A Probable Case of Gigantism in a Fifth Dynasty Skeleton from the Western Cemetery at Giza, Egypt
Published online 31 December 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/oa.781
[In my opinion the following skeleton shows distinctive traits of the Borreby type which relate him to the archaic element of Northern Europe after the end of the Ice Age, the "Giant Warrior Strain" thought to be a very old combination of Neanderthal and Cromagnon traits and carried on distinctively by the Scandinavian Berserks most notably. This individual was between 6 feet two and six feet six in life, probably a not so very large individual of the type: the type is known to have inclined unusually toward both glanduar Gigantism and to Acromegaly. It is possibly this is inferably an individual descended from this warrior strain native to Northern Europe but brought to Ancient Egypt for the sole purpose to use him in the military and as a weapon of intimidation-DD]
Pituitary gigantism is a rare endocrine disorder caused by excess secretion of growth hormone during childhood. Individuals with this condition exhibit unusually tall stature due to prolonged growth as well as associated degenerative changes. Continued secretion of excess growth hormone during adulthood results in acromegaly, a related condition that results in bony overgrowth of the skull, hands and feet. The remains of a large adult male, probably in his late 20s or early 30s, from a Fifth Dynasty tomb (2494–2345 BC) were excavated in 2001 from Cemetery 2500 in the Western Cemetery at Giza, Egypt, as part of the Howard University Giza Cemetery Project. This individual exhibits characteristics of pituitary gigantism, including tall but normally-proportioned stature, delayed epiphyseal union, a large sella turcica, advanced arthritis and a transepiphyseal fracture of the left femoral head. Additional pathological features, including osteopenia and thinness of the parietal bones, suggest that this individual may also have been hypogonadal. Craniometric comparisons with other ancient Egyptian groups as well as modern normal and acromegalic patients show some tendency toward acromegalic skull morphology. Differential diagnosis includes eunuchoid gigantism, Sotos syndrome, Beckwith-Wiedemann syndrome, Marfan syndrome, homocystinuria, Weaver syndrome and Klinefelter syndrome. In conclusion, the pathological features associated with this skeleton are more consistent with pituitary gigantism than any of the other syndromes that result in skeletal overgrowth. Copyright 2004 John Wiley & Sons, Ltd.
Key words: gigantism; acromegaly; pituitary; Giza; Egypt; skeletal
Pituitary gigantism is a rare disorder generally caused by hypersecretion of growth hormone, or somatotrophin, during childhood. Excess growth hormone causes prolonged stimulation at the endochondral growth plates, resulting in tall stature with normal body proportions. A pituitary tumour can provide the stimulus for the overproduction of growth hormone. Onset of the tumour during adulthood, or continued production of growth hormone into adulthood, results in acromegaly. Acromegaly is characterised by periosteal apposition and bone overgrowth, particularly of the mandible, hands and feet (Resnick, 1988). If excess growth hormone is produced during childhood and continues into adulthood, the features of gigantism and acromegaly are both expressed. Acromegaly, the more common of the two conditions, has been reported in the palaeopathological literature, including cases from Egypt, Illinois and New Mexico (Ortner, 2003). Very few cases of gigantism have been described in prehistoric skeletons. A probable case of gigantism in a female skeleton from Ostro´w Lednicki, in Lednogo´ ra, Poland, dating to about the 12th to 13th century AD was described by Gladykowska-Rzeczycka et al. (1998). This specimen exhibited a pituitary lesion and tall stature (215.5 cm) as well as overgrowth of the mandible, suggesting gigantism and acromegaly. The purpose of this paper is to present a case of probable gigantism in a Fifth Dynasty skeleton (2494–2345 BC) from Cemetery 2500 in the Western Cemetery at Giza, Egypt. In this paper, metric data are compared with data from ancient Egyptian populations and data reported for other cases of gigantism. The pathological features of this skeleton are compared with skeletal symptoms reported in pituitary giants. Differential diagnosis is also discussed
Materials and Methods
