1/14. carney complex--an unexpected finding during puerperium.carney complex is an extremely rare, autosomal dominant, multi-system disorder characterized by multiple neoplasias and lentiginosis. The genetic defect responsible for this complex has been localized to the short arm of chromosome 2 (2p16). The most prevalent clinical manifestations in patients with carney complex are spotty skin pigmentation, skin and cardiac myxomas, Cushing's syndrome and acromegaly. Here we report the case of a 31-year-old woman with a spontaneous pregnancy. At 32 weeks of gestation, she was admitted to our Department of obstetrics with hypertension and severe back pain. In addition, she had unusual pigmentation and typical cushingoid features. One day after admission, the pregnancy was terminated by emergency cesarian section because of preeclampsia and pathological CTG. During the postoperative period the severe back pain persisted, and radiographic evaluation revealed a collapse of L(2)/L(3) with severe osteopenia. A CT scan showed a mass in the right suprarenal area. Histopathological examination revealed a primary pigmented nodular adrenocortical disease. After biochemical confirmation of the diagnosis of Cushing's syndrome, it was recognized that the patient met the diagnostic criteria for carney complex.- - - - - - - - - - ranking = 1keywords = pigmented (Clic here for more details about this article) |
2/14. Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease.Primary pigmented nodular adrenocortical disease (PPNAD) is a cause of ACTH-independent Cushing's syndrome. This condition can be difficult to diagnose because hypercortisolism may be periodic and adrenal imaging may not demonstrate an adrenal tumor. PPNAD can be part of the carney complex (CNC), an autosomal dominant multiple neoplasia syndrome. Germline mutations of the regulatory subunit R1A of PKA (PRKAR1A) have been observed in about 45% of CNC kindreds. To improve our understanding of sporadic PPNAD and develop a potential diagnostic tool, we investigated the genetics of patients with sporadic and isolated PPNAD. patients undergoing surgery for bilateral ACTH-independent Cushing's syndrome in whom pathological examination revealed PPNAD were subjected to endocrinological investigations and a systematic search for other manifestations of CNC. The PRKAR1A gene was sequenced using dna from frozen adrenal tissues and leukocytes from three patients with sporadic isolated PPNAD and using leukocyte dna from two additional patients. Different inactivating germline mutations of the PRKAR1A gene were found in the five patients. For three cases, study of the parents' dna demonstrated a de novo mutation. One patient presented with an unusual 2.5-cm macronodule of the right adrenal mimicking an adrenal adenoma. A somatic 16-bp deletion of PRKAR1A gene was also found in this macronodule. Inactivating germline mutations of PRKAR1A are frequent in sporadic and isolated cases of PPNAD. The wild-type allele can be inactivated by somatic mutations, consistent with the hypothesis of the gene being a tumor suppressor gene. Thus, genetic analysis can be of help to the clinician in the diagnosis of this difficult form of adrenal Cushing's syndrome.- - - - - - - - - - ranking = 5keywords = pigmented (Clic here for more details about this article) |
3/14. carney complex, a familial Cushing's syndrome due to primary pigmented nodular adrenocortical disease: a case report.A 45-year-old woman with adrenocorticotropin (ACTH)-independent hypercortisolism, diabetes mellitus, and hypertension had undergone left adrenalectomy for ACTH-independent Cushing's syndrome 20 years prior to this presentation. There was cushingoid appearance 1 year after surgery. However, Cushing's syndrome recurred; ACTH-independent Cushing's syndrome was diagnosed and abdominal computerized tomography showed a right adrenal tumor, which was removed. histology revealed primary pigmented nodular adrenocortical disease (PPNAD). The patient had also undergone hysterectomy for uterine masses diagnosed as uterine myxoma. Right breast and neck skin masses were also found, both of which were removed and diagnosed as mammary myxoid fibroadenoma and cutaneous myxoma. She had a homozygotic twin sister who also had Cushing's syndrome and had undergone bilateral adrenalectomy 13 years previously with a pathologic diagnosis of PPNAD. The twin sister also had skin, breast, and uterine masses, all of which were resected. The pathologic results were the same as this patient's. According to the clinical presentations, histologic findings, and positive family history, familial PPNAD (carney complex) was diagnosed.- - - - - - - - - - ranking = 5keywords = pigmented (Clic here for more details about this article) |
4/14. 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.- - - - - - - - - - ranking = 1keywords = pigmented (Clic here for more details about this article) |
5/14. A six month mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and carney complex.A low-dose mitotane (MT) regimen was evaluated as a pharmacological approach for correcting the severe hypercortisolism in a young woman affected by carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD). In the first 12 week period, the MT daily dose was progressively increased from 0.5 to 4.0 g/day. This dosage was maintained for an additional 16 weeks (cumulative dose 602 g, plasma MT maximum level 12 microg/ml), and then stopped because of sustained signs of hypoadrenalism requiring prednisone replacement. Complete regression of seborrhea, acne, and plethora was observed after 8 weeks of treatment (cumulative dose 95 g). Regular menses returned after 13 weeks (cumulative dose 197 g, plasma MT 8 microg/ml). Profound decrease of both serum cortisol (from 615 to 220 nmol/l) and urinary free cortisol (UFC) values (from 1498 to 477 nmol/day) was noted after 16 weeks of treatment (cumulative dose 314 g, plasma MT 8 microg/ml). MT treatment was associated with mild gastric discomfort and reversible increase of cholesterol plasma levels. Low serum cortisol and UFC were still observed 41 weeks after MT was discontinued (plasma MT 0.2 microg/ml). Our report demonstrates that low dose MT treatment may be a safe and effective modality for a sustained correction of hypercortisolism by PPNAD in subjects with CNC waiting for surgery.- - - - - - - - - - ranking = 1keywords = pigmented (Clic here for more details about this article) |
