Predictive value of postoperative day 1 parathyroid hormone levels for early and late hypocalcaemia after thyroidectomy.

PURPOSE: Early parathyroid hormone (PTH) levels after total thyroidectomy can predict patients at low risk of hypocalcaemia who can be discharged early without calcium supplementation. For centres without facility to perform early PTH levels, PTH levels sent on the first postoperative day (POD1) may be an alternative. However, there is less data regarding optimal cut-off PTH levels for POD1 discharge. METHODS: Retrospective review of prospective database of thyroid operations between September 2009 and February 2020 at tertiary referral centre. Main outcome measure was symptomatic hypocalcaemia. RESULTS: Five hundred seventy patients undergoing total (521) or completion thyroidectomy with POD1 PTH levels available were included. Among patients with POD1 PTH levels ≥ 20 pg/ml and POD1 calcium ≥ 2.0 mmol/l, the incidence of symptomatic hypocalcaemia was 1% (3/300), and need for intravenous calcium 0.3% (1/300). For POD1 PTH levels 15-19 pg/ml and POD1 calcium ≥ 2.0 mmol/l, the incidence of symptomatic hypocalcaemia and need for intravenous calcium was 5.4% (3/55). For PTH levels 10-14 pg/ml and calcium ≥ 2.0 mmol/l, the incidence of symptomatic hypocalcaemia and need for intravenous calcium was 11.7% (7/60). The risk of permanent hypoparathyroidism was < 1% for POD1 PTH levels ≥ 15 pg/ml; 5.4% for levels 10-14 pg/ml; and 19.8% for levels < 10 pg/ml. CONCLUSIONS: POD1 PTH levels ≥ 15 pg/ml along with calcium ≥ 2.0 mmol/l are associated with low risk of symptomatic hypocalcaemia, and represent a safe criterion for discharge of most patients without calcium supplementation. For certain patient groups, a higher threshold of 20 pg/ml could be considered.

Association between number of parathyroid glands identified during total thyroidectomy and functional parathyroid preservation.

PURPOSE: Systematic identification of all 4 parathyroid glands has been recommended during total thyroidectomy (TT); however, it is unclear whether this strategy necessarily translates into optimized functional parathyroid preservation. We wished to investigate the association between number of parathyroids identified intraoperatively during TT, and incidence of incidental parathyroidectomy, and postoperative hypoparathyroidism. METHODS: Retrospective review of prospectively maintained database of 511 consecutive patients undergoing TT at an academic teaching hospital. The association between number of parathyroid glands identified intraoperatively and incidence of biochemical hypocalcaemia (defined as any calcium < 2 mmol/L n first 48 h after surgery), symptomatic hypocalcaemia; permanent hypoparathyroidism (defined as any hypocalcaemia or need for calcium or vitamin D > 6 months after surgery), and incidental parathyroidectomy, was investigated. The association between number of parathyroid glands visualized and postoperative parathyroid hormone (PTH) levels was investigated in a subset of 454 patients. RESULTS: Patients in whom a greater number of parathyroids had been identified had a significantly higher incidence of biochemical and symptomatic hypocalcaemia, and significantly lower postoperative PTH levels, than patients with fewer glands identified. There were no significant differences in incidence of permanent hypoparathyroidism or incidental parathyroidectomy. On multivariate analysis, malignancy, Graves disease, and identification of 3-4 parathyroids were independent predictors of biochemical hypocalcaemia. For symptomatic hypocalcaemia, identification of 2-4 parathyroids, and identification of 3-4 parathyroids, were significant. CONCLUSIONS: Systematic identification of as many parathyroid glands as possible during TT is not necessary for functional parathyroid preservation.

Perioperative magnesium levels in total thyroidectomy and relationship to hypocalcemia.

