Biliopancreatic diversion for severe obesity: long-term weight maintenance and occurrence of nutritional complications are two facets of the same coin.

BACKGROUND: Despite the widespread clinical use of hypoabsorptive metabolic bariatric surgery, very long-term outcomes are still lacking. The aim of the study was to assess the long-term safety and efficacy of biliopancreatic diversion at 30 years in patients with class 3 obesity (BMI over 40 kg/m2). METHODS: This retrospective single-centre study used data from a prospectively collected database on a sample of consecutive patients submitted to biliopancreatic diversion with a minimum follow-up of 30 years. Outcomes assessed included overall survival, long-term weight loss and weight maintenance, remission of obesity-related co-morbidities, and short- and long-term surgical and/or nutritional or metabolic complications. RESULTS: Among 199 consecutive patients (136 female, 63 male) who had surgery between November 1992 and April 1994, the mean age at operation was 38 (range 14-69) years and mean preoperative BMI was 48.7 (32.0-74.3) kg/m2. At baseline, 91 of 199 patients (45.7%) had type 2 diabetes. At 20 and 30 years, 122 (61%) and 38 (19%) of the 199 patients respectively were available for follow-up. At 30 years, the overall mortality rate was 12% (23 of 199). Surgical complications were concentrated in the short-term follow-up, whereas nutritional or metabolic complications increased progressively over time. A nutritional complication was diagnosed in 73 of 122 patients (60%) at 20 years and 28 of 38 (74%) at 30 years. Weight loss and glycaemic control were maintained throughout the follow-up; mean % total weight loss was 32.8 (range 14.1-50.0) at 1 year and 37.7 (range 16.7-64.8) at 30 years. One patient presented with recurrence of type 2 diabetes at 20 and 30 years; there were no patients with new-onset type 2 diabetes. CONCLUSION: Biliopancreatic diversion leads to good and sustained weight maintenance up to 30 years with low perioperative risk, but at the cost of a high long-term prevalence of nutritional complications.

Management of Malnutrition and Hepatic Impairment After Duodenal Switch.

BACKGROUND: Malnutrition and liver impairment after duodenal switch (DS) are possible and undesired complications, often conservatively treated. However, in specific cases, surgical revision may be necessary. This study aims to describe outcomes achieved by two bariatric surgery centers and address effectiveness and safety of revisional surgical procedures to resolve these complications. METHODS: A retrospective chart review was performed in two bariatric surgery centers from 2008 to 2022. Patients who required revisional surgery to treat malnutrition and/or liver impairment refractory to nutritional and total parenteral nutrition intervention (TPN) after duodenal switch were included. No comparisons were performed due to the descriptive nature of this study. RESULTS: Thirteen patients underwent revisional surgery, the mean age was 44.7, the 53.8% were females, and the mean preoperative BMI was 54.7 kg/m2; the mean time between DS and revisional procedure was 26.5 months, and 69.1% of patients were placed on TPN. One patient developed hepatic encephalopathy; one patient presented with ascites, pleural effusion, and renal insufficiency, undergoing reoperation after revisional procedure due to a perforated ileal loop. Mortality rate was 0%; all patients regained weight after the revisional procedure, and the mean total protein and albumin blood levels 12 months after surgery were 6.3 and 3.6 g/dl, respectively. CONCLUSIONS: While refractory malnutrition and/or liver failure are rare among patients post-DS, if underdiagnosed and untreated, this can lead to irreversible outcomes and death. All revisional procedures included in this study resulted in improvement of the nutritional status and reversal of liver impairment, with low complication rates.

Wernicke Encephalopathy After Bariatric Surgery: a Literature Review.

Wernicke encephalopathy (WE) is an acute neurological disorder classically characterized by ataxia, ophthalmoplegia, and altered mental status. This is caused by thiamine deficiency and is usually seen in malnourished populations. However, with the advent and rise of bariatric surgery in the last 50 years, WE has become an increasingly recognized and potentially deadly complication. Here, we review the populations at risk, clinical presentation, and the incidence of WE in the bariatric surgery population from 1985 to 2023. While the predominant procedure shifts throughout the years, the overall incidence of WE per 100,000 cases for the following procedures are sleeve gastrectomy (1.06), gastric band (1.16), RYGB (4.29), and biliopancreatic diversion with duodenal switch (8.92). Thus, early intervention and post-operative supplementation is recommended to prevent WE.