The skeletal remains of a large adult male (Burial 2507X) were excavated in 2001 from a Fifth Dynasty mastaba tomb in Cemetery 2500 of the Western Cemetery at Giza, Egypt, as part of the Howard University Giza Cemetery Project. Skeletal analysis was conducted in 2002. This individual is represented by a cranium, mandible and largely complete postcranial skeleton in fair condition. The cranial base, ribs and articular ends of the lower long bones exhibit postmortem fragmentation. Analysis of sex is based on the morphology of the cranium and pelvis, following Buikstra & Ubelaker (1994). Age at death is based primarily on stages of epiphyseal closure following Scheuer & Black (2000). Secondary age assessment was based on cranial suture closure following the method of Meindl & Lovejoy (1985), as well as dental attrition following Smith (1984). The morphology of the pubic symphysis and auricular surfaces were not used for age assessment, due to pathological changes. Craniometric analysis follows Buikstra & Ubelaker (1994). Postcranial measurements are consistent with definitions from Bass (1987), Moore-Jansen et al. (1994) and Zobeck (1983). Stature was calculated using formulae revised by Robins & Shute (1986) for ancient Egyptians, based on original formulae published by Trotter & Gleser (1958) for blacks. Stature was calculated using the left humerus, both radii, both ulnae and the left fibula. The length of the left fibula was estimated due to slight postmortem damage. Craniometric data for 2507X were compared with measurements for the other males from Cemetery 2500, as well as a sample of 26th– 30th dynasty males from Giza (Howells, 1989) using z scores. Measurements from Egyptian populations from 4th–11th Dynasty Qau (Morant, 1925), 4th–5th Dynasty Medum and 4th Dynasty Sakkarah (Morant et al., 1936) were also compared with 2507X, but statistical analysis was not conducted because standard deviations were not reported. In addition, the pattern of craniometric differences between normal and acromegalic males from the Czech Republic (Dosta´lova´ et al., 2003) and Japan (Takakura & Kuroda, 1998) was compared with differences between 2507x and other Egyptian males using z scores.
Age and Sex
Pelvic and cranial morphology are consistent with male sex. Although bones are large, musculature is not pronounced, except for bilateral pilastering of the femoral shafts. Age estimation was complicated by a number of factors. Hypertrophy of the pubic symphysis and iliosacral joint surfaces obscures age estimation based on pelvic morphology, as these changes appear to be pathological and not related to normal ageing. Epiphyseal closure and cranial suture closure do not provide consistent evidence of age at death. The epiphyseal lines of the distal radii and ulnae, proximal humeri, iliac crests and ischial tuberosities are still grossly visible, suggesting relatively recent fusion. As shown in Figures 1 and 2, the proximal left humerus shows poor alignment of the epiphysis and diaphysis and still shows evidence of an epiphyseal line. The inferior three sternal segments and inferior lumbar rims also exhibit evidence of recent fusion. The rib heads are partially fused. The left inferior scapular border is unfused. Anterior rib ends show billowing or flat surfaces. These epiphyseal indicators suggest an age of over 20 years, but younger than 27 years. The right proximal femur, proximal radii and ulnae and the distal tibiae and fibulae exhibit complete fusion, with no remnant epiphyseal lines. The medial clavicles, distal femora and proximal tibiae and fibulae are unobservable due to postmortem damage. The sagittal and coronal sutures exhibit complete closure endocranially. Partial to complete cranial suture closure is also present at the following landmarks: lambda, obelion, anterior sagittal suture, bregma, midcoronal suture and pterion. Cranial suture closure suggests a mean age of about 45 years for the vault landmarks (age range about 30–60 years) and a mean age of about 40 years (age range about 27–52 years) for the lateral-anterior landmarks. Tooth wear is moderate to pronounced and is consistent with patterns observed in the 30–40 year age range compared with 20 other adolescent and adult individuals from this site. Pronounced degenerative changes of the pelvis and spine, as well as arthritis of the long bones and generalised osteopenia, are present and are usually indicative of more advanced age, but in this case appear to be part of an overall pattern of pathological changes and therefore need to be considered with caution.
Maximum length measurements for long bones and the resulting statures are shown in Table 1. Values for stature range from 189.7 cm for the fibula to 195.3 cm for the left radius. Table 2 shows all postcranial measurements. Table 3 shows measurements of the cranium and mandible for 2507X as well as comparative data for other males from Cemetery 2500 and Egyptian males from other ancient sites. The frontal and left lateral views of the skull are shown in Figures 3 and 4, respectively. In general, cranial and mandibular measurements for 2507X were larger than the mean values for
Figure 1. Anterior view of left proximal humerus with clear epiphyseal line.
