Endocrine Abstracts

Gonadotropin-releasing hormone (GnRH) neurons represent the primary neuroendocrine link between the brain and the reproductive system. Although they play a key role in stimulating the release of LH and FSH from the anterior pituitary gland, the underlying mechanism by which they trigger the onset of puberty is unclear. To address this issue, RT-PCR, in situ hybridization histochemistry, and Affymetrix gene arrays were used to profile hypothalamic GnRH gene expression in prepub...

While the association between maternal nutrition and female reproductive fitness and offspring health is well recognised, the role that paternal diet plays in shaping male reproductive health is relatively poorly understood. It is, however, well established that poor diet has adverse effects on sperm quality, which in turn have a negative impact on embryo development and offspring health. It is conceivable that behind any alterations to sperm quality, there are certain underly...

Maternal diabetes is known to impair placental function; however, its effect on placental expression of progesterone and oestrogen receptors has not been well documented. Fructose has been used to induce insulin resistance in animal models (Suga et al., 2000). The study aimed to assess maternal serum levels of progesterone, oestriol, oestradiol; placental morphology and its expression of progesterone and oestrogens receptors in fructose-induced diabetic rats. Twelve f...

Previous studies have shown beneficial effects of the corticotropin releasing hormone (CRH) family, including the urocortins (UCN1, UCN2 and UCN3), on pancreatic islets and subsequent glucose homeostasis. However, the physiological relevance of this interaction is not currently understood. CRH and urocortins are also expressed by placenta, so this study investigated whether signalling through CRH receptor 1 or 2 (CRHR1/CRHR2) plays a role in the islet adaptation to pregnancy. ...

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) is abundant in decidua but its role in placental development is unclear. We hypothesized that decidual 1,25(OH)2D promotes placentation in early-pregnancy via actions on trophoblastic cell invasion. Using trophoblastic JEG3, BeWo and HTR8 cells we showed that 1,25(OH)2D has no effect on trophoblastic cell proliferation and migration in plasticware culture. However, in Matrigel t...

The heterodimeric pituitary glycoprotein hormone, follicle-stimulating hormone (FSH) and its target G protein-coupled receptor (FSHR) are essential for reproduction. As an important drug target for IVF, the need for more effective treatment drives interest in understanding what modulates FSH/FSHR functions. In vivo, two predominant FSH glycosylation variants have been identified; partially glycosylated FSH (FSH21) has faster binding kinetics to the FSHR and is more potent at a...

Gestational diabetes (GDM) is a form of diabetes that is first diagnosed during pregnancy, complicating 8–24% of all pregnancies. Despite treatment, substantial numbers of babies are born large for gestational age (LGA), predisposing them to cardio-metabolic disease in adulthood. It is difficult to predict which pregnancies are most at risk. The study aimed to determine if circulating maternal serum small extracellular vesicle (sEV) miRNAs have the potential to predict al...

Introduction: Hypothalamic amenorrhoea (HA) is a condition characterised by reduced GnRH pulsatility and is a common cause of anovulatory subfertility. Kisspeptin is an endogenous neuropeptide that regulates hypothalamic GnRH function. Hypothalamic kisspeptin expression is reduced, and kisspeptin receptor expression is increased, in a rodent model of HA. The kisspeptin analogue MVT-602 has a 3-4-fold longer half-life than native kisspeptin-54 (t1/2 0.5 h). We invest...

Introduction: Abnormal fetal growth can cause perinatal morbidity and mortality. The placenta regulates materno-fetal nutrient transfer and secretes hormones with maternal physiological effects. In mice, global loss of insulin-like growth factor 2 (Igf2), a paternally-expressed imprinted gene, causes fetoplacental growth restriction in association with changes in placental transport and endocrine zone (Jz) formation. However, the role of Igf2 in regulating pl...

Oxytocin was suggested to affect sperm volume and ejaculation. The most distal part of the epididymis stores the sperm until ejaculation and was therefore our main focus when investigating parts of the rat epididymis and vas deferens for local differences of the contractile responses to oxytocin in comparison to norepinephrine regarding their usability for targeted drug development. Single loops of the coiled epididymal duct from defined parts of the epididymis and the adjacen...

