Douglas Politz

Hyperparathyroidism during pregnancy and the effect of rising calcium on pregnancy loss: a call for earlier intervention

Introduction  Hyperparathyroidism (HPT) during pregnancy is rare but poses a significant danger to mother and baby yet the incidence of pregnancy loss and its relationship to the degree of calcium elevation is not known.

Calcium, parathyroid hormone, and vitamin D in patients with primary hyperparathyroidism: normograms developed from 10,000 cases.

OBJECTIVE To better define the typical and atypical biochemical profiles of patients with surgically proven primary hyperparathyroidism. METHODS In this single-center, prospectively conducted study of consecutive patients with surgically proven primary hyperparathyroidism over a 7-year period, we analyzed serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations. RESULTS A total of 10 000 patients were included, and more than 210 000 calcium, parathyroid hormone, and 25-hydroxyvitamin D values were evaluated. Both calcium and parathyroid hormone levels demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/mL. The average highest calcium and parathyroid hormone concentrations were 11.4 ± 0.7 mg/dL and 115.3 ± 50 pg/mL, respectively. At least 1 calcium value of 11.0 mg/dL was seen in 87% of patients, but only 21% had 1 or more calcium value above 11.5 mg/dL. Only 7% had a single serum calcium level reaching 12.0 mg/dL. Normocalcemic hyperparathyroidism was seen in just under 3% of patients who had identical findings at surgery. An average parathyroid hormone concentration less than 65 pg/mL was seen in 16%, with 10% of patients who had no high parathyroid hormone values. The average 25-hydroxyvitamin D concentration was 22.4 ± 9 ng/mL, with levels decreasing as calcium levels increased (P<.001); 36% had 25-hydroxyvitamin D levels below 20 ng/mL. CONCLUSIONS Patients with PHPT present with a number of distinct biochemical profiles, but as a group, they present with a near-normal Gaussian distribution of both calcium and parathyroid hormone levels. Either serum calcium or parathyroid hormone remained normal in 13% of patients, yet the findings at surgery are similar to those of patients with elevated calcium or parathyroid hormone. Low 25-hydroxyvitamin D is an expected finding in patients with PHPT, decreasing as serum calcium levels increase.

Safety of immediate discharge after parathyroidectomy: a prospective study of 3,000 consecutive patients.

OBJECTIVE To evaluate the safety of immediate discharge after parathyroidectomy and to establish a protocol for the amount and duration of supplemental orally administered calcium for patients with varied clinical presentations of primary hyperparathyroidism. METHODS A 40-months, prospective, single institution, cohort study of 3,000 consecutive patients undergoing parathyroidectomy and discharged within 2.5 hours after the operation is reviewed. The amount of oral calcium supplementation prescribed postoperatively varied according to a protocol that considered the degree of serum calcium elevation preoperatively as well as the intraoperative findings (hyperplasia versus adenoma). Symptoms of hypocalcemia were tracked, and all surgical outcomes were monitored. RESULTS With use of the reported protocol, less than 7% of patients had postoperative symptoms of hypocalcemia, most of whom were successfully self-treated with additional orally administered calcium. Only 6 patients (0.2%) required a visit to the emergency department for intravenous calcium infusion, all occurring on postoperative day 3 or later, and none of these patients required rehospitalization. Postoperative calcium requirements varied on the basis of the degree of serum calcium elevation preoperatively, number of parathyroid glands removed or subjected to biopsy, presence of morbid obesity, and presence of severe osteoporosis. CONCLUSION Patients with primary hyperparathyroidism can be sent home immediately after successful parathyroidectomy, provided specific measures are taken regarding postoperative oral calcium supplementation. Use of a specific calcium dosing protocol that considers several patient variables will prevent the postoperative development of symptomatic hypocalcemia in 93% of patients, identify patients at high risk of hypocalcemia, and allow most patients who develop symptoms of hypocalcemia to self-medicate in a simple and predictable fashion. Routine monitoring of postoperative serum calcium levels in the hospital can be safely eliminated if the details of this protocol are followed.

Postoperative Calcium Requirements in 6,000 Patients Undergoing Outpatient Parathyroidectomy: Easily Avoiding Symptomatic Hypocalcemia

BACKGROUND To determine the amount and duration of supplemental oral calcium for patients with varying clinical presentations discharged immediately after surgery for primary hyperparathyroidism. STUDY DESIGN A 4-year, prospective, single-institution study of 6,000 patients undergoing parathyroidectomy for primary hyperparathyroidism and discharged within 2.5 hours. Based on our previous studies, patients are started on a sliding scale of oral calcium determined by a number of preoperative measures (ie, serum calcium, body weight, osteoporosis) beginning 3 hours postoperation and decreasing to a maintenance dose by week 3. Patients reported all hypocalcemia symptoms daily for 2 weeks. RESULTS Seven parameters were found to have a substantial impact on the amount of calcium required to prevent symptomatic hypocalcemia: preoperative serum calcium >12 mg/dL, >13 mg/dL, and >13.5 mg/dL, bone density T score less than -3, morbid obesity, removal of >1 parathyroid, and manipulation/biopsy of all remaining glands (all p < 0.05). Each independent variable increased the daily calcium required by 315 mg/day. Using our scaled protocol, <8% of patients showed symptoms of hypocalcemia, nearly all of whom were successfully self-treated with additional oral calcium. Only 6 patients (0.1%) required a visit to the emergency room for IV calcium, all occurring on postoperative day 3 or later. CONCLUSION After outpatient parathyroidectomy, a specific calcium protocol has been verified that eliminates development of symptomatic hypocalcemia in >92% of patients, identifies patients at high risk for hypocalcemia, and allows self-medication with confidence in a predictable fashion for those patients in whom symptoms develop.

