Klinefelter Syndrome and Testosterone Treatment in Puberty

Evaluation of body fat percentage by whole body dual energy x-ray absorptiometry (DEXA) scan

Tanner genital (G) staging from G1 to G5. G1 is the prepubertal stage and G5 is the fully develloped stage.

Tanner pubic hair (PH) staging from PH1 to PH6. PH1 is the prepubertal stage and PH6 is the fully develloped stage.

Measurement of voice frequency using the app "Voice Analyst" (Speechtools Ltd.).

Evaluation of testicular volume by palpation with orchidometer

Presence of gynecomastia (yes/no)

Measurement of luteinizing hormone (LH) (IU/L) in serum

Measurement of serum concentration of testosterone (nmol/L)

Measurement of folliclestimulating hormone (FSH) (IU/L) in serum

Measurement of serum concentration of estradiol (pmol/L)

Measurement of serum concentration of inhibin B (ng/L)

Measurement of serum concentration of anti mullerian hormone (AMH) (pmol/L)

Measurement of the concentration of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the first, fasting, morning voiding. Measured in IU/L.

Measurement of height (cm)

Measurement of weight (kg)

Measurement of sitting height (cm)

Measurement of head circumference (cm)

Measurement of arm span (cm)

Measurement of whole body bone mineral content (BMC) evaluated by whole body DXA scan

Evaluation of bone health index (BHI) from X-ray of left hand and evaluated using the software BoneXpert version 3 (Hørsholm, Denmark)

Measurement of 25-OH-vitamin D in blood sample

Measurement of calcium in blood sample

Measurement of phosphate in blood sample

Measurement of parathyroid hormone (PTH) in blood sample

Measurement of carboxy terminal telopeptide of collagen type I (CTX) in blood sample

Measurement of alkaline phosphatase in blood sample

Measurement of osteocalcin in blood sample

Measurement of procollagen type I N-terminal peptide (PINP) in blood sample

Evaluation of bone age by X-ray of left hand and evaluated using the software BoneXpert version 3 (Hørsholm, Denmark)

Measurement of IGF1, IGF2, IGF1BP-1-6 and acid-labile subunit (ALS)) (microg/L)

Measurement of standing jump length (cm)

Measurement of hand grip strength using a digital hand dynamometer (Baseline BIMS, digital hand dynamometer, functional model)

Evaluation of QT Interval with electrocardiogram (ECG)

Measurement of cholesterol in blood sample

Measurement of adiponectin in blood sample

Measurement of leptin in blood sample

Measurement of glucose in blood sample

Measurement of insulin in blood sample

Measurement of HbA1C in blood sample

Measurement of CRP in blood sample

The Weschler Intelligence Scale for Children - Fifth Edition (WISC-V). The result is based on a combination of seperate index scores. A higher score generally indicates stronger cognitive abilities.

The Test of Variables of Attention, version 9 (T.O.V.A) is a computerized, performance-based assessment tool used to measure attention and impulsivity. The result is based on a combination of scores.

The Test of Memory and Learning, Second Edition (Tomal-2). The results are presented as standard scores, scaled scores, percentile ranks, and index scores. A higher score is a better outcome.

The Judgement of Line Orientation Test. The result is based on a combination of scores. Higher scores indicate better visual-spatial judgment.

The Mental Rotation Test

The Beery-Buktenica Developmental Test of Visual-Motor Integration

The Baseline Speed subtask of the Amsterdam Neuropsychological Tasks program (ANT)

The Children's Communication Checklist (CCC-2). The result is evaluated based on 10 subscores. Higher scores indicate stronger communication skills.

The Social Responsiveness Scale-2 (SRS-2) is a standardized questionnaire used to assess social behavior and autism-related traits. Higher scores indicate greater social difficulties, while lower scores suggest stronger social skills.

The Delis-Kaplan Executive Function System (D-KEFS). Higher scores indicate better executive functioning, while lower scores may suggest difficulties with problem-solving, impulse control, or flexibility.

The Behavior Rating Inventory of Executive Function, Second Edition rating scale , parent version (BRIEF-2) assesses executive functioning. The result is based on a combination of scores. Higher scores indicate greater executive function difficulties.

Behavior Assessment System for Children, Third Edition (BASC-3), parent and self-report version. The result is based on a combination of scores. A higher score indicates more difficulties.

Self-report version of The Multidimensional Anxiety Scale for Children - 2nd edition (MASC-2). The result is based on a combination of scores. Higher scores suggest greater levels of anxiety and more severe symptoms.

The parent version of the ADHD-rating scale. The result is based on a combination of scores. Higher scores on the inattention and hyperactivity/impulsivity subscales suggest more significant ADHD symptoms.

The Adaptive Behavior Assessment System, Third Edition (ABAS-III) is a comprehensive tool used to assess adaptive functioning. The result is based on a combination of scores. A higher score indicates better adaptive functioning.

The Beck Youth Self-Concept Inventory is a tool designed to assess self-concept and self-esteem in children and adolescents. A high percentile rank (above 70) indicates a strong self-concept, while a low percentile rank (below 30) suggests low self-esteem or dissatisfaction.

PedsQL Multidimentional Fatigue Scale, parent, and self-report versions is a tool designed to assess fatigue levels in children and adolescents. The result is based on a combination of scores. A higher score indicates less fatigue (better energy levels and functioning). A lower score indicates more fatigue, suggesting that fatigue is significantly affecting the child's daily activities.

If the patient is able and willing he will have the possibility to deliver a semen sample for cryopreservation of potential spermatozoa

The effects on epigenetics will be evaluation by evaluating changes in DNA methylation patterns. This will be analyzed on DNA from white blood cells by applying Illumina methylation arrays.

DNA will be analyzed using a selected set of genetic polymorphisms in target genes with established or theoretic effects on hormone production and hormone receptor sensitivity. They will be analysed either by PCR genotyping or targeted sequencing (max. 200 selected genes). SNP arrays that exclusively target common variants, and not any rare variants, will be used to determine the influence of common genetic variation on the observed associations.

RNA analysis of circulating, small, non-coding RNA will be performed as a biomarker for the circulating concentrations of reproductive hormones and for overweight.