BACKGROUND: We have previously shown an association between hypomagnesemia and hypocalcemia after thyroidectomy. However, little is known regarding the trend in magnesium levels in the days after thyroidectomy. Our objective was to study this trend in magnesium levels after thyroidectomy. METHODS: Retrospective review of 173 thyroidectomies with analysis of calcium and magnesium levels on postoperative day 1 (POD1) and POD2. RESULTS: Across the whole group, there was a highly significant decline in magnesium levels between preoperative (0.87 ± 0.06 mmol/L), POD1 (0.80 ± 0.07 mmol/L), and POD2 (0.78 ± 0.08 mmol/L) (P < .0001). The magnitudes of the magnesium level declines were significantly higher, and the absolute magnesium levels on POD1 and POD2 significantly lower, in patients developing hypocalcemia (n = 69). CONCLUSION: Magnesium levels after total thyroidectomy demonstrate a downward trajectory which persists through POD2 and is highly correlated with hypocalcemia. Further study is required to determine if magnesium replacement can alter the course of hypocalcemia in hypocalcemic patients after total thyroidectomy.

Absolute and relational control of a sequential auditory discrimination by pigeons (Columba livia).

Recent evidence indicates that pigeons can readily learn visual discriminations based on both absolute and relational stimulus factors. To examine how these two types of control function in their non-dominant auditory modality, we tested four pigeons in a go/no-go sequential auditory discrimination in which both absolute and relational cues were redundantly available. In this task, sequences of different sounds created from one set of pitches were reinforced, while different sequences created from another set of pitches and any same sequences made from either set of pitches were not. Across three experiments, we independently varied the relative discriminability of the absolute and relational components. The pigeons were consistently and primarily controlled by the absolute fundamental pitch of our notes in all of the experiments, although this was influenced by the range and arrangement of the pitches used in each set. A majority of the pigeons also demonstrated relational control when this component was made more salient. The more robust control exhibited by absolute factors is consistent with the comparative hypothesis that birds in general may have a well-developed aptitude for processing absolute pitch in many auditory settings. The relational control is consistent with our recent evidence of same/different auditory learning by pigeons.

Impact of postoperative magnesium levels on early hypocalcemia and permanent hypoparathyroidism after thyroidectomy.

BACKGROUND: Postoperative hypocalcemia is a common complication of thyroidectomy. Magnesium is known to modulate serum calcium levels and hypomagnesemia may impede correction of hypocalcemia. The purpose of this study was to investigate whether hypomagnesemia after thyroidectomy has any impact on early hypocalcemia and/or permanent hypoparathyroidism. METHODS: We conducted a retrospective review of prospectively maintained databases. Inclusion criteria were total or completion total thyroidectomy with postoperative magnesium levels available. The incidence of postoperative hypocalcemia was correlated with postoperative hypomagnesemia and other risk factors. RESULTS: Two hundred one cases were included. Twenty-six patients (13%) developed postoperative hypomagnesemia. Hypomagnesemia (p = .002), cancer diagnosis (p = .01), central neck dissection (p = .02), and inadvertent parathyroid resection (p = .02) were significantly associated with hypocalcemia. On multivariate analysis, only hypomagnesemia (p = .005) remained significant. Hypomagnesemia was also a significant predictor of permanent hypoparathyroidism (p = .0004). CONCLUSION: Hypomagnesemia is significantly associated with early hypocalcemia and permanent hypoparathyroidism after thyroidectomy. Magnesium levels should be closely monitored in patients with postthyroidectomy hypocalcemia.

Pigeons use high spatial frequencies when memorizing pictures.

The ability of animals to visually memorize and categorize a large number of pictures is well established. Determining the kinds of information animals use to accomplish these goals has been more difficult. This experiment examined the contribution of spatial frequency information to picture memorization by pigeons. A series of grayscale pictures were notch-filtered to eliminate different portions of the spatial frequency spectrum of memorized pictures. The results indicated that the higher spatial frequencies in the pictures were most important to accurate recognition, suggesting that the detection of fine detail at the high range of pigeon visual acuity was a critical component to their memorized representations. Subsequent tests with band-pass and hybrid conflict stimuli confirmed this conclusion. It is suggested that cognitive and task demands may determine how spatial frequency is used by pigeons, with higher frequencies more important to item memorization, while lower spatial frequencies may contribute to categorization in other types of discrimination tasks.

Outcome of Subclassification of Indeterminate (Thy-3) Thyroid Cytology into Thy-3a and Thy-3f.