Minimally invasive radio-guided parathyroidectomy in 152 consecutive patients with primary hyperparathyroidism.

OBJECTIVE To examine the results of minimally invasive radio-guided parathyroidectomy (MIRP) in the treatment of patients with primary hyperparathyroidism, including factors associated with negative technetium-labeled sestamibi scanning. METHODS We retrospectively analyzed the findings in a group of 152 consecutive patients encountered during the period 2001 through 2004. The overall accuracy of preoperative sestamibi scanning was assessed, and the success of MIRP was determined on the basis of operative time, duration of hospital stay, and rate of complications. RESULTS All 152 patients underwent preoperative sestamibi scanning; 118 (78%) had positive scans and were treated with MIRP, whereas 34 (22%) had negative scans and underwent traditional neck explorations. Patients with negative sestamibi scans had 5 times the incidence of concomitant thyroid disease in comparison with those who had positive sestamibi scans (P<0.01), and they had higher rates of parathyroid hyperplasia (26% versus 0%; P<0.01). In comparison with traditional neck dissection, MIRP-treated patients had shorter operative times (38 minutes versus 86 minutes; P<0.01) and shorter hospital stays (0.67 day versus 1.09 days; P<0.01). Among the MIRP-treated patients, 67% were discharged the same day as performance of the outpatient surgical procedure. Correction of hypercalcemia was accomplished in 116 of 118 patients (98%) who underwent MIRP. Complications in the MIRP group were low, including 1 postoperative hemorrhage. No cases of recurrent laryngeal nerve injury occurred. There were 2 false-positive sestamibi scans (1.3%). CONCLUSION Parathyroid hyperplasia and concomitant thyroid pathologic conditions are associated with negative preoperative sestamibi scans. MIRP is applicable in 78% of patients with primary hyperparathyroidism and is a safe, effective operation that results in shorter surgical time, reduced hospital stay, and minimal complications.

Prospective Study in 3,000 Consecutive Parathyroid Operations Demonstrates 18 Objective Factors that Influence the Decision for Unilateral versus Bilateral Surgical Approach

BACKGROUND Although localizing studies are well-known predictors of which patients are candidates for unilateral versus bilateral parathyroid exploration, there are a number of other factors that have positive or negative influence preoperatively and intraoperatively. STUDY DESIGN A prospective study was conducted during 20 months on 3,000 consecutive patients undergoing surgery for primary hyperparathyroidism to determine which factors caused the surgeons to explore bilaterally or, in contrast, influenced a unilateral approach. Seventeen preoperative and 5 intraoperative objective points were documented on all patients to see how decisions were made. RESULTS Parathyroidectomy was unilateral in 32% and bilateral in 68%. Preoperative factors that had a positive predictive value in dictating a unilateral approach were (in decreasing frequency): positive sestamibi, previous parathyroid/thyroid surgery, age older than 80 years, anticoagulation medications, morbid obesity, and presence of large goiter (all p < 0.001). Preoperative parameters dictating a bilateral approach included negative sestamibi, more than one focus on sestamibi, contralateral thyroid disease, family history, lithium use, history of radiation, MEN, age younger than 20 years, and pregnancy (all p < 0.001). Intraoperative parameters influencing conversion of unilateral to bilateral were false-positive sestamibi, hormone measures not meeting sufficient levels, abnormal ipsilateral gland, and contralateral thyroid pathology identified (all p < 0.001). Factors that had no effect were gender, degree of calcium, and/or parathyroid hormone elevation, and age between 20 and 80 years. Cure rates were 99.9% for bilateral and 99.0% for unilateral (p = 0.057). CONCLUSIONS High-volume surgeons use a number of identifiable objective factors to determine the best candidates for unilateral versus bilateral parathyroid exploration. Localizing studies such as sestamibi scans ultimately play a minor role in determining how many parathyroid glands are evaluated.

