208 results found
Abbara A, Clarke S, Eng PC, et al., 2018, Clinical and biochemical characteristics of patients presenting with pituitary apoplexy., Endocr Connect, ISSN: 2049-3614
PURPOSE: To review the clinical and biochemical characteristics and clinical outcome of patients presenting with pituitary apoplexy to a tertiary centre. METHODS: We retrospectively reviewed the clinical features, predisposing factors, biochemistry and clinical outcome of patients presenting with pituitary apoplexy to Imperial College Healthcare NHS Trust between 1991 to 2015. RESULTS: We identified 64 patients with pituitary apoplexy (more complete clinical records were available in 52 patients). The median age at presentation was 46.7 years (IQR 31.5-57.0 years). Pituitary apoplexy was the first presentation of pituitary disease in 38/52 of patients and predisposing factors were identified in 28/52. Pituitary apoplexy predominantly occurred in patients with non-functioning pituitary adenomas (47/52). Headache was most commonly described as sudden-onset, severe, lateralising to the frontal or temporal regions. Symptoms of meningeal irritation were reported in 7/18 and visual abnormalities in 22/35. A pre-treatment serum cortisol <100nmol/l was recorded in 12/31 of patients. All patients with visual disturbance had some resolution of their visual symptoms whether managed surgically (14/14) or conservatively (5/5), although pituitary endocrine function did not fully recover in any patient. CONCLUSIONS: In conclusion, these data describe the clinical features of pituitary apoplexy to aid the clinician in diagnosing this rare emergency presentation of pituitary disease. Prospective multicentre studies of the presentation of pituitary apoplexy are required to further characterise presentation and outcomes.
Abbara A, Clarke S, Islam R, et al., 2018, Reply: Clinical trial registry alone is not adequate: on the perception of possible endpoint switching and P-hacking, HUMAN REPRODUCTION, Vol: 33, Pages: 342-344, ISSN: 0268-1161
Abbara A, Clarke SA, Dhillo WS, 2018, Novel concepts for inducing final oocyte maturation in IVF (In Vitro Fertilization) Treatment., Endocr Rev
Infertility affects 1 in 6 of the population and increasingly couples require treatment with assisted reproductive techniques (ART). In vitro fertilization (IVF) treatment is most commonly conducted using exogenous FSH to induce follicular growth and human chorionic gonadotrophin (hCG) to induce final oocyte maturation. However, hCG may cause the potentially life-threatening iatrogenic complication 'ovarian hyperstimulation syndrome' (OHSS), which can cause significant morbidity and rarely even mortality in otherwise healthy women. The use of GnRH agonists (GnRHa) has been pioneered over the last two decades to provide a safer option to induce final oocyte maturation. More recently, the neuropeptide kisspeptin, a hypothalamic regulator of GnRH release, has been investigated as a novel inductor of oocyte maturation.The hormonal stimulus used to induce oocyte maturation has a major impact on the success (retrieval of oocytes and chance of implantation) and safety (risk of OHSS) of IVF treatment. This review aims to appraise experimental and clinical data of hormonal approaches used to induce final oocyte maturation by either hCG, GnRHa, both GnRHa and hCG administered in combination, recombinant LH, or kisspeptin. We also examine evidence for the timing of administration of the inductor of final oocyte maturation in relation to parameters of follicular growth and the subsequent interval to oocyte retrieval.In summary, we review data on the efficacy and safety of the major hormonal approaches used to induce final oocyte maturation in clinical practice, as well as some novel approaches that may offer fresh alternatives in future.
Abbara A, Clarke SA, Nesbitt A, et al., 2018, Interpretation of serum gonadotropin levels in hyperprolactinemia., Neuroendocrinology
<br>Background/Aims: Hyperprolactinemia is a common cause of amenorrhea due to hypogonadotropic hypogonadism. Prolactin is hypothesized to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exists to aid the interpretation of serum gonadotropins in the context of hyperprolactinemia. METHODS: Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete etiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinemia was categorized by an experienced endocrinologist / pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were Microprolactinoma (n=88), Macroprolactinoma (n=46), Non-Functioning Pituitary Adenoma (NFPA) (n=72), Drug-Induced Hyperprolactinemia (DIH) (n=22) and Polycystic Ovarian Syndrome (PCOS) (n=15). RESULTS: In patients with prolactinoma and modestly raised serum prolactin levels (<4000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic GnRH pulsatility. Patients with prolactinoma and higher prolactin values (>4000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH >8 IU/L) were more likely to have NFPA than prolactinoma. Patients with polycystic ovarian syndrome (PCOS) and hyperprolactinemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. CONCLUSION: The pattern of gonadotropin secretion in patients may reflect the etiology of hyperprolactinemia.<br>.
