Neoplasia oncocítica adrenocortical de potencial maligno incierto: reporte de un caso / Adrenocortical oncocytic neoplasm with uncertain malignant potential: a case report

Resumen Objetivo Describir el caso clínico de una paciente con neoplasia oncocitica adrenocortical, tratado quirúrgicamente en una clínica de Lima, Perú. Caso clínico Paciente mujer de 26 años ingresa a emergencia por dolor abdominal inespecífico. Se evidencia tumoración de 15x14x12 cm dependiente de glándula suprarrenal izquierda por lo que se decide tratamiento quirúrgico. Al análisis patológico se evidencia neoplasia oncocítica de potencial maligno incierto. Discusión Las neoplasias oncocíticas adrenocorticales son entidades poco frecuentes, con escasos reportes de casos de esta enfermedad. Para clasificarlas, se usa la escala de Weiss modificada. Obtenemos una neoplasia oncocítica de potencial maligno incierto, cuyo tratamiento incluye la cirugía de resección de tumor y observación. Conclusión Considerar a las neoplasias oncocíticas dentro del diagnóstico diferencial de incidentalomas adrenales.

Objective To describe a case report of a oncocytic adrenocortical neoplasm, treated surgically in a clinic in Lima, Peru. Case report A 26-year-old woman is admitted to the emergency due to nonspecific abdominal pain. A tumor measuring 15x14x12 cm dependent on left adrenal gland is evidenced, so surgical treatment is decided. Pathological analysis evidences oncocytic neoplasia of uncertain malignant potential. Discussion Oncocytic adrenocortical neoplasms are rare entities, with few case reports of this disease. To classify them, the modified Weiss scale is used. We obtain an oncocytic neoplasm of uncertain malignant potential, whose treatment includes surgery for tumor resection and observation. Conclusion Consider oncocytic neoplasms within the differential diagnosis of adrenal incidentalomas.

Role of losartan on the renal cortex damage induced by cisplatin in adult male albino rats

Cisplatin is a potent anticancer agent for the treatment of solid tumors, but its use is limited by its adverse effects. This research aimed to evaluate the effect of losartan on cisplatin nephrotoxicity in adult male albino rats. Twenty-five male albino rats were divided into four groups. The first was the control group. Group II received a single injection of cisplatin. Group III received losartan for 6 days. Group IV received a single injection of cisplatin in addition to losartan ingestion for 6 days. Renal tissues were prepared for light and transmission electron microscopic examinations. Glomerular diameter and cell number were measured by means of an image analyzer. Also, glomerular capillary basement membrane [GBM] thickness, filtration slit width, and pedicel length were recorded and statistically analyzed. The renal cortical sections of group II rats showed loss of normal appearance of renal corpuscles with enlarged glomeruli and increased glomerular cellularity. Degenerative changes and necrosis of the lining cells of proximal convoluted tubule were noted. Intertubular hemorrhage and cellular infiltration were detected. Electron microscopic examination revealed fusion of the foot processes with significant increase in the thickness of GBM and filtration slit width. Damage of proximal convoluted tubule cells was seen more than damage of distal convoluted tubules. The renal cortical sections of group III rats showed vacuolated cytoplasm of some tubules lining cells. Electron microscopic examination revealed some ultrastructural changes in the distal convoluted tubule lining cells. Most of the renal corpuscles of rats treated with losartan and cisplatin appeared normal, with presence of some enlarged corpuscles as well as cytoplasmic vacuolation of the tubular cells. Electron microscopic examination revealed a significant decrease in GBM thickness and filtration slit width in comparison with cisplatin-received rats. From this study, it was obvious that losartan ameliorates the histological changes induced by cisplatin given at a dose of 3 mg/kg in adult male rats

possible toxic effect of different doses of Nigella sativa oil on the histological structure of the liver and renal cortex of adult male albino rats

