BIOCHEMICAL DYNAMICS OF UNTREATED PRIMARY HYPERPARATHYROIDISM: AN OBSERVATIONAL STUDY.

Objective: The natural biochemical history of untreated primary hyperparathyroidism (PHPT) is poorly understood. The purpose of this study was to determine the extent of biochemical fluctuations in patients with PHPT. Methods: Retrospective cohort study from January 1, 1995, to December 31, 2014. Serum calcium and parathyroid hormone (PTH) levels in patients with classic (Ca >10.5 mg/dL, PTH >65 pg/mL) and nonclassic (Ca >10.5 mg/dL, PTH 40 to 65 pg/mL) PHPT were followed longitudinally at 1, 2, and 5 years. Biochemical profiles in follow-up were ranked in descending biochemical severity as classic PHPT, nonclassic PHPT, normal calcium with elevated PTH (Ca <10.5 mg/dL, PTH >65 pg/mL), possible PHPT (Ca >10.5 mg/dL, PTH 21 to 40 pg/mL), or absent PHPT (Ca >10.5 mg/dL, PTH <21 pg/mL or Ca <10.5 mg/dL, PTH <65 pg/mL). Results: Of 10,598 patients, 1,570 were treated with parathyroidectomy (n = 1,433) or medications (n = 137), and 4,367 were censored due to study closure, disenrollment, or death. In the remaining 4,661 untreated patients with 5 years of follow-up, 235 (5.0%) progressed to a state of increased biochemical severity, whereas 972 (20.8%) remained the same, and 3,454 (74.1%) regressed to milder biochemical states. In 2,522 untreated patients with classic PHPT, patients most frequently transitioned to the normal calcium with elevated PTH group (n = 1,257, 49.8%). In 2,139 untreated patients with nonclassic PHPT, patients most frequently transitioned to the absent PHPT group (n = 1,354, 63.3%). Conclusion: PHPT is a biochemically dynamic disease with significant numbers of patients exhibiting both increases and decreases in biochemical severity. Abbreviations: IQR = interquartile range; KPSC = Kaiser Permanente Southern California; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; PTx = parathyroidectomy.

The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study.

BACKGROUND: The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown. OBJECTIVE: To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT. DESIGN: Retrospective cohort study. SETTING: An integrated health care delivery system. PARTICIPANTS: All enrollees with biochemically confirmed PHPT from 1995 to 2010. MEASUREMENTS: Bone mineral density (BMD) changes and fracture rate. RESULTS: In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and declined progressively in both women and men without these treatments (-6.6% and -7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery. LIMITATION: Retrospective study design and nonrandom treatment assignment. CONCLUSION: Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation. PRIMARY FUNDING SOURCE: National Institute on Aging.

Fertility and pregnancy outcomes in primary hyperparathyroidism: Observations from a large insured population.

CONTEXT: Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association. OBJECTIVE: To compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT. DESIGN: Retrospective matched-cohort study (2005-2020). SETTING: An integrated healthcare delivery system in Southern California. PATIENTS: Women aged 18-44 years were included. Patients with biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). MAIN OUTCOME MEASURES: Achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care). RESULTS: The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI: 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with co-existing PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (p=0.023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n=22), during (n=5), or after pregnancy/never (n=24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium <11.5 mg/dL [2.9 mmol/L]. CONCLUSIONS: We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).

Hypothyroidism after hemithyroidectomy.

