SUNCT syndrome with paroxysmal mydriasis: Clinical and pupillometric findings.

SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) is a primary headache characterised by a high frequency of attacks associated with marked autonomic periocular signs and symptoms. Activation of the hypothalamus via the superior salivary nucleus is probably responsible for some of the autonomic involvement observed during SUNCT attacks. We describe a case of SUNCT with unusual autonomic features (e.g., mydriasis) and early onset. Pupillometric studies were performed both in a basal condition (without anisocoria) and after instillation of phenylephrine (a drug with direct sympathomimetic activity) and pilocarpine (a parasympathetic agonist). The findings in this patient seem to indicate involvement of the ocular sympathetic supply in SUNCT, responsible for the mydriasis, and seem to strengthen the possibility that the autonomic phenomena in this syndrome vary with different levels of pain severity.

Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes.

Mesenchymal stem cells (MSCs) are multipotent non-haematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential together with their effects on immune response make them a promising therapeutic tool for severe refractory autoimmune diseases. Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic beta cells. While insulin replacement represents the current therapy for type 1 diabetes, its metabolic control remains difficult, as exogenous insulin cannot exactly mimic the physiology of insulin secretion. Pancreatic or islet transplantation can provide exogenous insulin independence, but is limited by its intrinsic complications and the scarcity of organ donors. In this context, stem cell therapy, based on the generation of insulin-producing cells (IPCs) derived from MSCs, represents an attractive possibility. In this review, we provide a brief characterization of MSC immunomodulatory effects, and present the current experimental evidence for the potential therapeutic efficacy of MSC transplantation in diabetes.

The Link Between Bone Osteocalcin and Energy Metabolism in a Group of Postmenopausal Women.

There is a dual relationship between bone and tissues involved in energy metabolism (fat tissue and beta-pancreatic cells). Thus, bone remodeling is an energy consuming process, but osteocalcin, the main on-collagenic protein, synthesized by osteoblas during bone formation exerts a number of biological effects on beta-pancreatic and adipose cells. With this data, we wanted to see if the presence of a chronic metabolic disorder such as type 2 diabetes mellitus (T2DM) influence this complex dual relationship. For this, we conducted a cross-sectional study to evaluate the relation between osteocalcin and energetic metabolism in a group of 146 postmenopausal womens with and without T2DM at CI Parhon National Institute of Endocrinology, Bucharest. Clinical, metabolic and hormonal parameters were evaluated. For statistical analysis we used Student t-test and the Spearman correlation (statistical significance: p <0.05). Results: 63 patients with T2DM (63.88±8.56 years) and 83 women in the control group (60.21±8.77 years) were included. Diabetic women showed a lower level of serum total osteocalcin (p<0.05) HDL-cholesterol (p=0.02), and 25-hydroxyvitamin D (25(OH)D). The body mass index (BMI), glycemic metabolism parameters and triglyceride levels (p<0.05) were higher in this group. We found correlations between osteocalcin and metabolic elements: negative with BMI (r=-0.329, p<0.05), glycated hemoglobin (HbA1c) (r=-0.398, p<0.05), and serum triglycerides (r=-0.329, p<0.05) respectively positive with HDL-cholesterol (r=0.279, p=0.001) for the entire group of patients. Conclusions: Our study indicated the presence of significant correlations between serum osteocalcin and glycemic and lipid metabolism parameters, independent of the presence of diabetes.

The multimodal management of GH-secreting pituitary adenomas: predictive factors, strategies and outcomes.

Object. The aim of this study was to analyze a series of 28 patients with acromegaly who underwent a multimodal surgical, medical and radiosurgical therapy, with a special attention to the advantages, complications, and predictive factors of a successful outcome. Methods. 28 consecutive cases of GH-secreting pituitary adenomas, who underwent transsphenoidal endoscopic or microscopic surgery, between 1 January 2014 and 31 December 2014 were retrospectively reviewed. Tumors were classified according to the diameter, measured on MRI, as micro- or macroadenomas, and parasellar (cavernous sinus) tumor extension was analyzed based on the Knosp grading score. The mean follow-up period was of 18.4 months. Criteria justifying the complete hormonal remission were preoperative basal serum GH < 2.5 µg/ L, preoperative nadirGH < 1 ng/ L after OGTT and normal preoperative IGF-I levels age and sex-matched. Results. An overall complete hormonal remission rate was achieved in 64.3% of the patients. The remission rate was higher in patients with microadenomas (77.8%) than in those with macroadenomas (57.9%). A number of predictive factors, which might have interfered with the hormonal remission rate from a statistical, clinical and paraclinical point of view, were identified: tumor size (r = 0.625), preoperative GH serum levels (r = -0.517), cavernous sinus extension was quantified according to Knosp grading score (r = 0.469) and the degree of tumor subtotal resection (r = 0.598). Conclusions. Favorable hormonal and visual remission rates can be achieved after transsphenoidal resection of GH-secreting pituitary adenomas; however, the management remains challenging, the increased surgical experience being important for higher cure rates. If a biochemical hormonal cure is not achieved postoperatively, adjuvant medical or radio surgical therapy can be recommended.

