Imperial College London

ProfessorWaljitDhillo

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Endocrinology & Metabolism
 
 
 
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Contact

 

+44 (0)20 7594 3487w.dhillo Website

 
 
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Assistant

 

Ms Suzanne Wheeler +44 (0)20 7594 3487

 
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Location

 

6N6ECommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

359 results found

Mowla S, Tharakan T, Farahani L, Lee YS, Kundu S, Khanjani S, Sindi E, Rai R, Regan L, Ramsay JWA, Bennett PR, Dhillo WS, Minhas S, Macintyre DA, Jayasena CNet al., 2022, Associations between seminal microbiota composition and ROS in men with fertility disorders, Publisher: ELSEVIER, Pages: S1187-S1187, ISSN: 0302-2838

Conference paper

Aceves-Martins M, Quinton R, Brazzelli M, Cruickshank M, Manson P, Hudson J, Oliver N, Hernandez R, Aucott L, Wu F, Dhillo WS, Bhattacharya S, Gillies K, Jayasena CN, NIHR Testosterone Efficacy & Safety TestES Consortiumet al., 2022, Identifying the outcomes important to men with hypogonadism: A qualitative evidence synthesis, Andrology, Vol: 10, ISSN: 2047-2919

OBJECTIVE: Men with male hypogonadism (MH) experience sexual dysfunction, which improves with testosterone replacement therapy (TRT). However, randomised controlled trials provide little consensus on functional and behavioural symptoms in hypogonadal men; these are often better captured by qualitative information from individual patient experience. METHODS: We systematically searched major electronic databases to identify qualitative data from men with hypogonadism, with or without TRT. Two independent authors performed the selection, extraction, and thematic analysis of data. Quality of eligible studies was assessed using the Critical Appraisals Skills Programme and Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research tools. RESULTS: We analysed data from five studies published in nine reports that assessed a total of 284 participants. Published data were only available within North America, with no ethnic minority or other underserved groups included. In addition to sexual dysfunction, men with MH experienced adverse changes in physical strength, perceptions of masculinity, cognitive function, and quality of life. The experience of MH appeared dependent on the source(s) of educational material. DISCUSSION: We propose a patient-centred approach to clinician interactions rather than focusing on discreet MH symptoms. Current evidence about the experience of MH is limited to North America and predominantly white ethnicity, which may not be broadly applicable to other geographic regions. Broadening our understanding of the MH experience may improve the targeting of information to patients. In addition, a multidisciplinary approach may better address symptoms neither attributable to MH nor alleviated by TRT.

Journal article

Clarke SA, Abbara A, Dhillo WS, Clarke SA, Abbara A, Dhillo WSet al., 2022, Impact of COVID-19 on the Endocrine System: A Mini-review, ENDOCRINOLOGY, Vol: 163, ISSN: 0013-7227

Journal article

Phylactou M, Abbara A, Al-Memar M, Daniels E, Patel B, Eng PC, Nadir R, Izzi-Engbeaya C, Clarke S, Mills E, Hunjan T, Pacuszka E, Yang L, Bech P, Tan T, Comninos A, Kelsey T, Kyriacou C, Fourie H, Bourne T, Dhillo Wet al., 2022, Changes in circulating kisspeptin levels during each trimester in women with antenatal complications, Journal of Clinical Endocrinology and Metabolism, Vol: 107, Pages: e71-e83, ISSN: 0021-972X

ContextAntenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all three trimesters in women with antenatal complications.ObjectiveTo assess whether kisspeptin levels are altered in women with antenatal complications.DesignWomen with antenatal complications (n=105) and those with uncomplicated pregnancies (n=265) underwent serial ultrasound scans and blood-sampling at least once during each trimester (March 2014 to March 2017).SettingEarly Pregnancy Assessment Unit at Hammersmith Hospital, UK.ParticipantsWomen with antenatal complications: HDP (n=32), FGR (n=17), GDM (n=35) and PTB (n=11), and 10 women with multiple complications, provided 373 blood samples, and a further 265 controls provided 930 samples.Main outcomeDifferences in circulating kisspeptin levels.ResultsThird trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking and parity were increased by 30% (95%CI 16-47%; p<0.0001), and of FGR were reduced by 28% (95%CI 4-46%; p=0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (p=0.014), and lower in those affected by GDM (p=0.020), but not significantly on multivariable analysis.ConclusionWe delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.

