Atypical Presentation of Testicular Adrenal Rest Tumor (TART) Leading to Bilateral Partial Orchiectomy in a 31-Year-Old Adult Revealing Primary Adrenal Insufficiency with CYP11A1 Deficiency

Adrenogenital syndrome is commonly associated with a deficiency in 21-hydroxylase but can be present in other rare enzymatic blocks. We report here the case of a 31-year-old man who presented with bilateral painful testicle lesions leading to bilateral partial orchiectomy as they were suspected for malignancy. These lesions were finally identified as benign testicle adrenal rest tumors (TARTs), and the patient was actually belatedly diagnosed with primary adrenal insufficiency due to 2 mutations of the CYP11A1 gene encoding the cholesterol side-chain cleavage enzyme (P450scc); the mutations were 940G > A (p.Glu314Lys) and c.1393C > T (p.Arg465Trp). The same mutations were found in his 29-year-old sister, who was then also diagnosed for primary adrenal insufficiency. Deficiency in P450scc is an extremely rare genetic autosomal recessive disorder with around 40 described families in the literature and 30 different mutations. As the diagnosis of delayed onset of P450Scc mutation is difficult, this case illustrates the need for a systematic endocrinological assessment in any case of bilateral testicle lesions, thus avoiding unnecessary surgery.

Hepatic adrenal rest tumor in a patient with multifactorial liver cirrhosis: a case report with CT and MRI findings and pathologic correlation

Background Adrenal rest tumor is an ectopic collection of adrenocortical cells in an extra-adrenal site, more frequently located around the kidney, retroperitoneum, spermatic cord, para-testicular region and broad ligament, but very rarely occurring also in the liver. Hepatic adrenal rest tumor poses a diagnostic challenge in differentiating it from hepatocellular carcinoma, particularly in a cirrhotic liver. Case presentation An 83-years-old male was referred to our hospital by his family doctor for hepatological evaluation due to multifactorial liver cirrhosis. Ultrasound revealed a centimetric hypoechoic nodule in the VI hepatic segment in the context of a liver with signs of cirrhosis and steatosis. The patient first underwent MRI and then CT, which showed a fat containing focal liver lesion in the subcapsular location of the right lobe, strictly adjacent to the homolateral adrenal gland. The nodule was hypervascular in the arterial phase, washed out in the portal-venous and transitional phases, resulting hypointense in the hepato-biliary phase at MR imaging. In the suspicion of a hepatocellular carcinoma, the nodule was surgically removed, and the patient’s postoperative course was unremarkable. The final histopathological diagnosis was of adrenal rest tumor of the liver. Conclusions Hepatic adrenal rest tumor is an extremely rare hepatic tumor, often without any clinical manifestation, that can also occur in the cirrhotic liver as in our case. Although there are not specific imaging findings, the possible diagnosis of HART should be considered when we observe a well-defined lesion in the subcapsular location of the right lobe, with fat containing, hypervascularity after contrast medium injection and vascular supply from the right hepatic artery.

BIRDS OF THE SAME FEATHER DO NOT ALWAYS FLOCK TOGETHER: AN ADRENAL CASE SERIES

Introduction: Most common adrenocortical biosynthetic defect is 21-hydroxylase deciency usually presenting as atypical genitalia at birth in girls and adrenal crisis in males at 2-3 weeks of age. We present to you a case series of congenital adrenal hyperplasia(CAH) with heterogeneous presentation at varied ages.Case 1:Thirty-six-day old baby presented with atypical genitalia, failure to thrive and shock. Laboratory evaluation revealed:hyperkalemia, hyponatremia, markedly elevated 17OH-progesterone(24200ng/dl)and karyotype 46XX.Case 2: One-year-4-month old boy known case of salt-wasting CAH who was on regular oral hydrocortisone and udrocortisone brought with the acute gastroenteritis. Investigations revealed elevated markers for sepsis, hypocortisolemia(1.37 mcg/dl) and high 17-OH-progesterone(588 ng/dl). Case 3: Five-year10-month old boy, known case of salt-wasting CAH on irregular medication and poor compliance presented with enlarged penile length. On evaluation his SMR staging=A1P3TV4/4ml, Height age:7.6 year and bone-age was 11.6 years. Endocrine evaluation demonstrated gonadotropinindependent precocity(Testosterone=109ng/dl, FSH=0.31 IU/ml, LH<0.10 IU/ml, 17-OH-Progesterone:25400ng/dl).Scrotal ultrasound showed hypoechoic areas in rete-testis suggestive of probable tesicular-adrenal-rest-tumor(TART).All patients were treated with hydrocortisone, udrocortisone and uid resuscitation.Conclusion:Diagnosis of CAH doesn't always depend on atypical genitalia. Continued adherence to the optimal dose of steroids, regular monitoring and strict advice during illness is as important as appropriate and timely management of the adrenal crisis.