Figure 2. Anterioposterior radiograph of proximal left humerus.
ancient Egyptian males from several sites. As shown in Table 3, 13 out of 21 measurements show significant differences between 2507X and the other males from Cemetery 2500. The z scores indicate that for these measurements, 2507X exhibits significantly larger values than the rest of the sample. Seven out of 16 measurements differed significantly between 2507X and the sample of 26th–30th Dynasty males from Giza. Measurements represented in both groups that are significantly different from 2507X include biauricular breadth, upper facial height, nasal height, orbital height and biorbital breadth. Maximum cranial length and breadth and orbital breadth are significantly different between 2507X and the Cemetery 2500 males, but not between 2507X and the 26th–30th Dynasty males. Interorbital breadth is significantly different between 2507X and the 26th–30th Dynasty males, but not between 2507X and the Cemetery 2500 males. Minimum frontal breadth, chin height, mandibular body height, minimum ramus breadth and maximum ramus breadth are significantly different between 2507X and the Cemetery 2500 males. These measurements were not reported in the 26th–30th Dynasty sample. Finally, upper facial breadth is significantly different between 2507X and the 26th–30th Dynasty sample; only one comparative individual was available for the Cemetery 2500 sample, so a z score was not calculated.
Description of pathological changes
The cranium exhibits a small, lytic lesion on the endocranial surface of the clivus. The lesion is 5mm (anterioposterior) by 3mm (mediolateral) with slightly raised edges. A spicule of bone bisects the inside of the lesion. The pituitary area appears grossly and radiologically normal with no lytic destruction, but the dorsum sellae is porous. Gross observation was possible due to some postmortem damage to the cranial base. The anterioposterior diameter of the sella turcica is 15 mm. Pronounced degenerative changes are present throughout the skeleton. Both shoulder joints exhibit arthritic lipping and erosive lesions. Both elbow joints show lipping and complete Figure 3. Frontal view of skull. subchondral destruction of the radiocapitular joints as well as the lateral half of the ulnar and trochlear articular surfaces. Wrist joints, carpometacarpal joints and metacarpophalangeal joints also show moderate to severe arthritic lipping and erosion. The left hip joint shows lipping and complete subchondral destruction of the femoral head. Arthritic erosion and porosity cover the posterior surface of the left patella, which also exhibits atrophy of the medial half of the bone. Pronounced arthritic changes, including profuse lipping and some erosion, also affect the left and right tarsals. Vertebral apophyseal joints show lipping, porosity and erosion. Advanced degenerative joint disease is present in the spine. Vertebral osteophytes with curved spicules and marginal porosity are present on the superior rims of C4–C6, the superior and inferior rims of T5–T11 and L3–L5. Porosity is also present on the superior end plates of C4–C6 and the superior and inferior rims of T5– T11 and L3–L5. Porosity and erosion of the superior L4 and L5 end plates are shown in Figure 5. Vertebral osteophytes with elevated rims are present on the superior and inferior rims of T12–L2. Schmorl’s nodes are present on T12–L5. The fourth and fifth thoracic vertebrae exhibit superior end plate depressions without wedging, and T10 and T11 show superior end plate depressions with wedging, resulting in slight kyphosis. The entire skeleton exhibits general osteopenia with cortical thinning. This is illustrated in the radiograph of the proximal humerus (Figure 2). The maximum thickness of the left humeral midshaft cortex is 2.2mm. The maximum thickness of the left tibial midshaft is 1.5mm. As shown in Figure 6, the cranium exhibits biparietal thinning. A large depression is present on the superioposterior aspect of the left parietal that measures about 58mm in diameter. Three or four smaller depressions are present on the superioposterior aspect of the right parietal that cover an area about 51mm (anterioposterior) by 72mm (mediolateral). The morphology, location and size of the lesions is consistent with parietal thinning, as opposed to healed trauma. The outer Figure 4. Left lateral view of skull. table and diploe¨ are involved and the inner table is spared. The left femur exhibits a subcapital fracture with non-union (Figure 7). The femoral head is normal in shape, but is completely separated from the rest of the femur. The fractured surface of the femoral head