Hypercalcemic Crisis Due to a Giant Intrathyroidal Parathyroid Adenoma, with Postsurgical Severe Hypocalcemia and Hungry Bone Syndrome: A Case Report.

BACKGROUND: Parathyroid adenoma is the most common cause of hypercalcemia and rarely leads to a hypercalcemic crisis, which is an unusual endocrine emergency that requires timely surgical excision. CASE PRESENTATION: A 67-year-old male was admitted to the ER of the Euroclinic Hospital, Athens, Greece, because of elevated calcium levels and a palpable right-sided neck mass, which were accompanied by symptoms of nausea, drowsiness, and weakness for six months that increased prior to our evaluation. A gradual creatinine elevation and decreasing mental state were observed as well. The initial laboratory investigation identified severely elevated serum calcium (3.6 mmol/L) levels consistent with a hypercalcemic crisis (HC) and parathyroid hormone PTH (47.6 pmol/L) due to primary hyperparathyroidism. Neck ultrasonography (USG) identified a large, well-shaped cystic mass in the right thyroid lobe. With a serum calcium concentration of 19.5 mg/dL and a PTH of 225.3 pmol/L, the patient underwent partial parathyroidectomy and total thyroidectomy, which decreased serum calcium and PTH to 2.5 mmol/L and 1.93 pmol/L, respectively. Histology revealed a giant intrathyroidal cystic parathyroid adenoma, which was responsible for the hypercalcemic crisis. Postoperatively, the patient developed severe biochemical and clinical hypocalcemia, with calcium concentrations as low as 1.65 mmol/L, consistent with hungry bone syndrome (HBS), which was treated with high doses of intravenous calcium gluconate and oral alfacalcidol, and a slow recovery of serum calcium. After discharge, parathyroid function recovered, and symptomatology resolved entirely in more than one month. DISCUSSION/CONCLUSIONS: We present a case involving an exceptionally large intrathyroidal parathyroid adenoma that is characterized by clinical manifestations that mimic malignancy. The identification and treatment of such tumors is challenging and requires careful preoperative evaluation and postoperative care for the risk of hungry bone syndrome.

Elevated Preoperative TPO Ab Titers Decrease Risk for DTC in a Linear Fashion: A Retrospective Analysis of 1635 Cases.

CONTEXT: For some, chronic lymphocytic thyroiditis (Hashimoto thyroiditis) is an important risk factor for differentiated thyroid cancer (DTC). Surgical cohort studies even suggested a potential role for thyroid peroxidase antibodies (TPO-Abs) on that risk. OBJECTIVE: Our clinical observations argued against that possibility. We designed the present study to evaluate the relationship of TPO-Abs and DTC in a large patient population. METHODS: We recruited individuals who underwent thyroidectomies at 4 different clinical sites (USA: 1 clinic, 2000-2013, and Greece: 3 clinics, 2007-2021). We gathered data on TPO-Abs titers measured with commercially available chemiluminescence immunoassays, and reviewed patients' data including surgical pathology. TPO-Abs of 34 IU/mL or greater was deemed positive (TPO+) and TPO-Abs less than 34 IU/mL was deemed negative (TPO-). Odds ratios (OR) for DTC were calculated with the Fisher exact test and P less than .05 was deemed significant. RESULTS: We reviewed data from 8461 consecutive thyroid surgery cases. TPO-Abs titers were available for 1635 individuals: DTC n = 716 (43.8%), benign pathology n = 919 (56.2%), TPO+ n = 540 (33.0%), and TPO- n = 1095 (67.0%). DTC was found at a lower frequency in TPO+ (198/540, 36.7%) compared to TPO- (518/1095, 47.3%) patients, OR 0.64 (0.52-0.80; P < .0001). Rising TPO-Abs titers conferred protection against DTC in a linear fashion: TPO-Abs less than 10 IU/mL: 59.3%, TPO-Abs less than 34 IU/mL: 47.4%, TPO-Abs 34 to 100 IU/mL: 42.6%, TPO-Abs 100 to 500 IU/mL: 32.0%, TPO-Abs greater than 1000 IU/mL: 19.4%; P less than .0001. CONCLUSION: Higher TPO-Ab titers appear protective against DTC in our large multicenter cohort of patients who underwent thyroidectomies. Rising preoperative TPO-Abs titers conferred linearly increasing protection against DTC.