Taking it with a Grain of Salt: A Woman with ‘PCOS’ and Infertility Diagnosed with Nonclassic Congenital Adrenal Hyperplasia and a Large Renal Mass

Background: Clinical manifestations of Nonclassic CAH (NCCAH) in women may range from asymptomatic to hirsutism, oligo-menorrhea, or infertility. Testicular adrenal rest tumors are common in men with classic CAH though uncommon in NCCAH. In women with classic CAH, ovarian adrenal rest tumors are even rarer. 11–58% of patients with classic CAH will have at least one adrenal nodule but the prevalence is unknown in NCCAH (1). Clinical Case: A 34-year-old Hispanic woman was seen by reproductive endocrinology for evaluation of infertility. She had been unable to conceive for the past 7 years. She was diagnosed with PCOS by her PCP. She was referred to our clinic for further workup. The patient denied galactorrhea. Laboratory evaluation revealed prolactin 49.3 (&lt; 20.0 ng/ml), TSH 2.290 (0.5–5.0 μU/mL), fT4 1.14 (0.9–2.3 ng/dL), total testosterone 92 (15 -70 ng/dL for women), DHEAS 361 (45 -270 µg/dL), 8 AM cortisol 20.0 (5–23 μg/dL), ACTH 59.0 (6–76 pg/ml), 17-hydroxyprogesterone (17OHP) &gt;2000 ng/dL, and A1c 5%. 24-hour urinary free cortisol was 26.4 (3.5–45 mcg/day). MRI of the pituitary did not show any adenoma. Pelvic ultrasound did not reveal any ovarian cysts. Cosyntropin stimulation test showed baseline 17OHP 1076 ng/dL, 30 minutes 8812 ng/dL, and 60 minutes 9452 ng/dL. She was begun on hydrocortisone and cabergoline. CT of the abdomen did not reveal any adrenal masses but showed mildly thickened adrenal limbs suggesting adrenal hyperplasia. A 4.5 cm exophytic enhancing mass on the left kidney was noted representing an adrenal rest tumor versus angiomyolipoma. Given the exophytic nature of the mass and increased risk of hemorrhage with angiomyolipomas greater than 4 cm, the patient was referred to urology and interventional radiology for radioembolization and possible biopsy of the mass. We are unsure if this renal mass is an angiomyolipoma or an adrenal rest tumor, which are uncommon in the kidneys. The patient was also referred for genetic counseling. Patients with CAH typically have CYP21A2 gene mutations, and the chance that a patient with NCCAH will have a child with classic CAH is reported to be 1 to 2% in two large cohort studies (2). Conclusion: This case is a reminder that evaluation of infertility/subfertility includes less common diagnoses, such as NCCAH. This genetic disorder is seen more frequently in certain ethnic groups, including Hispanics; and after diagnosis, patients should be referred to a genetic specialist. Additional abdominopelvic imaging should be considered in both men and women with a new diagnosis of NCCAH to evaluate for rare but clinically significant tumors. Reference: 1. Nordenström, A., Falhammar H. Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency Eur J Endocrinol. 2019 Mar;180(3):R127-R145.2. Merke, D, Auchus, R Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. NEJM 2020;383:1248–61.

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

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.

