HYPERNEPHROMA ASSOCIATED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE I: A CASE REPORT
PAUL S. DENKER, DAVID WRIGHT, JUDY R. HILSCHER, SABIHA R. SABA AND GERMAN RAMIREZ*
From the Nephrology Section, Department of Internal Medicine and Department of Pathology, Tampa Veterans Administration Medical Center and University of South Florida College of Medicine, Tampa, Florida
ABSTRACT
We report a case of multiple endocrine neoplasia type I and hypernephroma. Parathyroid hyperplasia, adrenocortical hyperplasia, a nodular goiter, multiple lipomas, a chromophobe adenoma of the pituitary and hypernephroma had all been diagnosed previously. All but the last are features consistent with the diagnosis of multiple endocrine neoplasia type I (Wermer’s syndrome). The association of multiple endocrine neoplasia type I and hypernephroma may represent a new manifestation of this pleiotropic syndrome.
Multiple endocrine neoplasia type I (Wermer’s syndrome) is a pleomorphic, polyglandular disease that classically affects the pituitary, parathyroids and pancreas. It is transmitted in an autosomal dominant fashion with a high degree of penetrance. Patients of all ages may be affected but presentation in the young and elderly populations is less common. Adenomas, hyperplasia or frank carcinoma may characterize organ involve- ment in this disease. The appearance of symptoms or tumors may be synchronous or separated by time.
Organs outside the classical triad may be affected in multiple endocrine neoplasia type I. Ballard and associates reported involvement of the adrenal cortex and thyroid in 38 and 19 per cent of the patients, respectively.1 Thyroid involvement in- cludes carcinoma, adenoma, goiter and thyroiditis. Adrenal involvement includes adenoma and hyperplasia. Bronchial car- cinoids,1,2 gastric leiomyoma,2 lipomas1-4 and liposarcoma4 have all been described. Systemic and pancreatic amyloid involve- ment also has been reported.3,5
Symptoms may be owing either to direct organ involvement or to elaboration of various hormones. Gastrin, insulin, proin- sulin, adenocorticotropic hormone, glucagon, vasoactive intes- tinal peptide, pancreatic polypeptide, antidiuretic hormone and calcitonin have all been associated with pancreatic tumors.2,6 Pituitary adenomas may secrete prolactin, causing amenorrhea or galactorrhea. Parathyroid hyperplasia, which typically in- volves multiple glands,7 is present in approximately 80 per cent of the patients with multiple endocrine neoplasia type I.1,6 Associated symptoms may include kidney stones, nephrocalci- nosis and bone disease. Carcinoid tumors may produce sero- tonin, which can result in flushing, wheezing and diarrhea. Rarely, multiple endocrine neoplasia type I may present with Cushing’s disease, acromegaly or hyperthyroidism.8 We de- scribe a man with a history of a nodular goiter, parathyroid hyperplasia, multiple cutaneous lipomas, adrenocortical hyper- plasia, a chromophobe adenoma of the pituitary and hyperne- phroma.
CASE REPORT
A 68-year-old white man presented for followup and evalua- tion of a right renal mass on January 2, 1985. In January 1982 the patient had a ureteral stone, serum calcium was 11.0 mg./ dl. and N-terminal parathormone was 861 pg./ml. (normal 230 to 630 pg./ml.). Subsequently, excision of 31/2 parathyroid glands revealed diffuse hyperplasia (fig. 1, A). The ureteral
stone consisted of 93 per cent calcium oxalate and 3 per cent uric acid. A thyroid scan had revealed previously a cystic lesion that also was removed at parathyroidectomy. Histological ex- amination revealed a nodular goiter (fig. 1, B).
In June the patient was rehospitalized for evaluation of left lower quadrant abdominal pain. Urinalysis showed 5 to 10 red blood cells per high power field. Excretory urography demon- strated a lobulated left upper pole mass with blunting of the left caliceal system. Computerized tomography (CT) showed a large mass of the superoanterior aspect of the left kidney, which enhanced with contrast material (fig. 1, C). A 2 to 3 cm. mass within the parenchyma of the right kidney also was noted. Renal arteriography revealed the left mass to be hypervascular. The right renal mass was without neovascularization. Subse- quently, left radical nephrectomy was performed. Pathological examination demonstrated a hypernephroma (fig. 1, D) and adrenocortical hyperplasia (fig. 1, E).
The patient did well until 1984 when he suffered from a persistent headache and a visual field defect. A skull series with coned-down views revealed enlargement of the sella turcica with bony erosion. Cerebral angiography failed to yield any evidence of neovascularization. A CT scan of the brain corrob- orated a large pituitary mass (fig. 1, F). Further evaluation included a growth hormone of 0.4 ng./ml. (normal 0 to 5), prolactin 20.0 ng./ml. (normal 0 to 25.0), follicle-stimulating hormone 4 MIU/ml. (normal 4 to 20), luteinizing hormone 3 MIU/ml. (normal 2 to 12), free testosterone 0.7 ng./dl. (normal 5 to 30) and 8 a.m. cortisol 21.9 µg./dl. (normal 7 to 25). A sublabial, transseptal, transsphenoidal hypophysectomy was performed. The pathological specimen revealed a chromophobe adenoma. In October the patient was evaluated because of 2 nonfixed, nontender soft tissue masses of the anterior right thigh. Removal revealed mature adipose tissue, consistent with the diagnosis of lipomas.
At the present hospitalization the patient appeared to be in good health. Blood pressure was 190/110 mm. Hg, pulse 78 per minute and regular, temperature 37C, and respirations 18 per minute and unlabored. Medications included 30 mg. hydrocor- tisone orally, 0.15 mg. thyroxine orally and 25 mg. transdermal nitroglycerin every morning, 10 mg. hydrocortisone orally every night, 500 mg. calcium carbonate orally twice a day and 200 mg. testosterone ethanate intramuscularly every 3 weeks. Fam- ily history was pertinent only for a brother who died when he was 37 years old of a cerebellar hemangioma.
Physical examination revealed only an S4 gallop and a right central seventh nerve paralysis. Laboratory evaluation included a white blood count of 11,200/mm.3 with a normal differential, hemoglobin 17.5 gm./dl. and normal coagulation studies. Cre- atinine was 1.8 mg./dl. CT of the abdomen demonstrated a
Accepted for publication May 2, 1986.
* Requests for reprints: Nephrology Section, James A. Haley Veter- ans’ Hospital, 13000 North 30th St., Tampa, Florida 33612.
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right renal mass that was unchanged from the previous exam- ination (fig. 2, A). A renal arteriogram showed a homogeneous blush without neovascularity (fig. 2, B).
N-terminal parathormone was 830 pg./ml., fasting insulin radioimmunoassay 23 microunits per ml., prolactin 26.1 ng./ ml. (normal 5 to 18) and thyroid profile, including a free triiodothyronine, normal. Ionized calcium was 4.9 mg./dl. (nor- mal 4.7 to 5.2). Fasting glucose and glucose tolerance tests were normal. Gastrin radioimmunoassay was 36 pg./ml. (normal 0 to 200). Fasting cortisol was less than 1.0 µg./dl. but the patient was on replacement therapy. The patient did well and was discharged from the hospital to be followed as an outpatient.
DISCUSSION
The frequency of organ involvement in multiple endocrine neoplasia has been studied by various authors.1,2,4,6,7,9 The parathyroids are affected most commonly, followed by the pancreas and pituitary. Involvement of other organs is less common but these may include the thyroid, cutaneous struc-
tures and adrenal cortex. Ballard and associates reported an interstitial cell tumor of the testis in association with this syndrome.1 Larraza-Hernandez and associates reported a leiomyoma of the stomach.3 A bronchial carcinoid was described by Vieto and associates.2 Johnson and associates reported as- sociated cases of a liposarcoma of the hip and metastatic carcinoma of the bladder.4
Our patient had a hypernephroma and features consistent with the diagnosis of multiple endocrine neoplasia type I. Since the primary defect of the multiple endocrine neoplasia type I syndrome is not completely understood, it is difficult to say whether this association represents a random occurrence or an unusual manifestation of the disease. However, in a pleiotropic disorder such as Wermer’s syndrome physicians should be aware of this possible new manifestation.
Dr. Diana Pollock provided critical comments.
REFERENCES
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RIGHTS LINK KOESPIELE CHEESEEEN CHELES
2. Vieto, R. J., Hickey, R. C. and Samaan, N. A .: Type I multiple endocrine neoplasias. Curr. Probl. Cancer, 7: 1, 1982.
3. Larraza-Hernandez, O., Albores-Saavedra, J., Benavides, G., Krause, L. G., Perez-Merizaldi, J. C. and Ginzo, A .: Multiple endocrine neoplasia. Pituitary adenoma, multicentric papillary thyroid carcinoma, bilateral carotid body paraganglioma, para- thyroid hyperplasia, gastric leiomyoma, and systemic amyloi- dosis. Amer. J. Clin. Path., 78: 527, 1982.
4. Johnson, G. J., Summerskill, O. M., Anderson, V. E. and Keating, F. R., Jr .: Clinical and genetic investigation of a large kindred with multiple endocrine adenomatosis. New Engl. J. Med., 277: 1379, 1967.
5. Cryer, P. E. and Kissane, J .: Fasting hypoglycemia, hypercalcemia and hyperprolactinemia. Multiple endocrine neoplasia, type I?
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