Cushing's disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment.

Cushing's disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing's disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality. It is vital to diagnose Cushing's disease as early as possible and to implement a treatment plan to lead to a successful prognosis and a low number of complications. The goal of this article was to review the clinical, diagnostic and treatment aspects of Cushing's disease using the most recent available guidelines.

A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas: The PERSEUS experience.

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.

Phenotypic spectrum and hormonal profile in hypogonadotropic hypogonadism.

BACKGROUND: Hypogonadotropic hypogonadism (HH) is characterized by inappropriately low serum concentration of LH (luteinizing hormone) and FSH (follicle-stimulated hormone) in the setting of hypogonadism. A number of pathologic processes cause Hypogonadotropic hypogonadism but it can also occur as a part of various congenital syndromes. Objectives. To characterize the morphotypes and the hormonal profile of the HH patients enrolled in the COST Action BM1105 within "C.I. Parhon" National Institute of Endocrinology from May 2012 onward. Methods. The eligible patients were selected by using a general protocol that included: a detailed familial and personal history; a clinical evaluation focusing on genital development; a hormonal evaluation that aimed to exclude the acquired causes of HH and to characterize the basal/stimulated (triptoreline) profile of gonadotropins; a DNA extraction for genetic studies. RESULTS: We examinated the medical records of patients admitted in our institute with the diagnosis of hypogonadotropic hypogonadism from May 2012 onward. There were 19 patients: 12 males and 7 females, age at diagnosis 28.03 ± 11.45 years (13.4-56 years). The phenotypic expressions were variable and the hormonal evaluation showed low values of basal and stimulated gonadotropins. CONCLUSIONS: Although hypogonadotropic hypogonadism is a rare disease, the monospeciality profile of National Institute of Endocrinology enable the enrolment of a high number of patients in order to create clinical guidelines for evaluation/diagnosis and for treating GnRH deficient patients.

Genetic and epigenetic alterations in differentiated thyroid carcinoma.

Differentiated thyroid carcinoma (DTC) has a favorable prognosis, but it is important to identify those patients who have a high risk of progressive disease and DTC-related death at the time of diagnosis. Analyzing genetic and epigenetic alterations in thyroid cancer may play a role in tumor diagnosis, prognostic and therapeutic strategies.

Adrenalectomy by laparoscopic anterolateral transperitoneal approach for patients with previous abdominal surgery.

Adrenal surgery has been radically changed by laparoscopic approach and we wonder whether the increase in the number of adrenalectomies is entirely justified by better understanding of the pathology and a developed diagnosis methods. The type of approach (transabdominal/retroperitoneal) remains a matter of the surgeon's experience. Method: In the past 8 years, we have performed more than 200 laparoscopic adrenalectomies by transperitoneal approach, 24 of them having previously significant abdominal surgery (cholecistectomy, gastric surgery, colectomy, bowel obstruction, exploratory laparoscopy, and adrenalectomy). The patients had a variety of adrenal pathologies such as Cushing disease, Cushing syndrome, Conn syndrome, incidentaloma, pheochromocytoma and even carcinoma. Results: 3 cases were converted to open approach, only one because of the adhesions. Reasons for conversion were also: spleen intarctisation and a difficulty in mobilizing the tumor. Operating time was not significantly prolonged because of the adhesions (40-360 min, median time 127 min). Postoperative evolution was simple with no morbidity or mortality and a fast recovery was recorded. Conclusions: Choosing the type of approach is related to surgeon experience, although 79-94% of the surgeons prefer the transabdominal lateral approach. We believe that with an experienced surgical team, there is no difficulty in performing adrenalectomy by transabdominal approach, with no significantly prolonged operating time, even though the patient has previously had abdominal surgery.

Genetic testing for multiple endocrine neoplasia type 2.

Multiple endocrine neoplasia type 2 (MEN 2) represents a complex autosomal dominant inherited syndrome characterized by occurrence of distinct proliferative disorders of endocrine tissues. The identification of RET proto-oncogene mutations in MEN 2 and FMCT has provided a precise method for identifying gene carriers. 30 subjects (9 males, 21 females, age range 11-63 years) with multiple endocrine neoplasia type 2 have been investigated from 1998 till 2006. 20 patients were considered as index cases and 10 patients were identified after a screening programme for MEN 2. Tumoral associations permitted the MEN 2A diagnosis in 21 cases, MEN 2A with cutaneous lichen amyloidosis in 6 cases and FMCT in 3 cases. We selected 22 patients from 14 families to investigate mutations in the RET proto-oncogene. In 7 subjects no mutations could be detected in the exons 10 and 11 of the RET proto-oncogene. Heterozygous missense mutations in exon 11 were found in 15 subjects consisting of three different mutations in codon 634 (TGC --> TGG, TGC --> GGC, TGC --> CGC). We conclude that our 15 patients have the most frequent mutations described in MEN 2A families. Because the testing for exons 10 and 11 is negative for other 7 patients, the remaining 13, 14, 15 and 16 exons should be sequenced in these cases.

