Acknowledgments br P c is expressed in

Acknowledgments
P450c17 is expressed in several steroidogenic tissues, including the adrenal cortex, the ovary, and the testes (). Thus, 17α-hydroxylase/17,20-lyase is a key enzyme required for the production of both cortisol and sex steroids. This enzyme defect blocks the synthesis of cortisol, androgens, and estrogens. Consequently, karyotypic females (46,XX) with complete combined 17α-hydroxylase/17,20-lyase deficiency have absent pubertal development, primary amenorrhea, and a lack of axillary and pubic hair and frequently develop hypertension in adolescence (). In contrast, isolated 17,20-lyase deficiency is an extremely rare condition and, to date, very few 46,XX females with this diagnosis have been reported (, ). Here, we describe the clinical characteristics and biochemical profile of a Turkish patient with an apparent isolated deficiency of 17,20-lyase (desmolase), which was associated with hypergonadotropic hypogonadism, but in whom analysis of failed to reveal a mutation. Materials and methods For the ACTH test, a venous catheter was inserted, and serum levels of several hormones were determined in blood samples taken before and at 30, 60, and 90 minutes after the IV administration of 0.25 mg ACTH (Synachten 0.25 mg ampules; Ciba-Geigy, Basel, Switzerland). For the hCG test (Pregnyl, 1,500 ampules; NV Organon Oss, The Netherlands), hCG 1,500 IU/24 hours was injected SC for 3 days and a serum sample was taken on day 4 for measurement of P, DHEA, 17-hydroxyprogesterone (17 OHPG), androstenedione, T, and E2 levels. A blood sample was taken for analysis of anti-steroid YM 022 to ovaries. Gonadotropins (FSH, LH), E2, T, and DHEAS were measured by immunochemiluminometric assay (Immulite one, Diagnostic Products; Los Angeles, CA). Progesterone, 17-hydroxyprogesterone, and DHEA levels were measured by radioimmunoassay (RIA) using commercial kits (Diagnostic Products). The androstenedione level was measured by RIA using a commercial kit (Diagnostic System Laboratories, Webster, TX). All eight coding exons of CYP17 were polymerase chain reaction (PCR) amplified using variations on primers and conditions described previously (3). The PCR reactions were purified using Exo (NEB)-SAP (USB) (exonuclease I 1 unit/μL and shrimp alkaline phosphatase 0.1 unit/μL) and sequenced directly in forward and reverse using a BigDye Terminator v1.1 cycle sequencing kit (Applied Biosystems, Warrington, UK). Sequencing was performed on a MegaBACE1000 capillary DNA sequencer (Amersham Biosciences, Little Chalfont, UK). Sequence results were analyzed both manually and automatically using Sequencher v4.1 (Genecodes, Ann Arbor, MI).
Case report A 13.5-year-old girl presented with lack of pubertal development, primary amenorrhea, and parental concern about severe growth retardation. She was born at 37 weeks' gestation by normal delivery, but with a birth weight of 2,800 g. She was the first child of nonconsanguineous parents. Family history was unremarkable. On physical examination, she was prepubertal with Tanner stage I breast development and no pubic or axillary hair (Fig. 2). She had no clinical stigmata of Turner syndrome, and her karyotype was 46,XX. Her height of 130.5 cm (−4.04 standard deviation score) was below the first percentile (midparental height, 25th percentile), but her bone age was delayed by 4.5 years (Greulich and Pyle method) (4), giving her a predicted height of 158.4 cm (between the 25th and 50th percentiles) (Bayley-Pinneau method) (5). A skeletal survey was normal, and she was normotensive (110/65 mmHg, 50th percentile for age). Pelvic ultrasound revealed a small uterus measuring 22 mm by 10 mm in diameter and enlarged ovaries (left ovary, 31.2 mm by 21.5 mm; right ovary, 43.5 mm by 27.5 mm) with multiple cysts, the biggest being 24 mm in diameter (FIGURE 1, FIGURE 2). A baseline blood screen (urea, electrolytes, calcium, phosphate, liver enzymes, full blood count), thyroid function, and adrenal magnetic resonance imaging scan were all normal, and auto-antibodies (thyroid, adrenal, ovary) were negative. However, given the finding of elevated basal gonadotropins (LH, 65 U/L; FSH, 50 U/L), further detailed endocrine investigation was undertaken. Steroid assays were performed in basal conditions, and after short ACTH (Synacthen 0.25 mg) and hCG stimulation (Table 1). ACTH stimulation produced a normal rise in P and 17-hydroxyprogesterone, but no significant rise in DHEA and androstenedione levels. Steroid concentrations in fluid aspirated from a follicular cyst are shown in Table 2. Taken together, these basal and stimulated steroid hormone levels are consistent with the diagnosis of isolated 17,20-lyase deficiency.