Analysis of the Impact of the Learning Curve on the Safety Outcome of the Totally Robotic-Assisted Biliopancreatic Diversion with Duodenal Switch: a Single-Institution Observational Study.

INTRODUCTION: Totally robotic-assisted biliopancreatic diversion with duodenal switch (BPD/DS) learning curve has been described to be longer at approximately 50 cases, at which point operative time and complications rate decrease and tend to stabilize. This study aimed to form an analysis of the impact of the learning curve on the safety outcomes of the totally robotic-assisted BPD/DS. METHODS: A retrospective review of patients who underwent primary totally robotic-assisted BPD/DS by one of our certified bariatric and metabolic surgeon member of our institution was performed. The patients were classified into two groups, the learning stage group (first 50 cases) and the mastery stage group. Differences in operative time in minutes and postoperative outcomes were analyzed. RESULTS: Two hundred seventy-six patients were included. The operative time and the postoperative length of stay were significantly higher in the learning stage group (173.8 ± 35.8 min vs. 139.2 ± 30.2 min, p= 0.0001; 3.4 ± 1.4 days vs. 2.6 ± 0.9 days, p= 0.0002). The overall leakage rate was significantly higher in the learning stage group (8% vs. 0.4%, p= 0.0001). The global rate of complications for the learning stage group was 14%, and for the mastery stage group was 6.6% (p= 0.08). CONCLUSIONS: After the first 50 cases, the operative time, the length of stay, and the overall rate of complications decreased, being especially significant the decrease in the duodeno-ileal anastomosis leakage rate after reaching the learning curve.

Optimal Small Bowel Limb Lengths of Roux-en-Y Gastric Bypass.

PURPOSE OF REVIEW: Gastric bypass and biliopancreatic diversion (BPD) have come full circle, from a loop configuration to a Roux-en-Y and finally back to a loop configuration as one anastomosis gastric bypass and single-anastomosis duodenal switch. Most surgeons performing Roux-en-Y gastric bypass (RYGB) do not measure the common channel (CC) length and most surgeons performing BPD do not measure the biliopancreatic limb length (BPL). RECENT FINDINGS: The small bowel length in humans is variable from as short as < 400 cm to as long as > 1000 cm. The combination of these two facts means that even if surgeons keep the limb lengths constant, surgeons will get variable limb length due to the variability of small bowel length in patients. Hence, outcomes of weight loss, resolution of medical problems, or developing nutritional deficiencies which are related to limb length are variable. In this article, we evaluate the published literature related to the effect of varying the Roux limb, BPL, CC, and total alimentary limb lengths on the outcomes of RYGB. We have focused on historical and current randomized controlled trials as well as systematic reviews and meta-analysis to outline the current literature and our interpretation of this literature.

Short-Term (30-Day) Morbidity of Biliopancreatic Diversion Compared to Roux-en-Y Gastric Bypass as Revisional Procedures for Failed Vertical Banded Gastroplasty.

BACKGROUND: Silastic ring vertical gastroplasty (SRVG) and vertical banded gastroplasty (VBG) are associated with a high failure rate due to weight regain and complications at long-term follow-up. Consequently, surgical correction for such procedures is warranted. Controversy exists as to which surgical procedure is the ideal choice for such correction. Our aim is to compare short-term outcome of Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) repair for failed VBG/SRVG bariatric procedures. METHODS: The medical records of patients with failed SRVG who underwent corrective procedures at our institute between 2004 and 2018 were retrospectively reviewed. Patients characteristics, surgical approaches, and intraoperative and post-operative complications were examined and compared. RESULTS: Sixty patients in total underwent a surgical corrective procedure for failed SRVG. Thirty-one patients underwent RYGB, and 29 patients underwent BPD. Major complications were seen more in the RYGB group (35% = 11) compared to the BPD (6.9% = 2). Even though anastomotic leak rates were not statistically significant (p = 0.053), an apparent tendency for such a complication was noted in the RYGB group. RYGB procedure had an increased 30-day complication rate (p = 0.055) compared to RYGB. Laparoscopic approach had statistically fewer complications than open approach. No mortality was observed in either group. CONCLUSION: Our study showed that BPD is a safe option with less complication rates than RYGB in the short-term period for surgical correction of failed VBG/SRVG procedures.