Abbara A, Islam R, Clarke SA, et al., 2018, Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment, CLINICAL ENDOCRINOLOGY, Vol: 88, Pages: 920-927, ISSN: 0300-0664
Abbara A, Narayanaswamy S, Izzi-Engbeaya C, et al., 2018, Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men, NEUROENDOCRINOLOGY, Vol: 106, Pages: 401-410, ISSN: 0028-3835
Abbara A, Vuong LN, Ho VNA, et al., 2018, Follicle Size on Day of Trigger Most likely to Yield a Mature Oocyte, FRONTIERS IN ENDOCRINOLOGY, Vol: 9, ISSN: 1664-2392
Algeffari M, Jayasena CN, MacKeith P, et al., 2018, Testosterone therapy for sexual dysfunction in men with Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials, DIABETIC MEDICINE, Vol: 35, Pages: 195-202, ISSN: 0742-3071
Cassatella D, Howard SR, Acierno JS, et al., 2018, Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures, EUROPEAN JOURNAL OF ENDOCRINOLOGY, Vol: 178, Pages: 377-388, ISSN: 0804-4643
Comninos AN, Dhillo WS, 2018, Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing, NEUROENDOCRINOLOGY, Vol: 106, Pages: 195-202, ISSN: 0028-3835
Comninos AN, Yang L, Abbara A, et al., 2018, Frequent falls and confusion: recurrent hypoglycemia in a patient with tuberous sclerosis complex, CLINICAL CASE REPORTS, Vol: 6, Pages: 904-909, ISSN: 2050-0904
Izzi-Engbeaya C, Comninos AN, Clarke SA, et al., 2018, The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans., Diabetes Obes Metab
AIMS: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans. MATERIALS AND METHODS: In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m-2 ), we compared the effects of 1 nmol kg-1 h-1 kisspeptin versus vehicle administration on glucose-stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose-stimulated insulin secretion in vitro in human pancreatic islets and a human β-cell line (EndoC-βH1 cells). RESULTS: Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose-stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men. CONCLUSIONS: Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin-based therapies for reproductive and potentially metabolic conditions.
Jayasena CN, Luo R, Dimakopoulou A, et al., 2018, Prevalence of abnormal semen analysis and levels of adherence with fertility preservation in men undergoing therapy for newly diagnosed cancer: A retrospective study in 2906 patients., Clin Endocrinol (Oxf)
BACKGROUND: Sperm cryopreservation (freezing) should be offered to all men with cancer due to risk of infertility. However, many men with cancer already have impaired spermatogenesis prior to sperm cryopreservation. Furthermore, physical ill-health may hinder attendance of freeze visits. Investigating both the distribution of sperm function and freeze attendance rates in men with newly diagnosed cancer, may identify patients benefiting from targeted reproductive fertility support. METHODS: We performed a retrospective study of 2906 male patients undergoing sperm cryopreservation prior to cancer therapy at a single UK tertiary centre between 1989 and 2013; all patients were asked to attend three hospital semen collection visits prior to cancer therapy. RESULTS: Fifteen percent (433/2906) of men with newly diagnosed cancer had had severely impaired semen quality (i.e. sperm total motile count, TMC<1 million) during the first semen collection visit. However, patients with severely impaired semen quality had the poorest attendance of subsequent semen collection visits despite being requested to do so (non-attendance in TMC < 1 million: 43.4%; TMC<1-30 million; 35.7%, P<0.05 vs. <1million; TMC>30 million: 33.2%, P<0.01 vs. <1million). CONCLUSIONS: This study expands understanding of the semen quality of men with newly diagnosed cancer, and their ability to adhere to fertility preservation recommendations. Our data suggest that patients with the poorest semen quality paradoxically suffer the poorest attendance rates of sperm cryopreservation appointments prior to commencing cancer therapy. We suggest that additional support may be of clinical benefit to men with newly diagnosed cancer and TMC<1million sperm. This article is protected by copyright. All rights reserved.
Law J, Morris DE, Izzi-Engbeaya C, et al., 2018, Thermal Imaging Is a Noninvasive Alternative to PET/CT for Measurement of Brown Adipose Tissue Activity in Humans, JOURNAL OF NUCLEAR MEDICINE, Vol: 59, Pages: 516-522, ISSN: 0161-5505
Lehman MN, Coolen LM, Steiner RA, et al., 2018, The 3rd World Conference on Kisspeptin, "Kisspeptin 2017: Brain and Beyond": Unresolved questions, challenges and future directions for the field, JOURNAL OF NEUROENDOCRINOLOGY, Vol: 30, ISSN: 0953-8194
Ma Y, Ratnasabapathy R, Izzi-Engbeaya C, et al., 2018, Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis, DIABETES OBESITY & METABOLISM, Vol: 20, Pages: 2246-2254, ISSN: 1462-8902
Mills EG, Dhillo WS, Comninos AN, 2018, Kisspeptin and the control of emotions, mood and reproductive behaviour., J Endocrinol
Reproduction is fundamental for the survival of all species and requires meticulous synchronisation of a diverse complement of neural, endocrine and related behaviours. The reproductive hormone kisspeptin (encoded by the KISS1/kiss1 gene), is now a well-established orchestrator of reproductive hormones, acting upstream of gonadotrophin releasing hormone (GnRH) at the apex of the hypothalamic-pituitary-gonadal (HPG) reproductive axis. Beyond the hypothalamus, kisspeptin is also expressed in limbic and paralimbic brain regions, which are areas of the neurobiological network implicated in sexual and emotional behaviours. We are now forming a more comprehensive appreciation of extra-hypothalamic kisspeptin signalling and the complex role of kisspeptin as an upstream mediator of reproductive behaviours, including olfactory-driven partner preference, copulatory behaviour, audition, mood and emotion. An increasing body of research from zebrafish to humans has implicated kisspeptin in the integration of reproductive hormones with an overall positive influence on these reproductive behaviours. In this review, we critically appraise the current literature regarding kisspeptin and its control of reproductive behaviour. Collectively, these data significantly enhance our understanding of the integration of reproductive hormones and behaviour and provide the foundation for kisspeptin-based therapies to treat related disorders of body and mind.
Owens LA, Abbara A, Lerner A, et al., 2018, The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function, HUMAN REPRODUCTION, Vol: 33, Pages: 292-302, ISSN: 0268-1161
Prague JK, Roberts RE, Comninos AN, et al., 2018, Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action, MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY, Vol: 25, Pages: 862-869, ISSN: 1072-3714
Takacs S, Bardoczi Z, Skrapits K, et al., 2018, Post mortem single-cell labeling with DiI and immunoelectron microscopy unveil the fine structure of kisspeptin neurons in humans, BRAIN STRUCTURE & FUNCTION, Vol: 223, Pages: 2143-2156, ISSN: 1863-2653
Yang L, Comninos AN, Dhillo WS, 2018, Intrinsic links among sex, emotion, and reproduction, CELLULAR AND MOLECULAR LIFE SCIENCES, Vol: 75, Pages: 2197-2210, ISSN: 1420-682X
Yang L, Comninos AN, Dhillo WS, 2018, Intrinsic links among sex, emotion, and reproduction (vol 75, pg 2197, 2018), CELLULAR AND MOLECULAR LIFE SCIENCES, Vol: 75, Pages: 2489-2489, ISSN: 1420-682X
de Tassigny XD, Jayasena CN, Murphy KG, et al., 2018, Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo (vol 12, e0176821, 2017), PLOS ONE, Vol: 13, ISSN: 1932-6203
Abbara A, Clarke S, Islam R, et al., 2017, A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial, HUMAN REPRODUCTION, Vol: 32, Pages: 1915-1924, ISSN: 0268-1161
Bhatt PS, Dhillo WS, Salem V, 2017, Human brown adipose tissue - function and therapeutic potential in metabolic disease, CURRENT OPINION IN PHARMACOLOGY, Vol: 37, Pages: 1-9, ISSN: 1471-4892
Comninos AN, Wall MB, Demetriou L, et al., 2017, Kisspeptin modulates sexual and emotional brain processing in humans, JOURNAL OF CLINICAL INVESTIGATION, Vol: 127, Pages: 709-719, ISSN: 0021-9738
Hameed S, Patterson M, Dhillo WS, et al., 2017, Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight, CELL REPORTS, Vol: 19, Pages: 2202-2209, ISSN: 2211-1247
Katugampola H, King PJ, Chatterjee S, et al., 2017, Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 102, Pages: 3349-3359, ISSN: 0021-972X
Prague JK, Dhillo WS, 2017, Neurokinin 3 receptor antagonism - the magic bullet for hot flushes?, CLIMACTERIC, Vol: 20, Pages: 505-509, ISSN: 1369-7137
Prague JK, Dhillo WS, 2017, Treating hot flushes with a neurokinin 3 receptor antagonist, ONCOTARGET, Vol: 8, Pages: 106153-106154, ISSN: 1949-2553
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