[en] Familial acromegaly is an exceptional clinical entity when not associated with features of multiple endocrine neoplasia type 1 (MEN1). We report here 3 pedigrees in each of which 2 patients have been shown to develop acromegaly. In 4 patients, clinical follow-up, and biological screening allowed to confidently exclude MEN1. Absence of mutation in the MEN1 gene after direct DNA analysis in 2 pedigrees reinforces the conviction that the families do not have MEN1. In families 1 and 2, diagnosis was made at a very early age and voluminous adenomas with suprasellar expansion were already present at the time of diagnosis. We review the 20 previous reports of familial acromegaly, some of them questionable. Our 3 families, combined with some other published pedigrees, allow the delineation of a familial form of acromegaly, distinct from MEN1. Dominant inheritance with reduced, age-dependant penetrance is the most parsimonious model to explain the recurrences. Gs protein pathway could be the site of action of the gene responsible of familial acromegaly, but no data have been published to sustain or reject this hypothesis.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Verloes, Alain ; Université de Liège - ULiège > Génétique
Stevenaert, Achille ; Université de Liège - ULiège > Neurochirurgie
Teh, B. T.
Petrossians, Patrick ; Université de Liège - ULiège > Endocrinologie clinique
Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Language :
English
Title :
Familial Acromegaly: Case Report and Review of the Literature
Koch, G., Tiwisina, T., Contribution to the hereditary of acromegaly and hyperostosis generalisata with pachyderma (chromophobe hypophysis adenoma in father and son) (1959) Arznemittel Furschung, 13, pp. 489-504
Stevenaert, A., Beckers, A., Presurgical octreotide: Treatment in acromegaly (1996) Metab Clin Exp, 45 (1 SUPPL.), pp. 72-74
Teh, B.T., Kytölä, S., Farnebo, L., Bergman, F.K., Wong, K., Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type I, familial acromegaly and familial isolated hyperparathyroidism (1998) J Clin Endocrinol Metab, 83, pp. 2621-2628
Poncin, J., Abs, B., Velkeniers, M., Bonduelle, M., Abramovicz, M., Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases (1998) Human Mutation, , in press
Alexander, L., Appleton, D., Hall, R., Ross, W.M., Wilkinson, R., Epidemiology of acromegaly in the Newcastle region (1980) Clin Endocrinol (Oxf), 12, pp. 71-79
Bengtsson, B.A., Eden, S., Ernest, I., Oden, A., Sjoegren, B., Epidemiology and long-term survival in acromegaly (1988) Acta Medica Scand, 223, pp. 327-335
McCarthy, M.I., Noonan, K., Wass, J.A.H., Munson, J.P., Familial acromegaly: Studies in 3 families (1990) Clin Endocrinol (Oxf), 32, pp. 719-728
Beckers, A., Courtoy, R., Stevenaert, A., Bonniver, J., Closset, J., Mammosomatotropes in human pituitary adenomas as revealed by electron microscopic double gold immunostaining method (1988) Acta Endocrinol (Copenh), 118, pp. 503-512
Herman, V., Fagin, J., Govsky, R., Kovacs, K., Melmed, S., Clonal origin of pituitary adenomas (1990) J Clin Endocrinol Metab, 71, pp. 1427-1433
Vallar, L., Spada, A., Giancannattasio, G., Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas (1987) Nature, 330, pp. 566-568
Hosoi, E., Yokogoshi, Y., Horie, H., Yamada, S., Saito, S., Analysis of the GS alpha gene in growth hormone-secreting pituitary adenomas by the polymerase chain reaction-direct sequencing method using paraffin-embedded tissues (1993) Acta Endocrinol (Copenh), 129, pp. 301-306
Landis, C.A., Masters, S.B., Spada, A., Pace, A.M., Bourne, H.R., GTPase inhibiting mutations activate the alpha chain of of Gs and stimulate adenylate cyclase in human pituitary tumors (1989) Nature, 340, pp. 692-696
Faglia, G., Arosio, M., Spada, A., GS protein mutations and pituitary tumors: Functional correlates and possible therapeutic implications (1996) Metabolism, 45 (1 SUPPL.), pp. 117-119
Lania, A., Persani, L., Ballare, E., Mantovani, S., Losa, M., Constitutively active Gs alpha is associated with an increased phosphodiesterase activity in human growth hormone-secreting adenomas (1998) J Clin Endocrinol Metab, 85, pp. 1624-1628
Weinstein, L.S., Shenker, A., Gejman, P.V., Merino, M.J., Friedman, E., Activating mutations of the stimulatory G protein in the McCune-Albright syndrome (1991) New Engl J Med, 325, pp. 1738-1740
