Late onset adrenal insufficiency after adrenalectomy due to latent nonclassical 21-hydroxylase deficiency

Abstract

Rationale:Adrenal incidentaloma is sometimes complicated with 21-hydroxylase deficiency (21-OHD). Latent nonclassical 21-OHD in incidentaloma is difficult to diagnose. Although adrenalectomy in 21-OHD has been conducted when malignancy could not be excluded, adrenal insufficiency sometimes occurs, and it might not be observed immediately after operation. Here, we report a case of a 71-year-old man who experienced adrenal insufficiency over 2 decades postadrenalectomy, leading to a diagnosis of latent nonclassical 21-OHD.Patient concerns:A 71-year-old man was admitted to the hospital due to difficulty in movements and a sodium level of 119 mEq/L. His medical history revealed precocious puberty and left adrenalectomy because of an incidentaloma at 49 years of age, diagnosed pathologically as an adenoma. He did not attend follow-up visits because he did not have any symptoms. In 2017, 3 months before hospitalization, he experienced general fatigue. A few days before admittance, he complained of difficulty in moving and visual hallucination of small animals.Diagnoses:Laboratory evaluations revealed a high level of adrenocorticotropic hormone (ACTH) and low cortisol level. ACTH-stimulating test revealed a low basal level and low response for cortisol, and a high basal level and low response for 17-hydroxyprogesterone. We analyzed large gene deletion or conversion and the 9 most common micro mutations in the CYP21A2 gene by polymerase chain reaction; micro mutation of I172N and heterozygous large gene deletion or conversion were detected leading to the diagnosis of nonclassical 21-OHD.Interventions:Immediately, 100 mg hydrocortisone was administered, followed by daily hydrocortisone and saline. The symptoms and hyponatremia improved in a few days. He was discharged from the hospital on day 34 with a daily dose of 15 mg hydrocortisone.Lessons:Clinicians should be aware of late onset of adrenal insufficiency after adrenalectomy. In such cases, clinicians should not overlook the latent nonclassical 21-OHD.

Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia

“…The median age at tumour diagnosis in these CAH individuals was 46. Most of these mentioned patients with pathogenic variants of CYP21A2 were diagnosed with CAH after the discovery of an adrenal tumour (N = 20) [51][52][53][54][55][56][57][58][59][60][61][62][63][64]66,67]. Only five persons were previously known with CAH [50,54,64,65] (two more cases' data were not available).…”

“…Only five persons were previously known with CAH [50,54,64,65] (two more cases' data were not available). In terms of CAH form, most patients presented with SV-CAH (N = 13) [50,51,[55][56][57][58][61][62][63][64]66], followed by NC-CAH (N = 11) [51][52][53][54]59,60,66,67]; only two patients had SW-CAH [64,65], while another subject had a carrier status [51] (Table 1).…”

“…Table 1. Case reports (n = 13)/series (n = 5) with data regarding the clinical features of the patients diagnosed with CAH (CYP21A2 deficiency) and adrenal tumours/masses according to our strategy; the display starts with the earliest publication date within the decade of analysis [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67]. [51,53,55,59,64,66].…”

“…Case reports (n = 13)/series (n = 5) with data regarding the clinical features of the patients diagnosed with CAH (CYP21A2 deficiency) and adrenal tumours/masses according to our strategy; the display starts with the earliest publication date within the decade of analysis [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67]. [51,53,55,59,64,66]. Two adrenal incidentalomas were classified as adrenocortical adenoma following the post-adrenalectomy pathological report [59,64]; two adrenal masses were classified as hyperplasia, one being an adenomatous hyperplasia [67] and the other "hyperplasia with mild atypia" according to the original terms [57].…”

Clinical Features and Risk Factors of Adrenal Insufficiency in Patients With Cancer Admitted to the Hospitalist-Managed Medical Unit

“… 4 5 6 The development of AI is also associated with metastatic lesions in the adrenal glands, resection of the adrenal glands, and the use of immune checkpoint inhibitors. 7 8 9 10 Supplement of glucocorticoids could alleviate AI-related symptoms, but can also lead to adverse effects such as osteoporosis, muscle atrophy, hyperglycemia, dyslipidemia, and heart failure. 11 Therefore, it is important to appropriately diagnose and treat AI in patients with malignancy.…”