Parathyroid Adenoma Orientation for Gland Embryologic Origin on Ultrasonography

This diagnostic study aims to determine if the association between the long axis of a parathyroid adenoma candidate and strap musculature on sagittal ultrasonography can be used to predict the embryologic origin of the gland.

Key Points

Question

Can the angulation of a parathyroid adenoma in the sagittal plane on ultrasonography be used to predict its embryologic origin?

Findings

This diagnostic study of 426 patients with 442 adenomas compared intraoperative findings to ultrasonography images to calculate the accuracy of a novel imaging assessment in predicting gland embryologic origin. The test showed clinical utility in distinguishing superior from inferior parathyroid adenomas.

Meaning

This simple ultrasonography assessment can be used by surgeons to guide surgical treatment of primary hyperparathyroidism.

Abstract

Importance

Accurate preoperative localization is critical to success in targeted parathyroidectomy for primary hyperparathyroidism.

Objective

To determine if the association between the long axis of a parathyroid adenoma (PTA) candidate and strap musculature on sagittal ultrasonography (US) can be used to predict the embryologic origin of the gland.

Design, Setting, and Participants

This diagnostic study was performed using the Stanford Research Repository. Patients 18 years or older with primary hyperparathyroidism who underwent parathyroidectomy between January 2009 and October 2021 were considered. Additional inclusion criteria were having clear sagittal view of the adenoma candidate on US, confirmation of the gland of origin intraoperatively, and confirmation of hypercellular parathyroid on final pathology. Data were analyzed from October 2021 to June 2022.

Exposures

B-mode US and surgical parathyroidectomy.

Main Outcomes and Measures

The index test was using US to measure the angle between the long axis of an adenoma candidate and the strap musculature in the sagittal plane. This angle was used to test whether inferior and superior PTAs could be accurately assigned. The hypothesis was formulated prior to data collection.

Results

A total of 426 patients (mean [range] age, 61.1 [20-96] years; 316 [74.2%] female) with 442 adenomas met inclusion criteria. Of the 442 adenomas, 314 (71.0%) had measurable angles, of which 204 (46.2%) were assigned a superior origin, 238 (53.8%) were assigned an inferior origin, and 128 (29%) were indeterminate. Of the surgically identified superior PTAs, 144 (70.6%) had a definable angle, and of the surgically identified inferior PTAs, 170 (71.4%) had a definable angle. The receiver operating characteristic analysis found 94° as the optimized angle for differentiating true negatives from true positives, with an overall sensitivity of 74% and specificity of 72%. This supported using 90° as a break point for US review. True positives were considered superior adenomas with an angle greater than 90°; true negatives were inferior adenomas with an angle less than 90°. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of angulation analysis for determining PTA origin were 72.2% (95% CI, 64.9%-79.5%), 73.5% (95% CI, 66.9%-80.1%), 69.8% (95% CI, 62.5%-77.1%), 75.8% (95% CI, 69.3%-82.3%), and 72.9%, respectively. A subgroup analysis of 426 adenomas using the posterior carotid artery border on transverse US as a surrogate for predicting gland origin showed the following for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy: 49.5% (95% CI, 42.6%-56.4%), 82.3% (95% CI, 77.3%-87.3%), 71.4% (95% CI, 63.9%-78.9%), 64.6% (95% CI, 59.1%-70.1%), and 66.9%, respectively.

Conclusions and Relevance

This diagnostic study showed that PTA angulation on sagittal plane US can be used to predict gland of origin and guide surgery. The relationship between adenoma and posterior carotid artery border on transverse US can also be used to predict gland origin. These easy-to-apply US-based tests can be used in conjunction with other imaging modalities to guide targeted parathyroidectomy.

