17α-Hydroxylase deficiency syndrome associated with bilateral streak gonads and impaired development of Müllerian ducts derivatives

Abstract

We report severe 17\g=a\-hydroxylase deficiency in a 17 year-old black girl with 46,XX genotype. The diagnosis was suspected because of primary amenorrhoea, absence of sexual maturation, hypertension and hypokalaemia with renal potassium wasting. Endocrine investigation revealed low basal levels of all steroid hormones which require 17\g=a\-hydroxylation for biosynthesis (i.e. glucocorticoids, androgens and oestrogens). No increase in their basal levels was seen following adrenal stimulation, indicating a severe block. Plasma concentrations of ACTH, FSH and LH were elevated as were progesterone, 11-deoxycorticosterone and corticosterone. Plasma renin activity was suppressed and aldosterone levels were very low. After 4 months of glucocorticoid replacement therapy, aldosterone was still low, even though the suppression was otherwise effective. Our case is unusual because bilateral streak gonads and impaired development of M\l=u"\llerianducts derivatives were also present. To our knowledge, a similar case has never been reported before. Steroid 17a-hydroxylation is an obligatory step in the biosynthesis of glucocorticoids, androgens and oestrogens ( Table 1). The 17a-hydroxylase defi¬ ciency syndrome (17-OHDS) is a very rare entity, first described by Biglieri et al. (1966) in a female patient and by New (1970) in a male patient. To date, no more than 25 patients have been reported. We report a female patient presenting typical signs of severe 17cx-hydroxylase deficiency, associated with bilateral streak gonads and impaired develop¬ ment of Müllerian duct derivatives. Case ReportThe patient was first seen at the age of 17 years because of primary amenorrhoea and complete lack of secondary sex development. She had been born after a normal pregnancy and delivery, and her infancy and childhood were uneventful. Her parents are not related and no family history of endocrine disease was found.Physical examination showed a black girl, 162 cm in height and 55 kg in weight. Breasts were undeveloped and no pubic or axillary hair was present. There was no webbing of the neck nor cubitus valgus. External geni¬ talia were those of an immature female. The vagina was short. On rectal examination, the uterus and the internal genitalia were not detected. The blood pressure was 170/120 mmHg in both arms and remained unchanged in the upright position. This hypertension was well tolerated.The bone age was determined to be 12 years. Films of the skull were normal. Films of the chest revealed a posteroinferior mediastinal ovoid mass. This mass showed a cystic appearance on CT-scan. The sodium was 143 mmol/1, potassium 3.2 mmol/1, chloride 103 mmol/1, bicarbonate 28 mmol/1, creatinine 62 u.mol/1, glucose 3.88 mmol/1, calcium 2.34 mmol/1, phosphorus 1.67 mmol/1 and alkaline phosphatase 191 IU/1. The urinary daily 1 To whom requests for reprints should be addressed. Service d'Endocrinologie Métabolisme, Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75013 Paris

Bases Moleculares da Hiperplasia Adrenal Congênita

“…A deficiência dos esteróides gonadais, por sua vez, determina a ausência de desenvolvimento dos caracteres sexuais secundários no paciente 46XX ou presença de pseudohemafroditismo masculino. Alguns aspectos relacionados à fisiopatologia da HAC por D17OH ainda não estão totalmente elucidados, como: 1) níveis elevados de aldosterona em alguns pacientes japoneses (76); 2) os possíveis casos de deficiência parcial da enzima, com genitália ambígua, menarca, níveis pressóricos ou de potássio dentro da normalidade; 3) definição clínica e laboratorial da deficiência isolada de 17,20 liase (77); e 4) a associação de achados fortuitos como restos de tecido adrenal em testículo (78), mielolipoma (79), adenoma adrenal (80), gônadas disgenéticas e desenvolvimento incompleto de ductos müllerianos (81).…”

The immunocytochemical heterogeneity of silent pituitary adenomas

“…Blood was taken for the measurement of PRL, GH, ACTH and/or cortisol, LH, testosterone, estradiol-17ß, FSH, TSH and free T4 index, and 24-h urine was collected to determine 17-ketosteroids, 17-hydroxycorticosteroids and free cortisol by use of the previously described methods(Savoie Sc Massin 1970;Turpin et al 1980;de Gennes et al 1982).Pituitary tumours were obtained during surgery by transsphenoidal route in 35 patients and by transcranial route. The tumour tissues were fixed in Bouin-Hol-…”