BACKGROUND: The risk of hypothyroidism after hemithyroidectomy is variable, and most estimates come from single institutional studies. The purpose of the present study was to determine the incidence of hypothyroidism at the population level, and to evaluate predictive factors for hypothyroidism after hemithyroidectomy. METHODS: This retrospective study identified euthyroid patients who underwent hemithyroidectomy between 2000 and 2010 for benign disease in Kaiser Permanente Southern California regional hospitals. The incidence of hypothyroidism [thyroid stimulating hormone (TSH) levels >4 µIU/ml] was analyzed. The independent effect of age-quartile, gender, race, thyroiditis, and preoperative TSH level on the development of hypothyroidism was evaluated. RESULTS: Of 1,240 euthyroid patients identified, 417 (34 %) developed hypothyroidism, and 314 (25 % of total group) needed levothyroxine. Hypothyroidism was more common in age-quartile 2 (32 %), age-quartile 3 (37 %), and age-quartile 4 (42 %) than in age-quartile 1 (25 %) [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI) 1.27-2.76, p = 0.002; age-quartile 4 compared to age-quartile 1]. Hypothyroidism was more frequent with increasing preoperative TSH levels 36, 72, and 92 % in patients with TSH levels of 1.0-2, 2.01-3, and 3.01-4 µIU/ml, respectively, compared to 17 % in those with TSH levels <1 µIU/ml [adjusted OR = 45.1; 95 % CI 13.5-151, p < 0.0001; 3.01-4 µIU/ml compared to <1 µIU/ml]. Thyroiditis was also an independent predictor of hypothyroidism. CONCLUSIONS: About one third of euthyroid patients who undergo hemithyroidectomy develop hypothyroidism. The most significant predictor is the preoperative TSH level, with an approximate doubling of risk for each 1 unit of TSH increase over 1 µIU/ml. Our categorical scale is simple and allows for easy recall when counseling patients preoperatively.

Long-term effects of primary hyperparathyroidism and parathyroidectomy on kidney function.

IMPORTANCE: Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT). OBJECTIVE: To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes. DESIGN: Matched control study. SETTING: A vertically integrated health care system serving 4.6 million patients in Southern California. PARTICIPANTS: 6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016. EXPOSURES: Biochemically confirmed PHPT with varying serum calcium levels. MAIN OUTCOMES: Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74 mmol/L (10.5-11 mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively. RESULTS: Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (−1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (−1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of −1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (−1.5 mL/min/1.73 m2/year, P < .001) and >2.99 mmol/L (−2.1 mL/min/1.73 m2/year, P < .001), comprising 9% and 7% of cases, respectively. In the propensity score­matched population, patients with serum calcium >2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (−2.0 [95% CI: −2.6 to −1.5] to −0.9 [95% CI: −1.5 to 0.4] mL/min/1.73 m2/year). CONCLUSIONS AND RELEVANCE: Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87 mmol/L (11.5 mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87 mmol/L.

Surgery for primary hyperparathyroidism: are the consensus guidelines being followed?

OBJECTIVE: To determine parathyroidectomy (PTx) rates in patients who satisfy the consensus guidelines for surgical treatment of primary hyperparathyroidism (PHPT). BACKGROUND: Surgery for PHPT is recommended for all symptomatic patients and select asymptomatic patients meeting established consensus criteria. Adherence to the consensus guidelines has not been examined systematically, because of inadequate information regarding patients managed nonoperatively. METHODS: All nonuremic patients with PHPT during the period 1995-2008 were identified using the Kaiser Permanente-Southern California laboratory database, encompassing 3.5 million individuals annually. Multivariate logistic regression was used to examine predictors of PTx. RESULTS: We found 3388 patients with PHPT, of whom 265 (8%) were symptomatic (nephrolithiasis). Nephrolithiasis was predictive of PTx (OR 2.94 vs asymptomatic), with 51% of symptomatic patients undergoing surgery. Among asymptomatic patients, the proportion meeting consensus criteria was 39% during the early period (1995-2002) and 51% during the late period (2003-2008). The PTx rate for these patients exceeded that for asymptomatic patients not meeting consensus criteria but remained low (early 44% vs 19%, P < 0.0001; late 39% vs 16%, P < 0.0001). The following individual criteria were predictive of PTx: calcium >11.5 mg/dL (OR 2.27), hypercalciuria (OR 3.28, P < 0.0001), and age < 50 years (OR 1.54, P < 0.0001). However, the absolute PTx rates associated with satisfaction of these criteria were in the 50% range. Bone density scores did not influence likelihood of PTx and renal impairment predicted against PTx (OR 0.35, P < 0.0001). CONCLUSIONS: The consensus guidelines regarding PHPT have not been followed in our study population. PTx appears to be underutilized in both asymptomatic and symptomatic patients.

Defunctioning loop ileostomy for pelvic anastomoses: predictors of morbidity and nonclosure.

