Double, Synchronous Pituitary Adenomas Causing Acromegaly and Cushing’s Disease. A Case Report and Review of Literature
A 47-year-old male was admitted to the Neurosurgical Department with typical clinical features of acromegaly (enlarged doughy hands and feet, frontal bossing, coarsening of facial features with increased interdental spacing and prognathism, thickened lips, etc.) with 2 years duration. On admission to hospital, clinical examination showed oily skin, weight gain with central fat distribution, slight purple striae on the abdomen, and spontaneous ecchymosis. Patient’s body weight was 117 kg and gained over 20 kg per last year. His height was 181 cm and body mass index (BMI) was 35.7 kg/m2. Observed central obesity was not typically cushingoid without moon face and buffalo hump. Patient’s main complaints were progressive headaches, lowered mood, and decreased libido. His blood pressure was slightly elevated and controlled with antihypertensive drugs (selective beta blocker, ACE inhibitor and diuretic); measured in supine position was 130/90 mmHg. His pulse rate was 64 beats per minute. Neurological examination revealed no impairment of visual acuity and visual fields and intact function of other cranial nerves. Fundoscopic examination showed no optic nerve atrophy. The patient had neither family history of pituitary adenoma nor multiple endocrine neoplasia. Endocrine investigation revealed slightly elevated basal serum level of growth hormone (GH) and somatomedin-C (insulin-like growth factor-1) with abnormal oral glucose tolerance test (OGTT) and abnormal circadian rhythm of adrenocorticotropin hormone (ACTH) and cortisol (Table ). The high dose dexamethasone suppression test (8 mg) markedly reduced the concentration of ACTH, cortisol, and its metabolites (17-OHCS and 17-KS) although this effect was not observed with low dose (1 mg) of dexamethason. Serum levels of GH and thyroid-stimulating hormone (TSH) were increased in response to an intravenous administration of thyrotropin-releasing hormone, as shown in Table . The preoperative serum prolactin (PRL) level was within normal limits—15.1 ng/ml. Other pituitary hormones including TSH and gonadotrophins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)) were also within normal ranges. Intravenous administration of LH-RH caused increased secretion of LH, FSH, and PRL (Table ). Serum level of testosterone was low but within normal limits. The function of the thyroid gland was normal and intact parathyroid hormone concentration was normal. Plain skull X-ray film showed slightly enlarged pituitary fossa with thickening of its floor without destruction of the dorsum sellae. Initial MR imaging of the sellar region (coronal and sagittal T1-weighted before Gd-DTPA administration) demonstrated a slightly enlarged and asymmetrical pituitary gland (Ryc 1). Coronal T1-weighted scan after administration of the contrast medium revealed a nonhomogenic region on the right side of the pituitary gland and a hypointensive area on its left side. Coronal T2-weighted MR visualized a hyperintensive signal of the smaller microadenoma on the right side, close to the right cavernous sinus, and a nonhomogenic region on the left side. Preoperative MR imaging suggested the presence of two different tumors in the sella. Both of them are intrasellar microadenomas without cavernous sinus invasion (Fig. ).\nBoth, endocrine investigation and neuroimaging of the pituitary gland strongly indicated coincidence of two different (double) pituitary tumors causing acromegaly and Cushing’s disease. No additional invasive diagnostic procedures (bilateral inferior petrosal sinus or cavernous sinus sampling) were performed.\nThe patient underwent transsphenoidal operation. During the surgery, the sella was exposed and the H-shaped incision of the dura was made. The dura mater was opened and separated from the pituitary capsule to expose the entire anterior surface of the pituitary. Then the gland was carefully explored, regardless of MRI findings. Preoperative suggestion about the presence of two different, clearly separated tumors was confirmed. The mass on the left side of the sella was yellowish, fibrous, and compact and that on the right side was creamy, soft, and brittle. Both tumors were separated by normal pituitary tissue. Excised lesions were fixed separately for further histological examination.\nMaterial was fixed in 10 % formalin, embedded in paraffin, and routinely stained with hematoxylin and eosin (H&E). Immunohistochemical staining was performed on paraffin-embedded specimens according to the labeled EnVision Flex Visualization System (Dako, K8000) with DAB as chromogen using antibodies against anterior pituitary hormones or subunits: prolactin (PRL, dilution 1:200), growth hormone (GH, dilution 1:500), ACTH (dilution 1:500), β-TSH (dilution 1:200), β-FSH (dilution 1:500), β-LH (dilution 1:200)—all antibodies from Neo Markers; the glycoprotein α-subunit (dilution 1:100, Novocastra); somatostatin receptors: sstr2A and sstr5 (dilution 1:1500, BioTrend) and Ki-67 (MIB1 clone)—from Dako. MIB-1 labeling index was established.\nFor electron microscopy, small pieces of tissue were fixed in 2.5 % cold glutaraldehyde, washed in cacodylate buffer, postfixed in 1 % osmium tetroxide, dehydrated in a graded series of ethanol, and embedded in Epon 812. Ultrathin sections were counterstained with uranyl acetate and lead citrate and examined with a Philips CM120 BioTWIN electron microscope (Fig. ).