Journal article

Mills EG, Yang L, Nielsen MF, Kassem M, Dhillo WS, Comninos ANet al., 2021, The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens (vol 42, pg 691, 2021), ENDOCRINE REVIEWS, Vol: 42, Pages: 872-872, ISSN: 0163-769X

Journal article

Mills EG, Yang L, Nielsen MF, Kassem M, Dhillo WS, Comninos ANet al., 2021, The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens, ENDOCRINE REVIEWS, Vol: 42, Pages: 691-719, ISSN: 0163-769X

Journal article

Abbara A, Eng PC, Phylactou M, Clarke SA, Mills E, Chia G, Yang L, Izzi-Engbeaya C, Smith N, Jayasena CN, Comninos AN, Anand-Ivell R, Rademaker J, Xu C, Quinton R, Pitteloud N, Dhillo WSet al., 2021, Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism, NEUROENDOCRINOLOGY, Vol: 111, Pages: 1176-1186, ISSN: 0028-3835

Journal article

Izzi-Engbeaya C, Forlano R, Mullish BH, Tan TM, Yee M, Manousou P, Dhillo WSet al., 2021, Outcomes of postmenopausal women with non-alcoholic fatty liver disease (NAFLD), Society for Endocrinology BES 2021, Pages: 58-58

Conference paper

Guzman S, Dragan M, Kwon H, Bhatt V, Shah A, Rustgi VK, Dhillo WS, Bech PR, Abbara A, Izzi-Engbeaya C, Wang H, Guo GL, Guo JY, Wondisford FE, Babwah AV, Bhattacharya Met al., 2021, KISSPEPTIN RECEPTOR: NEW TARGET TO TREAT NONALCOHOLIC FATTY LIVER DISEASE, Publisher: WILEY, Pages: 1074A-1075A, ISSN: 0270-9139

Conference paper

Abou Sherif S, Newman R, Haboosh S, Al-Sharefi A, Papanikolaou N, Dimakopoulou A, Webber LJ, Abbara A, Franks S, Dhillo WS, Jayasena CNet al., 2021, Investigating the potential of clinical and biochemical markers to differentiate between functional hypothalamic amenorrhoea and polycystic ovarian syndrome: A retrospective observational study, CLINICAL ENDOCRINOLOGY, Vol: 95, Pages: 618-627, ISSN: 0300-0664

Journal article

Abbara A, Dhillo WS, Abbara A, Dhillo WSet al., 2021, Targeting Elevated GnRH Pulsatility to Treat Polycystic Ovary Syndrome, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 106, Pages: E4275-E4277, ISSN: 0021-972X

Journal article

Phylactou M, Abbara A, Al-Memar M, Kyriacou C, Pei Chia E, Nadir R, Izzie-Engbeaya C, Clarke S, Mills E, Daniels E, Huo L, Pacuszka E, Yang L, Patel B, Tan T, Bech P, Comninos A, Fourie H, Kelsey T, Bourne T, Dhillo W, Abbara Aet al., 2021, Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestation during the first trimester, Fertility and Sterility, Vol: 116, Pages: 809-819, ISSN: 0015-0282

