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A Rare Case of Invasive Pituitary Macroadenoma with Hemorrhage in MEN 1 Syndrome - a Case Report

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A Rare Case of Invasive Pituitary Macroadenoma with Hemorrhage in MEN 1 Syndrome - a Case Report E.A. Ashok Kumar, M. Ravi Teja Raidu. A rare case of invasive pituitary macroadenoma with hemorrhage in MEN 1 syndrome - A case report. IAIM, 2021; 8(4): 106-117. Case Report A rare case of invasive pituitary macroadenoma with hemorrhage in MEN 1 syndrome - A case report E.A. Ashok Kumar1*, M. Ravi Teja Raidu2 1Professor, 2Assistant Professor Department of General Medicine, Malla Reddy Institute of Medical Sciences, Hyderabad, India *Corresponding author email: [email protected] International Archives of Integrated Medicine, Vol. 8, Issue 4, April, 2021. Available online at http://iaimjournal.com/ ISSN: 2394-0026 (P) ISSN: 2394-0034 (O) Received on: 25-03-2021 Accepted on: 05-04-2021 Source of support: Nil Conflict of interest: None declared. How to cite this article: E.A. Ashok Kumar, M. Ravi Teja Raidu. A rare case of invasive pituitary macroadenoma with hemorrhage in MEN 1 syndrome - A case report. IAIM, 2021; 8(4): 106-117. Abstract Multiple Endocrine Neoplasia (MEN) disorders are very rare. These are hereditary diseases which develop into a number of endocrine glands and result in tumor formation. The MENs are run in families because they are the exact consequence of genetic mutations and their symptoms are completely dissimilar dependent on the involving glands. Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands in a single patient. Four major forms of MEN, which are autosomal dominant disorders, are recognized and referred to as: MEN type 1 (MEN1), due to menin mutations; MEN2 (previously MEN2A) due to mutations of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) protoncogene; MEN3 (previously MEN2B) due to RET mutations; and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations. Each MEN type is associated with the occurrence of specific tumors. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors. In this case report we present a patient who developed an Invasive Pituitary Macroadenoma with Hemorrhage in MEN 1 Syndrome. Key words MEN 1 Syndrome, Pituatory macroadenoma, Hemorrhage. Introduction single patient [1-4]. Four major forms of MEN, Multiple Endocrine Neoplasia (MEN) is which are autosomal dominant disorders, are characterized by the presence of tumors recognized and referred to as: involving two or more endocrine glands in a Page 106 E.A. Ashok Kumar, M. Ravi Teja Raidu. A rare case of invasive pituitary macroadenoma with hemorrhage in MEN 1 syndrome - A case report. IAIM, 2021; 8(4): 106-117. MEN type 1 (MEN1) due to menin mutations; penetrance such that clinical and biochemical MEN1 is characterized by the occurrence of manifestations of the disorder will have parathyroid, pancreatic islet and anterior pituitary developed in 80% and greater than 98% of tumors. MEN1 patients, respectively, by the fifth decade MEN2 (previously MEN2A) due to mutations [3, 6, 7]. of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) Genetics protoncogene; MEN2 is characterized by the MEN1 is an autosomal dominant disorder that is occurrence of medullary thyroid carcinoma due to mutations in the tumor suppressor gene (MTC) in association with pheochromocytoma MEN1, which encodes a 610-amino acid protein, and parathyroid tumors. menin. In this way, the finding of MEN1 in a MEN3 (previously MEN2B) due to RET patient has important implications for family mutations; MEN3 is characterized by the members because first-degree relatives have a occurrence of MTC and pheochromocytoma in 50% risk of developing the disease and can often association with a marfanoid habitus, mucosal be identified by MEN1 mutational analysis. neuromas, medullated corneal fibers and MEN1 is characterized by the occurrence of intestinal autonomic ganglion dysfunction, parathyroid, pancreatic islet and anterior pituitary leading to megacolon. tumors. Some patients may also develop MEN4 due to cyclin-dependent kinase inhibitor carcinoid tumors, adrenocortical tumors, (CDNK1B) mutations. Each MEN type is meningiomas, facial angiofibromas, associated with the occurrence of specific collagenomas and lipomas. Patients with MEN1 tumors. MEN4, which is also referred to as have a decreased life expectancy, and the MENX, is characterized by the occurrence of outcomes of current treatments, which are parathyroid and anterior pituitary tumors in generally similar to those for the respective possible association with tumors of the adrenals, tumors occurring in non-MEN1 patients, are not kidneys, and reproductive organs [2]. as successful because of multiple tumors, which may be larger, more aggressive, and resistant to The sellar region is a site of various types of treatment, and the concurrence of metastases. tumors, pituitary adenoma are the most common, The prognosis for MEN1 patients might be arise from epithelial pituitary cells and account improved by presymptomatic tumor detection for 10-15% of intra cranial tumors, tumor >10 and undertaking treatment specific for MEN1 