Mild Primary Hyperparathyroidism Research Articles

Surgery for ‘asymptomatic’ mild primary hyperparathyroidism improves some clinical symptoms postoperatively

Most primary hyperparathyroidism (pHPT) patients do not conform to the guidelines for parathyroidectomy established by an international panel of specialists and have a mild pHPT. This group is typically defined as 'asymptomatic'. The primary aim of this study was to determine symptom improvement in this 'asymptomatic' group after parathyroidectomy. Secondly, we aimed to create a preoperative clinical score predicting postoperative symptom resolution. A prospective nonrandomized study included patients with mild pHPT. A questionnaire (22 items) was given to 'asymptomatic' patients preoperatively and at 3, 6, and 12 postoperative months. A logistic regression was performed to create a preoperative clinical score. One hundred and sixteen patients were included. Postoperatively, HPT was resolved in 98% of patients. Twelve of 22 nonspecific symptoms were improved at 1 year. Subgroups analysis showed a greater improvement in patients <70 years and those with a serum calcium level ≥2.6 mmol/l preoperatively. A clinical score, based on age and five symptoms, was established to predict the clinical improvement after surgery in mild pHPT patients with a positive predictive value of 81%. Patients with asymptomatic pHPT have clinical improvement of their symptoms postoperatively even after 1 year. Younger patients and those with higher preoperative calcium levels show the best improvement.

Multigland Disease and Slower Decline in Intraoperative PTH Characterize Mild Primary Hyperparathyroidism

Many patients with primary hyperparathyroidism (PHPT) present with less severe biochemical parameters. The purpose of this study was to compare the presentation, operative findings, and outcomes of these patients with "mild" PHPT to patients with "overt" disease. A retrospective review of a prospectively collected parathyroid database was performed to identify cases of PHPT undergoing an initial neck operation. Patients were classified as mild when either the preoperative calcium or PTH was within the normal limits. Comparisons were made with the Student's t test, Chi-squared test, or Wilcoxon rank-sum test where appropriate. Kaplan-Meier estimates were plotted for disease-free survival and compared by the log-rank test. Of the 1,429 patients who met inclusion criteria, 1,049 were classified as overt and 388 (27.1 %) were mild. Within the mild group, 122 (31.4 %) presented with normocalcemic PHPT and 266 (68.6 %) had a normal PTH. The two groups had similar demographics and renal function. Interestingly, the mild group had more than double the rate of kidney stones (3.1 vs. 1.3 %, p = 0.02). The mild group was less likely to localize on sestamibi scan (62.4 vs. 78.7 %, p < 0.01). Intraoperatively, more mild patients exhibited multigland disease (34.3 vs. 14.1 %, p < 0.01). When examining intraoperative PTH (IoPTH) kinetics where single adenomas were excised, the IoPTH fell at a rate of 6.9 pg/min in mild patients compared with 11.5 pg/min in the overt group (p < 0.01). Accordingly, 62.2 % of patients in the overt group and 53.3 % in the mild group were cured at 5 min postexcision (p < 0.01). There was no difference in the rates of persistence or recurrence between the groups, and disease-free survival estimates were identical (p = 0.27). Patients with mild PHPT were more likely to have multigland disease and a slower decline in IoPTH, but these patients can be successfully treated with surgery.

SAT0396 High Frequency of Asymptomatic Primary Hyperparathyroidism in Patients with Fibromyalgia: A Fortuitous Association or a Misdiagnosis?

BackgroundFibromyalgia (FM) and primary hyperparathyroidism (PHPT) are diseases that can present similar symptoms such as musculoskeletal pain, cognitive impairment, nonrefreshing sleep, depression and anxiety, and thus, cause diagnostic confusion.ObjectivesTo determine...

