We present a patient who, when treated for macroprolactinoma with a dopamine agonist (DA), was able to stop insulin treatment of his autoimmune diabetes for 2 years. The patient was diagnosed with autoimmune diabetes after presenting to emergency services in diabetic ketoacidosis aged 50 years. On presentation, he had high titers of autoantibodies associated with pancreatic islet cell destruction and a high level of glycated hemoglobin. On review in the endocrinology clinic, he displayed signs and symptoms of hypogonadism. Subsequent investigations revealed low testosterone and high prolactin with a pituitary macroadenoma on magnetic resonance imaging. He was diagnosed with a macroprolactinoma and treated with DA. This treatment reversed his insulin requirement and he achieved excellent glycemic control without any hypoglycemic agent. At this point, his diagnosis was revised to latent autoimmune diabetes of adults. Two years after commencing the DA, insulin had to be restarted. We hypothesize that in addition to autoimmune destruction of the pancreatic β cells, there were several other causes of hyperglycemia in this patient, including hyperprolactinemia and hypogonadism. The correct diagnosis led to significant weight loss and appropriate therapy, with a dramatic improvement in quality of life.

Pituitary macroadenomas are neuroendocrine tumors residing in the base of the skull. First-line therapies for prolactin-secreting adenomas (prolactinoma) include medical treatment with dopamine agonists and neurosurgical intervention. Cerebrospinal fluid (CSF) rhinorrhea is a well-known complication following skull base tumor treatment; however, spontaneous CSF rhinorrhea as the initial presenting feature of such tumors is rare. We present two cases of spontaneous CSF rhinorrhea in pre-operative invasive pituitary macroadenomas. Invasive pituitary macroadenomas have the potential to disrupt local skull base structures such as the sellar floor and cavernous sinus. Early warning signs can help aid in prompt diagnosis and successful treatment. Spontaneous CSF rhinorrhea as the initial presenting symptom is rare and may be pivotal in the early diagnosis of pituitary adenomas.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract Background: Giant prolactinomas (GPs) are rare representing 2-3% of prolactinomas and only ~ 0.5% of all pituitary tumors. Various definitions have been proposed for GP but commonly accepted criteria is tumor dimension of ≥4 cm. GP is often associated with very high prolactin (PRL) ranging 1,000 -100,000 ng/ml, significant extrasellar extension and no concomitant growth hormone or ACTH secretion. Patients predominantly present with neurological symptoms rather than endocrine dysfunction, and so the primary goal of treatment is amelioration of neurological symptoms. The literature search reveals approximately 190 papers on this topic and most are single case reports or series describing only unusual clinical manifestations. Hence, evidence based recommendations for treatment are lacking. Dopamine agonist (DA) is considered first line of therapy, as these tumors are highly sensitive to medical therapy. Surgery and radiation may be warranted in special situations. Low starting doses of cabergoline (CAB) are generally recommended due to concern for complications of apoplexy and cerebrospinal fluid (CSF) leak from rapid tumor shrinkage. However, no recommendations for a specific starting dose exist. Objective: Individual tumor and hormonal response were assessed on 15 patients (pts) with GP on low dose CAB; 0.25-0.5 mg weekly to determine the effectiveness of DA therapy. Methods: 15 GP pts from two tertiary care centers, meeting the diagnostic criteria mentioned above, were reviewed. Reduction in tumor volume and maximal tumor diameter along with PRL, after initiation of CAB, at or before 6 months and 1 year post diagnosis, was calculated. Results: Presenting symptom: visual disturbance (56%), headache (20%), apoplexy (13%) and incidental finding (6%). Mean age at diagnosis: 61 years. Male to Female: 4: 1. Basal prolactin concentration: >2000 ng/dl (12/15pts), and > 900 ng/ml (2/15). Initial total CAB dose/week: 0.25-0.5 mg (13/15) and 1-2 mg (2/15). Cranial surgery: 4/15. Complications: CSF leak (1/15). Tumor volume assessed at 6 months (11/15) and 1 year (4/15) along with decrease in maximum tumor diameter in the same period of time. PRL assessed at or before 6 months (13/15) and at 1 year (2/15). Improvement in tumor size occurred promptly even with low dose CAB (0.25-0.5mg/week). 100% of patients initiated on low dose CAB responded to therapy. Mean reduction in tumor volume at or before 6 months was 47% in 11/15, and 52% at 1 year (10/15). Mean decrease in maximal tumor dimension was calculated as 0.95 cm at 6 months (12/15) and 1.4 cm at 1 year (9/15). The overall prolactin response rate at or before 6 months was > 90% in 7/15 patients (53%) and >50% in 11/15 patients (73%). Conclusion: Our data confirms excellent tumor response to low dose cabergoline therapy. Dose as low at 0.25 mg twice weekly is proven to be effective, leading to decrease in both tumor volume and PRL levels.

