Endocrine Abstracts

Purpose: High serum prolactin concentrations have been associated with adverse health outcomes in some but not all studies. This study aimed to examine the morbidity and all-cause mortality associated with hyperprolactinaemia.Methods: A population-based matched cohort study in Tayside (Scotland, UK) from 1988 to 2014. Record-linkage technology (biochemistry, prescribing, hospital admissions, cancer registration, mat...

Background: IgG4-related disease is a rare immune-mediated inflammatory condition associated with extensive multi-organ involvement. Little is known about the epidemiology of pituitary involvement as a part the IgG4-related disease spectrum.Objectives: We aimed to identify patients with pituitary involvement amongst those with systemic IgG4-related disease, and to compare these individuals to patients with isolated ...

The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is however limited information on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual be...

Background: Determining post-operative remission in Cushing’s disease is challenging. There is no consensus for the post-operative serum cortisol value which reliably predicts remission of Cushing’s disease following trans-sphenoidal surgery. Traditionally, an early post-operative serum cortisol of below 50 nmol/L has been used to predict remission, but achieving this is often at the expense of hypopituitarism.<p class="abst...

Aims: 11C-methionine positron emission tomography co-registered with MRI (met-PET/MRI) is a new imaging technique used for functioning pituitary adenomas. In patients with persistent acromegaly after primary therapy, met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (Trans-sphenoidal surgery-TSS or radiotherapy).<p class="ab...

Introduction: Histology is a poor predictor of the malignant potential of phaeochromocytomas and paragangliomas (PPGL) and only the presence of distant metastasis confirms malignancy. This study reviews patterns of recurrence, treatment and mortality in patients with malignant PPGL presenting to our department at UCLH over 30 years.Materials and Methods: In our series of 128 patients with PPGL, 26 (20%) with maligna...

Background: Cross-sectional imaging (e.g. CT/MRI) can not always reliably identify the site of ACTH secretion in Cushing’s disease (CD) or the ectopic ACTH syndrome (EAS). We report our experience of localising the source of ACTH-dependent Cushing’s syndrome, using functional imaging with 11C-methionine positron emission tomography (Met-PET).Methods: Forty consecutive patients with: (i) de novo ...

Choriogonadotrophin-alpha (Cga) is one of the first molecular markers for the developing pituitary gland previously known as ‘alpha-subunit’, common to thyroid-stimulating hormone (TSH), luteinising hormone (LH) and follicle-stimulating hormone (FSH). Mice lacking Cga are hypogonadal and exhibit profound hypothyroidism and dwarfism. Light microscopy of Cga null mice has shown that pituitary thyrotrophs...

X-linked IGSF1 (immunoglobulin superfamily, member 1) loss-of-function mutations in males are associated with central hypothyroidism, macroorchidism, and a variable spectrum of anterior pituitary dysfunction. Igsf1 deficient male mice also exhibit central hypothyroidism, however, the physiological and molecular function of IGSF1 in both species has not yet been elucidated. Although partial transient GH deficiency is a ra...

Nausea/vomiting induced by smoke inhalation is a common phenomenon, possibly explaining why many people who have a naturally strong reaction rarely take up smoking tobacco. The tachykinins are an ancient family of bioactive peptides distinguished by the common C-terminal motif, Phe-X-Gly-Leu-Met-amide. In humans, there are four members: substance P (SP), endokinin (EK) also known as hemokinin (HK), neurokinin A and neurokinin B, which sig...

Over the past decade there has been increased recognition of the dangers associated with inpatient management of diabetes insipidus (DI) and omission of desmopressin. An NHS England patient safety alert was issued in 2016 highlighting this risk.Method: Using electronic prescribing records we reviewed all desmopressin prescriptions and omissions over a 12 month period in a large teaching hospital.Results: Ninety-seven inpatients wer...

