Multiple Endocrine Neoplasia-1 (MEN-1) Presenting as Primary Hyperaldosteronism: A Rare Association : The Endocrinologist

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00019616-200803000-00006ReportThe EndocrinologistThe Endocrinologist© 2008 Lippincott Williams & Wilkins, Inc.18March 2008 p 68-70Multiple Endocrine Neoplasia-1 (MEN-1) Presenting as Primary HyperaldosteronismA Rare AssociationCase ReportBhansali, Anil DM*; Chanukya, G V. DM*; Bhadada, Sanjay Kumar DM*; Behera, Arunanshu MS†; Radotra, Bishan Das MD, PhD‡From the Departments of *Endocrinology, †Surgery, and ‡Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.Reprints: Anil Bhansali, DM, Postgraduate Institute of Medical; Education and Research, Chandigarh 160012, India. E-mail: [email protected] endocrine neoplasia-1 (MEN-1) is characterized by multiple endocrine tumors including parathyroid, islets of Langerhans, pituitary, and adrenal tumors. Most of these patients present with primary hyperparathyroidism. The adrenal tumors in MEN-1 are rare and usually bilateral and nonfunctional. To the best of our knowledge, this is the first report of primary hyperaldosteronism due to an adenoma as the presenting manifestation of MEN-1.Multiple endocrine neoplasia-1 (MEN-1) is characterized by tumors of the parathyroid glands, islets of the pancreas, pituitary, and adrenal glands.1 Primary hyperparathyroidism is the most common manifestation (95%). It is usually associated with multiglandular involvement and rarely with a single gland adenoma/hyperplasia.1 Gastrinomas and prolactinomas are also common.1,2 Bilateral adrenal gland enlargement due to adrenocortical hyperplasia is observed in 5% to 40% of patients with MEN-1. In a majority of cases it is nonfunctional.2,3 Rarely, adrenomegaly is unilateral and associated with tumorous proliferation of zona glomerulosa presenting with severe hypertension with hypokalemia and metabolic alkalosis.4,5We describe a patient with MEN-1 who presented with episodic hypokalemic weakness with severe hypertension due to an aldosteronoma. He was subsequently found to have primary hyperparathyroidism and a microprolactinoma.CASE REPORTA 28-year-old man presented with episodic leg weakness and polyuria of 3 years duration. He was a teetotaler, born to a nonconsanguineous couple with a noncontributory family history pertaining to his illness. He was found to be hypertensive with repeated values of serum potassium varying between 2 and 3.2 mEq/L. He received atenolol 50 mg once daily with partial remission of symptoms. When referred to our clinic, he was hypertensive (160/110 mm Hg) with persistent hypokalemia (2–2.5 mEq/L). His medications were changed to prazosin and oral potassium chloride.Hemogram, renal, and liver function tests were normal. Renal arterial ultrasonography was normal. Blood samples were obtained for plasma renin activity (PRA) and serum aldosterone in supine position after 1 hour and 4 hours of standing. Supine values of serum aldosterone and PRA were 59 ng/dL (N, 4–31 ng/dL) and 0.07 ng/mL/hr (N, 0.15–2.88), respectively yielding a serum aldosterone/PRA ratio of 843 (N <25). After 4 hours of standing, the serum aldosterone and PRA were 42 ng/dL and 0.22 ng/mL/hr (normal range, 1.31–3.95) with a ratio of 190. Despite potassium supplementation, serum potassium was 2.6 mEq/L. Contrast enhanced computerized tomography of the abdomen showed 1 × 1 cm enhancing left adrenal mass (Fig. 1) and nephrolithiasis on the same side. Chest x-ray film showed healed rib fractures. The patient could not recall any pertinent history such as graveluria, flank pain, or trauma to the chest.JOURNAL/endst/04.03/00019616-200803000-00006/figure1-6/v/2021-02-17T201845Z/r/image-tiff Contrast enhanced CT abdomen showing hypodense mass in the left adrenal region (arrow). The right adrenal is normal.Albumin adjusted calcium was 9.9 mg/dL (N, 9–10.5), phosphate 3.5 mg/dL (N, 3.5–5.5), alkaline phosphatase 10 KAU (N, 3–13), and 24 hours urine calcium was 352 mg (N, 150–270). Serum parathormone (intact, immunoradiometric assay) was 130 pg/mL (N, 10–69) and serum 25(OH) Vitamin D was 21 ng/mL (N, 9–38). Ultrasonography of the neck revealed 0.7- × 0.8-cm parathyroid gland on the left side. This was confirmed by 99mTc-sestamibi scan. Quantitative computerized tomography of the lumbar vertebra showed osteopenia. Fasting serum prolactin was 95 ng/mL (N, 2.1–17.7). Serum gastrin was 133 pg/mL (N, 13–115). Contrast enhanced magnetic resonance imaging of the sella showed a 5-mm pituitary microadenoma (Fig. 2). A clinical diagnosis of MEN-1 was considered in view of the primary hyperparathyroidism, aldosteronoma, and pituitary microadenoma. The patient underwent simultaneous left parathyroid adenectomy and left adrenalectomy. Other parathyroid glands were normal. Histopathology of the parathyroid tissue showed chief cell hyperplasia (Fig. 3). Adrenal tumor weighed 10 g, measuring 3 × 4 × 1.5 cm, and was consistent with aldosteronoma. He received cabergoline (1 mg/wk) for prolactinoma. Three months