Introduction: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women and polycystic ovaries are characterized by excess ovarian stroma that has implications for disordered follicle development in PCOS. The factors contributing to proliferation and increased density of stroma remain unclear but local overproduction of androgens may be involved.Aim: To examine differential expression of genes that regulate key proteins that comprise ...

Introduction: The risk of maternal death from aortic-dissection(AoD) during pregnancy/post-partum in TS is increased, due to TS-associated risk factors (bicuspid-aortic-valve(BAV), aortic-coarctation, aortic-dilatation, hypertension) and the increased cardiovascular strain of pregnancy itself. TS-guidelines advice against pregnancy in the presence of severe aortic-dilatation or moderate dilatation with AoD-risk factors; and after aortic surgery a high risk remains. However, fe...

Pregnancy is characterised by profound changes in maternal physiology. For instance, there are changes in the metabolic, cardiovascular, immune and renal systems of the mother which enable her to support fetal nutrient supply and growth. These changes are signalled in part by the production of protein hormones by the placenta (Napso et al., 2018). Failures in maternal adaptation and placental function lead to pregnancy complications such as abnormal birth weight and g...

Kisspeptin (Kp) and its receptor (KISS1R) are essential for reproduction, with dysfunction in their activities leading to reproductive disorders, such as precocious puberty and hypogonadotrophic hypogonadism. Kp is synthesised and secreted within specialist nuclei of the hypothalamus, modulating the HPG axis. Kp is a 54 amino acid peptide, which can undergo proteolytic cleavage into smaller peptides, including Kp10, which retain biological activities. However, little is known ...

The heterodimeric glycoprotein hormone, follicle stimulating hormone (FSH) and its receptor (FSHR) are vital for reproductive function, driving ovarian function via follicular recruitment, selection and development. FSH exists as two predominant glycoforms in females; partially glycosylated (FSH21) and fully glycosylated (FSH24), based on differing glycosylation patterns of the β subunit. The FSH glycoforms have different bioactivities, with FSH21 displaying a higher bind...

Endocrine disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans and wildlife are exposed to and which interfere with the action of hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity and is recognized by the WHO as a chemical with potentially potent effects on humans throughout different phases of development. A significant knowledge gap still exists regarding the complete spectrum of BPA-induced effects on human physiology,...

Introduction: Idiopathic hypogonadotrophic hypogonadism (IHH) with normal sense of smell is a complex and rare disease entity characterised by insufficient gonadotropin releasing hormone (GnRH) neuronal action on an intact hypothalamo–pituitary–gonadal axis. IHH has an incidence of 1–10 in 100 000 live births with a variable mode of inheritance and five-fold male predominance. Gene mutations have been discovered of which 10–40% of the familial cases are due...

Developmental exposure to endocrine-disrupting compounds may adversely affect female reproductive physiology. The present study investigated the effect of Pirimiphos-methyl (PM), an organophosphate pesticide, widely used to protect crops and grains against pests, on puberty onset in female rats. Female weanling rats were orally treated with 20 mg/kg and 40 mg/kg of PM for ten consecutive days from postnatal day 22 to 31. Following vagina opening and attainment of estrus and di...

Spontaneous pregnancy (SP) in TS is rare (4.8–7.6%). Oocyte-donation-in-vitro-fertilization (IVF-OD) and fertility-preservation increasingly offer the possibility of childbearing. Nevertheless, pregnancy is associated with an increased risk of complications. Adoption/surrogacy represents alternative parenting options.Aim: To analyse parenting options and pregnancy outcomes inTS.Methods: Data was collected in 154 TSwom...

Gestational Diabetes Mellitus (GDM) is associated with adverse outcomes, including large-for-gestational age (LGA) babies who are are at greater risk of developing cardiovascular and metabolic diseases in adulthood. The mechanisms responsible for LGA are unclear but it is associated with altered placental development/function. Recent data also shows a link between temporal changes in maternal glucose and LGA; women with GDM that deliver appropriate for gestational age (AGA) in...