Introduction: Obstructive sleep apnoea (OSA) is reported to have effects on a number of hormone systems including glycaemic control, catecholamines, and the HPA axis. In this study we aimed to determine the impact of OSA on IGF-I levels.Patients & Methods: This is a prospective cohort study performed at Leeds Teaching Hospitals. Patients were recruited from the Sleep Apnoea Clinic between November 2014 and May 2...

Adamantinomatous craniopharyngiomas (ACPs) are among the most common intracranial tumours in children and they originate from undifferentiated pituitary progenitors. Mutations in the gene encoding for β-catenin (CTNNB1), which lead to the constitutive activation of the Wnt/β-catenin signalling pathway, have been associated with ACP. These tumours can invade adjacent structures, such as the hypothalamus, which makes comp...

Introduction: The tumour microenvironment significantly influences tumour behaviour. Little is known about the pituitary adenoma microenvironment. AIP mutation positive (AIPpos) patients develop often aggressively growing pituitary tumours and the study of their microenvironment might identify factors leading to this aggressive phenotype which could help predict tumour behaviour and identify novel therapeutic targets.</p...

Introduction: Incompletely controlled acromegaly has a three-fold excess all-cause mortality, with stroke being the predominant cause of death. Debate exists about the relationship between fractionated radiation (FRT) and risk of stroke, with radiation damage to cerebral vasculature potentially being a cause. We present outcomes in patients treated by gamma knife STRS at the National Centre for Stereotactic Radiosurgery in Sheffield, with...

Background: Growth hormone deficiency (GHD) is an increasingly recognized potential consequence following traumatic brain injury (TBI). Outside of a formal, blinded RCT to demonstrate treatment effects, long term adherence to hGH replacement in a full reimbursement setting may serve as a pragmatic indicator of patient-perceived therapy benefits. Our objective was to evaluate adherence to therapy at one year for patients with GHD secondary...

Introduction: Copeptin is the C-terminal fragment of proAVP and provides an alternative measure of AVP secretion. While direct measurement of AVP during hypertonic saline infusion has been recommended as a diagnostic test for diabetes insipidus (DI), the number of reports examining the utility of copeptin in this context is limited. Here we describe a series of cases where measurement of copeptin during saline infusion has contributed to ...

Background: Opioid analgesics are commonly used for chronic non-cancer pain but may impair gonadal and adrenal axis function. We measured pituitary function, rates of hormone deficiency, sexual function and quality of life (QoL) in patients on oral or transdermal opioids versus age and sex-matched controls.Methods: Participants with chronic non-malignant pain receiving oral or transdermal opioids for more than six m...

Background: BIPSS is considered the gold-standard procedure for differentiating autonomous pituitary [Cushing’s Disease (CD)] and ectopic ACTH syndrome (EAS) sources of ACTH hypersecretion. A basal (i.e. unstimulated) pituitary:peripheral ACTH ratio >2, and/or a CRH stimulated pituitary:peripheral ACTH ratio >3, have been proposed as indicative of CD, with a range of sensitivities and specificities cited in the literature. Ad...

Background: Pituitary radiotherapy (RT) is known to have metabolic, cardiovascular and cerebrovascular complications due to the effects of radiation on normal pituitary tissue and surrounding neurological structures.Objectives: Retrospective evaluation of effects of RT on pituitary dysfunction, type 2 diabetes mellitus, cardio- and cerebrovascular morbidity and mortality in unselected consecutive pituitary adenomas ...

Introduction: Current guidelines from The Endocrine Society indicate that 2 different tests from urinary free cortisol (UFC) measurement, salivary cortisol (SC) measurement, low-dose dexamethasone suppression test (LDDST) or overnight dexamethasone suppression test (ODST) are required to diagnose Cushing’s syndrome (CS). The low-dose dexamethasone test (LDDST) is often used as the confirmatory test when diagnosing CS. The overnight d...

