The analysis of 17-hydroxyprogesterone is 1 of the 3 analytes along

with cortisol and androstenedione, that constitutes the best screening

test for congenital adrenal hyperplasia (CAH), caused by either 11- or

21-hydroxylase deficiency.

Analysis for 17-hydroxyprogesterone is also useful as part of a

battery of tests to evaluate females with hirsutism or infertility.

Both can result from adult-onset CAH.

Congenital adrenal hyperplasia (CAH) is caused by inherited defects

in steroid biosynthesis. The resulting hormone imbalances with

reduced glucocorticoids and mineralocorticoids and elevated

17-hydroxyprogesterone (OHPG) and androgens can lead to life-

threatening, salt-wasting crisis in the newborn period and incorrect

gender assignment of virtualized females. Adult-onset CAH may

result in hirsutism or infertility in females.

The adrenal glands, ovaries, testes, and placenta produce

OHPG. It is hydroxylated at the 11 and 21 position to produce cortisol.

Deficiency of either 11- or 21- hydroxylase results in decreased cortisol

synthesis, and feedback inhibition of adrenocorticotropic hormone (ACTH)

secretion is lost. Consequent increased pituitary release of ACTH

increases production of OHPG. But, if 17-alpha-hydroxylase (which

allows formation of OHPG from progesterone) or 3-beta-ol-dehydrogenase

(which allows formation of 17-hydroxyprogesterone formation from

17-hydroxypregnenolone) are deficient, OHPG levels are low with

possible increase in progesterone or pregnenolone respectively.

OHPG is bound to both transcortin and albumin and total OHPG is

measured in this assay. OHPG is converted to pregnanetriol, which

is conjugated and excreted in the urine. In all instances, more specific

tests are available to diagnose disorders or steroid metabolism than

pregnanetriol measurement.

Most (90%) cases of CAH are due to mutations in the steroid

21-hydroxylase gene (Cyp21). CAH due to 21-hydroxylase

deficiency is diagnosed by confirming elevations of OHPG

and androstenedione (#9709 "Androstenedione, Serum")

with decreased cortisol (#9369 "Cortisol, Serum, LC-MS/MS").

By contrast, in 2 less common forms of CAH, due to

17-hydroxylase or 11-hydroxylase deficiency, OHPG and

androstenedione levels are not significantly elevated and

measurement of progesterone (#8141 "Progesterone, Serum")

and deoxycorticosterone (#90134 "Deoxycorticosterone [DOC],

Serum"), respectively, are necessary for diagnosis.

#87815 "Congenital Adrenal Hyperplasia (CAH) Profile for

21-Hydroxylase Deficiency" allows the simultaneous

determination of OHPG, androstenedione, and cortisol.

 Children

                                            Preterm infants:

                                            Preterm infants may exceed 630 ng/dL,

                                            however, it is uncommon to see levels

                                            reach 1,000 ng/dL.

                                            Term infants:

                                            0-28 days:  <630 ng/dL

                                            Levels fall from newborn (<630 ng/dL) to

                                            prepubertal gradually within 6 months.

                                            Prepubertal males:  <110 ng/dL

                                            Prepubertal females:  <100 ng/dL 

Adults

                                            Males:  <220 ng/dL

                                            Females

                                                Follicular:  <80 ng/dL

                                                Luteal:  <285 ng/dL

                                                Postmenopausal:  <51 ng/dL

Note:     For pregnancy reference ranges, see clinical reference:

                  Soldin OP, Guo T, Weiderpass E, et al:  Steroid hormone

                  levels in pregnancy and 1 year postpartum using isotope

                  dilution tandem mass spectrometry. Fertil Steril 2005

                  Sept;84(3):701-710

Diagnosis and differential diagnosis of CAH always requires the

measurement of several steroids. Patients with CAH due to steroid

21-hydroxylase gene (Cyp21) mutations usually have very high

levels of androstenedione, often 5-fold to 10-fold elevations. OHPG

levels are usually even higher, while cortisol levels are low or

undetectable. All 3 analytes should be tested.

In the much less common Cyp11A1  mutation, andostenedione

levels are elevated to a similar extent as in Cyp21 mutation, and

cortisol is also low, but OHPG is only mildly, if at all, elevated.

In the also very rare 17-alpha-hydroxylase deficiency, androstenedione,

all other androgen-precursors (17-alpha-hydroxypregnenolone,

OHPG, dehydroepiandrosterone sulfate [DHEA-S]), androgens

(testosterone, estrone, estradiol), and cortisol are low, while

production of mineral corticoid and its precursors, in particular

progesterone, 11-deoxycorticosterone, and 18-hydroxycorticosterone,

are increased.

The goal of CAH treatment is normalization of cortisol levels and

ideally also of sex-steroid levels. Traditionally, OHPG and urinary

pregnanetriol or total ketosteroid excretion are measured to guide

treatment, but these tests correlate only modestly with androgen

levels. Therefore, androstenedione and testosterone should also

be measured and used to guide treatment modifications. Normal

prepubertal levels may be difficult to achieve, but if testosterone

levels are within the reference range, androstenedione levels of

up to 100 ng/dL are usually regarded as acceptable.

At birth the hypothalamic-pituitary-adrenal axis and the

hypothalamic-pituitary-gonadal axis are activated and adrenal

and sex steroid levels are high. In pre-term infants the elevations

can be even more pronounced due to illness and stress. As a

result, preterm infants may occasionally have OHPG levels of up

to 1,000 ng/dL. Term infants (0-28 days) will have levels <630 ng/dL.

These then fall over the following 1 to 6 months to prepubertal levels

of <110 ng/dL (males) and <100 ng/dL (females).

1.   Therrell BL:  Newborn screening for congenital adrenal hyperplasia.

      Endocrinol Metab Clin North Am 2001;30(1):15-30

2.   Bachega TA, Billerbeck AE,  Marcondes JA, et al:  Influence of different

      genotypes on 17-hydroxyprogesterone levels in patients with non-

      classical congenital adrenal hyperplasia due to 21-hydroxylase

      deficiency. Clin Endocrinol 2000;52(5):601-607

3.   Von Schnaken K, Bidlingmaier F, Knorr D:  17-hydroxyprogesterone,

      androstenedione, and testosterone in normal children and in

      prepubertal patients with congenital adrenal hyperplasia. Eur J

      Pediatr 1980;133(3):259-267

4.   Sciarra F, Tosti-Croce C, Toscano V:  Androgen-secreting

      adrenal tumors. Minerva Ednocrinol 1995;20(1):63-68

5.   Collett-Solberg PF:  Congenital adrenal hyperplasia:  from

      genetics and biochemistry to clinical practice, part I. Clin Pediatr

      2001;40(1):1-16

6.  Soldin OP, Guo T, Weiderpass E, et al:  Steroid hormone levels

      in pregnancy and 1 year postpartum using isotope dilution tandem

      mass spectrometry. Fertil Steril 2005 Sept;84(3):701-710