A spontaneous pregnancy and live birth in a woman with primary infertility following the excision of an ovarian adrenal rest tumor: A rare case

Adrenal rest tumors are a rare extra-adrenal complication of congenital adrenal hyperplasia (CAH) in women although they are more commonly found in the testes of male patients with CAH. An ovarian adrenal rest tumor (OART) may coexist with CAH or imitate its symptoms without CAH. In this case report, we present the case of a woman with OART without CAH, whose main complaint was infertility and who had a baby after successful surgical treatment.

Usefulness of Modified CEUS LI-RADS for the Diagnosis of Hepatocellular Carcinoma Using Sonazoid

The Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) was introduced for classifying suspected hepatocellular carcinoma (HCC). However, it cannot be applied to Sonazoid. We assessed the diagnostic usefulness of a modified CEUS LI-RADS for HCC and non-HCC malignancies based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Patients with chronic liver disease at risk for HCC were evaluated retrospectively. Nodules ≥1 cm with arterial phase hyperenhancement, no early washout (within 60 s), and contrast defects in the Kupffer phase were classified as LR-5. Nodules showing early washout, contrast defects in the Kupffer phase, and/or rim enhancement were classified as LR-M. A total of 104 nodules in 104 patients (median age: 70.0 years; interquartile range: 54.5–78.0 years; 74 men) were evaluated. The 48 (46.2%) LR-5 lesions included 45 HCCs, 2 high-flow hemangiomas, and 1 adrenal rest tumor. The PPV of LR-5 for HCC was 93.8% (95% confidence interval (CI): 82.8–98.7%). The 22 (21.2%) LR-M lesions included 16 non-HCC malignancies and 6 HCCs. The PPV of LR-M for non-HCC malignancies, including six intrahepatic cholangiocarcinomas, was 100% (95% CI: 69.8–100%). In conclusion, in the modified CEUS LI-RADS for Sonazoid, LR-5 and LR-M are good predictors of HCC and non-HCC malignancies, respectively.

A case of Williams syndrome with suspected coexisting ectopic aldosterone-producing tumor in the liver

Summary A 31-year-old man with Williams syndrome (WS) was referred to our hospital because of a 9-year history of hypertension, hypokalemia, and high plasma aldosterone concentration to renin activity ratio. A diagnosis of primary aldosteronism (PA) was clinically confirmed but an abdominal CT scan showed no abnormal findings in his adrenal glands. However, a 13-mm hypervascular tumor in the posterosuperior segment of the right hepatic lobe was detected. Adrenal venous sampling (AVS) subsequently revealed the presence of an extended tributary of the right adrenal vein to the liver surrounding the tumor. Segmental AVS further demonstrated a high plasma aldosterone concentration (PAC) in the right superior tributary vein draining the tumor. Laparoscopic partial hepatectomy was performed. The resected tumor histologically separated from the liver was composed of clear cells, immunohistochemically positive for aldesterone synthase (CYP11B2), and subsequently diagnosed as aldosterone-producing adrenal adenoma. After surgery, his blood pressure, serum potassium level, plasma renin activity and PAC were normalized. To the best of our knowledge, this is the first report of WS associated with PA. WS harbors a high prevalence of hypertension and therefore PA should be considered when managing the patients with WS and hypertension. In this case, the CT findings alone could not differentiate the adrenal rest tumor. Our case, therefore, highlights the usefulness of segmental AVS to distinguish adrenal tumors from hepatic adrenal rest tumors. Learning points: Williams syndrome (WS) is a rare genetic disorder, characterized by a constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. WS is a disease with a high frequency of hypertension but the renin-aldosterone system in WS cases has not been studied at all. If a patient with WS had hypertension and severe hypokalemia, low PRA and high ARR, the coexistence of primary aldosteronism (PA) should be considered. Adrenal rest tumors are thought to arise from aberrant adrenal tissues and are a rare cause of PA. Hepatic adrenal rest tumor (HART) should be considered in the differential diagnosis when detecting a mass in the right hepatic lobe. Segmental adrenal venous sampling could contribute to distinguish adrenal tumors from HART.