroids glands in patients with primary hyperparathyroidism (HPT1) associated with multiple endocrine neoplasia type 1 (MEN1), as well as the importance of thymectomy, and the benefits of localizing examinations for those glands. Forty-one patients with hyperparathyroidism associated with MEN1 who underwent parathyroidectomy between 1997 and 2007 were retrospectively studied. The location and number of supernumerary parathyroids were reviewed, as well as whether cervical ultrasound and parathyroid SESTAMIBI scan (MIBI) were useful diagnostic tools. In five patients (12.2%) a supernumerary gland was identified. In three of these cases (40%), the glands were near the thyroid gland and were found during the procedure. None of the imaging examinations were able to detect supernumerary parathyroids. In one case, only the pathologic examination could find a microscopic fifth gland in the thymus. In the last case, the supernumerary gland was resected through a sternotomy after a recurrence of hyperparathyroidism, ten years after the initial four-gland parathyroidectomy without thymectomy. MIBI was capable of detecting this gland, but only in the recurrent setting. Cervical ultrasound did not detect any supernumerary glands. The frequency of supernumerary parathyroid gland in the HPT1/MEN1 patients studied (12.2%) was significant. Surgeons should be aware of the need to search for supernumerary glands during neck exploration, besides the thymus. Imaging examinations were not useful in the pre-surgical location of these glands, and one case presented a recurrence of hyperparathyroidism.

Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Imaging of hyperparathyroidism: Comparing combined technetium-99m sestamibi/high-resolution ultrasound with technetium-99m sestamibi or high-resolution ultrasound alone

Objective. Ultrasound (US) and technetium-99m sestamibi scintigraphy (MIBI) are frequently used to detect abnormal parathyroid glands in hyperparathyroidism, as this allows the option of minimally invasive parathyroidectomy. This retrospective study compares US, MIBI and combined MIBI/US for detecting uni- and multiglandular disease of the parathyroid. Material and methods. A total of 29 patients with biochemically proven hyperparathyroidism were evaluated. Each parathyroid focus was considered individually. Comparison was made with histopathology. Results. When all cases were considered, combined MIBI/US imaging was significantly superior in terms of excluding parathyroid abnormality to either US or MIBI alone. When only uniglandular disease was considered, MIBI/US was again found to be superior. There was no statistical difference between techniques in terms of excluding multiglandular disease. When all cases were considered, both MIBI/US and MIBI were superior in terms of positively diagnosing unigland...

The relative merits of ultrasound, CT, sestamibi scans and peri-operative methylene blue in localising the position of parathyroid glands in hyperparathyroidism

The relative merits of ultrasound, CT, sestamibi scans and peri-operative methylene blue in localising the position of parathyroid glands in hyperparathyroidism

GCMB gene, a master regulator of parathyroid gland development, expression, and regulation in hyperparathyroidism

The glial cell missing gene, GCMB , encodes a transcription factor, which is a master regulator of parathyroid development. We postulated that the GCMB gene might play a role in parathyroid tumorigenesis in hyperparathyroidism. We used real-time quantitative reverse transcriptase polymerase chain reaction to study GCMB mRNA expression in parathyroid tissue: normal (n = 3), hyperplastic (n = 16), adenomas (n = 19), and cancers (n = 8). In primary parathyroid culture, the effect of CaCl 2 on parathyroid hormone secretion and GCMB mRNA expression was studied by using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction, respectively. GCMB mRNA expression was lower in normal (0.4 +/- 0.1, mean +/- standard error of mean) parathyroid glands as compared to adenoma (3.5 +/- 1.7), hyperplasia (3.2 +/- 1.3 primary hyperparathyroidism [n = 11] and 7.6 +/- 4.8 secondary hyperparathyroidism [n = 5]), and cancer (3.6 +/- 1.3) ( P = .001). There was no difference in the level of GCMB mRNA expression between parathyroid adenoma, hyperplasia, and cancer. In primary culture of parathyroid adenoma (n = 9) and hyperplasia (n = 2), parathyroid hormone secretion was increased 2- to 15-fold with low calcium concentration (0.5 to 4.0 mmol/L CaCl 2 from 2 to 6 hours, P < .005). The level of GCMB mRNA expression was down-regulated with lower extracellular CaCl 2 concentration ( P < .005). GCMB expression is upregulated in abnormal parathyroid glands of hyperparathyroidism and decreases in response to hypocalcemia. The GCMB transcription factor might mediate the effect of calcium on parathyroid cell parathyroid hormone expression/secretion.