Conversion of gastric sleeve to Roux-en-Y gastric bypass and biliopancreatic diversion/duodenal switch: safe and viable options.

BACKGROUND: Sleeve gastrectomy (SG) remains the most performed bariatric surgery. As numbers of SG increase, so do the numbers of patients requiring conversion for insufficient weight loss or weight regain. However, the literature has cited complication rates as high as 30% for reoperative bariatric surgery. OBJECTIVE: With the recent inclusion of conversion surgery variables in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database, we compared the safety and efficacy of SG conversion to Roux-en-Y gastric bypass (RYGB) versus biliopancreatic diversion and duodenal switch (BPD/DS). SETTING: MBSAQIP database. METHODS: Analysis of the 2020 MBSAQIP Participant Use Files revealed 6020 patients who underwent SG conversion to RYGB (5348) and BPD/DS (672). We examined 30-day outcomes including death, anastomotic leak, readmission, any complication, dehydration, and weight loss. RESULTS: There was no statistically significant difference in mortality (.12% versus 0%) or; complication rate (6.5% versus 5.1%) with SG conversion to RYGB or BPD/DS. There was a statistically significant difference in anastomotic leak (.5% versus 1.2%, P = .024). Interestingly, BPD/DS was less likely to require dehydration treatments (4.2% versus 2.2%, P = .009) and had fewer readmissions within 30 days (7.3% versus 5.4%, P = .043). CONCLUSIONS: Complication rates after conversion of SG to RYGB or BPD/DS may be significantly lower than previously reported and only slightly higher than after primary weight loss surgery. SG conversion to either RYGB or BPD/DS remain safe, viable options for patients who had insufficient weight loss or regain, and BPD/DS may be the better option in the appropriate patient.

Jejunal adenocarcinoma after biliopancreatic diversion. Report of a case.

The effects of bariatric surgery on the development of gastrointestinal cancers remain ill defined. We present a case of jejunal adenocarcinoma developing 19 years after biliopancreatic diversion (BPD) procedure according to Scopinaro's technique. The patient developed a marked distension of the biliopancreatic limb caused by a jejunal mass, evolving towards the so called "duodenal blowout". Emergency jejunal resection of the biliopancreatic limb, with creation of a new end-to-side jejunal-ileal anastomosis was necessary. The histological examination resulted in a moderately-differentiated ulcerated adenocarcinoma, with reactive lymph nodes and tumor-free resection margins. Tumors of the gastrointestinal system can arise following malabsorptive operations for morbid obesity, and they may be difficult to diagnose, since the symptoms are often attributed to the anatomical-functional changes resulting from this type of surgery. The case reported herein suggests that there is a need for surveillance in patients complaining of digestive symptoms after malabsorptive bariatric surgery.

Long-Term Outcomes of Revisional Malabsorptive Bariatric Surgery: Do the Benefits Outweigh the Risk?

PURPOSE: To evaluate the long-term outcomes of revisional malabsorptive bariatric surgery. MATERIALS AND METHODS: Malabsorptive bariatric procedures are increasingly performed in the revisional setting. We collated and analysed prospectively recorded data for all patients who underwent a revisional Biliopancreatic diversion + / - duodenal switch (BPD + / - DS) over a 17-year period. RESULTS: We identified 102 patients who underwent a revisional BPD + / - DS. Median follow-up was 7 years (range 1-17). There were 21 (20.6%) patients permanently lost to follow-up at a median of 5 years postoperatively. Mean total weight loss since the revisional procedure of 22.7% (SD 13.4), 20.1% (SD 10.5) and 17.6% (SD 5.5) was recorded at 5, 10 and 15 years respectively. At the time of revisional surgery, 23 (22.5%) patients had diabetes and 16 (15.7%) had hypercholesterolaemia with remission of these occurring in 20 (87%) and 7 (44%) patients respectively. Nutritional deficiencies occurred in 82 (80.4%) patients, with 10 (9.8%) patients having severe deficiencies requiring periods of parenteral nutrition. Seven (6.9%) patients required limb lengthening or reversal procedures. There were 16 (15.7%) patients who experienced a complication within 30 days, including 3 (2.9%) anastomotic leaks. Surgery was required in 42 (41.2%) patients for late complications. CONCLUSION: Revisional malabsorptive bariatric surgery induces significant long-term weight loss and comorbidity resolution. High rates of temporary and permanent attrition from follow-up are of major concern, given the high prevalence of nutritional deficiencies. These data question the long-term safety of malabsorptive bariatric procedures due to the inability to ensure compliance with nutritional supplementation and long-term follow-up requirements. KEY POINTS: • Revisional bariatric surgery workload is increasing • Revisional malabsorptive surgery is efficacious for weight loss and comorbidity resolution • Revisional malabsorptive surgery is associated with high rates of nutritional deficiencies • Attrition from follow-up in this specific cohort of patients is of particular concern due to the risk of undiagnosed and untreated nutritional deficiencies.