ObjectiveTo compare the performance of kisspeptin and beta human chorionic gonadotropin (βhCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester.DesignProspective, nested case-control study.SettingTertiary Centre, Queen Charlotte Hospital, London, United Kingdom.Patient(s)Adult women who had miscarriages (n = 95, 173 samples) and women with healthy pregnancies (n = 265, 557 samples).Intervention(s)The participants underwent serial ultrasound scans and blood sampling for measurement of plasma kisspeptin and βhCG levels during the first trimester.Main Outcome Measure(s)The ability of plasma kisspeptin and βhCG levels to distinguish pregnancies complicated by miscarriage from healthy pregnancies unaffected by miscarriage.Result(s)Gestation-adjusted levels of circulating kisspeptin and βhCG were lower in samples from women with miscarriages than in women with healthy pregnancies by 79% and 70%, respectively. The area under the receiver-operating characteristic curve for identifying miscarriage during the first trimester was 0.874 (95% confidence interval [CI] 0.844–0.904) for kisspeptin, 0.859 (95% CI 0.820–0.899) for βhCG, and 0.916 (95% CI 0.886–0.946) for the sum of the two markers. The performance of kisspeptin in identifying miscarriage improved with increasing length of gestation, whereas that of βhCG worsened. A decision matrix incorporating kisspeptin, βhCG, and gestational age had 83% to 87% accuracy for the prediction of miscarriage.Conclusion(s)Plasma kisspeptin is a promising biomarker for miscarriage and provides additional value to βhCG alone, especially during later gestational weeks of the first trimester.

Journal article

Wernig F, Jayasena CN, Dhillo WS, 2021, Carcinoid syndrome and neuroendocrine tumours, Medicine, Vol: 49, Pages: 544-547, ISSN: 1357-3039

Neuroendocrine tumours (NETs) arise from neuroendocrine cells of the gastrointestinal tract, pancreas, bronchi or other rare primary sites and comprise a variety of different tumour types. NETs can be associated with a variety of clinical syndromes. For instance, classic symptoms of carcinoid syndrome, such as flushing and diarrhoea, occur because of the release of hormones, including serotonin, tachykinins and peptide hormones. However, most NETs are non-secretory in nature and are detected incidentally or through compression of surrounding structures. Liver metastasis has usually already occurred at the time of diagnosis. Surgery can be curative if disease is entirely localized. Injections of somatostatin analogues are the mainstay of non-surgical treatment for well-differentiated NETs. Surgical debulking and embolization techniques are useful to reduce tumour bulk in patients who remain symptomatic despite medical treatment. Peptide receptor radionucleotide therapy using radiolabelled somatostatin analogues has recently been shown to prolong progression-free survival. Furthermore, several novel agents, such as everolimus or sunitinib, have emerged in the treatment of patients with metastatic disease. This article aims to summarize the pathophysiology and clinical features of NETs, with a focus on carcinoid syndrome. It also discusses recent advances in clinical management of NETs.

Journal article

Phylactou M, Clarke S, Patel B, Baggaley C, Jayasena C, Kelsey T, Comninos A, Dhillo W, Abbara Aet al., 2021, Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS), Clinical Endocrinology, Vol: 95, Pages: 239-252, ISSN: 0300-0664

BackgroundSecondary oligo/amenorrhoea occurs in 3%–5% of women of reproductive age. The two most common causes are polycystic ovary syndrome (PCOS) (2%–13%) and functional hypothalamic amenorrhoea (FHA) (1%–2%). Whilst both conditions have distinct pathophysiology and their diagnosis is supported by guidelines, in practice, differentiating these two common causes of menstrual disturbance is challenging. Moreover, both diagnoses are qualified by the need to first exclude other causes of menstrual disturbance.AimTo review clinical, biochemical and radiological parameters that could aid the clinician in distinguishing PCOS and FHA as a cause of menstrual disturbance.ResultsFHA is uncommon in women with BMI > 24 kg/m2, whereas both PCOS and FHA can occur in women with lower BMIs. AMH levels are markedly elevated in PCOS; however, milder increases may also be observed in FHA. Likewise, polycystic ovarian morphology (PCOM) is more frequently observed in FHA than in healthy women. Features that are differentially altered between PCOS and FHA include LH, androgen, insulin, AMH and SHBG levels, endometrial thickness and cortisol response to CRH. Other promising diagnostic tests with the potential to distinguish these two conditions pending further study include assessment of 5‐alpha‐reductase activity, leptin, INSL3, kisspeptin and inhibin B levels.ConclusionFurther data directly comparing the discriminatory potential of these markers to differentiate PCOS and FHA in women with secondary amenorrhoea would be of value in defining an objective probability for PCOS or FHA diagnosis.