Preoperative contrast-enhanced MRI of the parathyroid glands in hyperparathyroidism.

To evaluate the sensitivity of contrast-enhanced MRI in the preoperative detection of abnormal parathyroid glands in patients with clinical evidence of hyperparathyroidism. Twenty-eight patients with biochemical evidence of hyperparathyroidism underwent contrast-enhanced preoperative MRI of the parathyroid glands. Two blinded readers assessed the MR images by consensus, and MR results were subsequently correlated with those from surgery (location, diameter, weight) and histopathology. MRI depicted 32 of 39 surgically proved abnormal parathyroid glands (sensitivity 82%; 95% confidence interval, 66%-92%), and 1 of 114 (0.9%) was incorrectly considered abnormal. All ectopic glands were correctly identified (2 mediastinal, 1 submandibular). Sensitivity was superior for adenomas but less for hyperplasia (adenomas 87%; 95% confidence interval, 67%-97%; hyperplasia 75%; 95% confidence interval, 47%-92%). Among all lesions, atypical signal characteristics on MRI were observed in 34% of lesions (9% hyperintense signals on T2- and T1-weighted images; 25% isointense signals on T2- and T1-weighted images), with improved lesion detection after contrast administration in 17% of lesions. MRI of the parathyroid glands presented a sensitive imaging modality, thus demonstrating its high potential to preoperatively detect abnormal glands. Moreover, in a minor proportion of patients with atypical parathyroid lesion characteristics, contrast administration may increase lesion detectability.

Thoracoscopic resection of ectopic parathyroid glands

Background. The vast majority of parathyroid glands in hyperparathyroidism can be resected through a cervical approach. In approximately 2% of the cases, the ectopic gland is in the mediastinum in a location that requires a thoracic approach.Methods. We report 7 such cases that were resected using video-assisted thoracic surgery to avoid the need for an open surgical procedure.Results. All glands were successfully identified preoperatively and subsequently resected. Hospital stay averaged less than 3 days with only one minor complication.Conclusions. Ectopic mediastinal parathyroid glands may be safely and accurately resected using video-assisted thoracic surgery to avoid open approaches.

Efficacy of preoperative diagnostic imaging localization of technetium 99m-sestamibi scintigraphy in hyperparathyroidism

Background. Until now, preoperative parathyroid imaging has been considered unnecessary because currently available techniques do not provide any better results than an expert surgeon. We conducted a multicenter prospective study evaluating the capability of technetium 99m sestamibi scintigraphy in the preoperative identification of pathologic glands. Methods. Ninety-three patients with hyperparathyroidism, seven of them reoperative cases, were studied. In addition, 20 age-matched normocalcemic control subjects were also studied. Results. Surgical confirmation of scintigraphic images was obtained in 91 of 93 cases (sensitivity, 97.8%). In all reoperative cases (n = 7), in all cases of ectopic glands (whether operated or not; n = 6), and in all patients with a single-gland disease (n = 70), topographic identification of the pathologic gland was correct in 100%. In multiple-gland disease (n = 23), involvement of more than one gland was visualized in only 61% of the patients; however, in 91% of patients, at least one gland was localized. Surgical success—defined as postoperative normocalcemia—with this approach was 100%. All scans of normocalcemic control subjects were negative. Of 31 patients in whom a multinodular goiter coexisted, seven presented a significant radionuclide background at 120 minutes' scan. False-positive images were found together with those corresponding to the pathologic glands in only three cases. Conclusions. 99mTc-sestamibi is a highly reliable, sensitive, and specific technique for imaging of pathologic glands in hyperparathyroidism, especially in single-gland disease. It may be considered as a first line single-procedure when a preoperative topographic diagnosis is required.