Hashimoto's encephalopathy (HE) is rarely reported with only a few hundred cases published. Diagnosis is made in patients with an appropriate clinical picture and high antithyroperoxidase (anti-TPO) antibodies after infectious, toxic and metabolic causes of encephalopathy have been excluded. There is little objective data on the neurocognitive impairment in patients with HE and their improvement with treatment. We present the case of a 28-year-old woman with HE. Approach to management was novel as objective neuropsychological assessment was used to assess her clinical condition and response to treatment. Intravenous immunoglobulin (IVIg) as the first-line treatment instead of steroids. She responded well. The case illustrates that a different approach is required for the diagnosis and treatment of HE. A new diagnostic criteria is proposed that includes neurocognitive assessment, serum and CSF antibodies, an abnormal EEG and exclusion of other causes of encephalopathy. Furthermore, treatment should be tailored to the patient.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Background/Aim: Congenital malformations still represent one of the most important causes of prenatal and infant death. The study goal was to analyze occurrence and outcomes of different types of congenital anomalies from the tertiary referral center during a ten-year period. Moreover, study aimed at examining potential predictors of congenital anomalies based on patients? characteristics and medical history data. Methods: Study included all pregnant women directed to Clinic of Obstetrics and Gynecology Clinical Center of Serbia due to prenatally diagnosed congenital fetal anomalies during past ten years. Upon admission to our clinic a detailed general medical and obstetrical history were taken from every patient. All women underwent genetic testing. Ultrasonography and magnetic resonance were diagnostic methods for fetal malformations confirmation. Results: Study included 773 pregnant women aged from 18 to 46 years. Out of registered nine different groups of fetal anomalies/malformations, the most common were malformations of the central nervous system, while majority of fetuses had combined multiple anomalies. Genetic cause for congenital anomalies was present in 25.2% of pregnancies. Medical pregnancy abortion was performed in 71.8% of cases. Only 10.2% of pregnancies ended in term. The best outcome for children was obtained in case of gastrointestinal anomalies (52% live-born). Contrary only one child with neck and thorax malformations could be saved. According to logistic regression the most important predictor of having a child with combined multiple anomalies was mother?s age, while predictor of central nervous system anomalies was gestational diabetes. The significant predictor of genetic anomalies was mother?s age. Conclusion: In our sample neurological congenital anomalies were the most common, although abnormalities of all organ systems were registered. Majority of pregnancies had to be discontinued due to combined multiple anomalies caused by genetic disorders. Older mother?s age and diabetes can imply on the increased risk for fetal malformations.

 On hormone replacement therapy and carbegoline Pituitary apoplexy is both a medical and an endocrine emergency. It can typically present with sudden onset of headaches, impaired level of consciousness, fever and visual disturbances, nausea or vomiting. Apoplexy ensues when pre-existing pituitary tumour presumably outgrows its blood supply leading to ischaemia, necrosis and haemorrhage or infarction. Introduction

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

CONTEXT Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate. OBJECTIVE Our objective was to provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used. DESIGN Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalized estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group. SETTING Thirteen centers of secondary/tertiary endocrine care across the United Kingdom were included. RESULTS There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42-62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97 mg (20-377) and 232 mg (91-551), respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24-42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Summary Prolactinomas constitute the largest subsection of all secretory pituitary adenomas. Most are microprolactinomas and are satisfactorily treated by medical management alone. Giant prolactinomas, measuring more than 4 cm in diameter, are rare and usually occur more commonly in men. Macroprolatinomas tend to present with symptoms of mass effect rather than those of hyperprolactinaemia. Dopamine agonists (DA) are the treatment of choice for all prolactinomas. Surgery is usually reserved for DA resistance or if vision is threatened by the mass effects of the tumour. We describe the case of a 52 year-old woman with a giant invasive prolactinoma who required multiple surgical procedures as well as medical management with DA. One of the surgical interventions required a posterior approach via the trans cranial sub occipital transtentorial approach, a surgical technique that has not been previously described in the medical literature for this indication. The giant prolactinoma was reduced significantly with the above approach and patient symptoms from the compressing effects of the tumour were resolved. This case highlights the importance of a multidisciplinary approach to the management of such patients who present with florid neurological sequelae secondary to pressure effects. Although this presentation is uncommon, surgery via a sub occipital transtentorial approach may be considered the treatment of choice in suitable patients with giant invasive prolactinomas compressing the brainstem. Learning points Giant prolactinomas present with symptoms of mass effect or those of hyperprolactinaemia. Interpretation of the pituitary profile is crucial to guide further investigations and management. Treatment of giant invasive prolactinomas may involve a combination of medical management and multiple surgical interventions. Treatment with DA may cause pituitary haemorrhage or infarction in patients with these tumours. A sub occipital transtetorial approach may be considered the treatment of choice in invasive prolactinomas compressing the brainstem. Multidisciplinary approach of such patients is fundamental for a better outcome.

INTRODUCTION Lipid peroxidation (LPO) results from oxidative damage to membrane lipids. Whereas LPO rises in normal pregnancy, the effect of gestational diabetes mellitus (GDM) on this process has not been clearly defined. MATERIALS AND METHOD Fasting blood concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as LPO index, TNFa soluble receptors (sTNF-R1 and sTNF-R2), and soluble adhesion molecules (sICAM-1, sVCAM-1), were measured in 51 women at 28 weeks of gestation. The women were divided according to the results of 50.0 g glucose challenge test (GCT) and 75.0 g oral glucose tolerance test (OGTT): Controls (n=20), normal responses to both GCT and OGTT; Intermediate Group (IG) (n=15), abnormal GCT but normal OGTT; GDM group (n=16), abnormal both GCT and OGTT. RESULTS Glucose concentrations in women diagnosed with GDM were within the range of impaired glucose tolerance. There were no significant differences in concentrations of either TNF a soluble receptors R1 and R2, or sICAM-1 or sVCAM-1. LPO concentrations [MDA+4-HDA (nmol/mg protein)] were significantly higher in women with GDM than in the other two groups [64.1±24.3 (mean±SD), 39.3±23.1, 47.0±18.1, for GDM, IG and Controls, respectively; p<0.05]. In multivariate analysis, the only significant independent correlation was between LPO level and glucose at 120 minutes of OGTT (rs=0.42; p=0.009). CONCLUSIONS Oxidative damage to membrane lipids is increased in GDM and might result directly from hyperglycaemia. Physiological significance of this phenomenon remains to be elucidated.

To assess the effectiveness of vaginal administration of the probiotic Lactobacillus rhamnosus BMX 54 in preventing the occurrence of abnormal vaginal flora and the alteration of parameters relevant to the progression of pregnancy.