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Search for other papers by Evangelos Karvounis in
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Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
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Summary
Large-cell neuroendocrine carcinoma (LCNEC) is a rare neuroendocrine prostatic malignancy. It usually arises after androgen deprivation therapy (ADT), while de novo cases are even more infrequent, with only six cases described. The patient was a 78-year-old man with no history of ADT who presented with cervical lymphadenopathy. Diagnostic approaches included PET/CT, MRI, CT scans, ultrasonography, biopsies, and cytological and immunohistochemical evaluations. Results showed a poorly differentiated carcinoma in the thyroid gland accompanied by cervical lymph node enlargement. Thyroid surgery revealed LCNEC metastasis to the thyroid gland. Additional metastases were identified in both the adrenal glands. Despite appropriate treatment, the patient died of the disease. De novo LCNEC of the prostate is a rare, highly aggressive tumor with a poor prognosis. It is resistant to most therapeutic agents, has a high metastatic potential, and is usually diagnosed at an advanced stage. Further studies are required to characterize this tumor.
Learning points
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De novo LCNECs of the prostate gland can metastasize almost anywhere in the body, including the thyroid and adrenal glands.
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LCNECs of the prostate are usually associated with androgen-depriving therapy, but de novo cases are also notable and should be accounted for.
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Further studies are required to fully understand and treat LCNECs more effectively.
Department of Endocrinology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
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Department of Endocrinology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
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Summary
Primary adrenal insufficiency is a rare disease and can masquerade as other conditions; therefore, it is sometimes incorrectly diagnosed. Herein, we reported the case of a 39-year-old Vietnamese male with primary adrenal insufficiency due to bilateral adrenal tuberculosis. The patient presented to the emergency room with acute adrenal crisis and a 3-day history of nausea, vomiting, epigastric pain, and diarrhoea with a background of 6 months of fatigue, weight loss, and anorexia. Abdominal CT revealed bilateral adrenal masses. Biochemically, unequivocal low morning plasma cortisol (<83 nmol/L) and high plasma adrenocorticotropic hormone levels were consistent with primary adrenal insufficiency. There was no evidence of malignancy or lymphoma. As the patient was from a tuberculosis-endemic area, extra-adrenal tuberculosis was excluded during the work up. A retroperitoneal laparoscopic left adrenalectomy was performed, and tuberculous adrenalitis was confirmed by the histopathological results. The patient was started on antituberculous therapy, in addition to glucocorticoid replacement. In conclusion, even without evidence of extra-adrenal tuberculosis, a diagnosis of bilateral adrenal tuberculosis is required. A histopathological examination has a significant role along with clinical judgement and hormonal workup in establishing a definitive diagnosis of adrenal tuberculosis without evidence of active extra-adrenal involvement.
Learning points
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Primary adrenal insufficiency can be misdiagnosed as other mimicking diseases, such as gastrointestinal illness, leading to diagnostic pitfalls.
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Adrenal insufficiency can be confirmed with significantly low morning plasma cortisol levels of <83 nmol/L without a dynamic short cosyntropin stimulation test.
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Tuberculous adrenalitis is an uncommon treatable condition; however, it remains an important cause of primary adrenal insufficiency, especially in developing countries. In the absence of extra-adrenal involvement, adrenal biopsy plays a key role in the diagnostic process. Alternatively, adrenalectomy for histopathological purposes should be considered if CT scan-guided fine needle aspiration is infeasible in cases of small adrenal masses.
Search for other papers by Mariana Aveiro-Lavrador in
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Summary
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to enzyme deficiencies in the adrenal steroidogenesis pathway leading to impaired corticosteroid biosynthesis. Depending on the extension of enzyme defect, there may be variable severities of CAH – classic and non-classic. We report the case of a 37-year-old male patient with a previously unknown diagnosis of classic CAH referred to Endocrinology evaluation due to class III obesity and insulin resistance. A high diagnostic suspicion was raised at the first Endocrinology consultation after careful past medical history analysis especially related to the presence of bilateral adrenal myelolipomas and primary infertility. A genetic test confirmed the presence of a variant of the CYP21A2 in homozygous with an enzymatic activity of 0–1%, corresponding to a classic and severe CAH form. Our case represents an unusually late definitive diagnose of classic CAH since the definition was established only during adulthood in the fourth decade of life. The missing diagnosis of classic 21 hydroxylase deficiency during infancy led to important morbidity, with a high impact on patients’ quality of life.
Learning points
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Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive enzyme disorders responsible for an impaired cortical adrenal hormonal synthesis.
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CAH may be divided into two major forms: classic and non-classic CAH.