Safety of Vitamin D Replacement in Patients with Primary Hyperparathyroidism and Concomitant Vitamin D Deficiency

To evaluate the safety of vitamin D replacement in patients with vitamin D deficiency and primary hyperparathyroidism. Retrospective chart review of 35 patients from our endocrine clinic, age 22 to 89 years, diagnosed with primary hyperparathyroidism and vitamin D deficiency, and treated with either 1,000 to 2,000 international units (IU) of vitamin D daily or 50,000 IU of vitamin D weekly for 5 months. Data were collected before and after treatment on serum calcium, 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), phosphorus, alkaline phosphatase, nephrolithiasis, fractures, and osteoporosis. 25-OH D increased significantly, from a baseline of 14.65 ± 6.57 ng/mL to 42.17 ± 12.98 ng/mL after weekly treatment with 50,000 IU of vitamin D (P<.0001), and from 22.42 ± 5.47 ng/mL to 33.33 ± 6.39 ng/mL following daily treatment with 1,000 to 2,000 IU of vitamin D (P<.0001). Pre- and posttreatment unadjusted serum calcium remained stable in the high-dose group (10.80 ± 0.43 mg/dL vs. 10.72 ± 0.67 mg/dL; P = .47), but decreased slightly in the low-dose group (10.76 ± 0.58 mg/dL vs. 10.11 ± 0.54 mg/dL; P = .0007). After adjusting for age, sex, vitamin D, and PTH levels, the small calcium difference in the low-dose group became statistically insignificant. Treatment with either high or low doses of vitamin D did not significantly change iPTH levels. Creatinine remained stable in all patients, and no new cases of nephrolithiasis were reported. Replacing vitamin D in mild primary hyperparathyroidism is safe, effective, and does not increase calcium to dangerous levels.

The value of intraoperative PTH measurements in patients with mild primary hyperparathyroidism

Intraoperative parathyroid hormone (ioPTH) measurement has facilitated a move to minimally invasive parathyroidectomy. Patients are referred for surgery earlier with milder hypercalcaemia and smaller tumours. Whilst previous research has shown that glands size can affect ioPTH kinetics in patients with multiple gland disease, the dynamics of ioPTH in patients with mild hyperparathyroidism (HPT) has not been studied. We therefore investigated the relationship between biochemical parameters and parathyroid adenoma weight, and determined the dynamics and accuracy of ioPTH assay in patients with milder hypercalcaemia undergoing parathyroidectomy. Patients undergoing parathyroidectomy for single gland disease from January 2004 to March 2011 were divided prospectively into two groups according to preoperative serum calcium: patients with a preoperative calcium ≥ 2.85 mmol/L (11.4 mg/dL) and <2.85 mmol/L were grouped as severe and mild hypercalcaemia, respectively. Correlation coefficients were calculated to assess the relationship between biochemical markers of calcium homeostasis and ioPTH measurements with respect to parathyroid gland weight. There was a weak correlation of preoperative serum calcium (r = 0.248, r = 0.207), PTH (r = 0.392, r = 0.275), and baseline ioPTH (r = 0.516, r = 0.244) with parathyroid gland weight in severe (n = 113) and mild groups (n = 190), respectively. No correlation between the magnitude in ioPTH drop with parathyroid gland weight at 5 or 10 min post-excision for either group was observed. Success rates (post-operative normocalcaemia) were similar for each group (99.1 % severe, 98.9 % mild). This prospective study provides evidence that ioPTH assay is a valuable tool in predicting adequate tissue removal in patients with milder and more severe hypercalcaemia due to single gland primary HPT.

What is the Diagnosis? Familial Hypocalciuric Hypercalcemia or Primary Hyperparathyroidism with Vitamin D Deficiency

Elevated calcium levels are a common finding in elderly patients. The most common causes are PHPT (Primary Hyperparathyroidism) and malignancy. FHH, which is also a cause of hypercalcemia, occurs less commonly. It is important to differentiate FHH from mild PHPT with concomitant vitamin D deficiency as both conditions have elevated serum PTH and calcium levels as well as normal or low 24-hour urinary calcium excretion. Serum 25-OHD should be measured in both cases. In mild PHPT with concomitant vitamin D deficiency, urinary calcium excretion increases with vitamin D repletion, thereby distinguishing it from FHH.