shows some sclerosis. The subchondral surface of the femoral head shows complete destruction due to arthritic erosion. The neck is no longer present and the shaft shows extensive healing in the location of the neck base. The proximal shaft is deformed, including probable displacement of the lesser trochanter. The extent of healing and deformation suggests that this condition existed for some time. It is likely that this represents a transepiphyseal fracture that occurred prior to full closure of the growth plate. Healed fractures of the anterior third of the left sixth and seventh ribs are also present. The left third and right second metatarsal shafts exhibit probable healed fractures. All of the left metatarsal shafts, the right second, third and fourth metatarsal shafts and the dorsal surfaces of the first to third proximal toe phalanges also show periostitis. Periostitis covers the middle and distal thirds of the left fibular shaft and the medial aspect of the left middle and distal tibial shaft. A large osteoma is present on the left zygomatic arch (Figure 4). The radiograph shows that the structure comprises of uniform, dense bone. It is 13mm in diameter and is raised 10mm above the normal bone surface. Dental pathology includes several carious lesions and abscesses. The mesial half of the right mandibular first molar crown shows a large carious lesion and is associated with a periapical abscess with facial drainage. The mandibular right lateral incisor shows complete carious destruction of the crown and is associated with a periapical abscess with facial and lingual drainage. The mandibular left second molar shows an abscess exposing the buccal aspect of the distal root. The mandibular right canine exhibits Figure 5. Superior view of lumbar vertebrae 4 and 5 showing degenerative changes. Figure 6. Superior view of the cranium showing thinness of the parietal bones. unaligned hypoplastic pits in a band between 2.9mm and 5.3mm from the cervico-enamel junction. Slight calculus formation is present on the mandibular teeth. The maxillary dentition shows antemortem loss of the left second premolar, both first molars and the right second molar. Using Smith’s (1984) eight stage system for dental attrition, dental wear is moderate for the right third molar (score 4) and advanced for the anterior dentition and premolars (scores 6–7). Antemortem loss of the left first mandibular molar is present. Dental wear is moderate to advanced for the anterior teeth and premolars (scores 4–6) and slight for the mandibular second and third molars (scores 2–3).
Skeleton 2507X has an unusual suite of pathological features, a number of which are related to a condition that resulted in abnormal skeletal growth. The combination of an apparent delay in epiphyseal fusion, tall stature with normal proportions and superimposed degenerative changes is indicative of a growth-related dysfunction such as pituitary gigantism. Pituitary gigantism is caused by overproduction of growth hormone, which stimulates cartilaginous growth at the growth plates, ultimately resulting in increased linear growth. The normal period of epiphyseal fusion is extended due to the suppression of gonadotropin production (Aegerter & Kirkpatrick, 1975; Aufderheide & Rodrı´guez-Martı´n, 1998), resulting in increased growth and immature skeletal age compared to chronological age. Excess growth hormone can be caused by a pituitary tumour, usually a benign adenoma, but occasionally by diffuse hyperplasia (Aegerter & Kirkpatrick, 1975). A study of 19 cases of gigantism by Scheithauer et al. (1995) included 18 adenomas, 22% of which were grossly invasive, and one case of pure hyperplasia. If a tumour causes the condition, the sella turcica may show evidence of enlargement and lytic destruction (Ortner & Putschar, 1985). Gross observation and radiographic examination showed a large anterioposterior sella turcica diameter (15 mm) and porosity of the dorsum sellae. Gross observation was possible due to postmortem damage to the cranial base. The normal range of anterioposterior diameter measurements for the sella turcica is 8 to 12mm (Paul & Juhl, 1962). The sella turcica of 2507X is slightly larger than normal, but no lytic destruction is present. Although clear evidence of a pituitary lesion would facilitate diagnosis, the size and morphology of the sella turcica can be normal in cases of pituitary hyperplasia (Ortner, 2003). It is unknown whether the lytic lesion observed on the clivus is related to this condition. No reference to any similar lesions was found in the literature.
Figure 7. Anterior view of the left femur with non-union fracture.
