Xiang et al. BMC Endocrine Disorders (2020) 20:144 https://doi.org/10.1186/s12902-020-00625-1 CASE REPORT Open Access Flash glucose monitoring system was applied to cortisol treatment for a patient with congenital adrenal hyperplasia and 17α-hydroxylase deficiency Chenyu Xiang1†, Minmin Han1,2†, Yi Zhang3, Jianhong Yin1,Li’e Pei1, Jing Yang1* and Yunfeng Liu1* Abstract Background: Congenital adrenal hyperplasia (CAH) with 17α-hydroxylase deficiency is a rare disease; patients often require lifetime cortisol treatment. In this case report, we presented a patient with CAH and 17α-hydroxylase deficiency, who was previously misdiagnosed as having primary aldosteronism. Furthermore, the flash glucose monitoring system (FGMS) was used to ascertain a suitable cortisol therapeutic regimen for this patient. Case presentation: A 29-year-old woman presented with sex dysgenesis, hypertension and hypokalaemia. She had been diagnosed with primary aldosteronism at a local hospital. The re-measured aldosterone level in our hospital was below the normal range after antihypertensive medication adjustment, suggesting that the primary aldosteronism was a misdiagnosis. The patient was finally diagnosed as having CAH with 17α-hydroxylase deficiency according to the endocrine profile, adrenocorticotropic hormone stimulation test, and genetic analysis. Then, the patient was recommended cortisol treatment, during which the endocrine profile, blood pressure, plasma potassium level, and blood glucose level were observed to ascertain a suitable dosage. The FGMS was used to monitor blood glucose level, which indicated that the patient’s glucose metabolism was maintained normally under the final treatment dosage. Conclusion: The misdiagnosis might have been because of the effects of the antihypertension medications on aldosterone and renin levels. The final dosage of cortisol treatment achieved a normal endocrine profile, while maintaining the homeostasis of blood glucose level, plasma potassium level and blood pressure. FGMS may be an effective method to ascertain a suitable cortisol therapeutic regimen for patients with CAH and 17α-hydroxylase deficiency. Keywords: 17α-hydroxylase deficiency, Primary aldosteronism, Misdiagnosis, Cortisol treatment, Flash glucose monitor system * Correspondence: [email protected]; [email protected] †Chenyu Xiang and Minmin Han contributed equally to this work. 1Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan 030000, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Xiang et al. BMC Endocrine Disorders (2020) 20:144 Page 2 of 6 Background hydrochlorothiazide. Laboratory tests suggested an in- Congenital adrenal hyperplasia (CAH) is an autosomal re- creased aldosterone to renin ratio (ARR) and aldosterone cessive hereditary disease, which results from mutations of level (Table 1). A computed tomography scan revealed the genes that encode the enzymes participating in the hyperplasia in the left adrenal gland. The patient was di- steroidogenesis. These enzymes involving in steroidogenic agnosed with PA based on the hypertension, hypokal- process mainly include 21-hydroxylase, 11β-hydroxylase, aemia, increased ARR and adrenal hyperplasia, and and 17α-hydroxylase. While 21-hydroxylase deficiency is discharged with antihytention drugs and potassium the most common cause of the CAH [1], 17α-hydroxylase supplementation. deficiency accounts for very few cases [2]. In December 2018, the patient returned to our hos- 17α-hydroxylase is responsible for the biosynthesis of pital for extensive examination. The results of the exam- cortisol and sex hormones; its deficiency results in defi- ination revealed that the patient had no secondary ciencies of cortisol and sex hormones, accumulation of female sexual characteristics; the patient reported no steroid precursors proximal to the blocks, and compensa- menstruation during adolescence. Further examination tory hypersynthesis of mineralocorticoids. As a result of revealed the patient had an infantile vulva and absence the mineralocorticoid effect of 11-deoxycorticosterone of breast development, pubic hair, or auxiliary hair. Her and corticosterone, the activity of the renin-angiotensin- blood