Lower quality of life in longstanding mild primary hyperparathyroidism

To describe the non-classical manifestations and quality of life in patients with primary hyperparathyroidism (PHPT). We evaluated non-classical manifestations and quality of life of 22 patients with PHPT using the SF-36 questionnaire according to the time since diagnosis. In the scores of quality of life, a significant difference was found comparing the groups with previous and recent diagnosis of PHPT in terms of functional capacity (39 + 22.83 vs. 76.25 + 22.37; p = 0.001), limitation of physical aspects (30 + 38.73 vs. 75 + 21.32; p = 0.006), general health (57.20 + 19.16 vs. 77.75 + 15.70; p = 0.012), and vitality (49.00 + 21.19 vs. 70.00 + 24.12; p = 0.044). We found a significant difference in quality of life in relation to the time of the diagnosis of PHPT.

Endothelial function in mild primary hyperparathyroidism

It is not known if endothelial dysfunction, an important early event in the pathogenesis of atherosclerosis, is present in mild primary hyperparathyroidism (PHPT) and if so, whether it improves following parathyroidectomy. We measured flow-mediated vasodilation (FMD), which estimates endothelial function by ultrasound imaging, in patients prior to and 6 and 12months after parathyroidectomy. Forty-five patients with mild PHPT [80% female, 61±1 (mean±SE) years, serum calcium 2·65±0·03mm (10·6±0·1mg/dl), PTH 10·5±0·7pm (99±7pg/ml), 25-hydroxyvitamin D (25OHD) 70·3±3·7nm (28·2±1·5ng/ml)] were studied. Baseline FMD was normal (4·63±0·51%; reference mean: 4·4±0·1%) and was not associated with serum calcium, PTH or 25OHD levels. In the group as a whole, FMD did not change after surgery (6months: 4·38±0·83%, P=0·72; 12 months: 5·07±0·74%, P=0·49). However, in those with abnormal baseline FMD (<2·2%; n=15), FMD increased by 350%, normalizing by 6months after surgery (baseline: 0·81±0·19%; 6months: 3·18±0·79%, P=0·02 vs baseline; 12months: 3·68±1·22%, P=0·04 vs baseline). Baseline calcium, PTH and 25OHD levels did not differ between those with abnormal vs normal FMD, nor did these indices predict postoperative change in FMD. FMD is generally normal in patients with mild PHPT and is unchanged 1year after parathyroidectomy. Although FMD may normalize after surgery in patients with baseline abnormalities, data do not support using endothelial dysfunction as an indicator for parathyroidectomy.

Nontraditional Manifestations of Primary Hyperparathyroidism

Classical primary hyperparathyroidism (PHPT) was previously a multisystemic symptomatic disorder not only with overt skeletal and renal complications but also with neuropsychological, cardiovascular, gastrointestinal, and rheumatic effects. The presentation of PHPT has evolved, and today most patients are asymptomatic. Osteitis fibrosa cystica is rarely seen today, and nephrolithiasis is less common. Gastrointestinal and rheumatic symptoms are not part of the clinical spectrum of modern PHPT. It remains unclear whether neuropsychological symptoms and cardiovascular disease, neither of which are currently indications for recommending parathyroidectomy (PTX), are part of the modern phenotype of PHPT. A number of observational studies suggest that mild PHPT is associated with depression, decreased quality of life, and changes in cognition, but limited data from randomized controlled trials (RCTs) have not indicated consistent benefits after surgery. The increased cardiovascular morbidity and mortality in severe PHPT has not been definitively demonstrated in mild disease, although there is some evidence for more subtle cardiovascular abnormalities, such as increased vascular stiffness, among others. Results from observational studies that have assessed the effect of PTX on cardiovascular health have been conflicting. The single RCT in this area did not demonstrate that PTX was beneficial. Despite recent progress in these areas, more data from rigorously designed studies are needed to better inform the clinical management of patients with asymptomatic PHPT.

