Virilisation due to an ovarian steroid cell tumour in a child with Turner syndrome

A 4 years and 10 months old girl had presented to a tertiary care hospital with enlarged clitoris and Tanner stage II pubic hair. Her mother had noted these changes since 2 years of age. However, there was no breast enlargement or vaginal bleeding. Trans-abdominal ultra sound scan had been normal, but ovaries were not visualised. Her serum 17-hydroxy-progesterone level was 2.8ng/ml (0.07-1.7). She was diagnosed as having non salt losing congenital adrenal hyperplasia (NSL-CAH). She had been started on hydrocortisone (10 mg/m 2 /day) and fludrocortisone.

(Key words: virilisation, Turner syndrome, steroid cell tumour) This is the story of a girl previously diagnosed to have non-salt losing congenital adrenal hyperplasia presenting with progressive virilisation in spite of adequate replacement therapy is presented.

Case report
A 4 years and 10 months old girl had presented to a tertiary care hospital with enlarged clitoris and Tanner stage II pubic hair.Her mother had noted these changes since 2 years of age.However, there was no breast enlargement or vaginal bleeding.Trans-abdominal ultra sound scan had been normal, but ovaries were not visualised.Her serum 17-hydroxy-progesterone level was 2.8ng/ml (0.07-1.7).She was diagnosed as having non salt losing congenital adrenal hyperplasia (NSL-CAH).She had been started on hydrocortisone (10 mg/m 2 /day) and fludrocortisone.
At 6 years she presented with a hoarse voice, hirsutism and acne.Her height was 127 cm (Figure 1  An androgen secreting tumour was suspected and a left oophorectomy was performed at laparotomy which also revealed a streak right ovary from which a biopsy was taken.Histology revealed an encapsulated tumour of left ovary with abundant granular eosinophillic cytoplasm and inconspicuous stromal component.Crystals of Reinke were not seen.Appearance was in keeping with a steroid cell tumour not otherwise specified, nuclear grade I with no mitotic activity.Excision appeared complete.Biopsy of streak right gonad showed fibroblastic tissue suggestive of ovarian stroma. There were no clinical features of Turner syndrome in our patient but a karyotype was done in view of the streak gonad and this was found to be 46, X, idic(X) (q22), one X chromosome being a dicentric isochromosome (Figure 2).
Fourteen days after excision of the tumour serum free testosterone level was less than 0.1 pg/ml.Virilisation gradually reduced and seven months after excision of the tumour her height was 128 cm (97 th centile) with a velocity of 3.4 cm/year (below 3 rd centile) and weight had reduced to 22.5 kg (Figure 3), confirming that the steroid cell tumour was the underlying cause of the virilization.

Figure 3 Patients weight plotted on a NCHS chart
Axillary hair had disappeared and there was a marked reduction in hirsutism and pubic hair (Tanner stage II) but the hoarse voice persisted.

Discussion
Virilising ovarian tumours are rare in children 1 .An eleven year review of endocrine manifestations of ovarian tumours had reported only one child out of 26 with virilisation which was due to a Sertoli-Leydig cell tumour.
Ovarian steroid cell tumors can be divided into different categories according to their originating cells 2 .However, the cellular origin of a large subset is uncertain, and this group has been frequently designated 'not otherwise specified'.Steroid cell tumours are rare in children 3 .These tumours commonly secrete testosterone 4 but are known to cause isosexual or heterosexual precocious pseudopuberty 3,4,5 and are thought to be benign when they occur in prepubertal children 3 .
Eleven to fifteen percent of girls with Turner syndrome have isochromosomes 6 .Turner syndrome due to 46, X, idic(X) (q22) karyotype is rare 7 .This girl did not have any dysmorphic features of Turner syndrome 8,9 but she was tall.Investigations did not reveal any cardiac or renal complications.There are other case reports of Turner syndrome patients with the same karyotype who had normal growth, development and no dysmorphism 10 while one other report indicated mild dysmorphism 7 .
Turner syndrome patients who have whole or parts of Y chromosome are known to have a higher risk of ovarian gonadoblastomas 11 .Deletions of Xq are known to be associated rarely with myelodysplastic syndromes (MDS) and refractory anaemia with excess blasts (RAEB) 12 .No other reports were found indicating increased incidence of tumours in 46, X, idic(X) (q22) karyotype.
The commonest cause for the rare manifestation of virilisation in a girl presenting in childhood is NSL-CAH.But if the clinical features are progressive with an increasing height velocity in spite of adequate replacement therapy reinvestigation and a review of the diagnosis are indicated.

Figure 1
Figure 1 Patient's height plotted on a NCHS chart.She had Tanner stage II axillary hair, Tanner stage III pubic hair without any breast development.Examination of the other systems was normal with normal blood pressure.She was re-investigated since the clinical features were progressing in spite of treatment and good compliance Results of investigations are given in table 1.

Table 1 Results of investigations Investigation Result Reference range
Trans-abdominal-ultrasound scan showed a mass arising from the left ovary.Right ovary and the adrenal glands were normal.An abdominal CT scan confirmed a well defined rounded soft tissue mass (2.94 x 2.77 cm) without calcification arising from the left ovary; there were no para-aortic lymphadenopathy or free fluid in the abdomen.