Pheochromocytomas are rare catecholamine producing neuroendocrine tumors. The incidence of these tumors is estimated to affect 0. We describe a case of an year-old male who presented with cycling episodes of severe hypertension and hypotension after an elective cardiac catheterization. Of note, this is the second eldest patient known to be published to date with a pheochromocytoma. Those arising from the extra-adrenal neural ganglia are called paragangliomas.
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Pheochromocytoma is a rare tumor arising from chromaffin cells in adrenal medulla or other paraganglia in the body, which may be associated with many genetic syndromes and mutation. The role of endocrinologist is in biochemical diagnosis of suspected cases; its anatomic and functional localization with the help of imaging like CT, MRI, and nuclear scanning; preoperative control of hypertension; and postoperative follow-up of cases that have undergone surgical resection.
Familial and genetic screening of cases and their family is important to detect occult cases. Endocrinologist will also play a role in cases with malignant pheochromocytoma in assessment of metastasis, control, chemoradiotherapy, and follow-up. Pheochromocytoma is a rare tumor arising from chromaffin cells in adrenal medulla or other paraganglia in the body. Pheochromocytoma derives its name from phaios dusky , chroma color , cytoma tumor. The term pheochromocytoma was coined by Pick in Extra-adrenal pheochromocytomas are usually called paragangliomas.
Pheochromocytoma as an entity is known since and its first successful surgical removal was reported in by Roux. The most common extra-adrenal site in abdomen is at the origin of the inferior mesenteric artery called the area of Zuckerkandl.
Pheochromocytoma is present in about 0. Patients with pheochromocytomas may present with sustained hypertension that is resistant to conventional treatment. Patients presenting with normal blood pressure usually have a small or large tumor due to intratumoural metabolism ; or pheochromocytoma that has been incidentally detected during familial screening, pure epinephrine secreting pheochromocytoma as in MEN-associated tumors, associated volume depletion, receptor down regulation due to persistently high levels of catecholamines, catecholamine induced dilated cardiomyopathy, or release of adrenomedullin by the tumor which is a vasodilatory peptide.
Less commonly, severe hypertensive reactions may occur during incidental surgery, following trauma, exercise, drug intake, or micturition in the setting of bladder pheochromocytoma when the diagnosis is unsuspected [ Table 1 ]. An unrecognized pheochromocytoma may lead to death as a result of a hypertensive crisis, arrhythmia, myocardial infarction, or multisystem crisis.
But still clinical recognition of pheochromocytoma is missed many times;[ 10 ] and missed diagnosis or improperly treated can prove fatal; thus its early detection and complete treatment is a must which usually involves surgical resection. Classically pheochromocytomas are described as catecholamine secreting tumors but it is important to understand that though secretion of catecholamines is episodic but their metabolism is constantly going on inside pheochromocytomas,[ 12 ] which has important implication in screening for pheochromocytomas as the best screening test for pheochromocytoma is assessment of metabolites of epinephrine and nor-epinephrine which are metanephrine and nor-metanephrine respectively.
Also plasma-free metanephrine assays are still not standardized world over. One advantage of urinary assays is that they are more standardized; however, hour urine samples are difficult to collect in children and are quite cumbersome to the patient and many times urinary sampling is inaccurate so it is advised to measure urinary creatinine along with it to confirm adequacy of specimen.
Importantly due to lower prevalence of pheochromocytoma and high sensitivity of the plasma metanephrine test; false positive cases are likely to exceed true positive cases. Thus, one clinical dilemma in the case of positive biochemical test is to rule out false positive results. False positive results can be minimized by collecting plasma samples with patients lying supine for at least 20 minutes before sampling. To avoid any stress associated with the needle stick, samples should ideally be collected through a previously inserted intravenous line.
Patients should have refrained from nicotine and alcohol for at least 12 hours, and to minimize analytical interference should have fasted overnight before blood sampling. There is also often a need for patients to avoid medications which affect assays or which interfere with catecholamine metabolism. Most common drugs causing false positive results are tricyclic antidepressants and antihypertensive medications. About one-fourth of pheochromocytomas are familial and are associated with various syndromes.