Background: Management of pituitary conditions is notoriously difficult and patients often experience high levels of distress which are often not addressed by health professionals. As a result, pituitary conditions have been found to have a large negative impact on quality of life. The aims of this study were 1) to identify the psychosocial symptoms associated with pituitary conditions, and 2) to identify any differences in symptomatology...

Background: It has been proposed that menopause has a beneficial effect on the natural history of hyperprolactinaemia attributed to prolactinoma. Nonetheless, series systematically assessing outcome in females with prolactinoma who have passed through menopause are very limited.Aim: To investigate the impact of menopause on prolactinomas in patients not on dopamine agonist (DA) treatment.Patie...

Background: Non-functioning pituitary adenomas (NFPA) account for 30-35% of pituitary adenomas. They can lead to hypopituitarism and visual field defects. Trans-sphenoidal resection of pituitary adenoma remains the treatment of choice.Methods: We compared clinical, biochemical, and imaging characteristics of NFPAs at presentation with post-surgical outcomes in a retrospective cohort study. Patients who underwent end...

Introduction: Mutations in the succinate dehydrogenase gene (SDH) predispose to the development of paraganglioma (PGL) which arise from parasympathetic and extra-adrenal sympathetic-associated chromaffin tissues. Identification of an index case results in family ‘cascade’ screening, often of asymptomatic individuals.Aims: To identify prevalence of PGL tumours and elevated plasma metanephrines at first scre...

Aims: Endocrine Society (ES) acromegaly guidelines (2014) addressed complication screening. Uncontrolled acromegaly is associated with elevated cardiovascular mortality due to risk factors including hypertension (HT), diabetes mellitus (DM), obstructive sleep apnoea (OSA), and with an increased risk of colorectal cancer and polyps among other types of neoplasias. We audited our clinical practice with regards to acromegaly complication screening.Methods: ...

The Royal College of Physicians (RCP) published a report called Referring Wisely in June 2017. The report asked specialty physicians for a short list of conditions they felt would benefit from specialist input in the context of acute inpatient management (recommended referrals). It also asked for a list of conditions which need not be referred (avoid referrals).Methods: We retrospectively audited inpatient referrals from our electronic inpatient referral...

Objective: Various treatment modalities are used for acromegalic patients to normalise growth hormone and IGF-1 values to those matched with the normal population in order to normalise morbidity and mortality. A retrospective audit was undertaken to review the treatment outcomes of four therapy groups. 1. Surgery alone, 2. Surgery and radiotherapy, 3. Surgery, radiotherapy and adjunct therapy, 4. Surgery and adunct without radiotherapy.</...

Aim: Endocrine Society (2016) published guidelines for hormonal replacement in hypopituitarism. Central hypothyroidism (CH) is defined as fT4 below reference range and mild CH is defined as fT4 in the low-normal range with suggestive symptoms in the context of pituitary disease. In patients with panhypopituitarism levothyroxine in doses sufficient to achieve fT4 levels in the upper half of the reference range is recommended. In our centre...

Background: Short Synacthen test (SST) is commonly used for the assessment of the hypothalamus-pituitary-adrenal (HPA) axis after pituitary surgery. In our centre, patients are discharged on hydrocortisone on day 3 post-surgery and 9am cortisol on day 8 post-surgery is measured. Hydrocortisone is stopped if cortisol is ≥350 nmol/L on day 8. Six weeks post-surgery SST is performed and treatment adjusted. We aimed to assess the perfor...

Background & Aims: The aims of transsphenoidal surgery (restoration/preservation of vision and amelioration of hormonal excess) are balanced against the risk of inducing new post-operative pituitary deficits. This study aims to assess the rate of new anterior hormonal deficits following transsphenoidal pituitary adenoma surgery in our centre and to assess whether the visibility of normal pituitary gland on pre-operative imaging predic...

Introduction: Patients with acromegaly are often left with long-term sequelae, among which arthropathy is the most common. Studies have shown impaired quality of life (QoL) in patients with acromegaly, even after long-term remission. Arthropathy is a negative predictive factor of QoL, due to its impact on physical symptoms and functioning.Patients/Methods: To characterise further the extent of the acromegalic arthop...

