CLINICS 2012;67(S1):29-32 REVIEW Familial gigantism Wouter W. de Herder DOI:10.6061/clinics/2012(Sup01)06 Department of Internal Medicine, Sector of Endocrinology, Erasmus MC, Rotterdam, the Netherlands. Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas. KEYWORDS: Acromegaly; Gigantism; Pituitary; History; Hereditary. de Herder WW. Familial gigantism. Clinics. 2012;67(S1):29-32. E-mail: w.w.deherder@erasmusmc.nl Tel.: 31 10 7035950 HISTORICAL OVERVIEW In 1886, Dr Pierre Marie used the term ‘‘acromegaly’’ for the first time and described the full clinical characteristics of this condition (1). However, twenty-two years prior in 1864, Dr. Andrea Verga had already named the same disorder ‘‘prosopo-ectasia’’ [widening of the face] (2). At the postmortem examination of an acromegalic woman (with ‘‘prosopo-ectasia’’), he found a walnut-sized sellar tumor and displacement of the optic nerves (2). A normal pituitary gland was not found. He wondered whether the normal pituitary gland had disappeared because of pressure from the tumor or whether the tumor itself was a degeneration of the gland (2). Also, Dr. V. Brigidi described in 1877 a case report that included findings obtained at the autopsy of the acromegalic Italian actor Ghirlenzoni (3). Dr. V. Brigidi had diagnosed this condition as ‘‘rheumatitis deformans’’ and made the significant observation of a hypertrophied pituitary gland on the first microscopic examination of a pituitary tumor (3). In 1887, Dr. Oskar Minkowski reported that pituitary enlargement is found in all postmortem studies on patients with acromegaly (4). In 1892, Dr. Roberto Massalongo was able to correlate acromegaly with increased pituitary function by demonstrating that a pituitary tumor taken from a patient with acromegaly contained specific granulated cells (5). At the end of the 19th century, the relationship between pituitary hyperfunction- hypertrophy (or a hyperfunctioning pituitary tumor) and acromegaly was clearly established and confirmed by many investigators (6–12). Dr. Henri Henrot had already pub- lished in 1877 an autopsy report of a patient with gigantism, in whom a 4.5 6 3.0 cm tumor was found in the position of the pituitary body (13,14). Initially, it was believed that acromegaly and gigantism were two totally different diseases. Dr. Pierre Marie (15–21), his intern Dr. J.D. Souza-Leite (22) and Dr. Georges Guinon Copyright 2012 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. 29 (23) were convinced that acromegaly and gigantism were two entirely different disorders. Gigantism was considered an exaggerated variant of normal development, whereas acromegaly was considered as a pathological condition. However, in 1884, Drs. Christian F. Fritsche and Theodor Albrecht Edwin Klebs (24), supported by the work of Dr. Karl Langer (1872) (25), concluded that in contrast to gigantism, which they considered a congenital disorder, acromegaly is an acquired variety of gigantism that occurs at a later age after growth is completed. In 1894, Dr. M. Sternberg concluded that there are many similarities between acromegaly and gigantism (26). However, in 1897 he changed his view and agreed with Dr. Pierre Marie and others that both disorders have different origins (27). In 1891, Dr. D.J. Cunningham, after studying the skeleton of the Irish giant Cornelius Magrath (1736–1760; height: 2.26 m [7 ft, 5 in]), pointed out the connection between acromegaly and gigantism (28–30). In 1893, Dr. Charles Dana (31) and Dr. Woods Hutchinson (32) described the case report and postmortem studies of the French giantess Emma Aline Bataillard (also known as Lady Aama, 1877–1895; height: 2.03 m [6 ft, 8 in]) and reached the same conclusion. After studying the acromegalic giant Jean-Pierre Mazas (1847– 1901; height: 2.30 m [7 ft, 6K in]), the so-called ‘‘giant of Montastruc’’ (Monastruc, Haute-Garonne, France) in 1895, Drs. E´douard Brissaud and Henry Meige also concluded that acromegaly and gigantism can coexist in the same person (33,34). It gradually became evident that acromegaly and gigant- ism have the same pathogenetic mechanism, but differ regarding the age of onset. Gigantism occurs much earlier in life when the skeleton still has the potential to grow, a developmental phase now known as ‘‘prepubertal’’ (33–35). Finally, the cause of acromegaly and gigantism — the overproduction of pituitary growth hormone — became known in the early years of the 20th century (36). Familial acromegaly and familial gigantism are extremely rare. The earliest report of familial gigantism may be that of Goliath, described in in the Bible, where it is stated that his father and three brothers were also giants. The first description of familial acromegaly in the medical literature is most likely a report by Fraenkel that was published in 1901 (37,38). The Ugo brothers, or Hugo brothers, also