Localization of Pheochromocytomas is only done once biochemical diagnosis is confirmed. On T1 imaging pheochromocytomas are isointense to liver, kidney, and muscle while highly intense signal is seen on T2 images and no signal loss on opposed phase images because of the absence of fat in pheochromocytomas.
This can lead to a dilemma in patients with only borderline elevation of catecholamine levels, especially norepinephrine or normetanephrine , in whom a negative I-MIBG scan fails to bring closure to the search for a pheochromocytoma, causing anxiety in the patient and doctor. However, these are prone to false-positive or false-negative results. Selective venous sampling may also be used to locate the pheochromocytoma, but this is a specialized technique requiring an expert interventional radiologist which is easy to misinterpret and carries risks including the provocation of a hypertensive crisis and is therefore rarely used.
Thus, the more specific cellular uptake mechanisms are mainly confined to cells of neuroendocrine origin, while those for glucose uptake are more globally expressed. This explains the differences in sensitivity and specificity of the various radiotracers in pheochromocytoma tissue. Optimal therapy for pheochromocytoma is surgical resection of the tumor. However, it is associated with high rates of mortality if not properly prepared.
Various drugs can precipitate adrenergic and hypertensive crisis in patients with pheochromocytoma, hence are contraindicated [ Table 1 ].
It is started with initial dose of 10 mg twice daily and increased by mg every third day. In the author's experience short-acting prazosin has good results similar to phenoxybenzamine. Prazosin can be used in doses of 1 mg thrice daily initially and increased to maximal doses of up to total 12 mg daily dose. Doxazosin has a long half-life allowing once daily dosing while prazosin is short acting. Diuretics should not be used. Calcium channel blockers do not cause hypotension or orthostatic hypotension during the normotensive period.
Metyrosine is a very effective drug for BP control; it acts by inhibiting tyrosine hydroxylase, thus causing depletion of adrenal stores of catecholamines.
It is started with doses of mg thrice daily and then doses are increased gradually up to a total dose of 1. It is usually used as short-course treatment because of its side effect profile sedation, depression, anxiety, galactorrhoea, rarely extrapyramidal side effects.
Though there are thoughts that preoperative BP control do not alter outcome of surgery and intraoperative complications,[ 30 ] we believe in adequate BP control prior to surgery should be achieved like in any other elective surgery and vigilant cardiovascular status assessment during surgery. Also preoperatively the patient should be assessed thoroughly as any other major surgery with particular stress on cardiac evaluation. Volume status of the patient should be assessed and if the patient has large left-sided pheochromocytoma and t is likely to require splenectomy; then preoperative vaccination for H.
During the intraoperative period patients are prone to accelerated hypertension, hypotension, arrhythmias, and cardiovascular instability due to release of catecholamines during intraoperative handling of the tumor and effects of anesthetic agents. Thus patients require a trained anesthetist team during surgery.
Currently laproscopic surgery is most commonly performed for pheochromocytomas. In an immediate postoperative period hypotension is a common problem which is managed with intravenous fluids because vascular bed is effectively paralyzed by preoperative medications.
Volume replacement is quite large during initial hours. Another important issue is persistent hypertension which in the immediate postoperative period can be because of the residual tumor, autonomic instability, pain, volume overload; however, coexisting essential hypertension is still most likely diagnosis if it persists longer.
Twenty-five percent patients may remain hypertensive after pheochromocytoma removal. Importantly, normal postoperative biochemical test results do not exclude remaining microscopic disease, so patients should not be misinformed that they are cured and no further follow-up is necessary.
Repeat evaluations are done annually thereafter or recurrence of symptoms whichever is early. However, we have observed that these patients develop hypertrophy of adrenal rest tissue and steroid replacement can be tapered after documenting appropriate response to the ACTH stimulation test. Pheochromocytomas are rare tumors in the general population and even more uncommon in the pediatric population.
Clinical presentation and management is quite similar to adult pheochromocytomas. Surgical resection remains the treatment of choice for pheochromocytoma and paraganglioma. Familial screening and the patient's genetic analysis are must in pediatric pheochromocytoma cases. Pregnancy is a hyperdynamic state and normal pregnancy has many symptoms similar to pregnancy and detection of pheochromocytomas during pregnancy require high index of suspicion.