Maternal diabetes is known to impair placental function; however, its effect on placental expression of progesterone and oestrogen receptors has not been well documented. Fructose feeding has been used to induce insulin resistance in animal models (Suga et al., 2000; Arikawe et al., 2004; Iranloye et al., 2011). The study aimed to assess maternal serum levels of progesterone, oestriol and oestradiol; placental morphology and its expression of progest...

Turner syndrome is a common chromosomal disorder affecting 1 in 2500 life female births. Turner syndrome is associated with congenital cardiovascular malformations of the aortic arch, systemic and pulmonary venous return with reported incidences ranging from 23 to 45%. These vascular malformations cause significant morbidity and mortality with increased incidence of aortic pathology, right heart strain and pulmonary hypertension as a result. In this investigation we retrospect...

Liquid Chromatography tandem mass spectrometry (LC–MS/MS) is gold-standard for androgen analysis in biological fluids, superseding immunoassays in specificity, particularly at low concentrations. While LC–MS/MS is well established for analysis of testosterone (T) and androstenedione (A4), 5α-dihydrotestosterone (DHT) presents greater analytical challenges. DHT circulates at low nanomolar concentrations in men and lower in women, ionising inefficiently. Thus, eve...

Introduction: Peptide-YY (PYY) is produced by intestinal L-cells following nutrient ingestion. PYY analogues are an emerging class of anti-obesity medication. Peripheral administration of PYY has potent anorectic effects in rodents and humans. Interestingly, rodent studies have demonstrated that PYY has additional effects on reproductive hormone secretion depending on the model studied. In humans, hypogonadism occurs in up to 40% of men with obesity. Therefore, the effects of ...

Although the steroidogenesis in testis occur in a paracrine rather than in an endocrine, the comparative metabolic pathways between fetal and adult mice are not fully understood. Here, gas chromatography-mass spectrometry-based assay for profiling of 23 androgens, 7 estrogens, 13 corticoids, and 14 progestagens has been developed and applied to quantify their testis levels from both fetal and adult mice. Testis samples were purified with Oasis HLB solid-phase extraction and se...

Background: Gestational diabetes mellitus (GDM) occurs in every 23 UK pregnancies. GDM identifies the mother as high-risk for development of type 2 diabetes. The National Institute for Health and Care Excellence (NICE) published updated guidance in February 2015 recommending routine follow-up of women with GDM.Aims: This cohort study compared follow-up rates of women with GDM before and after the updated guidance. We also investigated for an association ...

Fetal growth restriction (FGR), which describes the failure of a fetus to achieve its genetic growth potential, not only increases the risk of perinatal mortality and morbidity but also predisposes to metabolic disease in adulthood. In developed countries, FGR is typically attributed to dysfunction of the placenta – a transient organ that mediates nutrient supply, eliminates waste, and protects the fetus from maternal immune response. The placenta also functions as a majo...

A 46 year old female presented with 12 months history of secondary amenorrhoea. Prolactin was 4746 mIU/l without macroprolactin complexes, LH & FSH were low, oestradiol was undetectable. She had normal visual fields. No other clinical or biochemical features of pituitary dysfunction. She had no regular medication. Pituitary MRI was normal. She was started on cabergoline 250 mcg twice weekly which was subsequently increased to 500 mcg twice weekly. Repeat serum prolactin 5 ...

Background: Klinefelter syndrome (KS), karyotype 47XXY, affects 1 in 650 males. Subjects develop primary gonadal failure requiring life-long testosterone replacement. Many different testosterone formulations are available and long-term monitoring is necessary to avoid secondary polycythaemia.Objective: To investigate the effect of testosterone formulations used in KS subjects and estimate frequency of association with secondary polycythaemia.<p class...

Due to decreasing ovarian reserve from young age, counselling is vital as chances to conceive spontaneously decrease rapidly and early consideration of fertility options essential. Maternal/fetal-risks are high and patients/specialists face important considerations.Aim: Service-evaluation of adequacy/appropriateness/sufficiency of information about fertility provided to TS patients.Methods: TS women attending two TS-dedicated-centr...

