Multiple Endocrine Neoplasia
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A 42-year-old male presented with prominence of both the eyeballs for the last 6 months. He was detected to have hypertension 7 years earlier and for that he was receiving telmisartan, atenolol, and amlodipine. He had history of recurrent pain abdomen and dyspeptic symptoms for the last 5 years, and he frequently used to take proton pump inhibitors to relieve these symptoms. He had no history of headache, vomiting, or visual disturbances. There was no history of anorexia, constipation, bone pains, polyuria, graveluria, or renal stone disease. However, he had history of tightening of rings, palmar sweating, decreased libido and erectile dysfunction, and reduced frequency of shaving. There was history of fatigue and progressive increase in weakness for the last 2–3 years, and he was diagnosed to have iron deficiency anemia. There was no history of symptoms suggestive of thyrotoxicosis, chronic obstructive airway disease, or chronic kidney or liver disease. He was a nonsmoker and nonalcoholic. On examination his height was 169 cm, weight 90 Kg, BMI 31.3 Kg/m2, blood pressure 130/80 mmHg, and pulse rate 96 bpm and had multiple skin tags and grade 3 acanthosis nigricans. He did not have other cutaneous markers like collagenoma, angiofibroma, and lipoma. There was bilateral mild proptosis and he had palmar sweating and seborrhea. He did not have goiter and deep tendon reflexes were normal. His sexual maturation score was A+, P3, testicular volume 20 ml (bilateral), and sparse facial and body hair. He also had bilateral lipomastia. Visual fields, visual acuity, and optic disk were normal. Other systemic examination was unremarkable. On investigations, hemoglobin was 9.8 g/dl with normal leucocytes and platelet counts, and liver and renal function tests were normal. Corrected serum calcium was 11.4 mg/dl, phosphorus 2.4 mg/dl, alkaline phosphatase 104 IU/L, iPTH 1,098 pg/ml (N 15–65), and 25(OH)D 6 ng/ml (N 30–70). 0800-h serum cortisol was 262 nmol/L (N 171–536), prolactin 9,291 ng/ml (N 4–15.2), free T4 0.5 ng /dl (N 0.8–1.8), TSH 2.92 μIU/ml (N 0.27–4.2), LH 0.21 mIU/ml (N 1.7–8.6), FSH 0.26 mIU/ml (N 1.5–12.4), and testosterone 0.206 nmol/L (N 9.9–27). Serum IGF1 was 363 ng/ml (N 101–267, age matched), basal serum GH 15 ng/ml, and nadir serum GH after glucose load 5.6 ng/ml. Serum gastrin level was 284 pg/ml (N 13–115), basal acid output 40 mEq/L (N <15), fasting plasma insulin 10.2 μIU/ml, C-peptide 3.19 ng/ml with corresponding plasma glucose 98 mg/dl, and HbA1c 5.2 % (N <5.7 %). One microgram ACTH stimulation test showed a peak cortisol response 455 nmol/L (N >550 nmol/l). Twenty-four-hour urinary metanephrine was 93 μg (N <350) and normetanephrine 161 μg (N <600). CEMRI sella showed a 5 × 4.6 × 3.2 cm sellar–suprasellar mass with right parasellar extension. The CECT abdomen showed small enhancing focal lesion in the head of the pancreas, circumferential wall thickening in D1 and D2 segment of the duodenum, and bilateral adrenal gland enlargement. Endoscopic ultrasonography showed two lesions in the pancreas (8 × 8 mm in the body and 6 × 4 mm in the tail of the pancreas). DOTANOC–PET CT showed somatostatin receptor expressing lesions in the sella turcica, thyroid gland, and posterior to the thyroid gland (parathyroid gland); however, focal non-avid hypodense lesions were identified in the pancreas and in the adrenal gland. Upper gastrointestinal endoscopy showed multiple superficial ulcers in D1 and D2 segment of the duodenum. Ultrasonography of the neck showed 1 × 0.9 cm size heterogeneous lesion with central vascularity in antero-inferior aspect of left lobe of the thyroid gland. Sestamibi parathyroid scan showed uptake in the right superior and the left superior and inferior parathyroid glands. SPECT–CT fusion image showed increased tracer uptake in the left superior parathyroid gland. The patient was initiated with L-thyroxine and cabergoline. Patient underwent transsphenoidal surgery (TSS) and resection of the pituitary tumor was carried out. Postoperatively, patient was continued with L-thyroxine supplementation and hydrocortisone was added. Cabergoline was also continued as there was large residual tumor postoperatively. After 3 months of pituitary surgery, he underwent bilateral neck exploration, and three enlarged parathyroid glands were identified (left superior and inferior parathyroid, and right inferior parathyroid gland) and were excised. Simultaneously, open laparotomy was also performed; intraoperative ultrasonography confirmed the lesions in the head and body of the pancreas, and these were excised accordingly. Postoperatively 3 months after TSS, serum prolactin was 23 ng/ml (on cabergoline) and GH was non-suppressible (nadir GH 1.3 ng/ml) after glucose load, however, IGF 1 was normalized (226 ng/ml; N 101–267, age matched). Repeat CEMRI sella revealed 1.5 × 2.8 × 2.8-cm sellar–suprasellar mass with parasellar extension. After parathyroid surgery with one gland in situ, serum calcium and phosphorus was normalized (9.3 mg/dl and 3.3 mg/dl, respectively), serum iPTH was 46.6 pg/ml, and serum gastrin was undetectable (<10 pg/ml). Histopathology of the sellar mass confirmed pituitary adenoma and showed diffuse positivity for GH and prolactin on immunohistochemistry (IHC). Parathyroid gland histology showed parathyroid adenoma in all three resected glands. Pancreatic tumor histology was consistent with neuroendocrine tumor. Genetic analysis for MEN1 gene demonstrated duplication of C1546 gene in exon 10 and frame-shift mutation at P-Arg 516 consistent with MEN1 syndrome. The pedigree of the index patient is shown in the figure given below. The patient was continued with cabergoline and received external beam radiotherapy (EBRT) for residual pituitary lesion. However, serum GH still remained non-suppressible after glucose load with elevated IGF1; therefore, he was initiated with octreotide LAR (20 mg once a month). He did not have features of hungry bone syndrome postoperatively. He was continued with proton pump inhibitor along with calcium carbonate and calcitriol (Fig. 11.1).
KeywordsParathyroid Gland Medullary Thyroid Carcinoma Parathyroid Adenoma Bilateral Neck Exploration Multiglandular Disease
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