De novo purely prostatic large-cell neuroendocrine carcinoma with thyroid and adrenal metastases.

Summary: Large-cell neuroendocrine carcinoma (LCNEC) is a rare neuroendocrine prostatic malignancy. It usually arises after androgen deprivation therapy (ADT), while de novo cases are even more infrequent, with only six cases described. The patient was a 78-year-old man with no history of ADT who presented with cervical lymphadenopathy. Diagnostic approaches included PET/CT, MRI, CT scans, ultrasonography, biopsies, and cytological and immunohistochemical evaluations. Results showed a poorly differentiated carcinoma in the thyroid gland accompanied by cervical lymph node enlargement. Thyroid surgery revealed LCNEC metastasis to the thyroid gland. Additional metastases were identified in both the adrenal glands. Despite appropriate treatment, the patient died of the disease. De novo LCNEC of the prostate is a rare, highly aggressive tumor with a poor prognosis. It is resistant to most therapeutic agents, has a high metastatic potential, and is usually diagnosed at an advanced stage. Further studies are required to characterize this tumor. Learning points: De novo LCNECs of the prostate gland can metastasize almost anywhere in the body, including the thyroid and adrenal glands. LCNECs of the prostate are usually associated with androgen-depriving therapy, but de novo cases are also notable and should be accounted for. Further studies are required to fully understand and treat LCNECs more effectively.

Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers.

Background: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3+CD4-CD8-), which are believed to enable or promote tumorigenesis. In the present work, we try to use the DN T cells' proportion in thyroid fine-needle aspiration (FNA) material as a predictor of the risk of malignancy. Methods: We recruited 127 patients and obtained ultrasound-guided FNA samples from subjects with cytology-positive or suspicious for malignancy and from those with benign nodular goiter associated with compressive symptoms (such as dysphagia, shortness of breath, or hoarseness), Hashimoto thyroiditis, and Graves' disease. Out of 127, we investigated 46 FNA samples of patients who underwent total thyroidectomy and for which postoperative histological diagnosis by the academic pathologists was available. We specifically measured the number of cells expressing CD3+CD4-CD8- (DN T) as a function of total CD3+ cells in FNA samples using flow cytometry. We correlated their FNA DN T-cell proportions with the pathological findings. Results: The DN T cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer cases compared to benign nodule controls (p < 0.0001). When the DN T-cell population exceeded a threshold of 9.14%, of total CD3+ cells, the negative likelihood ratio of being cancer-free was 0.034 (96.6% sensitivity, 95% CI, 0.915-1.000, p < 0.0001). DN T cells at <9.14% were not found in any subject with benign disease (specificity 100%). The high specificity of the test is promising, since it abolishes a false-positive diagnosis and in turn unnecessary surgical procedures. Conclusion: The present study proposes DN T cells' proportion as a preoperative diagnostic signature for thyroid cancer that with integration of RNA transcriptomics can provide a simplified technology based on the PCR assay for the ease of operation.

Large, Slowly Growing, Benign Thyroid Nodules Frequently Coexist With Synchronous Thyroid Cancers.

CONTEXT: Thyroid nodules' size should not be the sole criterion for thyroidectomy; however, many patients undergo surgery for large or slowly growing nodules. OBJECTIVE: We evaluated risk for clinically significant thyroid cancer in patients with large or slowly growing nodules. METHODS: We reviewed data from 2 prospectively collected databases of patients undergoing thyroidectomies in tertiary referral centers in the USA and Greece over 14 consecutive years. We collected data on the preoperative surgical indication, FNA cytology, and surgical pathology. We included subjects operated solely for large or growing thyroid nodules, without any known or presumed thyroid cancer or high risk for malignancy, family history of thyroid cancer, or prior radiation exposure. RESULTS: We reviewed 5523 consecutive cases (USA: 2711; Greece: 2812). After excluding 3059 subjects, we included 2464 subjects in the present analysis. Overall, 533 thyroid cancers were identified (21.3%): 372 (69.8%) microcarcinomas (<1 cm) and 161 (30.2%) macrocarcinomas (≥1 cm). The histology was consistent with papillary cancer (n = 503), follicular cancer (n = 12), Hürthle cell cancer (n = 9), medullary cancer (n = 5), and mixed histology cancers n = 4. Only 47 (1.9%) of our subjects had any form of thyroid cancer in the nodule that originally led to surgery. The cancers were multifocal in 165 subjects; had extrathyroidal extension in 61, capsular invasion in 80, lymph node involvement in 35, and bone metastasis in 2 subjects. CONCLUSION: The risk of synchronous, clinically important thyroid cancers is small, but not null in patients with large or slow growing thyroid nodules. Therefore, more precise preoperative evaluation is needed to separate the patients who would clearly benefit from thyroid surgery from the vast majority of those who do not need to be operated.

