Table 5.11.1 Open in new tab...

Table 5.11.1

Differential diagnosis of congenital adrenal hyperplasia—clinical, biochemical, and genetic characteristics

	Deficiency
Characteristic	21-hydroxylase		11β-hydroxylase	17α-hydroxylase	3β-HSD type 2	P450 oxidoreductase	Lipoid adrenal hyperplasia	P450 side chain cleavage	Aldosterone synthase	Apparent cortisone reductase
OMIM No.	+201910		#202010	#202110	+201810	#201750	^*600617	^*118485	^*124080	^*138090
Gene/protein	CYP21A2		CYP11B1	CYP17A1	HSD3B2	POR	StAR	CYP11A1	CYP11B2	H6PDH
alias	P450c21		P450c11	P450c17	3β-HSD	CPR, CYPOR		P450scc	P450aldo
Subtype	Classic	Nonclassic
Incidence	1: 10 000 to 15 000	1:500 to 1:1000	1: 100 000 to 1: 200 000	Rare	Rare	Unknown	Rare	Rare	Rare	Rare
DSD	46,XX	No	46,XX	46,XY	46,XY^a	46,XX + 46,XY^c	46,XX	46,XX	No	No
Primary affected organ	Adrenal	Adrenal	Adrenal	Adrenal, gonads	Adrenal, gonads	Adrenal, gonads, liver, all CYP type 2 expressing tissues	Adrenal, gonads	Adrenal, gonads	Adrenal	Liver, adrenal all H6PDH/HSD11B1 expressing tissues
Glucocorticoids	Reduced	Normal	Reduced	Reduced	Reduced	Reduced to normal, impaired stress response	Reduced	Reduced	Normal	Normal, but reduced tissue levels due to increased cortisol clearance
Mineralocorticoids	Reduced in SW	Normal	Increased, mainly precursors	Increased	Reduced often	Reduced to increased	Reduced	Reduced	Reduced	Normal
Sex hormones	Increased	Increased	Increased	Reduced	Reduced in males Increased in females^b	Reduced	Reduced	Reduced	Normal	Increased
Increased marker metabolite
Plasma	17OHP 21-deoxycortisol		DOC, S	Pregnenolone, Progesterone DOC, S	17OH-Pregnenolone, DHEA	Pregnenolone, progesterone, 17OHP			DOC, B 18OH-B
Urine	Pregnanetriol, 17OHpregnanolone, pregnanetriolone		THDOC, THS	THDOC, THB, Pregnenediol, pregnanediol	Pregnantriol	Pregnenediol, pregnanediol pregnanetriol, 17OHpregnanolone
PRA	Increased	Normal–mildly increased	Reduced	Reduced	Increased		Increased	Increased	Increased	Normal
Hypertension	No	No	Yes	Yes	No	No or mild	No	No	No	No
Plasma sodium	Reduced in SW	Normal	Increased	Increased	Reduced in SW	Normal	Reduced	Reduced	Reduced	Normal
Plasma potassium	Increased in SW	Normal	Reduced	Reduced	Increased in SW	Normal	Increased	Increased	Increased	Normal
Urinary salt loss	Yes	No	No	No	Yes	No	Yes	Yes	Yes	No

Skeletal malformation	No	No	No	No	No	Yes^d	No	No	No	No

	Deficiency
Characteristic	21-hydroxylase		11β-hydroxylase	17α-hydroxylase	3β-HSD type 2	P450 oxidoreductase	Lipoid adrenal hyperplasia	P450 side chain cleavage	Aldosterone synthase	Apparent cortisone reductase
OMIM No.	+201910		#202010	#202110	+201810	#201750	^*600617	^*118485	^*124080	^*138090
Gene/protein	CYP21A2		CYP11B1	CYP17A1	HSD3B2	POR	StAR	CYP11A1	CYP11B2	H6PDH
alias	P450c21		P450c11	P450c17	3β-HSD	CPR, CYPOR		P450scc	P450aldo
Subtype	Classic	Nonclassic
Incidence	1: 10 000 to 15 000	1:500 to 1:1000	1: 100 000 to 1: 200 000	Rare	Rare	Unknown	Rare	Rare	Rare	Rare
DSD	46,XX	No	46,XX	46,XY	46,XY^a	46,XX + 46,XY^c	46,XX	46,XX	No	No
Primary affected organ	Adrenal	Adrenal	Adrenal	Adrenal, gonads	Adrenal, gonads	Adrenal, gonads, liver, all CYP type 2 expressing tissues	Adrenal, gonads	Adrenal, gonads	Adrenal	Liver, adrenal all H6PDH/HSD11B1 expressing tissues
Glucocorticoids	Reduced	Normal	Reduced	Reduced	Reduced	Reduced to normal, impaired stress response	Reduced	Reduced	Normal	Normal, but reduced tissue levels due to increased cortisol clearance
Mineralocorticoids	Reduced in SW	Normal	Increased, mainly precursors	Increased	Reduced often	Reduced to increased	Reduced	Reduced	Reduced	Normal
Sex hormones	Increased	Increased	Increased	Reduced	Reduced in males Increased in females^b	Reduced	Reduced	Reduced	Normal	Increased
Increased marker metabolite
Plasma	17OHP 21-deoxycortisol		DOC, S	Pregnenolone, Progesterone DOC, S	17OH-Pregnenolone, DHEA	Pregnenolone, progesterone, 17OHP			DOC, B 18OH-B
Urine	Pregnanetriol, 17OHpregnanolone, pregnanetriolone		THDOC, THS	THDOC, THB, Pregnenediol, pregnanediol	Pregnantriol	Pregnenediol, pregnanediol pregnanetriol, 17OHpregnanolone
PRA	Increased	Normal–mildly increased	Reduced	Reduced	Increased		Increased	Increased	Increased	Normal
Hypertension	No	No	Yes	Yes	No	No or mild	No	No	No	No
Plasma sodium	Reduced in SW	Normal	Increased	Increased	Reduced in SW	Normal	Reduced	Reduced	Reduced	Normal
Plasma potassium	Increased in SW	Normal	Reduced	Reduced	Increased in SW	Normal	Increased	Increased	Increased	Normal
Urinary salt loss	Yes	No	No	No	Yes	No	Yes	Yes	Yes	No

Skeletal malformation	No	No	No	No	No	Yes^d	No	No	No	No

Masculinization of the external genitalia in females at birth is rare and if present in most cases mild, signs of increased androgens usually present later.

Steroid hormone conversion by 3β-HSD type 1 in peripheral tissues.

DSD observed in both sexes as well as normal sex-specific sexual development reported.

In majority of cases published thus far, but absence of skeletal malformations does not rule out P450 oxidoreducatase deficiency.

S,11-deoxycortisol; DOC, 11-deoxycorticosterone; B, corticosterone; THS, tetrahydrodeoxycortisol; THDOC, tetrahydrodeoxycorticosterone; PRA, plasma renin activity; SW, salt-wasting.

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