OBJECTIVE: The aim of this study was to determine the morbidity of a defunctioning loop ileostomy and the subsequent closure rate, and to identify the predictors of complications and nonclosure of stoma. DESIGN: This study is a retrospective review of a single-institution experience. PATIENTS: All patients who underwent a planned temporary defunctioning loop ileostomy performed synchronously with a pelvic anastomosis during a 6-year period were included. MAIN OUTCOME MEASURES: The primary outcome measures were the ileostomy complication rate for the entire spectrum of care, readmission and reoperation rates to treat ileostomy complications, and subsequent closure rate. Patient and treatment factors were evaluated for their independent effect on complications and closure rate with the use of multivariable logistic regression. RESULTS: One hundred twenty-three patients were identified (median age, 51 years). Of these patients, 64.2% developed ≥1 minor or major ileostomy complications (13.8% during index hospitalization, 52.8% as outpatient, and 23.4% after closure). Readmitted for dehydration following ileostomy formation were 11.4% of patients. The ileostomy was closed in 76.4% of patients with 8.6% requiring a midline laparotomy. The overall ileostomy-related reoperation rate was 10.4% (2.4% during index hospitalization, 1.6% at readmission, and 6.4% following ileostomy closure). Obesity (BMI ≥30 kg/m) was associated with a higher overall ileostomy complication rate (OR 8.56, 95% CI 1.64-44.74) and outpatient complication rate (OR 7.69, 95% CI 2.48-23.81). Age >65 years (OR 53.34, 95% CI 4.21-676.14) and hypertension (OR 8.36, 95% CI 1.09-64.43) increased the risks of high ileostomy output and dehydration. Obesity (OR 4.61, 95% CI 1.14-18.54) and smoking (4.47, 95% CI 1.43-13.98) decreased the likelihood of ileostomy closure. LIMITATION: This study was limited by its retrospective nature. CONCLUSIONS: The morbidity of a defunctioning loop ileostomy remains significant. Obesity is an independent predictor of ileostomy complications. Older age and hypertension increase the risks of high-output stoma and dehydration. Almost one quarter of patients never have the ileostomy closed. Obesity and smoking are associated with less likelihood of a subsequent ileostomy closure.

Parathyroidectomy for nephrolithiasis in primary hyperparathyroidism: Beneficial but not a panacea.

BACKGROUND: Nephrolithiasis is a classic indication for parathyroidectomy in primary hyperparathyroidism patients; however, the effects of parathyroidectomy on nephrolithiasis recurrence are not well studied. The aim was to determine effect of parathyroidectomy on time to first nephrolithiasis recurrence and recurrence rate per patient-years. METHODS: A retrospective cohort study of patients diagnosed with primary hyperparathyroidism and at least one episode of nephrolithiasis was performed. The patients were divided into observation, presurgery, and postsurgery groups. Endpoints were time to first recurrence of nephrolithiasis and average recurrence rate per patient-years. RESULTS: The cohort was comprised of 1,252 patients. In addition, 334 (27%) patients underwent parathyroidectomy and 918 (73%) were observed. The surgical and nonsurgical groups differed significantly in age, sex, Charlson, calcium, and primary hyperparathyroidism level. Overall recurrence rate was 31.3%. The 5-, 10-, and 15-year recurrence-free survival rates were 74.4%, 56.3%, 49.5%, respectively (presurgery), 82.4%, 70.9%, 62.8%, respectively (postsurgery; P < .0001), and 86.3%, 77.7%, and 70.6%, respectively (observation). The presurgery group had an increased risk of first recurrence compared with the observation group (hazard ratio 1.89; 95% confidence interval, 1.44-2.47). The average recurrence rates among all surgical patients who recurred were 1 event per 4.3 patient-years presurgery versus 1 event per 6.7 patient-years postsurgery (P = .0001). CONCLUSION: Recurrent nephrolithiasis is a significant problem in patients with primary hyperparathyroidism. Parathyroidectomy prolongs the time to first recurrence and decreases the number of re-recurrences over time but does not eliminate recurrences. Observation may also be a reasonable approach in selected patients.

Outpatient treatment of acute diverticulitis: rates and predictors of failure.

