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Spironolactone bodies in an adrenal adenoma.Arch
Pathol. 1975 Aug;99(8):416-20.
Spironolactone
bodies were observed in an adrenal cortical adenoma that was removed
from a patient with primary hyperaldosteronism (Conn syndrome) treated
preoperatively with spironolactone. The electron microscopical
evaluation of this adrenal cortical adenoma shows origin of
spironolactone bodies from whorls of endoplasmic reticulum in cells
with the cytoplasmic features of those from the zona glomerulosa of
the adrenal gland. There was no evidence that the bodies were derived
from mitochondria, which confirms recent ultrastructural findings in
patients treated with spironolactone. These bodies have been described
in the adrenal cortex only in patients who have received
spironolactone, and the pharmacologic specificity of the bodies
strongly suggests a direct mode of action by spironolactone on
aldosterone production by cells of the adrenal zona glomerulosa.
Spironolactone
bodies. Light and electron microscope study apropos of 4 cases of
adrenal adenomas with primary hyperaldosteronism.
Ann Pathol . 1982;2(4):311-9.
So-called
Spironolactone bodies are reported in four adrenal cortical adenomas
that were removed from patients with primary hyperaldosteronism,
treated preoperatively with spironolactone. Their morphology is
described optically : these round acidophilic cytoplasmic bodies have
a laminated appearance that ranges in size from 2 to 20 mu in
diameter. Electron microscopy of the zona glomerulosa non adenomatous
cells and of adenomatous cells of glomerular type reveals numerous
membranes arranged concentrically around a central core. Connections
between the endoplasmic reticulum and mitochondria in the cytoplasm of
the cell and lining layers of the body are described and analysed. The
authors attempt to explain the formation and the increase of the
bodies. Correlations appear between the number of spironolactone
bodies and duration of administration of spironolactone and total drug
dosage. The results are discussed with those of the literature.
Diagnosis and treatment outcome in primary aldosteronism based on a
retrospective analysis of 187 cases.Orv
Hetil. 2006 Jan 15;147(2):51-9.
INTRODUCTION:
Primary aldosteronism is the most common form of mineralocorticoid
hypertension. The disease has been described by Jerome W. Conn in
1955; since that time there has been a great progress in the knowledge
concerning the prevalence, diagnostics and treatment of the disease.
AIMS: The authors retrospectively analyzed the efficacy of diagnostic
procedures and the outcome of treatment by the analysis of data of 187
patients with primary aldosteronism examined between 1958 and 2004 at
the 2nd Department of Medicine of Semmelweis University. METHODS: The
efficacy of different methods used for the diagnosis, the frequency of
the different subtypes of primary aldosteronism, as well as the
surgical outcomes in patients with surgically treated subtypes of
primary aldosteronism were studied. RESULTS: Aldosterone-producing
adenoma was detected in more than two thirds of patients (n = 135),
whereas idiopathic hyperaldosteronism was found in 46 patients. Other
subtypes of primary hyperaldosteronism occurred less frequently
(unilateral primary adrenocortical hyperplasia in 5 patients and
adrenocortical carcinoma in one patient). For the diagnosis of
familial hyperaldosteronism type I, molecular biological studies of
the aldosterone-synthase/11beta-hydroxylase gene chimera were carried
out in 30 patients but none of them showed the presence of the
chimeric gene. When comparing the clinical parameters of patients with
aldosterone-producing adenoma and idiopathic hyperaldosteronism, no
significant differences were found in the time period between the
diagnosis of hypertension and the diagnosis of primary aldosteronism,
or in the systolic and diastolic blood pressure values. The mean of
the lowest documented serum potassium concentration was slightly lower
in patients with aldosterone-producing adenoma (2.8 +/- 0.1 mmol/l)
compared to those with idiopathic hyperaldosteronism (3.1 +/- 0.2 mmol/l),
but the difference was not significant. Normokalemic primary
hyperaldosteronism was found in 7 cases. The ratio of plasma
aldosterone concentration (ng/dl) to plasma renin activity (ng/ml/h)
was above 20 in all patients with aldosterone-producing adenoma and in
all but 5 cases with idiopathic hyperaldosteronism. To confirm the
diagnosis and to differentiate the subtypes of primary aldosteronism,
the postural test combined with furosemide administration was
performed in the majority of patients. When cases showing an elevation
of plasma cortisol level during the test were excluded, this test
differentiated patients with aldosterone-producing adenoma from those
with idiopathic hyperaldosteronism with a sensitivity of 69% and a
specificity of 92%. In cases of adrenocortical adenomas not or not
clearly detectable by radiological imaging techniques, as well as in
cases with bilateral adrenocortical adenomas, selective adrenal vein
sampling was performed (n = 55). All but 4 patients with aldosterone-producing
adenoma underwent adrenalectomy. Histology and postoperative hormone
results confirmed the preoperative diagnosis in all operated patients.