Introduction

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in nonhospitalized patients, with an overall age-adjusted prevalence rate of 233 per 100 000 women and 85 per 100 000 in men.¹ The diagnosis is made based on clinical and biochemical data, with imaging reserved for patients considered for surgery.² A single benign parathyroid adenoma (PTA) is the cause of PHPT in the majority of cases.² Surgery remains the criterion-standard treatment for PHPT, with an evolution from routine bilateral neck exploration toward targeted parathyroidectomy since the advent of localization studies and rapid parathyroid hormone assays.³ Traditional parathyroid imaging techniques include technetium-99m sestamibi scintigraphy (MIBI), ultrasonography (US), and, more recently, 4-dimensional computed tomography (4D CT).⁴ Still-newer techniques such as fluorocholine–positron emission tomography/CT may be additionally useful as imaging studies. Choice of imaging modality is commonly based on clinician experience and resources within the medical center. US is well recognized as the least costly, least time- and resource-intensive, and only nonradiation-exposing technique.⁴ Although US is the most operator dependent with respect to image acquisition, the skill and experience of the image interpreter in addition to the modality-specific strengths and weaknesses affect localization accuracy for US, 4D CT, and MIBI.

Surgeon-performed US has been shown to be highly useful in PTA localization. PTAs are most commonly oval to ellipsoid, hypoechoic, homogeneous, smooth-bordered nodular structures that (in contrast to lymph nodes) lack a central hilum and have a polar vessel on color Doppler.⁵ Gurney and Orloff⁶ showed 90% accuracy in localizing to the correct side and 83% accuracy in localizing to the correct quadrant by surgeon-performed US. Steward et al³ showed similar results, with a sensitivity of correct quadrant localization by US at 87%. A meta-analysis by Cheung et al⁷ on preoperative localization found that US had an overall sensitivity of 76.1% and positive predictive value (PPV) of 93.2%.

Accurate preoperative localization is of added importance when considering the higher rates of complications such as postoperative hypocalcemia, persistent hyperparathyroidism, and recurrent laryngeal nerve (RLN) paresis/paralysis associated with revision surgery.⁸ Furthermore, operating room and surgeon schedules are influenced by the accuracy and predictability of parathyroid localization.

A consistent anatomic relationship is that inferior parathyroid glands occupy a plane superficial (ventral) to the RLN, while superior parathyroid glands arise deep (dorsal) to the RLN.² On 4D CT, the tracheoesophageal groove, which approximates the plane of the RLN, may be used to differentiate superior vs inferior gland embryologic origin.⁹ Ectopic parathyroid glands may be found in various locations, including the mediastinum, carotid sheath, thymus, intrathyroidal, and retropharyngeal/retroesophageal.⁴ In a retrospective series of 270 patients, Duke et al¹⁰ showed that an overly descended superior PTA (ODSPTA) was the most common ectopic site in patients undergoing primary parathyroid surgery (52.3%) and in patients undergoing reoperative surgery (33%). Although it can be debated whether these ODSPTAs are truly ectopic, they may be misinterpreted as inferior glands on 2-dimensional planar imaging, leading to a failed operation. Superior parathyroid glands are not necessarily in the vicinity of the superior thyroid pole, nor even necessarily superior in a vertical, longitudinal position relative to inferior parathyroid glands. Some techniques for differentiating superior from inferior glands have been described, such as using the posterior border of the carotid artery to distinguish superior from inferior adenomas.¹¹ Inferior adenomas tend to lie at least partially superficial to the posterior border of the carotid, while superior adenomas tend to lie deep to this plane.

Our experience with surgeon-performed US has led us to note a relationship common to superior and inferior PTAs when viewing these lesions in the sagittal plane on US. On comparing findings at surgery with preoperative US, we have noted that for superior PTAs, the cranial aspect often lies ventral to the caudal aspect. In comparison, for inferior PTAs we have noted that the caudal aspect often lies ventral to the cranial aspect (Figure 1). The relationship appears to be retained even in cases of ectopic location. Our goal for this study was to objectively assess this association and determine its usefulness as an ancillary US localization technique.

Figure 1. Parathyroid Adenoma (PTA) Angulation.

A, In the sagittal plane, the inferior pole of an inferior PTA may point superficially (anteriorly), whereas the inferior pole of a superior PTA may point deep (posteriorly). B, When angulation is indeterminate, the superficial surface and inferior pole may appear neutral (pointing neither superficial nor deep) or the lesion may appear rounded without a long axis. RLN indicates recurrent laryngeal nerve. This figure is reproduced with permission from the artist.