PURPOSE: Many patients with acute diverticulitis can be managed as outpatients, but the success rate of this approach has not been thoroughly studied. We analyzed a large cohort of patients treated on an outpatient basis for an initial episode of acute diverticulitis to test our hypothesis that outpatient treatment of acute diverticulitis is highly effective. METHODS: We analyzed patients within the Kaiser Permanente Southern California system (from 2006 to 2007) who were diagnosed with an initial episode of diverticulitis during an emergency room visit and subsequently discharged home. Each patient underwent a computed tomography (CT) scan for diagnosis or for confirmation of a diagnosis, and each radiologic report was evaluated regarding the presence of free fluid, phlegmon, perforation, and abscess. Treatment failure was defined as a return to the emergency room or an admission for diverticulitis within 60 days of the initial evaluation. RESULTS: Our study included 693 patients, of whom 54% were women, the average age was 58.5 years, and 6% failed treatment. In multivariate analysis, women (odds ratio, 3.08 [95% CI, 1.31-7.28]) and patients with free fluid on CT scan (odds ratio, 3.19 [95% CI, 1.45-7.05]) were at significantly higher risk for treatment failure. Age, white blood cell count, Charlson score, and duration of antibiotics were not significant predictive factors. CONCLUSIONS: In a retrospective analysis, among a cohort of patients who were referred for outpatient treatment, we found that such treatment was effective for the vast majority (94%) of patients. Women and those with free fluid on CT scan appear to be at higher risk for treatment failure.

Should barium enema be the next step following an incomplete colonoscopy?

INTRODUCTION: Double contrast barium enema (DCBE) is used to screen and diagnose colorectal disease and is often recommended following an incomplete colonoscopy. The purpose of this study was to determine the value of DCBE following an incomplete colonoscopy. MATERIALS AND METHODS: A retrospective review was conducted of all patients who had an incomplete colonoscopy at Kaiser Permanente, Los Angeles in a 6-year period. Patient data was extracted from the endoscopy and radiology databases. Variables collected included demographics, indication for colonoscopy, reason for incompletion, findings of DCBE, and findings of repeat colonoscopy if subsequently performed. RESULTS: The incomplete colonoscopy rate was 1.6%. The mean age was 62 years with a predominance of females. The most common indication for colonoscopy was screening. The most frequent reason attributed to an incomplete colonoscopy was patient discomfort. Two hundred thirty three patients underwent DCBE and 42 patients underwent a repeat colonoscopy without DCBE; 13.3% of the DCBE were of poor quality and could not be interpreted. A repeat colonoscopy following DCBE was performed in 7% of patients. In 50% of these patients, the repeat colonoscopy revealed significant findings not noted on the DCBE or ruled out positive DCBE findings. In patients who had repeat colonoscopy without DCBE, completion rate was 95%. CONCLUSION: The rate of incomplete colonoscopy in a high-volume modern endoscopy unit is extremely low. DCBE following incomplete colonoscopy has limited value. A repeat colonoscopy under deeper sedation and/or better bowel preparation may be the preferred next step.

Skeletal effects of combined medical and surgical management of primary hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX) increases bone mineral density and decreases fracture risk in patients with primary hyperparathyroidism. This study examined the effect of adding bisphosphonates either before or after PTX on skeletal outcomes. METHODS: A retrospective cohort study of bisphosphonate-naïve patients (1995-2016) with osteoporosis and primary hyperparathyroidism (calcium >10.5 mg/dL; PTH >65) was performed. Time-varying Cox regression was used to estimate an adjusted risk of any fracture in 5 comparison groups: observation, bisphosphonates alone, PTX alone, bisphosphonates then PTX, and PTX then bisphosphonates. The secondary outcome was change in bone mineral density of the hip. RESULTS: The cohort comprised 1,737 patients, of whom 303 underwent PTX (17%), 433 received bisphosphonates only (25%), 125 had bisphosphonates then PTX (7%), and 69 had PTX then bisphosphonates (4%). PTX was associated with a decrease in fracture risk (HR 0.55, 95% CI 0.35-0.84), as was bisphosphonates then PTX (HR 0.46, 95% CI 0.25-0.83). In contrast, the fracture risks associated with PTX then bisphosphonates (HR 1.09, 95% CI 0.65-1.81) and bisphosphonates alone (HR 0.82, 95% CI 0.62-1.08) were similar to observation. Hip bone mineral density increased after both PTX (5.50%, 95% CI 3.39-7.61) and PTX then bisphosphonates (6.30%, 95% CI 2.53-10.07). CONCLUSION: Bisphosphonate initiation after PTX may interfere with the beneficial effects of PTX on fracture risk in osteoporotic patients with primary hyperparathyroidism.

Who is at risk for developing chronic anal fistula or recurrent anal sepsis after initial perianal abscess?

PURPOSE: This study was designed to determine factors that contribute to chronic anal fistula or recurrent sepsis after initial perianal abscess. METHODS: A retrospective cohort study was conducted in patients with a first-time perianal abscess who were treated at Kaiser Permanente Los Angeles between 1995 and 2007. Univariate and multivariable analyses were performed with the Cox proportional hazards model to determine predictors of risk for recurrent disease. RESULTS: One hundred and forty-eight patients met inclusion criteria (105 men, 43 women; mean age, 43.6 years). During a mean follow-up of 38 months, the cumulative incidence of chronic anal fistula or recurrent sepsis was 36.5 percent. Univariate and multivariable analyses showed more than two-fold increased risk of recurrence in patients <40 years vs. those >/=40 years (P < 0.01), and univariate analysis showed nondiabetics were 2.69 times as likely to experience recurrence as diabetics (P = 0.04). No significant differences in risk of recurrence were noted for men vs. women (HR = 0.78; P = 0.39), nonsmokers vs. smokers (HR = 1.17; P = 0.58); perioperative antibiotics vs. no antibiotics (HR = 1.51; P = 0.19); or HIV-positive vs. HIV- negative status (HR = 0.72; P = 0.44). CONCLUSIONS: Age younger than 40 years significantly increased risk of chronic anal fistula or recurrent anal sepsis after a first-time episode of perianal abscess. Patients with diabetes may have a decreased risk compared with nondiabetic patients. Gender, smoking history, perioperative antibiotic treatment, and HIV status were not risk factors for chronic anal fistula or recurrent anal sepsis.

Botulinum toxin A with fissurectomy is a viable alternative to lateral internal sphincterotomy for chronic anal fissure.

Lateral internal sphincterotomy (LIS) is the gold standard surgical treatment for anal fissure. However, it carries potential complications, including fecal incontinence. The goal of this retrospective study was to compare the outcome of botulinum toxin A injection coupled with fissurectomy ([BTX + FIS) versus LIS. There were 59 patients who underwent BTX + FIS or LIS over a 5-year period. LIS was performed in the standard fashion without fissurectomy. BTX + FIS entailed internal sphincter injection with 80 units of botulinum toxin A coupled with fissurectomy. Forty patients underwent LIS and 19 had BTX + FIS. The choice of operation was based on the patient's preference. Primary healing rate was 90 and 74 per cent in the LIS and BTX + FIS groups, respectively (P = 0.13). The complication rate was 10 per cent in the LIS vs 0 per cent in the BTX + FIS groups (P = 0.29). Complications of LIS included anal sepsis in one patient and flatal and/or fecal incontinence in three patients. During a mean follow up of 19 months; recurrence rate was 0 and 5 per cent in the LIS and BTX+FIS groups, respectively (P = 0.32). The results of this study demonstrate that BTX + FIS is a viable alternative to LIS for patients with chronic anal fissure and should be considered as an alternative first-line surgical therapy.

Hypocalcemia after Total Thyroidectomy in Graves Disease.