6/14. Successful pregnancy after unilateral adrenalectomy in a case of primary pigmented adrenocortical disease.We describe a case of successful pregnancy in a patient with primary pigmented nodular adrenocortical disease. Unilateral adrenalectomy was performed pre-conception as treatment for the patient's bilateral adrenal disease. She later delivered a healthy infant by cesarean section at week 38 of gestation. There was no evidence of either hyper- or hypo-cortisolism during the pregnancy. The unilateral laparoscopic adrenalectomy was successful in controlling her hypercortisolism during the ensuing pregnancy, and might provide a valid (albeit temporary) solution in similar situations.- - - - - - - - - - ranking = 5keywords = pigmented (Clic here for more details about this article) |
7/14. A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds.CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent cushing syndrome, can be part of carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation. OBJECTIVE: The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at two referral centers. patients: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD. RESULTS: We describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12 unrelated kindreds that were referred for cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers. CONCLUSIONS: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype.- - - - - - - - - - ranking = 5keywords = pigmented (Clic here for more details about this article) |
8/14. Familial Cushing's syndrome due to nodular adrenocortical dysplasia. A putative receptor-antibody disease?Two sisters aged 13 and 19 years suffering from familial Cushing's syndrome due to nodular adrenocortical dysplasia are described. Pituitary adrenocortical function tests indicated the presence of adrenal autonomy. Adrenal scintigraphy showed bilateral symmetrical uptake indicating the bilateral character of the autonomous process. Complete adrenalectomy was performed in both girls. The adrenals were of about normal weight showing numerous dark brown pigmented nodules and small perivascular lymphocytic infiltrates. serum immunoglobulin preparations obtained from both girls stimulated adrenocortical cell growth in a cytochemical bioassay system. It is proposed that circulating growth factors may be involved in the pathogenesis of the disease.- - - - - - - - - - ranking = 1keywords = pigmented (Clic here for more details about this article) |
9/14. Cushing's syndrome resulting from primary pigmented nodular adrenocortical disease.In a 10-year-old boy with Cushing's syndrome, the dexamethasone suppression test, the metyrapone test, and both basal and corticotropin-releasing factor-stimulated corticotropin levels all indicated a primary adrenal disorder. However, a computed tomographic scan failed to detect an adrenal tumor. At surgery, the adrenal glands were not enlarged but were studded with small pigmented nodules composed of enlarged nonmalignant adrenocortical cells. This unusual abnormality, referred to as primary pigmented nodular adrenocortical disease, is associated with autonomous hypersecretion of cortisol primarily in children and young adults. Our patient was cured by total bilateral adrenalectomy and corticosteroid replacement therapy, the treatment of choice for this condition.- - - - - - - - - - ranking = 6keywords = pigmented (Clic here for more details about this article) |
10/14. The complex of myxomas, spotty pigmentation, and endocrine overactivity.Of 40 patients (16 males and 24 females), 29 had cardiac myxoma(s), 14 had skin pigmentation (lentigo and several types of nevi) which also commonly affected the lips, 6 had skin myxoma(s), and 12 had both pigmentation and myxoma(s); 18 had primary pigmented nodular adrenocortical disease (cushing syndrome was present in 11); 10 had myxoid mammary fibroadenomas; 9 had testicular tumor(s) (large-cell calcifying sertoli cell tumor, leydig cell tumor, or adrenocortical rest tumor, or a combination); and 4 had pituitary adenoma with gigantism or acromegaly. The maximum number of conditions present together was five, occurring in two patients; each of the remaining patients had at least two of the conditions. The overlap, in this sizeable number of patients, of various combinations of the same rare or very rare conditions unlikely to occur together by chance with any degree of frequency is striking evidence for a unique syndrome. The patients were young (mean age at diagnosis of the first component, 18 years). Pathologic involvement tended to be multicentric (heart and skin) and bilateral in paired organs (adrenal, breast, and testis). Thirteen patients (32%) are alive and well. Twelve patients are alive but with complications of cardiac myxoma (in 8), testicular tumors (in 2), residual cushing syndrome (in 1), or bilateral pulmonary nodules (in 1). Twelve patients are dead: 9 of cardiac myxoma, 1 of intracranial (nonpituitary) tumor, and 2 postoperatively. The status of three is unknown.- - - - - - - - - - ranking = 1keywords = pigmented (Clic here for more details about this article) |
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