Point-of-care ultrasound is a useful adjunct tool to a clinician's assessment in the evaluation of severe hyponatraemia.

INTRODUCTION: Hyponatraemia is the most common electrolyte disorder in inpatients resulting mainly from an imbalance in water homeostasis. Intravascular fluid status assessment is pivotal but is often challenging given multimorbidity, polypharmacy and diuretics use. We evaluated the utility of point-of-care ultrasound (POCUS) as an adjunct tool to standard practice for fluid assessment in severe hyponatraemia patients. METHODS: Patients presenting with severe hyponatremia (Serum Sodium [Na] < 120 mmol/L; Normal range: 135-145 mol/L), managed by standard care were included. Hyponatraemia biochemistry work-up and POCUS examination were undertaken. Both clinician and POCUS independently assigned one of the three fluid status groups of hypovolaemia, hypervolaemia or euvolaemia. The final diagnosis of three fluid status groups at admission was made at the time of discharge by retrospective case review. Clinician's (standard of care) and POCUS fluid assessments were compared to that of the final diagnosis at the time of discharge. RESULTS: n = 19 patients were included. Median Na on admission was 113 mmol/L (109-116), improved to 129 ± 3 mmol/L on discharge. POCUS showed the higher degree of agreement with the final diagnosis (84%; n = 16/19), followed by the clinician (63%; n = 12/19). A trend towards higher accuracy of POCUS compared to clinician assessment of fluid status was noted (84% vs. 63%, p = 0.1611). Biochemistry was unreliable in 58% (n = 11/19) likely due to renal failure, polypharmacy or diuretic use. Inappropriate emergency fluid management was undertaken in 37% (n = 7/19) of cases based on initial clinician assessment. Thirst symptom correlated to hypovolaemia in 80% (4/5) cases. CONCLUSION: As subjective clinical and biochemistry assessments of fluid status are often unreliable due to co-morbidities and concurrent use of medications, POCUS can be a rapid objective diagnostic tool to assess fluid status in patients with severe hyponatraemia, to guide accurate emergency fluid management.

COVID-19-related adrenal haemorrhage: Multicentre UK experience and systematic review of the literature.

OBJECTIVE: Adrenal haemorrhage (AH) is an uncommon, usually incidental imaging finding in acutely unwell patients. AH has been reported during coronavirus disease 2019 (COVID-19) infection and following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccination. The Society for Endocrinology (SfE) established a task force to describe the UK experience of COVID-19-related AH. DESIGN: A systematic literature review was undertaken. A survey was conducted through the SfE clinical membership to identify patients with COVID-19-related AH using a standardized data collection tool. RESULTS: The literature search yielded 25 cases of COVID-19-related AH (19 bilateral; 13 infection-related, and 12 vaccine-related). Eight UK centres responded to the survey with at least one case. A total of 18 cases were included in the descriptive study, including 11 from the survey and 7 UK-based patients from the systematic review. Seven patients (4 males; median age 53 (range 26-70) years), had infection-related AH (four bilateral). Median time from positive COVID-19 test to AH detection was 8 (range 1-30) days. Eleven cases of vaccine-related AH (eight bilateral) were captured (3 males; median age 47 (range 23-78) years). Median time between vaccination (nine Oxford-AstraZeneca and two Pfizer-BioNTech) and AH was 9 (range 2-27) days; 9/11 AH occurred after the first vaccine dose. Acute abdominal pain was the commonest presentation (72%) in AH of any cause. All 12 patients with bilateral AH and one patient with unilateral AH required glucocorticoid replacement. CONCLUSION: Adrenal haemorrhage with consequential adrenal insufficiency can be a complication of COVID-19 infection and vaccination. Adrenal function assessment is mandatory to avoid the potentially fatal consequences of unrecognized adrenal insufficiency.

UK practice on incidentally detected non-functioning pituitary microadenomas: analysis of two national surveys during a 12-year interval.