OBJECTIVES: The British Thy system is a widely used classification system for reporting thyroid fine-needle aspiration (FNA) cytology. The Royal College of Pathologists in 2009 recommended the subdivision of the Thy-3 (indeterminate) category into Thy-3a (atypia) and Thy-3f (follicular neoplasm). Our objective was to examine the malignancy rates of Thy-3a and Thy-3f cases at our institution and to investigate whether the risk of malignancy in Thy-3a cases is reduced by FNA on a different occasion showing benign cytology. METHODS: This is a retrospective study of 748 thyroid nodules undergoing 1,032 FNAs, with indeterminate (Thy-3) cytology subdivided into Thy-3a and Thy-3f. Cases were correlated with final histology in surgical cases. Incidental carcinomas occurring outside the biopsied nodule were discounted. RESULTS: A total of 109 nodules had a final cytological diagnosis of Thy-3a, of which 67 underwent surgery, with an incidence of malignancy of 13.4% (9/67); 90 nodules had a final cytological diagnosis of Thy-3f, of which 84 underwent surgery, with an incidence of malignancy of 17.9% (15/84). The difference in malignancy rates was not significant (p = 0.51). The incidence of malignancy in nodules with benign and Thy-3a cytology on separate occasions was not significantly different from cases with a single Thy-3a cytology. CONCLUSIONS: Thyroid nodules with Thy-3a cytology have a slightly lower risk of malignancy than Thy-3f cases. However, the difference is not significant and does not appear to be reduced by FNA on a separate occasion showing benign cytology. Management decisions for patients with Thy-3a cytology should be taken carefully to avoid missing cancers.

A Case Report Demonstrating How the Clinical Presentation of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Can Mimic Benign Riedel's Thyroiditis.

A 44-year-old female presented with a two-month history of a neck mass, sore throat, hoarseness, and intermittent dysphagia. Examination revealed a "woody" hard swelling arising from the right lobe of the thyroid. Clinically this was felt to be classical Riedel's thyroiditis (RT). Thyroid ultrasound showed a diffusely enlarged, low echogenicity thyroid with a multinodular goitre. An abnormal nodule extending across the isthmus was noted. Following a nondiagnostic fine needle aspiration, an open core biopsy was performed. This showed dense sclerotic fibrosis punctuated by nodular mononuclear inflammatory cells, which obscured follicular epithelial cells consistent with a fibrosing thyroiditis (Riedel's thyroiditis). A biopsy of pretracheal lymph nodes showed a sclerotic process throughout the lymph nodes and nests of epithelium bands with squamous differentiation obscured by a fibrous process. These findings raised the differential diagnosis of diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) with metastasis to lymph nodes. A total thyroidectomy and pretracheal lymph node dissection were performed. The final histological diagnosis was DSV-PTC. When managing a patient with presumed RT it is important to consider malignancy in the differential. DSV-PTC is one of the more aggressive forms of thyroid cancer but with early diagnosis and appropriate treatment patients may have excellent outcomes.

Vitamin D and risk of postoperative hypocalcemia after total thyroidectomy.

IMPORTANCE: Transient hypocalcemia is a well-recognized occurrence after total thyroidectomy. It has been hypothesized that underlying vitamin D deficiency may increase the risk of this complication, although to date there are few data in the literature supporting this hypothesis. OBJECTIVE: To investigate whether perioperative vitamin D levels have any effect on postthyroidectomy hypocalcemia. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of a prospectively maintained database of thyroidectomies from November 1, 2009, through September 30, 2012, at an academic teaching hospital. The study included 121 patients with available vitamin D levels undergoing total or completion thyroidectomy. Patients with preexisting hypercalcemia or hyperparathyroidism were excluded. INTERVENTIONS: All patients underwent total removal of all thyroid tissue by a capsular dissection technique. Routine calcium or vitamin D supplementation was not administered. Biochemical hypocalcemia was defined as any single postoperative corrected calcium level less than 8.0 mg/dL (to convert to millimoles per liter, multiply by 0.25) and symptomatic hypocalcemia as any symptoms of hypocalcemia. MAIN OUTCOMES AND MEASURES: Outcome measures were incidence of postoperative hypocalcemia and association with vitamin D levels. A multivariate analysis was performed to study the effect of other variables, including performance of central neck dissection, incidental parathyroidectomy, and hyperthyroidism, on the incidence of postoperative hypocalcemia. RESULTS: The incidence of transient biochemical hypocalcemia was 24% (n = 29/121). There was no correlation between vitamin D levels and risk of postoperative hypocalcemia. On univariate analysis, performance of concomitant central compartment neck dissection revealed an increased risk of hypocalcemia (P = .06), but this finding was not significant on multivariate analysis. CONCLUSIONS AND RELEVANCE: Vitamin D levels do not appear to have a significant effect on the risk of postthyroidectomy hypocalcemia.

Thyroid tubercle of zuckerkandl is more consistently present and larger on the right: a prospective series.

OBJECTIVE: The tubercle of Zuckerkandl (TZ) is a lateral projection from the thyroid lobe in the vicinity of the extralaryngeal termination of the recurrent laryngeal nerve (RLN), which is a very useful landmark for identification of the RLN during thyroidectomy. The purpose of the present study was to test our hypothesis that the TZ is more consistently found and is larger on the right than on the left side, and to investigate the frequency of anatomic variations of the TZ. STUDY DESIGN: Prospective cohort study of 156 consecutive patients undergoing primary total thyroidectomy at an academic teaching hospital. Thyroidectomy was performed using a capsular dissection technique, with identification of the RLN only at its entry point into the larynx, using the TZ as a landmark. In vivo recording of size of right and left TZ was performed. The size of the right and left TZ was compared. RESULTS: Identification of the TZ was 72.6% right side and 53.9% left side (p = 0.003). The mean size of the TZ, when present, was 11.2 mm on the right and 7.5 mm on the left (p = 0.0002). In matched-pair analysis, the right TZ was significantly larger than the left TZ (p < 1 × 10(-7)). The TZ overlay the RLN in nearly all cases; however, there were 2 cases (0.8%) of a TZ extending medial to the RLN. In 12 cases (4.7%), the TZ appeared as a bilobed structure. CONCLUSION: The right TZ is consistently larger and more often identified than the left.

Follicular variant of papillary thyroid carcinoma: differences from conventional disease in cytologic findings and high-risk features.

IMPORTANCE: The follicular variant (FV) of papillary thyroid carcinoma (PTC) is an important subtype that can be difficult to diagnose using preoperative cytologic analysis. OBJECTIVE: To compare conventional and FV PTC with regard to preoperative cytologic diagnosis using a tiered thyroid cytologic reporting system, tumor size at diagnosis, presence of invasion, and implications on prognostic scores. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study was conducted in an academic teaching hospital and included 99 patients with conventional (n = 65) or FV (n = 34) PTC. INTERVENTIONS: Preoperative thyroid cytologic findings, originally reported using the tiered British Thy system, were recategorized according to the Bethesda classification system. Pathologic features recorded included tumor size, presence of extrathyroid extension (ETE), and metastases. Prognostic scores were calculated according to the MACIS system. MAIN OUTCOMES AND MEASURES: Differences in patient demographics, preoperative cytologic findings, tumor pathologic features, and prognostic risk categories between conventional and FV PTC were studied. RESULTS: There were no differences in patient age or sex. Cytologic findings from FV PTC were significantly more likely to be reported in a lower-risk category than those from conventional PTC for (1) malignant vs lower-risk category (22 [56%] vs 2 [8%]); (2) suspected malignant or malignant vs lower-risk category (26 [66%] vs 6 [23%]); and (3) follicular neoplasm or higher-risk category vs lower-risk category (34 [87%] vs 10 [38%]) (P < .001 for all 3 comparisons). There was also a significantly higher likelihood of false-negative cytologic findings among FV PTC cases (5 [19%] vs 1 [3%]) (P = .03). The mean size of FV PTC lesions (25.9 mm) at the time of pathologic diagnosis was significantly greater than that of conventional PTC lesions (15.5 mm) (P = .02). Even after exclusion of "coincidental" carcinomas, FV PTC tumors were significantly larger than conventional PTC tumors (31.7 vs 22.4 mm; P = .03). In contrast, FV PTC was significantly less likely to show ETE (0 of 34 vs 10 of 65; P = .01). There were no significant differences between FV PTC and conventional PTC in proportion of patients in intermediate- and high-risk prognostic groups combined (21 [62%] vs 38 [58%]) (P = .83) or in mean MACIS scores (4.68 and 4.38, respectively; P = .18). CONCLUSIONS AND RELEVANCE: Preoperative cytologic findings from FV PTC were more likely than those from conventional PTC to indicate a lower risk category, and FV PTC tumors were larger at time of diagnosis. On the other hand, owing to a lower incidence of ETE in conventional PTC, there was no difference in prognostic score at diagnosis.