Skeletal age of this individual is between 20– 26 years based on epiphyseal fusion. This age range is not consistent with cranial suture closure and tooth wear, which suggest an age over 30 years. This discrepancy suggests the presence of a growth abnormality, where epiphyseal fusion is delayed, so this individual is probably at least in his middle to late 20s, or possibly as old as early 30s, with an age range of 25–35 years. Irregular epiphyseal closure can also lead to asymmetric growth (Aufderheide & Rodrı´guez-Martı´n, 1998). The radii and ulnae were the only long bones with measurable maximum lengths from both sides. The ulnae did not exhibit asymmetry. The maximum lengths of the radii were 331mm and 326mm for the left and right sides, respectively. Stature estimates for individual 2507X range from 189.7 to 195.3 cm, with an average of 192.4 cm (Table 1). Statures of pituitary giants who lived during the 1700s–1900s were reported by Gladykowska-Rzeczycka et al. (1998) and Whitehead et al. (1982). Adult male stature varies widely, ranging from 185 cm to 272 cm for 16 individuals. Stature for individual 2507X is at the lower end of this range, but also must be considered in the context of ancient Egyptian stature. Robins & Shute (1986) reported average male stature of 168.7 cm using the femur and 169.4 cm using the humerus in a sample of predynastic skeletons from Naqada. Zakrzewski (2003) provided stature estimates for Egyptians from various time periods using the formulae revised for ancient Egyptians presented by Robins & Shute (1986). Early Dynastic, Old Kingdom and Middle Kingdom males had mean statures of 169.6 5.1 cm (n¼11), 168.8 3.6 cm (n¼16) and 166.4 5.1 cm (n¼13), respectively, based on femoral and tibial length. Aufderheide & Rodrı´guez-Martı´n (1998) defined gigantic stature as three or more standard deviations above the mean stature of the population. The stature of 192.4 cm for skeleton 2507X is greater than three standard deviations above the mean statures reported by Zakrzewski (2003) for ancient Egyptian groups. Stature comparisons between 2507X and each of these population means are highly significantly different
(P< 0.001), with z scores of 4.47, 6.56 and 5.10 for the Early Dynastic,Old andMiddle Kingdoms, respectively. It is also important to note that the amount of skeletal overgrowth in gigantism depends on the age of onset of the condition. If the condition begins at a young age, growth is extreme, but if onset is closer to puberty, increased growth is not as pronounced (Resnick, 1988). Skeleton 2507X shows skeletal growth at the lower end of the range for modern giants, suggesting onset in later childhood. Persistence of growth hormone excess into adulthood can result in acromegaly. The skeletal effects of acromegaly include bone overgrowth in the skull, hands, feet and vertebral bodies (Resnick, 1988). This leads to exaggerated features, particularly the protrusion of the mandible and supraorbital area. Individual 2507X does exhibit a large skull, but more detailed comparative data are needed to determine whether a pattern typical of acromegaly is present. In a comparative cephalometric study including 26 acromegalic males and 50 normal males from the Czech Republic, Dosta´lova´ et al. (2003) found that acromegalic patients showed increased facial height, neurocranial length, mandibular ramus and mandibular body lengths. They also found increased anterioposterior sella turcica length. Mandibular ramus and body lengths were not measured for 2507X due to postmortem damage, but other measurements are compared below between 2507X and clinical data using z scores. Anterior upper face height, measured from nasion (N) to the anterior nasal spine (ANS) was reported by Dosta´lova´ et al. (2003) as 52.563.47mm for the normal group and 57.805.65mm for the acromegalic group (z¼1.51, ns). Nasal height (n-ns), which is comparable to N-ANS, is 58mm for 2507X, 48.05.0mm for the other males from Cemetery 2500, and 51.72.7mm for the 26th–30th Dynasty males from Giza (Table 3). Nasal height differs significantly (z¼2.00; P< 0.05) between 2507X and the Cemetery 2500 males and also between 2507X and the 26th–30th Dynasty males (z¼2.33; p< 0.05) between 2507X and the Cemetery 2500 males and also between 2507X and the 26th–30th Dynasty males (z¼2.33; p< 0.01). Upper facial height (n-pr) was 80mm for 2507X, 70.2 4.7mm for other males from Cemetery 2500, and 68.43.0mm for 26th–30th Dynasty males. Differences are significant between 2507X and the Cemetery 2500 males (z¼2.09; P< 0.05) and the 26th–30th Dynasty sample (z¼3.87; P< 0.001). Dosta´lova´ et al. (2003) found that neurocranial length, measured from nasion (N) to opisthocranion (OP) was 176.324.96mm for the normal group and 187.497.68mm for the acromegalic group (z¼2.25; P< 0.05). Maxiumum cranial length (g-op), a slightly shorter measurement than neurocranial length, was 192mm for 2507X, 182.34.3mm for the other males from Cemetery 