Is routine 24-hour urine calcium measurement useful during the evaluation of primary hyperparathyroidism?

BACKGROUND: Primary hyperparathyroidism and familial hypocalciuric hypercalcemia have similar biochemical profiles, and calcium-to-creatinine-clearance ratio helps distinguish the two. Additionally, 24-hour urine calcium >400 mg/day indicates surgery and guidelines recommend obtaining 24-hour urine calcium preoperatively. Our aim was to assess how 24-hour urine calcium altered care in the evaluation of suspected primary hyperparathyroidism. METHODS: Consecutive patients assessed for primary hyperparathyroidism from 2018 to 2020 were reviewed. Primary hyperparathyroidism was diagnosed by 2016 American Association of Endocrine Surgeons Parathyroidectomy Guidelines criteria. 24-hour urine calcium-directed change in care was defined as familial hypocalciuric hypercalcemia diagnosis, surgical deferment for additional testing, or 24-hour urine calcium >400 mg/day as the sole surgical indication. RESULTS: Of 613 patients, 565 (92%) completed 24-hour urine calcium and 477 (84%) had concurrent biochemical testing to calculate calcium-to-creatinine-clearance ratio. 24-hour urine calcium was <100 mg/day in 9% (49/565) and calcium-to-creatinine-clearance ratio was <0.01 in 17% (82/477). No patient had confirmed familial hypocalciuric hypercalcemia, although 1 had a CASR variant of undetermined significance. When calcium-to-creatinine-clearance ratio was <0.01, familial hypocalciuric hypercalcemia was excluded by 24-hour urine calcium >100 mg/day (56%), prior normal calcium (16%), renal insufficiency (11%), absence of familial hypercalcemia (3%), normal repeat 24-hour urine calcium (10%), or interfering diuretic (1%). 24-hour urine calcium-directed change in care occurred in 25 (4%), including 4 (1%) who had genetic testing. Four-gland hyperplasia was more common with calcium-to-creatinine-clearance ratio <0.01 (17% vs calcium-to-creatinine-clearance ratio ≥ 0.01, 4%, P < .001), but surgical failure rates were equivalent (P = .24). CONCLUSION: 24-hour urine calcium compliance was high, and results affected management in 4%, including productive identification of hypercalciuria as the sole surgical indication in 2 patients. When calcium-to-creatinine-clearance ratio <0.01, clinical assessment was sufficient to exclude familial hypocalciuric hypercalcemia and only 1% required genetic testing. 24-hour urine calcium should be ordered judiciously during primary hyperparathyroidism assessment.

How and when is multiglandular disease diagnosed in sporadic primary hyperparathyroidism?

BACKGROUND: In total, ∼15% of patients with sporadic primary hyperparathyroidism have multiglandular disease, which may be suspected preoperatively but can only be confirmed intra or postoperatively. The study aim is to determine how and when patients are diagnosed with multiglandular disease and to what extent different modalities contribute. METHODS: Consecutive cases of sporadic primary hyperparathyroidism (2013-2019) undergoing initial exploration were reviewed from a single-institution prospective database. Preoperative single-photon emission tomography/computed tomography and neck ultrasound were routinely performed to help direct either bilateral or unilateral exploration guided by intraoperative parathyroid hormone monitoring using the dual criteria. Multiglandular disease was defined as either resection of >1 enlarged parathyroid or hypercalcemia at ≥6 months after single gland resection. RESULTS: Of 1,890 patients with sporadic primary hyperparathyroidism, multiglandular disease was identified in 254 (13.4%); 244 (96.1%) were diagnosed intraoperatively and 10 (3.9%) postoperatively. In these multiglandular disease patients, single gland disease was suggested on single-photon emission tomography/computed tomography in 54.0%, ultrasound in 49.2%, and both were concordant for single gland disease in 29.4%. Intraoperative multiglandular disease diagnosis was prompted by an inadequate intraoperative parathyroid hormone monitoring drop in 38.5%, by surgeon interpretation of imaging in 38.1%, by observing ipsilateral gland enlargement in 11.0%, by finding an initial gland <200 mg in 10.3%, and 2.0% had unexpected multiglandular disease during thyroidectomy. Multiglandular disease was diagnosed by postoperative hypercalcemia in 10 of 254 patients (4.9%). CONCLUSION: To avoid failure at parathyroidectomy for primary hyperparathyroidism, expert surgeons use multiple approaches to diagnose and manage multiglandular disease. Preoperative localization studies alone are insufficient, missing multiglandular disease in at least 30% of cases. All examined adjuncts are informative, including intraoperative parathyroid hormone monitoring, imaging, and intraoperative visual cues.