Journal article

Abbara A, Clarke SA, Dhillo WS, 2021, Clinical Potential of Kisspeptin in Reproductive Health, TRENDS IN MOLECULAR MEDICINE, Vol: 27, Pages: 807-823, ISSN: 1471-4914

Journal article

Pawsey S, Mills EG, Ballantyne E, Donaldson K, Kerr M, Trower M, Dhillo WS, Pawsey S, Mills EG, Ballantyne E, Donaldson K, Kerr M, Trower M, Dhillo WSet al., 2021, Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 106, Pages: E3221-E3234, ISSN: 0021-972X

Journal article

Comninos A, Yang L, OCallaghan J, Mills E, Wall M, Demetriou L, Wing V, Thurston L, Owen B, Abbara A, Rabiner E, Dhillo Wet al., 2021, Kisspeptin modulates gamma-aminobutyric acid levels in the human brain, Psychoneuroendocrinology, Vol: 129, Pages: 1-5, ISSN: 0306-4530

Gamma-aminobutyric acid (GABA) is a key inhibitory neurotransmitter that has been implicated in the aetiology of common mood and behavioural disorders. By employing proton magnetic resonance spectroscopy in man, we demonstrate that administration of the reproductive neuropeptide, kisspeptin, robustly decreases GABA levels in the limbic system of the human brain; specifically the anterior cingulate cortex (ACC). This finding defines a novel kisspeptin-activated GABA pathway in man, and provides important mechanistic insights into the mood and behaviour-altering effects of kisspeptin seen in rodents and humans. In addition, this work has therapeutic implications as it identifies GABA-signalling as a potential target for the escalating development of kisspeptin-based therapies for common reproductive disorders of body and mind.

Journal article

Clarke S, Phylactou M, Patel B, Mills E, Muzi B, Izzi-Engbeaya C, Choudhury S, Khoo B, Meeran K, Comninos A, Abbara A, Tan T, Dhillo Wet al., 2021, Normal adrenal and thyroid function in patients who survive COVID-19 infection, Journal of Clinical Endocrinology and Metabolism, Vol: 106, Pages: 2208-2220, ISSN: 0021-972X

ContextThe COVID-19 pandemic continues to exert an immense burden on global health services. Moreover, up to 63% of patients experience persistent symptoms, including fatigue, after acute illness. Endocrine systems are vulnerable to the effects of COVID-19 as many glands express the ACE2 receptor, used by the SARS-CoV-2 virion for cellular access. However, the effects of COVID-19 on adrenal and thyroid gland function after acute COVID-19 remain unknown. ObjectivesOur objectives were to evaluate adrenal and thyroid gland function in COVID-19 survivors. DesignA prospective, observational study was undertaken. SettingClinical Research Facility, Imperial College NHS Healthcare Trust. ParticipantsSeventy patients ≥ 18 years at least 3 months after diagnosis of COVID-19 were included. InterventionParticipants attended a research study visit (08:00-09:30), during which a short Synacthen test (250 µg IV bolus), and thyroid function assessments were performed.ResultsAll patients had a peak cortisol ≥450 nmol/l after Synacthen, consistent with adequate adrenal reserve. Basal and peak serum cortisol did not differ according to disease severity or history of dexamethasone treatment during COVID-19. There was no difference in baseline or peak cortisol after Synacthen or in thyroid function tests, or thyroid status, in patients with fatigue (n=44) compared to those without (n=26).ConclusionsAdrenal and thyroid function ≥3 months after presentation with COVID-19 was preserved. Whilst a significant proportion of patients experienced persistent fatigue, their symptoms were not accounted for by alterations in adrenal or thyroid function. These findings have important implications for the clinical care of patients after COVID-19.

