Patients with prediabetes improve insulin resistance after surgery for primary hyperparathyroidism.

BACKGROUND: The objective of this study was to evaluate the evolution of insulin resistance at 12 months after parathyroidectomy for primary hyperparathyroidism according to the preoperative severity of glucose metabolism abnormalities. METHODS: Observational study of patients who underwent parathyroidectomy between 2016 and 2021. Prediabetes and insulin resistance were defined as fasting glucose ≥1.00 g/L (American Diabetes Association) and homeostatic model assessment of insulin resistance >2.5, respectively. RESULTS: A total of 231 patients were included. Preoperatively, 75 patients (32%) had prediabetes, and 108 patients (47%) had insulin resistance. At 12 months postoperative, homeostatic model assessment of insulin resistance values significantly decreased in patients with prediabetes (-0.69; P = .04) and in patients with insulin resistance (-0.85; P < .001). In patients with prediabetes, 48/75 (64%) decreased their insulin resistance, including 15/48 (31%) with normalization of fasting glucose. In multivariate analysis, preoperative prediabetes (1.82, 1.03-3.21; P = .037) or preoperative homeostatic model assessment of insulin resistance >2.5 (3.90, 2.23-6.75; P < .001) remained independent predictors for insulin resistance reduction observed between preoperative and 12 months postoperative. CONCLUSION: Parathyroidectomy is more likely to reduce insulin resistance in patients with primary hyperparathyroidism and prediabetes or in patients with higher preoperative homeostatic model assessment of insulin resistance values. These data support the use of the preoperative prediabetes criterion in addition to the international workshop criteria for parathyroidectomy to better select patients for surgery.

Prognostic indicators in pituitary adenoma surgery: a comprehensive analysis of surgical outcomes and complications.

Objective: The primary aim of this study was to identify predictive factors associated with onset of de-novo clinically significant pituitary insufficiencies following endoscopic endonasal surgery (EES) for pituitary adenomas. The secondary objective explored the predictive factors of surgical success. Methods: A retrospective analysis was conducted on 211 patients who underwent EES. Logistic regression models were employed for the primary and secondary objectives. Patients were stratified into specific groups based on surgical indications and prolactin levels for nuanced analysis. Results: Significant predictors for de-novo pituitary insufficiencies included male sex (OR 3.3, CI95% 1.3-8.1, p=0.01), immediate postoperative insufficiencies (OR 5.6, CI95% 2.8-11.1, p<0.001), and HYPRONOS criteria (OR 5.7, CI95% 1.6-20.9, p=0.008). For surgical success, preoperative insufficiencies (OR 0.7, CI95% 0.5-0.9, p=0.008), repeat surgeries (OR 0.1, CI95% 0-0.4, p=0.001), and gonadotroph or somatotroph adenomas were significant. Age and adenoma size were not predictive in multivariate analysis. Furthermore, we observed a "dip and recover" effect of prolactin after surgery and lower prolactin levels at follow-up (< 3 ng/ml) are correlated with more anterior pituitary insufficiencies than normoprolactinemic patients (p = 0.004). Conclusion: This study identifies key predictors for outcomes in pituitary surgery. Our research is the first to employ individualized success criteria for EES, challenging existing perceptions about the role of age and adenoma size. These findings open avenues for nuanced, individualized preoperative risk assessment and postoperative management.