Nigella sativa seeds are commonly known as black seed or black cumin. It has been used for thousands of years as a spice and food preservative and also as a protective and curative remedy for numerous disorders. Our research aimed to study the possible toxic effect of different doses of N. sativa oil on the liver and kidney. Twenty-one adult male albino rats were used and divided equally into three groups. The first group was the control group. The second and third groups received the oil in two gradually increasing doses of 15 and 25 ml/kg, respectively, for 1 month. The animals were then sacrificed and samples of liver and kidney were taken and prepared for histological examination. In the kidney of group II there was epithelial shedding and necrosis of some cells of the proximal and distal convoluted tubules, but there was no effect on renal glomeruli. In contrast, in group III there was glomerular injury in the form of degeneration of the tuft of capillaries, ill-defined basement membrane, and destruction of endothelial cells, in addition to tubular necrosis. In group II there was minimal effect on the liver in the form of perivascular cellular infiltration; in group III was seen a markedly vacuolated foamy cytoplasm of hepatocytes, with dilated sinusoids and perivascular cellular infiltration. In conclusion, large doses of N. sativa oil have toxic effects on the histological structure of the kidney and to a lesser degree on the liver. Therefore, Nigella oil should be used in proper doses, and further studies on the effect of large doses of oil are recommended

Effect of shark liver oil on renal cortical structure in hypercholesterolemic rats

Numerous studies reported the association between hypercholesterolemia and renal damage. Elevated plasma cholesterol is involved in the onset and progression of renal diseases. Shark liver oil is reported to be an antioxidant and hypolipidemic. This study was conducted to investigate the possible effects of two different doses of shark liver oil in reducing renal cortical changes associated with high cholesterol diet feeding in correlation with serum lipids. Forty rats were divided into two groups: control group [group 1 = 1 0 rats] and high cholesterol diet-fed group [group 2 = 30 rats]. Group 2 was further subdivided into three subgroups: group 2a, nonsupplemented with shark liver oil; group 2b, supplemented with 1 0% shark liver oil; and group 2c supplemented with 20% shark liver oil. Kidney samples were processed for general histological, immunohistochemical, and ultrastructural study of the renal cortex. Blood samples were collected for assessment of serum lipids. High cholesterol diet-fed group showed prominent podocyte injury characterized by de novo desmin staining and flattening and fusion of foot processes. Some renal corpuscles exhibited thickening and distortion of the glomerular basement membrane. Renal tubular cells showed intracellular vacuoles and mitochondrial degeneration. These structural changes were associated with altered serum lipids. Shark liver oil dietary supplement noticeably ameliorated renal cortical damage and corrected the changes in serum lipids with better improvement in the 20% shark liver oil-supplemented group. This study reveals the beneficial effect of shark liver oil, as a health supplement, in ameliorating the structural renal cortical damage and hypercholesterolemia associated with high cholesterol diet feeding

Acute heat stress and adrenal cortex: biochemical, histological and ultrastrureal study in albino rats

Stress can be defined as a state of threatened balance induced by external stressor and appear as the display of somatic, and psychic reaction, struggling to regain homeostasis. Among stressful stimuli, heat stress is an environmental factor capable of causing a wide range of physiological alteration chiefly at the level of the hopothalamic- pituitary-adrenocortical [HPA] axis. The objective of the present study was to evaluate the effect of acute heat exposure on the ACTH and cortisol levels as well as structurally and ultrastructurally changes of the adrenal cortical glands in rats. Twenty normal adult male albino rats, weighting 180-200 grams, were divided into two equal groups. Group A represented the control rats and group B acted as a heat stressed rats that were exposed to hear at 38-40[degree sign]C for sixty minutes. At the end of experiment, rats were anesthetized, blood sample withdrawn for hormonal study and suprarenal glands were dissected out and prepared for microscopical and ultrasctructural examinations. A significant increase in ACTH and cortisol levels were reported in heat stressed group when compared with control group. Light microscopic examination of suprarenal cortical layers of heat-stressed rats revealed foamy cytoplasm with pyknotic nuclear changes as compared to control rats. In addition, ultrastructure examination of group B showed mitochondrial changes in all zones especially zona reticularis, decreased number of lipid droplets in both zona fasciculate and reticularis, and prominent dilatation of smooth endoplasmic reticulum vesicles when compared with group A. In conclusion, acute heat exposure was a stressful condition affecting the suprarenal glands as evidenced by the altered biochemical hormonal levels along with both structural and ultra structural changes