Methods

This diagnostic study was performed using the Stanford Research Repository (STARR). STARR is a database that permits collection and aggregation of clinical data from patients seen at Stanford University or Stanford-affiliated clinics for research purposes. Using STARR-derived clinical data, corresponding parathyroid images were then gathered from the image viewers eUnity (Mach7 Technologies) and Synapse (Fujifilm). This study was approved by the institutional review board at Stanford University. All patient data were deidentified. As a study of diagnostic accuracy, the Standards for Reporting of Diagnostic Accuracy (STARD) reporting guidelines were followed.¹²

All patients 18 years or older with a diagnosis of PHPT based on International Classification of Diseases, Ninth Revision, or Tenth Revision, along with any Current Procedural Terminology codes associated with parathyroidectomy, performed between January 2009 and October 2021 were included in the study to yield an initial cohort of 1359 patients. We then applied inclusion criteria as follows: (1) clear sagittal view of the PTA candidate on available US image, (2) confirmation of site of origin of the PTA intraoperatively by the attending surgeon, and (3) confirmation of hypercellular parathyroid on final pathology. From this cohort, 426 patients with 442 adenomas remained after further excluding patients with multigland hyperplasia to form a convenience sample. Patients with double PTAs had their PTA data separated for end point analysis without duplicating demographic or clinical data. All adenomas with measurable angles were identified by a medical student (J.A.) and verified by a surgical fellow (K.R.H.). In the event of discrepancies, 2 attending surgeons with a combined experience of 27 years performing parathyroid US (J.E.N. and L.A.O.) provided additional review until consensus was reached.

Demographic information was collected along with levels of preoperative serum parathyroid hormone, preoperative serum calcium, and postoperative serum calcium at least 5 days after surgery. Data from preoperative US, MIBI, and 4D CT was noted along with the suspected origin of the PTA candidate. Angulation of PTA candidates was assessed using sagittal US images in a plane with the largest lesion diameter. The observers (J.A. and K.R.H.) were blinded to the surgical findings until after US assessment was complete. Two straight lines were drawn, one along the average cranial-caudal axis of the strap musculature and another along the long axis of the PTA candidate. The long axis of the lesion was defined as a straight line connecting the 2 furthest points along the capsule. The cranial angle formed by the intersection of these 2 lines was used as the end point angle (Figure 2). In some instances, the lines required extension beyond the image to reach the point of intersection for both superior and inferior PTAs. As can be seen in Figure 2, superior PTAs can form an obtuse cranial angle, while inferior PTAs can form an acute cranial angle. Some PTAs were noted to be rounded with no distinct long axis or were oriented with their long axis parallel to the strap musculature. These PTAs were designated as indeterminate and not included in the end point analysis, yet tabulated to calculate the percentage of cases where this phenomenon occurred.

Figure 2. Sagittal Ultrasonography Images for 4 Parathyroid Adenoma (PTA) Orientations.

For PTAs with definable angles, a superior PTA has an obtuse cranial angle with respect to the plane of the strap muscles (A), and an inferior PTA has an acute cranial angle (B). Indeterminate PTAs without definable angles include an adenoma with a long axis parallel to the strap musculature (C) and an adenoma with no definable long axis (D). The latter 2 PTAs are inferior glands, as their proximity to the strap muscles suggests. Other anatomic clues besides angulation can help distinguish origin, including overall depth (superior glands are generally deeper/prevertebral, whereas inferior glands are generally more superficial).

For the end point analysis, superior PTAs (as determined at surgery) forming an obtuse angle were considered true positives, while inferior PTAs with an acute angle were considered true negatives. A receiver operating characteristic analysis determined the ideal mathematical break point to distinguish the true-positive and true-negative populations and validated this approach.

Intraoperatively, a subset of ODSPTAs were identified by the surgeon. A subgroup analysis using angulation to differentiate these from inferior-origin PTAs was performed. In a second subgroup analysis on all adenomas, we recorded if the PTA was located entirely deep to the posterior border of the common carotid artery (CCA) in the transverse US plane. Superior PTAs deep to the posterior border of the CCA were considered true positives, and inferior PTAs superficial to the posterior border of the CCA were considered true negatives. PTAs that crossed the plane of the posterior carotid wall to any degree were deemed superficial and, therefore, designated inferior glands. We calculated the efficacy of this test in distinguishing superior PTAs from inferior PTAs as a secondary end point.

Statistical Analysis

Analyses were performed using R, version 4.0.0 (R Project for Statistical Computing). Calculations were performed in Excel, version 2201 (Microsoft). Mean (SD) values are reported for continuous variables.

