Endocrine Abstracts

JOINT3772

Introduction: Congenital adrenal hyperplasia (CAH) is due to enzyme deficiencies, most frequently of the enzyme 21-hydroxylase, leading to increased synthesis of adrenal androgens associated, in severe forms, with adrenal insufficiency. In women, this condition manifests clinically with signs of virilization or hyperandrogenism. Leydig cell tumors of the ovary are extremely rare androgen-secreting tumors, and there are very few cases described in the literature of women with CAH who developed this tumor.

Case report: We present the case of a 59-year-old woman who came to our attention for effluvium capillorum. In remote pathological history she had post-surgical hypothyroidism for benign multinodular goiter on levothyroxine replacement therapy. Menopause since 2017. Nulliparous. On hormonal examinations she presented: 17-OH-progesterone 87 ng/ml, testosterone 1.78 ng/ml, ACTH 33 pg/ml, cortisol 205 ng/ml, DHEA-S 0.7 ng/ml, 17-beta-estradiol 30 pg/ml. In light of 17-OH-progesterone values a standard ACTH stimulation test was performed with findings of: basal 17OH progesterone 15.4 ng/ml, at 30 minutes 66.9 ng/ml, at 60 minutes 85.8 ng/ml; basal DHEAS 1266 ng/ml, at 30 minutes 1224 ng/ml, at 60 minutes 1302 ng/ml. An MRI of the abdomen was also requested, which showed no findings suspected for adrenal adenomas. Genetic testing was then requested, which led to the diagnosis of 21-hydroxylase deficiency by compound heterozygosity in the CYP21A2 gene: for the classical mutation in one allele (p.Arg357Trp), for the nonclassical one in the other (p.Val282Leu). After that, the patient started suppressive corticosteroid therapy with modified-release hydrocortisone 10 mg in the evening and 5 mg in the morning resulting at control after 4 months in: ACTH <5 pg/ml, cortisol 162 ng/ml, 17-OH progesterone 6.9 ng/ml, testosterone 1.78 ng/ml, 17-beta-estradiol 44 pg/ml, DHEA-S 231 ng/ml, androstenedione 10.2 ng/ml. Due to persistence of elevated testosterone values despite optimized medical therapy, the situation was further investigated by transvaginal pelvic ultrasound, which showed a 27x25x15mm cystic formation at the right ovary. After consultation with the gynecologist and collecting the patient’s consent, hystero-annessiectomy surgery was performed: histological examination on surgical piece then revealed a stage IA ovarian Leydig cell tumor. At the last follow-up, 2 months after surgery, the patient presented a hormonal picture of normalization of testosterone levels.

Conclusions: The present case highlights the difficult differential diagnosis of hyperandrogenism in women. Moreover, although there is limited literature to support it, it lays the foundation for the association between CYP21A2 mutations and the augmented incidence of germ cell tumors.