11 beta-hydroxylase Deficiency

Adrenal glands produce the hormones cortisol, aldosterone, and androgens (delta4-androstenedione and dehydroepiandrosterone). Under certain conditions, the adrenal enzymes involved in hormone production may not function properly. To compensate for this, adrenal glands may increase in volume (adrenal hyperplasia). This mechanism successfully produces some hormones, but can lead to an excess production of others.
Deficit of 11 beta-hydroxylase causes a form of Congenital Adrenal Hyperplasia (CAH). CAH encompasses a group of conditions characterized by inadequate production of essential hormones derived from cholesterol –cortisol, aldosterone or both– because of a genetic defect in one of the enzymes involved in their production. 11 beta-hydroxylase deficiency accounts for approximately 5-8% of CAH cases, and has an annual incidence of 1 in 100,000-200,000 live births, being more common in North Africa and the Middle East. 11 beta-hydroxylase deficiency is a Variantions of Sex Characteristic (VSCs)/Differences of Sex development (DSDs). 
In 11 beta-hydroxylase Deficiency, reduced cortisol production leads to an increase in adrenocorticotropic hormone (ACTH), which stimulates both cortisol production and the adrenal glands. Therefore, an accumulation of cortisol precursors are diverted towards the production of typically male sex hormones, like testosterone. Additionally, the lack of aldosterone –which helps regulate blood sodium and potassium levels– indirectly affects blood pressure regulation.
The clinical presentation of 11 beta-hydroxylase Deficiency varies depending on the severity of enzyme deficit. Approximately two-thirds of cases exhibit arterial hypertension, sometimes with low blood potassium levels (hypokalemia) and high sodium levels (hypernatraemia). Newborns with a typically female karyotype (46,XX) may show atypical genitalia, such as clitoromegaly (enlarged clitoris), fusion of the labia majora, and the presence of an urogenital sinus (a shared opening for the urinary tract and the external genitalia). Newborns with a typically male karyotype (46,XY) do not usually show unexpected genital characteristics, except for an enlarged penis in rare cases.
Partial 11 beta-hydroxylase Deficiency impacts individuals with a 46,XY karyotype with precocious puberty, while those with a 46,XX karyotype may show menstrual irregularities and hirsutism (abundant hair growth).

Genetic traits
11 beta-hydroxylase Deficiency is caused by a mutation in the CYP11B1 gene located on chromosome 8q21. To date, over 130 mutations in this gene have been found. Transmission is autosomal recessive. This means that for the gene variation to occur, it must be inherited from both parents. Individuals who have inherited the gene variation from only one parent will not exhibit it in any way, but they may still pass it on to their offspring.

Identification
Laboratory analyses reveal an increase in cortisol precursor levels and elevated androgens in the blood. The diagnostic confirmation is obtained through molecular analysis of the CYP11B1 gene.

Medical Options
The treatment for 11 beta-hydroxylase Deficiency entails administering glucocorticoids, usually hydrocortisone, to prevent further virilisation in individuals with a 46,XX karyotype and improve blood pressure values. Close monitoring of blood pressure is necessary for affected individuals. If blood pressure values are altered, antihypertensive therapy with potassium-sparing diuretics or calcium-channel blockers may be required.
According to the scientific literature, newborns 46.XX karyotype with atypical external genitalia are generally assigned female at birth and report a female gender identity. However, according to the most recent international recommendations, all partially reversible or irreversible interventions (including surgical procedures aimed at feminising or masculinising the genitals) should be postponed until the individual can give informed consent. If atypical genitalia cause distress for the individual or their family, professional multidisciplinary support and counselling should be offered. This approach aims to optimise the person's psychosocial well-being, and allow them to explore their desires and needs regarding gender-affirming treatments, including external genital feminisation surgery, which should be performed by an experienced surgical team.
Individuals assigned to the female gender at birth who then identify as male may pursue medical and/or surgical gender-affirming procedures if they feel it necessary, just like individuals without 11 beta-hydroxylase Deficiency.

Bibliography
Khattab A et al. Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Proceedings of the National Academy of Sciences of the United States of America. 2017 Mar 7;114(10):E1933-E1940. doi: 10.1073/pnas.1621082114

Further Links
Orphanet. Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency