| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Special Articles |
Departments of Medicine, Section of Endocrinology Diabetes and Nutrition (A.T.S., A.O.M., J.C.M.), Radiology (M.A.B.), Pathology (A.d.l.M.), and Surgery (R.C.), Boston University Medical Center, Boston, Massachusetts 02118
Address all correspondence and requests for reprints to: Dr. James C. Melby, Endocrine Hypertension Unit, Department of Medicine and Physiology, Boston University School of Medicine, Evans Building, Room 232, Boston, Massachusetts 02118. E-mail: James.Melby{at}bmc.org
 |
Introduction |
|---|
 Top Introduction Case ReportDiscussionReferences |
|---|
|
Case Report |
|---|
|
TopIntroductionCase ReportDiscussionReferences |
|---|
Physical examination revealed a thin female writhing in pain. Her blood
pressure was 182/155 mm Hg, heart rate was 116 beats/min, respirations
were shallow at 22/min, and temperature was 36.5 C. Her fundi were
without hemorrhages or exudates, and disk margins were sharp. Her
cardiac exam revealed a hyperdynamic precordium, normal first and
second heart sounds, and a II/VI systolic flow murmur at the left
sternal border. Examination was otherwise significant for a distended
abdomen with decreased bowel sounds and diffuse tenderness. Initial
laboratory studies revealed a white blood cell count of 19,000
mm-3 (SI; 19
x 109/L; normal range conventional; SI;
4:000–11.,000 mm-3;
4.0–11 x 109/L) with a left shift,
hemoglobin of 14 g/dL (140 g/L; 13.5–18.0 g/dL; 135–180 g/L),
platelet count of 276 x
103/mm3 (276 x
109/L; 150–400 x
103/mm3; 150–400 x
109/L), and normal electrolytes. Her abdominal
radiograph revealed large dilated loops of colon, a large amount of
stool in the cecum, and no gas within the rectum (Fig. 1
). The cecum was dilated to 10 cm. A
diagnosis of large bowel obstruction secondary to fecal impaction was
made. Attempt at manual disimpaction was unsuccessful.
|
After 5 days in the hospital, her clinical situation worsened as she
developed increasing abdominal pain and distention. Abdominal plain
film demonstrated cecal dilatation to 13 cm. Urgent surgical
exploration revealed a megacolon with volvulus. A subtotal colectomy
with primary ileorectal anastamosis was performed. She was
significantly hypertensive during surgery and required multiple doses
of iv labetolol for blood pressure control. The patient did well
postoperatively until day 6, when she redeveloped acute abdominal pain
with peritoneal signs. A computed tomographic scan of the abdomen was
performed and revealed a small amount of fluid in the pelvis,
persistent pneumoperitoneum, and a 6 x 7-cm adrenal mass (Fig. 2).
|
Her 24-h urine results confirmed the diagnosis of pheochromocytoma. The 24-h urine collection revealed: norepinephrine, 883 µg (5,219 nmol; normal, 11–86 µg/day; 65–508 nmol/day); epinephrine, 675 µg (3,685 nmol; 0–15 µg/day; 0–81.9 nmol/day); dopamine, 441 µg (2,879 pmol; 100–400 µg/day; 653–2,612 pmol/day); total unconjugated catecholamines, 1,999 µg (11,816 nmol; <540 µg/day; <3,191 nmol/day); and total metanephrines, 17.1 mg (93.33 µmol; <1.3 mg/day; <7.13 µmol/day). Other laboratory results included serum calcitonin, 2 pg/mL (0.58 pmol/L; <5 pg/mL; <1.45 pmol/L); intact PTH, 34 pg/mL (34 ng/L; 10–65 pg/mL; 10–65. ng/L); and calcium, 10.0 mg/dL (2.50 mmol/L; 8.4–10.2 mg/dL; 2.1–2.55 mmol/L).
After adequate 
and ß blockade, she underwent surgical resection
of her right adrenal gland. Intraoperatively her blood pressure was
labile during manipulation of the tumor, and she required large doses
of iv nitroprusside and esmolol. A 200-g, well circumscribed mass was
removed without complications. Postoperatively she was transiently
hypotensive and required a large amount of fluid as well as temporary
support with vasopressors.
Pathology
Gross examination revealed a 200-g, 4 x 7 x 8-cm
encapsulated pheochromocytoma. The cut surface was reddish brown with
yellow areas of necrosis. Microscopically, the tumor cells were
arranged in circular clusters separated by endothelium lined spaces;
this characteristic pattern for pheochromocytoma is termed zellballen
(Fig. 3).
|
Follow-up
She was last seen 10 months after surgery; she remains normotensive without medication and has experienced no further spells. Her constipation has completely resolved. Repeat 24-h urine for total catecholamines, metanephrines, and vanillylmandelic acid returned within normal limits. The serum chromogranin A level was within the normal range, and screening for mutations in the RET protooncogene was negative. No mutations were detected in exons 10 (codons 609, 611, 618, and 620), 11 (codon 634), 13, 14, or 16 (codon 918) of the RET protooncogene.
|
Discussion |
|---|
|
TopIntroductionCase ReportDiscussionReferences |
|---|
The typical gastrointestinal manifestations of pheochromocytoma include nausea, vomiting, and abdominal pain. Constipation has been reported in 5–13% of cases in a larger series (4). Megacolon and pheochromocytoma may occur together in MEN 2A and MEN 2B. Hirschprung’s disease, or congenital aganglionic colon, has been reported in association with both MEN 2A and 2B syndromes (5). In MEN 2A, at least six germline mutations (involving codons 609, 611, 618, and 620) of the RET protooncogene located on chromosome 10 (10q11.2) have been identified (6). Evidence has demonstrated that Hirschsprung’s disease is also linked to the RET protooncogene (7). Patients with MEN 2B and neurofibromatosis may also develop megacolon (8). Diffuse ganglioneuromatosis of the colon in MEN 2B is thought to cause a dysmotility syndrome that may precipitate megacolon (9). A germline missense mutation in the tyrosine kinase domain of the RET protooncogene (exon 16, codon 918) has been reported to be present in 95% of patients with MEN 2B (10). Our patient’s phenotypic features, colon pathology, and genetic testing clearly were not consistent with Hirschprung’s disease, MEN 2A, or MEN 2B.
Sustained high catecholamine levels secreted by a high tumor burden may
explain the mechanism by which constipation, paralytic ileus, and
megacolon occur in association with pheochromocytoma. The effects of
catecholamines on intestinal smooth muscle and the splanchnic
circulation are well known (11). Stimulation of
receptors causes hyperpolarization and relaxation of intestinal smooth
muscle (1), constriction of intestinal
vascular smooth muscle (1 and
2), and contraction of ileocolic sphincters
(2). Stimulation of ß2
receptors causes arteriolar dilatation and intestinal smooth muscle
relaxation. Therefore, high levels of circulating catecholamines will
result in a decrease in intestinal peristalsis, motility, and tone.
Clinically this may manifest initially as intermittent constipation,
but when catecholamine levels become persistently elevated, they may
precipitate an ileus or perhaps a megacolon. Cruz and Colwell reported
a series of seven patients who developed ileus with large
pheochromocytomas (>70 g) and catecholamine levels at least twice
normal (>1,000 µg/day; 5,910 nmol/day) (12). As shown
in Table 1, only the largest
pheochromocytomas (>200 g) with circulating catecholamine levels
approaching 4 times normal (>1,999 µg/day; 11,814 nmol/day)
developed megacolon.
|
Some patients with pheochromocytoma and pseudo-obstruction,
however, have been reported to have a dramatic relief after the iv
administration of phentolamine, an -adrenergic blocker. This
suggests that -adrenergic activation by high circulating
catecholamine levels is largely responsible for pseudo-obstruction
observed in patients with pheochromocytoma (14, 15).
The effects of catecholamines on the intestine were initially described by Blacket et al. in 1950 (16). They continuously infused noradrenaline to four rabbits over 4 days. This resulted in the premature death of one rabbit that at autopsy was found to have enormous dilatation of the large gut. Two of the other rabbits subsequently became ill and on postmortem exam also exhibited gross dilatation of the terminal large gut.
Review of the literature reveals that the presence of megacolon in
association with pheochromocytoma carries a grave prognosis (see Table 1
). Our patient was extremely fortunate to have survived a total
colectomy before the discovery of her pheochromocytoma. Perhaps the
diagnosis could have been made sooner had the association of megacolon
and pheochromocytoma been recognized.
Conclusion
In summary, we describe a patient with a history of hypertension, migraine headaches, and constipation presenting with severe abdominal pain and megacolon who ultimately was found to have a pheochromocytoma. High circulating catecholamine levels secreted by the large tumor undoubtedly precipitated the megacolon. We conclude that the diagnosis of pheochromocytoma should be considered in any patient who presents with megacolon, pseudo-obstruction, and features of catecholamine excess.
Received January 20, 2000.
Revised July 10, 2000.
Accepted July 18, 2000.
|
References |
|---|
|
TopIntroductionCase ReportDiscussionReferences |
|---|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
