Pheochromocytoma- a case presentation

M.F., woman, 51 years old, From Pitesti, Arges County, Hospitalized in Parhon National Institute of Endocrinology Bucharest in November 2010 for evaluation 1 year after left adrenalectomy for pheocromocytoma. Complain: weight-gain of 20 kg during the last 10 months (normal appetite, sedentary life) Family history: irrelevant

Menarche at 13 years of age, menopause at 48 years of age, P3, D2, A1

Personal history:

Hypertensive 2007-2009, diabetes mellitus April 2009-January 2010, laparoscopic colecistectomy in April 2009 with high BP during surgery, laparoscopic left adrenalectomy for pheochromocytoma in october 2009

History of the disease:

First admission in Parhon National Institute of Endocrinology in october 2009 for oscillating blood-pressure (systolic BP 33080mmHg) appearing as paroxysms accompanied by

nausea and vomiting, palpitations, headache, diaphoresis, cold hands and feet, fear of impending death.

Abdominal CT showed

left adrenal tumor with clear borders diameters of 9/ 8.7/ 8.6 cm, without liver metastases and no lymph nodes involved; no contrast was given due to high BP (270 mm Hg)

The EKG showed sinus tachycardia ST segment subdenivelation deep, symmetric T wave inversion (10-14 mm) in leads V2V6 T waves inverted in leads I, II, aVL, suggesting acute ischemia-lesion; QT interval was prolonged at 460 ms. Total CK was slightly elevated 452 u/l (N: 26-192 u/l) but CK-MB and troponin I were normal (CK-MB 47; troponin 0,055 mg/l). Takotsubo stress cardiomiopathy, induced by pheochromocytoma.

During the first admission in Parhon, the patient was highly unstable, with BP 260mmHg- 40mmHg, she was immediately transferred to Floreasca Emergency Hospital for hemodynamic stabilization
Blood pressure variation during the hours before admission to the ICU
SBP
300 250 200 150 100 50 0

30

45

60

105

130

150

225

235

245

340

355 385 395 min

During spells Plasma MN (pg/ml) Plasma NMN (pg/ml) 3365 (N<90) 4943 (N<200)

Repeated CgA (ng/ml) 1640 3009 CEA (ng/ml) NSE (microg/L) 1439 (N 19-98) 12,06 (N<5) 20,33 (N<18,3)

After the administration of selective and non-selective alpha blockers, a left laparoscopic adrenalectomy was performed

Good postop recovery 2 weeks postop:

Plasma MN (pg/ml) : 14 (N<90) Plasma NMN (pg/ml): 76 (N<200) CgA (ng/ml): 120 9.47

Cortisol (microg/dl): Glucose: 62/78mg/dl

Abdominal CT showed normal right adrenal (arrow) and normal space in the left retroperitoneal area (*) in arterial (up figure) and venous phase of contrast CT (down figure).

HP exam showed pheocromocytoma with sinusoids, areas of edema and hemorrhage, cell pleomorphism

Histopathology cannot reliably determine whether a pheochromocytoma is malignant!!!

2 months postop:
Plasma MN (pg/ml) Plasma NMN (pg/ml) CgA (ng/ml) 10 (N<90) 30 (N<200) 40 (N 19-98)

OGTT: 86,8- 172- 122mg/dl- no DM!

6 months postop:
Plasma MN (pg/ml) Plasma NMN (pg/ml) CgA (ng/ml) Cortisol (microg/dl) 14 76 120 9.47

OGTT: 87-118-92mg/dl

Abdominal ultrasound: absent left adrenal gland, right adrenal normal in size and shape.

Physical exam:

obese (BMI 36 kg/m2), no marfanoid body habitus, normal skin aspect,

no mucosal neuromas, no neurofibromas, no caf-au-lait spots, inguinal and axillary freckling absent, iris hamartomas absent, no lipomas,

normal HR, BP 120/80mmHg, no orthostatic hypotension

Lab exams

Plasma MN: 10 pg/ml Plasma NMN: 72pg/ml TSH: 1,8microUI/ml, FT4: 17,9 pmol/l- euthyroidism Abdominal ultrasound: similar aspect with last examination Cardiac examination: normal ECG, normalization of the previous ischaemic aspects, BP 110/75mmHg, HR 72/min Ophthalmologic exam: hypertensive retinopathy I/II.

Additional investigations needed:

24 hours-urine fractionated catecholamines and metanephrines (x2)

Clinicians should have an increased index of suspicion for a hereditary syndrome:

calcitonine + thyroid ultrasound (to rule out a possible MTC), PTH +repeated Ca, P (to rule out HPTH)- MEN 2a syndrome? MEN 2b von Hippel-Lindau disease - retinal angiomas, cerebellar tumor, Neurofibromatosis type 1 - cafe au lait spots, axillary and inguinal freckling, and subcutaneous neurofibromas Familial paraganglioma: mutations in the SDH subunit genes (SDHB, SDHC, SDHD, SDHAF2, SDHA) other neurocutaneous syndromes (ataxia-teleangiectasia, tuberous sclerosis, Sturge-Weber syndrome, Carney triad)?

All first-degree relatives of a patient with pheochromocytoma/ paraganglioma should have biochemical testing

24-hour urine for fractionated metanephrines and catecholamines

If mutation testing in a patient is positive, first-degree relatives should be offered genetic testing

Endocrine causes of hypertension

Adrenal dependent:
-pheochromocytoma -primary aldosteronism -hyperdeoxycorticosteronism -congenital adrenal hyperplasia -11beta-hydroxylase deficiency -17alpha-Hydroxylase deficiency -deoxycorticosterone-producing tumor -primary cortisol resistance -Cushings syndrome

Apparent mineralocorticoid excess (AME)/11beta-hydroxysteroid dehydrogenase deficiency

-genetic (type 1 AME, type 2 AME) -acquired (licorice or carbenexolone ingestion, type 1 AME; Cushings syndrome, type 2 AME)

Thyroid dependent (hypothyroidism, hyperthyroidism) Parathyroid dependent (hyperparathyroidism)

Pituitary dependent (acromegaly, Cushings syndrome)

Long-term postoperative follow-up

Survival rate after removal of a benign pheochromocytoma is nearly that of age-matched and sex-matched normal control
All patients with pheochromocytomas require long-term postoperative surveillance !! A postoperative 123I-MIBG scan or PET scan is recommended for all patients - especially for those in whom there is any doubt about complete resection of the pheochromocytoma and for any patients with paraganglioma or multiple tumors.

The postoperative scan is usually obtained several months after surgery*

Annual biochemical testing assesses for metastatic disease, tumor recurrence in the adrenal bed, and delayed appearance of multiple primary tumors. Patients with secretory tumors are usually followed with plasmafractionated free metanephrine determinations.

Follow-up CT/MRI is not needed unless the metanephrine/catecholamine levels become elevated
* Fitzgerald PA. Chapter 11. Adrenal Medulla and Paraganglia. In: Gardner DG, Shoback D, eds. Greenspans Basic & Clinical Endocrinology. 9th ed. New York: McGraw-Hill; 2011.