3-Hydroxysteroid dehydrogenase deficiency

Rosenfield RL, Rich BH, Wolfsdorf JI, Cassorla F, Parks JS, Bongiovanni AM, Wu CH, Shack-leton CH (1980) Pubertal presentation of congenital A5-3/ -hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab 51 345-353... 

There are three other recognised varieties of disorders leading to congenital adrenal hyperplasia, including 3/3-hydroxysteroid dehydrogenase deficiency. Patients with this defect have grossly elevated levels of 3/3-hydroxy-5-ene steroids in their plasma and urine. Complete lack of the enzyme is incompatible with life however, an incomplete deficiency has been reported [262,263] where GC-MS identification of saturated C19 and C21 steroids revealed that some enzyme activity was present in the liver. 

Elevated plasma concentrations of 17-hydroxypreg-nenolone, DHEA, and DHEAS are found in patients with 3 -hydroxysteroid dehydrogenase deficiency (see Chapter 51). Plasma concentrations of 17-hydroxyprogesterone may be elevated due to peripheral conversion of 17-hydroxy pregnenolone. The ratio of 17-hydroxypreg-nenolone to 17-hydroxyprogesterone is strikingly elevated in these patients. 

In two cases prolonged intake of relatively small amounts of licorice resulted in hypertension, encephalopathy, and pseudohyperaldosteronism (37). Both patients were highly susceptible to the adverse effects of glycyrrhizinic acid because of 11-beta-hydroxysteroid dehydrogenase deficiency. 

Boys with 17fi-hydroxysteroid dehydrogenase deficiency fail to form testosterone from androstenedione, androstenediol fi om DHEA, or estradiol from estrone in a normal manner (see Figure 53-4). At puberty, plasma concentrations of testosterone and DHT are low, and plasma androstenedione and estrone are elevated in those individuals. ... 

Classical congenital hyperplasia 21-Hydroxylase deficiency 11-Hydroxylase deficiency 3P-Hydroxysteroid dehydrogenase deficiency Adult or attenuated adrenal hyperplasia Androgen-producing adrenal tumors... 

Pang S. Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase deficiency. Endocrinol Metab Clin North Am 2001 30 81-99, vi-vii. 

Pang SY, Lerner AJ, Stoner E, Levine LS, Oberfield SE, Engel I, et al. Late-onset adrenal steroid 3 beta-hydroxysteroid dehydrogenase deficiency. I. A cause of hirsutism in pubertal and postpubertal women. 

Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CHL, Edwards CRW. Mineralocorticoid acitivity of liquorice 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet 1987 ii 821—3. 

In the 3 jS-hydroxysteroid dehydrogenase deficiency, the conversion of pregnenolone or pregnenolone derivatives to progesterone is blocked. Such a block precludes the formation of glucocortico- and mineralo-corticosteroids. Consequently, most individuals with complete dehydrogenase deficiency die in early infancy. A small number of cases have been reported in which the enzymic block is incomplete, and enough cortisol is secreted to secure survival. 

Hydroxylase DeGcIency. The 18-hydroj lase deficiency can present as infection triggered, life threatening salt-loosing state with hyperka lemia in newborns and young infants, ft is characterized by aldosterone biosyn thetic defects both in 18 hydroxlase deficiency (CMO I) and in 18 hydroxysteroid dehydrogenase deficiency (CMO If) [28]. The urinary steroid profile in 18-hy droxylase deficiency is characterized by increased excretion of free corticosterone and metabolites of corticosterone, while 18-hydroxylated corticosterone metabo lites are absent or very low. The excretion of cortisol metabolites is normal (Fig. 5). 

Hydroxysteroid Dehydrogenase DeGciency. Failure to thrive, polyuria, polydipsia, hypertension, hypokalemia, and nephrocalcinosis are the symptoms for apparent mineralocorticoid excess due to lip hydroxysteroid dehydrogenase deficiency (cortisol oxidase deficiency) and/or a steroid ring A reductase defect [31]. In the urinary steroid profile, the excretion of THE is much too low compared with the high THF, 5a-THF and free cortisol excretion [32]. 

Figure 6 Urinary steroid profile (FID) in 18-hydroxysteroid-dehydrogenase deficiency (CMO II). Male, age 5 yrs. 18-OH-THA 17-hydroxy tetrahydro-11-dehydrocorticosterone. 18 OH-THB 18-hydroxy-tetrahydrocorticosterone.