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If untreated, CAH may be fatal or may be responsible for important multi-organ long-term consequences that can be undervalued during adulthood.
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Adrenal myelolipomas are associated with chronic exposure to high ACTH levels and continuous androgen hyperstimulation typically found in undertreated CAH patients.
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Testicular adrenal rest tumours (TART) and primary infertility can be the first manifestation of the disease during adulthood.
Search for other papers by Paweena Chunharojrith in
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Search for other papers by Tanawan Kongmalai in
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Summary
Ectopic adrenocorticotropic hormone (ACTH) secretion is responsible for 5–15% of Cushing’s syndrome (CS). Neuroendocrine tumor (NET) is a common cause of ectopic ACTH syndrome (EAS). However, primary renal NET is exceedingly rare. Fewer than 100 cases have been reported and only a few cases presented with CS. Because of its rarity and lack of long-term follow-up data, clinical manifestations, biological behavior and prognosis are not well understood. Here, we report the case of a 51-year-old man who presented with clinical and laboratory findings compatible with EAS. CT scan revealed a lesion of uncertain nature at the lower pole of the left kidney. Octreotide scan found a filling defect at the lower pole of left kidney. It was difficult to determine if this finding was the true etiology or an incidental finding. Unfortunately, the patient’s clinical status rapidly deteriorated with limited medical treatment. The patient underwent left nephrectomy and left adrenalectomy. Histopathological examination confirmed NET with oncocytic features. Immunohistochemistry staining was positive for ACTH. The patient’s condition gradually improved. Additionally, glucocorticoid replacement was required only 6 months during a gradual recovery of hypothalamic pituitary adrenal axis achieved approximately three years after tumor removal. Although extremely rare, primary renal NET should be considered as a cause of EAS particularly in a patient with rapid clinical deterioration. Thorough investigation, early diagnosis and careful management are crucial to reduce morbidity and mortality.
Learning points
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Primary renal NET is an extremely rare cause of ectopic ACTH syndrome.
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Ectopic ACTH syndrome has a rapid onset with severe clinical manifestations. In this case, the patient’s condition deteriorated rapidly, resulting from severe hypercortisolism. Resection of the tumor is the most effective treatment.
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Localization of ectopic ACTH-secreting tumors is very challenging. Multimodality imaging including CT, MRI, octreotide scan, and positron emission tomography plays a crucial role in identifying the tumors. However, each imaging modality has limitations.
Search for other papers by Takuya Higashitani in
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Department of Internal Medicine, Keiju Medical Center, Nanao, Ishikawa, Japan
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Department of Health Promotion and Medicine of the Future, Kanazawa University, Kanazawa, Ishikawa, Japan
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Search for other papers by Yoshiyu Takeda in
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Summary
Renovascular hypertension (RVHT) is an important and potentially treatable form of resistant hypertension. Hypercortisolemia could also cause hypertension and diabetes mellitus. We experienced a case wherein adrenalectomy markedly improved blood pressure and plasma glucose levels in a patient with RVHT and low-level autonomous cortisol secretion. A 62-year-old Japanese man had been treated for hypertension and diabetes mellitus for 10 years. He was hospitalized because of a disturbance in consciousness. His blood pressure (BP) was 236/118 mmHg, pulse rate was 132 beats/min, and plasma glucose level was 712 mg/dL. Abdominal CT scanning revealed the presence of bilateral adrenal masses and left atrophic kidney. Abdominal magnetic resonance angiography demonstrated marked stenosis of the left main renal artery. The patient was subsequently diagnosed with atherosclerotic RVHT with left renal artery stenosis. His left adrenal lobular mass was over 40 mm and it was clinically suspected the potential for cortisol overproduction. Therefore, laparoscopic left nephrectomy and adrenalectomy were simultaneously performed, resulting in improved BP and glucose levels. Pathological studies revealed the presence of multiple cortisol-producing adrenal nodules and aldosterone-producing cell clusters in the adjacent left adrenal cortex. In the present case, the activated renin-angiotensin-aldosterone system and cortisol overproduction resulted in severe hypertension, which was managed with simultaneous unilateral nephrectomy and adrenalectomy.
Learning points:
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Concomitant activation of the renin-angiotensin-aldosterone system and cortisol overproduction may contribute to the development of severe hypertension and lead to lethal cardiovascular complications.
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Treatment with simultaneous unilateral nephrectomy and adrenalectomy markedly improves BP and blood glucose levels.
