Madhva Prasad Sarvothaman
Ambiguous genitalia at birth is a rare but challenging scenario faced by an obstetrician/ gynaecologist. An equally difficult scenario is the occurrence of virilization which causes a change of female habitus to a masculine one. Way back in the 1st century, Pliny the Elder in his magnum opus “Natural history” had described females transforming into males, as observed by himself in Africa. The basis of this is now ascertained. It is the biochemical interchangeability of the female and male hormones.
Congenital Adrenal Hyperplasia is a syndrome complex which results from the disturbances in adrenal steroidogenesis. Historically, Tilesius (1803) is believed to be the first to report a relationship between adrenal tumours and precocious puberty, and Marchand (1891) is believed to have reported the first case of pseudo-hermaphroditism in the presence of an adrenocortical hyperplasia.
The primary pathology is mutation of genes encoding enzymes involved in adrenal steroid synthesis. The most commonly affected is the 21-hydroxylase enzyme. The reduced activity of this enzyme results in deficiency of glucocorticoids and mineralocorticoids and diversion of the substrates, resulting in excessive androgen production. The classic CAH which is a result of loss-of-function mutation results in neonatal presentation. The screening test is 17-hydroxy progesterone, which is raised in CAH. The simple virilising type of CAH results in the early childhood presentation with virilisation. The late-onset non-classical CAH is the mildest form, and is an overlap with the polycystic ovarian syndrome.
Glucocorticoid supplementation is the cornerstone of the management of CAH. Management involves balancing between overtreatment which can result in hypercortisolism and undertreatment which fails to correct the hyperandrogenism. 17-hydroxyprogesterone can be a marker for adequacy of treatment of CAH, though it does not correlate with androgen levels. Recent studies have shown raised risk of infertility, cardiovascular disease and psychological issues among those with CAH. A multi-disciplinary approach to a patient with CAH is advisable. Modified release glucocorticoids, parenteral glucocorticoids given as subcutaneous infusions, chemotherapeutic agents like mitotane, androgen synthesis inhibitors like abiraterone are novel agents being investigated for this condition.
Pregnancy in a patient with risk of offspring with CAH is a complex issue. Involvement of endocrinologist is imperative. Prenatal diagnosis may be considered in those with couples having affected children. Though only those carrying female offspring need treatment, the issue of fetal sex determination raises complex questions. Prednisolone is preferred and dexamethasone is avoided; and treatment should be initiated by 8 weeks of gestation.
In this issue, we bring to you two interesting cases of CAH. One is a simple virilising form who required genitoplasty. Another is one who had undergone genitoplasty in her childhood and had 3 successful pregnancy outcomes. We are sure that the readers will enjoy reading these, and a variety of other interesting cases presented in this March issue of our journal.
The month of March brings the memory of Dr Patrick Steptoe, a British obstetrician and gynaecologist who pioneered fertility research. His 30th death anniversary is celebrated on 21st March.
Also, March 8th is celebrated as world women’s day. On this occasion, a special note of appreciation is made to all our readers, who are unceasingly committed to the improvement of health of the women of the world.