scholarly journals PREVALENCE AND CHARACTERISTICS OF ADRENAL TUMORS AND MYELOLIPOMAS IN CONGENITAL ADRENAL HYPERPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 26 (11) ◽  
pp. 1351-1361
Author(s):  
Ingrid Nermoen ◽  
Henrik Falhammar
Keyword(s):  
Cytochrome P450 ◽  
Congenital Adrenal Hyperplasia ◽  
Case Reports ◽  
Meta Analysis ◽  
Adrenal Tumors ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Adrenal Imaging ◽  
Cytochrome P450 Family ◽  
21 Hydroxylase Deficiency

Objective: The prevalence of adrenal tumors in congenital adrenal hyperplasia (CAH) is uncertain. Our objective was to estimate the prevalence and characteristics of adrenal tumors and myelolipoma in CAH, and investigate clinical features of this population. Methods: We carried out systematic searches in Medline Ovid and Embase for articles published until January, 2020. Studies with confirmed CAH, biochemically and/or genetically, were included. The two authors independently extracted data from each study. Results: Six cohort studies were included in the prevalence calculation. In addition, 32 case reports on adrenal myelolipomas and CAH were included. The prevalence of adrenal tumors in CAH was 29.3%. When only studies with genetically verified cytochrome P450, Family 21, subfamily A, polypeptide 2 gene ( CYP21A2) mutations were included the prevalence was 23.6%. The prevalence of myelolipoma in CAH was 7.4% (verified CYP21A2 mutations 8.6%). The proportion of myelolipoma in the adrenal tumors was 25.4% (genetically verified 36.6%). The median (range) age at tumor diagnosis was 36.0 (12 to 60) years and there were more tumors in males than in females (37.9% versus 22.1%; P<.05). In patients with myelolipomas, 93.5% had an undiagnosed or poorly managed CAH. Conclusion: Patients with CAH had a high prevalence of adrenal tumors, particularly myelolipomas. Those with myelolipomas had a high frequency of late-diagnosed or poorly controlled CAH. Adrenal imaging may be considered in patients with CAH, especially if abdominal pain is present. Abbreviations: ACTH = adrenocorticotropic hormone; CAH = congenital adrenal hyperplasia; CT = computed tomography; CYP21A2 = cytochrome P450, Family 21, subfamily A, polypeptide 2 gene; HU = Hounsfield units; MRI = magnetic resonance imaging; 21-OHD = 21-hydroxylase deficiency; 17-OHP = 17-hydroxyprogesterone; SV = simple virilizing

scholarly journals Ectopic Adrenal Tumor in a Patient With Untreated Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A128-A129
Author(s):  
Eva L Alba ◽  
Kruti K Patel ◽  
Alice C Levine
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Case Reports ◽  
Broad Ligament ◽  
Adrenal Tumors ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Adrenal Rest Tumor ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency

Abstract Case Presentation: A 43 year-old female was diagnosed at birth with non-salt wasting congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and underwent clitoral reduction surgery. She was treated with hydrocortisone and had menarche at age 7 with irregular and heavy menses. At age 15 she had a D&C with removal of “something in her ovaries.” She stopped hydrocortisone at age 30 except for stress doses during illness. At age 35 she stopped oral contraceptives and thereafter has been amenorrheic. She presented with abdominal distention and constipation. On exam she had short stature, marked frontal and temporal balding, hirsutism, increased musculature and a large distended abdomen. Labs showed AM cortisol 3.1 mcg/dL (nl 10–20), ACTH 440 pg/ml (nl &lt;46), 17-OH Progesterone 11000 ng/dL (nl &lt;206), DHEAS 362 mcg/dl (nl &lt;430), FSH 0.2 mIU/ml, LH 2.7 mIU/ml, testosterone 618 ng/dl (nl 10–75), and estradiol 162 pg/ml (nl post menopause &lt;41). MRI showed a massive fibroid (30 cm), bilateral adrenal hyperplasia and a left paraaortic, retroperitoneal mass (5.9 cm). She underwent hysterectomy with removal of a 9.5 kg uterus containing degenerated fibroids, left adrenalectomy and removal of the left paraaortic mass that was initially read as oncocytic adrenal cortical neoplasm, metastatic. A similar oncocytic neoplasm was noted in the left adrenal gland and on further review with pathology the revised report read paraaortic mass, probable adrenal rest tumor. Discussion: Excess androgens and chronically elevated ACTH levels in untreated CAH can lead to adverse effects beyond adrenal insufficiency and virilization. We present a woman with untreated classic CAH who developed a large fibroid and paraaortic adrenal cortical tumor. Fibroids have been described in CAH patients, a potential consequence of elevated androgens that are converted by aromatase in the endometrium to estrogens driving growth of fibroid tumors. Chronic ACTH can further act as a growth factor, leading to adrenal hyperplasia, adrenal tumors and ectopic adrenal rest tissue. Intra-adrenal tumors in untreated CAH are generally benign with rare cases of adrenal cortical carcinoma reported. Ectopic adrenal rest tissue in untreated CAH is most commonly reported in testes. There have been rare case reports of ectopic adrenal rest tumors in the adnexa, broad ligament, and perirenal area. Our patient presents as an unusual case of ectopic adrenal rest tumor in the paraaortic region. Based on the atypical location and incomplete history available to the pathologist, it was initially read as metastatic adrenocortical carcinoma. Upon further review given the clinical information, the diagnosis was revised to indicate a pararenal adrenal rest tumor. This case highlights the importance of glucocorticoid compliance in CAH and the necessity to provide a clinical context for the pathologist in cases of extra-adrenal tumors in untreated CAH.

Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: A meta-analysis

2001 ◽  
Vol 138 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Erica A. Eugster ◽  
Linda A. DiMeglio ◽  
James C. Wright ◽  
Gary R. Freidenberg ◽  
Roopa Seshadri ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Meta Analysis ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

scholarly journals Large Bilateral Adrenal Myelolipomas in the Setting of Congenital Adrenal Hyperplasia

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A138-A139
Author(s):  
Karolina E Anderson ◽  
Carmen Solorzano ◽  
Shichun Bao
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Incidentaloma ◽  
Adrenal Tumors ◽  
Adrenal Hyperplasia ◽  
Hematopoietic Tissue ◽  
Hydroxylase Deficiency ◽  
Retroperitoneal Hemorrhage ◽  
The Right ◽  
The Masses ◽  
21 Hydroxylase Deficiency

Abstract Adrenal myelolipomas (AMLs) are rare benign adrenal tumors containing adipose and hematopoietic tissue, with a reported incidence of 0.08 to 0.4% on autopsy. AMLs are the second most common primary adrenal incidentaloma. Congenital adrenal hyperplasia (CAH) is associated with 10% of analyzed AML cases, half of which are bilateral in CAH patients. This is a 40-year old male with CAH diagnosed shortly after birth, due to 21-hydroxylase deficiency. He was doing well on a maintenance dose of hydrocortisone 20mg PO qAM and 10mg PO qPM and fludrocortisone 0.2mg PO daily until two years ago when he was incidentally found to have large bilateral AMLs while undergoing abdominal MRI and CT scans. These measured 6.6x3.6x7.7cm on the right (R) and 12.3x8.4x6.8cm on the left (L) at the time. He was asymptomatic, denying flank and abdominal pain. Follow up adrenal CT a year later revealed his AMLs increased in size to 8.7x4.2x6.6cm (R) and 13.9x6x8cm (L). Repeat CT another year later showed further rapid enlargement of his AMLs, measuring 11.1x6.1x7.9cm (R) and 17.1x7.8x10.8cm (L). He also exhibited a rising 17-hydroxyprogesterone level of 11,547ng/dL, despite an increased hydrocortisone dose (20mg BID). Although he remained asymptomatic, due to the precipitous growth of the masses and his increasing steroid requirement, a surgical approach was recommended. Open bilateral adrenalectomy was performed by an experienced endocrine surgeon and patient was discharged from the hospital with maintenance hydrocortisone and fludrocortisone therapy as well as strict sick day instructions. AMLs were first described in 1905 by Gierke. In the past, they were often discovered on autopsies, but more recently, due to the increase in imaging, have been incidentally diagnosed on more patients. Mostly, they occur unilaterally and are small (&lt;4 cm) in size. Individuals with hormonal dysfunction such as those with Cushing’s Syndrome, Conn’s syndrome and CAH, particularly with difficult-to-control corticotropin levels, may be at a greater risk of developing AMLs concurrently, however this phenomenon is still not well understood. Small asymptomatic AMLs can be monitored with serial imaging over time. Spontaneous rupture of AMLs was found in 4.5% of cases, mostly occurring in tumors &gt; 10cm, some resulting in retroperitoneal hemorrhage or even hemorrhagic shock. Although there is no clear consensus on surgery, development of symptoms or significant growth (to &gt;10cm), as in our case, is a reason to pursue surgical evaluation especially in a young, otherwise relatively healthy adult.

