AFJOG

African Journal of Obstetrics and Gynaecology | Volume 2 | Issue 2 | 2024 | 33 CASE REPORT African Journal of Obstetrics and Gynaecology | Volume 2 | Issue 2 | 2024 | Polycystic Ovary Syndrome: An update from the 2023 international guideline A Computer Assisted Tomography Scan revealed evidence of bilateral adrenal hyperplasia with no discrete adrenal lesions. The kidney, ureter, bladder, abdominal and pelvic organs were normal. Her karyotype was reported as 46,XX. At that stage our differentials included CAH, however the low 17-OHP made this diagnosis uncertain. Following a multidisciplinary team meeting involving general endocrinologists, reproductive endocrinologists, paediatric endocrinologists and chemical pathologists, a recommendation was made to repeat the test with diluted samples. All tests were performedusing theBeckmanCoulter 17α-hydroxyprogesterone (REF 1452) radioimmunoassay (RIA) kit in the same laboratory. 17-OHP samples were frozen and batched for monthly analysis or when 20 to 30 samples were accrued, as was routine practice in the laboratory. As the original sample was not available, a repeat sample for 17OHP was collected from the patient and the result was elevated beyond the upper limit of detection (>115nmol/L). This necessitated sample dilution (1:10) and the final result was to 454nmol/L. Additionally, 11-deoxycortisol was elevated, 43.5nmol/L (reference interval <21.8nmol/L). Results of the Adrenocorticotrophic Hormone (ACTH) (0.25mg) Stimulation Test are presented in Table 1 below. There was no cortisol response after ACTH stimulation. Table 1: ACTH stimulation test Time (minutes) Cortisol (nmol/L) 17-OHP (nmol/L) DHEAS (umol/L) Testosterone (nmol/L) ACTH (pmol/L) - 15 (8.40am) No results: sample rejected. Hemolysed 0 150 Invalid result hemolysed 17.9 15.5 85.1 +20 103 369 13.5 13.4 +60 125 374 15.3 15.2 Lab Specific Reference Interval : Cortisol: Morning (06:00-10:00) 133 - 537 nmol/L; Afternoon (16:00- 20:00) 68 - 327 nmol/L 17-OHP: 1.1-11.1 nmol/L DHEAS: 1.8-10.0umol/L Testosterone: 0.3-1.7 nmol/L ACTH: 1.6-13.9 pmol/L 11-deoxycortisol was not routinely measured during the ACTH stimulation test in our unit, while 17α-hydroxypregnenolone testing was not available on our laboratory platform at the time. Due to unequivocal elevation of 17-OHP, a diagnosis of CAH due to 21OHD was made. The patient expressed a desire to retain female gender identity and to have genital reconstructive surgery in the future. Treatment was commenced with hydrocortisone 10mg am, 5mg at noon and 5mg at 4pm; and premarin 0.3mg once daily. At review after 6 months of treatment, the breasts had developed to Tanner stage III. However, the patient had defaulted premarin and hydrocortisone for almost a month due to lack of supplies at her local hospital. Her blood pressure measurements and serum electrolytes at follow-up visits remained normal. Hormone profiles showed appropriate adrenal response to hydrocortisone therapy and then a relapse after defaulting glucocorticoid therapy (Table 2). Table 2: Hormone profile at subsequent visits Time from diagnosis 17-OHP (nmol/L) DHEAS ( umol/L) Testosterone (nmol/L) ACTH (pmol/L) Estradiol (pmol/L) 4months 95.0 4.4 3.0 14.8 5 months 25.4 4.8 Test not processed erroneously 269 8months a Sample inadequate for analysis 11.0 9.3 609 Lab Specific Reference Interval : 17-OHP: 1.1-11.1 nmol/L DHEAS: 1.8-10.0umol/L Testosterone: 0.3-1.7 nmol/L ACTH: 1.6-13.9 pmol/L Estradiol Follicular phase: 45 - 854 pmol/L, Ovulation phase: 151 - 1461 pmol/L, Luteal phase: 82 - 1251 pmol/L a Patient had defaulted hydrocortisone She had experienced light bleeding over four consecutive days in the preceding month. No medication related adverse events were reported. Hydrocortisone and premarin were continued. Provera 5mg from day 16 to 25 of each menstrual cycle was added. Adherence to treatment was emphasized. She was uncertain about future fertility plans. We plan to refer her to a surgical team with experience in reconstructive surgery for DSD when she requests for it, as well as a psychologist and social worker for psychological support. DISCUSSION We present a female patient with CAH secondary to 21OHD and possible 11βHD, who was born with ambiguous genitalia, experienced premature adrenarche and subsequently presented at 18 years of age with absent thelarche and primary amenorrhoea. The specific enzyme defect was mystifying following a falsely low 17-OHP level on initial screening. A repeat 17-OHP assay on a diluted specimen and an ACTH stimulation test clarified the diagnosis. She was treated with hydrocortisone, premarin and provera, while awaiting reconstructive surgery. The Endocrine Society recommends that baseline screening 17-OHP be performed in the follicular phase before 8am by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in suspected cases (3) . A 17-OHP level of <6nmol/L excludes CAH secondary to 21OHD, a value>30nmol/L is diagnostic, while a value of 6-30nmol/L mandates an ACTH stimulation test (3) . Inaccurate results can be caused by (i) pre-analytical factors related to the patient’s physiological and medical condition, and sample collection; (ii) analytical errors related to the type of assay used, potential interferences and specimen handling; and (iii) post-analytical factors related to the handling and dissemination of results. Pre-analytical errors contribute to more than half of errors in laboratory diagnosis (5) . Timing of the blood test within the follicular phase prevents false positive results due to physiological elevation of progesterone in the luteal phase. This was not relevant in our patient as she had not yet experienced menarche. Diurnal variation could not have affected the result because the sample was collected at 8.10am.