Is systematic identification of all four parathyroid glands necessary during total thyroidectomy?: a prospective study.

OBJECTIVES/HYPOTHESIS: Routine identification of all four parathyroid glands has been advocated as a means of reducing rates of postoperative hypocalcemia and inadvertent parathyroidectomy. The object of the present study was to investigate whether identification of more parathyroid glands during thyroidectomy performed by capsular dissection technique had any impact on incidence of postoperative hypocalcemia and unintentional parathyroid resection. STUDY DESIGN: Prospective cohort study of consecutive patients undergoing total thyroidectomy by capsular dissection technique over a 3-year period. Exclusion criteria included performance of concomitant central neck dissection, hyperparathyroidism, revision surgery, and invasive cancer. METHODS: The number of parathyroid glands identified intraoperatively was recorded. No effort was made to find glands that were not obviously apparent during the course of dissection. Patients were not placed on routine calcium supplementation. RESULTS: The final study population consisted of 126 patients. The mean number of parathyroid glands identified was 2.3. The incidence of biochemical (any postoperative calcium <2 mmol/L) and clinical hypocalcemia was 22.2% and 10.3%, respectively. Patients in group A (0-2 parathyroids identified) had a significantly lower incidence of clinical hypocalcemia than patients in group B (3-4 parathyroids identified) (3.2% vs. 17.1%, P = .02). The differences in biochemical hypocalcemia were not significant (16.1% vs. 28.1%, P = .13). The incidence of inadvertent parathyroidectomy was 9.5%. There was no difference between the groups in incidence of inadvertent parathyroidectomy (9.7% vs. 9.4%, P = 1.0). CONCLUSIONS: Routine identification of all four parathyroid glands is not necessary in thyroidectomy performed using capsular dissection technique.

False negatives in thyroid cytology: impact of large nodule size and follicular variant of papillary carcinoma.

OBJECTIVES/HYPOTHESIS: Fine-needle aspiration (FNA) cytology is well established in the diagnosis of thyroid nodules. However, false-negative rates for malignancy of 3% to 10% are reported. The purpose of the present study was to investigate the impact of nodule size and follicular variant of papillary carcinoma (FVPTC) on false-negative FNA rates in thyroid nodules and on malignancy rates in nodules with indeterminate cytology. STUDY DESIGN: Retrospective study. METHODS: A total of 765 consecutive ultrasound-guided FNAs were reviewed. Histological correlation was available in 262 cases. RESULTS: The overall sensitivity of FNA for malignancy was 84%, and the false-negative rate 9.1%. Nodules ≥ 3 cm were significantly more likely to ultimately be diagnosed as cancer by histology than nodules <3 cm (14% vs. 6.8%, P = .006); however, they were also significantly more likely to undergo surgery than smaller nodules (P < .0001). Among the surgical series, the false-negative rate was 10.9% in nodules ≥ 3 cm and 6.1% in nodules <3 cm (P = .71). Most false negatives were due to FVPTC. FVPTC was significantly more likely to be missed by preoperative cytology than conventional or other variants of papillary carcinoma (P < .001). Among cases with indeterminate cytology, nodule size and Thy-3f versus Thy-3a subclassification did not have any significant impact on likelihood of malignancy. CONCLUSIONS: The sensitivity of FNA for detection of FVPTC is reduced compared to conventional papillary carcinoma. The impact of nodule size is not significant. LEVEL OF EVIDENCE: 4.

Risk factors for recurrent laryngeal nerve neuropraxia postthyroidectomy.