After surgery serum potassium concentration returned to normal in all
patients showing low serum potassium levels before surgery. Also, the
moderate to severe preoperative hypertension disappeared or improved
after surgery. CONCLUSIONS: These observations are in contrast with
the results of international studies which showed a high frequency of
normokalemic primary aldosteronism and a more frequent occurrence of
idiopathic hyperaldosteronism well treatable with aldosterone-antagonists.
Therefore, it can be presumed that a significant number of primary
aldosteronism cases that are not accompanied with severe hypokalemia
remain undetected in Hungary.
The Conn
syndrome. The clinical and surgical aspects of 18 cases of adrenal
adenoma.
Actas Urol Esp. 1999
Jan;23(1):14-21.
OBJECTIVES:
Presentation of a series of 18 patients who underwent surgery of
aldosterone-producing adrenal adenoma (Conn's syndrome) over the last
10 years. Assessment of the most significant clinical and pathological
aspects from a surgical point of view. METHODS: Retrospective study
evaluating a broad range of features: clinical, analytical, hormonal,
imaging, types of anaesthesia, approaches, technique used, intra and
post-operative morbidity and mortality, evolution and pathoanatomical
diagnosis. RESULTS: The most frequent clinical data of primary
hyperaldosteronism were: 94.4% volume-dependent HBP, 50% headaches and
dizziness, 27.8% epistasis and/or episodes of angor or acute
myocardial infarction, and 22.2% heart failure. The biochemical study
and hormonal testing evidenced: hypokalemia in 88.9%, metabolic
alkalosis 66.7% and hypernatremia in 61.1%. Mean aldosterone levels
were 517.5 pg/mL, and urinary levels 85.9 mcg/day. Resting plasma
renin activity (PRA) < 0.2 ng/mL/h in 77.8% cases and positive
aldosterone stimulation test in 61.1%: captopril test positive.
Imaging diagnosis was based in CAT which was conclusive in 88.9% and
ultrasound which was diagnostic in 27.8% cases. The surgical approach
was: lumbotomy (over the 11th or 12th rib) in 14 patients and
transpleurodiaphragmatic in all remaining patients. The intraoperative
complications reported were placement of endothoracic tube due to
iatrogenic pneumothorax in two occasions. Duration of the procedure
(mean 136.1 min) and post-operative hospitalization (mean 7.76 days),
as well as post-surgery follow-up for up to 96 months were also
studied. At final time point there was 66.7 asymptomatic patients,
33.3% cases of HBP, and no deaths. CONCLUSIONS: Primary
hyperaldosteronism due to adrenal adenoma is an uncommon reason for
HBP, but in most cases can be cured with surgery. Biochemical and
hormonal testing is determinant to research a diagnosis. Ultrasound
and CAT are essential for imaging diagnosis, and occasionally NMR can
be of help. Lumbotomy is considered the choice approach for these
small tumours as it is a familial technique for urologists with a low
complications rate.
A
clinicopathological and ultrastructural study on 147 cases of primary
aldosteronism.
Zhonghua Bing Li
Xue Za Zhi. 1990
Jun;19(2):103-5.
147 cases of
primary aldosteronism was analysed, including 133 cases of adenoma
(90%), 13 cases of cortical hyperplasia, and 1 case of carcinoma. The
size of aldosteronoma was usually 1-2 cm in diameter. All the adenomas
were well capsulated and the cut surface showed a homogeneous yellow
color. The largest one in this group was 6 cm in diameter. The
diameter of aldosteronoma was over 10 cm and the cut surface showed a
brownish yellow color. Microscopically, the aldosteronoma was composed
principally of clear cells arranged in a glomerular pattern, while the
malignant one consisted of more granular cells with nuclear atypia and
mitoses. Ultrastructure of the majority of tumor cells showed presence
of numerous lipid vacuoles representing content of the steroid
hormones. In those patients who had received spironolactone before
operation, some eosinophilic concentric laminated spironolactone
bodies could be obtained in the lipid vacuoles, which indicated that
the steroid hormone had been blocked or destroyed. Additionally, the
laminated cristae within the mitochondria in aldosteronoma looked
closely similar to those of the normal cells in the zona glomerulosa,
suggesting that these tumors are mainly derived from zona glomerulosa
of the adrenals.