Retropharyngeal Parathyroid Glands: Important Differences.

INTRODUCTION: In primary hyperparathyroidism (PHPT), parathyroid ectopia is seen in up to 22% leading to more difficult surgery. We aimed to determine the rate and characteristics of retropharyngeal (RP) parathyroid glands. METHODS: A prospective database was queried for patients with sporadic PHPT who had surgery from 1997 to 2016. The data of RP patients were compared to those who had surgery for sporadic PHPT over the same time period with hyperfunctioning parathyroids in anatomically normal positions (N). RESULTS: RP glands occurred in 47/3006 (1.6%) patients and were more common at reoperative than initial surgery (5.5 vs 1.4%, p < 0.01). RP patients had prior failed surgery more often than N patients (17 vs 3.1%, p < 0.01). Preoperative calcium levels (p = 0.06), PTH levels (p = 0.15), and mean gland weights (p = 0.07) were similar among groups. For RP glands, ultrasound imaging was negative in all but one patient, while 99mTc-sestamibi accurately indicated a posterior midline position in only 13/47 (28%) and was negative in 21%. All RP glands were anatomically superior. RP patients more often required > 1 post-resection intraoperative PTH level (36 vs 21%, p = 0.02). Failure due to persistent PHPT was more likely in RP patients (4.7 vs 2.1%, p = 0.2). CONCLUSION: In PHPT, hyperfunctioning RP glands are seen in 1.6% of cases and often associated with initial failure (17%). At reoperation, RP ectopia is 4X more common. RP glands are associated with a high rate of negative imaging, but imaging results suggestive of a midline abnormality can guide exploration. The RP space should be evaluated prior to ending an otherwise unfruitful surgery.

Does impotence improve after parathyroidectomy in men with primary hyperparathyroidism?

BACKGROUND: Erectile dysfunction (ED) is a common diagnosis associated with age, hypertension, cardiovascular disease, and diabetes. Primary hyperparathyroidism (PHP) is also seen with these comorbidities, but its association with ED has yet to be studied. We evaluated the rate and resolution of impotence after curative surgery for PHP. METHODS: Prospectively collected data, including a self-reported questionnaire of symptoms, were reviewed for men who had curative parathyroid exploration for sporadic PHP from July 2010 to January 2014. Data were compared with an age-matched cohort of men who had thyroidectomy during the same period. RESULTS: Among 160 men with PHP and mean age of 60 years (range, 19-88), preoperative ED was reported by 13%, and this group was older than patients without ED (mean age, 70 vs 58 years, P < .01). Self-reported resolution of ED after parathyroidectomy occurred in 67% compared with 43% of patients in a thyroidectomy cohort. Preoperative mean arterial blood pressure was less in men with postoperative resolution of ED (96.6 vs 105.4 mm Hg, P = .03). Among 3 of 21 men on specific ED medications, 2 no longer required them postoperatively. CONCLUSION: Impotence is reported often by men undergoing parathyroidectomy for PHP. After curative surgery, 67% of those affected may self-report ED resolution, which may be more pronounced in those patients with a lesser preoperative mean arterial blood pressure.

Surgeon volume and adequacy of thyroidectomy for differentiated thyroid cancer.

INTRODUCTION: We aimed to determine influence of surgeon volume on (1) frequency of appropriate initial surgery for differentiated thyroid cancer (DTC) and (2) completeness of resection. METHODS: We reviewed all initial thyroidectomies (Tx; lobectomy and total) performed in a health system during 2011; surgeons were grouped by number of Tx cases per year. For patients with histologic DTC ≥ 1 cm, surgeon volume was correlated with initial extent of the operation, and markers of complete resection including uptake on I(123) prescan, thyrotropin-stimulated thyroglobulin levels, and I(131) dose administered. RESULTS: Of 1,249 patients who underwent Tx by 42 surgeons, 29% had DTC ≥ 1 cm without distant metastasis. At a threshold of ≥ 30 Tx per year, surgeons were more likely to perform initial total Tx for DTC ≥ 1 cm (P = .01), and initial resection was more complete as measured by all 3 quantitative markers. For patients with advanced stage disease, a threshold of ≥ 50 Tx per year was needed before observing improvements in I(123) uptake (P = .004). CONCLUSION: Surgeons who perform ≥ 30 Tx a year are more likely to undertake the appropriate initial operation and have more complete initial resection for DTC patients. Surgeon volume is an essential consideration in optimizing outcomes for DTC patients, and even higher thresholds (≥ 50 Tx/year) may be necessary for patients with advanced disease.