Neurosurg Focus 29 (4):E1, 2010 Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities Historical vignette ANTONIOS Mamm IS , M.D., JE A N AN D ERSON ELOY , M.D., A N D Jam ES K. LIU, M.D. Department of Neurological Surgery, Division of Otolaryngology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Neurological Institute of New Jersey, Newark, New Jersey Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. How- ever, it was Pierre Marie, in 1886, who established the term “acromegaly” for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth” as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with ac- romegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity. (DOI: 10.3171/2010.7.FOCUS10160) KEY WOR D S • acromegaly • gigantism • historical vignette • pituitary tumor CROMEG A LIC individuals and giants have been the very marked prognathism, flattened and indented laterally, as if the cheeks had been elevated by a blow from the hatchet on subject of fascination for millennia. Whereas there 7,8 have been a multitude of descriptions in the lay lit- each side. Aerature since the beginnings of the written word, the first Taruffi described the skeletal deformities associated scientific description was probably made by Dutch physi- with acromegaly in 1877.41,42 A series of descriptions cian and occultist Johannes Wier. His medical description were to follow during the late 19th century.10,11,18,19,24,46 of a giantess was published in 1567 in the Medicarum Even though multiple descriptions of this condition were Observationum.48 Further descriptions surfaced in the reported by other physicians, the term “acromegaly” did late 18th and early 19th centuries by Noel (1779), Sau- not exist until 1886 when Pierre Marie defined the disease cerotte (1801), Gall (1810), and Magendie (1839).15,24,27,36 in his classic essay titled “Sur deux cas d’acromégalie; In 1835, French dermatologist Jean-Louis-Marc Alibert hypertrophie singulière non congénitale des extrémités described “Geant scrofuleux” in his monograph on der- supérieures, inférieures et céphalique.”29 1 matological disorders. In 1857, W. O. Chalk described a Pierre Marie: Establishment of Acromegaly as a Diagnosis case of pathological dislocation of the jaw secondary to macroglossia in a patient with acromegaly.9 In 1864, the Despite early descriptions of acromegalic patients, Italian neurologist Andre Verga described “prosopecta- there was no consensus on a unifying underlying diagno- sia” (widening of the face), while in 1868, Lombroso sis. Early in the 19th century, the concept of an endocrine described “macrosomia.”25,26,45 These were followed by system was not yet discovered. Therefore, most physicians case descriptions by Friedreich in 1868 and Henrot in at that time attributed the clinical findings of acromegaly 1877, the latter including an autopsy report in which a 45 to manifestations of other diseases such as Paget disease, × 30–mm tumor in the position of the pituitary body was myxedema, tuberculosis, syphilis, rheumatism, or gout. It described.14,20,21 Brigidi, in 1877, described the case of the was not until 1885 when Pierre Marie described 2 cases Italian actor Ghirlenzoni, stating: of an unusual noncongenital hypertrophy of the head … unfortunately, he could not speak clearly, on account of and the upper and lower extremities, which were subse- 29 the excessive size of his tongue … the rest of the face had more quently published in 1886. It was in this manuscript that the appearance of an ape than a man. It was lengthened, with the term “acromegaly” was first coined, and where it was Neurosurg Focus / Volume 29 / October 2010 1 Unauthenticated | Downloaded 09/30/21 02:22 AM UTC A. Mammis, J. A. Eloy, and J. K. Liu FIG. 1. Photographs of Marie’s acromegalic patients in the clinic of Professor Charcot. deemed a distinct clinical disease (also known as “Ma- to note that Marie frequently observed the occurrence of rie’s malady”). These 2 cases were observed in Professor great hypertrophy of the pituitary body.38 Charcot’s clinic at the Salpêtrière Hospital in Paris. Marie’s first case was that of a 37-year-old woman Pituitary Tumors and Sellar Enlargement: an Observation who had not sought medical attention before, but who had in Patients With Acromegaly developed amenorrhea and headaches at the age of 24 The underlying pathophysiological mechanism of ac- years (Fig. 1). Describing his findings, he stated: romegaly and gigantism was an area of great debate since It was at the age of twenty-four, at the time the menstrua- the time of Saucerotte