Absence of PRKAR1A loss of heterozygosity in laser-captured microdissected pigmented nodular adrenocortical tissue from a patient with Carney complex caused by the novel nonsense mutation p. Y21X / Ausência da perda de heterozigose do PRKAR1A em células capturadas por microdissecção a laser de tecido de nódulo pigmentoso adrenocortical de um paciente com complexo de Carney causado por uma nova mutação nonsense

OBJECTIVE: Primary pigmented nodular adrenocortical disease (PPNAD) is the main endocrine manifestation of Carney complex, a multiple neoplasia syndrome caused by PRKAR1A gene mutations. The presence of PRKAR1A loss of heterozygosity (LOH) in adrenocortical tumorigenesis remains controversial. The aim of the present study is to investigate the presence of PRKAR1A LOH in adrenocortical cells in a patient with Carney complex. METHODS: The LOH was investigated using a PRKAR1A informative intragenic marker by GeneScan software analysis in DNA obtained from laser-captured microdissected cells of several adrenal nodules. Patients: A young adult male patient with Carney complex and his family were studied. RESULTS: A novel heterozygous mutation (p. Y21X) was identified at PRKAR1A in blood DNA of the male proband and his relatives. No PRKAR1A LOH was evidenced in the laser-captured microdissected cells from PPNAD tissue by different methodologies. CONCLUSION: We identified a new PRKAR1A nonsense mutation and in addition we did not evidence PRKAR1A LOH in laser-captured nodules cells, suggesting that adrenocortical tumorigenesis in PPNAD may occurs apart from the second hit.

OBJETIVO: A doença adrenocortical nodular pigmentosa primária (PPNAD) é uma das manifestações do complexo de Carney, uma neoplasia endócrina múltipla causada por mutações no PRKAR1A. A perda de heterozigose (LOH) do PRKAR1A na tumorigenese adrenal permanece controversa dada à possibilidade de contaminação com o tecido normal. Nosso objetivo foi investigar a presença de LOH no PRKAR1A a partir de células do nódulo adrenal de um paciente com complexo de Carney. MÉTODOS: A pesquisa da LOH do PRKAR1A foi realizada através do estudo de um marcador intragênico em DNA de células do nódulo adrenal microdissecadas a laser, evitando contaminação com o tecido normal. Pacientes: Um paciente com PPNAD e cinco familiares foram estudados. RESULTADOS: A nova mutação (p. Y21X) foi identificada no PRKAR1A sem evidência de LOH no tecido adrenal. CONCLUSÃO: Identificamos uma nova mutação no PRKAR1A e não evidenciamos LOH nas células dos nódulos adrenocorticais, sugerindo que a PPNAD possa ocorrer na ausência de um segundo evento molecular.

Insuficiencia glucocorticoidea en pacientes críticos / Glucocorticoid insufficiency in critically ill patients

Objetivo: Describir la respuesta grucocorticoidea en los pacientes admitidos en Terapia Intensiva y su correlación pronóstica. Diseño: Prospectivo, observacional en 2 Unidades de Terapia Intensiva de adultos polivalente de la ciudad de Buenos Aires Argentina: Hospital Cosme Argerich del GCBA e Instituto A Lanari, de la Universidad de Buenos Aires. Período comprendido: diciembre 2006 hasta abril 2007. Material y métodos: Pacientes adultos admitidos consecutivamente a Terapia Intensiva que no presentaron condición clínica previa o terapéutica que altere los dosajes de cortisol. Se establecieron tres grupos, a partir de la determinación basal de cortisol. -Grupo A: cortisol basal de 34 µg/dl. -Grupo C: cortisol basal entre 15 µg/dl y 34 µg/dl. Se consideró respuesta adecuada al incremento en 9 µ/dl o mayor de cortisol a los 30'o 60' de administrada 25 unidades Internacionales (UI) de ACTCH semisintética. La variable dependiente fue la mortalidad en UTI/hospitalaria...

