Diana Paun

Testicular histological and immunohistochemical aspects in a post-pubertal patient with 5 alpha-reductase type 2 deficiency: case report and review of the literature in a perspective of evaluation of potential fertility of these patients

BackgroundTesticular morphology and immunohistochemical studies have never been reported in genetically documented adult patients with 5 alpha-reductase type 2 deficiency (5α-R2 deficiency).Case presentationWe describe the testicular histopathology of a 17-year-old XY subject with 5α-R2 deficiency caused by the recurrent homozygous Gly115Asp loss of function mutation of the SRD5A2 gene.We also performed an immunohistochemical analysis in order to further study the relationship between seminiferous tubules structure, Sertoli cell differentiation and androgenic signaling impairment in this case. We thus evaluated the testicular expression of the anti-Müllerian hormone (AMH), androgen receptor (AR) and 3β-hydroxysteroid dehydrogenase (3βHSD). Histological analysis revealed a heterogeneous aspect with a majority (92%) of seminiferous tubules (ST) presenting a mature aspect but containing only Sertoli cells and devoid of germ cells and spermatogenesis. Focal areas of immature ST (8%) were also found. Testicular AR and 3βHSD expression were detected in adult male control, 5α-R2 deficiency and CAIS subjects. However, AMH expression was heterogeneous (detectable only in few AR negative prepubertal ST, but otherwise repressed) in the 5α-R2 deficiency, conversely to normal adult testis in which AMH was uniformly repressed and to an adult CAIS testis in which AMH was uniformly and strongly expressed.ConclusionIntratesticular testosterone can repress AMH by itself, independently of its metabolism into dihydrotestosterone. We also compare our results to the few post pubertal cases of 5α-R2 deficiency with available histological testicular description, reported in the literature. We will discuss these histological findings, in the more general context of evaluating the fertility potential of these patients if they were raised as males and were azoospermic.

A 2018 Italian and Romanian Survey on Subclinical Hypothyroidism in Pregnancy

Objectives: Pregnancy induces changes in thyroid function, and thyroid dysfunction during gestation is associated with adverse outcomes. We examined the management of subclinical hypothyroidism and chronic autoimmune thyroiditis in pregnancy among Italian and Romanian endocrinologists. Methods: Members of the Associazione Medici Endocrinologi (AME) and Romanian Society of Endocrinology (RSE) were invited to participate in a web-based survey investigating the topic. Results: A total of 902 individuals participated in the survey, 759 of whom completed all sections. Among the respondents, 85.1% were aware of the 2017 American Thyroid Association guidelines about thyroid disease and pregnancy, and 82.9% declared that thyroid-stimulating hormone (TSH) screening at the beginning of pregnancy should be warranted. In a patient negative for peroxidase antibodies, 53.6% considered 2.5 mIU/L and 26.2% considered 4.0 mIU/L as the upper normal limit of TSH, and 50% would treat a patient with TSH 3.5 mIU/L with levothyroxine. About 20% did not suggest iodine supplementation. Isolated hypothyroxinemia detected in the first trimester would be treated by 40.8%. In patients undergoing ovarian stimulation, a TSH < 2.5 mIU/L would be targeted by 70%. Conclusions: Respondents globally appeared well informed about the management of thyroid autoimmunity and subclinical hypothyroidism in pregnancy. A more aggressive attitude in implementing iodine supplementation would be desirable. Most endocrinologists were convinced about an evident association between mild thyroid impairment and adverse outcomes in pregnancy, thus using a TSH value of 2.5 mIU/L as the threshold for diagnosing hypothyroidism and starting levothyroxine in pregnant women.

Menopause and prolactin secreting tumours

ABSTRACT Introduction Prolactinomas without galactorhhea may be considered menopause or not diagnosed. This is a cases series. Case1. 76-year female with menopause at age of 52 was discovered at 66 yrs with high prolactin and a pituitary micro-nodule. Bromocriptin was continued for 6 years then switched to cabergoline with constant imagery. The patient did not display at all galactorrhea. Osteoporosis was diagnosed at age of 66 with previous 2 fragility fractures. Case2. 45-year female is known with secondary amenorrhea (without galactorrhea) for the last 7 years being considered menopause. She experienced headaches thus a MRI was performed and found a pituitary tumour of 1.5cm. Low FSH with increased prolactin was revealed. Cabergoline was started. Within 2 months the menses resumed and headache mildly improved. After 3 months prolactin normalised under weekly 2 mg of cabergoline. Periodical prolactin control is necessary as well as a pituitary scan at 6 months. Case3. 39-year female had a 3 yrs history of secondary amenorrhea. A prolactin of 117ng/mL and a microprolactinoma of 0.77cm were found. Cabergoline was started and progressively increased up to 1.5mg per week. The prolactin quickly normalised up to 8ng/mL within 4 months. She was followed for 2 years and the imagery found a tumour reduction to 0.44cm. Conclusion Prolactinomas associate a great variety of clinical presentations. They interfere with menopause by mimicking it in cases without galactorrhea. Also a newly diagnosed prolactinoma during menopause needs long term therapy and followed-up for especially for bone safety.

MICRORNAS WITH SPECIFIC ROLES IN DIABETES AND PSYCHIATRIC DISEASES

Diabetes mellitus is one of the most cited non communicable diseases and the most common metabolic disorder. Epigenetics represents the field of study of heritable changes in gene expression which are not directly related to DNA. Epigenetics is concerned, alongside histone modifications, short interfering RNAs etc., with microRNAs (miRNAs) as well. These are small noncoding RNAs, 21 to 23 nucleotides in length, which either inhibit translation or affect mRNA stability and degradation. At present, there are dozens of miRNAs which have been proven to be involved in the animal and human pathology of diabetes (type 1 or 2). This review focuses on the miRNAs which have been identified as playing a role in both psychiatric diseases and diabetes.

GH dynamics in oral glucose tolerance test in children and adolescents with tall stature

Conclusions Assessment of GH dynamics in OGTT in children and adolescents with tall stature in various stages of pubertal development for documenting a possible autonomous GH secretion. Our study included 44 subjects, 18 girls and 26 boys, aged between 6.5 years and 17.3 years diagnosed with constitutional tall stature. • The inclusion criterion was height ≥+2 DS. • The exclusion criteria were: diabetes, thyroid dysfunction, Cushings syndrome, hypothalamicpituitary pathology, renal failure, medication that alters glucose/ GH dynamics such as estrogen and thyroid hormones. • The following parameters were assesed: historical and auxological data, clinical examination, laboratory evaluations: karyotype, thyroid function, androgens, IGF1 (CLIA method with detection limit 3-1500ng/ml), IGFBP3, prolactin, evaluation of other pituitary hormone deficiency, bone age, cardiac ultrasound, eye examination, CT/MRI of the hypothalamic-pituitary region. OGTT was performed with 1.75 g/kg of glucose po. Glucose and GH (CLIA method with detection limit 0,1-80 ng/ml) were tested at 0, 30, 60, 90 and 120 minutes. • Brain imaging was performed in 20 cases. • Statistical analysis was performed using PASW software version 18, 2010 using Pearson correlation, T test, and Mann-Whitney test and the level of significance used was p 1ng/ml. • For girls GH nadir was higher than for boys. • The lowest value of GH both for girls and boys was at 90 minutes. • 2 patients with IGF1>+2DS for chronological age had normal levels of IGFBP3. • In 6 patients with GH suppression >1ng/ml, the levels of IGF1 and IGFBP3 were normal. • CT/MRI of the hypothalamic-pituitary region revealed an inhomogeneous pituitary gland. P 805