2500 (z¼2.26; P< 0.05) and about 185–186mm for other ancient Egyptian males (Table 3). No significant differences were observed between 2507X and the 26th–30th Dynasty Egyptian males in maximum cranial length. Dosta´lova´ et al. (2003) found that mean sella turcica diameter was 9.541.27mm for the normal sample and 12.343.74mm for the acromegalic sample (z¼2.20; P <P < 0.05) and the 26th–30th Dynasty sample (z¼3.87; P < 0.001). Dosta´lova´ et al. (2003) found that neurocranial length, measured from nasion (N) to opisthocranion (OP) was 176.324.96mm for the normal group and 187.497.68mm for the acromegalic group (z¼2.25; P < 0.05). Maxiumum cranial length (g-op), a slightly shorter measurement than neurocranial length, was 192mm for 2507X, 182.34.3mm for the other males from Cemetery 2500 (z¼2.26; P < 0.05) and about 185–186mm for other ancient Egyptian males (Table 3). No significant differences were observed between 2507X and the 26th–30th Dynasty Egyptian males in maximum cranial length. Dosta´lova´ et al. (2003) found that mean sella turcica diameter was 9.541.27mm for the normal sample and 12.343.74mm for the acromegalic sample (z¼ 2.20; P < 0.05). The sella turcica diameter of 2507X is 15 mm. Comparative data for other Egyptian males was not available, so comparisons were made with the normal and acromegalic values reported by Dosta´lova´ et al. (2003). Sella turcica diameter differed significantly between 2507X and normal males (z¼4.30; P < 0.001), but no significant difference was found between 2507X and acromegalic males. Takakura & Kuroda (1998) reported similar results in a sample of 28 acromegalic males and 23 normal males from Japan. They observed increased facial height, mandibular length and mandibular ramus length as well as mandibular height in acromegalic patients compared with a normal sample. Mandibular height was measured from supramentale (B) to menton (ME). This is a slightly shorter measurement than chin height (id-gn), but generally measures the height of the anterior mandible. In the Japanese study, the mean value for mandibular height (B-ME) in acromegalic males was 30.84.7mm and the mean value for normal males was 24.62.8mm (z¼2.21; P < 0.05). Chin height (id-gn) was 42mm for 2507X, 32.62.3mm for males from Cemetery 2500 (z¼ 4.09; P < 0.001), and 33.8mm for Egyptian males from Qau (Table 3). Values for 2507X and the Qau males were not compared statistically because standard deviations were not provided. Although the cranium and mandible of 2507X do not exhibit the exaggerated characteristics associated with advanced acromegaly, comparative measurements reveal a pattern suggesting acromegalic morphology. Facial height, cranial length and mandibular height are increased in 2507X compared with normal Egyptian males. Also, the anterioposterior diameter of sella turcica is long compared with the range for normal individuals, a characteristic found in acromegalic individuals.
Prolonged linear growth coupled with increased muscular weakness leads to degenerative changes in gigantism (Aufderheide & Rodrı´guez- Martı´n, 1998). In addition, excess secretion of growth hormone increases the risk of osteoarthritis (Boullion, 1991). Peripheral and axial joint abnormalities have been observed in many cases of gigantism (Whitehead et al., 1982; Podgorski et al., 1988; Gladykowska-Rzeczycka et al., 1998). Individual 2507X exhibits pronounced degenerative changes throughout the postcranial skeleton, including osteoarthritis of all major joints and advanced degenerative joint disease of the spine. The pubic symphysis and iliosacral joints show degenerative changes superimposed on hypertrophy of the joint surfaces. Conditions characterised by increased growth hormone, such as gigantism and acromegaly, are usually associated with increased bone mass (Frost, 1998). This could be due to stimulation of bone turnover which results in a net positive bone balance, despite the fact that high remodelling rates usually result in bone loss over time (Boullion, 1991). It is also possible that biomechanical factors are important. For example, increased bone mass could result indirectly from the stimulation of bone growth and increased body weight caused by growth hormone (Frost, 1998). In some cases of gigantism and acromegaly, osteopenia results from a decrease in oestrogens and androgens due to deficient basophilic cell function (Aegerter & Kirkpatrick, 1975). Disorders such as eunuchoidism, a type of male hypogonadism, are sometimes found in individuals with gigantism or acromegaly (Musa et al., 1972). Lower bone mineral density in the spine and femur has been observed in hypogonadal acromegalic patients compared with eugonadal acromegalic patients (Kayath & Vieira, 1997; Lesse et al., 1998). Individual 2507X shows pronounced osteopenia of the axial and appendicular skeleton, possibly indicating insufficient sex hormone production. The aetiology of thinness of the parietal bones has been a matter