Risk of type 2 diabetes mellitus in polycystic ovary syndrome is associated with obesity: a meta-analysis of observational studies.

PURPOSE: The exact risk of type 2 diabetes mellitus (T2DM) in women with polycystic ovary syndrome (PCOS) is unknown. It is also unclear if obesity independently increases T2DM risk in this population. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between PCOS and T2DM, stratified according to obesity status. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to October 31, 2020. Data are expressed as relative risk (RR) with 95% confidence interval (CI). The I2 index was employed for heterogeneity. RESULTS: The eligibility criteria were fulfilled by 23 studies (319,780 participants; 60,336 PCOS and 8847 type 2 diabetes cases). Women with PCOS demonstrated a higher risk of T2DM than those without PCOS (RR 3.45, 95% CI, 2.95-4.05, p < 0.001; I2 81.6%). This risk remained significant both in studies matched or unmatched for participants' age. With regard to body mass index (BMI), the RR for developing T2DM in obese and non-obese PCOS women compared with their non-PCOS counterparts was 3.24 (95% CI 2.25-4.65; p < 0.001; I2 30.9%) and 1.62 (95% CI 0.14-18.50; p = 0.70; I2 89.9%), respectively. The RR for developing T2DM was 3.85 (95% CI 1.99-7.43; p < 0.001; I2 46.2%) in obese compared with non-obese women with PCOS. This was also the case for overweight compared with lean women with PCOS. CONCLUSIONS: Women with PCOS present an increased risk of T2DM compared with non-PCOS women only if they are obese/overweight.

Higher TSH Is Not Associated With Thyroid Cancer Risk in the Presence of Thyroid Autoimmunity.

BACKGROUND: Higher-but-within-normal thyrotropin (thyroid-stimulating hormone, TSH) is associated with higher risk for differentiated thyroid cancer (DTC) in surgical series. Our recent clinical observations suggest that this is not the case in the presence of autoimmune thyroid disease (AITD). We designed the present study to clarify this controversy. METHODS: We analyzed our prospectively collected database of patients referred for thyroid surgery at 2 tertiary care referral centers in Greece and the United States. We collected data for preoperative TSH, postoperative pathology, and thyroid peroxidase (TPO) antibodies titers. Subjects were subdivided into 2 groups, those with AITD (i.e., lymphocytic thyroiditis) and non-AITD. We excluded subjects with Graves disease, abnormal TSH (< 0.40 or > 4.50 mIU/mL), or recent use of levothyroxine. We compared the serum TSH among different groups using the Mann-Whitney test. RESULTS: A total of 3973 subjects were screened; 1357 met exclusion criteria. After all exclusions, data from 1731 non-AITD subjects and 329 AITD subjects were included in the analysis. AITD subjects had higher TSH than non-AITD subjects (2.09 vs 1.48; P < 0.0001). TSH values were higher in DTC compared with benign histology only in non-AITD subjects (1.65 vs 1.40; P < 0.0001). Progressively higher TSH was associated with higher incidence of DTC only in non-AITD subjects (P < 0.0001). In AITD subjects, TSH was similar between groups with or without DTC (2.02 vs 2.14; P = 0.21). CONCLUSIONS: TSH concentrations are not associated with the risk of developing DTC in the presence of thyroid autoimmunity, even though this seems to be the case for all other patients.

Incidentally Discovered Papillary Thyroid Microcarcinomas Are More Frequently Found in Patients with Chronic Lymphocytic Thyroiditis Than with Multinodular Goiter or Graves' Disease.