Journal article

Salem V, Demetriou L, Behary P, Alexiadou K, Scholtz S, Tharakan G, Miras A, Purkayastha S, Ahmed A, Bloom S, Wall M, Dhillo W, Tan Tet al., 2021, Weight loss by low calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns: an functional MRI study, Diabetes Care, Vol: 44, Pages: 1842-1851, ISSN: 0149-5992

OBJECTIVE: Weight loss achieved with very-low-calorie diets (VLCDs) can produce remission of type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference.RESEARCH DESIGN AND METHODS: Sixteen participants underwent gastric bypass surgery, and 19 matched participants undertook a VLCD (meal replacement) for 4 weeks. Brain responses to food cues and resting-state functional connectivity were assessed with functional MRI pre- and postintervention and compared across groups.RESULTS: We show that Roux-en-Y gastric bypass surgery (RYGB) results in three divergent brain responses compared with VLCD-induced weight loss: 1) VLCD resulted in increased brain reward center food cue responsiveness, whereas in RYGB, this was reduced; 2) VLCD resulted in higher neural activation of cognitive control regions in response to food cues associated with exercising increased cognitive restraint over eating, whereas RYGB did not; and 3) a homeostatic appetitive system (centered on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD.CONCLUSIONS: Taken together, these findings point to divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast to enduring weight loss after RYGB.

Journal article

Kyriacou C, Abbara A, Bobdiwala S, Fourie H, Al-Memar M, Phylactou M, Eng CP, Izzi-Engbeaya C, Mills E, Bech P, Comninos A, Huo L, Dhillo W, Bourne Tet al., 2021, Circulating kisspeptin levels in ectopic pregnancy and pregnancy of unknown location, Publisher: WILEY, Pages: 38-39, ISSN: 1470-0328

Conference paper

Zaman S, Almazrouei R, Sam AH, DiMarco AN, Todd JF, Palazzo FF, Tan T, Dhillo WS, Meeran K, Wernig Fet al., 2021, Synacthen stimulation test following unilateral adrenalectomy needs to be interpreted with caution, Frontiers in Endocrinology, Vol: 12, Pages: 1-7, ISSN: 1664-2392

Background: Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center.Methods: Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing’s syndrome were excluded.Results: The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement.Conclusions: Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Journal article

Salem V, Demetriou L, Behary P, Alexiadou K, Miras A, Scoltz S, Purkayastha S, Ahmed S, Dhillo W, Tan Tet al., 2021, Weight loss by low-calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns which may explain differences in long-term outcomes: an FMRI study, The Diabetes UK Professional Conference 2021, Publisher: Wiley, Pages: 1-1, ISSN: 0742-3071

Objective: Clinically significant weight loss can produce remission of type 2 diabetes. Bariatric surgery (specifically, Roux-en-Y gastric bypass, RYGB) produces durable weight loss that translates into reductions in mortality. In contrast, weight regain is very common after very low-calorie diets (VLCD). No study has investigated longitudinal changes in brain activity using functional MRI in patients living with obesity and prediabetes/type 2 diabetes to explain this difference.Methods: Visual food cue responses and resting state connectivity was assessed with functional MRI pre- and post-intervention and compared between 16 participants who underwent gastric bypass surgery and 19 age, gender, and disease stage matched participants who undertook a VLCD for 4 weeks.Results: Brain responses to RYGB-induced weight loss diverge from those induced by VLCD in three domains: (i) dieting resulted in increased responsiveness to visual food cues in reward areas whereas after RYGB this was reduced; (ii) dieting therefore engaged greater activation of brain regions involved in cognitive control, associated with the need to exercise increased restraint over eating; and (iii) a homeostatic appetitive system (centred on the hypothalamus) was better engaged following RYGB-induced weight loss than dieting.Conclusion: This study provides a holistic view of multiple divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast with the enduring weight loss after RYGB.

