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Aims Optimal modality for pre-operative radiological parathyroid localization in primary hyperparathyroidism (PHPT) is controversial. Four-dimensional computed tomography (4DCT) is a newer imaging technique that can provide detailed anatomic information. We aimed to evaluate the performance of 4DCT as a localization tool for patients with PHPT. Methods Between 03/2018 and 05/2021, 121 patients were operated for primary hyperparathyroidism at our institution. 4DCT was used as a second line investigation in patients Results Mean age of the study population was 68.4 years (Range27–88). Mean tumour size on CT was 16.13mm (range 4–38). Mean serum calcium and PTH levels were 2.89mmol/L and 20.76pmol/L. 4DCT identified a lesion in 61 patients (sensitivity 76.2%) and correctly lateralized a pathological parathyroid in 58/61 patients (specificity 95.1%). Hyperplasia and smaller gland size were non-significantly associated with non-detection (p>0.05). Of the 61 patients with a positive 4DCT, 4 (6.5%) developed persistent disease – in two a lymph node/thyroid nodule was excised and two had multigland disease. In this study 4DCT correctly localized recurrent disease in 4 of 5 patients, and 12 of 15 patients with negative Sestamibi SPECT CT scan. Discussion 4DCT offers accurate localization of abnormal glands in first-time parathyroidectomy for PHPT. Advantages include simplicity and speed of scan. Using 4DCT for first-time localisation is changing conventional practice of ultrasound+sestamibi scanning. It may have an added role in localizing disease in recurrent HPT and in patients who have a negative nuclear scan.

Objective To evaluate the use of two questionnaires assessing awareness of hypoglycemia, in a pediatric type 1 diabetes (T1D) population. Methods Prospective observational study with children (aged 9‐18 years) and parents (for children aged 2‐11 years) answering the Gold and Clarke questionnaires assessing awareness of hypoglycemia. Psychometric properties of the questionnaires were evaluated, and the most appropriate cut‐off score to classify participants as having normal vs impaired awareness of hypoglycemia (IAH) was determined by ability to recognize subsequent hypoglycemia and hypoglycemia severity, documented in a 4‐week blood glucose diary. Questionnaires were readministered at follow‐up assessment approximately 1.5 years later. Results In total, 112 participants (51% male) with median (IQR) age 13.7 (11.1‐15.8) years, T1D duration 4.7 (2.2‐7.8) years, and HbA1c 62 (57‐73) mmol/mol (7.8%) were included. Both questionnaires demonstrated acceptable psychometric properties. Using score ≥3 to classify IAH gave a prevalence of IAH of 41% (Gold) and 22% (Clarke). When classified using the Gold questionnaire, IAH participants had higher incidences of mild asymptomatic hypoglycemia, whereas with the Clarke questionnaire, they had higher incidences of clinically significant and severe hypoglycemia. Subgroup analyses confirmed these associations only in participants aged ≥9 years. Follow‐up was completed in 90% of the participants, and a change of awareness status was observed in 22% to 36%. Conclusions The Gold and Clarke questionnaires may be used to assess awareness of hypoglycemia in pediatric T1D in those ≥9 years of age, but the more detailed Clarke questionnaire has higher specificity and is superior in predicting risk of clinically significant hypoglycemia. © 2019 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Aims This study examined the effect of experimentally‐induced hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes. Methods In a prospective, randomised, open‐label, blinded, endpoint cross‐over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non‐diabetic volunteers, underwent hyperinsulinaemic‐euglycaemic (blood glucose 4.5–5.5 mmol/L) and hypoglycaemic (2.2–2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high‐sensitivity cardiac troponin I (hs‐cTnI) concentration. Results During hypoglycaemia, coronary flow reserve trended non‐significantly lower in those with type 1 diabetes than in the non‐diabetic participants (3.54 ± 0.47 vs. 3.89 ± 0.89). A generalised linear mixed‐model analysis examined diabetes status and euglycaemia or hypoglycaemia as factors affecting CFR. No statistically significant difference in CFR was observed for diabetes status (p = .23) or between euglycaemia and hypoglycaemia (p = .31). No changes in hs‐cTnI occurred during hypoglycaemia or in the recovery period (p = .86). Conclusions A small change in CFR was not statistically significant in this study, implying hypoglycaemia may require more than coronary vasomotor dysfunction to cause harm. Further larger studies are required to investigate this putative problem., Hypoglycaemia may require more than coronary vasomotor dysfunction to mediate harm

Driving is an important everyday activity for many people with diabetes, which is designated a prospective disability as it may impair driving performance as it progresses in severity. In effect, the principal threat to driving performance is hypoglycaemia associated with insulin therapy. Regular assessment of medical fitness to drive is undertaken to identify drivers with diabetes who are at greatest risk of experiencing motor vehicle accidents. Many countries do not restrict the licensing of drivers with insulin-treated diabetes and fail to review and/or restrict the driving of large goods vehicles or those carrying passengers. The European Union has formulated regulations for driving licensing for diabetes through successive directives, which have been implemented by individual countries including the UK. In response to submissions to relax licensing restrictions, some of these have been amended recently and were implemented in the UK in January 2018. Their rationale and potential value are discussed.

