We present the clinical case of a patient who was admitted with an onset of diabetes mellitus (DM) with associated ketosis and whose clinical, hormonal, and radiological evolution revealed the presence of primary hyperparathyroidism, pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the context of multiple endocrine neoplasia type 1 (MEN1). DM is relatively common in cases of acromegaly, but it is not generally associated with ketosis. Simultaneously, the patient presented a meningioma, which is associated with pituitary macroadenoma only in extremely rare cases.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by the combined appearance of tumors in the parathyroid glands, pancreas islet cells, and the anterior pituitary. This type of syndromes is known to be associated with the secretion of a wide range of hormones which are often responsible for alterations in the glucose metabolism. However, the presence of diabetic ketosis and/or ketoacidosis is a rare clinical situation, with very few cases reported so far. Also, and in an even less common case, the patient simultaneously presented a GH-producing pituitary macroadenoma and a meningioma, a combination which is extremely rare.
We present the clinical case of a 35-year-old woman with a history of Chagas disease who was admitted in the Unit of Endocrinology with hyperglycemia and ketosis in the context of onset of DM with weakness, polydipsia, and polyuria of 4 months of evolution, together with a weight loss of 10 kg over the last 6 months. Also, she presented amenorrhea for 4 months and hyperhidrosis. The examination revealed a slight prognathism, growth of acral parts of the body, and grade 1 goiter with a 2-cm left thyroid nodule.
The analysis showed glucose 248 mg/dL, HbA1c 14.6%, calcium 11.3 mg/dL, phosphorus 2.3 mg/dL, and urine calcium 513 mg/24 h. Given the initial findings, the study was expanded to include a hormone profile test (Table
Hormone measurements in plasma.
Hormone | Value | Normal range |
---|---|---|
TSH ( |
4.7 | 0.27–4.2 |
Free T4 (ng/dL) | 1.1 | 0.82–1.78 |
FSH (mUI/mL) | 3.3 | 3.5–12.5 |
LH (mUI/mL) | 1.9 | 2.4–12.6 |
Estradiol (pg/mL) | <5 | 12.5–166 |
Prolactin (ng/mL) | 59.2 | 4.79–23.3 |
GH (ng/mL) | 48.1 | 0–8 |
IGF1 (ng/mL) | 702 | 109–284 |
Cortisol ( |
10.5 | 2.69–18 |
PTH (pg/mL) | 203.4 | 11–67 |
The endocrine study confirmed the clinical suspicion of primary hyperparathyroidism and GH hypersecretion. The parathyroid SPECT/CT was compatible with right parathyroid adenoma. A nuclear magnetic resonance (NMR) revealed a pituitary macroadenoma of 20 × 13 × 15 mm which spread to the right cavernous sinus, with displacement of the optic chiasm, and a left superior extra-axial parietal lesion of 20 × 20 × 12 mm which suggested a meningioma (Figure
(NMR) pituitary macroadenoma and left superior parietal extra-axial lesion compatible with meningioma.
Given these findings and the clinical suspicion of MEN1, the study was completed with a CT scan of the neck, chest, abdomen, and pelvis, which showed a hypervascular heterogeneous mass with lobulated and well-defined edges of 6.8 × 7.7 × 6.4 cm in the tail of pancreas, plus another mass of similar characteristics of 6 × 4.2 cm in the uncinate process and at least three more pancreatic focal lesions of less than 1 cm on the head and neck of pancreas (Figure
(CT) tail of pancreas with hypervascular heterogeneous and well-defined mass with lobulated edges measuring 6.8 × 7.7 × 6.4 cm.
A somatostatin receptor scintigraphy (OctreoScan) was performed showing a pathological deposit in the tail of pancreas which suggested a tumor with expression of somatostatin receptors and also at the upper left parietal level, which was caused by a meningioma (Figure
OctreoScan showing a pathological deposit at the upper left parietal level caused by meningioma and in the tail of pancreas.
The patient started treatment with high doses of basal-bolus insulin therapy, somatostatin analogs, and cinacalcet. Afterwards, cabergoline was added due to the persistence of high levels of IGF1. The pituitary macroadenoma was resected through a transnasal transsphenoidal and the IGF1 levels went back to normal, with octreotide treatment. The anatomic pathology revealed a pituitary somatotroph adenoma (densely granulated) and the immunohistochemical study: CAM 5.2 (+++), GH (+++), p53 (−), and MIB-1 <1%. An abdominal NMR was performed to control the evolution of her condition, and it still showed two heterogeneous lesions on the head and tail of pancreas, of 5.5 × 4.5 × 4 cm and 6 × 7.5 × 8 cm, respectively, contrast-enhanced and with well-defined edges. Also, the liver had normal size, morphology, and intensity, and the image did not reveal the lesions described in the CT scan image.
After an assessment by an interdisciplinary board, the patient underwent total pancreaticoduodenectomy, cholecystectomy, and splenectomy. The anatomical pathology showed 7 well-differentiated (G1) NETs in the pancreas, 1 well-differentiated NET (G1) in the pylorus of <0.5 cm, 14 lymph nodes in the tail of pancreas with no sign of malignancy, and 2 lymph nodes with NET metastasis out of 12 isolated nodes on the head of pancreas (pT2N1). All the tumors expressed chromogranin A and synaptophysin, with proliferation mediated by Ki67 <1%, except for the node found in the neck of pancreas, in which it reached 2-3%. Also, 2 out of the 7 tumors were intensely positive for glucagon (100%) (Figure
Immunohistochemistry with positive cells for glucagon.
We present the case of a patient with MEN1 with some peculiar features.
The authors declare that there are no conflicts of interest.
Dr. Herrero-Ruiz collected data, analyzed all patient data, wrote the final paper, and intervened in the care of the patient; Dr. Villanueva-Alvarado collected data, analyzed all patient data, wrote the first draft, and intervened in the care of the patient; Dr. Corrales-Hernández, Dr. Higueruela-Mínguez, and Dr. Feito-Pérez intervened in the care of the patient; Dr. Recio-Cordova intervened in the care and follow-up of the patient.