of some debate. It is unclear whether this condition is progressive and due to age-related bone loss or whether it is static and caused by a developmental abnormality. Steinbach & Obata (1957) suggested that both situations may exist based on several case studies, including one case of documented thinning over time in an elderly female and two cases of parietal thinning in males diagnosed with gonadal insufficiency. Biparietal thinning has been described in a number of ancient Egyptian crania, including five by Lodge (1967), one by Ortner & Putschar (1985) and one by Barnes (1994) dating from the Ninth and Twelfth Dynasties as well as the New Empire Period. The non-union fracture of the left femoral head may have occurred during growth, since a prolonged growth period increases joint vulnerability. The capital femoral epiphyseal plate is more susceptible to shearing stress during growth, when a shortage of sex hormone compared with growth hormone causes a widening of the growth plate. Slipped femoral capital epiphysis has been associated with endocrine diseases including gigantism and acromegaly (Reeves et al., 1978; Resnick et al., 1988; Feydy et al., 1997). A large osteoma of the zygomatic arch was observed on skeleton 2507X. This is not a pathological feature commonly associated with growth abnormalities like gigantism, but Gladykowska- Rzeczycka et al. (1998) observed an osteoma that obliterated the external auditory meatus of a probable giant from Ostro´w Lednicki. The possible healed metatarsal fractures and periostitis are probably indirectly related to the overall observed condition. The metatarsals show severe osteopenia and were probably susceptible to trauma and related infection.
Differential diagnosis includes eunuchoid gigantism, which is caused by gonadal failure before puberty. In males, this condition results in increased stature due to delayed epiphyseal fusion, although not as extreme as that observed in pituitary gigantism. In addition, the lower half of the body shows greater growth than the upper half (Aegerter & Kirkpatrick, 1975). Bones are long and tubular and the condition may be associated with osteoporosis and lack of normal muscle development (Chew, 1991). The stature of skeleton 2507X is not extreme compared with modern pituitary giants, although stature is very tall compared with other ancient Egyptians. The lower half of the body does not exhibit more pronounced growth compared with the upper half based on stature estimates of the fibula compared with the humerus, radius and ulna. In general, bones show less muscular development than expected for an individual of this size, except for the femora. Osteopenia is present throughout the skeleton. Thinness of the parietal bones, which was noted in two cases of hypogonadism by Steinbach & Obata (1957), is also present. In a study of 30 males with eunuchoidism, radiographic analysis showed normal skull shape, small sella turcica dimensions, small mastoid processes and thin cranial bones (Kosowicz& Rzymski, 1975). Skull 2507X does exhibit thin parietal bones, but does not have a small mastoid process or sella turcica. Mastoid process length for 2507X is 33 mm, within the range of 24– 37mm observed for the nine other adult males from Cemetery 2500. The length of the sella turcica is slightly higher than the normal range. In summary, some of the features of this skeleton are also consistent with eunuchoid gigantism. Hypogonadism can exist along with gigantism, so it is possible that both conditions were present. In addition to endocrine abnormalities, a number of syndromes are associated with accelerated growth and tall stature, including Sotos syndrome, Beckwith-Wiedemann syndrome, Marfan syndrome, homocystinuria, Weaver syndrome and Klinefelter syndrome (Eugster & Pescovitz, 1999). The clinical features of these syndromes differ from those associated with endocrine disorders. For example, several are associated with advanced skeletal age, as opposed to delayed skeletal maturation, including Sotos, Beckwith-Wiedemann and Weaver syndromes (Goodman & Gorlin, 1983; Trabelsi et al., 1990; Melo et al., 2002). Marfan syndrome is characterised by overgrowth of the lower half of the skeleton compared with the upper half, and elongated limbs compared with the trunk (Goodman & Gorlin, 1983; Goldman, 1988). Homocystinuria can be characterised by an increased or decreased rate of skeletal maturation and is also associated with osteoporosis, codfish vertebrae and calcified spicules in the distal radius and ulna (Goodman & Gorlin, 1983; Goldman, 1988). Klinefelter syndrome, a form of male hypogonadism caused by a chromosomal abnormality, can be associated with delayed skeletal maturation as well as decreased cranial length and breadth, short metacarpals, radioulnar synostosis and accessory epiphyses (Kosowicz & Rzymski, 1975; McAlister, 1988). It is unlikely that the pathological features of 2507X were caused by any of these syndromes.