pressure was 154/98 mmHg; a medical history in- aldosterone system activity is suppressed; therefore, low terrogation indicated she had suffered hypertension and aldosterone level is observed in the patients with 17α- hypokalaemia since she was 13 years old. hydroxylase deficiency. Concurrently, cortisol and sex hor- The results of subsequent laboratory panels are pre- mones deficiencies lead to increased adrenocorticotropic sented in Table 2. The corticosterone level increased re- hormone (ACTH) and gonadotropic hormone levels via markably, and the progesterone level was higher than the negative feedback system. Adrenal hyperplasia occurs the normal value; oestradiol and testosterone levels were as a result of excessive secretion of ACTH [3]. low; and the plasma potassium concentration was ap- In female patients, 17α-hydroxylase deficiency is char- proximately within the normal range for a patient acterized by primary amenorrhea and sexual infantilism. treated with a potassium supplement. Considering that In those male patients, they present with female genitalia arotinolol, valsartan, spironolactone, and hydrochlorothi- and tend to be brought up as female. Patients of both azide might affect the ARR result, we re-examined the sexes present with hypertension and hypokalaemia [4]. ARR more than 14 days after the gradual withdrawal of Lifetime cortisol replacement is the recommended thera- these medications. At this point, the aldosterone level peutic regimen for these patients. was below the normal, and the revalued ARR was in Herein, we report the case of a patient misdiagnosed contrast to the value observed during her last with primary aldosteronism (PA), and subsequently diag- hospitalization (Table 1). In addition, we assessed the nosed as having CAH with 17α-hydroxylase deficiency. patient’s adrenal function. After performing an overnight Flash glucose monitoring system (FGMS, FreeStyle 1 mg dexamethasone suppressing test (DST), ACTH and Libre, Abbott Laboratories) was used to observe glucose cortisol levels were suppressed. Furthermore, an ACTH metabolism in this patient before and after cortisol treat- stimulation test was performed. The patient was injected ment to ascertain a suitable dosage. intravenously with 1 μg ACTH; blood samples were col- lected at baseline, after 30 min, 1 h, 2 h and 3 h to meas- Case presentation ure the cortisol level. The stimulated cortisol level did A 29-year-old woman was admitted to our hospital with not increase. hypertension and hypokalaemia. In October 2018, the Based on the high levels of ACTH and corticosterone, patient had visited her local hospital with symptoms of low levels of cortisol and aldosterone, abnormal sex hor- hypertension and fatigue. During admission, her blood mone profile, combined with the results of the ACTH pressure reached 220/120 mmHg. Immediately, antihy- stimulating test and 1 mg DST, we conceived a diagnosis pertension medications were prescribed, specifically, aro- of CAH with 17α-hydroxylase deficiency. Blood samples tinolol, valsartan and amlodipine, spironolactone, and were collected for genetic analysis and informed consent Table 1 Comparison of two ARR evaluations ARR evaluation Our hospital Local hospital Normal range PRA upright (ng/ml/h) 0.01 0.14 0.93–6.56 Aldosterone upright (pg/ml) 59.63 299.16 65–295 PRA recumbent (ng/ml/h) 0.01 0.10 0.05–0.79 Aldosterone recumbent (pg/ml) 40.42 230.70 59.5–173 Xiang et al. BMC Endocrine Disorders (2020) 20:144 Page 3 of 6 Table 2 Laboratory examinations in our hospital desired level with amlodipine besylate 5 mg once daily, Laboratory examinations Measured value Normal range although unsatisfactory blood pressure occurred transi- ACTH (pmol/L) 54.77 1.6–13.9 ently during the treatment. We gradually tapered the Cortisol at 8 AM (nmol/L) 216.60 171–536 dosage of potassium chloride and the plasma potassium level was 4.32 mmol/L (3.5–4.5 mmol/L) a week after Cortisol at 4 PM (nmol/L) 158.60 64–327 potassium supplement suspension. – Cortisol at 0 AM (nmol/L) 108.40 More importantly, we performed sequential observa- 24 h UFC(nmol/24 h) 137 100–379 tion of the blood glucose level before treatment and after 17-OHP (ng/ml) 0.22 < 0.93 the