Robert A. Wermers

Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: An update on the changing epidemiology of the disease

We updated the incidence of primary hyperparathyroidism in Rochester, Minnesota. The lower rates previously noted persisted, whereas parathyroidectomies at our institution remained high. These data suggest an etiologic factor may be responsible for the peak incidence in the 1970s.

Increased Mortality of Patients With Diabetes Reporting Severe Hypoglycemia

OBJECTIVE Hypoglycemia is a cause of significant morbidity among patients with diabetes and may be associated with greater risk of death. We conducted a retrospective study to determine whether patient self-report of severe hypoglycemia is associated with increased mortality. RESEARCH DESIGN AND METHODS Adult patients (N = 1,020) seen in a specialty diabetes clinic between August 2005 and July 2006 were questioned about frequency of hypoglycemia during a preencounter interview; 7 were lost to follow-up and excluded from analysis. Mild hypoglycemia was defined as symptoms managed without assistance, and severe hypoglycemia was defined as symptoms requiring external assistance. Mortality data, demographics, clinical characteristics, and Charlson comorbidity index (CCI) were obtained from the electronic medical record after 5 years. Patients were stratified by self-report of hypoglycemia at baseline, demographics were compared using the two-sample t test, and risk of death was expressed as odds ratio (95% CI). Associations were controlled for age, sex, diabetes type and duration, CCI, HbA1c, and report of severe hypoglycemia. RESULTS In total, 1,013 patients with type 1 (21.3%) and type 2 (78.7%) diabetes were questioned about hypoglycemia. Among these, 625 (61.7%) reported any hypoglycemia, and 76 (7.5%) reported severe hypoglycemia. After 5 years, patients who reported severe hypoglycemia had 3.4-fold higher mortality (95% CI 1.5–7.4; P = 0.005) compared with those who reported mild/no hypoglycemia. CONCLUSIONS Self-report of severe hypoglycemia is associated with 3.4-fold increased risk of death. Patient-reported outcomes, including patient-reported hypoglycemia, may therefore augment risk stratification and disease management of patients with diabetes.

Survival after the Diagnosis of Hyperparathyroidism: A Population-based Study

BACKGROUND Reports of increased mortality from cardiovascular disease and malignancy in primary hyperparathyroidism have been based primarily on patients who have undergone parathyroidectomy. In order to assess the true impact of primary hyperthyroidism on mortality in the general population, we assessed survival in a large inception cohort of Rochester, Minnesota residents with primary hyperparathyroidism initially diagnosed over a 28-year span, the majority of whom were followed with uncomplicated disease. METHODS All Rochester residents with primary hyperparathyroidism first recognized in 1965 to 1992 were identified through the Rochester Epidemiology Project medical records linkage system. Included as cases were patients with pathologic confirmation of hyperthyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia for more than a year with no other cause. Survival was estimated using the Kaplan Meier product-limit method. The Cox proportional hazards model was used to determine associations, as relative hazards (RR) with 95% confidence intervals (CI), of various risk factors with time to death. RESULTS During the study period, 435 cases of primary hyperparathyroidism were identified. Altogether, parathyroid surgery was performed on 126 patients (29%), with a mean delay between the initial elevated serum calcium level and surgery of 3.3 years. Patients who underwent surgery had higher maximum serum calcium levels than the patients who were observed (mean+/-SD, 11.3+/-0.7 versus 10.7+/-0.4 mg/dL, P <0.00 1), but their mean ages were similar (54+/-16 versus 56+/-17 years). Overall survival in the patients with primary hyperthyroidism was better than expected (P=0.02), but by age-adjusted multivariate analysis, higher maximal serum calcium level was an independent predictor of mortality (RR=1.3 per mg/dL; 95% CI: 1.1-1.6; P <0.02). CONCLUSION Overall survival is not adversely affected among unselected patients with mild primary HPT in the community, although patients with more severe disease, as manifested by higher serum calcium levels, may have an increased risk of death.

The glucagonoma syndrome. Clinical and pathologic features in 21 patients.

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.