Insulin resistance is more severe in patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is associated with an increased cardiovascular mortality, and its underlying mechanisms remain unclear. Insulin resistance has been suggested with low level of evidence. The goal of this study was to evaluate glucose metabolism and insulin resistance in primary hyperparathyroidism patients, to compare with control subjects, and to identify risk factors for insulin resistance in patients with primary hyperparathyroidism. METHODS: Cross-sectional study of consecutive primary hyperparathyroidism patients without history of diabetes or severe chronic kidney disease (glomerular filtration rate ≤30 mL/min/1.73 m2). Fasting glucose and insulin were evaluated before parathyroidectomy. Glucose metabolism was compared with population-based control subjects (n = 171). RESULTS: One hundred and seventy-four patients with primary hyperparathyroidism (140 females) were included. Mean fasting glucose was 0.983 ± 0.129 g/L, and 63 patients (36%) had prediabetes (>1.0 g/L). Mean Homeostatic model assessment of insulin resistance (HOMA-IR) was 3.386 ± 3.111 mUI/L, and 78 patients (45%) had insulin resistance (HOMA-IR >2.6). Blood calcium levels (0.171; P = .023) and body mass index (0.450; P < .001) were correlated positively with HOMA-IR. Insulin secretion (HOMA-B%) was correlated positively with preoperative systolic blood pressure in mm Hg (0.187; P = .013). In multivariate analysis, classic hypercalcemic primary hyperparathyroidism (18.47, 6.84-49.87; <.001), mild hypercalcemic primary hyperparathyroidism (5.35, 2.40-11.95; <.001), and body mass index (1.27, 1.17-1.38; <.001) remained independent predictors for insulin resistance (HOMA-IR >2.6). When compared with control subjects, mean HOMA-IR was significantly higher in primary hyperparathyroidism patients (3.386 ± 3.111 vs 1.919 ± 1.158; P < .001). CONCLUSION: Insulin resistance was significantly higher in primary hyperparathyroidism patients than in control subjects. The impact of parathyroidectomy on insulin resistance should be evaluated in patients with higher calcium levels.

What is the impact of continuous neuromonitoring on the incidence of injury to the recurrent laryngeal nerve during total thyroidectomy?

BACKGROUND: Continuous intraoperative neuromonitoring may facilitate reversal of intraoperative injurious operative maneuvers in comparison with intermittent intraoperative neuromonitoring. The aim of this study was to evaluate the impact of the routine use of continuous intraoperative neuromonitoring on intraoperative injuries to the recurrent laryngeal nerve. METHOD: This study was a prospective case series with retrospective analysis of consecutive patients undergoing total thyroidectomy from August 2013 to August 2019. During this period, intermittent intraoperative neuromonitoring (before Mar 2016) and continuous intraoperative neuromonitoring (after Mar 2016) were used in all patients. RESULTS: We reviewed the outcomes of 603 patients (466 female patients) comprising 236 who underwent intermittent intraoperative neuromonitoring and 367 who underwent continuous intraoperative neuromonitoring. Intraoperative adverse electromyography events (>50% decrease in amplitude between VN1 and VN2) were observed in 87 patients (14.5%) and were less frequent in the continuous intraoperative neuromonitoring group (10.6 vs 20.3%, P = .001). Intraoperative loss of signal (electromyography events with VN2 ≤100µV) were observed in 35 patients (5.8%) without any difference between the 2 groups of patients (5.2 vs 6.8%, P = .415). Postoperative recurrent laryngeal nerve palsies were observed in 36 patients (5.9%) without any difference between the 2 groups of patients (4.9 vs 7.6%, P = .168). CONCLUSION: The routine use of continuous intraoperative neuromonitoring improves the rate of intraoperative adverse electromyography events but does not impact significantly the rates of loss of signal and recurrent laryngeal nerve palsy.

Robotic adrenalectomy: when and how?

Currently, laparoscopic adrenalectomy is considered as the preferred technique to manage adrenal tumors. However, there are no prospective randomized studies evaluating this strategy. With the recent advances in surgical equipment and the widespread of robotic technology, a robotic approach is considered as an interesting option in some medical centers. This approach seems to be feasible and safe but high-level evidence of its benefits is still lacking. This review summarizes indications, advantages and drawbacks of robotic adrenalectomy and describes its surgical technique.

Ultrasound and cytological characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features compared to papillary carcinomas.

