Parathyroidectomy for adults with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and postmenopausal women. While most people with PHPT are asymptomatic at diagnosis, symptomatic disease can lead to hypercalcaemia, osteoporosis, renal stones, cardiovascular abnormalities and reduced quality of life. Surgical removal of abnormal parathyroid tissue (parathyroidectomy) is the only established treatment for adults with symptomatic PHPT to prevent exacerbation of symptoms and to be cured of PHPT. However, the benefits and risks of parathyroidectomy compared to simple observation or medical therapy for asymptomatic and mild PHPT are not well established. OBJECTIVES: To evaluate the benefits and harms of parathyroidectomy in adults with PHPT compared to simple observation or medical therapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, LILACS, ClinicalTrials.gov and WHO ICTRP from their date of inception until 26 November 2021. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing parathyroidectomy with simple observation or medical therapy for the treatment of adults with PHPT. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. cure of PHPT, 2. morbidity related to PHPT and 3. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. health-related quality of life and 3. hospitalisation for hypercalcaemia, acute renal impairment or pancreatitis. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We identified eight eligible RCTs that included 447 adults with (mostly asymptomatic) PHPT; 223 participants were randomised to parathyroidectomy. Follow-up duration varied from six months to 24 months. Of the 223 participants (37 men) randomised to surgery, 164 were included in the analyses, of whom 163 were cured at six to 24 months (overall cure rate 99%). Parathyroidectomy compared to observation probably results in a large increase in cure rate at six to 24 months follow-up: 163/164 participants (99.4%) in the parathyroidectomy group and 0/169 participants in the observation or medical therapy group were cured of their PHPT (8 studies, 333 participants; moderate certainty).  No studies explicitly reported intervention effects on morbidities related to PHPT, such as osteoporosis, osteopenia, kidney dysfunction, urolithiasis, cognitive dysfunction or cardiovascular disease, although some studies reported surrogate outcomes for osteoporosis and cardiovascular disease. A post-hoc analysis revealed that parathyroidectomy, compared to observation or medical therapy, may have little or no effect after one to two years on bone mineral density (BMD) at the lumbar spine (mean difference (MD) 0.03 g/cm2,95% CI -0.05 to 0.12; 5 studies, 287 participants; very low certainty). Similarly, compared to observation, parathyroidectomy may have little or no effect on femoral neck BMD after one to two years (MD -0.01 g/cm2, 95% CI -0.13 to 0.11; 3 studies, 216 participants; very low certainty). However, the evidence is very uncertain for both BMD outcomes. Furthermore, the evidence is very uncertain about the effect of parathyroidectomy on improving left ventricular ejection fraction (MD -2.38%, 95% CI -4.77 to 0.01; 3 studies, 121 participants; very low certainty). Four studies reported serious adverse events. Three of these reported zero events in both the intervention and control groups; consequently, we were unable to include data from these three studies in the pooled analysis. The evidence suggests that parathyroidectomy compared to observation may have little or no effect on serious adverse events (RR 3.35, 95% CI 0.14 to 78.60; 4 studies, 168 participants; low certainty).  Only two studies reported all-cause mortality. One study could not be included in the pooled analysis as zero events were observed in both the intervention and control groups. Parathyroidectomy compared to observation may have little or no effect on all-cause mortality, but the evidence is very uncertain (RR 2.11, 95% CI 0.20 to 22.60; 2 studies, 133 participants; very low certainty). Three studies measured health-related quality of life using the 36-Item Short Form Health Survey (SF-36) and reported inconsistent differences in scores for different domains of the questionnaire between parathyroidectomy and observation. Six studies reported hospitalisations for the correction of hypercalcaemia. Two studies reported zero events in both the intervention and control groups and could not be included in the pooled analysis. Parathyroidectomy, compared to observation, may have little or no effect on hospitalisation for hypercalcaemia (RR 0.91, 95% CI 0.20 to 4.25; 6 studies, 287 participants; low certainty). There were no reported hospitalisations for renal impairment or pancreatitis. AUTHORS' CONCLUSIONS: In accordance with the literature, our review findings suggest that parathyroidectomy, compared to simple observation or medical (etidronate) therapy, probably results in a large increase in cure rates of PHPT (with normalisation of serum calcium and parathyroid hormone levels to laboratory reference values). Parathyroidectomy, compared with observation, may have little or no effect on serious adverse events or hospitalisation for hypercalcaemia, and the evidence is very uncertain about the effect of parathyroidectomy on other short-term outcomes, such as BMD, all-cause mortality and quality of life. The high uncertainty of evidence limits the applicability of our findings to clinical practice; indeed, this systematic review provides no new insights with regard to treatment decisions for people with (asymptomatic) PHPT. In addition, the methodological limitations of the included studies, and the characteristics of the study populations (mainly comprising white women with asymptomatic PHPT), warrant caution when extrapolating the results to other populations with PHPT. Large-scale multi-national, multi-ethnic and long-term RCTs are needed to explore the potential short- and long-term benefits of parathyroidectomy compared to non-surgical treatment options with regard to osteoporosis or osteopenia, urolithiasis, hospitalisation for acute kidney injury, cardiovascular disease and quality of life.

