Journal of Diabetes and Its Complications 22 (2008) 295 – 296 WWW.JDCJOURNAL.COM
Pheochromocytoma presenting as diabetic ketoacidosis Stella Doumaa, Konstantinos Petidisa, Nikoleta Kartalia,4, Konstantina Maherab, Christos Sabanisa, Chrysanthos Zamboulisa a
Second Propaideutic University Clinic, Ippokrateio General Hospital, Thessaloniki, Greece b Agios Pavlos General Hospital, Thessaloniki, Greece
Received 16 November 2006; received in revised form 28 January 2007; accepted 20 February 2007
Abstract Pheochromocytoma is a rare form of secondary hypertension and may be potentially lethal if left untreated. The classical symptoms are paroxysmal hypertension, headaches, palpitations and sweating. They are caused by sudden catecholamine release. Hyperglycemia is reported in some patients with pheochromocytoma but diabetic ketoacidosis is an extremely rare complication of pheochromocytoma with only four cases reported. We report a case of a young woman with pheochromocytoma manifested as diabetic ketoacidosis. D 2008 Elsevier Inc. All rights reserved. Keywords: Pheochromocytoma; Ketoacidosis; Catecholamines
Diabetic ketoacidosis as a first symptom of pheochromocytoma is extremely rare, and only four cases have been published in the literature (Blu¨her, Windgassen, & Paschke, 2000; Ishii et al., 2001; Isotani, Fujimura, Furukawa, & Morita, 1996; Saito et al., 2000). Diabetes is present in approximately one third of patients with pheochromocytoma (La Batide-Alanorea, Chatellierb, & Plouina, 2003). The main cause of pheochromocytoma-related diabetes is considered to be decreased insulin secretion (Blu¨her et al., 2000). We report a case of pheochromocytoma presenting as diabetic ketoacidosis. A 39-year-old woman was admitted to the hospital because of malaise, vomiting, and polydipsia of 3 days’ duration. She had a history of polycystic ovary syndrome (PCOS) diagnosed at the age of 14 years. The patient had irregular menstrual cycle, obesity, polycystic ovaries as shown on ultrasound, and a left adrenal mass of 33 cm, which was diagnosed 10 years ago without hormonal secretion. A diagnosis of pheochromocytoma was excluded because of normal levels of urine catecholamines on 4 Corresponding author. E-mail address:
[email protected] (N. Kartali). 1056-8727/08/$ – see front matter D 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jdiacomp.2007.02.006
repeated measurements over the next 2 years. There was no glucose intolerance or hypertension in the recent past. At the time of admission, the patient was pale and anxious, with palpitations. The temperature was 37.48C, the heart rate was 108 beats/min, and the blood pressure was 170/110 mmHg. Laboratory tests showed hyperglycemia, with glucose levels of 745 mg/dl and metabolic acidosis (pH 7.32, HCO3=12 mEq/l, anion gap=14, positive ketones in the urine). The patient received intravenous insulin, hydration, and electrolytes; after the resolution of diabetic acidosis, she was treated with diet and regular insulin. During hospitalization, the patient had frequent hypertensive crises, with blood pressure readings up to 220/120 mmHg. Computed tomography was performed and revealed a large left adrenal mass of 8.510 cm (Fig. 1). Hormonal tests showed the following: plasma norepinephrine=2040 pg/ml (normal value, b350 pg/ml), plasma epinephrine=2733 pg/ml (normal value, b120 pg/ml), urine catecholamine=347 Ag NA/24 h (normal value, b150 Ag NA/24 h), cortisol=8.8–10 Ag/dl, dehydroepiandrosterone=198 ng/ml (normal range, 1200–3600 ng/ml), parathyroid hormone=60.5 pg/ml (normal range, 9–55 pg/ml), and calcitonin 10 min after administration of pentagastrin=1.9 pg/ml.
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Fig. 1. A large mass, 8.5 10 cm of the left adrenal.
The iodine-123 metaiodobenzylguanidine scan showed uptake in the area of the left adrenal gland. The patient received terazosin (a-adrenergic receptor blocker), 10 mg, and atenolol (h-adrenergic receptor blocker), 100 mg, preoperatively. The patient underwent adrenalectomy, and a diagnosis of pheochromocytoma was established by histology. After the operation, glucose levels returned to the normal range without the need for diet and insulin therapy (she received insulin at 70 IU/day before the operation). Blood pressure returned to normal levels without any need for antihypertensive therapy. C-peptide levels before and after surgery were 6.8 and 3.4 ng/ml (normal value, 1.1–3.2 ng/ml), respectively, indicating a normal production of insulin. Four months after surgery, the patient is in good health, has normal blood pressure, and has normal oral glucose tolerance test (OGGT). Although the patient had PCOS, she had not taken any medication for insulin resistance in the past. PCOS is known to cause insulin resistance and glucose intolerance (Ben-Haroush, Yoger, & Fisch, 2004), in general; however, in our patient, we believe it was not the case because (a) she did not have insulin resistance in the past, although she had PCOS for a number of years; (b) the OGGT after surgery was normal; and (c) the presence of insulin resistance, although common (about 40–50%) (Ben-Haroush et al., 2004), is not an obligatory finding in PCOS. Impaired glucose tolerance is reported in patients with pheochromocytoma, with incidence ranging from 25% to
75% (Wiesner, Blu¨her, Windgassen, & Paschke, 2003). The inhibitory effect of catecholamines on insulin secretion is thought to be mediated by a2-receptors. Elevation of epinephrine levels has a profound effect on glucose intolerance. It also induces lipolysis and hepatic gluconeogenesis, and inhibits peripheral glucose utilization (Ishii et al., 2001). On the other hand, elevated norepinephrine stimulates glucogenolysis in the liver, suppresses insulin secretion, increases plasma glucagon concentration, and increases ketone body production (Ishii et al., 2001). However, norepinephrine has much less pronounced direct hyperglycemic effects (Porte & Sherwin, 1997). In our patient, the possible mechanisms that led to diabetic ketoacidosis could be increased lipolysis due to reduced insulin secretion and increased glucose production from the liver. The trigger of these mechanisms is unknown. In patients with pheochromocytoma, impaired glucose tolerance results from multiple mechanisms such as inhibition of insulin secretion, stimulation of glucogenolysis, and enhanced lipolysis. Administration of a-adrenergic blockers improves glucose tolerance, and surgical removal of the tumor restores or improves glucose tolerance (Porte & Sherwin, 1997).
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