Over half of all episodes of severe hypoglycaemia (requiring external help) occur during sleep, but nocturnal hypoglycaemia is often asymptomatic and unrecognised. The precise incidence of nocturnal hypoglycaemia is difficult to determine with no agreed definition, but continuous glucose monitoring has shown that it occurs frequently in people taking insulin. Attenuation of the counter-regulatory responses to hypoglycaemia during sleep may explain why some episodes are undetected and more prolonged, and modifies cardiovascular responses. The morbidity and mortality associated with nocturnal hypoglycaemia is probably much greater than realised, causing seizures, coma and cardiovascular events and affecting quality of life, mood and work performance the following day. It may induce impaired awareness of hypoglycaemia. Cardiac arrhythmias that occur during nocturnal hypoglycaemia include bradycardia and ectopics that may provoke dangerous arrhythmias. Treatment strategies are discussed that may help to minimise the frequency of nocturnal hypoglycaemia.

Some therapies for type 2 diabetes (T2DM) are limited by hypoglycaemia, and this underestimated side effect carries an associated morbidity and financial burden. Large trials that have examined strict glycaemic control and cardiovascular outcomes in T2DM have highlighted the potential harm of exposure to hypoglycaemia in people with coronary heart disease.The responses to, and the morbidity associated with, hypoglycaemia in T2DM are discussed with identification of people most at risk of severe hypoglycaemia. The evidence base for non-pharmacological strategies and the risks of hypoglycaemia associated with various treatment modalities are examined. This review provides the clinician with a rational approach to the selection of different anti-diabetes drugs to minimize the risk of hypoglycaemia.When managing T2DM, insulin and insulin secretagogues should be used judiciously and glycaemic targets individualized to avoid hypoglycaemia. Incretin mimetics present a lower risk of hypoglycaemia with similar efficacy as traditional agents in treating hyperglycaemia. The potential relationship between hypoglycaemia and precipitation of acute cardiovascular events is a highly topical area of research and may help determine what glycaemic targets are appropriate in people with T2DM.

Impaired awareness of hypoglycaemia (IAH) is an acquired complication of insulin therapy, which affects people with type 1 and insulin-treated type 2 diabetes mellitus, whereby the ability to perceive the onset of hypoglycaemia becomes diminished or absent. Deficiencies of the counter-regulatory hormonal responses to hypoglycaemia usually co-exist. The development of IAH and counter-regulatory failure greatly increases the risk of severe hypoglycaemia. Scoring systems have been developed that can be used in the clinical setting and assist with identification of this group of individuals at risk of severe hypoglycaemia. The mainstay of treatment of IAH is the scrupulous avoidance of hypoglycaemia.

Strict glycaemic control is strongly advocated in people with type 2 diabetes to prevent vascular disease. However, the outcomes of two large clinical trials have indicated the potential dangers of pursuing this policy in those at high risk of cardiovascular disease, with an excess of fatal vascular events being associated with a higher frequency of severe hypoglycaemia. Hypoglycaemia secondary to insulin and sulphonylurea therapy is often associated with serious morbidity; anecdotal evidence has long implicated hypoglycaemia as a potential cause of myocardial ischaemia or a cardiac arrhythmia. Hypoglycaemia provokes sympatho-adrenal activation and counterregulatory hormone secretion, which exert pronounced cardiovascular effects. Although well tolerated in healthy people, the superimposition of these profound physiological effects on a diseased coronary vasculature and a dysfunctional cardiac conductive system may induce serious or even fatal cardiovascular events. These risks should influence therapeutic targets and the approach to diabetes management in people with diabetes with established vascular disease in whom exposure to severe hypoglycaemia could be dangerous.

Hypoglycaemia is a frequent side-effect of treatment with insulin and sulfonylureas for people with diabetes, threatening potentially serious morbidity and preventing optimal glycaemic control. Fear of hypoglycaemia and development of syndromes such as impaired awareness and counterregulatory deficiency provide additional hazards for intensification of treatment. Rapid lowering of HbA1c may be potentially dangerous in type 2 diabetes because of the adverse cardiovascular effects induced by hypoglycaemia. Hypoglycaemia can disrupt many everyday activities such as driving, work performance and recreational pursuits. Measures to reduce the risk of hypoglycaemia are labour-intensive and require substantial resources.