BMD improvements after operation for primary hyperparathyroidism

This study aims to quantify bone mineral density (BMD) changes following surgery in patients with primary hyperparathyroidism (PHPT) and to assess their relationship with clinical and biochemical variables. A historic cohort of 236 PHPT patients with DXA scans pre- and 1-year postoperatively, clinical data, and biochemical data was analyzed. The mean age was 60 years (range 19-86) and 81 % of the patients were women. A significant postoperative 2.6 % (95 % CI, 2.1; 3.1) increase in lumbar spine BMD was seen. The increase in BMD was positively associated with preoperative plasma PTH (p = 0.002), Ca(2+) (p < 0.001), and alkaline phosphatase (p = 0.014). Hip BMD increased 1.5 % (1.1; 1.9). The increase in BMD was positively associated with preoperative plasma PTH (p = 0.005) and Ca(2+) (p < 0.001) and inversely associated with plasma creatinine (p = 0.004) and age (p = 0.018). Total forearm BMD did not change significantly (-0.2 % (-0.5; 0.1)). An increase in forearm BMD was seen in 38 % of all patients, and the changes were positively associated with plasma PTH (p < 0.001) and Ca(2+) (p = 0.009). In all 91 patients with mild PHPT (plasma Ca(2+) < 1.45 mmol/l), there was a significant postoperative increase in spine BMD (1.9 % (1.2; 2.7)) and in hip BMD (1.0 % (0.4; 1.6)), but not in the forearm BMD (-0.3 % (-0.7; 0.2)). The postoperative BMD gain was higher in the hip and forearm in patients operated for adenomas compared with patients treated for hyperplasia. We found significant postoperative BMD improvements both at the hip and the spine. BMD improvements were also significant in mild cases. At all scan sites, there were positive associations between preoperative plasma PTH levels and postoperative BMD increases. The measured BMD changes may mainly be due to a decrease in PTH-induced bone turnover with refilling of the remodeling space.

PDB20 Safety of Preoperative Vitamin D Replacement in Mild Primary Hyperparathyroidism With Vitamin D Deficiency: A Meta-Analysis

lected: cardiovascular disease, peripheral neuropathy, renal disease, retinopathy, cataract, hypoglycemia, ketoacidosis and adverse birth outcomes. CONCLUSIONS: Since 2003, 281 reports of 72 studies (including many large, observational studies) have been published. These reports have substantially increased the available evidence describing complications in T1DM patients. The DCCT/EDIC studies uniquely provide long-term follow-up (now more than 23 years) of patients managed using strategies that are reasonably representative of contemporary T1DM management.

The association between the IGF-I axis, thyroid hormones and cortical bone in patients with mild primary hyperparathyroidism

Objectives. Primary hyperparathyroidism (PHPT) is associated with low bone mineral density (BMD) and increased risk of osteoporotic fractures. This study investigated whether the IGF-I axis and thyroid hormones are associated with BMD and osteoporotic fractures before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with mild PHPT were examined before and 1 year after PTX. Circulating concentrations of IGF-1, IGFBP-3, and thyroid hormones were measured and related to BMD in hip and lumbar (L:2-L:4) spine. Results. Serum IGFBP-3 concentration decreased 1 year after PTX (p < 0.01), whereas serum IGF-1 and thyroid hormone concentrations were unchanged. Serum IGF1 concentration correlated positively with IGFBP-3 concentration (p < 0.0001) and BMD in the femoral neck (p < 0.05), both pre- and postoperatively. Serum IGFBP-3 concentration correlated positively with BMD in the femoral neck postoperatively (p < 0.05). Serum TSH correlated positively, and free thyroxine (T4) negatively, with all measures of hip BMD at baseline. Patients suffering from previous osteoporotic fractures before inclusion had lower serum TSH concentration compared to patients without fractures (p < 0.01). Conclusion. Serum IGFBP-3 concentration decreased after successful PTX in patients with mild PHPT, while serum IGF1 and thyroid hormone concentrations were unchanged. Both the IGF-I axis and thyroid hormones associated with cortical bone as serum IGF-1 and IGFBP-3 concentrations correlated positively, and free T4 negatively with hip BMD. Moreover, serum TSH concentration was reduced in patients with previous osteoporotic fractures.

