Resolution of grade IV hypertensive retinopathy in an adult with pheochromocytoma: post-tumor resection

Abstract

A 64-year-old hypertensive woman presented with complaints of a painless, progressive decrease in vision, headache, dizziness for the last month. She was a known case of diabetes mellitus on insulin therapy. On examination, best-corrected visual acuity was 6/12 in the right eye and 6/18 in the left eye. The fundus examination in both eyes revealed features of grade IV hypertensive retinopathy. Systemic examination revealed the raised blood pressure of 200/110 mm Hg. Diagnosis of pheochromocytoma was made on the basis of increased urinary norepinephrine (892.8 mg/dL) and mass in the left adrenal gland (measuring 31×28 mm) at contrast-enhanced CT. Medical management to control hypertension was done and ultimately, she underwent left laparoscopic adrenalectomy. After 10 months of surgery, the patient was asymptomatic, blood pressure was within normal limit and her vision improved to 6/6 in both the eyes. The retinal features of hypertensive retinopathy had completely disappeared.

Background

Arterial hypertension is a very common disease of which 10%–15% cases have a curable secondary cause.¹ Pheochromocytoma represents one such rare cause. It is a rare neuroendocrine tumour among the various endocrine causes of secondary hypertension which secretes catecholamines and other neuropeptides.² Most of the cases are sporadic in nature although 10%–25% cases may have genetic associations like multiple endocrine neoplasia type 2, type 1 neurofibromatosis and Von Hippel-Landau disease, which implies the need for genetic testing in these cases.³ Ocular manifestations of pheochromocytoma include headache and loss of vision. Few such case reports have been reported where these patients presented with a decrease in vision due to the development of hypertensive retinopathy. This case highlights the complete restoration of vision in a patient of pheochromocytoma, presenting with grade IV hypertensive retinopathy.

Case presentation

A 64-year-old hypertensive woman presented with complaints of a painless, progressive decrease in vision, along with headache and dizziness for the last 1 month. She was a known case of diabetes mellitus, well-controlled on insulin therapy for 3 years. On examination, best-corrected visual acuity was 6/12 in the right eye and 6/18 in the left eye. Slit-lamp biomicroscopic examination of the anterior chamber was unremarkable in both the eyes. Intraocular pressure was 14 and 16 mm Hg in right and left eye, respectively. Pupils in both the eyes were 4 mm, round with mild sluggish reaction to light. Fundus examination in both eyes revealed disc oedema along with cotton wool spots and hard exudates in the macula in a macular star configuration (figure 1). There were no signs of diabetic retinopathy such as dot and blot haemorrhages, microaneurysms, intraretinal microvascular abnormality and venous beading.

Figure 1.

(A) Right eye fundus shows disc oedema, tortuosity of vessels, arterial attenuation and macular exuadates. (B) Left eye fundus shows disc oedema, tortuosity of vessels, arterial attenuation and macular exuadates.

Investigations

Systemic blood pressure was raised (200/110 mm Hg). Routine blood examination showed anaemia (8.2 mg/dL). Other blood investigations including fasting and postprandial blood sugar, serum lipid profile, urea, creatinine and uric acid were within normal limits. The cardiac ECG showed sinus tachycardia. Chest X-ray was normal. The presence of normal routine blood investigations guided us to search for a cause of secondary hypertension. Serum aldosterone, cortisol, potassium, calcium and thyroid profile were also advised whose levels were within normal limits. Urinary norepinephrine was found to be raised (892.8 mg/dL), whereas urinary epinephrine and plasma metanephrines were within normal limits. Contrast-enhanced CT (CECT) of the abdomen and pelvis showed a large heterogeneous mass in the left adrenal gland (measuring 31×28 mm) with areas of attenuation and contrast enhancement, features suggestive of pheochromocytoma.

Differential diagnosis

As the patient was having bilateral grade IV hypertensive retinopathy with the hypertensive crisis, there were many differential diagnoses to it. One was essential hypertension and the others were pheochromocytoma, aldosteronism, Cushing syndrome, hyperthyroidism, hyperparathyroidism and renal artery stenosis. Pheochromocytoma was confirmed by increased catecholamines in urine and CT scan of the abdomen. Other diseases were ruled out by the presence of normal serum urea, creatinine, aldosterone, cortisol, potassium, calcium and thyroid profile As the patient was diabetic, diabetic retinopathy was also considered in the differential diagnosis. The presence of disc oedema, arterial attenuation, cotton wool spots and hard exudates in the form of macular star configuration and the absence of microaneurysms, dot and blot haemorrhages, intraretinal microvascular abnormality and venous beading or neovascularisation went more in favour of hypertensive retinopathy than diabetic retinopathy.

Treatment

The patient underwent medical management to control hypertension and ultimately, she underwent left laparoscopic adrenalectomy. The surgery was uneventful. The histopathology of the excised tissue biopsy confirmed the pathology as pheochromocytoma. (figure 2)

Figure 2.

(A) Photomicrograph showing tumour capsule and a highly cellular tumour, there is no capsular invasion, H&E stain, 100x (B) Tumour cells are arranged in nests separated by thin fibrovascular septae, the cells are polygonal with abundant granular eosinophilic cytoplasm, no mitosis or necrosis was noted, H&E stain, 400x.

Outcome and follow-up

After 10 months of surgery, the patient was asymptomatic, blood pressure was within normal limit and her vision improved to 6/6 in both the eyes. Fundus examination in both the eyes showed resolved disc oedema along with disappeared hard and soft exudates. The retinal features of hypertensive retinopathy had completely disappeared (figure 3).

Figure 3.

(A) Right eye fundus shows resolution of disc oedema, decreased tortuosity of vessels and macular exudates. (B) Left eye fundus shows resolution of disc oedema, decreased tortuosity of vessels and macular exudates.

Discussion

Typical clinical manifestations of the pheochromocytoma include sustained or paroxysmal hypertension, sweating, headache and palpitation.⁴ Because of its varied presentations, the diagnosis is often challenging and can be a life-threatening situation if it remains undiagnosed. Ocular manifestation includes a decrease in vision due to the development of hypertensive retinopathy.

In the present case, apart from the described presenting symptoms, the fundus finding is consistent with grade IV hypertensive retinopathy in malignant hypertension as outlined by the Modified Scheie Classification System.⁵ Few such case reports have been reported where these patients present with a decrease in vision due to the development of hypertensive retinopathy.

Petkou et al ⁶ reported severe hypertensive retinopathy with optic neuropathy in a 31-year-old woman with malignant hypertension due to pheochromocytoma in which the retinal changes disappeared after tumour ablation in the perioperative period.

Marisa maeibel Alface et al also reported a case of grade 2 hypertensive retinopathy in a 15-year-old girl with pheochromocytoma who underwent laparoscopic adrenalectomy and remained symptom-free in the postoperative period.¹

Laboratory confirmation of the diagnosis requires increased levels of serum catecholamines (especially norepinephrine) and urinary metanephrines. Serum and urinary assays of metanephrines are the most sensitive and reliable tests.⁷ The specificity of total 24 urinary metanephrine and catecholamines is more than that of fractionated plasma metanephrines. Apart from this, tumour localisation is necessary with imaging tests like abdominal CT or MRI and I123-MIBG or I131-MIBG scintigraphy, as reported in our case with CECT scan showing a large heterogeneous mass in the left adrenal gland, with areas of attenuation greater than 10 symptom-free units, compatible with a pheochromocytoma, differentiating it from other similar diseases like adrenal adenoma, carcinoma and metastasis.⁸

The sensitivity of CT scan in detecting pheochromocytoma is 93%, whereas specificity is 95%, is cheaper and easily available. The sensitivity of ¹²³I-metaiodobenzylguanidine (MIBG) ranges between 85% and 88% for pheochromocytoma whereas its specificity ranges from 70% to 100% and is expensive also.⁹

Based on the previously documented reports, this patient underwent adrenalectomy after the control of hypertension with medical management. Literature suggests that within a matter of months after the control of hypertension, the fundus abnormalities described under malignant hypertension resolve.¹⁰ In our case, as the primary factor causing hypertension, was pheochromocytoma within a matter of few months after adrenalectomy, systemic blood pressure was under control (134/84 mm Hg) without any antihypertensive medications, the patient was symptom-free, serum and urinary metanephrines normalised. Retinal features of grade IV hypertensive retinopathy (disc oedema and hard exudates) had completely disappeared.

Hence, this case highlights the importance of adequate and timely medical and surgical intervention in a case of secondary cause (pheochromocytoma) of grade IV hypertensive retinopathy, which not only is life-saving but can also cause complete disappearance of retinal features of hypertensive retinopathy and restoration of vision.

Patient’s perspective.

I am satisfied with the investigations and treatment process for my disease. Now I have controlled blood pressure and my vision has been improved.

Learning points.

• Although pheochromocytoma is a rare cause for hypertension, it should be considered when a patient presents with headache, sweating, palpitation and a decrease in vision.

• Although pheochromocytoma is more common in age 20–50 years of age, it should be considered even in older patients, as these cases present as diagnostic challenges, and a delayed diagnosis can be life-threatening.

• The retinal examination serves as an important diagnostic tool in patients complaining of headache and blurring of vision.