Androstenedione is the most important precursor hormone of androgens in females. Plasma levels are often increased in hirsute women. Next to 17a-hydroxy-progesterone, it is an important diagnostic parameter of 21-hydroxylase deficiency in plasma and amniotic fluid [52], A decreased ratio between testosterone and androstenedione is indicative of 17P-hydroxysteroid dehydrogenase deficiency. The first mass-spectrometrically determined concentrations of plasma an-... 

Fig. 5.1.2 Cholesterol biosynthesis branch of the isoprenoid biosynthetic pathway. Enzymes are numbered as follows 1 squalene synthase 2 squalene epoxidase 3 2,3-oxidosqua-lene sterol cyclase 4 sterol A24-reductase (desmosterolosis) 5 sterol C-14 demethylase 6 sterol A14-reductase (hydrops-ectopic calcification-moth-eaten, HEM, dysplasia) 7 sterol C-4 demethylase complex (including a 3/ -hydroxysteroid dehydrogenase defective in congenital hemidyspla-sia with ichthyosiform nevus and limb defects, CHILD, syndrome) 8 sterol A8-A7 isomerase (Conradi-Hunermann syndrome CDPX2) 9 sterol A5-desaturase (lathosterolosis) 10 sterol A7-reductase (Smith-Lemli-Opitz syndrome). Enzyme deficiencies are indicated by solid bars across the arrows...

Table 5.3.5 Steroid excretions (/,ig/24 h) and diagnostic ratios in patients with 3fi-hydroxysteroid dehydrogenase type II (3(iHSD II) deficiency... 

Bongiovanni AM (1962) The adrenogenital syndrome with deficiency of 3/ -hydroxysteroid dehydrogenase. J Clin Invest 41 2086-2092... 

Jamieson A, Wallace AM, Andrew R, Nunez BS, Walker BR, Fraser R White PC, Connell JMC (1999) Apparent cortisone reductase deficiency a functional defect in 11 /J-hydroxysteroid dehydrogenase type 1. J Clin Endocrinol Metab 84 3570-3574... 

Nikkila H, Tannin CM, New MI, Taylor NF, Kalaitzoglou G, Monder C, White PC (1993) Defects in the HSD11 gene encoding 11/J-hydroxysteroid dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11 -oxoreductase deficiency. J Clin Endocrinol Metab 77 687-691... 

E, White PC, Hewison M, Mason PJ, Connell JM, Shackleton CH, 49. Stewart PM. Mutations in the genes encoding 11 P-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat. Genet. 50. 2003 34 434-439. 

Specific defects in bile acid synthesis Cerebrotendinous xanthomatosis Intrahepatic cholestasis familial neonatal hepatitis) 3-p-hydroxysteroid dehydrogenase/isomerase deficiency A -3-oxosteroid 5-P-reductase deficiency C24 steroid 7-a-hydroxylase deficiency Peroxisomal disorders... 

Figure 51-15 Formation of steroids in patients with adrenogenital syndrome caused by 21 -hydroxylase deficiency. Bold lettering indicates steroids that are found elevated in the circulation. ACTH, Adrenocorticotropic hormone SpSDH 3p-hydroxysteroid dehydrogenase.

A deficiency of ll -hydroxylase is the second most common form of CAH, with an incidence of 1 per 100,000 births, and is associated with manifestations of virilization, elevated concentrations of plasma androstenedione and DHEA-S, and hypertension. The mineralocorticoid-induced hypertension is caused by an elevation of DOC 11-deoxycortisol concentrations are markedly raised in subjects with this enzyme defect,The major distinguishing characteristic of this disorder from 21-hydroxylase deficiency, besides the elevated plasma concentrations of 11-deoxycortisol, is hypertension elicited by the salt retention caused by increased concentrations of DOC, A deficiency of 3 -hydroxysteroid dehydrogenase-isomerase has been reported and leads to an elevation in the ratio of 17a-hydroxypregnenolone to that of 17a-hydroxyprogesterone and to an increased ratio of DHEA to androstenedione. In severe forms of this rare disorder, female infants have pseudohermaphroditism, and male infants present with incomplete masculinization. Patients with this disorder usually present in early infancy with complete adrenal insufficiency including salt wasting. A late-onset form has also been reported in patients with premature pubarche with hirsutism, acne, and menstrual irregularities. The... 

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