Conference paper

Yang L, Demetriou L, Wall MB, Mills EG, Wing VC, Thurston L, Schaufelberger CN, Owen BM, Abbara A, Rabiner EA, Comninos AN, Dhillo WS, Yang L, Demetriou L, Wall MB, Mills EG, Wing VC, Thurston L, Schaufelberger CN, Owen BM, Abbara A, Rabiner EA, Comninos AN, Dhillo WSet al., 2021, The Effects of Kisspeptin on Brain Response to Food Images and Psychometric Parameters of Appetite in Healthy Men, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 106, Pages: E1837-E1848, ISSN: 0021-972X

Journal article

Sands CJ, Gómez-Romero M, Correia G, Chekmeneva E, Camuzeaux S, Izzi-Engbeaya C, Dhillo WS, Takats Z, Lewis MRet al., 2021, Representing the metabolome with high fidelity: range and response as quality control factors in LC-MS-based global profiling., Analytical Chemistry, Vol: 93, Pages: 1924-1933, ISSN: 0003-2700

Liquid chromatography-mass spectrometry (LC-MS) is a powerful and widely used technique for measuring the abundance of chemical species in living systems. Its sensitivity, analytical specificity, and direct applicability to biofluids and tissue extracts impart great promise for the discovery and mechanistic characterization of biomarker panels for disease detection, health monitoring, patient stratification, and treatment personalization. Global metabolic profiling applications yield complex data sets consisting of multiple feature measurements for each chemical species observed. While this multiplicity can be useful in deriving enhanced analytical specificity and chemical identities from LC-MS data, data set inflation and quantitative imprecision among related features is problematic for statistical analyses and interpretation. This Perspective provides a critical evaluation of global profiling data fidelity with respect to measurement linearity and the quantitative response variation observed among components of the spectra. These elements of data quality are widely overlooked in untargeted metabolomics yet essential for the generation of data that accurately reflect the metabolome. Advanced feature filtering informed by linear range estimation and analyte response factor assessment is advocated as an attainable means of controlling LC-MS data quality in global profiling studies and exemplified herein at both the feature and data set level.

Journal article

Khoo B, Tan T, Clarke S, Mills E, Patel B, Modi M, Phylactou M, Eng PC, Thurston L, Alexander E, Meeran K, Comninos A, Abbara A, Dhillo Wet al., 2021, Thyroid function before, during and after COVID-19, Journal of Clinical Endocrinology and Metabolism, Vol: 106, Pages: e803-e811, ISSN: 0021-972X

Context: The effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported. Objective: We aimed to detail the acute effects of COVID-19 on thyroid function and determine if these effects persisted upon recovery from COVID-19. Design: Cohort observational study. Participants and setting: Adult patients admitted to Imperial College Healthcare National Health Service Trust, London, UK with suspected COVID-19 between March 9 to April 22, 2020 were included, excluding those with pre-existing thyroid disease and those missing either free thyroxine (FT4) or TSH measurements. Of 456 patients, 334 had COVID-19 and 122 did not.Main Outcome Measures: TSH and FT4 measurements at admission, and where available, those taken in 2019 and at COVID-19 follow-up. Results: Most patients (86·6%) presenting with COVID-19 were euthyroid, with none presenting with overt thyrotoxicosis. Patients with COVID-19 had a lower admission TSH and FT4 compared to those without COVID-19. In the COVID-19 patients with matching baseline thyroid function tests from 2019 (n=185 for TSH and 104 for FT4), both TSH and FT4 were reduced at admission compared to baseline. In a complete cases analysis of COVID-19 patients with TSH measurements at follow-up, admission and baseline (n=55), TSH was seen to recover to baseline at follow-up. Conclusions: Most patients with COVID-19 present with euthyroidism. We observed mild reductions in TSH and FT4 in keeping with a non-thyroidal illness syndrome. Furthermore, in survivors of COVID-19, thyroid function tests at follow-up returned to baseline.