Histopathology of benign versus malignant sympathoadrenal
paragangliomas: clinicopathologic study of 120 cases including unusual
histologic features.Hum
Pathol. 1990 Nov;21(11):1168-80.
The clinical and
pathologic features of 120 adrenal and extraadrenal paragangliomas
were studied in an attempt to identify features which might predict
malignant behavior. Clinical follow-up was obtained in 98 cases (82%);
64 tumors were clinically benign, and 34 were malignant as evidenced
by regional or distant metastases and/or extensive local invasion.
Thirty-two of the 34 malignant tumors (94%) were functionally active.
Features noted more frequently in malignant tumors included male
predominance (74%; P2 [two-sided P value] = .002), extraadrenal
location (52%; P2 less than .0001), greater tumor weight (mean 383 g
versus 73 g for nonmalignant tumors), confluent tumor necrosis, and
the presence of vascular invasion and/or extensive local invasion.
Intracytoplasmic hyaline globules were seen in 59% and 32% of benign
and malignant tumors, respectively (P2 = .001). Logistic regression
analysis of 16 nonhistologic and histologic parameters showed four of
them to be most predictive of malignancy--extraadrenal location,
coarse nodularity of the primary tumor, confluent tumor necrosis, and
absence of hyaline globules. Most malignant paragangliomas had two or
three of these features (71%), while 89% of benign tumors had only one
(or none; P less than .0001). According to the statistical model
developed, there was better than a 95% probability that more than 70%
of tumors could be classified correctly
on the basis of the four factors indicated. Although limitations still
exist, results of this study provide some basis for evaluating
malignant potential of these tumors.
Histological grading of adrenal and extra-adrenal pheochromocytomas
and relationship to prognosis: a clinicopathological analysis of 116
adrenal pheochromocytomas and 30 extra-adrenal sympathetic
paragangliomas including 38 malignant tumors.Endocr
Pathol. 2005 Spring;16(1):23-32.
Pheochromocytomas
and extra-adrenal sympathetic paragangliomas show varied histological
patterns, and it is difficult to diagnose malignancy or predict the
clinical course using current histological criteria. In the present
study, we reviewed 146 sympathetic paragangliomas including 116
adrenal (102 unilateral, 14 bilateral) and 30 extra-adrenal tumors
including 38 metastatic tumors. We developed a scoring scale according
to the following six factors: histological pattern, cellularity,
coagulation necrosis, vascular/capsular invasion, Ki-67
immunoreactivity, and types of catecholamine produced. The tumors were
classified as well (WD), moderately (MD), and poorly differentiated
(PD) types according to their scores. The frequency of these tumor
types were 113 WD (77%), 27 MD (19%), and 6 PD (4%). Metastasis was
observed in 15 of 113 WD (13%), 17 of 27 MD (63%), and all 6 PD
(100%). Five-year survivals of patients with metastases were 92% with
WD, 69% with MD, 0% with PD. Respective 10-yr survivals were 83%, 38%,
and 0%. Differences between groups were statistically significant. The
data show that using this grading scoring system for sympathetic
paragangliomas correlates with both metastatic potential and patient
survival.
Prediction of malignant behavior of pheochromocytomas and
paragangliomas using immunohistochemical techniques.
Endocr Pathol. 2002
Summer;13(2):149-56.
Pheochromocytomas
and paragangliomas arise from the adrenal glands and extraadrenal
paraganglia, respectively. Malignant behavior of these tumors is
uncommon and is, in part, dependent on their sites of origin, such as
extraadrenal location. Morphologic criteria for malignancy of
pheochromocytoma and paragangliomas have not been clearly defined. In
this study, to clarify the histologic features that distinguish the
benign from malignant pheochromocytomas and paragangliomas, we
examined metastatic and nonmetastatic tumors using immunohistochemical
techniques. A total of eight cases, five pheochromocytomas from the
adrenal glands (four benign and one malignant tumor) and three
paragangliomas with invasion or metastasis, were studied. The markers
used in this study were chromogranin A, synaptophysin, NCAM (CD56),
SNAP25, neuron-specific enolase, S-100 protein, and MIB-1. Our results
suggest that MIB-1 immunostaining is a useful adjunct marker to
predict malignant behavior in these tumors.
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