Cellular and molecular abnormalities of a macronodular adrenal hyperplasia causing beta-blocker-sensitive Cushing's syndrome

Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) can be associated with abnormal responses of aberrantly expressed adrenocortical receptors. This study aimed to characterize in vitro the pathophysiology of hypercortisolism in a b-blocker-sensitive Cushing's syndrome due to AIMAH. Cortisol secretion profile under aberrant receptors stimulation revealed hyperresponsiveness to salbutamol (beta2-adrenoceptor agonist), cisapride (5-HT4 receptor agonist), and vasopressin in AIMAH cultured cells, but not in normal adrenocortical cells. By RT-PCR, AIMAH tissues revealed beta2-adrenoceptor overexpression rather than ectopical expression. MC2R expression was similar in both AIMAH and normal adrenocortical tissues. Curiously, cortisol levels of AIMAH cells under basal condition were 15-fold higher than those of control cells and were not responsive to ACTH. Analysis of culture medium from AIMAH cells could detect the presence of ACTH, which was immunohistochemically confirmed. Finally, the present study of AIMAH cells has identified: a) cortisol hyperresponsiveness to catecholamines, 5-HT4 and vasopressin in vitro, in agreement with clinical screening tests; b) abnormal expression of beta2-adrenoceptors in some areas of the hyperplastic adrenal tissue; c) autocrine loop of ACTH production. Altogether, the demonstration of aberrant responses to hormonal receptors and autocrine hormone production in the same tissue supports the assumption of multiple molecular alterations in adrenal macronodular hyperplasia.

A síndrome de Cushing secundária à hiperplasia adrenal macronodular independente de ACTH (AIMAH) pode estar associada com respostas anômalas a estímulos sobre receptores hormonais expressos de maneira aberrante no córtex adrenal. O objetivo deste trabalho foi caracterizar a fisiopatologia do hipercortisolismo in vitro na síndrome de Cushing responsiva a beta-bloqueadores decorrente de AIMAH. Em cultura de células, a secreção de cortisol apresentou resposta aumentada ao salbutamol (agonista beta2-adrenérgico), à cisaprida (agonista de receptor 5-HT4) e à vasopressina, na AIMAH mas não no córtex adrenal normal. O estudo de receptores aberrantes por RT-PCR demonstrou que o gene do receptor beta2-adrenérgico estava superexpresso (e não expresso ectopicamente) nos fragmentos da AIMAH quando comparado ao tecido normal. A expressão de MC2R foi semelhante em ambos. Curiosamente, o nível basal de secreção de cortisol pelas células da AIMAH foi 15 vezes superior às células normais, não havendo resposta das células AIMAH ao estímulo com ACTH. A análise do meio de cultura das células AIMAH revelou a presença de ACTH, que foi confirmada por estudo imuno-histoquímico. Em suma, este estudo demonstrou: a) aumento dos níveis de cortisol in vitro em resposta a catecolaminas, 5-HT4 e vasopressina, correspondendo aos resultados dos testes clínicos para pesquisa de receptores aberrantes; b) expressão anormal de receptores beta2-adrenérgicos em algumas áreas de hiperplasia; c) produção autócrina de ACTH. Estes resultados envolvendo ativação de receptores aberrantes e estímulo hormonal autócrino no mesmo tecido favorecem a hipótese da existência de alterações moleculares múltiplas na hiperplasia adrenal macronodular.