Failure to diagnose pheochromocytomas during pregnancy can lead to adverse fetal and maternal outcomes varying from hypertension to fetal and maternal death. During medical management main stress is to prevent hypertensive crisis which can be lethal for both mother and fetus. Follow-up is the same as in nonpregnant patients. Management of hypertension is similar to benign pheochromocytoma. There are no definite molecular and cellular markers to differentiate benign from malignant pheochromocytoma; it is only diagnosed on detection of metastasis.
Biochemical confirmation of recurrence and localization of metastatic lesions with I-MIBG scans can confirm the presence of metastasis. The large tumor size 5.
Complete surgical resection, if possible, is the treatment of choice with adjunct-targeted radiation therapy using I MIBG if residual disease ; however, recurrence rates are high. Radiation therapy or combination chemotherapy may be palliative for symptoms or morbidity resulting from local invasion by the tumor. Second line of management is chemotherapy in which combination of cyclophosphamide, vincristine, and dacarbazine CVD therapy is most commonly used.
The median duration of the response is 20 months. Since hypertensive episodes have been reported following chemotherapy, patients need to be prepared with adrenergic blockers prior to treatment. Somatostatin analogs have not been found to be efficacious in treatment. Source of Support: Nil. Conflict of Interest: None declared. National Center for Biotechnology Information , U. Indian J Endocrinol Metab. Garg , Sandeep Kharb , K.
Brar , Abhay Gundgurthi , and Rakesh Mittal 1. Author information Copyright and License information Disclaimer. Corresponding Author: Col. E-mail: moc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. This article has been cited by other articles in PMC.
Abstract Pheochromocytoma is a rare tumor arising from chromaffin cells in adrenal medulla or other paraganglia in the body, which may be associated with many genetic syndromes and mutation.
Keywords: Adrenal, hypertension, secondary hypertension, adrenal tumour. Open in a separate window. Figure 1. Localization of pheochromocytomas Localization of Pheochromocytomas is only done once biochemical diagnosis is confirmed. Figure 2. Pheochromocytoma in pregnancy Pregnancy is a hyperdynamic state and normal pregnancy has many symptoms similar to pregnancy and detection of pheochromocytomas during pregnancy require high index of suspicion.
J Clin Hypertens. PPick L. Das Ganglioma embryonale sympatheticum sympthoma embryonale Berl Klin Wochenschr. Welbourn RB.
The Highs and Lows of an Unknown Pheochromocytoma in an Elderly Patient
Pheochromocytomas are rare endocrine tumors that can present insidiously and remain undiagnosed until death or onset of clear manifestations of catecholamine excess. These tumors can no longer be regarded as a uniform disease entity, but rather as a highly heterogeneous group of chromaffin cell neoplasms with different ages of onset, secretory profiles, locations, and potential for malignancy according to underlying genetic mutations. These aspects all have to be considered when the tumor is encountered, thereby enabling optimal management for the patient. Referral to a center of specialized expertise for the disease should be considered wherever possible. This is not only important for surgical management of patients, but also for post-surgical follow up and screening of disease in patients with a hereditary predisposition to the tumor. While preoperative management has changed little over the last 20 years, surgical procedures have evolved so that laparoscopic resection is the standard of care and partial adrenalectomy should be considered in all patients with a hereditary condition.
Pheochromocytoma – update on disease management
Metrics details. Catecholamine-producing tumors may arise in the adrenal medulla pheochromocytomas or in extraadrenal chromaffin cells secreting paragangliomas. Their prevalence is about 0. These tumors may be sporadic or part of any of several genetic diseases: familial pheochromocytoma-paraganglioma syndromes, multiple endocrine neoplasia type 2, neurofibromatosis 1 and von Hippel-Lindau disease. Familial cases are diagnosed earlier and are more frequently bilateral and recurring than sporadic cases. The most specific and sensitive diagnostic test for the tumor is the determination of plasma or urinary metanephrines. The tumor can be located by computed tomography, magnetic resonance imaging and metaiodobenzylguanidine scintigraphy.