Nonsurgical management of mild primary hyperparathyroidism – a reasonable option

Primary hyperparathyroidism (PHPT) is a relatively common disorder which is often diagnosed incidentally and characterized in the majority of those affected by mild stable biochemical abnormalities and lack of symptoms. Nephrolithiasis and bone loss leading to an increased risk of fracture are generally accepted complications of PHPT. Some epidemiological studies report associations between PHPT and a wide range of common diseases, but these relationships may be confounded by the increased body weight observed in PHPT. Because there is a dearth of controlled clinical trial evidence in PHPT, optimal management is controversial. For individuals with mild stable PHPT, low fracture risk and no renal stones, observation without intervention is reasonable. Surgical treatment is clearly indicated for patients at risk of severe hypercalcaemia or with nephrolithiasis. For individuals with increased risk of fracture, antiresorptive therapies improve bone mineral density to a similar degree to surgical treatment. Calcimimetic agents may have a role in managing patients with symptomatic PHPT who cannot undergo, or fail, surgical treatment. There is a need for additional randomized clinical trials to inform management of PHPT.

Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism

We recently demonstrated that mild primary hyperparathyroidism (PHPT) is associated with increased carotid intima-media thickness (IMT) and stiffness, and increased aortic valve calcification. It is unclear whether parathyroidectomy (PTX) improves these abnormalities. The purpose of this study was to determine whether cardiovascular abnormalities in PHPT improve with PTX. Forty-four patients with PHPT were studied using carotid ultrasound and transthoracic echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness, left ventricular mass index (LVMI), myocardial and valvular calcification, and diastolic function were measured before, 1- and 2-year post-PTX. Two years after PTX, increased carotid stiffness tended to decline to the normal range (17%, P=0.056) while elevated carotid IMT did not improve. Carotid plaque number and thickness, LVMI and cardiac calcifications did not change after PTX, while some measures of diastolic function (isovolumic relaxation time (IVRT) and tissue Doppler peak early diastolic velocity) worsened within the normal range. Indices did improve in patients with cardiovascular abnormalities at baseline. Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of clinical significance. More limited improvements also occurred in elevated IMT (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic dysfunction. In mild PHPT, PTX led to modest changes in some cardiovascular indices. Improvements were mainly evident in those with preexisting cardiovascular abnormalities, particularly elevated carotid stiffness. These findings are reassuring with regard to current international guidelines that do not include cardiovascular disease as a criterion for PTX.

Metabolic disorders and hypertension in mild primary hyperparathyroidism

Metabolic disorders and hypertension in mild primary hyperparathyroidism

Impact of vitamin D‐related serum PTH reference values on the diagnosis of mild primary hyperparathyroidism, using bivariate calcium/PTH reference regions

BACKGROUND, OBJECTIVE: An international consensus conference underlined the importance of defining upper parathyroid hormone (PTH) reference values based on 25-OH-vitamin D [25(OH)D] to diagnose mild primary hyperparathyroidism. We determined the importance of this factor in a Belgian population. Intact PTH and 25(OH)D were measured in 261 healthy controls (18-65 years, winter/summer). They were classified as 25(OH)D replete (50-153 nmol/l; n = 129) or deplete (8-50 nmol/l; n = 132). PTH was determined in 49 patients with surgically proven primary hyperparathyroidism. PTH thresholds for 95% specificities and corresponding sensitivities were computed from both 25(OH)D replete and deplete receiver operating characteristic (ROC) curves. The 95% bivariate reference ellipses, relating PTH to calcium for 25(OH)D replete and deplete controls, were compared to the PTH/calcium pairs of patients with primary hyperparathyroidism. Parathyroid hormone correlated with 25(OH)D (r = -0.3232; P < 0.0001). PTH normative values were 20% lower in 25(OH)D replete than deplete controls (P < 0.0001). PTH thresholds, providing 95% specificities for primary hyperparathyroidism diagnosis, were 7.6 pmol/l and 5.8 pmol/l, using ROC curves derived from 25(OH)D deplete or replete controls, respectively. Corresponding sensitivities were of 56%vs 88%, respectively (P < 0.05). The 95% PTH/calcium bivariate reference ellipses for?deplete and replete 25(OH)D controls differed, but the PTH/calcium pairs of patients with primary hyperparathyroidism did not overlap these ellipses. For a given specificity, primary hyperparathyroidism diagnostic parathyroid hormone thresholds were lower and sensitivities higher using ROC curves, derived from 25(OH)D replete vs deplete controls. The 25(OH)D status does not affect the efficiency of primary hyperparathyroidism diagnosis, using bivariate PTH/calcium reference density ellipses.

