Clinical evaluation and Laboratory exams

The clinical evaluation plan specific to each of the Variations of Sex Characteristics (VSCs)/Differences of Sex Development (DSDs) will be described in detail in the dedicated sections. In general, from a clinical perspective, the diagnostic assessment of VSCs/DSDs includes both a physical examination and laboratory tests.

The physical examination must be detailed and aimed at detecting the right VSCs/DSDs, but also at ruling out potential abnormalities in organs and structures (e.g. heart, lungs, urinary system and skeletal system). The appearance of the external genitalia can be performed by standardised instruments such as the Prader scale (i.e., a visual scale in which the external genitalia are represented in varying degrees, from more typically female to more typically male). Internal genitalia (vagina, uterus, fallopian tubes, ovaries, considered typically female; testicles, epididymis, vas deferens, prostate, seminal vesicles, and bulbo-urethral glands considered typically male) are also studied: position, size and development are evaluated by ultrasound, MRI and, if necessary, exploratory laparoscopy (a minimally invasive surgical technique that allows organs and tissues within the abdomen and pelvis to be viewed on a monitor in high definition, by using a thin tube with a video camera at the end).

Laboratory tests are still essential, even though they have been recently overshadowed by genetic investigations. As with the clinical evaluation, the laboratory tests required for diagnosis may vary according to the VSC/DSD, and are partly dependent on the findings from the physical examination. Tests may include non-hormonal assays (e.g. blood glucose and electrolytes in suspected 21-hydroxylase deficiency), and hormonal assays, which should be carried out using specific methods such as chromatography and mass spectrometry to be considered reliable. In particular, hormone assays may include measurements of various hormones produced by the gonads (testes and ovaries), adrenal glands or tissues: testosterone, dihydrotestosterone (DHT), androstenedione, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone sulphate (DHEAS), 11beta-deoxycortisol, anti-mullerian hormone (AMH), luteinising hormone (LH), follicle-stimulating hormone (FSH) and adrenocorticotropic hormone (ACTH). These assessments can be combined with so-called 'dynamic tests' to evaluate hormone synthesis by the gonads and adrenal glands.

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