hrp0092lb-3 | Late Breaking Posters | ESPE2019

Insights into the Regulation of Androgen Biosynthesis from Males with Congenital Hypogonadotropic Hypogonadism: Quantification of Bioactive Steroid Hormones Reveals Differences Between Gonadotropin Replacement and Testosterone Replacement

Rohayem Julia , Holterhus Paul-Martin , Kliesch Sabine , Nieschlag Eberhard , Zitzmann Michael , Kulle Alexandra

Background: In males with congenital hypogonadotropic hypogonadism (CHH), LH/FSH stimulation of gonads is deficient. In clinical practice, two hormone replacement strategies are employed to induce and maintain virilisation: Treatment with testosterone and gonadotropin replacement with hCG/rFSH.Objective: To delineate the role of gonadotropins in pathways of male androgen biosynthesis and to thereby better define the gona...

hrp0084p2-437 | Gonads | ESPE2015

Implementation of a High Sensitive LC-MS/MS Method for Measurement of Oestradiol, Oestrone and Oestriol

Kulle Alexandra , Reinehr Thomas , Simic-Schleicher Gunter , Roscheswsky Jule , Welzel Maik , Holterhus Paul-Martin

Background: Specific measurement of low serum/plasma concentrations of 17β-oestradiol (E2) is important in pre-pubertal and pubertal children in routine paediatric endocrinology. The role of oestrone (E1) and oestriol (E3) is not as comprehensively well understood in different pediatric endocrine disease states. We describe a method for high sensitivity analysis of estradiol (E2), oestrone (E1) and oestriol (E3) using LC-MS/MS.Objective and hypothes...

hrp0094p1-9 | Adrenal A | ESPE2021

Backdoor Pathway hormones and 11-oxygenated Androgens are elevated in Patients with 21-hydroxylase deficiency

Kulle Alexandra , Lamprecht Tabea , Pinto Francisca , Wulf Kristina , Hornig Nadine , Reinehr Thomas , Holterhus Paul-Martin ,

Background: Patients with 21-Hydroxylase deficiency (21OHD) present increased levels of cytochrome P450 21-hydroxylase substrates, like progesterone and 17α-hydroxyprogesterone. Previous studies could show that these hormones are involved in the production of androgens via the backdoor pathway. As a second source of androgens, 11-oxyandrogens derived from the human adrenal glands are recognized as being major androgens. Specifically, 11-oxyandrogens ...

hrp0094p1-147 | Sex Endocrinology and Gonads B | ESPE2021

A pre-analytical challenge to determine estradiol in children: A monovette systematically causing increased estradiol-concentrations in LC-MS/MS analysis

Lamprecht Tabea , Kleber Michaela , Rothermel Juliane , Holterhus Paul-Martin , Kulle Alexandra ,

Introduction: In children, estradiol (E2) concentrations are 1000-times lower in comparison to their precursors, the androgens. Depending on sex, age, and pathology, plasma concentrations vary in a broad range. The sensitive and specific determination of E2 is a particular challenge in pediatric endocrinology. Here we report a female patient aged 12 6/12 years and Tanner stage B1 with a presumed diagnosis of ovarian insufficiency. She showed a very high E2 con...

hrp0092p1-42 | Fat, Metabolism and Obesity | ESPE2019

De-novo and Depot-Specific Androgen Production in Human Adipose Tissue - a Source of Hyperandrogenism in Obese Females

Wagner Isabel Viola , Sahlin Lena , Kulle Alexandra , Klöting Nora , Döbeln Viola , Savchuk Iuliia , Dötsch Jörg , Söder Olle

Background: Obesity in females is often associated with metabolic complications and hyperandrogenism but the role of adipose tissue (AT) in androgen synthesis remains unclear.Aims/Objectives: Employing human subcutaneous and visceral AT and cultured adipocytes, we studied whether AT could be a source of androgens promoting hyperandrogenism in lean and especially in obese females.Methods</st...

hrp0082p2-d1-264 | Adrenals &amp; HP Axis | ESPE2014

LC–MSMS Profiling of Plasma Steroids in Different Types of Congenital Adrenal Hyperplasia

