Cushing hastalığı ve sendromu, Primer hiperaldosteronizm, Feokromasitoma, Primer adrenokortikal kanser ve metastatik adrenal kitleler
Best Pract Res Clin Endocrinol Metab. 2009 Oct;23(5):607-23.
Bertagna X, Guignat L, Groussin L, Bertherat J.
Service des Maladies Endocriniennes et Métaboliques, Centre de Référence des
Maladies Rares de la Surrénale, Hôpital Cochin, 27, rue du Fg St Jacques, 75014
Paris, France. firstname.lastname@example.org
Cushing's syndrome refers to the clinical manifestations induced by chronic
exposure to excess glucocorticoids. There are three pathological conditions that
can result in the chronic overproduction of endogenous cortisol in man: the most
frequent is Cushing's disease where adrenocorticotropic hormone (ACTH) is
overproduced by a pituitary corticotroph adenoma, rarely ACTH can be produced in
an 'ectopic' manner by a non-pituitary tumour, finally cortisol can be directly
over-secreted by one or (rarely) the two adrenals that have become tumourous,
either benign or malignant. The positive diagnosis of Cushing's syndrome requires
that chronic hypercortisolism is unequivocally demonstrated biologically, using
24-h urinary cortisol, late-evening plasma or salivary cortisol, midnight 1-mg or
the classic 48-h-low-dose dexamethasone suppression test, etc., all with
essentially the same diagnosis potencies. The search for the responsible tumour
then relies on the assessment of the corticotroph function, and imaging:
suppressed ACTH plasma levels indicate an 'adrenal' Cushing, and the responsible
unilateral adrenocortical tumour is always visible at computed tomography (CT)
scan, whereas its benign or malignant nature may be difficult to diagnose before
surgery. Imaging can suspect bilateral 'adrenal' Cushing, when the two adrenals
are small, as in the primary pigmented nodular adrenal dysplasia associated with
Carney complex, or enlarged, as in the ACTH-independent macronodular
adrenocortical hyperplasia. Measurable or increased ACTH plasma levels indicate
either Cushing's disease or the ectopic ACTH syndrome. When the dynamics of the
corticotroph function (high-dose dexamethasone suppression test, the CRH test)
are equivocal, and/or the imaging is non-contributive, it may be difficult to
distinguish between the two. This is the situation where sampling ACTH plasma
levels in the inferior petrosal sinus may be necessary. The best treatment option
of Cushing's disease is when the responsible corticotroph adenoma can be entirely
removed by the trans-sphenoidal approach, with sufficient skill to preserve the
normal anterior pituitary function. When it fails, all other options directed
towards the pituitary (radiation therapies), or the adrenals (medications or
surgery), have numerous side effects. There is at present no recognised efficient
medical treatment towards the corticotroph adenoma -still an orphan disease.
J Clin Endocrinol Metab. 2008 May;93(5):1526-40. Epub 2008 Mar 11.
The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice
Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori
Program on Reproductive and Adult Endocrinology, National Institute of Child
Health and Human Development, National Institutes of Health, Bethesda, MD 20892,
OBJECTIVE: The objective of the study was to develop clinical practice guidelines
for the diagnosis of Cushing's syndrome.
PARTICIPANTS: The Task Force included a chair, selected by the Clinical
Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts,
a methodologist, and a medical writer. The Task Force received no corporate
funding or remuneration.
CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and
discussions. The guidelines were reviewed and approved sequentially by The
Endocrine Society's CGS and Clinical Affairs Core Committee, members responding
to a web posting, and The Endocrine Society Council. At each stage the Task Force
incorporated needed changes in response to written comments.
CONCLUSIONS: After excluding exogenous glucocorticoid use, we recommend testing
for Cushing's syndrome in patients with multiple and progressive features
compatible with the syndrome, particularly those with a high discriminatory
value, and patients with adrenal incidentaloma. We recommend initial use of one
test with high diagnostic accuracy (urine cortisol, late night salivary cortisol,
1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that
patients with an abnormal result see an endocrinologist and undergo a second
test, either one of the above or, in some cases, a serum midnight cortisol or
dexamethasone-CRH test. Patients with concordant abnormal results should undergo
testing for the cause of Cushing's syndrome. Patients with concordant normal
results should not undergo further evaluation. We recommend additional testing in
patients with discordant results, normal responses suspected of cyclic
hypercortisolism, or initially normal responses who accumulate additional
features over time.
Clin Endocrinol (Oxf). 2007 May;66(5):607-18.
Primary aldosteronism: renaissance of a syndrome.
Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic; and
Mayo Clinic College of Medicine, Rochester, MN 55905, USA. email@example.com
Great strides have been made in our understanding of the pathophysiology of
primary aldosteronism syndrome since Conn's description of the clinical
presentation of a patient with an aldosterone-producing adenoma (APA) more than
50 years ago. It is now recognized that the APA is just one of the seven subtypes
of primary aldosteronism. APA and bilateral idiopathic hyperaldosteronism (IHA)
are the most common subtypes of primary aldosteronism. Although most clinicians
had thought primary aldosteronism to be a rare form of hypertension for more than
three decades, it is now recognized to be the most common form of secondary
hypertension. Using the plasma aldosterone to plasma renin activity ratio as a
case-finding test, followed by aldosterone suppression confirmatory testing, has
resulted in much higher prevalence estimates of 5-13% of all patients with
hypertension. In addition, there has been a new recognition of the
aldosterone-specific cardiovascular morbidity and mortality associated with
aldosterone excess. Although thought to be daunting and complex in the past, the
diagnostic approach to primary aldosteronism is straightforward and can be
considered in three phases: case-finding tests, confirmatory tests and subtype
evaluation tests. Patients with hypertension and hypokalaemia (regardless of
presumed cause), treatment-resistant hypertension (three antihypertensive drugs
and poor control), severe hypertension (>or= 160 mmHg systolic or >or= 100 mmHg
diastolic), hypertension and an incidental adrenal mass, onset of hypertension at
a young age or patients being evaluated for other forms of secondary hypertension
should undergo screening for primary aldosteronism. In patients with suspected
primary aldosteronism, screening can be accomplished by measuring a morning
(preferably between 0800 and 1000 h) ambulatory paired random plasma aldosterone
concentration (PAC) and plasma renin activity (PRA). An increased PAC:PRA ratio
is not diagnostic by itself, and primary aldosteronism must be confirmed by
demonstrating inappropriate aldosterone secretion. Aldosterone suppression
testing can be performed with orally administered sodium chloride and measurement
of urinary aldosterone or with intravenous sodium chloride loading and
measurement of PAC. Unilateral adrenalectomy in patients with APA or unilateral
adrenal hyperplasia results in normalization of hypokalaemia in all these
patients; hypertension is improved in all and is cured in approximately 30-60% of
them. In bilateral adrenal forms of primary aldosteronism, unilateral or
bilateral adrenalectomy seldom corrects the hypertension and they should be
treated medically with a mineralocorticoid receptor antagonist.
J Clin Endocrinol Metab. 2008 Sep;93(9):3266-81. Epub 2008 Jun 13.
Case detection, diagnosis, and treatment of patients with primary aldosteronism:
an endocrine society clinical practice guideline.
Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, Young
WF Jr, Montori VM; Endocrine Society.
Prince Henry's Institute of Medical Research, Clayton, VIC, Australia.
OBJECTIVE: Our objective was to develop clinical practice guidelines for the
diagnosis and treatment of patients with primary aldosteronism.
PARTICIPANTS: The Task Force comprised a chair, selected by the Clinical
Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts,
one methodologist, and a medical writer. The Task Force received no corporate
funding or remuneration.
EVIDENCE: Systematic reviews of available evidence were used to formulate the key
treatment and prevention recommendations. We used the Grading of Recommendations,
Assessment, Development, and Evaluation (GRADE) group criteria to describe both
the quality of evidence and the strength of recommendations. We used "recommend"
for strong recommendations and "suggest" for weak recommendations.
CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and
discussions during one group meeting, several conference calls, and multiple
e-mail communications. The drafts prepared by the task force with the help of a
medical writer were reviewed successively by The Endocrine Society's CGS,
Clinical Affairs Core Committee (CACC), and Council. The version approved by the
CGS and CACC was placed on The Endocrine Society's Web site for comments by
members. At each stage of review, the Task Force received written comments and
incorporated needed changes.
CONCLUSIONS: We recommend case detection of primary aldosteronism be sought in
higher risk groups of hypertensive patients and those with hypokalemia by
determining the aldosterone-renin ratio under standard conditions and that the
condition be confirmed/excluded by one of four commonly used confirmatory tests.
We recommend that all patients with primary aldosteronism undergo adrenal
computed tomography as the initial study in subtype testing and to exclude
adrenocortical carcinoma. We recommend the presence of a unilateral form of
primary aldosteronism should be established/excluded by bilateral adrenal venous
sampling by an experienced radiologist and, where present, optimally treated by
laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal
hyperplasia, or those unsuitable for surgery, optimally be treated medically by
mineralocorticoid receptor antagonists.
Endocr Relat Cancer. 2007 Dec;14(4):935-56.
Pheochromocytoma: an update on genetics and management.
Karagiannis A, Mikhailidis DP, Athyros VG, Harsoulis F.
Division of Endocrinology, Second Propedeutic Department of Internal Medicine,
Medical School, Hippokration Hospital, Aristotle University of Thessaloniki,
Thessaloniki 54642, Greece.