Results

A total of 426 patients met the inclusion criteria. Of these, 16 patients (3.8%) were found to have double PTAs. Demographic and clinical data are summarized in Table 1. Of the 426 patients, 342 had preoperative serum calcium levels available for review. Of these, 238 (69.6%) were hypercalcemic preoperatively compared to 7 (2.0%) after surgery. No patients had prolonged hypocalcemia after surgery. Some patients presented with normocalcemic hyperparathyroidism and associated findings, such as osteopenia/osteoporosis. Sixty-seven patients (15.7%) underwent parathyroid protocol 4D CT in addition to US, which correctly attributed PTAs to their gland of origin (superior vs inferior) in 67% of patients. A total of 373 patients (87.6%) had MIBI imaging in addition to US; within that group, 247 PTAs (66.2%) were correctly attributed to their gland of origin (Table 1).

Table 1. Demographic, Radiographic, Laboratory, and Adenoma Data.

Characteristic	No. (%)
Patients (N = 426)
Sex
Female	316 (74.2)
Male	110 (25.8)
Age, mean (range), y	61.1 (20-96)
Preoperative PTH level, mean (range), pg/mL	126.9 (22-1026)
Preoperative calcium level, mean (range), mg/dL	10.7 (7.6-13.1)
Postoperative calcium level, mean (range), mg/dL	9.3 (8.2-10.4)
Candidates with sestamibi	373 (87.6)
Candidates with 4D CT	67 (15.7)
Localizing adenomas on sestamibi, No./total No. (%)	247/373 (66.2)
Localizing adenomas on 4D CT, No./total No. (%)	45/67 (67)
Adenomas (N = 442)
Angle adenomas	314 (71.0)
Indeterminate adenomas	128 (29.0)
Superior adenomas at surgery	204 (46.2)
Inferior adenomas at surgery	238 (53.8)
Superior adenoma with definable angle, No./total No. (%)	144/204 (70.6)
Inferior adenoma with definable angle, No./total No. (%)	170/238 (71.4)

Abbreviations: 4D CT, 4-dimentional computed tomography; PTH, parathyroid hormone.

SI conversion factors: To convert calcium to mmol/L, multiply by 0.25; PTH to ng/L, multiply by 1.

Of 442 total PTAs evaluated by US, 204 PTAs (46.2%) at surgery were superior in origin vs 238 PTAs (53.8%) that were inferior in origin. Of the superior PTAs, 144 (70.6%) had a definable angle, while 170 (71.4%) inferior glands had a definable angle for a total of 314 adenomas (71.0%) with a measurable angle (Table 1). The remaining 128 PTAs were deemed indeterminate on angle analysis (eFigure in Supplement 1). The receiver operating characteristic analysis found 94° as the optimized angle for differentiating true negatives from true positives, with an overall sensitivity of 74% and specificity of 72%. The mean (SD) obtuse angle for true-positive superior adenomas was 156.6° (12.1°) and for acute angle true-negative inferior adenomas was 28.1° (16.2°). These findings supported using 90° as a break point for the US review. The mean (SD) angle of superior and inferior adenomas was 119° (62.5°) and 63° (60.3°), respectively. Sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy of the angulation analysis for determining PTA origin were 72.2% (95% CI, 64.9%-79.5%), 73.5% (95% CI, 66.9%-80.1%), 69.8% (95% CI, 62.5%-77.1%), 75.8% (95% CI, 69.3%-82.3%), and 72.9%, respectively (Table 2). Forty-four superior PTAs with definable angles were identified as ODSPTAs by the surgeon. A subgroup analysis comparing ODSPTAs and inferior PTAs showed the following for sensitivity, specificity, PPV, NPV, and accuracy: 72.3% (95% CI, 59.1%-85.5%), 73.5% (95% CI, 66.9%-80.1%), 41.6% (95% CI, 30.6%-52.6%), 91.2% (95% CI, 86.5%-95.9%), and 73.4%, respectively (Table 2).

Table 2. Results for Defined Angle on Sagittal Ultrasonography and Relation to Carotid on Transverse Ultrasonography.