Journal article

Rumpler E, Skrapits K, Takacs S, Gocz B, Trinh SH, Racz G, Matolcsy A, Kozma Z, Ciofi P, Dhillo WS, Hrabovszky Eet al., 2021, Characterization of Kisspeptin Neurons in the Human Rostral Hypothalamus, NEUROENDOCRINOLOGY, Vol: 111, Pages: 249-262, ISSN: 0028-3835

Journal article

Abbara A, Phylactou M, Dhillo WS, Abbara A, Phylactou M, Dhillo WSet al., 2021, Commentary on "Pharmacodynamic Activity of the Novel Neurokinin-3 Receptor Antagonist SJX-653 in Healthy Men" Comment, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 106, Pages: E1028-E1030, ISSN: 0021-972X

Journal article

Sharma A, Minhas S, Dhillo WS, Jayasena CN, Sharma A, Minhas S, Dhillo WS, Jayasena CNet al., 2021, Male infertility due to testicular disorders, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 106, Pages: E442-E459, ISSN: 0021-972X

Journal article

Vessey W, Saifi S, Sharma A, McDonald C, Almeida P, Figueiredo M, Minhas S, Virmani A, Dhillo WS, Ramsay JW, Jayasena CNet al., 2021, Baseline levels of seminal reactive oxygen species predict improvements in sperm function following antioxidant therapy in men with infertility, Clinical Endocrinology, Vol: 94, Pages: 102-110, ISSN: 0300-0664

BACKGROUND: Poor sperm function is a major cause of infertility. There is no drug therapy to improve sperm function. Semen oxidative stress is a recently identified pathway for sperm damage. Commercial antioxidants such as L-carnitine and acetyl-L-carnitine (LAL) are commonly self-administered by infertile men. However, concerns have been raised whether inappropriate LAL therapy causes reductive stress-mediated sperm damage. It is imperative to investigate whether: (1) LAL improves sperm function by reducing reactive oxidative species (ROS); (2) LAL has differential effects on sperm function between men with normal and elevated ROS. METHODS: A prospective cohort study of routine clinical practice was performed in infertile men with abnormal sperm quality. Changes in sperm function and semen ROS levels following three months of oral LAL therapy were compared between participants with baseline seminal normal ROS (≤10RLU/SEC/106 sperm; n = 29) and High ROS (>10 RLU/SEC/106 sperm; n = 15) levels measured using an established colorimetric-luminol method. RESULTS: In normal ROS group, sperm function did not change following LAL therapy. In high ROS group, LAL therapy reduced semen ROS fivefold, increased sperm count by 50% (mean count in mill/ml: 21.5 + 7.2, baseline; 32.6 + 9.5, post-treatment, P = .0005), and total and progressive sperm motility each by 30% (mean total sperm motility in % 29.8 + 5.0, baseline: 39.4 + 6.2, post-treatment, P = .004; mean progressive sperm motility in % 23.1 + 4.6, baseline: 30.0 + 5.5, post-treatment, P = .014 vs. baseline). CONCLUSIONS: We report for the first time that LAL only improves sperm quality in infertile men who have baseline high-ROS levels prior to treatment. These data have important potential implications for couples with male infertility and their clinicians.

Journal article

Modi M, Dhillo WS, 2021, The neuroendocrinology of the preoptic area in menopause: Symptoms and therapeutic strategies., Handb Clin Neurol, Vol: 179, Pages: 455-460, ISSN: 0072-9752

The preoptic area of the hypothalamus is the central hub of thermoregulation in mammals, coordinating autonomic heat-effector pathways in response to sensory information from the ambient and internal environment. This aims to maintain temperature homeostasis at a predetermined thermoregulatory set-point. However, hormonal and neuronal changes during the menopause, including estrogen deficiency, disrupt these normal thermoregulatory responses. This results in abnormal activation of heat dissipation effectors, manifesting clinically as hot flush symptoms. Neurokinin B (NKB) signaling via the neurokinin-3 receptor (NK3R) within the preoptic area is thought to play an important role in the pathophysiology of hot flushes. Therefore attenuation of the NKB/NK3R signaling pathway has garnered much interest as a novel therapeutic target for the amelioration of menopausal hot flushes. Recent clinical trials have demonstrated that NK3R antagonists can produce rapid and sustained improvements in hot flush frequency, severity, and quality of life, without the need for estrogen exposure. Therefore NK3R antagonists are fast emerging as a safe and efficacious alternative to hormone replacement therapy, the current gold standard of treatment.

Journal article

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