Congenital adrenal hyperplasia (CAH) Medical Assignment Help

PATHOPHYSIOLOGY

This condition, comprising six major types, results from an autosomal recessive deficiency of an enzyme in the cortisol synthetic pathways, most commonly 21- hydroxylase which occurs in about 1 in 15000 births. The 21-hydroxylase deficiency has been shown to be due to defects on chromosome 6 near the HLA-region affecting a cytochrome P450 enzyme (P450C21)’
As a result, cortisol secretion is reduced and feedback leads to increased ACTH secretion to maintain adequate cortisol- this in turn leads to diversion of the steroid precursors into the androgenic steroid pathways.
Thus, 17-hydroxyprogesterone, androstenedione and testosterone levels are increased, leading to virilization. Rarely, aldosterone synthesis is impaired with resultant salt wasting. The other forms affect l ljl-hydroxylase, 17ahydroxylase, 3f3-hydroxysteroid dehydrogenase and a cholesterol side chain cleavage enzyme.

Effects of congenital adrenal hyperplasia (21-hydroxylase deficiency) on steroid biosynthesis. Precursors and products present in excess appear in purple boxes. Those present in normal or reduced quantity appear in blue boxes.

Effects of congenital adrenal hyperplasia (21-hydroxylase deficiency) on steroid biosynthesis. Precursors and products present in excess appear in purple boxes. Those present in normal or reduced quantity appear in blue boxes.

CLINICAL FEATURES

If severe, this presents at birth with sexual ambiguity oradrenal failure. In the female, clitoral hypertrophy, urogenital abnormalities and labioscrotal fusion are common, but the syndrome may be unrecognized in the male. Some cases include salt-losing states. Precocious puberty with hirsuties is a later presentation, while some milder cases only present in adult life, usually accompanied by primary amenorrhoea. Hirsutism developing before menarche is suggestive of CAH.

INVESTIGATION

Expert advice is essential in the confirmation and differential diagnosis of deficiency.
• 17-Hydroxyprogesterone levels are increased.
• Urinary pregnanetriol excretion is increased.
• Basal ACTH levels are raised.

TREATMENT

Replacement of glucocorticoid activity and mineralocorticoid activity if deficient is as for primary hypoadrenalism (see above). Correct dosage is often difficult to establish in the child but should ensure normal 17-hydroxyprogesterone and ACTH levels while allowing normal growth; excessive replacement leads to stunting of growth. Uses and problems of therapeutic steroid therapy Apart from their use as therapeutic replacement for endocrine deficiency states, synthetic glucocorticoids are widely used for many non-endocrine conditions.
Short-term use (e.g. for acute asthma) carries little risk of significant side-effects except for the simultaneous suppression of immune responses. The danger lies in their continuance, often through medical oversight or patient default.
Long-term therapy with synthetic or natural steroids will, in most respects, mimic endogenous Cushing’s syndrome. Exceptions are the relative absence of hirsuties, acne, hypertension and severe sodium retention, as the synthetic steroids have low androgenic and mineralocorticoid activity.
Excessive doses of steroids may also be absorbed from skin when strong dermatological preparations are used but inhaled steroids very rarely cause Cushing’s syndrome, although they may cause adrenal suppression. The major hazards are detailed in Information box 16.9; in the long term many are of such severity that the clinical need for high-dose steroids should be continually and critically assessed.

Supervision of steroid therapy

All patients receiving steroids should carry a steroid card and know that:
LONG-TERM STEROID THERAPY MUST NEVER BE STOPPED SUDDENLY. Doses should be reduced very gradually, with most being given in the morning at the time of withdrawal-this minimizes adrenal suppression. Many authorities believe that ‘alternate day therapy’ produces less suppression.
DOSES NEED TO BE INCREASED in times of serious intercurrent illness (defined as presence of a fever), accident and stress. Double doses should be taken during these times.
OTHER PHYSICIANS, ANAESTHETISTS AND DENTISTS must be told about steroid therapy.

Some therapeutic uses of glucocorticoids.

Some therapeutic uses of glucocorticoids.Some therapeutic uses of glucocorticoids.

Adverse effects of corticosteroid therapy.

Adverse effects of corticosteroid therapy.

Steroid cover for operative procedures.

Steroid cover for operative procedures.

accident and stress. Double doses should be taken during these times.
OTHER PHYSICIANS, ANAESTHETISTS AND DENTISTS must be told about steroid therapy.

Steroids and surgery

Any patient receiving steroids or who has recently received them and may still be suppressed requires careful control of steroid medication around the time of surgery.

Posted by: brianna

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Endocrinology.

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