Adrenal tuberculosis in Cushing's disease with bilateral macronodular adrenocortical hyperplasia

Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.     

Adrenal black adenoma associated with Cushing's syndrome

We report a case of adrenal black adenoma associated with Cushing's syndrome. A 41-yr-old man presented to our hospital with a 6-yr history of severe hypertension and general fatigue, and a 1-mo history of diabetes mellitus. Physical examination disclosed cushing-oid manifestations. His serum cortisol concentrations ranged from 14.0 to 15.4 microg/dL, with an ACTH level <5 pg/mL. Urinary free cortisol level was increased (125 microg/d). Cortisol was not suppressed on the overnight 1 mg oral dexamethasone suppression test (DST), 2-d low-dose DST, and 2-d high-dose DST. Abdominal computed tomography and magnetic resonance imaging studies revealed a solid round tumor approx 3 cm in diameter, located in the left adrenal gland. Left adrenalectomy was performed; the surgical specimen revealed a black ade-noma consisting of compact cells within numerous pigments that seemed to be lipofuscin in nature.     

Primary pigmented nodular adrenocortical disease and Cushing's syndrome

Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with corticotrophin (ACTH)-independent Cushing's syndrome (CS) and is characterized by small to normal-sized adrenal glands containing multiple small cortical pigmented nodules (1,2). PPNAD may occur in an isolated form or associated with a multiple neoplasia syndrome, the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, or Carney complex, in which Cushing's syndrome is the most common endocrine manifestation (3). Molecular studies have led to the identification of several genes, defects in which may predispose PPNAD formation; all of these molecules play important role for the cAMP signaling pathway. This review intends to present the most recent knowledge of the pathology and molecular genetics of the benign bilateral adrenocortical lesions, as well as to discuss the modern tools for diagnostics and treatment of this condition.     

Cushing's syndrome due to bilateral adrenocortical adenomas with unique histological features

Cushing's syndrome due to bilateral cortisol-secreting adenomas rarely occurs. We present a case of Cushing's syndrome due to bilateral adenomas. Both adenomas had distinct cell compositions, and were compared with emphasis on immunohistochemical and enzyme histochemical analysis for cytochrome P450(11beta) and 3beta-hydroxysteroid dehydrogenase (3betaHSD). A 37 year-old female was diagnosed with ACTH-independent Cushing's syndrome based on physical findings and hormonal evaluation. High-resolution CT scan showed bilateral adrenocortical adenomas and atrophied glands. 131I-methylnorcholesterol incorporation into both glands suggested both adenomas were functional. Clinical diagnosis prior to surgery was ACTH-independent Cushing's syndrome due to functioning bilateral adenomas. The left adrenal gland was totally resected, while the right one was partially resected by laparoscopic approach. Both adenomas were black on cut sections, and were comparatively evaluated by immunohistochemical and enzyme histochemical analysis for P450(11beta) and 3betaSD. The left adenoma was 1.6 cm in diameter and had a complex cellular composition and enzyme expression similar to that of primary pigmented nodular adrenocortical disease (PPNAD), while the right adenoma was 1.8 cm in diameter with compact cells typical of a solitary cortisol-producing adenoma. Adjacent bilateral adrenal cortex showed marked atrophy, but contained several micronodules. Serum cortisol levels, both at basal and after a low dodexamethasone, normalized thirteen months after surgery. In conclusion, the present case of Cushing's syndrome with bilateral adrenal adenomas demonstrated for the first time the simultaneous occurrence of two distinct adenomas, an ordinary cortisol-producing adenoma and a PPNAD-like adenoma. Further case reports of multiple adrenal adenomas should be well-analyzed to clarify whether the results from this case represent a new subgroup of ACTH-independent Cushing's syndrome.     

Virilizing adrenocortical adenoma with Cushing's syndrome,thyroid papillary carcinoma and hypergastrinemia in a middle-aged woman

We report a rare case of virilizing adrenocortical adenoma complicated with Cushing's syndrome, thyroid papillary carcinoma and hypergastrinemia. A 45-year-old woman had a history of amenorrhea for 10 years, hypertension for 8 years, and diabetes mellitus for 3 years. Physical examination showed a masculinized woman with severe hirsutism, male-like baldness, deep voice, acne in the precordia, and clitorism. Plasma testosterone, DHEA-S and urinary 17-KS were high, and plasma cortisol level was it at the upper limit of the normal range, but it did not show a diurnal rhythm nor was suppressed by 2 and 8 mg of dexamethasone. Abdominal CT scan showed a left adrenal tumor (4.5 cm in size). Adrenal scintigram revealed uptake of the tracer on the left side, and plasma cortisol concentration was high in a blood sample from the left adrenal vein. Left adrenalectomy was performed. Histopathological features of resected adrenal tumor were consistent with those of adrenocortical adenoma, consisting of tumor cells with eosinophilic compact cytoplasm. Immunohistochemical staining for steroidogenic enzymes showed reactivity for P450sec, 3 beta-HSD, P450c17, P450c21 and P450c11. Plasma testosterone and cortisol levels decreased to the normal range postoperatively. The patient was also found to have a papillary thyroid carcinoma and hypergastrinemia. Our patient is a rare case of virilizing adrenocortical adenoma associated with Cushing's syndrome, thyroid papillary carcinoma, and hypergastrinemia.     