mm are macro adenoma and those < 10 mm are tumors. Thus, it is recommended that MEN1 micro adenomas, most pituitary adenomas are patients and their families should be cared for by micro adenomas. Most of the pituitary adenomas multidisciplinary teams comprising relevant are diagnosed accidentally, as they don’t have specialists with experience in the diagnosis and any physical symptoms and signs [5]. treatment of patients with endocrine tumors [8]. Criteria for diagnosis MEN type 1 Epidemiology There is a lack of evidence from the clinical trials The incidence of MEN1 as estimated from to evaluate methods of diagnosis and screening random postmortem studies is 0.25%, and is 1– for the tumors or treatment of MEN1 [8]. A 18% in patients with primary diagnosis of MEN1 may be established in an hyperparathyroidism, 16-38% in patients with individual by one of the three criteria (Figure - gastrinomas, and less than 3% in patients with 1) [6]: on the basis of the occurrence of two or pituitary tumors [3, 6, 7]. The disorder affects all more primary MEN1- associated endocrine age groups, with a reported age range of 5 to 81 tumors (i.e. parathyroid adenoma, yr [3, 6, 7]. MEN1 is inherited as an autosomal enteropancreatic tumor, and pituitary adenoma) dominant disorder with a high degree of (Figure - 1) ) [6, 9, 10]. The occurrence of one Page 107 E.A. Ashok Kumar, M. Ravi Teja Raidu. A rare case of invasive pituitary macroadenoma with hemorrhage in MEN 1 syndrome - A case report. IAIM, 2021; 8(4): 106-117. of the MEN1-associated tumors in a first-degree asymptomatic and has not yet developed serum relative of a patient with a clinical diagnosis of biochemical or radiological abnormalities MEN; and identification of a germline MEN1 indicative of tumor development (Figure - 1). mutation in an individual, who may be Figure – 1: Basis for MEN1 diagnosis [6]. CLASSIFICATION grade 2 = tumor extends to space between the Hardy’s classification [20, 21] intercarotid line and the lateral tangent Upper panel shows the classification of sphenoid grade 3 = tumor extends lateral to the lateral bone invasion tangent Grade 0: intact with normal contour; o 3A = above the intracavernous ICA into Grade I: intact with bulging floor; the superior cavernous sinus compartment Grade II: intact, with enlarged fossa; o 3B = below the intracavernous ICA into Grade III: localized sellar destruction; the inferior cavernous sinus compartment Grade IV: diffuse destruction. grade 4 = complete encasement of Only grade III and IV tumors are considered intracavernous ICA invasive. Lower panel depicts a classification of the Figure – 2: Knosp classification staging [22]. suprasellar extension of an adenoma which may be symmetrical or asymmetrical Grade A: suprasellar cistern only; Grade B: recess of the third ventricle; Grade C: whole anterior third ventricle; Grade D: intracranial extradural; Grade E: extracranial extradural (cavernous sinus) [20, 21]. Knosp classification staging (Figure – 2) [22] These lines are used to define 4 grades of tumor invasion: grade 0 = medial to medial tangent Treatment grade 1 = tumor extends to space between the The treatment for each type of MEN1-associated medial tangent and the intercarotid line endocrine tumor is similar to the respective tumors occurring in non-MEN1 patients. Page 108 E.A. Ashok Kumar, M. Ravi Teja Raidu. A rare case of invasive pituitary macroadenoma with hemorrhage in MEN 1 syndrome - A case report. IAIM, 2021; 8(4): 106-117. However, the treatment outcomes of MEN1- pricking type and was associated with associated tumors are not as successful as those photophobia and phonophobia. She also had one in non-MEN1 patients, for several reasons. First, episode of projectile vomiting, contained food MEN1-associated tumors, with the exception of particles and was blood tinged. She had pituitary NET, are usually multiple, thereby associated symptoms like giddiness, sweating, making it difficult to achieve a successful generalized weakness and body pains, tingling surgical cure. For example, MEN1 patients often sensation over both the upper and lower limbs develop multiple submucosal duodenal were present. No history of fever, loss of gastrinomas, thereby reducing surgical cure rates consciousness, involuntary movements, loss of compared with similar sporadic solitary tumors, appetite, pain abdomen, loose stools .Patient such that only approximately 15% of MEN1 developed blurring of vision and pain on eye patients, compared with 45% of non-MEN1 movements the next day. Patient is a K/C/O patients, are free of disease immediately after Diabetes Mellitus since 2 years and on surgery, and at 5 yr this decreased to glyciphage. approximately 5% in MEN1 patients, compared with 40% in non-MEN1 patients [6, 11-14]. Past history: Patient had a history of head injury MEN1 patients also develop multiple parathyroid 9 years ago, after which she had headache on and tumors, and subtotal parathyroidectomy has off. Underwent surgery for Renal Calculi 9 years resulted in persistent or recurrent hypercalcemia ago. No history of HTN, thyroid disorders or within 10 yr in 20 – 60% of MEN1 patients, as epilepsy.
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