Safety of Primary Versus Revisional Biliopancreatic Diversion with Duodenal Switch in Patients with Super Obesity Using the MBSAQIP database.

INTRODUCTION: For patients with super obesity (BMI > 50 kg/m2), biliopancreatic diversion/duodenal switch (BPD/DS) can be an effective bariatric operation. Technical challenges and patient safety concerns, however, have limited its use as a primary procedure. This study sought to assess the safety of primary versus revisional BPD/DS. MATERIALS AND METHODS: The MBSAQIP database was queried for primary and revisional BPD/DS (2015-2018). Inclusion criteria were patients ≥ 18 years of age, BMI > 50 kg/m2, and with no concurrent procedures. Preoperative variables were compared using a chi-square test or Wilcoxon two-sample tests. Multivariate logistic or robust linear regression models were used to compare outcomes. RESULTS: There were 3,378 primary BPD/DS and 487 revisional BPD/DS patients. Primary BPD/DS patients had higher BMI (56.5 [IQR4.4] versus 54.8 [IQR4] kg/m2, p < 0.0001) and had more diabetes mellitus type II (29.1% versus 17.2%, p < 0.0001). Intraoperatively, revisional BPD/DS had longer operative time (165 [IQR47] min versus 139 [IQR100] min, p < 0.0001). After adjusting for preoperative characteristics, there was no difference in 30-day readmission or ED visits (primary 12.9% versus revisional 14.6%), reoperation or reintervention (primary 5.7% versus revisional 7.8%), or mortality (primary 0.4% versus revisional 0.6%). In contrast, the revisional BPD/DS patients had higher odds of major morbidity (primary 3.4% versus revisional 5.3%, OR 1.9, CI 1.1-3.2, p = 0.019). CONCLUSIONS: Revisional BPD/DS is associated with higher morbidity than primary BPD/DS in patients with super obesity. These patients should thus be counselled appropriately when choosing a primary or revisional bariatric procedure.

Bile Reflux After Single Anastomosis Duodenal-Ileal Bypass with Sleeve (SADI-S): a Meta-analysis of 2,029 Patients.

BACKGROUND: Single anastomosis duodenal-ileal bypass with sleeve (SADI-S) is a novel bariatric surgery modified from the classic biliopancreatic diversion with duodenal switch (BPD-DS). These surgical modifications address most BPD-DS hurdles, but the risk of bile reflux may hinder SADI-S acceptance. We aimed to evaluate the event rate of bile reflux after SADI-S. METHODS: PubMed, ScienceDirect, Cochrane, Web of Science, and Google Scholar were used to search English articles between 2008 and 2021 by two independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The risk of bias was assessed using Newcastle-Ottawa Scale and the JBI tool. Event rates were meta-analyzed using Comprehensive Meta-Analysis (CME) V3. RESULTS: Out of 3,027 studies analyzed, seven were included. Studies were published between 2010 and 2020. Six out of 7 studies were retrospective. Three studies had a low risk of bias, three studies had a moderate risk of bias, and one had a high risk of bias. The mean follow-up was 10.3 months. The total number of patients was 2,029, with 25 reports of bile reflux, resulting in an incidence of 1.23%, with an event rate of 0.016 (95% CI 0.004 to 0.055). CONCLUSIONS: Bile reflux has not been demonstrated to be problematic after SADI-S in this meta-analysis. Further long-term studies are needed.