Background: Incidental finding of differentiated thyroid microcarcinomas (DTMc) in patients undergoing thyroid surgery for benign indications has become increasingly common. Even though carcinogenesis might relate to the background disease of the gland, the incidence of DTMc in the setting of various thyroid disorders remains unclear. We designed the present study to address this question. Materials and Methods: We reviewed data from two prospectively collected databases of consecutive patients undergoing thyroid surgery in two high-volume tertiary care referral centers, one in the United States (A) and the other one in Greece (B) over 18 years. We collected data on the preoperative surgical indication, fine-needle aspiration (FNA) cytology, and surgical pathology. We excluded subjects operated for thyroid cancer or with high risk for malignancy (FNA suspicious for thyroid cancer, follicular neoplasm, suspicious for follicular neoplasm, follicular lesion of undetermined significance/atypia of undetermined significance, or preoperative features of malignancy) and those with postsurgical pathology consistent with papillary thyroid cancer (PTC) ≥1 cm in largest diameter. We divided our subjects based on pathology data into those with chronic lymphocytic thyroiditis (CLT), Graves' disease (GD), or multinodular goiter (MNG). Results: We reviewed 6096 cases of thyroid surgery (A: 2711, B: 3385). We included 3909 subjects in the analysis. Overall, 569 (14.6%) PTC subjects were identified (A: 221/2003 [11%], B: 348/1906 [18.3%], odds ratios [OR] = 0.56, p < 0.0001). CLT was present in 617 subjects; PTC sonographic was present in 143 subjects (23.2%) (A: 79/404 [19.6%], B: 64/213 [30%], OR = 0.56, p = 0.003). GD was present in 359 subjects; PTC was present in 37 subjects (10.3%) (A: 12/197 [6.1%], B: 25/162 [15.4%], OR = 0.36, p = 0.004). MNG was present in 2933 subjects; PTC was present in 389 subjects (13.3%) (A: 130/1402 [9.3%], B: 259/1531 [16.9%], OR = 0.50, p < 0.0001). The incidence of PTC was significantly higher in CLT compared with MNG (OR = 1.75, p < 0.0001) or GD (OR = 2.25, p < 0.0001) but not in MNG compared with GD (OR = 1.29, p > 0.05). Conclusions: Incidentally discovered PTC are more commonly identified in surgical specimens from subjects with CLT compared with patients with MNG, while patients with GD present with a lower incidence compared with both groups. These data support previously published findings that euthyroid Hashimoto thyroiditis favors carcinogenesis, while GD may have a protective role.

The non-interventional approach to papillary thyroid microcarcinomas. An "active surveillance" dilemma.

BACKGROUND: Recent studies suggest that papillary-thyroid-microcarcinomas (PTMi) and follicular-variant-papillary-thyroid-cancers (FVPTC) are less aggressive overall. Our observations argue against. OBJECTIVES: To assess whether PTMi and FVPTC are indeed low-risk and could be safely followed without intervention. METHODS: We prospectively collected data of subjects with PTC on pathology post-thyroidectomy. Odds ratios (OR) were calculated with Fisher's exact test and differences between means were calculated using Mann Whitney's test. RESULTS: 696 met inclusion-criteria; 436 had macrocarcinomas (PTMa) and 260 had PTMi. PTMa were statistically significantly more likely to present multifocal [44.0% vs.28.1%], with extrathyroidal extension [22.1% vs.3.4%], lymph nodes involvement [25.5% vs.8.8%] and local invasion [3.1% vs.0.4%] (p < 0.05 for all), but not with distant metastasis [3.4% vs.1.3%, p > 0.05]. Therefore, PTMi measuring down to 0.01 cm, harbored aggressive features. We also identified 174 cases with FVPTC and 522 subjects with non-FVPTC. FVPTC had lower incidence of multifocality [40.1%, vs.60.9%], extrathyroidal extension [8.6% vs.17.4%] and lymphatic involvement [5.2% vs.24.0%], but not distant metastasis or local invasion [p > 0.05 for all]. Therefore, FVPTC measuring down to 0.5 cm, also harbored aggressive features. CONCLUSIONS: PTMi and FVPTC aggressive features are substantial enough to require careful evaluation, independent of their original tumor size before defaulting to just "active surveillance."

Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer.

BACKGROUND: Thyroid cancer and thyroid autoimmunity are considered opposite extremes of immune-responses. However, several studies have suggested that thyroid cancer coexists with autoimmune thyroid diseases like Hashimoto Thyroiditis (HT) and Graves disease (GD). We have shown that the risk of developing thyroid cancer is higher in patients with a silent form of autoimmune thyroid disease -Euthyroid Hashimoto Thyroiditis-(EHT). METHODS: We analyzed data from 2633 consecutive patients with GD, HT, EHT and non-Autoimmune Thyroid Disease (Non-AITD) for the presence of Differentiated Thyroid Cancer (DTC). We further investigated the microenvironment, and cellular mechanism of protection from DTC in GD/EHT by ex-vivo aspirating infiltrates from thyroid samples. We also re-constituted in vitro the in-vivo microenvironment to mimic an in-vivo context. We isolated NK cells and differentiated macrophages into M1 and M2 phenotype from healthy human peripheral blood monocytes. RESULTS: DTC was less frequent/aggressive in GD as compared to EHT or Non-AITD. Intra-thyroidal immune-cell profiling revealed differential Natural Killer (NK) cell activity and macrophage polarization in the settings of GD versus EHT. In GD, NK-cells were activated, and macrophages showed M1-like phenotype whereas, in EHT, NK-cells were less active and macrophages displayed M2-like phenotype. Furthermore, in vitro co-cultures of NK-cells with differentiated macrophage subsets revealed that the presence of activated NK (NA) cells favors M1 macrophages, boosts macrophage action and amplifies the innate defense mechanisms. Moreover, co-culture of M2 macrophages with NA, increases the cytotoxicity of NK-cells and favors a pro-inflammatory microenvironment that reverts the anti-inflammatory M2 towards pro-inflammatory M1. CONCLUSION: Surveillance innate immune-cells like Natural Killer (NK) cells and macrophages are complementary to each other in their actions. We discovered here that activated NK-cells in the background of the thyroid autoimmune disease, GD, drive macrophage differentiation to the M1/killer phenotype which in turn is cytotoxic to cancer cells and down regulates the M2/repair phenotype. Understanding the molecular basis of macrophage-NK cell interface in Thyroid Cancer, ETH and GD will open new vistas for immunopathology and therapeutic intervention. Macrophages/innate immunity can be modulated from M2 to M1 phenotype to help treat thyroid cancer as naturally done by GD.

Persistent apparent pancreatic ß-cell defects in premenarchal PCOS relatives.

CONTEXT: Polycystic ovary syndrome confers an increased risk for type 2 diabetes in affected women as early as adolescence. First-degree relatives (FDRs) of affected women are at increased risk for associated reproductive and metabolic phenotypes. OBJECTIVE: We sought to prospectively assess insulin sensitivity and secretion and to measure reproductive hormone levels using sensitive techniques. DESIGN, SETTING, AND PARTICIPANTS: Twelve premenarchal FDR girls and 10 control girls of comparable age, Tanner stage, and body mass index were studied at an academic medical center. INTERVENTIONS: Frequently sampled intravenous glucose tolerance tests and oral glucose tolerance tests were performed. MAIN OUTCOME MEASURES: Reproductive hormone levels, lipid profiles, glucose tolerance, and frequently sampled iv glucose tolerance test parameters of insulin sensitivity and secretion were investigated. RESULTS: Disposition index (DI), insulin secretion corrected for insulin sensitivity, was decreased in FDR compared with control girls at baseline (P = .01), independent of dysglycemia. Decreases in DI persisted in FDR girls during the 2-year follow-up (P = .003). T levels were increased (P = .02) in FDR compared with control girls at baseline, but this difference did not persist because T levels increased in control girls. CONCLUSIONS: DI is decreased in peripubertal FDR girls, and this decrease persists as puberty progresses. These findings suggest that ß-cell dysfunction is an early defect in glucose homeostasis preceding decompensation in glucose tolerance in FDR girls. T levels were increased in FDR girls earlier than previously reported, but these changes did not persist, suggesting an earlier onset of pubertal increases in glandular androgen secretion in FDR girls.

Hashimoto's thyroiditis pathology and risk for thyroid cancer.