双侧肾上腺皮质腺瘤致库欣综合征一例

患者 ,女 ,36岁。因渐进性肥胖 8年 ,头痛头晕 8个月于1998年 11月 11日入院。患者 1989年体重 6 4公斤 ,此后逐渐增加。 1998年 3月出现头痛和头晕 ,查血压为 16 0 / 115ｍｍＨｇ(1ｍｍＨｇ=0 .133ｋＰａ) ,给予“降压药”后 ,血压波动在12 0～ 130 / 85～ 90ｍｍＨｇ之间。每次测血压后患者前臂均出现出血点 ,四肢易发生淤斑。 1998年 9月出现腰痛 ,乏力 ,记忆力下降 ,月经周期延长和经量减少。体格检查 :身高 16 2ｃｍ ,体重 88公斤 ,血压 16 0 / 10 0ｍｍＨｇ ,轻度向心性肥胖 ,水牛背 ,满月脸 ,多血质面容。面部、前胸和后背可见痤疮 ,…     

Residual adrenocortical function after bilateral adrenalectomy for pituitary-dependent Cushing's syndrome.

The incidence of residual, functioning adrenal tissue in patients treated by total bilateral adrenalectomy for Cushing's disease is not known. Between 1962 and May 1988 50 patients with Cushing's disease were treated by bilateral adrenalectomy. Of these patients, 29 underwent surgery between 1962 and 1980, when bilateral adrenalectomy was the treatment of first choice in our hospital in patients with pituitary-dependent Cushing's syndrome. In 37 patients the presence or absence of cortisol-producing tissue could be evaluated (follow-up period, median and range, 8.3 and 0.1-18.9 yr). Evidence of functioning cortisol-producing tissue (plasma cortisol level > 50 nmol/L after stopping glucocorticoid and mineralocorticoid substitution therapy for 24 h) was found in 9 patients (24%). Plasma cortisol levels in these 9 patients varied between 60 and 330 nmol/L (mean +/- SD, 180 +/- 100 nmol/L). Signs and symptoms of recurrent Cushing's syndrome were present in only 1 patient. There was no difference in plasma ACTH levels and duration of follow-up between the patients with and without evidence of functioning cortisol-producing tissue. In all 9 patients detectable aldosterone levels indicated endogenous mineralocorticoid production, whereas in only 1 patient adrenaline was detectable in the circulation. In 8 of the 9 patients suspected of functioning cortisol-producing tissue we performed a stimulation test with synthetic ACTH (1-24). In 2 patients plasma cortisol levels rose, in 6 they remained virtually unchanged. Although we found clinically relevant signs and symptoms of Cushing's syndrome in only 1 of the 50 patients, the relatively high incidence of residual, functioning adrenal tissue after "total" adrenalectomy for pituitary-dependent Cushing's syndrome necessitates continuous surveillance for recurrent Cushing's syndrome. There is no place for routine administration of full replacement doses of glucocorticoids after total adrenalectomy.     

Concomitant Cushing's syndrome due to adrenal adenoma in a patient with systemic lupus erythematosus

A 51-year-old woman had been administered 5 mg/day of prednisolone due to systemic lupus erythematosus (SLE). She developed hypertension, hypokalemia and a pathologic pubic fracture during two years before admission. Although iatrogenic Cushing's syndrome was initially suspected, we diagnosed her as concomitant Cushing's syndrome due to a left adrenal tumor. The elevated endogeneous glucocorticoids were evaluated from urinary excretions of 17-hydroxycorticosteroids, which was 2-fold higher than normal and equivalent to 10 mg of prednisolone. After laparoscopic left adrenalectomy, SLE was favorably controlled with 15 mg of prednisolone, the dosage of which was equivalent to the estimated amount of preoperative glucocorticoids.     

Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias

Adrenocortical causes of Cushing's syndrome include the following: common cortisol-producing adenomas, which are usually isolated (without associated tumors) and sporadic (without a family history); rare, but often clinically devastating, adrenocortical carcinomas; and a spectrum of adrenocorticotropin-independent, and almost always bilateral, hyperplasias, which are not rare, and are the most recently recognized cause. The majority of benign lesions of the adrenal cortex seem to be linked to abnormalities of the cyclic AMP signaling pathway, whereas cancer is linked to aberrant expression of insulin-like growth factor II, tumor protein p53 and related molecules. In this article, we propose a new clinical classification and nomenclature for the various forms of adrenocorticotropin-independent adrenocortical hyperplasias that is based on their histologic and genetic features. We also review the molecular genetics of adrenocortical tumors, including recent discoveries relating to the role of phosphodiesterase 11A. This is a timely Review because of recent advances in the clinical and molecular understanding of these diseases.     

Unilateral adrenalectomy improves insulin resistance and polycystic ovaries in a middle-aged woman with virilizing adrenocortical adenoma complicated with Cushing's syndrome

A benign virilizing adrenal adenoma is rare among adrenal neoplasms in middle-aged women. A 39-yr-old Japanese woman who presented with hirsutism, obesity, diabetes mellitus and hypertension was admitted. Plasma concentrations of testosterone and DHEAS were high. While the basal level of plasma ACTH was suppressed, serum cortisol level was high and its circadian rhythm was absent. Serum cortisol level was not suppressed with the low- and high-dose overnight dexamethasone suppression test. Abdominal computed tomography showed a left adrenal tumor, and an adrenocortical scintigraphy revealed uptake of the tracer on the left side. Polycystic ovaries were also found and bone mineral density revealed osteoporosis. Histopathological features of resected adrenal tumor were consistent with those of adrenocortical adenoma. Immunoreactivity of all the steroidogenic enzymes was apparent in the tumor cells and particularly dehydroepiandrosterone sulfotransferase (DHEA-ST) immunoreactivity was markedly expressed. Cortical atrophy and reduced expression of DHEA-ST were detected in the cortex of the adjacent non-neoplastic adrenal gland. Plasma testosterone, DHEAS and cortisol levels returned to normal after surgery, concomitantly with the disappearance of polycystic ovaries. This is a very rare case of virilizing adrenocortical adenoma complicated with Cushing's syndrome (CS).