Long-term comparative study on open versus laparoscopic biliopancreatic diversion.

BACKGROUND: To date, bariatric surgery has been proposed as the most effective treatment to resolve morbid obesity, a multifactorial chronic disease with an epidemic and increasing tendency. The purpose of this study was to determinate the impact of the laparoscopy on weight loss parameters in morbid obese patients who underwent surgery according to Scopinaro's biliopancreatic diversion (BPD) and evaluate early and late complications related to the open and laparoscopic approach of this technique. MATERIALS AND METHODS: This is a longitudinal retrospective study in consecutive patients undergoing BPD due to morbid obesity between 1999 and 2015. From 2006 the laparoscopic technique was introduced in our group for obesity surgery. In both approaches, open and laparoscopic surgery, the procedure performed consists of a proximal gastric section with a long Roux-en-Y reconstruction. The following variables were assessed in the two groups: intervention duration (min), estimated blood loss (mL), conversions to open approach (%), preoperative stay, postoperative and global stay (days). Complications were divided into early and late postoperative complications. The early surgical complications were catalogued according to the Clavien-Dindo classification. RESULTS: Two hundred seventy-seven patients were consecutively enrolled and divided in two groups: open BPD and laparoscopic BPD. There were no significant differences in the comparison of the two groups and the mean age was 43.9 years (19-60) with a mean BMI of 52.5 kg/m2. A statistically significant reduction was observed in favor of the laparoscopic group with respect to the reduction in hospital stay and in the incidence of incisional hernia as a late complication. No statistically significant difference were found with respect to early postoperative complications. CONCLUSIONS: Laparoscopic BPD is a safe technique that allows a shorter hospital stay compared to open surgery and that allows a drastic reduction in the incidence of incisional hernias.

Late complications of biliopancreatic diversion in an older patient: a case report.

BACKGROUND: In the mid-seventies, biliopancreatic diversion became popular as weight-loss surgery procedure. This bariatric procedure combines distal gastric resection and intestinal malabsorption, leading to greater weight loss and improvement of co-morbidities than other bariatric procedures. Nowadays, biliopancreatic diversion has become obsolete due to the high risk of nutritional complications. However, current patients with biliopancreatic diversions are aging. Consequently, geriatricians and general practitioners will encounter them more often and will be faced with the consequences of late complications. CASE PRESENTATION: A 74-year old female presented with weakness, recurrent falls, confusion, episodes of irresponsiveness, anorexia and weight loss. Her medical history included osteoporosis, herpes encephalitis 8 years prior and a biliopancreatic diversion (Scopinaro surgery) at age 52. Cerebral imaging showed herpes sequelae without major atrophy. Delirium was diagnosed with underlying nutritional deficiencies. Biochemical screening indicated vitamin A deficiency, vitamin E deficiency, zinc deficiency and severe hypoalbuminemia. While thiamin level and fasting blood glucose were normal. However, postprandial hyperinsulinemic hypoglycemia was observed with concomitant signs of confusion and blurred consciousness. After initiating parenteral nutrition with additional micronutrient supplementation, a marked improvement was observed in cognitive and physical functioning. CONCLUSIONS: Long-term effects of biliopancreatic diversion remain relatively underreported in older patients. However, the anatomical and physiological changes of the gastrointestinal tract can contribute to the development of metabolic and nutritional complications that may culminate in cognitive impairment, functional decline and delirium. Therefore, it is warranted to evaluate the presence of metabolic disturbances and nutritional complications in older patients after biliopancreatic diversion.

Bone metabolism and fracture risk after Biliopancreatic Diversion.