later, serum albumin adjusted calcium was 8.7 mg/dL, phosphate 4.5 mg/dL, alkaline phosphatase 9 KAU, and 24-hour urine calcium was 196 mg (a decrease by 45%). Serum iPTH decreased to 20 pg/mL and prolactin was 43.5 ng/mL. He became normotensive without any antihypertensive medications.JOURNAL/endst/04.03/00019616-200803000-00006/figure2-6/v/2021-02-17T201845Z/r/image-tiff Magnetic resonance imaging of pituitary (T1W) showing hypointense lesion in the right half of the gland suggestive of microadenoma.JOURNAL/endst/04.03/00019616-200803000-00006/figure3-6/v/2021-02-17T201845Z/r/image-tiff Photomicrograph of parathyroid gland showing chief cell hyperplasia (H&E ×20).DISCUSSIONWe describe a case of MEN-1 who presented with episodic generalized muscular weakness due to hypokalemia. This is an unusual presenting manifestation, as majority of patients with MEN-1 present with primary hyperparathyroidism.1 This is the first description of an aldosteronoma as a presenting manifestation of the disease. Only 3 cases of aldosteronoma with MEN-1 are documented in the literature. Primary hyperparathyroidism was the presenting manifestation in all of them.6The diagnosis of MEN-1 is substantiated when 2 of the 3 MEN-1 related tumors viz. the parathyroids, pancreatic islets, anterior pituitary, and adrenals are present either at presentation or consecutively. Our patient had aldosteronoma, primary hyperparathyroidism, and prolactinoma, therefore qualifying for the diagnosis of MEN-1.Primary hyperaldosteronism accounts for 1% cases of hypertension in the general population.3,6 Aldosterone producing adenomas account for 60% to 73% of cases of primary hyperaldosteronism in adults. In children and adolescents, idiopathic adrenal hyperplasia is more common.6 Hypertension with hypokalemia is typical presentation of hyperaldosteronism. Sometimes, episodic weakness can be the sole manifestation.Our patient had primary hyperparathyroidism, which was evident by renal stone disease, multiple rib fractures, upper normal serum calcium, elevated serum PTH, and histopathologically verified chief cell hyperplasia. Normal serum calcium levels in our patient could be due to hypercalciuria and a relatively low normal serum 25(OH) vitamin D. The elevated urinary calcium excretion was inappropriately high in relation to serum calcium suggesting the additive effect of hyperaldosteronism. This results from the escape effect of aldosterone on sodium reabsorption, thereby enhancing the excretion of calcium through sodium-calcium cotransporters.7 After the removal of the aldosteronoma, a remarkable decrease in urinary calcium was observed.Prolactinoma is the most common pituitary tumor in patients with MEN-1.1,8 In general, the majority of men with prolactinomas have macroadenomas, whereas microadenomas are uncommon as observed in our case. He was treated with cabergoline. Serum prolactin fell into the normal range.In conclusion, we describe a rare presenting manifestation of MEN-1, hypertension, with hypokalemia due to aldosteronoma.REFERENCES1. Thump D, Farren B, Wooding C, et al. Clinical studies of multiple endocrine neoplasia type 1(MEN 1) in 220 patients. Q J Med. 1996;89:658–669.[Context Link]2. Brandi ML, Gagel RF, Angeli A, et al. Consensus statements on MEN1 and MEN2. J Clin Endocrinol Metab. 2001;86:5658–5691.[Context Link][Full Text][CrossRef][Medline Link]3. Skaggeid B, Larsen C, Lindgren PG, et al. Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 1992;75:76–81.[Context Link][CrossRef][Medline Link]4. Fertig A, Welsley M, Lynn J. Primary hyperparathyroidism in a patient with Conn's syndrome. Postgrad Med J. 1980;56:45–47.[Context Link][CrossRef][Medline Link]5. Dluhy RG, Williams GH. Primary aldosteronism in a hypertensive acromegaly patient. J Clin Endocrinol Metab. 1969;29:1319–1324.[Context Link][CrossRef][Medline Link]6. Beckers A, Abs R, Williams PJ, et al. Aldosterone-secreting adrenal adenoma as a part of multiple endocrine neoplasia type 1 (MEN 1): loss of heterozygosity for polymorphic chromosome 11 deoxy ribonucleotide and markers, including the MEN1 locus. J Clin Endocrinol Metab. 1992;75:564–570.[Context Link][CrossRef][Medline Link]7. Chhokar VS, Sun Y, Bhattacharya SK, et al. Hyperparathyroidism and calcium paradox of aldosteronism. Circulation. 2005;11:871–878.[Context Link][Full Text][CrossRef][Medline Link]8. Veldhuis JD, Norton JA, Wells JR, et al. Therapeutic controversy. Surgical versus medical management of multiple endocrine neoplasia (MEN) type 1. 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The right adrenal is normal. Magnetic resonance imaging of pituitary (T1W) showing hypointense lesion in the right half of the gland suggestive of microadenoma. Photomicrograph of parathyroid gland showing chief cell hyperplasia (H&E ×20).Multiple Endocrine Neoplasia-1 (MEN-1) Presenting as Primary Hyperaldosteronism: A Rare AssociationBhansali Anil DM; Chanukya, G V. DM; Bhadada, Sanjay Kumar DM; Behera, Arunanshu MS; Radotra, Bishan Das MD, PhDCase ReportCase Report218p 68-70