Society for Endocrinology UK Guidance on the Initial Evaluation of a Suspected Difference or Disorder of Sex Development (Revised 2021)

S. Faisal Ahmed; John Achermann; Julie Alderson; Naomi S. Crouch; Sue Elford; Ieuan A. Hughes; Nils Krone; Ruth McGowan; Talat Mushtaq; Stuart O'Toole; Leslie Perry; Martina E. Rodie; Mars Skae; Helen E. Turner


Clin Endocrinol. 2021;95(6):818-840. 

In This Article

Peptide Hormones

Analysis of peptide hormones is important in investigation of suspected DSD, and these hormones include the gonadotrophins, LH and FSH, anti-Müllerian hormone (AMH) and inhibin B. The absolute levels of gonadotrophins and the ratio of LH:FSH show sexually dimorphic patterns during the first year of life.[72] In addition, they are helpful in the assessment of primary hypogonadism and hypogonadotropic hypogonadism.[73] In those cases, where there is a suspicion of hypogonadotropic hypogonadism, an LHRH stimulation test may need to be considered as well as investigations that exclude other pituitary hormone deficiencies. AMH is strongly expressed in Sertoli cells from the time of testicular differentiation to puberty and to a much lesser degree in granulosa cells from birth to menopause and is widely used nowadays to assess ovarian reserve.[74] In the past, circulating AMH concentrations had to be interpreted with caution due to differences in the way immunoassays were standardized but nowadays commonly used assays show very low inter-assay variance.[75] In boys, AMH is detectable at birth at a much higher circulating concentration in boys than in girls and these concentrations rise over infancy before gradually declining at puberty. Therefore, up to date, age, sex and method-related reference ranges are necessary for interpretation.[73] In male neonates, levels that are close to the lower end of the normal range should be repeated later in infancy as they should rise further in boys with normal testes. The measurement of AMH is a powerful tool to assess Sertoli cell activity in children with suspected DSD and may also have a diagnostic utility in conditions associated with androgen deficiency or insensitivity where AMH may be raised and in hypogonadotropic hypogonadism where AMH may be low.[76] The discriminant value of AMH in cases of bilateral anorchia is so high that an undetectable AMH in such a case may avoid the need for invasive surgical exploration.[77] Inhibin B is a dimeric disulphide-linked glycoprotein consisting of two subunits (ie α and β) and like AMH, it is part of the TGFβ protein family. The main role of inhibin is the down-regulation of FSH synthesis, and like AMH, it can act as a marker of functioning testicular and ovarian tissue.[78] However, unlike AMH, the peptide hormone assays for inhibin B are not currently included in any external quality control exercise in the UK.[73] The utility of measuring circulating inhibin B maybe greatest from late childhood when unlike AMH which falls to low levels during adolescence, inhibin B levels rise higher.[76,78] Recently, INSL3 has been reported as a marker of Leydig cell activity[79] and its utility in the evaluation of conditions associated with DSD needs further exploration.