Chronic stress effects on the apoptotic index of the adrenal cortex of pregnant rats

Chronic stress by immobilization during gestation can alter several mechanisms that maintain homeostasis in adrenal gland. The aim of this work was to quantify the apoptotic index of adrenal cortex during mid-pregnancy and to prove cytological characteristics by electron microscopy. The apoptotic index did not present significant differences between the adrenal cortex areas of control and experimental rats in any of the three ages studied. The day of gestation influenced significantly on the apoptotic index in both groups. This index increased as gestation progressed. It may be concluded that chronic stress by immobilization might induce the increase of apoptotic index in adrenal cortex as gestation progresses which might be related variations of plasmatic corticosterone and prolactin, and to the decrease of specific growth factors. On the other hand, it might be concluded that each zone of adrenal cortex behaves independently in regards to apoptosis and cellular proliferation via paracrine and/or autocrine regulatory mechanisms without being affected by other zones.

Adrenocortical carcinomas: a 12-year clinicopathologic study of 15 cases.

Adrenal cortical carcinomas are rare neoplasms and the definitive diagnostic criteria are distant metastasis and / or local invasion. Due to advances in imaging techniques, adrenal cortical neoplasms are discovered earlier and are smaller, increasing the need for more accurate diagnosis and pathologic indicators of prognosis. A twelve year retrospective clinicopathologic analysis of 15 histopathologically proven cases of adrenocortical carcinomas was done. Clinical details including radiologic findings, endocrine manifestations and gross finding were analysed. Hematoxylin and eosin stained slides were reviewed. Emphasis was on application of Weiss criteria. All fifteen tumors fulfilled Weiss criteria of malignancy, ie. all 15 possessed 3 or more of these criteria of malignancy. Functional tumors showed a greater representation of mixed cell type. It was concluded that Weiss criteria is easy to apply and that a combined evaluation of clinical features, size, weight and microscopic appearance seems necessary for the diagnosis of adrenocortical carcinomas.

Adrenal cortical and medullar hyperplasia--a retrospective analysis of 6 cases / 华中科技大学学报（医学）（英德文版）

The features of the symptoms, laboratory tests and pathological characteristics of adrenal cortical and medullary hyperplasia were studied. In 6 cases of hypercatecholaminenia, plasma norepinephrine (NE), epinephrine (E), catecholamine (CA) and 24-h urinary vanillylmandelic acid (VMA), 17-hydroxycorticosteroid (OHCS) and 17-ketosteroid (KS) were determined. Adrenal glands were examined by CT scan and 131I-MIBG imaging. Pathological examination was performed after operation. The results showed that in 6 cases of hypercatecholaminenia (3 men and 3 women) aged from 34-50 years, the clinical features were just like "pheochromocytoma", for example, episodic headache, perspiration, palpitation, pallor, apprehension, nausea, tremor, anxiety and so on. Plasma levels of CA, NE and E were elevated in all 6 cases. 24-h urinary samples obtained at the onset revealed elevated VMA in 1 case. 24-h urinary cortisol was obviously elevated in all 6 cases. 24-h urinary 17-OHCS, 17-KS was normal. B-type ultrasound, CT, MRI and 131I-MIBG revealed 9 lateral adrenal gland diffuse or nodular enlargement in 6 cases. Pathologic examination showed adrenal cortical and medullary hyperplasia. Clinically, adrenal cortical and medullary hyperplasia resembled "pheochromocytoma". The most significant feature of this disease was both elevated plasma CA and 24-h urinary cortisol obviously. Pathologic examination showed adrenal cortex nodular hyperplasia and medullar diffuse or limit hyperplasia. Whether it is an independent disease or symptoms of the other disease has not final conclusion up till now.

