Insulinoma presenting with hyperandrogenism - Wiley Online Library

Journal of Internal Medicine 2003; 253: 484–489

CASE REPORT

Insulinoma presenting with hyperandrogenism: a case report and a literature review I. N. STANCIU1, S. PITALE1, R. A. PRINZ2, S. JAKATE3, G. WEBB3, D. STEINER3, S. BRAITHWAITE4, D. GORDON1 & M. A. EMANUELE1 From the 1Department of Endocrinology and Metabolism, Loyola University Medical Center and Hines VA Hospital, Maywood, IL, USA, 2 Department of Surgery, Rush Presbyterian St Luke’s Medical Center, Chicago, IL, USA, 3Department of Endocrinology and Metabolism, University of Chicago, Chicago, IL, USA, and 4Department of Endocrinology and Metabolism, UNC Diabetes Care Center, Durham, NC, USA

Abstract. Stanciu IN, Pitale S, Prinz RA, Jakate S, Webb G, Steiner D, Braithwaite S, Gordon D, Emanuele MA (Loyola University Medical Center and Hines VA Hospital, Maywood IL, USA; Rush Presbyterian St Luke’s Medical Center, Chicago, IL, USA; University of Chicago, Chicago, IL; and UNC Diabetes Care Center, Durham, NC, USA). Insulinoma presenting with hyperandrogenism: a case report and a literature review (Case Report). J Intern Med 2003; 253: 484–489. An 18-year-old woman presented with a 6-month history of amenorrhoea and hyperandrogenism. Three months later she developed several episodes of fasting hypoglycaemia and was subsequently diagnosed with an insulinoma. Hyperinsulinaemia was observed in association with an elevated serum testosterone level. Surgical removal of the insulinoma resulted in resolution of the clinical and bio-

Introduction Insulinoma is the most common pancreatic endocrine tumour and the most common cause of hypoglycaemia resulting from endogenous hyperinsulinism. In large series of patients with insulinoma, the median age at diagnosis was 51–55 years in sporadic cases [1, 2]. Patients classically present with fatigue, weakness, tremulousness and hunger, which become worse with fasting. Some patients may present with neuropsychiatric symptoms related to neuroglycopenia: blurred vision, changes in mental status and even frank psychosis, which often confuse and delay the 484

chemical features of the polycystic ovarian syndrome (PCOS). Polycystic ovarian syndrome is unusual in a patient having an insulinoma. The rarity of this association may be the result of the late age of onset of this type of tumour, intermittent secretion of excessive insulin by the tumour, the degree of hyperinsulinism or other factors extrinsic to the insulin receptor that may facilitate insulin activity. However, we could not discover how our patient differs in having had PCOS from the majority of women with insulinoma who do not. If other patients with insulinoma are subsequently found to have hyperandrogenism, then this tumour might be added to the differential diagnosis of causes of anovulatory cycles and hyperandrogenaemia, although rare the association would be uncommon. Keywords: hirsutism, insulin receptor, insulinoma, polycystic ovarian syndrome.

diagnosis. In addition to relative or actual hyperinsulinism, patients with insulinoma demonstrate insulin resistance [3, 4]. The most common cause of hyperandrogenism in women is polycystic ovarian syndrome (PCOS), which has been described in 5–10% of adult premenopausal women [5]. The pathophysiology of PCOS is heterogeneous but insulin resistance with consequent hyperinsulinism appears to be one of the most common reasons [5]. Yet, there have only been three reported cases of insulinoma associated with hyperandrogenism [6–8]. If hyperinsulinism leads to ovarian androgen excess in patients with PCOS, how come cases of Ó 2003 Blackwell Publishing Ltd

CASE REPORT: INSULINOMA PRESENTING WITH HYPERANDROGENISM

hyperandrogenism in insulinoma have been described so infrequently? We described a patient with an insulinoma and PCOS and explore the reasons and why the combination may not be found more frequently.

Case report An 18-year-old Caucasian female presented for evaluation of amenorrhoea in December 1997. She underwent puberty at age 11 and had menarche at the age of 12.5 years. Regular menstrual cycles of 30–40 days occurred until August 1997 when her cycles became irregular and they ceased completely in October 1997. She had noted an increase in her weight from 63.2 to 69.5 kg in addition to increased muscle mass and facial acne over the preceding 6 months. There was no use of any medications. Her family history was remarkable in that her father had undergone resection of a haemorrhagic pheochromocytoma and also had the antiphospholipid syndrome. Negative results of polymerase chain reaction (PCR) and direct sequence analysis for mutations in the von Hippel–Lindau disease gene, the lack of detection of the ret-oncogene, and a normal pentagastrin-stimulated calcitonin test on the father suggested the pheochromocytoma was sporadic. There was no premature frontal baldness in her father or anovulatory cycles, hirsutism, acne or male pattern baldness in her mother. On examination, the patient was a muscular young female with mild facial acne and minimal hirsutism above the upper lip as the only evidence of hirsutism (FG score ¼ 2). No acanthosis nigricans, male pattern baldness or deep voice was observed. Her height was 166.5 cm and her weight 69.5 kg. The remainder of the examination was normal. Initial tests showed elevated total testosterone 148 (normal 50–119 ng dL)1), luteinizing hormone (LH) 13.7 mIU mL)1, follicle-stimulating hormone (FSH) 5.9 mIU mL)1 with an elevated LH : FSH ratio [2, 3] but normal thyroid-stimulating hormone (TSH), free T4, and prolactin. The patient was suspected to have Polycystic ovarian syndrome. In March 1998 she had an episode of confusion, lip smacking and aphasia relieved by carbohydrate ingestion. Subsequent blood sugar levels on home glucose monitoring were 37–72 mg dL)1. Further laboratory studies revealed fasting glucose levels of 59–70 mg dL)1 with concomitant insulin levels

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ranging from 14 to 26 lU mL)1 (normal