Medical Management of Diabesity: Do We Have Realistic Targets?

PURPOSE OF REVIEW: The global prevalence of "diabesity"-diabetes related to obesity-is increasing steadily over the past few decades because of the obesity epidemic. Although bariatric surgery is an effective treatment option for patients with diabesity, its limited availability, invasiveness, relatively high costs and the potential for surgical and postsurgical complications restrict its widespread use. Therefore, medical management is the only option for a majority of patients with diabesity. Diabetes control with several anti-diabetic agents, including insulin, causes weight gain with probability of worsening diabesity. Rational use of anti-diabetic medications with weight loss potential in varying combinations may help to address this key issue for long-term management of diabesity. There is no consensus on such an approach from different professional bodies like American Diabetes Association, European Association for Study of Diabetes, or International Diabetes Federation. We attempt to discuss the key issues and realistic targets for diabesity management in this paper. RECENT FINDINGS: Rational use of anti-diabetic combinations can mitigate worsening of diabesity to some extent while managing patients. Retrospective studies showed that combination therapy with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose co-transporter 2 (SGLT-2) inhibitors, when administered along with other anti-diabetic medications, offer the best therapeutic benefit in the medical management of diabesity. Different combinations of other anti-diabetic drugs with minimum weight gain potential were also found useful. Because of insufficient evidence based on prospective randomised controlled trials (RCTs), future research should focus on evolving the appropriate rational drug combinations for the medical management of diabesity.

Is annual surveillance of all treated hypothyroid patients necessary?

BACKGROUND: Annual surveillance (with thyroid function testing) is widely recommended for the long-term follow-up of treated hypothyroid patients. It is based largely on consensus opinion and there is limited evidence to support the frequency of monitoring. The majority of patients in our hospital based thyroid register are on 18 monthly follow-up. METHODS: We carried out a retrospective analysis to see if there is evidence to support more frequent testing. We used a logistic regression model to assess whether any baseline characteristics could be applied to predict an abnormal test. RESULTS: We identified 2,125 patients with a minimum of 10 years follow-up (89% female, 65% autoimmune hypothyroidism, and mean age at registration 51 years). There were 2 groups: 1182 (56%) had been allocated to 18 monthly follow-up and the rest had annual surveillance. The groups were well matched at baseline. Overall, during follow-up the 12 monthly group had more abnormal tests requiring dose adjustment. However, on logistic regression analysis, people aged less than 60 years, individuals taking < 150 mug thyroxine per day and people on 18 monthly follow-up had less abnormal tests. CONCLUSION: 18 monthly surveillance may be adequate in the long term follow-up of hypothyroid patients less than 60 years of age on a stable thyroxine dose of 100-150 mug/day where there are robust follow-up mechanisms in place. Implementing this strategy has potential for cost saving.

Combination therapy with GLP-1 analogues and SGLT-2 inhibitors in the management of diabesity: the real world experience.

Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre. Out of 79 patients on this combination regimen with other anti-diabetic medications, 37 cases who had follow up at 3-6 months were studied. Mean age and duration of follow up were 57.4 (+/-7.8) and 139 (+/-32.6) days, respectively. Twenty-two patients (59.5 %) were Asians. Statistically significant improvements in clinical parameters such as body weight reduction (3.07 kg), glycated haemoglobin (HbA1c) reduction (1.05 %), lower BMI (-1.13 kg/M2) and insulin dose reduction (6.8 units) were observed (p < 0.05 for all) in patients on combination regimen. Linear regression analysis showed that baseline HbA1c and baseline insulin dose were independent predictors of HbA1c reduction and insulin dose reduction, respectively. Our results suggest that combination therapy with GLP-1 agonists and SGLT-2 inhibitors is a promising option for patients with diabesity.

Metabolic surgery: A paradigm shift in type 2 diabetes management.

Obesity and type 2 diabetes mellitus (T2DM) are major public health issues globally over the past few decades. Despite dietary interventions, lifestyle modifications and the availability of several pharmaceutical agents, management of T2DM with obesity is a major challenge to clinicians. Metabolic surgery is emerging as a promising treatment option for the management of T2DM in the obese population in recent years. Several observational studies and a few randomised controlled trials have shown clear benefits of various bariatric procedures in obese individuals in terms of improvement or remission of T2DM and multiple other health benefits such as improvement of hypertension, obstructive sleep apnoea, osteoarthritis and non-alcoholic fatty liver disease. Uncertainties about the long-term implications of metabolic surgery such as relapse of T2DM after initial remission, nutritional and psychosocial complications and the optimal body mass index for different ethnic groups exist. The article discusses the major paradigm shift in recent years in the management of T2DM after the introduction of metabolic surgery.