Adreno-cortical insufficiency

Adrenocortical insufficiency is not an uncommon disorder. It results from decreased corticosteroid hormones in the circulation, either due to complete or partial destruction of adrenal cortex or diseases of the hypothalamus pituitary axis. A variety of causes including infections, autoimmune disorders, tumourous infiltration and iatrogenic factors have been identified. The presentation of adrenocortical insufficiency may be insidious but Addisonian crisis is a potentially lethal condition which should be dealt with properly with rewarding results. A number of laboratory tests, simple and sophisticated have been used and applied to assess the adrenal functions are described. The management of Addisonian crisis and steroid replacement therapy, including their brand and generic names alongwith their relative potencies have also be discussed. It also includes the current concepts, controversies and the management of patients with adrenocortical insufficiency who either become pregnant or undergo major or minor surgery

Effect of burn on the histological and histochemical structures of the adrenal cortex of mouse

The adrenal glands were taken from nine male mice after exposure to burn on the thigh by a hot metal rod at different periods of time i.e. 0.5 hour, 1 hour and 24 hours [3 at a time]. The histological structure and histochemical localization of lipid, ascorbic acid, alkaline and acid phosphatase were studied. The results showed that half an hour after exposure to burn, the sinusoids in zona fasciculata were much dilated; while one hour after exposure to burn, zona fasciculata increased in depth and it was pale due to large number of vacuoles in the cells. The sinusoids were more dilated. Loss of subglomerulosal zone was noted. After 24 hours of exposure to burn, the histological pictures returned to that of control group. Gradual lipid depletion from zona reticularis and zona fasciculata started one hour after exposure to burn, followed by accumulation of lipid at twenty-four hours. A marked depletion of ascorbic acid in zona glomerulosa and depletion of ascorbic acid content started within 0.5 hour after burn from the outer zones inwards. Twenty-four hours after burn, ascorbic acid content returned to that of control group

Adrenocortical involvement in aluminium phosphide poisoning.

The effect of aluminium phosphide (AlP) which is a systemic poison on the adrenal cortex was studied in 30 patients of AlP poisoning. A significant rise in the plasma cortisol level (greater than 1048 nmol/l) was observed in the twenty patients. Mortality was 50 per cent. Autopsy study could be undertaken only in 10 patients. Histopathology showed mild to moderate changes. In the rest (10 patients), the adrenal cortex was critically involved and the cortisol level failed to rise beyond normal levels (less than 690 nmol/l). The histopathology revealed severe changes (complete lipid depletion, haemorrhage, necrosis etc.) and all these patients died. In the critically ill patients, the cortisol levels remained low because of severe adreno-cortical involvement. The changes in the adrenal cortex could be due to shock or to cellular toxic effect of phosphine. The histopathological changes in various viscera showed congestion, edema and cellular infiltration. In the heart, there were patchy areas of necrosis, while the liver showed fatty changes and the lungs showed, in addition areas of gray/red hepatization. There was no adrenal apoplexy or extensive haemorrhage that could explain shock in these patients. Cardiogenic shock could not be confirmed due to lack of facilities for haemodynamic monitoring, but there was histopathological evidence in support of cardiovascular shock.

Hipervitaminose A experimental no rato: estudo morfológico e morfométrico do cortex e da medula da adrenal / Experimental hypervitaminose A in the rat. Morfological and morfometric study of the cortex and medular of the adrenal

A administraçäo de 200 U. I. de vitamina A/grama de peso corporal, no rato, permitiu aos autores observarem: 1) O peso da glândula adrenal apresentou-se maior no animal com hipervitaminose A (19,58 mg) quando comparado ao animal controle (10,86 mg); 2) A zona glomerulosa do côrtex adrenal do rato tratadfo apresentou-se histologicamente, com células ligeiramente mais volumosas e com citoplasma mais abundante, mais acidófilo e com núcleos pouco mais volumosas. As zonas fasciculada a reticular também apresentaram células mais volumosas, com citoplasma mais abundante, com maior número de vacúolos e núcleos de volume maior, além de vasos bem dilatados; 3) A medula adrenal no animal tratado, revelou células com citoplasma menos granuloso, vasos dilatadores, congestos e edema. Os dados acima foram confirmados com o emprego de técnicas morfométricas