Congenital Adrenal Hyperplasia in Adults: A Review of Medical, Surgical and Psychological Issues

Cara Megan Ogilvie; Naomi S. Crouch; Gill Rumsby; Sarah M. Creighton; Lih-Mei Liao; Gerard S. Conway

Disclosures

Clin Endocrinol. 2006;64(1):2-11. 

In This Article

Adult Male Issues

Until recently, treatment of adult males with CAH has often been limited to mineralocorticoid and glucocorticoid replacement in severe cases to alleviate obvious deficiencies. Indeed, glucocorticoid treatment for nonsalt-wasting CAH men was often stopped after final height had been achieved. However, it is now apparent that long-term control of CAH in men is required to preserve fertility.

Jaaskelainen et al.[79] considered fecundity rates in men with CAH. In Finland, the men with CAH have a child rate of 0·07, significantly less than the average for the Finnish male population of 0·34. The authors suggest that psychological support for men with CAH is as important as for their female counterparts.

There have been a series of anecdotal reports of testicular abnormalities in male patients with CAH.[59] Recently, these abnormalities have been correlated with fertility and glucocorticoid suppression ( Table 3 ). Cabrera et al.[60] found semen analysis abnormalities in CAH men with normal testes. This report included two men who had successfully fathered pregnancies but subsequently became infertile after developing nodular testes. There was no significance difference in androgen levels in the men with testicular abnormalities and those without.

Stikkelbroeck et al.[61] found large palpable tumours were associated with low testosterone and normal LH levels; however, normal FSH levels did not reflect a normal semen analysis. In this report adrenal rest tissue is more likely to be present and to be larger in men who are heterozygous or homozygous for the deletion or conversion of the CYP21 gene. Repeat scanning of the subjects 2·6 years later showed a quantifiable relationship between glucocorticoid replacement and alteration in tumour size.[62]

Ultrasound examination has the same sensitivity for testicular masses as magnetic resonance imaging (MRI).[63] In most centres ultrasound is more accessible than MRI and therefore has become the investigation of choice for possible adrenal rest tissue. Ultrasound findings include hypoechoic lesions with hyperechoic reflections. Masses are often adjacent to the mediastinum testis.[61] Should testis sparing surgery be required, then MRI may be valuable for tissue margin delineation.[64]

When men with CAH present with testicular masses, concerns about possible malignancy arise immediately, but neither ultrasound nor MRI can differentiate between adrenal rest tissue and malignancy. [64] In one study, 18% of young males presenting with bilateral testicular masses to urology were found to have undiagnosed CAH.[65] In patients with known CAH, adrenal rest tissue can be clinically differentiated from Leydig cell tumours as it is more often bilateral, occurs in men who show evidence of poor adrenal suppression and the tumour regresses with increased glucocorticoid suppression.[64] If the mass is located near the mediastinum testis and does not show distortion of testicular contour then it is more likely to be an adrenal rest.[63] The differential diagnosis of malignancy needs to be remembered and, if in doubt, a biopsy needs to be considered. A case of Leydig cell malignancy has been reported in a male with salt-wasting CAH.[66] The diagnosis was made on clinical grounds as histology was difficult to differentiate from adrenal rest tissue.

Testicular sparing surgery has been suggested as the treatment of nonresponsive adrenal rest tissue,[64] although the effectiveness of this procedure for preservation of spermatogenesis is not clear.

Uncontrolled adrenal androgen secretion in men with CAH can result in increased aromatization of androgen to oestrogen. Oestrogen feeds back to the pituitary gland to cause gonadotrophin suppression.[67,68] Some men with CAH have hypogonadotrophic hypogonadism and small testes and this picture reverses with increased glucocorticoid suppression as androgen and oestrogen levels decrease and fertility is restored.[69] An example of oligospermia reversal with glucocorticoid treatment, and related biochemistry, is presented in Fig. 1.

Testicular response to glucocorticoid in a 26-year-old man with CAH who presented with primary infertility and oligospermia. He had been diagnosed with CAH at 6 months because of his family history of two affected brothers. Glucocorticoid treatment was stopped at age 16 years on achievement of final adult height. On restarting glucocorticoid, androgen and 17-hydroxyprogesterone levels dropped and LH and testicular size improved. The subject's partner conceived 5 months later and then went on to have two further pregnancies.

The natural history of fertility in men with CAH is still unclear. However, although such information is lacking it is desirable for all men with CAH for whom future fertility is a concern to have a testicular ultrasound, the timing of which is unknown but should probably begin after puberty and, if normal, be repeated on a 3to 5-yearly basis. Evidence of adrenal rest tissue can be a clinical indication for aggressive glucocorticoid treatment even in simple virilizing CAH; it is likely that such rest tissue causes oligospermia and subfertility and it is possible for adrenal rest tissue and semen abnormalities to respond to such suppression. The absence of adrenal rests with or without normal biochemistry cannot predict normal semen analysis. Therefore, routine semen analysis should be available for men with CAH. If glucocorticoid suppression is unsuccessful then testis sparing surgery should be considered and malignancy ruled out. Until we obtain more information it may be prudent to offer semen preservation to men with CAH.

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