CONTEXT: Total thyroidectomy has been shown to provide a cost-effective and efficient method of permanently treating Graves disease; however, hypocalcemia can be a common complication. OBJECTIVE: To evaluate the risk of hypocalcemia after total thyroidectomy in patients with vs without Graves disease. DESIGN: The 2016 American College of Surgeons National Surgical Quality Improvement Program participant use data files for procedure-targeted thyroidectomy and from 5871 patients were merged. This study included any patient who underwent total thyroidectomy. MAIN OUTCOME MEASURES: Whether symptomatic hypocalcemia developed anytime within 30 days after the thyroidectomy. A clinically severe hypocalcemic event was also evaluated as a secondary outcome measure. RESULTS: Of the 2143 patients who underwent total thyroidectomy, 222 patients experienced hypocalcemia after surgery, 124 of whom had symptomatic hypocalcemia postoperatively. Among patients with hypocalcemia, 16.3% had Graves disease, whereas only 9.4% of patients without Graves disease experienced significant hypocalcemia. Multivariable logistic regression analysis revealed that women (odds ratio = 1.79; 95% confidence interval = 1.16-2.76; p = 0.009) and patients who underwent parathyroid autotransplantation (odds ratio = 1.91; 95% confidence interval = 1.30-2.81; p = 0.001) were at greater risk of development of hypocalcemia. Older patients were less likely to experience hypocalcemia postoperatively (odds ratio = 0.586; 95% confidence interval = 0.44-0.79; p = 0.0001). CONCLUSION: Patients with Graves disease are about twice as likely to experience hypocalcemia or clinically severe hypocalcemia postoperatively than are patients without the disease.

End-organ effects of primary hyperparathyroidism: A population-based study.

BACKGROUND: Patients with primary hyperparathyroidism are at risk for skeletal and renal end-organ damage. METHODS: We studied patients with biochemically confirmed primary hyperparathyroidism from 1995-2014 and quantified the frequency of osteoporosis, nephrolithiasis, hypercalciuria, and decrease in renal function. RESULTS: The cohort comprised 9,485 patients. In total, 3,303 (35%) had preexisting end-organ effects (osteoporosis, 24%; nephrolithiasis, 10%; hypercalciuria, 5%). Of 6,182 remaining patients, 1,769 (29%) exhibited progression to 1 or more end-organ effects over a median 3.7 years. Among patients with classic primary hyperparathyroidism (calcium and parathyroid hormone increased), progression was unrelated to the degree of hypercalcemia (calcium >11.5 mg/dL, hazard ratio 1.03, 95% confidence interval 0.85-1.25; 11.1-11.5 mg/dL, HR 1.07, 95% confidence interval 0.93-1.23; 10.5-11.0 mg/dL = reference). Patients with nonclassic primary hyperparathyroidism (calcium increased, parathyroid hormone 40-65 pg/mL) had a lesser risk of progression (calcium >11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.50-0.94; 11.1-11.5 mg/dL, hazard ratio 0.68, 95% confidence interval 0.56-0.82; 10.5-11.0 mg/dL, hazard ratio 0.66, 95% confidence interval 0.59-0.74). End-organ damage developed before or within 5 years of diagnosis for 62% of patients. CONCLUSION: End-organ manifestations of primary hyperparathyroidism develop before biochemical diagnosis or within 5 years in most patients. End-organ damage occurred more frequently in patients with classic primary hyperparathyroidism versus nonclassic primary hyperparathyroidism, regardless of severity of hypercalcemia.

Skeletal effects of failed parathyroidectomy.

BACKGROUND: Parathyroidectomy improves bone mineral density and decreases risk for fracture in patients with primary hyperparathyroidism. The aim of this study was to determine skeletal consequences of failed parathyroidectomy. METHODS: A retrospective, cohort study of patients with biochemically confirmed primary hyperparathyroidism within a vertically integrated health system was performed (1995-2014). Failed parathyroidectomy was defined by hypercalcemia within 6 months of initial parathyroidectomy. Time-varying Cox regression was used to estimate the risk for any fracture and hip fracture in 3 comparison groups: observation, successful parathyroidectomy, and failed parathyroidectomy. Bone mineral density changes also were compared. RESULTS: The cohort included 7,169 patients, of whom 5,802 (81%) were observed, 1,228 underwent successful parathyroidectomy (17%), and 137 underwent failed parathyroidectomy (2%). The adjusted risk for any fracture (hazard ratio, 1.28; 95% confidence interval, 0.85-1.92) and hip fracture (hazard ratio, 1.63; 95% CI, 0.77-3.45) associated with failed parathyroidectomy was similar to that associated with observation. Successful parathyroidectomy was associated with a decrease in any fracture (hazard ratio, 0.68; 95% confidence interval, 0.57-0.82) and hip fracture (hazard ratio, 0.43; 95% confidence interval, 0.27-0.68) compared with observation. Bone mineral density changes in the failed parathyroidectomy group paralleled those associated with observation. CONCLUSION: Failed parathyroidectomy is associated with a high risk for fracture similar to that seen with observation.