Use of a Decision Aid to Improve Treatment Decisions in Osteoporosis: The Osteoporosis Choice Randomized Trial

OBJECTIVE Poor adherence to therapy, perhaps related to unaddressed patient preferences, limits the effectiveness of osteoporosis treatment in at-risk women. A parallel patient-level randomized trial in primary care practices was performed. METHODS Eligible postmenopausal women with bone mineral density T-scores less than -1.0 and not receiving bisphosphonate therapy were included. In addition to usual primary care, intervention patients received a decision aid (a tailored pictographic 10-year fracture risk estimate, absolute risk reduction with bisphosphonates, side effects, and out-of-pocket cost), and control patients received a standard brochure. Knowledge transfer, patient involvement in decision-making, and rates of bisphosphonate start and adherence were studied. Data came from medical records, post-visit written and 6-month phone surveys, video recordings of clinical encounters, and pharmacy prescription profiles. RESULTS A total of 100 patients (range of 10-year fracture risk, 6%-60%) were allocated randomly to receive the decision aid (n=52) or usual care (n=48). Patients receiving the decision aid were 1.8 times more likely to correctly identify their 10-year fracture risk (49% vs 28%; 95% confidence interval [CI], 1.03-3.2) and 2.7 times more likely to identify their estimated risk reduction with bisphosphonates (43% vs 16%; 95% CI, 1.3-5.7). Patient involvement improved with the decision aid by 23% (95% CI, 13.6-31.4). Bisphosphonates were started by 44% of patients receiving the decision aid and 40% of patients receiving usual care. Adherence at 6 months was similarly high across both groups, but the proportion with more than 80% adherence was higher with the decision aid (n=23 [100%] vs n=14 [74%]; P = .009). CONCLUSION A decision aid improved the quality of clinical decisions about bisphosphonate therapy in at-risk postmenopausal women, did not affect start rates, and may have improved adherence.

Effects of Teriparatide in Postmenopausal Women with Osteoporosis on Prior Alendronate or Raloxifene: Differences between Stopping and Continuing the Antiresorptive Agent

OBJECTIVE The aim of the study was to assess adding vs. switching to teriparatide 20 microg/d in patients on alendronate or raloxifene. DESIGN We conducted a randomized, open-label trial. PATIENTS AND INTERVENTIONS Postmenopausal women with osteoporosis on alendronate or raloxifene for at least 18 months added teriparatide (Add groups) or switched to teriparatide (Switch groups) for 18 months. MAIN OUTCOME MEASURES We measured bone turnover markers (BTM) and bone mineral density (BMD). RESULTS In the alendronate stratum, increases in BTM were smaller in the Add vs. Switch group [6-month PINP (64 vs. 401%); bone ALP (15 vs. 71%); betaCTX (27 vs. 250%); all P < 0.001]. However, at 6 months, total hip BMD increased more in the Add vs. Switch group (1.4 vs. -0.8%; P = 0.002). In the Add vs. Switch group, 18-month BMD increments were higher in lumbar spine (8.4 vs. 4.8%; P = 0.003) and total hip (3.2 vs. 0.9%; P = 0.02), but not in femoral neck (2.7 vs. 2.3%; P = 0.75). In the raloxifene stratum, increases in BTM were also smaller in the Add vs. Switch group [6-month PINP (131 vs. 259%; P < 0.001), bone ALP (31 vs. 44%; P = 0.035), and betaCTX (67 vs. 144%; P = 0.001)]. At 6 months, total hip BMD increase was greater in the Add vs. Switch group (1.8 vs. 0.5%; P = 0.028). At 18 months, increases in lumbar spine (9.2 vs. 8.1%), total hip (2.8 vs. 1.8%), and femoral neck (3.8 vs. 2.2%) were not significantly different between groups. CONCLUSIONS In women with osteoporosis treated with antiresorptives, greater bone turnover increases were achieved by switching to teriparatide, whereas greater BMD increases were achieved by adding teriparatide.

Morbidity and Mortality Associated With Paget’s Disease of Bone: A Population-Based Study

Introduction: Limited information is available about the clinical features of Pagets disease of bone among unselected patients in the community. We examined morbidity and mortality associated with this condition in a large inception cohort of Olmsted County, MN, residents with a new diagnosis of Pagets disease from 1950 through 1994.

Clinical Spectrum of Hyperglucagonemia Associated With Malignant Neuroendocrine Tumors

