CAH AND PUBERTY - CAH is us AND PUBERTY.pdf · testes and penis along with the appearance of pubic and axillary hair are brought about by a number of mechanisms. In association with

Professor Peter Hindmarsh Professor of Paediatric Endocrinology http://www.cahisus.co.uk Divisional Clinical Director for Paediatrics and Adolescents at UCLH

"The ideas expressed are independent of the authors' affiliations. Data provided is from current literature and should always be discussed with your endocrinologist first"

PUBERTY AND CONGENITAL ADRENAL HYPERPLASIA

Written by Professor Peter Hindmarsh and Kathy Geertsma

General Puberty is defined as the acquisition of reproductive capability and is attained through a series of physical changes which have their onset in more than 50% of boys and girls by their twelfth birthday. The appearances which consist in girls of changes in the breast tissue and the appearance of pubic hair, in boys the change of the size of the testes and penis along with the appearance of pubic and axillary hair are brought about by a number of mechanisms. In association with these changes, the puberty growth spurt contributes about 30 cms in boys and 25cms in girls to the adult height of the individual. Between the sexes there is a slight difference of the timing of the puberty growth spurt, occurring quite early on in puberty around the age of eleven years in girls and later in boys, around the age of thirteen to thirteen and a half. Hormonal Control of Puberty The system regulating puberty is known as the Hypothalamic-pituitary-gonadal axis. The hypothalamus is an area of the brain which produces hormones and is situated at the centre of the base of the brain. In this system the hypothalamus secretes a hormone called Gonadotropin-releasing hormone (GnRH) in little bursts every 90 minutes which stimulates the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. These hormones appear in a pulsatile form as shown in the graphs in Figure: 1. LH and FSH are sometimes called the sex hormones. Before 8-9 years of age the system is switched off but thereafter becomes more active at night initially and then during the day and night once puberty is established. Figure: 1

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Boys—development of external genitalia

Stage 1: Prepubertal.

Stage 2: Enlargement of scrotum and testes; scrotum skin reddens and changes in texture.

Stage 3: Enlargement of penis (length at first); further growth of testes.

Stage 4: Increased size of penis with growth in breadth and development of glans; testes and scrotum larger, scrotum skin darker.

Stage 5: Adult genitalia. Girls – Breast development

Stage 1: Prepubertal.

Stage 2: Breast bud stage with elevation of breast and papilla; enlargement of areola.

Stage 3: Further enlargement of breast and areola; no separation of their contour.

Stage 4: Areola and papilla form a secondary mound above level of breast.

Stage 5: Mature stage: projection of papilla only, related to recession of areola.

Boys and Girls—pubic hair

Stage 1: Prepubertal (can see velus hair similar to abdominal wall).

Stage 2: Sparse growth of long, slightly pigmented hair, straight or curled, at base of penis or along labia.

Stage 3: Darker, coarser and more curled hair, spreading sparsely over junction of pubes.

Stage 4: Hair adult in type, but covering smaller area than in adult; no spread to medial surface of thighs.

Stage 5: Adult in type and quantity, with horizontal distribution ("feminine"). Figure: 13 Stages of Puberty What happens in CAH when the adrenal glands make too many adrenal androgens? In CAH the situation becomes quite complicated because of the additional adrenal androgen production from the adrenals in both males and females especially when control of the condition is poor. For males, poor control in CAH will lead to a situation which looks rather similar to puberty known as precocious puberty and this starts earlier than normal puberty because of the increase in adrenal androgens. These are relatively weak androgens compared to testosterone but would be sufficient to produce an increase growth rate, appearance of pubic and axillary hair and also an enlargement of the penis. However, because there is feedback of the adrenal androgen on the pituitary gland the production of LH and FSH will be switched off so that there is no increase in the size of the testes. So from a simple examination using the beads (see Figure: 5) we can tell that the androgens are from the adrenal gland because the testes are not enlarged. In girls what would happen is that the adrenal androgen production would lead to an increase of body hair and sometimes an enlargement of the clitoris. Again because LH and FSH are suppressed by the adrenal androgens there would be no estradiol production and there would be no breast development. Although people often refer to these changes as puberty, strictly speaking they are not because the LH and FSH are suppressed and the drive to the change is not from the changes in LH and FSH production but from the over production of adrenal androgens. The figure below summarises all this. Normal puberty would see the pituitary gland make LH and FSH which would tell the testes or ovaries to make testosterone or estrogen. These would then modulate the activity of the pituitary but would not suppress LH and FSH production. If instead CAH was poorly controlled then there would be a lot of adrenal androgen such as androstenedione and testosterone which will feedback on the pituitary and suppress LH and FSH and therefore switch off or suppress gonad activity, as illustrated in the diagram below, Figure: 14.

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CAH AND PUBERTY - CAH is us AND PUBERTY.pdf · testes and penis along with the appearance of pubic and axillary hair are brought about by a number of mechanisms. In association with