[Turner's syndrome, diagnosis and therapeutical approach]. / Sindromul Turner. Abordare diagnostica si terapeutica actuala.

Turner's Syndrome is a rare chromosomal disorder of females (1 : 2500) characterized by short stature and the lack of sexual development at puberty. Other physical features may include a webbed neck, heart defects, kidney abnormalities, and/or various other malformations. Diagnosis should be considered in individuals with primary or secondary amenorrhea and adult women with unexplained infertility, particularly when such individuals also are short in stature. In childhood, growth hormone therapy is standard to prevent short stature as an adult. Estrogen replacement therapy usually is required, but starting too early can compromise adult height. The most frequent, the possibility of a good diagnosis appears at puberty. The early diagnosis needs the karyotyping as screening method. The correct treatment, which is made on time, has a good mental and social life influence.

Therapeutic methods in endocrinology. General considerations.

The integrative character of the endocrine system and its regulation ways generate and motivate the specificity of endocrine therapy. The latter tries, by its methods and means, to restore hormonal homeostasis, to imitate the biologic rhythms of secretion, to respond to the stress needs, in fact it ensures the dynamics of the normal integration of an individual in the daily life with all its changes. This requirement is ensured by the methods of stimulation and suppression, hormonal substitution or depression of hormone bio-synthesis, blockade of enzymatic activation or desensitivation of the receptors to the hormonal message, etc. The association of the therapeutic means and methods has the purpose of bringing relief and the expectancy of a decent, controlled survival in inevitable iatrogeny. Endocrine therapy also ensures a normal growth and development, an acceptable IQ, a reasonable degree of sexualization, responds to the most important demand of life: perpetuation of the species. The range of endocrine therapy is perhaps the widest in medicine, starting with the disease and ending with the esthetic aspects of the individual. A good knowledge of the methods, means and especially their dynamics and specificity gives the endocrinologist the pragmatic outlook measured only by its efficiency.

Alternatives in human reproduction. Methods, indications, prognosis, bioethical problems.

The alternative methods in human reproduction do nothing else than try to help an individual or a couple to achieve the primordial goal of life: perpetuation of the species. These methods try to reconstruct the biologic premises necessary for perpetuation by various means such as: a. in vitro fecundation correlated or not with artificial fecundation with donor, ovocyte donation, embryo donation, borrowed mother; b. intratubular transfer of gametes; c. unnatural circumstances, i.e., the possibility that men be a host for the embryo up to term, a hypothesis which for the time being is possible only in science-fiction. The birth of Louisa Brown in 1978 was the border between hope and certainty, between dream and pragmatism. Thus, the alternative methods of reproduction have become routine in the medical life and penetrated into the conscience of an ever greater number of people but at the same time have raised an immense number of questions regarding the status of the embryo and the foetus, but more important, of the child born under these circumstances. These questions await answers both from medicine and the law and have to be within the limits of the common sense. Those who participate in the in vitro fecundation programs should not lose their quality of being human, should pay respect to the nature and the natural, encourage hope and be moral.

Transsexualism; new observations.

Ten cases of transsexualism have been studied. All the patients present gonadal lesions, modifications of the morphotype and small hormonologic anomalies. It is supposed that the gonadal lesions are frequently associated with this psycho-behavioural disorder. Thus transsexualism may be considered a trouble of the whole process of post gonadal sexualization.

Dermatoglyphics in the virilizing polycystic ovary syndrome.

Quantitative and qualitative characteristics (form and orientation of the digital patterns, total digital ridges count, delta index, form and regional distribution of palmar patterns, palmar flexion creases, palmar delta index, atd angle, the direction of the A, B, C, and D palmar lines and the number of crests between the a, b, c, and d triradii) of digito-palmar dermatoglyphics in 33 women with virilizing polycystic ovary (VPO) were studied. The selection was made on the basis of the clinical examination and a complex bio-hormonal exploration of female patients with pilar virilism hospitalized in or treated at the outpatient clinic of the "C. I Parhon" Institute of Endocrinology between 1975 and 1984. The control lot was made up of 100 females and 100 males, clinically healthy, originally from various rural and urban areas in Romania. It was found that the VPO women come within the range of variability of the normal, with some dermatoglyphic peculiarities characteristic of the VPO syndrome; i.e., a lower total digital ridges count, and fewer ridges between the triradii at the basis of the fingers. Qualitatively, there is a preponderance of the loop-like digital patterns, especially those with radial orientation and palmar, compared to the normal, the VPO women present more frequently patterns in the interdigital space II. Palmar flexion lines indicate in VPO women a higher incidence of palmar transversal sulcus variants as compared to normal women. The existence of similar dermatoglyphic peculiarities both in VPO and in adrenogenital syndrome supports the hypothesis that the ovarian hormonogenesis disorders in the VPO syndrome may be genetically determined through an enzymatic defect.