OBJECTIVE To review the clinical features associated with hyperglucagonemia in malignant neuroendocrine tumors. MATERIAL AND METHODS We retrospectively reviewed the medical records of patients with hyperglucagonemia encountered at our institution from Oct. 17, 1988, through February 1993 who had a fasting serum glucagon level of at least 120 pg/mL (twice the normal value). The 71 study patients also had no evidence of a secondary cause of hyperglucagonemia and had pathologic confirmation of a neuroendocrine tumor. RESULTS The study group consisted of 46 men and 25 women with a median age of 57 years. Two patients had multiple endocrine neoplasia. Forty-nine patients had biochemically polyfunctional tumors, and 22 had hyperglucagonemia only. The most common initial symptoms were weight loss, abdominal pain, diarrhea, nausea, peptic ulcer disease, diabetes, and necrolytic migratory erythema (NME). Diabetes eventually developed in 25 patients and was associated with NME in 11. The highest median serum glucagon values occurred in patients with the glucagonoma syndrome or insulinomas, and the lowest median values were in those with carcinoid syndrome, Zollinger-Ellison syndrome, or diabetes without NME. Fasting glucagon and glucose measurements were not correlated. The most common hormonal syndromes were the Zollinger-Ellison syndrome and the glucagonoma syndrome. All the neuroendocrine tumors were malignant. Several methods of treatment, including surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization, were used. Death occurred in 29 patients at a median of 2.79 years after diagnosis; 42 patients were alive at a median of 2.86 years after diagnosis. CONCLUSION A mild degree of hyperglucagonemia can commonly be associated with multifunctional neuroendocrine tumors. The glucagonoma syndrome occurs in a few patients with malignant neuroendocrine tumors and hyperglucagonemia and is associated with very high serum glucagon levels. The correlation between serum glucagon levels and the development of diabetes is limited, and other factors such as insulin may be more important than hyperglucagonemia in the development of diabetes.

Hip and spine strength effects of adding versus switching to teriparatide in postmenopausal women with osteoporosis treated with prior alendronate or raloxifene

Many postmenopausal women treated with teriparatide for osteoporosis have previously received antiresorptive therapy. In women treated with alendronate (ALN) or raloxifene (RLX), adding versus switching to teriparatide produced different responses in areal bone mineral density (aBMD) and biochemistry; the effects of these approaches on volumetric BMD (vBMD) and bone strength are unknown. In this study, postmenopausal women with osteoporosis receiving ALN 70 mg/week (n = 91) or RLX 60 mg/day (n = 77) for ≥18 months were randomly assigned to add or switch to teriparatide 20 µg/day. Quantitative computed tomography scans were performed at baseline, 6 months, and 18 months to assess changes in vBMD; strength was estimated by nonlinear finite element analysis. A statistical plan specifying analyses was approved before assessments were completed. At the spine, median vBMD and strength increased from baseline in all groups (13.2% to 17.5%, p < 0.01); there were no significant differences between the Add and Switch groups. In the RLX stratum, hip vBMD and strength increased at 6 and 18 months in the Add group but only at 18 months in the Switch group (Strength, Month 18: 2.7% Add group, p < 0.01 and 3.4% Switch group, p < 0.05). In the ALN stratum, hip vBMD increased in the Add but not in the Switch group (0.9% versus –0.5% at 6 months and 2.2% versus 0.0% at 18 months, both p ≤ 0.004 group difference). At 18 months, hip strength increased in the Add group (2.7%, p < 0.01) but not in the Switch group (0%); however, the difference between groups was not significant (p = 0.076). Adding or switching to teriparatide conferred similar benefits on spine strength in postmenopausal women with osteoporosis pretreated with ALN or RLX. Increases in hip strength were more variable. In RLX‐treated women, strength increased more quickly in the Add group; in ALN‐treated women, a significant increase in strength compared with baseline was seen only in the Add group.

Depression in Primary Hyperparathyroidism: Prevalence and Benefit of Surgery

CONTEXT Patients with primary hyperparathyroidism (PHP) often report nonspecific symptoms including mood disturbances. OBJECTIVE The objective of the study was to determine the frequency of depression in PHP and assess its response to parathyroidectomy. METHODS A case-control study at a referral center in Rochester, MN, performed Patient Health Questionnaire-9 (PHQ-9) assessments in observed (n = 81) and surgical (n = 88) PHP and benign nontoxic surgical thyroid disease (n = 85) at baseline and 1, 3, 6, and 12 months after surgery or the initial questionnaire in observed PHP. Baseline PHQ-9 scores and their response to surgery were evaluated. RESULTS The groups were similar in gender and depression history, but PHP patients were older. Baseline PHQ-9 scores were 1.71 points higher in PHP than controls after adjusting for age and gender (P = .004). Clinically significant PHQ-9 scores (≥10) were twice as common in PHP (31.4%) compared with thyroid subjects (15.3%). Parathyroidectomy resulted in significant and sustained reductions in PHQ-9 scores, which were greater than observed PHP at all time points (P < .001). PHP patients with clinically significant PHQ-9 scores dropped to 7.4% (P < .001) and 7.6% (P < .001) at 1 month and 1 yr after parathyroidectomy. There were greater declines in PHQ-9 scores after parathyroidectomy at 1, 3, and 6 months (P < .001) and 1 yr (P = .061) compared with thyroid surgery. CONCLUSIONS Depression is common in patients with PHP. Parathyroidectomy results in greater improvement in PHQ-9 scores compared with thyroid surgery or observation of PHP.