Performance	% (95% CI)
	IPTA vs SPTA (n = 314)	ODSPTA vs IPTA (n = 214)	Carotid analysis (n = 426)
Sensitivity	72.2 (64.9-79.5)	72.3 (59.1-85.5)	49.5 (42.6-56.4)
Specificity	73.5 (66.9-80.1)	73.5 (66.9-80.1)	82.3 (77.3-87.3)
PPV	69.8 (62.5-77.1)	41.6 (30.6-52.6)	71.4 (63.9-78.9)
NPV	75.8 (69.3-82.3)	91.2 (86.5-95.9)	64.6 (59.1-70.1)
Accuracy, %	72.9	73.4	66.9

Abbreviations: IPTA, inferior parathyroid adenoma; NPV, negative predictive value; ODSPTA, overly descended superior parathyroid adenoma; PPV, positive predictive value; SPTA, superior parathyroid adenoma.

Finally, analysis was performed using all 442 PTAs to determine the utility of the posterior border of the common carotid artery on transverse US as a landmark in differentiating adenoma origin. The following were noted for carotid analysis: sensitivity, 49.5% (95% CI, 42.6%-56.4%); specificity, 82.3% (95% CI, 77.3%-87.3%); PPV, 71.4% (95% CI, 63.9%-78.9%); NPV, 64.6% (95% CI, 59.1%-70.1%); and accuracy, 66.9% (Table 2).

Discussion

This analysis shows that objectively measuring the angle of PTA candidates can be performed in the majority (71.0%) of cases when the lesion is identified on sagittal plane US. While we have described a technique for maximum objectivity for the sake of statistical analysis, we do not anticipate that this calculation will always be convenient for clinical practice. A simplified version for use in real-time US examinations is as follows: in the sagittal plane, the inferior pole of the PTA may point in a superficial (anterior, toward the strap muscles) or deep (posterior, toward the spine) direction, suggestive of an inferior or a superior origin PTA, respectively (Figure 1). Alternatively, the superficial surface and inferior pole may appear neutral (pointing neither superficial nor deep) and thus be classified as indeterminate by this technique (Figure 1). The ultrasonographer or reviewer may quickly apply this test and use this relationship as one factor in considering the site of origin of the PTA. Additionally, this technique may offer utility for identifying embryologic origin of a gland when an imaging report describes equivocal findings of a “midpole” candidate. Anticipating parathyroid embryologic origin is of critical importance in planning surgical approach and anticipating exposure or manipulation of the RLN. Superior parathyroid glands are positioned dorsal to the nerve, whereas inferior glands are ventral to the nerve, and this relationship is preserved even for ODSPTAs. Depending on origin, a midline vs more lateral surgical approach, as well as an anteroneural vs retroneural approach, may be necessary.

Accordingly, superior PTAs are classically located in a deeper tissue plane compared to inferior PTAs and may occasionally be paralaryngeal in location, leading to loss of US resolution from laryngeal shadowing. These features may cause difficulty in collecting adequate sagittal US images to analyze. Interestingly, the present study found that PTAs with a definable angle are distributed in similar proportions between superior (70.6%) and inferior (71.4%) glands.

ODSPTAs were twice as common in the reoperative setting and accounted for more than 20% of initial surgical failures according to Duke et al.¹⁰ Furthermore, the majority of reoperative cases are due to a missed single PTA rather than multigland disease.¹³ While the overall occurrence of reoperative surgery is low, ranging from 2.9% to 7%, the risk of surgical complications is higher than in the primary operation.¹⁰ Reoperative parathyroidectomy carries an elevated risk of vocal fold paresis compared with that of the initial case, along with decreased sensitivity of US and MIBI in part due to scarring and fibrosis of the tissue.^13,14

ODSPTAs can mimic inferior parathyroid glands on the frontal projection of planar (2-dimensional) nuclear medicine imaging, although careful review of the lateral projection will show these lesions to lie deep within the neck dorsal to the plane of the RLN.¹⁰ Given the large proportion of ODSPTAs in reoperative cases, it is of paramount importance to alert the operating surgeon to the likelihood of a descended superior gland. The current study aimed to validate a method of distinguishing these ODSPTAs from inferior PTAs in a manner that is complementary to, or even independent of, gland depth or relative location to the thyroid. With an NPV of 91.2% for distinguishing inferior adenomas from ODSPTAs, the described technique can effectively screen out ODSPTA with a negative test result (ie, an acute cranial angle; Figure 3). Still, reoperative cases are often those that had a nonlocalizing US, while the proposed technique is limited to cases in which a PTA candidate can be identified on US in the first place to calculate its angle and predict its embryologic origin.