Influence of a negative sestamibi scan on the decision for parathyroid operation by the endocrinologist and surgeon.

BACKGROUND: It has been observed that negative sestamibi scans may impact practice patterns in patients with primary hyperparathyroidism. However, there are no published data on the issue. The objective was to elucidate the influence of negative sestamibi scans on referrals by endocrinologists for parathyroidectomy and surgeon decision-making. METHODS: All patients with primary hyperparathyroidism were identified within a region-wide health care system over a 2-year period. Data, including age, calcium, parathyroid hormone, renal function, bone density, and sestamibi scan results, were collected from the electronic medical record of all patients. The electronic referral system was used to track consultations with endocrinologists and surgeons. Multivariable logistic regression analysis was done to model factors involved in endocrinologist recommendations (referral or no referral to operation) and surgeon recommendations (parathyroidectomy or no parathyroidectomy). RESULTS: A total of 539 patients with primary hyperparathyroidism were identified, and 452 were seen by endocrinologists. Of these, 260 patients had sestamibi scans done (120 negative and 140 positive), and 201 (77%) patients were referred to surgeons. Compared with positive sestamibi scans, negative sestamibi scans were independently associated with no referral to surgeons, after adjusting for presence of classic symptoms, age, fitness for operation, calcium, parathyroid hormone, glomerular filtration rate, and bone density (odds ratio = 0.36; 95% confidence interval 0.18-0.73). Surgeons saw an additional 54 patients referred from nonendocrinologists or primary care physicians and sestamibi scans were completed. Surgeons recommended parathyroidectomy in 236 of the 255 patients. Negative sestamibi scans were independently associated with no recommendation for operation (odds ratio = 0.32; 95% confidence interval 0.11-0.91). Surgeons initially scheduled and completed parathyroidectomies in 211/255 patients. Cure rate after operation was 98%, and this was not influenced by the sestamibi scan result. CONCLUSION: Negative sestamibi scans influence decision making in the management of patients with primary hyperparathyroidism. Endocrinologists commonly order sestamibi scans, and if negative, they are less likely to refer patients to surgeons. Surgeons are also influenced by sestamibi scans, and if negative, they are less likely to recommend parathyroidectomy. Cure rate in sestamibi-negative patients is excellent after operation.

Population-Level Incidence and Predictors of Surgically Induced Diabetes and Exocrine Insufficiency after Partial Pancreatic Resection.

CONTEXT: Endocrine and exocrine insufficiency after partial pancreatectomy affect quality of life, cardiovascular health, and nutritional status. However, their incidence and predictors are unknown. OBJECTIVE: To identify the incidence and predictors of new-onset diabetes and exocrine insufficiency after partial pancreatectomy. DESIGN: We retrospectively reviewed 1165 cases of partial pancreatectomy, performed from 1998 to 2010, from a large population-based database. MAIN OUTCOME MEASURES: Incidence of new onset diabetes and exocrine insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8% had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months, diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235 (34.7%) patients. Independent predictors of new-onset diabetes were higher Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02; HR = 1.95 for CCI ≥ 2, p < 0.01) and pancreatitis (HR = 1.51, p = 0.03). There was no difference in diabetes after Whipple procedure vs distal pancreatic resections, or malignant vs benign pathologic findings. Independent predictors of exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR = 1.85 for CCI of 1, p < 0.01; HR = 2.05 for CCI ≥ 2, p < 0.01). Distal resection and Asian race predicted decreased exocrine insufficiency (HR = 0.35, p < 0.01; HR = 0.54, p < 0.01, respectively). CONCLUSION: In a large population-based database, the rates of postpancreatectomy endocrine and exocrine insufficiency were 40% and 35%, respectively. These data are critical for informing patients' and physicians' expectations.