A 5-yr old boy presents with pubic hair development. He is tall and has increased pigmentation of his genitalia and phallic enlargement. Blood pressure is 130/90 mm Hg. Measurement of which of the following hormones would be most likely to be diagnostic?
Ans. is 'd' i.e., |11-Deoxycortisol Presence of Precocious puberty in a male child and hypertension (BP of 130/80 in a 5 year old child is considered hypertension) suggests a diagnosis of congenital adrenal hyperplasia due to 11-b Hydroxylase deficiency.11-b Hydroxylase deficiency.Deficiency of 11-b hydroxylase (CYP11B1) results in decreased conversion of 11-deoxycortisol and 11- deoxycorticosterone to cortisol and corticosterone, respectively.The decrease in cortisol production causes an increase in corticotropin (ACTH) secretion. The resulting adrenal stimulation leads to excessive production of 11-deoxycortisol, 11- deoxycorticosterone, and adrenal androgens.The clinical manifestations of the disorder result from excess adrenal androgens and the mineralocorticoid actions of 11-deoxycorticosterone;11-deoxycortisol has little biological activity.Clinical manifestationsNeonates Male - Ambiguous genitalia Female - Penile enlargementChildhood (sexual precocity)Both male and female child present with sexual precocity, early pubertyClinical features that would be present irrespective of age group and sexHypertensionHypokalemiaIncreased pigmentation increased ACTHHypertension and hypokalemia is seen in most of the patients due to increase in 11 deoxycorticosterone level.Hypertension and hypokalemia differentiates it from 17a hydroxylase deficiency.Lab diagnosis * Patients with CYP11B1 deficiency have a characteristic set of hormonal findings.High serum concentrations of 11-deoxycortisol, 11-deoxycorticosterone, and the androgens dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA sulfate), androstenedione, and testosterone.Increased urinary excretion of the tetrahydro metabolites of 11-deoxycortisol and 11-deoxycorticosterone, which are normally present in trace quantities.Urinary 17-hydroxycorticosteroid excretion is high, because 11-deoxycortisol reacts in the assay for these steroids. Urinary excretion of 17-ketosteroids, most of which are androgen metabolites, is also increased.Congenital adrenal hyperplasiaCongenital adrenal hyperplasia is a group of autosomal recessive disorder characterized by deficiency of an enzyme involved in the synthesis of cortisol or aldosterone or both.Clinical manifestations * The clinical manifestations are related to the degree of cortisol deficiency and / or the degree of aldosterone deficiency. In some cases these reflect the accumulation of precursor hormones.Clinical presentation in Males21 hydroxylase deficiency (Testosterone production increased)Generally not identified in the neonatal period because the genitalia are normal Toddlers present with signs of puberty.These male neonates present at age 1-4 weeks with failure to thriveRecurrent vomitingShock17 hydroxylase deficiency, 3 b hydroxysteroid dehydrogenase deficiencyAmbiguous genitalia (because of inadequate testosterone production in first 3 months of life).Clinical presentation in Females21 hydroxylase, 11 b hydroxylase, 3 b hydroxysteroidThey have ambiguous genitalia at birth due to excess androgen production in utero.17 hydroxylase deficiencyFemales appear phenotypically female at birth but later on in life do not develop breast or menstruate absence of estrogen.Diagnosis of congenital adrenal hyperplasiaThe common feature of all the congenital adrenal hyperplasia is:- - Inadequate production of cortisol, aldosterone or both in the presence of accumulation of excess concentrations of precursor hormones.Cortisol and aldosterone deficiency is common to all congenital adrenal hyperplasia the distinguishing feature is the accumulation of excess concentration of precursor hormones.Elevated precursor in 21 hydroxylase deficiencyHigh serum concentration of 17 hydroxyprogesteroneIncreased concentration of urinary pregnanetriol (metabolite of 17 hydroxy progesterone's)Elevated precursor hormones in 11 b hydroxylase deficiencyExcess concentration of 11 deoxy cortisol and deoxy-corticosterone.Elevation in the ratio of 24 hour urinary tetra hydro-compound S to tetrahydro compound F.Both are accompanied by elevated levels of 24 hour urinary 17 ketosteroids, the urinary metabolites of adrenal androgens.Elevated precursor hormones in 3 b hydroxysteroid dehydro- genase deficiency * Abnormal ratio of -17 hydroxypregnenolone to 17 hydroxyprogesterone and- Dehydroepiandrostenedione to AndrostenedioneMore on congenital adrenal hyperplasia 21 a hydroxylase deficiencyTwo forms of this deficiency include -Salt wasting adrenogenital ismSimple Virilizing adrenogenital ismA) Salt wasting syndrome (complete lack)The salt wasting syndrome results from complete lack of 21 hydroxylase. There is no synthesis of mineralocorticoids and glucocorticoids in the adrenal cortex.Decreased mineralocorticoids causes marked sodium loss in the urine, resulting in hyponatremia, hyperkalemia, acidosis and hypotension.Because of the enzyme block, there is increased formation of 17 - hydroxyprogesterone, which is then shunted into the production of testosterone.This may cause "virilization" (pseudo-hermaphroditism) in female infants. That is (XX) Female with 21 hydroxylase deficiency develops ovaries, female ductal structures and external male genitalia.But in the male child the effect of increased testosterone will not be manifested at the time of birth. Toddlers will present with signs of puberty.The complete 21 hydroxylase deficiency or salt wasting syndrome usually comes to light only after the birth because in utero the electrolytes and fluids can be maintained by maternal kidneys.Males with this disorder comes to clinical attention 5 to 15 days later because of salt losing crisis while females comes to attention soon after the birth because of the virilization.B) Simple Virilizing adrenogenital syndrome (Partial deficiency)Occurs in individuals with partial deficiency of 21 hydroxylaseLess severe deficiency of mineralocorticoid, is sufficient for salt reabsorption, but the lowered glucocorticoid fails to cause feedback inhibition of ACTH secretion. Thus level of aldosterone is mildly reduced testosterone increased and ACTH elevated with resultant adrenal hyperplasia.11b hydroxylase deficiency -RareLeads to decreased cortisol and increased ACTH.This in turn leads to the accumulation of DOC (deoxycorticosterone) and 11 deoxy cortisol both of which are strong mineralocorticoids. This results in increased sodium retention by the kidneys and hypertension, hypokalemia.Patients also develop virilization due to androgen excess.17 a hydroxylase deficiency -Patients with deficiency of 17 hydroxylase also have impaired cortisol production, increased ACTH and secondary increased DOC.These patients, however, cannot synthesize normal amount of androgens and estrogens.This is because the gene that codes for 17 a hydroxylase is the same for the enzyme in the adrenal cortex and the gonads and the deficiency is same in both organs.Because of decreased sex hormones genotypic females develop primary amenorrhoea and fail to develop secondary sex characterize tics while genotypic males will present as pseudohermaphrodite.
Increase 17b hydroxyl progesterone
Increase cortisol
Increase aldosterone
Increase 11 deoxycortisol
Adrenal Gland