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CYP11B2 immunohistochemistry staining revealed the existence of aldosterone-producing cell clusters (APCCs) in the adjacent non-nodular adrenal gland, suggesting that APCCs may contribute to aldosterone overproduction in patients with RVHT.
Department of Endocrinology, University Hospital of Farhat Hached Sousse
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Search for other papers by Perrine Wojewoda in
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Summary
Multiple endocrine metastases are a rare but possible complication of lung adenocarcinoma (LAC). Pituitary metastasis is a rare condition with poor clinical expression. Diabetes insipidus (DI) is its most common presenting symptom. Here we report an original case of a pituitary stalk (PS) metastasis from LAC presenting as central DI followed by adrenal insufficiency (AI) from bilateral adrenal metastasis, without known evidence of the primary malignancy. A 45-year-old woman whose first clinical manifestations were polyuria and polydipsia was admitted. She was completely asymptomatic with no cough, no weight loss or anorexia. Chest radiography was normal. Brain MRI showed a thick pituitary stalk (PS). DI was confirmed by water restriction test and treated with vasopressin with great clinical results. Explorations for systemic and infectious disease were negative. Few months later, an acute AI led to discovering bilateral adrenal mass on abdominal CT. A suspicious 2.3 cm apical lung nodule was found later. Histopathological adrenal biopsy revealed an LAC. The patient received systemic chemotherapy with hormonal replacement for endocrinological failures by both vasopressin and hydrocortisone. We present this rare case of metastatic PS thickness arising from LAC associated with bilateral adrenal metastasis. Screening of patients with DI and stalk thickness for lung and breast cancer must be considered. Multiple endocrine failures as a diagnostic motive of LAC is a rare but possible circumstance.
Learning points:
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Adrenal metastasis is a common location in lung adenocarcinoma; however, metastatic involvement of the pituitary stalk remains a rare occurrence, especially as a leading presentation to diagnose lung cancer.
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The posterior pituitary and the infundibulum are the preferential sites for metastases, as they receive direct arterial blood supply from hypophyseal arteries.
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Patients diagnosed with diabetes insipidus due to pituitary stalk thickness should be considered as a metastasis, after exclusion of the classical systemic and infectious diseases.
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The diagnosis of an endocrinological metastatic primary lung adenocarcinoma for patients without respiratory symptoms is often delayed due to a lack of correlation between endocrinological symptoms and lung cancer.
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The main originality of our case is the concomitant diagnosis of both endocrinological failures, as it was initiated with a diabetes insipidus and followed by an acute adrenal insufficiency.
Search for other papers by Kaja Grønning in
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Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Summary
Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency. More than 90% is of B-cell origin. The condition is bilateral in up to 75% of cases, with adrenal insufficiency in two of three patients. We report two cases of adrenal insufficiency presenting at the age of 70 and 79 years, respectively. Both patients had negative 21-hydroxylase antibodies with bilateral adrenal lesions on CT. Biopsy showed B-cell lymphoma. One of the patients experienced intermittent disease regression on replacement dosage of glucocorticoids.
Learning points:
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Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency.
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Bilateral adrenal masses of unknown origin or in individuals with suspected extra-adrenal malignancy should be biopsied quickly when pheochromocytoma is excluded biochemically.
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Steroid treatment before biopsy may affect diagnosis.
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Adrenal insufficiency with negative 21-hydroxylase antibodies should be evaluated radiologically.
Search for other papers by M A Shehab in
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Search for other papers by Tahseen Mahmood in
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Search for other papers by Md Fariduddin in
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Search for other papers by Mohammad Shahnoor Hossain in
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Summary
Congenital adrenal hyperplasia (CAH) due to the three-beta-hydroxysteroid-dehydrogenase (3β-HSD) enzyme deficiency is a rare autosomal recessive disorder presenting with sexual precocity in a phenotypic male. Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy presenting with hypergonadotropic hypogonadism in a male. However, only a handful of cases of mosaic KS have been described in the literature. The co-existence of mosaic KS with CAH due to 3β-HSD enzyme deficiency portrays a unique diagnostic paradox where features of gonadal androgen deficiency are masked by simultaneous adrenal androgen excess. Here, we report a 7-year-old phenotypic male boy who, at birth presented with ambiguous genitalia, probably a microphallus with penoscrotal hypospadias. Later on, he developed accelerated growth with advanced bone age, premature pubarche, phallic enlargement and hyperpigmentation. Biochemically, the patient was proven to have CAH due to 3β-HSD deficiency. However, the co-existence of bilateral cryptorchidism made us to consider the possibility of hypogonadism as well, and it was further explained by concurrent existence of mosaic KS (47,XXY/46,XX). He was started on glucocorticoid and mineralocorticoid replacement and underwent right-sided orchidopexy on a later date. He showed significant clinical and biochemical improvement on subsequent follow-up. However, the declining value of serum testosterone was accompanied by rising level of FSH thereby unmasking hypergonadotropic hypogonadism due to mosaic KS. In future, we are planning to place him on androgen replacement as well.