INTRODUCTION: NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features, formerly non-invasive encapsulated follicular variant of papillary thyroid carcinoma) has been removed from the carcinoma category because of its indolent character and good prognosis. This change impacts clinical and surgical management, since these tumors no longer require total thyroidectomy, or complementary radioactive iodine therapy for <4cm tumor. The aim of the present study was to identify preoperative ultrasound and cytological differences between NIFTP and papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A retrospective study included 81 patients who underwent total thyroidectomy or thyroid lobectomy with histologic diagnosis of PTC, NIFTP or invasive follicular variant of PTC (IFVPTC) between January 1st, 2016 and May 31st, 2018. Ultrasound and cytological data were analyzed and compared between NIFTP and non-NIFTP (PTC and invasive follicular variant of PTC). RESULTS: Fourteen NIFTPs, 67 PTCs, including 20 IFVPTCs, were included. In comparison with non-NIFTP PTC, nodules in NIFTP were more often isoechoic (69.2% vs. 17.4%; P=0.0007), with smooth borders (92.3% vs. 31.1%; P=0.0001) and TI-RADS score 2, 3 or 4a. Cytologically, NIFTPs were mainly in categories AUS/FLUS, FN and SusM of the Bethesda System for Reporting Thyroid Cytopathology. Only nuclear pseudo-inclusions were significantly associated with non-NIFTP (P=0.0031). CONCLUSION: NIFTP appears non-suspect on preoperative ultrasound and indeterminate on cytology. These differences with respect to PTC can guide diagnosis and surgical treatment.

When a Pathological Forearm Fracture Led to Explore the Neck: About a Case.

The majority of patients with parathyroid carcinoma (PC) have significant clinical signs and simultaneous symptoms related to the unregulated hypersecretion of parathyroid hormone (PTH) by the tumor. The aim of this case was to report a patient presenting an isolated bone fracture leading to the diagnosis of PC. A 20-years-old female patient presenting a fracture of both bones of the forearm following a fall from her own height. Imageries showed diffuse bone demineralization. Biology revealed malignant hypercalcemia at 4.1 mmol/L and PTH at 1331 pg/mL. Bone densitometry showed severe osteoporosis with a femoral and lumbar T-score < - 3DS. Imageries showed a right parathyroid mass of 32 mm. An one-piece excision of the pathological gland, right thyroid lobectomy and ipsilateral central lymph node dissection were performed. Postoperatively, the patient presented a hungry bone syndrome with severe hypocalcemia and required substitutive treatment. PTH on day 1 was normal. Pathology analysis found a PC with Ki67 at 3%, lymph node removal was negative. Complete one-piece surgical excision is the only potentially curative treatment for PC. Preoperative suspicion and intraoperative recognition of malignant features is important in order to propose an appropriate compartmental surgery, which can provide the lowest possible recurrence rate.

Coronary artery disease is more severe in patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is associated with an increased cardiovascular mortality, but mechanisms underlying this association are unclear. The goal of this study was to evaluate coronary artery calcifications via the coronary calcification score in primary hyperparathyroidism patients, to compare with control subjects, and to identify risk factors for high to intermediate risk coronary calcification scores (coronary calcification score >100). METHOD: Cross-sectional study of primary hyperparathyroidism patients without a history of coronary artery disease, diabetes, or severe, chronic kidney disease. Coronary calcification scores were compared with a cohort of population-based control subjects. RESULTS: The mean coronary calcification score was 120 ± 344 in 130 primary hyperparathyroidism patients. The coronary calcification score was >100 in 27 patients (21%). When compared with control subjects, the percentage of positive coronary calcification scores was similar in primary hyperparathyroidism patients (53% vs 50%); however, positive coronary calcification scores were at the 67th percentile of the control subjects cohort (P < .001). In multivariable regression, patient age (1.1; 1.1-1.2; P < .001), patients in the mild normocalcemic primary hyperparathyroidism group (5.1; 1.1-22.6; P = .037), and the need for antihypertensive medications (6.1; 1.8-20.9; P < .001) remained independent predictors for a coronary calcification score >100. CONCLUSION: Positive coronary calcification scores were greater in primary hyperparathyroidism patients than in population-based control subjects. These study data may provide new criteria for parathyroidectomy in patients with primary hyperparathyroidism.

Methyl donor deficiency impairs bone development via peroxisome proliferator-activated receptor-γ coactivator-1α-dependent vitamin D receptor pathway.

