A Chinese Woman with Congenital Adrenal Hyperplasiadue to 21-Hydroxylase Deficiency after Adrenalectomy: What Did We Ignore of?

Review Article

J Endocr Disord. 2014;1(1): 1007.

A Chinese Woman with Congenital Adrenal Hyperplasiadue to 21-Hydroxylase Deficiency after Adrenalectomy: What Did We Ignore of?

Kun Zhang, Xiao Ji, Chunyu Wang, Yaxi Chen, Junrong Ma and Xijie Yu*

Laboratory of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China

*Corresponding author: Xijie Yu, Laboratory of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, Sichuan , People’s Republic of China

Received: Aug 22, 2014; Accepted: Aug 28, 2014; Published: Aug 29, 2014


Congenital adrenal hyperplasia (CAH) is not a rare disease, but the possibility of misdiagnosis or late diagnosis is high especially in primary hospitals in China. Here, we report a case of a 53-year-old Chinese woman with CAH due to 21-hydroxylase deficiency after adrenalectomy. The primary physicians gave no diagnosis of CAH and directly performed the surgery for the possibility of compression caused by the large adrenal mass. Postoperatively, the patient experienced repeated hyperkalemia and cutaneous and gingival hyper pigmentation. Meantime, physicians ignored the patient with a history of noncompliance and postoperatively the patient was in danger many times. This study rein forces the close association between CAH and adrenal adenoma. CAH should be considered and baseline follicular-phase early-morning17- hydroxyprogesterone levels should be measured when discovered adrenal mass or nodule incidentally. Meanwhile, risk for noncompliance should be considered before surgery.

Keywords: CAH; Adenoma; Adrenalectomy; CYP21A2 gene mutations; Noncompliance


Congenital Adrenal Hyperplasia (CAH) is a group of inherited autosomal recessive disorders caused by deficiency in one of the enzymes necessary for cortical biosynthesis [1, 2]. The incidence ranges from 1:10,000 to 1:20,000 in births [3]. The most common type of CAH, accounting for approximately 90%cases, is due to 21-Hydroxlase (21-OH) deficiency [4]. The 21-hydroxlase enzyme converts 17-Hydroxy Progesterone (17-OHP) to 11-deoxycortisol and progesterone to deoxycorticosterone, precursors for cortisol and aldosterone respectively. When the enzyme is inadequate or absent the cortisol synthesis will be blocked, which leads to the chronic stimulation of Adrenal Cortex Byadrenocorticotropin(ACTH) and the accumulation of cortisol precursors [5]. Some of the precursors are diverted to the biosynthesis of sex hormones, which may cause phenotypes of androgen excess, such as androstenedione and DHEAS. The degree of enzyme activity is strongly in accordance with the clinical severity of CAH. Complete enzyme deficiency leads to classic Salt-Wasting (SW) is form presenting as failure to thrive, vomiting, hyperkalaemia, dehydration and shock. Partial enzyme deficiency results in classic Simple-Virilizing (SV) isoform characterizing by prenatal ambiguous genitalia in females and pseudo precocious puberty in both sexes. Patients with mild enzyme deficiency caused Non-Classic (NC)isoform, maybe asymptomatic or only present hirsutism, acne and precocious puberty later [5,6].

The CYP21A2 gene is located on the short arm of chromosome 6, HLA III region, adjacent to a pseudo gene (now namedCYP21P) [7]. 21-OH deficiency is caused by compound-heterozygous or homozygous mutations in CYP21A2 gene. More than90% of the point mutations result from intergenic recombination of DNA sequences between CYP21 and closely adjoined homologous CYP21P gene [8]. The degree of mutations compromising enzyme activity is strongly associated with the clinical severity of CAH. Patients carrying “severe” mutations which destroy all CYP21 activity present the classical SW isoform, whether homozygous or heterozygous mutations. Some “mild” mutations maintain partial enzyme activity, which result in on-classical isoform of CAH.The chronic stimulation of adrenal cortex in 21-OHD is associated with elevated prevalence of the adrenal tumors. Moreover, lack of adherence to regular treatment is also associated with development of adrenal adenoma [9,10]. Clinical physician and surgeon usually ignore this connection.

Case Presentation

A 53-year-old Chinese woman consulted for repeated fatigueandcutaneous and gingival hyper pigmentation over eightmonth period after unilateral adrenalectomy. During this period, the patient was admitted to the local hospital three times for hyperkalemia (plasmaK peaked 6.05mmol/L). Before adrenalectomy, she had no history of aforementioned symptoms. She was referred to hospital for knee joint pain and occasionally discovered adrenal mass by Computed Tomography (CT) abdomen. Further questioning history and physical examination revealed that she was a short fat woman and BMI was 27.4kg/m2 (weight 56.8kg with the height of 144cm). She was born with clitoromegalyandlabial fusion, and did not accept regular treatment and had no discomfort ordinarily. At present, her clitoris was enlarged measured the longitudinal axis of 3.6 cm and transverse diameter of 2.2 cm with small pubic hair (Figure 1). The urethral meat us was normal while the major and minor labia and vaginal introit us were not observed. She was primary amenorrhea with no marital and obstetric history. The systemic skin and gums showed abundant pigmentation because of postoperative complication. Physical examination revealed normal blood pressure (112/73mmHg), pulse rate (60bpm) and body temperature (36.7°C).The chromosomal analysis showed a normal 46, XX female karyotype.