AN ANALYSIS OF PREOPERATIVE LOCALIZATION OF PARATHYROID GLANDS IN HYPERPARATHYROIDISM ASSOCIATED WITH THYROID DISEASES

Recently hyperparathyroidism associated with some thyroid diseases, especially nonmedually thyroid carcinoma has been payed attention to. In this study we analyzed 12 cases of hyperparathyroidism (6 cases independent of thyroid diseases and 6 cases associated with thyroid diseases) and estimated the affect of association with thyroid diseases on the preoperative localization of the parathyroid glands. The results of preoperative localization of the parathyroid glands in cases independent of thyroid diseases were relatively satisfactory. On the other hand, the preoperative localization in cases associated with thyroid diseases came to false result in about half of them. It was far from satisfactory. Association of thyroid diseases strongly affected the preoperative localization of the parathyroid glands in hyperparathyroidism. Conventional imaging such as ultrasonography, CT, MRI and 201Tl-99mTC subtraction scintigraphy alone were not satisfactory. Now 99mTc-MIBI scintigraphy is expected to be one of reliable imaging methods for progress in the preoperative localization.

Ultrastructural Pathology of Parathyroid Glands in Hyperparathyroidism: A Report of 69 Cases

The ultrastructural features of 69 parathyroid glands from 43 patients with hyperparathyroidism were studied to distinguish between different parathyroid lesions causing hyperparathyroidism. Samples came from 44 cases of hyperplasia, 21 of adenoma, 3 of carcinoma, and 1 from a histologically normal gland. To establish the diagnosis we took into account intraoperative findings during surgery as well as light microscopic examination. Ultrastructural features, evaluated on a semiquantitative scale, were correlated with diagnostic, clinical, and biochemical parameters. Neoplastic glands were heavier than nonneoplastic ones, and carcinomatous glands were heavier than adenomatous glands. Our findings suggest that the cellular membrane of adenomatous glands shows more folding than that of hyperplastic glands, mainly in the capillary pole. Carcinomatous glands show the greatest degree of irregularity, with the formation of microvilli-like projections. Hyperplastic glands, in turn, are richer in glycogen deposition. Secretory granules appear in higher amounts when the serum calcium level is high. These findings are not of diagnostic value by themselves, but they can be taken in consideration to aid in differential diagnosis.

High-Resolution Parathyroid Ultrasonography in Familial Benign Hypercalcemia (Familial Hypocalciuric Hypercalcemia)

Familial benign hypercalcemia, or familial hypocalciuric hypercalcemia (FHH), is frequently confused with primary hyperparathyroidism, but the consistent failure of subtotal parathyroidectomy to normalize serum calcium levels in FHH makes accurate distinction from familial hyperparathyroidism imperative. Because ultrasonography frequently demonstrates enlargement of the parathyroid glands in hyperparathyroidism, we examined 14 hypercalcemic adults (who had not undergone operation) from seven kindreds with FHH by using a high-resolution real-time scanner. We compared our results with those from 156 patients (who had undergone scanning preoperatively) with surgically confirmed hyperparathyroidism. Enlargement of the parathyroid glands was detected ultrasonographically in 137 of 156 (88%) of the total group of patients with hyperparathyroidism and in 17 of 24 patients (71%) with hyperparathyroidism who had hypercalcemia (serum calcium, 10.6 to 11.0 mg/dl) comparable to that of the FHH group (mean value, 10.7 mg/dl). In contrast, the single possible parathyroid lesion seen in the FHH group was substantially smaller (4 mm) than the smallest (7 mm, 75 mg) abnormal gland reliably detected by ultrasonography in the group with hyperparathyroidism and was conceivably normal in size. Patients with FHH have a dramatic absence of ultrasonographic parathyroid enlargement. High-resolution parathyroid ultrasonography may be of ancillary diagnostic benefit in patients with familial hypercalcemia.