Figure 3. Transverse Ultrasonography Images of Superior and Inferior Parathyroid Adenomas (PTAs) With Relation to the Posterior Border of the Common Carotid Artery (CCA).

Characteristic transverse ultrasonography images of a superior PTA (A) deep to the posterior border of the CCA and an inferior PTA (B) superficial to the posterior border of the CCA. Also shown are 2 sagittal ultrasonography images of overly descended superior parathyroid adenomas (ODSPTAs; C and D) with retained obtuse angles characteristic of superior PTAs despite their caudal migration. L indicates left; R, right; SCM, sternocleidomastoid.

The posterior border of the CCA has been previously described as a surrogate for the plane of the recurrent laryngeal nerve to predict the origin of PTAs on US, although evidence of efficacy and accuracy of this landmark is lacking.^11,15 The present results show this to be a viable consideration that can be used alongside other anatomic features to predict the origin of a PTA. We observed that this relationship becomes less informative as the size of a PTA increases, which leads to lesions extending beyond their site of origin and spanning across the posterior and anterior border of the CCA. Classic transverse US images of a superior and inferior PTA with relation to the posterior border of the carotid are shown in Figure 3.

Limitations

There are several limitations of this novel test and within the study. As with many US-based techniques, the quality of image capture may be limited by the ultrasonographer’s experience. Surgeons who are not performing the US examination themselves must review acquired images and rely on the availability of a clear sagittal image of the PTA to apply this technique. Indeed, we found that many candidate patients had to be excluded due to poor quality of the stored images. Even with a clear image, indeterminate adenomas account for nearly one-third of all cases. Our assessment of the superficial surface and the inferior pole of the PTA orientation is inherently subjective and would likely show greater interobserver variability in equivocal (indeterminate) cases. In this study, we did not evaluate interobserver variability, even for determinate cases, but rather sought and achieved consensus on all assignments for angulation and for relationship to the carotid artery. However, in empirical application of this test, the variability may be greater. For PTAs that are spherical or lack a long axis, the objective angulation analysis cannot be performed. A similar situation arises in glands that are parallel to the strap muscles. This relatively large (29%) indeterminate rate is a limitation of the angle approach. The technique of predicting gland origin based on the relationship to the posterior carotid artery may reduce this indeterminate rate if applied in succession to the cranial angle analysis, but this retrospective analysis was not designed to study the application of these 2 tests in succession. Because of the exclusion of indeterminate-angle adenomas, diagnostic accuracy results with respect to cranial angle are reported for only the 71.0% of PTAs with a measurable cranial angle, whereas they are reported for 100% of PTAs with respect to the carotid artery posterior border. This reporting may inflate the utility of the angle compared to the utility of the carotid. A diagnostic performance analysis of a tiered approach, where first the angle is applied (if determinate) and then the carotid border approach is applied if indeterminate, compared to the performance of the carotid border applied to all, would demonstrate the added utility of the angle test in comparison to the carotid border alone. Thyroid nodularity may additionally distort the overlying sternothyroid (strap) muscle contour and reduce the accuracy of this reference structure. In reoperative cases, first-line imaging may frequently be nonlocalizing. In these cases, a localizing US already improves likelihood of successful surgery and may decrease utility of this technique.

Conclusions

Results of this diagnostic study show that accurate preoperative localization of PTAs remains an important component of operative success for PHPT. We report a novel technique to use parathyroid angulation on sagittal US to predict the gland of origin for the adenoma. This technique has shown to be useful for ruling out ODSPTAs when assessing inferior adenoma candidates. We also report data on the objective utility of using the posterior border of the CCA as a surrogate for predicting adenoma origin. This work supports US as a critical tool for providing cumulative information that can improve operative preparedness, and ideally success, for surgeons treating patients with PHPT.

Supplement 1.

eFigure. Standards for Reporting Diagnostic Accuracy Studies (STARD) Flow Chart of Participants

Supplement 2.

Data Sharing Statement