Pheochromocytomas (PHEOs) are rare neoplasms that produce catecholamines and
usually arise from the adrenal medulla and are considered to be an adrenal
paraganglioma (PGL). Closely related tumors of extraadrenal sympathetic and
parasympathetic paraganglia are classified as extraadrenal PGLs. Most PHEOs are
sporadic, but a significant percentage (approximately 25%) may be found in
patients with germline mutations of genes predisposing to the development of von
Hippel-Lindau disease, neurofibromatosis 1, multiple endocrine neoplasia type 1
(MEN1) and 2 (MEN2), and the PGL/PHEOs syndrome, based on the described mutations
of the genes for succinate dehydrogenase subunit D (SDHD), B (SDHB), and C
(SDHC). As one out of four PHEOs turns out to be a hereditary clinical entity,
screening for genetic alterations is important, as it provides useful information
for a rational diagnostic approach and management. This review discusses the
genetics, the pathophysiology of hypertension, the clinical picture, the
biochemical and imaging diagnosis, and the preferred therapeutic approach for
PGLs/PHEOs. Furthermore, it emphasizes the need for genetic testing in cases with
apparently sporadic PHEOs.
J Clin Endocrinol Metab. 2007 Nov;92(11):4069-79.
Preoperative management of the pheochromocytoma patient.
Section on Medical Neuroendocrinology, National Institute of Child Health and
Human Development, National Institutes of Health, Building 10, CRC, Room 1E-3140,
10 Center Drive MSC-1109, Bethesda, Maryland 20892-1109, USA. firstname.lastname@example.org
Pheochromocytomas are rare neuroendocrine tumors with a highly variable clinical
presentation, but they most commonly present as spells of headaches, sweating,
palpitations, and hypertension. Patients with pheochromocytoma may develop
complicated and potentially lethal cardiovascular and other complications,
especially in the setting of diagnostic or interventional procedures (e.g. upon
induction of anesthesia or during surgery). The serious and potentially lethal
nature of such complications is due to the potent effect of paroxysmal release of
catecholamines. Because this warrants prompt diagnosis and treatment, the
physician should be aware of the clinical manifestations and complications of
catecholamine excess and be able to provide proper preoperative management to
minimize catecholamine-related pre-, intra-, and postoperative adverse events.
The following clinical scenario and discussion aim to enhance the knowledge of
the physician regarding the behavior of pheochromocytoma and to outline current
approaches to comprehensive preoperative management of patients suffering from
Langenbecks Arch Surg. 2012 Feb;397(2):179-94. Epub 2011 Dec 16.
Surgical management of adrenal metastases.
Sancho JJ, Triponez F, Montet X, Sitges-Serra A.
Endocrine Surgery Unit, Department of General Surgery, Hospital del Mar,
Universitat Autònoma de Barcelona, Barcelona, Spain. email@example.com
PURPOSE: This paper aims to review controversies in the management of adrenal
gland metastasis and to reach an evidence-based consensus.
MATERIALS AND METHODS: A review of English-language studies addressing the
management of adrenal metastasis, including indications for surgery, diagnostic
imaging, fine-needle aspiration, surgical approach, and outcome was carried out.
Results were discussed at the 2011 Workshop of the European Society of Endocrine
Surgeons devoted to adrenal malignancies and a consensus statement agreed.
RESULTS: Patients should be managed by a multidisciplinary team. Positron
emission tomography coupled with computed tomography (PET/CT) scanning is the
technique of choice for suspected adrenal metastasis. When PET/CT is not
available or results are inconclusive, the CT scan or magnetic resonance imaging
can be used. Patients should undergo complete hormonal evaluation. Adrenal biopsy
should be reserved for cases in which the results of non-invasive techniques are
equivocal. If malignancy has been reliably ruled out, patients with adrenal
incidentalomas should be managed like noncancer patients.
CONCLUSIONS: A patient with suspected adrenal metastasis should be considered a
candidate for adrenalectomy when: (a) control of extra-adrenal disease can be
accomplished, (b) metastasis is isolated to the adrenal gland(s), (c) adrenal
imaging is highly suggestive of metastasis or the patient has a biopsy-proven
adrenal malignancy, (d) metastasis is confined to the adrenal gland as assessed
by a recent imaging study, and (e) the patient's performance status warrants an
aggressive approach. In properly selected patients, laparoscopic (or
retroperitoneoscopic) adrenalectomy is a feasible and safe option.
Surg Clin North Am. 2009 Oct;89(5):1255-67.
Wandoloski M, Bussey KJ, Demeure MJ.
Translational Genomics Research Institute, Clinical Translational Research
Division, Phoenix, AZ 85004, USA.
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy causing up to 0.2%
of all cancer deaths This article reviews the incidence, presentation, and
pathology of ACC. Particular attention is paid to the molecular oncogenesis of
this disease, and the surgical and therapeutic options available for its cure.