The effect of vitamin D levels on postoperative calcium requirements, symptomatic hypocalcemia, and parathormone levels following parathyroidectomy for primary hyperparathyroidism

BACKGROUND Low vitamin D-25 is common in primary hyperparathyroidism but the effect of this deficiency on postparathyroidectomy calcium requirements is unclear. METHODS A prospective study was conducted on 4 groups based on preoperative vitamin D-25 levels: very low (<20 ng/mL, n = 500); low (21 to 30 ng/mL, n = 500); normal (>30 ng/mL, n = 500); and supplemented (<25 ng/mL supplemented to >40 ng/mL, n = 285). Patients were placed on identical postoperative oral calcium regimens, and hypocalcemia symptoms were recorded. Total calcium requirements for 2 weeks postoperation were calculated and parathormone (PTH) levels were measured for 2-6 months. RESULTS Mean vitamin D levels (ng/mL) for each group were: very low (14.2); low (24.4); normal (38.3); and supplemented (16.5 supplemented to 54.3). Postoperative oral calcium requirements (in grams) were identical for all groups (18.7, 18.2, and 18.6, and 19.0, respectively, all P = NS); the incidence and timing of hypocalcemia symptoms were nearly identical for all groups: 8.1%, 7.9%, and 7.8% (P = .8). Elevated postsurgical PTH was identical (below 8%) and was not influenced by vitamin D levels. CONCLUSION The incidence of hypocalcemic symptoms and the postoperative calcium requirements are identical for patients with very low, low, normal, or supplemented (high) vitamin D. The incidence of persistently elevated PTH postoperatively is also unrelated to preoperative vitamin D levels. Vitamin D supplementation from very low to high levels has no clinical benefit.

Shingles (varicella zoster) outbreaks in patients with hyperparathyroidism and their relationship to hypercalcemia.

Shingles (varicella zoster) can be a presenting symptom of hyperparathyroidism and occurs twice as often (rate, 3.7%) among patients with hypercalcemia than in age-matched cohorts of patients >40 years of age who have normal calcium levels. The incidence of shingles increased in a linear fashion, from an annual rate of 1.5% among patients with serum calcium levels <10.5 mg/dL to 11% among patients whose calcium levels reached 13 mg/dL (P<.05), a rate that is 6 times greater than that among age-matched historical control individuals (P<.05).

Concentration of serum calcium is not correlated with symptoms or severity of primary hyperparathyroidism: An examination of 20,081 consecutive adults

Background. Guidelines for operative treatment of primary hyperparathyroidism include calcium levels >1 mg/dL above normal. We sought to determine whether greater calcium concentrations were associated with increased symptoms or disease severity. Methods. A retrospective review of a prospectively maintained database of adults undergoing parathyroidectomy for primary hyperparathyroidism, grouped according to greatest preoperative calcium level: those patients with calcium concentrations between 10.0 and 11.0 mg/dL and those with >11.0 mg/dL. We compared subjective symptoms and objective measures of disease severity. Results. The review included 20,081 adults who were split nearly evenly between calcium concentrations between 10.0 and 11.0 (10,430, 51.9%) and those with >11.0 mg/dL (9,651, 48.1%). In both groups, an absence of symptoms related to primary hyperparathyroidism was uncommon (<5%). All subjective and objective measures of disease severity were nearly identical with no significant differences (percentages for calcium concentrations between 10.0 and 11.0 and those with >11.0 mg/dL, respectively), including fatigue (72% for both groups), heartburn (37% vs 34%), bone pain (50% vs 48%), sleep disturbances (68% vs 65%), osteoporosis (40% in both groups), kidney stones (21% vs 22%), chronic kidney disease with glomerular filtration rate <60 (29% vs 32%), and hypertension (50% vs 53%). Conclusion. Serum calcium concentrations of greater than or less than 11 mg/dL are unrelated to symptoms and disease severity in primary hyperparathyroidism. There is no evidence to support a serum calcium threshold in parathyroidectomy guidelines.

Intrathyroid Parathyroid The Case against Thyroid Lobectomy

OBJECTIVE: Clinical trials have suggested suppression of EGFR pathway results in improved response to radiotherapy. AKT is a component of the phosphatidylinositol-3 kinase pathway that is downstream of the EGF receptor. Here we perform a preclinical assessment of the augmentation effect of AKT inhibitor on radiotherapy for head and neck squamous cell carcinoma. METHOD: Ex vivo ATP analysis on human tissue samples was performed to measure metabolic activity. Treatment groups were classified as control, AKT inhibitor, cetuximab and AKT i cetuximab. Nude mice with human SCC1-flank tumor xenografts were treated with combination treatments of 120 mg/kg AKT inhibitor, 10 mg/kg cetuximab, and 2 Gy radiation. Tumor size was assessed after each treatment using a pair of digital calipers. RESULTS: Ex vivo treatment with an AKT inhibitor alone significantly reduced ATP metabolic activity in human tissue specimens compared to control (64%, p 0.04). Combination treatment with cetuximab further enhanced this effect (29%, p 0.01). In vivo SCC1 flank tumor xenografts in Nude mice were significantly smaller following 2 weeks combination treatment with AKT i, cetuximab and radiation (15 mm) compared to control (102 mm, p 0.02) or radiation monotherapy (56 mm, p 0.05). CONCLUSION: Inhibition of the AKT pathway augments treatment with cetuximab on ex vivo human tissue and combination treatment with cetuximab and radiation in vivo.