Background Adolescents with childhood onset growth hormone deficiency (CO-GHD) require re-evaluation of their growth hormone (GH) axis on attainment of final height to determine eligibility for adult GH therapy (rhGH). Aim Retrospective multicentre review of management of young adults with CO-GHD in four paediatric centres in Scotland during transition. Patients Medical records of 130 eligible CO-GHD adolescents (78 males), who attained final height between 2005 and 2013 were reviewed. Median (range) age at initial diagnosis of CO-GHD was 10.7 years (0.1–16.4) with a stimulated GH peak of 2.3 μg/l (0.1–6.5). Median age at initiation of rhGH was 10.8 years (0.4–17.0). Results Of the 130 CO-GHD adolescents, 74/130(57 %) had GH axis re-evaluation by stimulation tests /IGF-1 measurements. Of those, 61/74 (82 %) remained GHD with 51/74 (69 %) restarting adult rhGH. Predictors of persistent GHD included an organic hypothalamic-pituitary disorder and multiple pituitary hormone deficiencies (MPHD). Of the remaining 56/130 (43 %) patients who were not re-tested, 34/56 (61 %) were transferred to adult services on rhGH without biochemical retesting and 32/34 of these had MPHD. The proportion of adults who were offered rhGH without biochemical re-testing in the four centres ranged between 10 and 50 % of their total cohort. Conclusions A substantial proportion of adults with CO-GHD remain GHD, particularly those with MPHD and most opt for treatment with rhGH. Despite clinical guidelines, there is significant variation in the management of CO-GHD in young adulthood across Scotland.

Background Hypoglycaemia impairs driving performance, so drivers with insulin-treated diabetes should try to avoid hypoglycaemia when driving, and treat it effectively if it occurs. It is not known how many insulin-treated drivers are familiar with, or adhere to, recommended safe practice. Methods We surveyed a representative sample of 202 current drivers with insulin-treated diabetes (115 with Type 1 diabetes), using a structured questionnaire. Data were obtained on driving history, estimated frequency of hypoglycaemia, and measures taken to avoid and treat hypoglycaemia when driving. Results The licensing authority (DVLA) and motor insurance company had been informed by almost all participants. Sixty-four participants (31.7%) had experienced hypoglycaemia while driving, and 27 (13.4%) reported that this had occurred within the preceding year. A minimum blood glucose level of 4.0 mmol/l or higher was considered necessary for driving by 151 drivers (74.8%), and 176 (87.1%) reported always keeping carbohydrate in their vehicle. However, 77 (38.1%) reported never carrying a glucose meter when driving, and 121 (59.9%) that they never test blood glucose before driving, or test only if symptomatic of hypoglycaemia. Most participants (89%) would stop driving to treat hypoglycaemia and would not resume driving immediately, although only 28 (13.9%) would wait longer than 30 min. Almost half of participants were failing to observe at least one essential aspect of safe driving. Conclusions Compliance with statutory requirements to inform the licensing authority and motor insurer is good, and drivers’ perceptions of the minimum safe blood glucose level for driving are encouraging. However, most drivers rely on symptoms to detect hypoglycaemia while driving, and seldom test blood glucose before driving. Patient education should emphasize the role of blood glucose monitoring in relation to driving, and highlight the potential deterioration in driving performance when blood glucose falls below 4.0 mmol/l.

A 35-year-old woman was referred with secondary amenorrhoea and galactorrhoea. She had been trying to conceive since stopping the combined oral contraceptive 18 months earlier. Serum prolactin was found to be grossly elevated with low oestradiol. MRI demonstrated a pituitary macroadenoma in contact with the optic structures. Dopamine agonist therapy was commenced and a pregnancy was achieved after an appropriate length of treatment and interval barrier contraception. This chapter explores the differential diagnosis of secondary amenorrhoea and galactorrhoea, together with discussion of the investigation and management of prolactinomas; with special focus on pre-pregnancy planning and management during pregnancy.

OBJECTIVE Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes. RESEARCH DESIGN AND METHODS Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes). RESULTS Compared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes. CONCLUSIONS Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed.

In adults with insulin-treated diabetes, hypoglycemia-associated autonomic failure (HAAF) is described as a syndrome that includes counterregulatory hormonal deficiencies and impaired symptomatic awareness in response to severe hypoglycemia (1). It is thought to result from failure of the central autonomic response to acute neuroglycopenia and is associated with recurrent exposure to hypoglycemia and increasing duration of diabetes. It is not known whether this syndrome occurs in children with type 1 diabetes, but the Diabetes Research in Children Network (DirecNet) Study Group has claimed that HAAF was present in at least a third of their participants with type 1 diabetes (2). Examination of the study design and methodology raises …

Smith et al. (1) have demonstrated that people with type 1 diabetes who have impaired awareness of hypoglycemia (IAH), diagnosed on clinical history alone, are less likely to adhere to therapeutic decisions. This finding is of clinical importance as the syndrome of IAH is often very difficult to manage, and the reluctance …

Driving is a complex process that places considerable demands on cognitive and physical functions. Many complications of diabetes can potentially impair driving performance, including those affecting vision, cognition and peripheral neural function. Hypoglycemia is a common side-effect of insulin and sulfonylurea therapy, impairing many cognitive domains necessary for safe driving performance. Driving simulator studies have demonstrated how driving performance deteriorates during hypoglycemia. Driving behavior that may predispose to hypoglycemia while driving is examined. Studies examining the risk of road traffic accidents in people with insulin-treated diabetes have produced conflicting results, but the potential risk of hypoglycemia-related road traffic accidents has led to many countries imposing restrictions on the type and duration of driving licenses that can be issued to drivers with diabetes. Guidance that promotes safe driving practice has been provided for drivers with insulin-treated diabetes, which is the group principally addressed in this review.