Kulle Alexandra E. , Reinehr Thomas , Akkurt Halit Ilker , Commentz Christian , Heger Sabine , Simic-Schleicher Gunter , Welzel Maik , Hornig Nadine C. , Holterhus Paul-Martin

Background: Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive disorders which lead to impairment of steroid biosynthesis in the adrenals and gonads. 21-hydroxylase deficiency (21OHD) is the most common form of CAH (95%), followed by 11β-hydroxylase deficiency (11OHD) and 3β-dehydrogenase steroid dehydrogenase type 2 deficiency (3bHSD2). LC–MSMS based steroid analysis has become an increasingly important method for steroid analyses i...

hrp0094p1-187 | Pituitary B | ESPE2021

The Adrenal Steroid Profile in Adolescent Depression: A Valuable Bio-Readout?

Hirtz Raphael , Libuda Lars , Hinney Anke , Focker Manuel , Judith Buhlmeier , Holterhus Paul-Martin , Kulle Alexandra , Kiewert Cordula , Hauffa Berthold , Hebebrand Johannes , Grasemann Corinna ,

Background: There is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been conducted in adults only, and conclusions are limited, mainly due to small sample sizes. Therefore, the present study was intended to assess whether adrenal steroids (progesterone, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, deoxycorticosterone, cortico...

hrp0094p2-370 | Pituitary, neuroendocrinology and puberty | ESPE2021

Size Matters: CAG Repeat Length of the Androgen Receptor Gene, Testosterone, and Male Adolescent Depression Severity

Hirtz Raphael , Libuda Lars , Hinney Anke , Focker Manuel , Buhlmeier Judith , Antel Jochen , Holterhus Paul-Martin , Kulle Alexandra , Kiewert Cordula , Hebebrand Johannes , Grasemann Corinna ,

Background: There is a distinct increase in the prevalence of depression with the onset of puberty. The role of peripubertal testosterone levels in boys in this context is insufficiently understood. Moreover, the number of CAG repeats of the androgen receptor gene (AR) and the depression status (subclinical vs. overt depression) may modulate the role of testosterone, but this has not yet been studied in a clinical sample.Methods:...

hrp0089rfc1.6 | Adrenals &amp; HPA Axis | ESPE2018

A Laboratory Harmonization Strategy for Steroid Hormone Profiling by MoM-Transformed, Normalized Reference Ranges Independent of Age, Sex and Units

Kulle Alexandra E , Zalas Dominika , Reinehr Thomas , Niedziela Marek , Borzikowsky Christoph , Pinto Francisca , Baumann Juliane , Flader Maciej , Simic-Schleicher Gunter , Akkurt Halit Ilker , Heger Sabine , Hornig Nadine , Holterhus Paul-Martin

Background/aims: The high complexity of Pediatric reference ranges across age, sex and units impairs clinical application and comparability of steroid hormone data, e.g., in CAHs. We developed a Multiples-of-Median (MoM) normalization tool to overcome this major drawback in Pediatric Endocrinology.Methods: LC–MS/MS data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to >16 years) from two previous datasets we...

hrp0082fc6.2 | Gonads &amp; DSD | ESPE2014

Next Generation Sequencing of the Androgen Receptor Gene in Patients With Androgen Insensitivity Syndrome and Controls

Hornig Nadine , Schweikert Hans-Udo , Ukat Martin , Kulle Alexandra , Welzel Maik , Wehner Gaby , Werner Ralf , Hiort Olaf , Drop Stenvert , Cools Martine , de Beaufort Carine , Siebert Reiner , Ammerpohl Ole , Holterhus Paul-Martin

Background: In a large fraction of patients with clinically presumed Androgen Insensitivity Syndrome, no mutation of the Androgen Receptor gene can be detected. However, established Sanger sequencing techniques of the AR gene are often limited to the coding region.Objective and Hypotheses: To set up a next generation sequencing (NGS) approach of the entire AR locus (including UTRs, exons, introns, up- and downstream regions) for a comprehensive ...