PURPOSE: The optimal management approach for presumed non-functioning pituitary microadenomas (microNFPAs) remains unclear. Our aim was to capture current UK practice and identify changes with time. METHODS: Two online surveys investigating clinicians' approaches were performed in 2009-2010 and 2021-2022 (advertised through Society for Endocrinology UK). RESULTS: 150 and 214 clinicians participated in the 2021 and 2009 survey, respectively (response rates 31.2% and 35.4%, respectively). At baseline, 2021 survey respondents were more likely to measure IGF-1 (96.0% vs 74.1%, p < 0.001) and morning cortisol (87.9% vs 62.6%, p < 0.001), and less likely GH (26.2% vs 42.6% p = 0.002), 24 h urine free cortisol (3.4% vs 23.2%, p < 0.0001) or dynamically assess adrenal reserve (11.4% vs 30.4%, p < 0.001). 47.2% of clinicians in 2021 would reassess pituitary function annually until discharge (in absence of tumour growth/symptoms). The 2021 survey respondents were more likely to stop imaging at or before 3 years (81.7% vs 44.3%, p < 0.001) and at or before 5 years (86.6.% vs 72.9%, p = 0.002), whilst 2009 survey respondents were more likely to continue imaging beyond 5 years (24% vs 7%, p < 0.001). Responses on imaging frequency/intervals showed notable variability in both surveys. CONCLUSIONS: Diagnostic and management approaches for microNFPAs have evolved in the UK. Biochemical investigations are performed in accord with consensus guidelines, though many clinicians perform annual biochemical surveillance without tumour growth/symptoms. A small number of clinicians request imaging beyond 5 years, but the frequency of imaging intervals until discharge remains variable. Robust evidence on the long-term natural history of microNFPAs is necessary to unify clinician approach.

Audit of long-term treatment outcomes of thyrotoxicosis in a single-centre virtual clinic: The utility of long-term antithyroid drugs.

OBJECTIVE: To investigate the long-term outcomes and prognosis of thyrotoxicosis in a large number of patients in a single UK county (Leicestershire). DESIGN: Retrospective cohort analysis of 56,741 thyroid function test (TFT) results, treatment modalities and outcomes in a well-established virtual thyrotoxicosis clinic database. PATIENTS: One thousand four hundred and eighty-nine patients were included with a median length of follow-up of 10.9 years. The aetiology of thyrotoxicosis was autoimmune (85.9%), nodular (9.1%) and mixed (5.0%). Treatment modalities included antithyroid drugs (ATDs), radioiodine (RAI; 555 MBq fixed dose) and thyroidectomy. METHODS: We analysed both individual TFTs and groups of sequential TFTs on or after the same thyroid treatment(s), which we describe as 'phase of thyroid care' (POTC). Patients studied entered the virtual clinic between 1 January 1995 and 1 January 2010; we exported data on every TFT sample up to April 2020. RESULTS: ATD had been used in 99.2% (median 2, maximum seven courses) with long-term ATD (>2 years) in 48%. RAI and thyroidectomy were used more commonly with nodular and mixed aetiology. Overall, T4 was more often controlled than thyroid-stimulating hormone (TSH), and at the latest follow-up, T4 was normal in >96%, TSH in >79% and both in >76% of different aetiologies. The mean percentage control of T4 was 85% and TSH 50%; in long-term ATD courses, this improved to 89% and 62%, respectively. In the latest POTC, control of T4 and TSH was best in cases off treatment (95%/87%) and on T4 without ablative therapy (94%/72%), but was broadly similar in patients on long-term ATD (90%/68%), after RAI (92%/60%) or after thyroidectomy (91%/58%). After the first course of ATD, remission or hypothyroidism was seen in 47.3% autoimmune, 20.9% nodular and 32.5% mixed, with 90% relapses seen within 4 years. Relapse was more common in patients with ophthalmopathy, but there was no difference between the sexes. CONCLUSIONS: Thyrotoxicosis can be well controlled with minimal specialist clinic attendance using a software-supported virtual shared-care scheme. Long-term ATD appears to be a valid patient choice achieving TFT control comparable to that seen after RAI or surgery. In patients with autoimmune disease, relapse is more common in patients with ophthalmopathy, and hypothyroidism is common after RAI. In nodular disease, we found that spontaneous remission may occur.

Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

Changing the name of diabetes insipidus: a position statement of The Working Group for Renaming Diabetes Insipidus.

"What's in a name? That which we call a rose/By any other name would smell as sweet." (Juliet, from Romeo and Juliet by William Shakespeare). Shakespeare's implication is that a name is nothing but a word and it therefore represents a convention with no intrinsic meaning. Whilst this may be relevant to romantic literature, disease names do have real meanings, and consequences, in medicine. Hence, there must be a very good rational for changing the name of a disease that has a centuries-old historical context. A working group of representatives from national and international endocrinology and pediatric endocrine societies now proposes changing the name of "diabetes insipidus" to "Arginine Vasopressin Deficiency (AVP-D)" for central etiologies, and "Arginine Vasopressin Resistance (AVP-R)" for nephrogenic etiologies. This editorial provides both the historical context and the rational for this proposed name change.

A review of the pathophysiology of functional hypothalamic amenorrhoea in women subject to psychological stress, disordered eating, excessive exercise or a combination of these factors.

INTRODUCTION: Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin-releasing hormone (GnRH) pulsatility results in reduced luteinizing hormone (LH) levels, with subsequent reduction in oestradiol, anovulation and cessation of menstruation. GnRH pulsatility suppression is a recognized complication of psychological stress, disordered eating, low body weight, excessive exercise or a combination of these factors. PATHOPHYSIOLOGY OF FHA: Individuals with FHA demonstrate low energy availability (EA), body fat percentage and energy expenditure. Documented adipocytokine changes notably, raised adiponectin, ghrelin, PYY, and decreased leptin, are associated with GnRH suppression. Other endocrine responses seen in this low EA state include low insulin levels, low total T3, increased basal cortisol levels and a reduced response to corticotrophin-releasing hormone (CRH) administration. FHA is associated with raised growth hormone (GH) and low insulin-like growth factor (IGF-1), suggesting relative GH resistance. Kisspeptins are a group of polypeptides, recently discovered to play a major role in the regulation of the reproductive axis through influencing GnRH release. KNDy (kisspeptin/neurokinin B/dynorphin) act on GnRH neurons and a multitude of factors result in their release. IMPLICATIONS FOR FUTURE TREATMENT: Management of FHA is imperative to prevent adverse outcomes in bone density, cardiovascular risk profile, psychological well-being and fertility. Outwith modification of nutritional intake and exercise, limited therapeutic strategies are currently available for women with FHA. Advancements in the understanding of the pathophysiological basis of this under-recognized and under-treated clinical entity will aid management and may result in the development of novel therapeutic approaches.

Long-term follow-up of a large prospective cohort of patients with nonfunctioning pituitary adenomas: The outcome of a conservative management policy.

OBJECTIVE: To assess the clinical outcome of a strategy of conservative monitoring of patients with nonfunctioning pituitary adenomas (NFPA) after pituitary surgery and in patients without surgery. DESIGN: Retrospective study of outcomes, using a clinical information system. PATIENTS: An unselected, clinical series of patients seen in a single centre between 1989 and 2015. MEASUREMENTS: Review of clinical information system data to obtain details and dates of surgery, radiotherapy, pituitary imaging and outcomes. RESULTS: We identified 190 cases of NFPA. Trans-sphenoidal surgery (TSS) had been performed as primary therapy in 132 cases (all macro-adenomas). At a mean 7.6-years follow-up after TSS without immediate pituitary radiotherapy, recurrence occurred in 10.7% of cases with no visible postoperative residual adenoma, 38.8% with intrasellar and 66.7% with extrasellar residuum. Recurrence was defined as growth of residual tumour requiring intervention. On survival analysis, at 10 years, recurrence-free survival was 75% in patients with no residual tumour and 40% with intrasellar residuum. Recurrence occurred in 12.5% of 24 patients who had received postop radiotherapy. Patients were monitored conservatively without initial surgery in 65 patients. After a mean of 5-year monitoring, only 20% required intervention during follow-up (18.5% TSS) and 30.8% died of nonpituitary causes during follow-up. CONCLUSION: This study suggests that a conservative approach may be safe and appropriate in patients with NFPA if followed up with appropriate imaging surveillance, whether postoperative or without primary surgery.

Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304* ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275-5,000) years. tMRCA-based simulations predicted 432 (90-5,175) current carriers, including 86 affected (18-1,035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease.

Clinical characteristics of polycystic ovary syndrome: investigating differences in White and South Asian women.

OBJECTIVE: To understand the phenotypic presentation of women with polycystic ovary syndrome (PCOS) of different ethnicities and at different ages. DESIGN: Cross-sectional, retrospective data analysis (1988 - 2009). SETTING: Specialist clinic in a University Hospital, Leicestershire, UK. PARTICIPANTS: Women with PCOS, n = 1310 (mean age 26·2 years), 70·9% White and 29·1% South Asian (SA) attending a speciality clinic in Leicester UK. MAIN OUTCOMES MEASURES: Clinical and demographic characteristics of women with PCOS including age at first clinic appointment, signs and symptoms, body mass index (BMI) and blood pressure (BP). RESULTS: Compared to White women, the SA were younger (24·3 vs 27·1 years, P < 0·001), less likely to smoke (3·7% vs 17·9% P < 0·001) and had a higher prevalence of acanthosis nigricans (AN) (16·8% vs 3·1% P < 0·001), type 2 diabetes (T2DM) (8·1% vs 5·6%, P < 0·01) and hirsutism (88·5% vs 77·4%, P < 0·001), with lower systolic (126·5 vs 133·0 mmHg, P < 0·001), diastolic BP (71·8 vs 75·1 mmHg P = 0·008) and BMI (29·3 vs 31·5 kg/m(2) P = 0·002). Differences in body weight remained when participants were classified as obese, overweight and normal according to ethnicity-specific cut-off points (P = 0·048). In both ethnicities, those aged ≥30 years old had higher rates of obesity, T2DM, hypertension and infertility, and less acne, and oligomenorrhoea. Obesity was associated with increased T2DM, AN, systolic/diastolic BP, hirsutism and infertility. CONCLUSION: The phenotypic and metabolic presentations of women with PCOS appear to be significantly different depending on ethnicity, obesity and age. This has implications for management strategies in these groups.

AIP mutation in pituitary adenomas in the 18th century and today.

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.

Management of a giant adrenal schwannoma.

In this case report, we present a man in his 60s who presented with an incidentally discovered right adrenal mass, which turned out to be an adrenal schwannoma. This is a very rare tumour that originates from Schwann cells and involves the peripheral nerves. The tumour was removed by open adrenalectomy, and this 15-cm adrenal schwannoma is one of the largest reported in the literature, with none >16 cm having ever been reported. This case highlights the importance of keeping an open mind about the cause of an incidentally discovered adrenal mass, which is an increasingly common way for adrenal tumours to present given the increased access to cross-sectional imaging. As well as presenting the case and the pathological basis behind adrenal schwannomas, we include a review of the literature and a general discussion about incidentally discovered adrenal masses.

Approach to the patient with suspected hypotonic polyuria.

Investigation and management of hypotonic polyura is a common challenge in clinical endocrinology. The three main causes, recently renamed to arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus), AVP-resistance (AVP-R, formerly nephrogenic diabetes insipidus), and primary polydipsia (PP) require accurate diagnosis as management differs for each. This new nomenclature more accurately reflects pathophysiology, and has now been adopted by the Systemised Nomenclature of Medicine (SNOMED). Advances in diagnosis over the last few years have centered around the use of copeptin measurement. Here, we use three patient case histories to highlight the use of this approach, and to demonstrate how it can succeed where other approaches, such as the water deprivation test, sometimes fail. We discuss the overall approach to each type of patient and the strengths and limitations of diagnostic strategies, illustrating the use of the new nomenclature.

Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20-year retrospective cohort study.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are potentially at increased risk of cardiovascular (CV) diseases due to well-established risk factors, including insulin resistance, obesity and type 2 diabetes mellitus (T2DM). However, data showing excess CV events in this population are still lacking. We investigated the incidence and prevalence of CV events in a cohort of women with PCOS. DESIGN: Retrospective cohort study (total follow-up >12,000 person-years). SETTING: Leicester, Leicestershire and Rutland (Total Female population of 434,859), UK. PARTICIPANTS: Two thousand three hundred and one women with PCOS (mean age = 29.6 years) attending a speciality clinic in Leicestershire, UK. MAIN OUTCOMES MEASURES: T2DM, myocardial infarction (MI), angina, heart failure (HF), stroke and CV-related death. RESULTS: Incidence of T2DM, MI, angina, HF, stroke and CV death was respectively 3.6, 0.8, 1.0, 0.3, 0.0 and 0.4 per 1000 person-years. At the end of follow-up, the prevalence of MI in the age groups 45-54, 55-64 and >65 years was 1.9%, 6.0% and 27.3% and of angina was 2.6%, 6.0% and 27.3%, respectively. Age-group-specific odds ratios for the prevalence of MI and angina compared to the local female population ranged between 2.6 (95% CI: 1.0-6.3) and 12.9 (CI: 3.4-48.6) with the highest ratio being for MI in the group >65 years old. Age, history of hypertension and smoking had significant correlations with CV outcomes in the PCOS patients. CONCLUSION: We have shown a high incidence and age-group-specific prevalence of T2DM, MI and angina in the women with PCOS, with over a quarter having had MI or angina in those >65 years. These findings should be considered in the treatment strategies and long-term planning for women with PCOS.

Nelson syndrome and perinatal challenges: A case report and systematic review of the literature.

Nelson syndrome is a rare and potentially life-threatening complication of treatment with total bilateral adrenalectomy for women with Cushing disease. A successful term pregnancy following fertility treatment in a patient with Nelson syndrome is presented. Our study provides guidance in the prenatal and intrapartum management of this condition. A case report and a systematic review of 14 papers describing 50 pregnancies are presented. An electronic database search included Medline (1946 to September 2022), Embase (1980 to September 2022), Cochrane Library, and UKOSS. A small number of pregnancies in women with Nelson syndrome are reported in literature, but there are no guidelines. Some authors detail the prenatal care provided to their patients. Four studies report prenatal monitoring with visual field checks and two report monitoring with X-rays. Five studies report the use of parenteral hydrocortisone at the time of delivery. Where described, women delivered appropriately grown newborns at term, with timing and mode of delivery dictated by obstetric indications. Preconception counseling and optimization of maternal health status improve pregnancy outcomes in women with Nelson syndrome. Multidisciplinary review in a combined obstetric-endocrine prenatal clinic is ideal. Awareness about potential complications during pregnancy and the postnatal period is crucial in providing optimal care to the mother and baby.

A study of acromegaly-associated headache with somatostatin analgesia.

The aim of this study is to characterise somatostatin analogue-responsive headache in acromegaly, hitherto not systematically documented in a significant cohort. Using the UK pituitary network, we have clinically characterised a cohort of 18 patients suffering from acromegaly-related headache with a clear response to somatostatin analogues. The majority of patients had chronic migraine (78%) as defined by the International Headache Society diagnostic criteria. Headache was present at the time of acromegaly presentation and clearly associated temporally with disease activity in all cases. Short-acting somatostatin analogues uniquely resolved pain within minutes and the mean duration of analgesia was 1-6 h. Patients on long-acting analogues required less short-acting injections (mean: 3.7 vs 10.4 injections per day, P = 0.005). 94% used somatostatin analogues to control ongoing headache pain. All patients presented with macroadenoma, most had incomplete resection (94%) and headache was ipsilateral to remnant tissue (94%). Although biochemical control was achieved in 78% of patients, headache remained in 71% of them. Patients selected for this study had ongoing headache post-treatment (mean duration: 16 years after diagnosis); only four patients reached headache remission 26 years (mean range: 14-33) after the diagnosis. Headache in acromegaly patients can be persistent, severe, unrelieved by surgery, long-lasting and uncoupled from biochemical control. We show here that long-acting analogues allow a decrease in the number of short-acting analogue injections for headache relief. Further studies are needed to understand the mechanisms, markers and tumour tissue characteristics of acromegaly-related headache. Until then, this publication serves to provide the clinical characteristics as a reference point for further study.