Longer term outcome in females with congenital adrenal hyperplasia (CAH): the Cardiff experience.
OBJECTIVE
The outlook for fertility and attaining full adult height is poor in women with congenital adrenal hyperplasia. Such outcomes have followed treatment regimes with variable ages at onset, compliance rates and monitoring. We review final height, vaginal anatomy, ovulation rates and fertility in a group of adult females with the disease.


METHODS
Sixteen adult females first diagnosed in infancy or early childhood were reviewed (age range 17-33 years; 11 with salt-wasting disease; five with simple virilizing disease). Case note and clinical review were combined with daily saliva progesterone and weekend 17-hydroxyprogesterone estimation in three consecutive menstrual cycles in a subgroup of eight patients in the ovulation study.


METHODS
Daily saliva progesterone concentrations were transformed into a cumulative sum curve using a computer program. T95 (defined as the number of days from the start of the luteal phase saliva progesterone rise, in which 95% of total saliva progesterone for the menstrual cycle was obtained) and log C95 (where C95 was defined as 95% of total saliva progesterone for the same cycle) were plotted for each cycle on a boundary diagram obtained from a normal reference population. Weekend saliva 17-hydroxyprogesterone concentrations were compared with published nomograms.


RESULTS
The majority of patients attained a final height below the parental target. Mean standard deviation scores (+/-SEM) and ranges were -1.49 (+/-0.34) and -4.2 to 0.8 for the patients and -0.38 (+/-0.24) and -1.89 to 0.97 for their parents. Of the combined group two-thirds had regular menses and one-third hirsutism; 94% had reconstructive genital surgery with 50% requiring second procedures; 77% had an adequate vaginal introitus (of them 84% in the salt-wasting group and 75% in the simple virilizing group were sexually active). Three of five patients with salt-wasting disease and 2/3 with simple virilizing disease who had both an adequate introitus and were sexually active conceived, resulting in eight pregnancies. In the ovulation study, a 40% ovulation rate was observed with good correlation between plasma testosterone concentrations and degree of control as assessed by weekend 17-hydroxyprogesterone concentrations.


CONCLUSIONS
Our study highlights the potential for improved fertility in female patients with congenital adrenal hyperplasia, who are treated early, comply with long-term treatment and have adequately reconstructed external genitalia. Attaining full adult height potential remains a problem.
Premawardhana
L D
LD
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Hughes
I A
IA
Read
G F
GF
Scanlon
M F
MF
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D000328:Adult; D001827:Body Height; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D005298:Fertility; D005438:Fludrocortisone / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008901:Mineralocorticoids / Q000627:therapeutic use; D010060:Ovulation; D011247:Pregnancy; D011374:Progesterone / Q000032:analysis; D012463:Saliva / Q000737:chemistry; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome; D014621:Vagina / Q000473:pathology / Q000601:surgery
D005938:Glucocorticoids; D008901:Mineralocorticoids; D013739:Testosterone; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D003907:Dexamethasone; D005438:Fludrocortisone