in 1801.36 Verga, 45 in 1864, report- tion suddenly ceased, that she noticed the sudden increase in ed sellar enlargement in a patient with acromegaly. After her hands. Her face at this time also underwent changes, … so that, multiple reports emerged suggesting the connection that when the patient returned home none of her relatives could between acromegaly and pituitary pathological entities. recognize her…. The whole feet are large, including the toes. 33 Though the latter are increased in size, they have preserved In 1887, Oscar Minkowski of Germany published a se- their form, there is no true deformity, their appearance is sim- ries of autopsy studies that strengthened this association. ply that of a very big person…. The tongue is enlarged. The He found pituitary enlargement in all patients with acro- patient is a little deaf, and the sight is also slightly defective…. megaly, and was probably the first to realize the causal The cranial vertex is of nearly the same size as the end of the relationship between acromegaly and pituitary enlarge- chin. The lower jaw is well developed…29 ment. Massalongo30,31 attributed acromegaly to pituitary In addition to a detailed description of this patient’s hyperfunction by demonstrating pituitary tumor cells that acromegalic appearance, Marie also reported a finding contained granular cytoplasm in a patient with acromega- consistent with diabetes insipidus: “The patient’s thirst is ly. In 1898, Woods Hutchinson22 described the association intense, obliging her to beg tea of her friends in order to between pituitary hyperfunction and clinical acromegaly. satisfy it. The quantity of urine is excessive.…”29 Despite the multiple observations of pituitary tumors in The second case was that of a 54-year-old woman patients with acromegaly, the link between the two re- who developed amenorrhea at the age of 29 years. The mained controversial for many years. year after that, the patient completely lost her vision and The relationship of acromegaly and gigantism was became permanently blind. This patient went on to notice also an area of contention. Marie28,29 and Souza-Leite38 incremental increases in the size of her head, hands, and believed that these were distinct entities. As detailed in feet. Marie described: Bartels’ account,3 Fritsche and Klebs, on the other hand, The borders of the orbits are very thick, also the frontal eminences, making between them and the upper border of the malar bone a deep depression, something similar to the cor- responding region of a cow. The nose is large. The lower jaw is very thick.…29 In addition to coining the term “acromegaly,” Marie’s major contribution to the field was the establishment of a unique clinical entity, whose characteristics he vividly described with his detailed case reports. Although he did not postulate on the underlying pathophysiological mech- anisms of acromegaly, he did state that he believed the dis- ease was not attributed to previously implicated origins, such as myxedema or Paget disease. Marie’s work was followed by a thesis on acromegaly by his intern, Souza- Leite, who further bolstered these arguments with more 38 case reports (Fig. 2). At this point in time, the cause of FIG. 2. Photographs of acromegalic patients, from Souza-Leite’s the- acromegaly was still not known. However, it is interesting sis on acromegaly published in 1890. 2 Neurosurg Focus / Volume 29 / October 2010 Unauthenticated | Downloaded 09/30/21 02:22 AM UTC Historical evolution of acromegaly and gigantism FIG. 3. The French giantess, Lady Aama, as photographed by Frank Wendt, New York. believed that acromegaly and gigantism were the same disorder, the former being acquired and the latter con- genital. Evidence for a pituitary cause of gigantism was supported by Hutchinson’s pathological descriptions of a French giantess known as Lady Aama (Fig. 3). She died at the age of 18 years and stood 6 feet, 7.75 in tall. Path- ological examination of her skull revealed a very large pituitary fossa (31 × 37 mm) and a huge frontal sinus. Hutchinson22 stated: “The pituitary body was found to be greatly enlarged…. It appeared to be about the size of a pigeon’s egg….” It was eventually recognized that both acromegaly and gigantism had the same underlying FIG. 4. Photographs of a 40-year-old tanner with acromegaly. Note pathogenesis, but differed in the patient’s age at onset. “the enormous paw-like hand with outsized, clubbish thick fingers and the short broad nails, as well as the monstrous foot, in which is also Acromegaly occurred in adulthood (Fig.