A case of phaeochromocytoma with normal metanephrine but high plasma aldosterone

Wafia Najifa; M A. Jalil Ansari; Indrajit Prasad; Mohammad Saifuddin; Moinul Islam; Mirza Sharifuzzaman; Mohammad Jahangir Alam; Farhana Afrooz; Sadia Jabeen Mustafa; A K. M Fahad

doi:10.4103/bjem.bjem_21_22

CASE REPORT

Year : 2023 | Volume : 2 | Issue : 1 | Page : 58-60

A case of phaeochromocytoma with normal metanephrine but high plasma aldosterone

Wafia Najifa, M A. Jalil Ansari, Indrajit Prasad, Mohammad Saifuddin, Moinul Islam, Mirza Sharifuzzaman, Mohammad Jahangir Alam, Farhana Afrooz, Sadia Jabeen Mustafa, A K. M Fahad
Department of Endocrinology, Dhaka Medical College, Dhaka, Bangladesh

Date of Submission	20-Dec-2022
Date of Acceptance	13-Jan-2023
Date of Web Publication	24-Feb-2023

Correspondence Address:
Wafia Najifa
Dhaka Medical College Hospital, Dhaka
Bangladesh

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjem.bjem_21_22

Abstract

Pheochromocytoma is one of the causes of endocrine hypertension leading to stroke in young patients. The tumor secretes not only catecholamines but also other hormones in rare occasions. Besides, symptomatic tumors may come with normal catecholamine metabolite levels. Here is a case of a 28-year-old male featuring these exceptions who was managed at Dhaka Medical College Hospital.

Keywords: Catecholamine, endocrine hypertension, phaeochromocytoma

How to cite this article:
Najifa W, Ansari M A, Prasad I, Saifuddin M, Islam M, Sharifuzzaman M, Alam MJ, Afrooz F, Mustafa SJ, Fahad A K. A case of phaeochromocytoma with normal metanephrine but high plasma aldosterone. Bangladesh J Endocrinol Metab 2023;2:58-60

How to cite this URL:
Najifa W, Ansari M A, Prasad I, Saifuddin M, Islam M, Sharifuzzaman M, Alam MJ, Afrooz F, Mustafa SJ, Fahad A K. A case of phaeochromocytoma with normal metanephrine but high plasma aldosterone. Bangladesh J Endocrinol Metab [serial online] 2023 [cited 2023 Jun 7];2:58-60. Available from: https://www.bjem.org/text.asp?2023/2/1/58/370508

Introduction

Pheochromocytomas are catecholamine-secreting tumors arising from the adrenal medulla. The tumor produces both epinephrine and norepinephrine.^[1] It constitutes 0.2%–0.6% of the etiologies of hypertension.^[2] Patients are diagnosed mostly in their 3^rd, 4^th, and 5^th decades of lives.^[3] It presents both sporadically and as part of genetic syndromes. The latter are inherited through germline mutations and hence come with family history.^[1] A “rule of ten” is commonly assigned to describe pheochromocytoma: 10% bilateral, 10% extra-adrenal, 10% malignant, and 10% familial.^[4] However, phaechromocytoma presenting with normal catecholamine but high aldosterone levels is extremely rare and has not been reported in Bangladesh so far.

Case Report

A 28 year old young man was referred to the Endocrinology department of Dhaka Medical College Hospital with an adrenal gland incidentaloma and a history of hemorrhagic stroke in December 2018. He reported of poor health for the previous 3 years. It included periodic bouts of undocumented fever with vomiting and raised blood pressure. He also complained of exertional palpitation and occasional profuse drenching sweating with and without exertion. But he never experienced headache, polyuria, and weight gain. He had no edema, abdominal striae, or rounding of the face. No previous family history of similar illness was given. The patient was to be treated in local health complex with intravenous fluid, antiemetic, and antipyretic and was prescribed Losartan 50 mg tablet daily. He took the antihypertensive irregularly only during the aforementioned illness. In November 2018, the patient developed vomiting, sudden loss of consciousness, urinary incontinence, and right-sided hemiplegia. Computed tomography (CT) scan of his head revealed intracerebral hemorrhage in the left capsule-ganglionic region. He was treated conservatively in a tertiary care hospital, where he regained consciousness, and the hemiplegia improved gradually. Further evaluation of the stroke led to a magnetic resonance imaging (MRI) of the KUB region. A rounded, solid left adrenal mass measuring about 5.5 cm × 5.2 cm × 5 cm compressing and displacing the left kidney inferiorly was noted in it. The mass was T1 hypointense and T2 hyperintense with internal nonenhancing areas. It was separate from the left kidney, spleen, pancreas, and left renal vessels. There was no sign of infiltration into the surrounding tissue. The report suggested the possibilities of pheochromocytoma and adenoma. Notable clinical findings after admission were pulse 102 BPM, blood pressure 160/100 mmHg, 4/5 power of both proximal and distal groups of muscles and exaggerated deep tendon reflexes in both upper and lower limbs on the right side, plantar response extensor on right and flexor on the left. Per abdominal examination was unyielding. Considering all these information, a provisional diagnosis of pheochromocytoma was made, and the differentials were aldosterone-producing adenoma and adenoma-secreting cortisol. Tablet amlodipine 5 mg b. i. d was prescribed instead of Losartan, and different biochemical investigations were done after 10 days to find out the nature of the left adrenal incidentaloma.

Serum electrolytes were normal-sodium 137, potassium 4.4, chloride 93, and TCO₂ 30 mmol/L. 24 hours urinary metanephrine levels were 1519.20 nmol/day and 1305.25 nmol/day respectively (normal level1775 nmol/day) measured on two occasions almost three months apart. 24 h urinary free cortisol was 208.8 nmol/L (normal range 50-190 ug /24 hours). Plasma renin was slightly raised, 42.01 pg/mL (normal range 4.0–37.52 pg/mL). Early morning serum aldosterone was high, 339.60 pg/mL (normal range 20–180 pg/mL) that did not fall after saline suppression test by infusing 2 l normal saline over 4 h (251.20 pg/mL). Besides, echocardiography was normal. Other routine investigation results were Hb12.3 g/dL, total white blood cell count 12,400/cmm (neutrophil 82%, lymphocyte 15%, monocyte 2%, eosinophil 1%), platelet 300,000/cu mm, erythrocyte sedimentation rate 99 mm in 1^st hour. Random blood sugar during admission at Endocrinology department was 8.9 mmol/L but before surgery at Urology department, fasting plasma glucose and plasma glucose 2 hrs after breakfast were 8.31 mmol/L and 9.74 mmol/L respectively. Based on this, the working diagnosis was changed to Conn's Syndrome due to aldosterone-secreting left adrenal adenoma with old hemorrhagic stroke with right-sided hemiplegia. The patient was referred to the urology department for the removal of the tumor in March 2019. The operated tumor was 7 cm × 6 cm × 2.5 cm in size, weighing 93 g. The cut surface was partly yellowish and partly necrotic. Histopathology revealed a neoplasm composed of pleomorphic cells, which were round to oval with moderate-to-abundant cytoplasm and occasional mitoses. The report concluded it to be a Pheochromocytoma.

The patient was discharged after recovery in normotensive and normoglycaemic state without needing respective medication. This status was maintained and he was doing physically well until submission of this case report. But follow-up biochemical investigations, advanced imaging, immunohistochemistry of the tumour specimen and surveillance for malignancy or recurrence could not be done after surgery due to financial constraint of the patient.

Discussion

The diagnosis of pheochromocytoma is based on clinical symptoms, biochemical investigations, suggestive features in imaging, and histopathology. A triad of paroxysmal palpitation, sweating, and headache are the most frequent symptoms. Often, the first presentation is with complications such as stroke, myocardial infarction, left ventricular failure, hypertensive retinopathy or accelerated hypertension as a sequel of uncontrolled hypertension.^[1] Symptoms produced by the tumor are attributed to excess catecholamines secreted episodically. However, the methylated metabolite, vanillylmandelic acid, is secreted continuously and the level in plasma or urine is used as a biochemical marker.^[2] Elevation by more than two times the upper normal limit is considered diagnostic. The test is repeated if not conclusive.^[5] CT and MRI of the abdomen as well as metaiodobenzyl guanidine scintigraphy are used for imaging.^[1] The gross appearance of the tumor is dark red to black in color.^[3]

In this case, the pheochromocytoma was unilateral but on the left side, which is contrary to the common occurrence of right (65%) sided unilateral tumors. Besides, it is found that right-sided tumors present with paroxysmal hypertension while left ones feature sustained hypertension.^[2] Here, the patient presented initially with episodic hypertension, which later became sustained. Moreover, all the presenting symptoms were in favor of pheochromocytoma. But the 24 hours urinary metanephrine levels were found low on both occasions.. Rather, serum aldosterone was high and was more than 100 pg/mL after the saline suppression test. Plasma renin was about 4 pg/mL above the upper normal limit. It was ignored and taken as normal because there are reports of elevated renin due to compression of a renal artery by large perinephric tumors.^[2] Hence, a working diagnosis of Conn's Syndrome was made initially though the renin level is always low in such cases. Later, the histopathology report suggested pheochromocytoma. Literature were searched to solve this diagnostic dilemma. Several papers reported the cosecretion of other hormones by pheochromocytoma besides catecholamines such as adrenocorticotropic hormone, parathyroid hormone-related peptide, vasopressin, vasoactive intestinal peptide, and growth hormone-releasing hormone. The effects of these hormones often dominated the presenting symptoms in these pheochromocytoma patients.^{[6],[7],[8],[9]} However, there were no data found about cosecretion of aldosterone. Rather, there are cases of secondary hyperaldosteronism due to stimulation of Renin-Angiotensin-Aldosterone System (RAAS) through β receptor activation by excess epinephrine from pheochromocytoma.^[10],[11] The mildly elevated plasma renin, in this case, supports this explanation. Still, the possibility of primary hyperaldosteronism due to cosecretion of aldosterone cannot be ruled out due to the result of the saline loading test.^[2] Moreover, symptomatic pheochromocytoma with normal 24 h urinary metanephrine, as in this case, is a rare occurrence. A probable reason is that some pheochromocytomas, particularly of small size, secrete unmetabolized catecholamines that undergo rapid turnover producing clinical symptoms but low metanephrine.^[12] In summary, this is an exceptional case of symptomatic pheochromocytoma with normal metanephrine and coexisting primary and secondary hyperaldosteronism.

Conclusion

This case indicates that adrenal gland pathology should always be suspected in the atypical presentation of hypertension or its complications. The hormone profiles of any adrenal incidentaloma need to be elaborately investigated before making a final diagnosis. The possibility of pheochromocytoma should not be ruled out even when catecholamine metabolites are within normal range.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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