Croizier, J.C., Azerad, E., Lubetski, J., L'adénomatose polyendocrinienne (syndrome de Wermer): A propos d'une observation personnelle. Revue de la littérature (1971) Sem Hôp Paris, 47, pp. 494-525
Eberle, F., Grün, R., Multiple endocrine neoplasia, type 1 (1981) Ergebn Inn Med Kinderheilk (Berlin), 46, pp. 75-142
Benson, L., Ljunghall, S., Akerström, G., Öberg, K., Hyperparathyroidism presenting as the first lesion in multiple endocrine neoplasia type 1 (1987) Am J Med, 82, pp. 731-737
Samaan, N.A., Ouais, S., Ordonez, N.G., Choksi, U.A., Sellin, R.V., Multiple endocrine syndrome type 1. Clinical, laboratory findings and management in five families (1989) Cancer, 84, pp. 741-752
Tateishi, A., Wada, A., Ishiguro, S., Ehara, M., Sakamoto, H., Coexistence of bilateral pheochromocytoma and pancreatic islet cell tumor: Report of a case and review of the literature (1978) Cancer, 42, pp. 2928-2934
Lemmens, I., Van De Ven, W.J., Kas, K., Zhang, C.X., Giraud, S., Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1 (1997) Hum Mol Genet, 6, pp. 1177-1183
Agarwal, S.K., Kester, M.B., Debelenko, L.V., Heppner, C., Emmert-Buck, M.R., Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states (1997) Hum Mol Genet, 6, pp. 1169-1175
Bassett, J.H., Forbes, S.A., Pannett, A.A., Lloyd, S.E., Christie, P.T., Characterization of mutations in patients with multiple endocrine neoplasia type 1 (1998) Am J Hum Genet, 62, pp. 232-244
Giraud, S., Zhang, C.X., Serova-Sinilnikova, O., Wautot, V., Salandre, J., Germ-Line Mutation Analysis in Patients with Multiple Endocrine Neoplasia Type 1 and Related Disorders (1998) Am J Hum Genet, 63, pp. 455-467
Hosoi, E., Yokogoshi, Y., Yokoi, K., Sano, T., Saito, S., A pituitary-specific point mutation of codon 201 of the GSalpha genein a pituitary adenoma of a patient with multiple endocrine neoplasia (MEN) type 1 (1992) Endocrinol Jpn, 39, pp. 319-324
O'Halloran, D.J., Shalet, S.M., A family pedigree exhibiting features of both multiple endocrine neoplasia type 1 and McCune-Albright syndromes (1994) J Clin Endocrinol Metab, 78, pp. 523-525
Carney, J.A., Gordon, H., Carpenter, P.C.S.B.V., Go, V.L.W., The complex of myxomas, spotty pigmentation and endocrine overactivity (1985) Medicine, 64, pp. 270-283
Levin, S.R., Hofeldt, P.D., Becker, N., Wilson, C.B., Seymour, R., Hypersomatotropism and acanthosis nigricans in 2 brothers (1974) Arch Intern Med, 1974, pp. 355-357
Himuro, H., Kobayashi, E.K.H., Jimbo, M., Kitazawa, M., Pituitary adenomas in two members of a family (1976) Neurol Surg, 4, pp. 371-377
Kurisaka, M., Takei, Y., Tsubokawa, T., Moriyasu, N., Growth hormone-secreting pituitary adenoma in uniovular twin brothers. Case report (1981) Neurosurgery, 8, pp. 226-230
Abbassioun, K., Fatourehchi, V., Amirjamshidi, A., Meibodi, N.A., Familial acromegaly with pituitary adenoma: Report of 3 affected siblings (1986) J Neurosurg, 64, pp. 510-512
Yuasa, H., Tokito, S., Nakagaki, H., Kitazawa, M., Familial pituitary adenoma, report of four cases from two unrelated families (1990) Neurol Med Chir (Tokyo), 30, pp. 1016-1019
Tamburrano, G., Jaffrain-Rea, M.L., Grossi, A., Lise, A., Bulletta, C., L'acromégalie familiale: A propos d'une observation. Revue de la litterature (1992) Ann Endocrinol (Paris), 53, pp. 201-207
Links, T.P., Monkelban, J.F., Dullaart, R.P.F., Van Haeften, T.W., Growth hormone-, alpha-subunit and thyrotrophin-cosecreting pituitary adenoma in familial setting of pituitary tumor (1993) Acta Endocrinol (Copenh), 129, pp. 516-518
Matsuno, A., Teramoto, A., Yamada, S., Kitanaka, T., Gigantism in siblings unrelated to multiple endocrine neoplasia: Case report (1994) Neurosurgery, 35, pp. 952-955
Benlian, P., Giraud, S., Lahlou, N., Roger, M., Blin, C., Familial acromegaly: A specific clinical entity - Further evidence from the genetic study of a three-generation family (1995) Eur J Endocrinol, 133, pp. 451-456
Stock, J.L., Warth, M.R., Teh, B.T., Coderre, J.A., Overdorf, J.H., A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus at chromosome region 11q13 (1997) J Clin Endocrinol Metab, 82, pp. 486-492
Chedid, A., Hoversi, Chefiec, McCune, S.A., Jurin, R.R., Hereditary pituitary proclamation: A new rat mode (1988) Acta Endocrinol (Copenh), 119, pp. 535-542