BACKGROUND: Hashimoto's thyroiditis (HT) has been found to coexist with differentiated thyroid cancer (DTC) in surgical specimens, but an association between the two conditions has been discounted by the medical literature. Therefore, we performed this study to determine any potential relationship between HT and the risk of developing DTC. METHODS: We collected data for thyrotropin (TSH), thyroxine (T4), thyroid peroxidase antibody (TPO-Ab) titers, surgical pathology, and weight-based levothyroxine (LT4) replacement dose for patients who were referred for thyroid surgery. Patients with HT at final pathology were studied further. To estimate thyroid function, patients with preoperative hypothyroid HT (Hypo-HT) were divided into three equal groups based on their LT4 replacement: LT4-Low (<0.90 µg/kg), LT4-Mid (0.90-1.43 µg/kg), and LT4-High (>1.43 µg/kg). A group of preoperatively euthyroid (Euth-HT) patients but with HT by pathology was also studied. All subjects were also grouped based on their TPO-Ab titer in TPO-high (titer >1:1000) or TPO-low/negative (titer <1:1000 or undetectable) groups. The relationship of HT and DTC was studied extensively. RESULTS: Of 2811 subjects, 582 had HT on surgical pathology, 365 of whom were Euth-HT preoperatively. DTC was present in 47.9% of the Euth-HT, in 59.7% of LT4-Low, 29.8% of LT4-Mid, and 27.9% of LT4-High groups. The relative risk (RR) for DTC was significantly elevated for the Euth-HT and LT4-Low groups (p<0.001), but not for the LT4-Mid or LT4-High replacement dose groups. TPO-low/negative status conferred an increased RR in the Euth-HT and LT4-Low replacement dose groups (p<0.001 both), while TPO-high status decreased it in Euth-HT group (p<0.05) and made it nonsignificant in the LT4-Low group. CONCLUSIONS: HT pathology increases the risk for DTC only in euthyroid subjects and those with partially functional thyroid glands (LT4-Low) but not in fully hypothyroid HT (LT4-Mid and LT4-High). High TPO-Ab titers appear to protect against DTC in patients with HT.

Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.

Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (<5%) DN T cells associated with thyroid autoimmunity increased in numbers (>20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity.

Laparoscopic reversal of Roux-en-Y gastric bypass: technique and utility for treatment of endocrine complications.

BACKGROUND: The anatomic and physiologic changes with Roux-en-Y gastric bypass (RYGB) may lead to uncommon but occasionally difficult to treat complications such as hyperinsulinemic hypoglycemia with neuroglycopenia and recalcitrant hypocalcemia associated to hypoparathyroidism. Medical management of these complications is challenging. Laparoscopic reversal of RYGB anatomy with restoration of pyloric function and duodenal continuity is a potential treatment. The objective of this study was to present the indications, surgical technique, and clinical outcomes of laparoscopic reversal of RYGB. METHODS: Prospective study of consecutive patients offered laparoscopic reversal of RYGB. RESULTS: Five patients with remote laparoscopic RYGB underwent laparoscopic reversal of RYGB to normal anatomy (n = 2) or modified sleeve gastrectomy (n = 3). Indications were medically refractory hyperinsulinemic hypoglycemia with neuroglycopenia (n = 3), recalcitrant hypocalcemia with hypoparathyroidism (n = 1), and both conditions simultaneously (n = 1). Before reversal, all patients had a gastrostomy tube placed in the excluded stomach to document improvement of symptoms. Laparoscopic reversal was accomplished successfully in all patients. Three postoperative complications occurred: bleeding that required transfusion, gallstone pancreatitis, and a superficial trocar site infection. Average length of stay was 3 days. At a mean follow-up of 12 months (range 3 to 22), no additional episodes of neuroglycopenia occurred, average number of hypoglycemic episodes per week decreased from 18.5 ± 12.4 to 1.5 ± 1.9 (P = .05), and hypocalcemia became responsive to oral replacement therapy in both patients. CONCLUSIONS: Laparoscopic reversal of RYGB to normal anatomy or modified sleeve gastrectomy is feasible and may be a therapeutic option for selected patients with medically refractory hyperinsulinemic hypoglycemia and/or recalcitrant hypocalcemia associated with hypoparathyroidism.