Adrenergic and cardiac dysfunction in primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity and premature death, but the underlying mechanisms are incompletely understood. The aim of this study was to investigate whether adrenergic dysfunction may be a contributing factor. Forty-nine patients with mild PHPT (serum calcium 2·7 ± 0·1 mM) and 48 control subjects, matched for age and sex, were examined; patients within 1 month before parathyroidectomy (PTX) and 6 months postoperatively; control subjects at inclusion. Heart rate variability (HRV) was analysed in 24-h electrocardiograms, and plasma concentrations of epinephrine and norepinephrine were measured at rest and immediately after standardized physical tests. At baseline, the patients showed, compared to the controls, reduced stress-related increase of circulating epinephrine (P < 0·05) and norepinephrine (P < 0·05). No significant change was observed 6 months after PTX. At baseline, there were no significant differences between patients and controls in HRV or heart rate, but 6 months after curative PTX, the patients showed significantly reduced HRV in both frequency and time domain, and their maximum and average heart rate had decreased (P = 0·011 and P = 0·018, respectively). The patients with the highest preoperative levels of circulating parathyroid hormone showed the greatest changes in heart rate and HRV postoperatively. This study demonstrates a previously unknown impairment of catecholamine response to physical stress in PHPT along with changes of HRV, also indicating adrenergic dysfunction. These factors should be considered in the ongoing controversy regarding the management of patients with mild 'asymptomatic' PHPT.

Hyperparathyroidism: Cancer and Mortality

Hyperparathyroidism is a commoner endocrinopathy today with a large number of asymptomatic patients in contrast to the scenario five decades ago. Surgery is indicated for patients fulfilling the NIH criteria who are mostly symptomatic while individuals with mild disease are managed conservatively. Several studies indicate increased risk of malignancy involving several sites and related mortality in primary hyperparathyroidism (PHPT) with the risk persisting for several years after surgery. PHPT is associated with structural & functional cardiac abnormalities and premature death from increased cardiovascular disease with risk normalising only several years after surgery. Mortality risk is associated with pre-operative serum calcium & parathormone and parathyroid adenoma weight. However, the issue of existence of similar risk and surgical benefit in mild PHPT is mired in controversy although some studies have shown an association and beneficial trends with surgery. With current evidence, it would be prudent to follow up PHPT patients for malignancy and cardiovascular disease and possibly adopt a more liberal attitude towards surgery.

Renal manifestations of primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is associated with nephrolithiasis and nephrocalcinosis. Hypercalciuria is one of the multiple factors that is implicated in the complex pathophysiology of stone formation. The presence of a renal stone (symptomatic or asymptomatic) categorizes PHPT as symptomatic and is an indication for parathyroid adenomectomy. Progression of nephrocalcinosis is largely reversible after successful surgery, but the residual risk persists. PHPT is also associated with declining renal function. In case of asymptomatic mild PHPT, annual renal functional assessment is advised. Guidelines suggest that an estimated glomerular filtration rate (eGFR) < 60 ml / minute / 1.73 m2 is an indication for parathyroid adenomectomy. This article discusses how to monitor and manage renal stones and other related renal parameters in case of PHPT.

Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy

Objectives: Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods: Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results: At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion: Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.