Afghanistan Endocrine Society AES CONGENITAL ADRENAL HYPERPLASIA DR

Afghanistan Endocrine Society (AES)

CONGENITAL ADRENAL HYPERPLASIA DR Mohammad Asif Aram MD(KUMS) PGD(MOPH) Internal Specialist&Diabetologist

Defination; Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis)

Most of these conditions involve excessive or deficient production of sex steroids and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults.

Symptom: of CAH vary depending upon the form of CAH and the sex of the patient Symptoms are grouped depending on the deficient hormone of the adrenal gland which include:

Due to low mineralocorticoids: vomiting due to salt-wasting leading to dehydration and my be death

Due to inadequate Androgen: functional and average sized penis in cases involving extreme virilization (but no sperm), ambiguous genitalia, in some females, such that it can be initially difficult to determine

Cortisol: is an adrenal steroid hormone that is required for normal endocrine function. Production begins in the second month of fetal life. Poor cortisol production is a hallmark of most forms of CAH.

Inefficient cortisol production results in rising levels of ACTH, which in turn induces overgrowth (hyperplasia) and overactivity of the steroid-producing cells of the adrenal cortex The defects causing adrenal hyperplasia are congenital ( present at birth).

Cortisol deficiency in CAH is usually partial, and not the most serious problem for an affected person. Synthesis of cortisol shares steps with synthesis of mineralocorticoids such as aldosterone, androgens such as testosterone, and estrogens such as estradiol,

The resulting excessive or deficient production of these three classes of hormones produce the most important problems for people with CAH. Specific enzyme deficiencies are associated with characteristic patterns of over or underproduction of mineralocorticoids or sex steroid

In all its forms, congenital adrenal hyperplasia due to 21 -hydroxylase deficiency accounts for about(9095)% of diagnosed cases of CAH. Unless another specific enzyme is mentioned, "CAH" in nearly all contexts refers to 21 -hydroxylase deficiency.

The terms "salt-wasting CAH", and "simple virilizing CAH" usually refer to subtypes of this condition. ) CAH due to deficiencies of enzymes other than 21 hydroxylase present many of the same management challenges as 21 hydroxylase deficiency, but some involve mineralocorticoid excess or sex steroid deficiency.

. . Milder degrees of inefficiency are usually associated with excessive or deficient sex hormone effects in childhood or adolescence, while the mildest form of CAH interferes with ovulation and fertility in adults.

Congenital Adrenal Hyperplasia • Classic congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with an incidence of 1 in 7, 000 -15, 000 • Non-classic CAH is less severe and effects 1 in 5001000 individuals • 90 -95% of cases are caused by deficiency of 21 hydroxylase, which catalyses the synthesis of cortisol and aldosterone from cholesterol

Cholesterol Pregnenolone 17 -hydroxypregnenolone Dehydroeplandrosterone (DHEA) Progesterone 17 hydroxyprogesterone 21 -hydroxylase Deoxycorticosterone Corticosterone Aldosterone Androstenedione (17 -OHP) 21 -hydroxylase 11 -deoxycortisol Cortisol Testosterone

21 -Hydroxylase Deficiency: 21 -OHD-CAH Classic: No or very little enzyme activity (1/15, 000 births) Nonclassic: Low enzyme activity (1/500 births) Feature: Classical: Non-classical: Prenatal virilization: Present in Females Absent Postnatal virilization: Males & Females Variable Salt-wasting: > 75% of cases Absent Cortisol Deficiency: 100% Rare

Clinical Presentation • Clinical severity depends on degree of 21 hydroxylase deficiency – Good genotype phenotype correlations • Classical CAH – Simple Virilsing: Ambiguous genitalia in females – Salt Wasting: Dehydration, vomiting and diarrhoea. If untreated can prove fatal • Non-classical CAH – Milder than classical CAH – Androgen excess can cause precocious puberty in either sex – Males are often undiagnosed/asymptomatic

Virilized Females: Adult Virilized emale: http: //psych. unn. ac. uk/users/nick/hormonespp 03/sld 023. htm

Other Findings: (1) No difference between CAH boys and control boys on interest patterns, personality, cognition, and sex orientation. (2) CAH girls are more masculine in interest patterns than control girls. (3) CAH girls have more “masculine” personality traits: more aggressive, less interested in infants, less maternal, and less empathetic than control girls. (4) CAH girls have higher spatial-visualization and spatial orientation than control girls. (5) Most CAH girls are heterosexual (c. 70%), but have a higher rate of same-sex orientation than their sisters. (6) Biggest difference between CAH and control girls is on interest patterns.

Treatment: all forms of CAH may include any of supplying enough glucocorticoid to reduce hyperplasia and overproduction of androgens of mineralocorticoids providing replacement mineralocorticoid and extra salt if the person is deficient

providing replacement testosterone or estrogen at puberty if the person is deficient additional treatments to optimize growth by delaying puberty or delaying bone maturation

Treatment Summary • Glucocorticoids which suppress ACTH, are used to reduce the levels of adrenal sex steroids in the blood • Individuals with salt wasting CAH also require mineralcorticoids and sodium chloride supplements • Surgery on virilised females • Growth monitoring to detect over and under treatment • Dexamethosone can be used to prevent/reduce prenatal virilisation. Side effects for the mother include weight gain, irritability and oedema

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