Case: A 19-year-old British-Asian man presented with a two-year history of gynaecomastia. He had no other symptoms of hypogonadism. On examination, BMI was 28 kg/m2 and he had post-pubertal-sized testes (20 ml) with normal secondary sexual characteristics. Hypogonadism was confirmed by two morning fasting total testosterone levels of 4.7 and 5.2 (RR 9.2–31.6 nmol/l). Haemoglobin was normal (152 g/l) and serum oestradiol was <100 pmol/l. He had inappropriate...

Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. PCOS is associated with future type 2 diabetes/cardiovascular disease. Accurate diagnosis is important for early preventative interventions. However, it can take >2 years and contact with 3 or more health professionals before PCOS is diagnosed. We aimed to determine patterns of biochemical investigations performed for PCOS following initial consultation and assess their ...

Background: Premature Ovarian Insufficiency (POI) is characterised by oligo-/amenorrhoea with elevated gonadotropins and low oestradiol before the age of 40 years.Objective: To evaluate management of non-Turner POI patients in line with European Society of Human Reproduction and Embryology (ESHRE) guidance (1)Methods: Retrospective evaluation of electronic and paper case records.Results: Over 23-year period (...

Peripartum hyponatraemia is an under-recognised complication of labour and poses a risk to both mother and baby. It is typically caused by water intoxication for physiological reasons and population health trends around water intake. We have recent experience of managing 2 patients with severe symptomatic hyponatraemia. Both patients had increased their oral intake of fluid during labour as well as receiving intravenous fluids. Dilutional hyponatraemia was found to be the unde...

Introduction: Over half of postmenopausal women suffer symptoms which can sometimes be non-responsive to hormone replacement therapy (HRT). Testosterone is implicated in regulating urogenital and sexual function in women. However, using testosterone therapy in postmenopausal women remains highly controversial, principally due to the lack of syndromic relationship between serum testosterone levels and onset of sexual dysfunction during menopause. Clinical practice is therefore ...

Introduction: Gestational diabetes mellitus (GDM) is a common metabolic disorder. The risk factors for GDM are often employed in selective screening. The impact of risk factors for GDM on newborn is yet to be fully evaluated.Objective: To determine the impact of maternal clinical risk factors for gestational diabetes mellitus on the anthropometric and clinical outcomes of the newborns.Method: The study was a prospective open cohort...

A 32-year-old man presented with a four year history of reduced libido, erectile dysfunction and inability to conceive with his partner. He went through puberty normally and had a normal sense of smell. Clinical examination revealed that he was 205 cm tall and normally virilised. Testicular volume was reduced, but the phallus was normal. Clinically, he appeared euthyroid and there were no features of hypercortisolism or growth hormone excess. Biochemical picture: prolactin 375...

Introduction: Hirsutism affects 10% of the female population caused by hyperandrogenism of benign aetiologies or androgen-secreting tumours. Tumorous causes of hyperandrogenism include androgen producing ovarian or adrenal tumours. Leydig cell tumours are rare ovarian testosterone producing tumours that comprise 0.1% of total ovarian tumours. It is rare in postmenopausal women and present with features of hyperandrogenaemia or hyperestrogenemia.Case: We ...

Introduction: Endocrine disrupting chemicals (EDC) are exogenous substances altering function(s) of the endocrine system. EDCs have been implicated in the decline in male reproductive health. We aimed to systematically review the pathophysiological effects of EDCs on male reproductive health.Methods: Searches of EMBASE, MEDLINE and PubMed were conducted using the following terms: ‘endocrine disrupt*’ OR ‘endocrine disruptors’ OR &#145...

Background: PCOS is a common female endocrine disorder, exacerbated by obesity. International guidelines therefore suggest weight loss as first line management. This service evaluation assessed the care pathway of patients referred to Queen Elizabeth Hospital Birmingham (QEHB) with suspected PCOS. We aimed to assess the referral wait time, reason for referral, treatment offered, and weight management in clinic.Methods: We undertook a cross-sectional stud...

Aim: To assess side effects of testosterone (TRT).Introduction: TRT in men with hypogonadism helps improve libido, erectile dysfunction, energy levels and bone density. However the risks/benefits of TRT in terms of ischemic heart disease (IHD), stroke and venous thromboembolism (VTE) is controversial no definitive answers from current evidence. We evaluated the side effects of TRT in patients attending endocrinology outpatient clinic between 2009 to 2019...