Learning points:
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Ambiguous genitalia with subsequent development of sexual precocity in a phenotypic male points towards some unusual varieties of CAH.
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High level of serum testosterone, adrenal androgen, plasma ACTH and low basal cortisol are proof of CAH, whereas elevated level of 17-OH pregnenolone is biochemical marker of 3β-HSD enzyme deficiency.
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Final diagnosis can be obtained with sequencing of HSD3B2 gene showing various mutations.
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Presence of bilateral cryptorchidism in such a patient may be due to underlying hypogonadism.
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Karyotyping in such patient may rarely show mosaic KS (47,XXY/46,XX) and there might be unmasking of hypergonadotropic hypogonadism resulting from adrenal androgen suppression from glucocorticoid treatment.
Search for other papers by Xin Feng in
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Search for other papers by Gregory Kline in
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Summary
In a 61-year-old Caucasian male with prostate cancer, leuprolide and bicalutamide failed to suppress the androgens. He presented to endocrinology with persistently normal testosterone and incidental massive (up to 18 cm) bilateral adrenal myelolipomas on CT scan. Blood test did not reveal metanephrine excess. The patient was noted to have short stature (151 cm) and primary infertility. Elementary school photographs demonstrated precocious puberty. Physical examination revealed palpable abdominal (adrenal) masses. Abiraterone and glucocorticoid treatment was commenced with excellent suppression of testosterone. Genetic testing revealed a mutation in CYP21A2 confirming 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). Association of large myelolipomas with CAH has been reported in the literature. Our case highlights the importance of considering CAH in patients with non-suppressed testosterone despite androgen deprivation therapy. Large myelolipomas should raise the suspicion of congenital adrenal hyperplasia.
Learning points:
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Adrenal myelolipomas are rare benign lesions that are more common in patients with longstanding untreated congenital adrenal hyperplasia thought to be due to ACTH stimulation.
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Consider undiagnosed congenital adrenal hyperplasia in patients with adrenal myelolipoma.
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Glucocorticoid replacement may be an efficacious treatment for patients with prostate cancer and CAH. Abiraterone therapy has a risk of adrenal crisis if glucocorticoids are not replaced.
Search for other papers by Geetanjali Kale in
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Summary
Myelolipomas have been reported in patients with congenital adrenal hyperplasia (CAH). ACTH excess, as seen with non-adherence to glucocorticoid therapy, may be responsible for tumor development. We report a case of a 51-year-old man with classic salt-wasting CAH managed on prednisone 7.5 mg daily and fludrocortisone who presented with chronic back pain and was found to have giant bilateral retroperitoneal masses. On computed tomography (CT) imaging, the masses were heterogeneous, but contained predominantly low-density fat attenuation. The tumors were resected due to concern for malignancy and mass symptoms. Pathologic examination identified both retroperitoneal masses as myelolipomas. The left tumor was 34×20×13 cm and weighed 4.7 kg and the right tumor was 20 cm in the largest dimension. Adrenal tissue was present in the specimen. The patient reported long-term compliance with glucocorticoid treatment. However, no biochemical monitoring of ACTH levels had occurred. Therefore, it is unclear if ACTH excess contributed to the development of these large tumors in this patient. It was presumed that both adrenal glands were inadvertently removed during surgery and the patient was treated with physiologic replacement doses of hydrocortisone and fludrocortisone postoperatively. In this case, the bilateral adrenalectomy was inadvertent. However, adrenalectomy can be considered as a treatment option in patients with classical CAH under certain circumstances to avoid complications of glucocorticoid excess.
Learning points
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Myelolipomas should be considered in the differential diagnosis of adrenal or retroperitoneal masses in patients with CAH.
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On CT imaging, myelolipomas are seen as heterogeneous masses with low-density mature fat interspersed with more dense myeloid tissue.
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Myelolipomas are usually unilateral and measure <4 cm; however, very large and bilateral tumors have been reported.
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Treatment of CAH typically involves using supraphysiologic doses of glucocorticoid to suppress adrenal hyperandrogenism. Bilateral adrenalectomy is an alternative treatment option in patients with CAH.
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There is an association between ACTH excess and increased incidence of adrenal myelolipoma but the direct causal link remains to be established.