scholarly journals SUN-204 Case of Non-Classic Congenital Adrenal Hyperplasia with Compound CYP21A2 Mutations Combined with CYP11B1 Mutation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rami Salameh ◽  
Janna Prater
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Case Reports ◽  
Total Testosterone ◽  
Carrier Status ◽  
Single Individual ◽  
Adrenal Hyperplasia ◽  
Significant Past Medical History ◽  
Hydroxylase Deficiency ◽  
Steroid Synthesis ◽  
21 Hydroxylase Deficiency

Abstract Introduction: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, caused by a deficiency in one of the enzymes involved in adrenal steroid synthesis. Homozygotes usually have a severe classical CAH phenotype. Heterozygotes, carrying only one abnormal copy of the gene, are thought to be generally asymptomatic, although could be associated with hyperandrogenism, decreased fertility, adrenal incidentalomas. 21-hydroxylase deficiency (21OHD) accounts for 90% of all CAH cases, while 11 β-hydroxylase deficiency (11OHD) accounts for 4–8% of CAH cases. The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence of gene mutation for both 21OHD and 11OHD CAH in a single individual is very unlikely to occur. Clinical case: A 22-year old female with no significant past medical history presented to endocrinologist for evaluation of facial hirsutism. Patient had menarche at age 11, and menstrual cycle was regular since. No concerns for virilization of external genitalia. She was not sexually active, no pregnancies. No Family history of infertility or genetic conditions. Patient’s father was Jewish, and mother was Slavic. Physical examination revealed female phenotype, normal Blood pressure and BMI, acne on the back and upper arm, Ferriman-Gallwey hirsutism score 5. Labs: AM cortisol, CMP, CBC and TSH were normal. Total testosterone 68 ng/dL (2–45), free testosterone 7 pg/mL (0.1 - 6.4), FSH 5.7 mIU/mL (2.5–10.2), LH 10.6 mIU/mL (1.9–12.5), Progesterone 2.1 ng/mL (&lt;1), Estradiol 51 pg/mL (19–144), 17-OH Progesterone 6728 ng/dL (45–285), Androstenedione 710 ng/dL (35–250), DHEA 1216 ng/dL (102 - 1185), 11-Deoxycortisol 204 ng/dL (&lt;107), Pregnenolone 661 ng/dL(22–237), DHEAS 435 ng/dL (18–391). Elevated 11-Deoxycortisol level raised a suspicion for 11-OHD CAH, or adrenal vs ovarian hormone-producing mass. Abdominal CT and pelvic US were negative for adrenal or ovarian masses. 3-day dexamethasone suppression test completely normalized all biochemical abnormalities the patient had. Genetic testing showed: CYP21A2 c.844G&gt;T (non-classic 21OHD CAH mutation), CYP21A2 c.923dupT (classic 21OHD CAH mutation), CYP11B1 c.953C&gt;G mutation. Thus diagnosis of non-classic 21OHD CAH, and carrier status of 11OHD CAH was made. She was started on oral Dexamethasone 0.25 mg every other day. 11-Deoxycortisol elevation could not be explained by 21OHD alone. Her carrier state of the CYP11B1 mutation also cannot cause elevated 11-Deoxycortisol level. We hypothesize that 11-Deoxycortisol was elevated either from extra adrenal conversion of 17-hydroprogesterone to 11-Deoxycortisol, or from 11 β-hydroxylase inhibition by excess intra-adrenal androgens. Conclusion: Our case reports a rare finding of both CYP21A2 and CYP11B1 mutations in the same individual, which has implications for relatives, family planning and partner genetic screening.

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