Pituitary apoplexy is a rare but life threatening condition if not diagnosed and treated promptly. Common causes include hypertension, head trauma, major surgery, dynamic pituitary tests, anticoagulant use and pregnancy. In pregnancy, hyperplasia and hypertrophy of the lactotroph cells increase pituitary volume by 45% returning to original size at 6 months post-partum. Pituitary apoplexy is uncommon in pregnancy and an underlying adenoma is usually the cause. Very few...

A 20 year old man otherwise fit and well, presented with a seizure, fall and fractured neck of femur. DEXA scan revealed osteoporosis; baseline blood tests were apparently normal in the endocrinology clinic with a Testosterone level of 24.3 nmol/l (Range 9.9–27.8) and normal bone and thyroid profile. He was then lost to follow-up. 4 years on, he was re-referred to the endocrinology clinic with a surprisingly elevated testosterone level of 34.6 nmol/l in combination with o...

We describe a 39-year-old lady who was managed as polycystic ovarian syndrome for nearly six years with an initial testosterone level of 5 nmol/l (0–1.8 nmol/l). She underwent laparoscopic ovarian drilling surgery followed by two unsuccessful IVF cycles for primary infertility. Deranged liver function and subsequent diagnosis of non-alcoholic fatty liver disease halted third trial of IVF. At that time, pelvic ultrasound demonstrated five follicles in both ovaries. In addi...

Aim: To compare efficacy of different formulations of TRT in treatment of hypogonadismBackground: Different formulations of testosterone are available for treatment of hypogonadism in men. TRT improves libido, sexual function, bone density and general well-being. We analysed data of 106 patients on TRT to compare efficacy of topical and injectable formulations.Methods: It’s a retrospective data analysis of 106 patient receivin...

62 year-old lady with a long history of hypokalaemia, hypertension and a random aldosterone of 786 pmol/l with suppressed renin of <8.0 mU/l at a time when she was taking Nebivolol, perindopril and Felodipine. Her Hypokalaemia improved after addition of Spironolactone and remained above 3.5 mmol/l. Biochemical work up confirmed a diagnosis of Conn’s syndrome and her BP control improved after addition of Aldosterone antagonist as above. Adrenal MRI revealed a 13 mm adr...

Introduction: Causes of Primary Congenital Hypogonadism in Males are Leydig cell Agenesis, Cryptorchidism, Chromosome abnormalities (e.g. Klinefelter syndrome, SRY positive 46 XX etc), Enzyme defects include 5α-reductase deficiency. Acquired Primary Hypogonadism includes Testicular torsion, Orchidectomy, Chemotherapy/Radiation toxicity, Orchitis, CKD, Cirrhosis, Sickle cell disease, etc. SRY (SEX determining region Y) is regulatory gene located on Y chromosome and is resp...

44 years old lady was referred to Endocrinology Clinic with history of secondary amenorrhea and hyperprolactinaemia (7800), that responded to Cabergolin treatment, which was discontinued after 2 months due to side effects (headaches). There was no galactorrhea or visual field defects. MRI Pituitary initially reported as Empty Sella. Her prolactin levels rose further along with headach after she discontinued Cabergoline (and refused alternatives). She eventually agreed for nigh...

Introduction: Congenital adrenal hyperplasia (CAH) is an endocrine disorder due to deficient adrenal corticosteroid synthesis inherited in an autosomal recessive manner. It is characterized by reduced negative feedback inhibition of cortisol with or without alteration in adrenal mineralocorticoid and androgen secretion. Ninety percent of cases of CAH is due to 21-hydroxylase deficiency. Classical CAH presents in new-born or in early childhood with ambiguous genitalia and/or sa...

Contraception is the use of artificial techniques in preventing pregnancy as a consequence of sexual intercourse by many women around the world. This study was carried out to investigate the biochemical effects of contraception on reproductive hormones in women using contraceptives. One hundred and eighty (180) women using different methods of contraception, were recruited for this study from Ekiti State University teaching hospital, Ado-Ekiti, Ekiti State, Nigeria, having obt...