Objective: Hyperprolactinaemia is one of the most common disorders of the hypothalamic-pituitary axis. Endocrine Society guidelines state that a single prolactin measurement in a blood sample obtained at any time of day is adequate to confirm hyperprolactinaemia. However, prolactin levels can be confounded by physiological stimuli, e.g sleep, stress or exercise. Our objective was to assess the clinical significance of prolactin level obta...

Background: Endoscopic trans-sphenoidal surgery is a technical advance for treatment of pituitary tumours. We present the outcomes of patients with Acromegaly or Cushing’s disease undergoing selective pituitary adenomectomy in a regional neurosurgical centre.Methods: Retrospective cohort study August 2010-August 2017. Imaging, histology and pituitary hormone assessments were collated pre and post-operatively to...

Background: Transition from paediatric to adult services is a crucial process for young adults with long term conditions (LTC) affecting quality of life and engagement with medical services. The recent NICE report has outlined overarching principles for an effective transition. This can be a challenge for paediatricians and adult physicians as both hospital sites and medical/nursing teams can change. There is a dearth of evidence regardin...

Background: Pituitary conditions have been found to have a significant impact on quality of life. As such it is important that patients have access to support services to ensure their ongoing physical and psychological needs are met. The aim of this study was to explore the experiences of patients with pituitary conditions who are members of the Pituitary Foundation to better understand how the Foundation supports their needs.<p class...

Background: Dopamine agonists (DA) have excellent result in controlling both hyperprolactinemia and tumor volume in macroprolactinomas. However, even after long term DA treatment, withdrawal of dopamine agonists results in recurrence of hyperprolactinemia in a significant proportion of patients.Aim: To assess recurrence rate of hyperprolactinemia after DA withdrawal in a large series of patients treated in a tertiar...

Case summary: A 55 year-old lady was referred by ophthalmology following diagnosis of bilateral central serous retinopathy, an accumulation of sub-retinal fluid at the fundus associated with Cushing’s syndrome. She also had proximal myopathy, bruising, centripetal weight gain and hypertension. Cushing’s was confirmed by 1 mg overnight DST (cortisol 581 nmol/L) and 48 hr-LDDST (407 nmol/L). 24 hr UFC was raised at 2666 nmol/L (12...

A 54-year old female presented with fluctuating consciousness and seizures 4-weeks after gastric sleeve surgery. On admission blood glucose was 1.1 mmol/l, GCS was 10 and she was tachycardic. Examination was otherwise unremarkable. Her GCS improved after Glucagon and Glucogel. She described episodes of disorientation, slurred speech, fatigue and dysthesia since her surgery. These occurred particularly in the morning and her symptoms impro...

Background: Neuroglycopenic symptoms in insulinoma could persist for years before localising the source of endogenous hyperinsulinaemia. 90% of insulinomas are sporadic, solitary and < 2 cm in diameter, and can be associated with multiple endocrine neoplasia-1 (MEN-1). Insulinoma is an emerging clinical entity with a huge diagnostic challenge as tumour growth varies from months to years before tumour localisation.<p class="abstext...

Introduction: Presentation of pituitary tumours can be variable.If is a functioning pituitary tumour the clinical manifestation will be that of excessive hormone secreted, and if is a non functioning pituitary tumour, the presentation will be that of target endocrine organ insufficiency.Bradycardia/complete heart block may be a non specific presentation of non functioning pituitary tumours.Cas...

75% of patients presenting with a phaeochromocytoma (PCC) or paraganglioma (PGL) have no relevant family history, but a germline pathogenic variant is identified in 30–40%. In our genetic endocrine clinic, over 80% of patients with malignant PCC or PGL have SDHA/SDHB/SDHC/SDHD/MAX or FH pathogenic variants identified, confirming high heritability in severe disease.We describe a series of seven patients from fiv...