Deficiency in methyl donor (folate and vitamin B12) and in vitamin D is independently associated with altered bone development. Previously, methyl donor deficiency (MDD) was shown to weaken the activity of nuclear receptor coactivator, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), for nuclear signaling in rat pups, including estrogen receptor-α and estrogen-related receptor-α; its effect on vitamin D receptor (VDR) signaling, however, is unknown. We studied bone development under MDD in rat pups and used human MG-63 preosteoblast cells to better understand the associated molecular mechanism. In young rats, MDD decreased total body bone mineral density, reduced tibia length, and impaired growth plate maturation, and in preosteoblasts, MDD slowed cellular proliferation. Mechanistic studies revealed decreased expression of VDR, estrogen receptor-α, PGC1α, arginine methyltransferase 1, and sirtuin 1 in both rat proximal diaphysis of femur and in MG-63, as well as decreased nuclear VDR-PGC1α interaction in MG-63 cells. The weaker VDR-PGC1α interaction could be attributed to the reduced protein expression, imbalanced PGC1α methylation/acetylation, and nuclear VDR sequestration by heat shock protein 90 (HSP90). These together compromised bone development, which is reflected by lowered bone alkaline phosphatase and increased proadipogenic peroxisome proliferator-activated receptor-γ, adiponectin, and estrogen-related receptor-α expression. Of interest, under MDD, the bone development effects of 1,25-dihydroxyvitamin D3 were ineffectual and these could be rescued by the addition of S-adenosylmethionine, which restored expression of arginine methyltransferase 1, PGC1α, adiponectin, and HSP90. In conclusion, MDD inactivates vitamin D signaling via both disruption of VDR-PGC1α interaction and sequestration of nuclear VDR attributable to HSP90 overexpression. These data suggest that vitamin D treatment may be ineffective under MDD.-Feigerlova, E., Demarquet, L., Melhem, H., Ghemrawi, R., Battaglia-Hsu, S.-F., Ewu, E., Alberto, J.-M., Helle, D., Weryha, G., Guéant, J.-L. Methyl donor deficiency impairs bone development via peroxisome proliferator-activated receptor-γ coactivator-1α-dependent vitamin D receptor pathway.

One carbon metabolism and bone homeostasis and remodeling: A review of experimental research and population studies.

Homocysteine (HCY) is a degradation product of the methionine pathway. The B vitamins, in particular vitamin B12 and folate, are the primary nutritional determinant of HCY levels and therefore their deficiencies result in hyperhomocysteinaemia (HHCY). Prevalence of hyperhomocysteinemia (HHCY) and related dietary deficiencies in B vitamins and folate increase with age and have been related to osteoporosis and abnormal development of epiphyseal cartilage and bone in rodents. Here we provide a review of experimental and population studies. The negative effects of HHCY and/or B vitamins and folate deficiencies on bone formation and remodeling are documented by cell models, including primary osteoblasts, osteoclast and bone progenitor cells as well as by animal and human studies. However, underlying pathophysiological mechanisms are complex and remain poorly understood. Whether these associations are the direct consequences of impaired one carbon metabolism is not clarified and more studies are still needed to translate these findings to human population. To date, the evidence is limited and somewhat conflicting, however further trials in groups most vulnerable to impaired one carbon metabolism are required.

Thyroid side effects prophylaxis in front of nuclear power plant accidents.

The better knowledge of the mechanisms of nuclear incidents and lessons learned from accidents in the recent past to improve the effectiveness of measures taken following a nuclear accident exposure to fallout of radioactive iodine isotopes. Thus, immediate, passive measures, such as containment, and stopping consumption of contaminated products are paramount. The earliest possible administration of stable iodine as potassium iodide (KI) reduces significantly (up to 90% if taken at the same time of the accident) thyroid radioactive contamination. These tablets should be given in priority to children and pregnant women. The side effects are minor. KI is not recommended for persons aged over 60 years, or for adults suffering from cardiovascular disorders.

Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. METHODS: This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. FINDINGS: 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. INTERPRETATION: The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications.