2. Presentation of CaseA 17-year-old girl was referred to our department for the investigation of a newly diagnosed diabetes mellitus and a severe arterial hypertension. She was the first child of consanguineous parents. Her past medical history was unremarkable. Her family history was notable for type 2 diabetes and dyslipidemia but no history of pheochromocytoma, paraganglioma, unexplained sudden death, or condition that may lead to thinking about VHL disease was reported.As symptoms, the patient complained of headaches, palpitations, diaphoresis, and hot flashes since one month. She reported also asthenia and body weight loss of five kilograms in two weeks.On examination, she had a body weight of 50 kg, a body height of 154 cm, a body mass index of 21.1 kg/m2, a blood pressure of 200/100 mmHg without orthostatic hypotension, a regular pulse of 120 bpm, and a large abdominal café-au-lait spot (Figure 1). Thyroid, abdominal, and neurological examinations were normal.Open in a separate windowFigure 1A large abdominal café-au-lait spot.Twenty-four-hour blood pressure monitoring confirmed the diagnosis of hypertension and the presence of peaks of 230/110 mmHg. Electrocardiogram showed a sinus tachycardia. Capillary glucose level was 2.68 g/l without ketosis.Fundoscopy showed grade 3 hypertensive retinopathy without any other abnormalities.The results of biological investigations are shown in Table 1.Table 1Biological parameters before and after surgery. Before surgeryAfter surgeryReference rangesFasting glucose level (mmol/l)16.394.784.12–5.55Glycated hemoglobin (%)10.125.91≤5.6Total cholesterol (mmol/l)11.835.233.1–5.18Triglycerides (mmol/l)2.431.210.57–1.71Natremia (mmol/l)135140135–145Kalemia (mmol/l)3.343.6–5Creatinine (mg/L)664–13Calcium (mg/L)111.29888–105Phosphate (mg/L)443627–45Albumin (g/l)47.22—35–52Intact PTH∗ (μg/L)1825411–62TSH (mUI/L)0.625—0.12–3.4FT4 (ng/dl)1.31—0.71–1.85Calcitonin (ng/L)2.70—<10.0024 h-urine NMN (μg/24)315057030–60024 h-urine MN (μg/24)40.21220–34524 h-urine sodium (mmol/24 h)88.5— 24 h-urine potassium (mmol/24 h)60— 24 h-urine calcium (mg/24 h)200— 24 h-proteinuria (g/24)0.3—<0.3Open in a separate windowPTH: parathormone, TSH: thyroid stimulating hormone, FT4: free-T4, NMN: normetanephrines, MN: metanephrines. ∗The intact PTH dosage was made using 3rd generation chemiluminescence immunoassay.The diagnosis of clinically suspected pheochromocytoma was confirmed by the dosage of urinary methoxylated derivatives at 5 times the upper limit of normal. In addition, the diagnosis of diabetes mellitus, dyslipidemia, and primary hyperparathyroidism were made.The abdominal computed tomography (CT) showed two adrenal masses: the first on the right measuring 35 × 55 × 70 mm with a spontaneous density of 30 HU heterogeneously enhanced in the arterial time showing areas of necrosis with an absolute washout of 40%, the second on the left measuring 24 × 27 mm with the same characteristics as the first one (Figure 2). There were neither other localizations nor lymph nodes. Metaiodobenzylguanidine (MIBG) scintigraphy exhibited a high accumulation of the tracer in both adrenal tumors with no other localization. Cervical ultrasound and 99mTc-sestamibi scintigraphy were normal. Cardiac ultrasound was normal.Open in a separate windowFigure 2Abdominal computed tomography showing the two adrenal masses (two white arrows).

The genetic testing revealed the presence of NF1 germline mutation (c.3516_3517delTC, p.D1172DfsX21). However, while the genetic analysis of the RET proto-oncogene did not reveal any mutation, the screening of the VHL gene revealed the presence of a so far undescribed missense variant (c.788 C>G, p.Pro192Arg). Both variants were present in the mother and absent in the healthy son.