OBJECTIVE: Despite preservation of the recurrent laryngeal nerve (RLN), transient vocal cord paralysis (VCP) occurs after 1.2% to 10.9% of thyroidectomies. The objective of this study was to study risk factors for transient VCP after thyroidectomy. STUDY DESIGN: Prospective cohort study. SETTING: Academic teaching hospital. SUBJECTS AND METHODS: Two hundred fifteen consecutive thyroid surgeries performed by a single surgeon. All patients underwent preoperative and postoperative laryngoscopy. Patients with preexisting VCP or without postoperative laryngoscopy were excluded. Clinical and operative data were recorded prospectively at the time of thyroid surgery. The association between possible risk factors and occurrence of postoperative transient VCP was studied. RESULTS: Six patients were excluded (2 with preexisting VCP and 4 without postoperative laryngoscopy). There was 1 intentional sacrifice of an RLN and 1 unintentional RLN transection. Of the remaining 322 RLNs at risk, 15 (4.7%) had postoperative VCP. Operative findings of cancer invading the RLN requiring sharp dissection to separate the nerve (P = .006) and operative findings of RLN extensively draped along the thyroid or intimately associated with the thyroid parenchyma at Berry's ligament (P = .03) were significantly associated with VCP. Revision surgery (P = .06) trended toward significance. Malignancy, central compartment neck dissection, extralaryngeal RLN branching, hyperthyroidism, and retrosternal extension were not significant. Of cases with follow-up laryngoscopic documentation of vocal function, 85% (11/13) showed full resolution of VCP, with 1 further case showing partial recovery. CONCLUSION: Invasive cancer and variants in the anatomic course of the RLN are risk factors for transient VCP after thyroidectomy.

Implicit and explicit categorization: a tale of four species.

Categorization is essential for survival, and it is a widely studied cognitive adaptation in humans and animals. An influential neuroscience perspective differentiates in humans an explicit, rule-based categorization system from an implicit system that slowly associates response outputs to different regions of perceptual space. This perspective is being extended to study categorization in other vertebrate species, using category tasks that have a one-dimensional, rule-based solution or a two-dimensional, information-integration solution. Humans, macaques, and capuchin monkeys strongly dimensionalize perceptual stimuli and learn rule-based tasks more quickly. In sharp contrast, pigeons learn these two tasks equally quickly. Pigeons represent a cognitive system in which the commitment to dimensional analysis and category rules was not strongly made. Their results may reveal the character of the ancestral vertebrate categorization system from which that of primates emerged. The primate results establish continuity with human cognition, suggesting that nonhuman primates share aspects of humans' capacity for explicit cognition. The emergence of dimensional analysis and rule learning could have been an important step in primates' cognitive evolution.

Thyroid Tubercle of Zuckerkandl: importance in thyroid surgery.

OBJECTIVE: The Tubercle of Zuckerkandl (TZ), which is the remant of the lateral thyroid process, is an important anatomic structure that serves as a reliable landmark for the recurrent laryngeal nerve in thyroid surgery. Furthermore, removal of the TZ is critical for the adequate performance of a total thyroidectomy. However, there is little mention of the TZ in surgical textbooks or papers. METHODS: Prospective observational study of 138 consecutive thyroid surgeries. The presence of the TZ, its size, and relationship to the recurrent laryngeal nerve, were recorded. RESULTS: A total of 211 thyroid lobes were included in the study. The TZ was identified in 61.1% of all thyroid lobes. The median size was 8 mm (range = 3-40 mm). A TZ was more commonly identified on the right (69.6%) than on the left side (53.2%) (P = .02). The recurrent laryngeal nerve was found deep to the TZ in 98.4% of cases. CONCLUSIONS: A TZ is present in the majority of thyroid lobes. Awareness of the TZ is critical in performing an adequate total thyroidectomy, and is very useful as a landmark for the recurrent laryngeal nerve.

Pigeons' categorization may be exclusively nonanalytic.

Recent theoretical and empirical developments in human category learning have differentiated an analytic, rule-based system of category learning from a nonanalytic system that integrates information across stimulus dimensions. In the present study, the researchers applied this theoretical distinction to pigeons' category learning. Pigeons learned to categorize stimuli varying in the tilt and width of their internal striping. The matched category problems had either a unidimensional (rule-based) or multidimensional (information-integration) solution. Whereas humans and nonhuman primates strongly dimensionalize these stimuli and learn rule-based tasks far more quickly than information-integration tasks, pigeons learned the two tasks equally quickly to the same accuracy level. Pigeons may represent a cognitive system in which the commitment to dimensional analysis and category rules was not strongly made. Their performance could suggest the character of the ancestral vertebrate categorization system from which that of primates emerged.

Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study.

OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30-60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. RESULTS: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8-10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6-9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3-4.7, adjusted for fasting insulin) in men and 1.6 (0.8-3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women. CONCLUSIONS: Fasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.