BACKGROUND: Bariatric surgery (BS) is an effective treatment. However, there have been concerns regarding the negative effect on the bone. The aim of this study was to assess changes in bone metabolism and the risk of fracture after biliopancreatic diversion (BPD). MATERIAL AND METHODS: A retrospective analysis of obese patients undergoing BPD between 1998 and 2017 was conducted, and patients with at least 1 year of follow-up were included. The incidence of fracture and of changes in bone metabolism was studied. RESULTS: In total, 216 patients were included (78.2% female), with a mean age of 42.5(10.6) years. The median follow-up was 6.8(IQR 10.2-3.2) years. The mean body mass index (BMI) was 49.7(6.3) kg/m2. 13.2% (n=29) suffered a bone fracture after surgery; the time until the first fracture was 7.9(3.8) years (55.2% secondary to a casual fall). The rate of fracture incidence was 19.6 per 1000 person-years (95%CI: 1.3-2.7), prevalence was 13.4% (95%CI: 8.9-18.0). The risk of bone fractures seems to increase with longer postoperative evolution time. PTH (pg/ml) levels were significantly higher in patients with fractures (1 year, 98.1 vs. 77.8; 5 years, 162.5 vs. 110.3 p<0.05, adjusted HR 1.10; 95%CI 1.01-1.11). Subjects with a higher %EWL had less risk of fractures after surgery (adjusted HR 0.97; 95%CI 0.94-0.99). Moreover, 25(OH)D levels were lower, and osteocalcin and ß-Crosslaps levels were slightly higher (not significant) in patients with fractures. CONCLUSION: BPD is related to important changes in bone metabolism, which can lead to an increased risk of bone fractures. Assessing the risk of fractures should be part of BS patient care.

In obesity with T2DM, biliopancreatic diversion increased T2DM remission vs. medical and lifestyle therapy at 10 y.

SOURCE CITATION: Mingrone G, Panunzi S, De Gaetano A, et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2021;397:293-304. 33485454.

The Influence of Different Alimentary and Biliopancreatic Limb Lengths in Gastric Bypass Patients.

PURPOSE: The aim of this study was to compare the effect of two different limb lengths after RYGB on weight loss, postoperative gastro-intestinal complications, and vitamin deficiencies. MATERIALS AND METHODS: A retrospective analyses of 100 patients after RYGB with 2 different limb lengths were done. Group A (50 patients) had a biliopancreatic limb (BPL) of 75 cm and an alimentary limb (AL) of 150 cm. Group B (50 patients) had a BPL of 150 cm and an AL of 75 cm. The effect on weight loss, body mass index, excess weight loss (EWL), total weight loss (TWL), and postoperative complications was analyzed up to 2 years postoperatively. RESULTS: Patients with a longer BPL achieved significantly more %EWL compared to a shorter BPL 2 years postoperatively (82.8 ± 31.2 versus 93.8 ± 15.1; p = 0.038). A significant difference was also seen in %TWL after 1 year (30.3 ± 10.1 versus 37.4 ± 6.9; p < 0.01) and 2 years (31.6 ± 7.5 versus 35.6 ± 8.6; p = 0.022), both in favor of group B. However, patients with a longer BPL (group B) showed significant more diarrhea and steatorrhea compared to group A (p < 0.01). CONCLUSION: BPL of 150 cm is associated with more %EWL and %TWL 2 years after RYGB. However, it is accompanied by an increase of diarrhea and steatorrhea to disadvantage off group B. Future studies need to focus on further tailoring BPL and AL lengths to achieve the best possible outcomes for patients with morbid obesity.

Embryopathy Following Maternal Biliopancreatic Diversion: Is Bariatric Surgery Really Safe?

Pregnancy after bariatric surgery is usually considered safe. Recently, a few studies reported that bariatric surgery represents a risk factor for birth defects. A case series of six patients, born from women who had undergone biliopancreatic diversion, is reported. The clinical pattern was characterized by psychomotor development delay (100%), microphthalmia (83%), growth retardation (66%), hearing loss (66%), and variable facial dysmorphism. Based on the clinical profile and symptoms reported by women during pregnancy, a causal association between maternal chronic post-surgical malabsorption, congenital anomalies, and neonatal outcome is proposed, with vitamin A deficiency representing a major causing factor. Educational follow-up support, continuous clinical monitoring, and appropriate nutritional assessment appear to be crucial to reduce the potential risk of congenital malformations and child disability.

Bilio-pancreatic diversion: report of a case involving bone metabolism complications.

Prolonged vitamin D deficiency may result in lower calcium absorption and osteoporosis, leading to pathologic fractures. We report the case of a young woman with severe, complicated osteoporosis, which developed several years after biliopancreatic diversion that was performed to treat morbid obesity. Chronic low vitamin D levels provided a continuous stimulus for parathormone secretion, which resulted in parathyroid hyperplasia/adenoma and autonomous production of the hormone.