This study describes a Fifth Dynasty skeleton of a large male from the Western Cemetery at Giza, Egypt, probably in his late 20s or early 30s, with metric and pathological features consistent with pituitary gigantism. The combination of tall stature, proportional growth, delayed epiphyseal union and a large sella turcica are consistent with a pituitary growth abnormality. Pathological changes superimposed on the skeleton, including advanced arthritis and a transepiphyseal fracture of the left proximal femur, further support this diagnosis. Additional pathological features, including osteopenia and thinness of the parietal bones, may be related to hypogonadism, a condition sometimes associated with gigantism. Comparative measurements of the cranium and mandible show that a tendency toward acromegalic morphology was also present, which means that the effects of excess growth hormone experienced during growth persisted into adulthood. Pituitary gigantism is a rare condition that has not been widely documented in ancient skeletal remains. The rarity of this disorder combined with the great antiquity of skeleton 2507X make this case an important contribution to the palaeopathological literature.
I would like to thank Dr Ann Macy Roth, the director of the Howard University Giza Cemetery Project, as well as Dr William B. Hafford and Dr Pia-Kristina Anderson, the archaeologists who conducted the excavation of tomb 2507X. I also thank Nicole Moss, for her assistance during the skeletal examination. I am grateful to Dr Azza Sarry el-Din and her staff for providing access to the laboratory facility at Giza and for conducting the radiographic documentation. Finally, I am indebted to Dr Zahi Hawass and the Permanent Committee of the Supreme Council for Antiquities for arranging permission to study the human remains from Cemetery 2500 at Giza. The skeletal analysis of the remains from Cemetery 2500 at Giza was funded by the Institute for Bioarchaeology.
Aegerter E, Kirkpatrick JA. 1975. Orthopedic Diseases.
Physiology, Pathology, Radiology (4th edn). WB
Saunders: Philadelphia, PA.
Aufderheide AC, Rodrı´guez-Martı´n C. 1998. The
Cambridge Encyclopedia of Human Paleopathology.
Cambridge University Press: Cambridge.
Barnes E. 1994. Developmental Defects of the Axial Skeleton in
Paleopathology. University Press of Colorado: Niwot,
Bass WM. 1987. Human Osteology: A Laboratory and Field
Manual (3rd edn). Special Publication No. 2. Missouri
Archaeological Society, Inc.: Columbia, MO.
Boullion R. 1991. Growth hormone and bone. Hormone
Research 36(Suppl. 1): 49–55.
Buikstra JE, Ubelaker DH. 1994. Standards for Data
Collection from Human Skeletal Remains. Arkansas
Archaeological Survey Research Series No. 44:
Chew FS. 1991. Radiologic manifestations in the
musculoskeletal system of miscellaneous endocrine
disorders. Radiological Clinics of North America 29(1):
Dosta´lova´ S, S ˇ onka K, S ˇ mahel Z, Weiss V, Marek J.
2003. Cephalometric assessment of cranial abnormalities
in patients with acromegaly. Journal of Cranio-
Maxillofacial Surgery 31: 80–87.
Eugster EA, Pescovitz OH. 1999. Commentary: Gigantism.
Journal of Clinical Endocrinology and Metabolism
Feydy A, Carlier RY, Mompoint D, Rougereau G, Patel
A, Vale´e C. 1997. Bilateral slipped capital femoral
epiphysis occurring in an adult with acromegalic
gigantism. Skeletal Radiology 26: 188–190.
Frost HM. 1998. Could some biomechanical effects
of growth hormone help to explain its effects on
bone formation and resorption? Bone 23(5): 395–
Gladykowska-Rzeczycka JJ, S ´ miszkiewicz-Skwarska
A, Soko´ l A. 1998. A giant from Ostro´w Lednicki
(XII–XIII c), Dist. Lednogo´ ra, Poland. Mankind
Quarterly 39: 147–172.
Goldman AB. 1988. Collagen diseases, epiphyseal
dysplasias, and related conditions. In Diagnosis of
Bone and Joint Disorders (Vol. 5, 2nd edn), Resnick D,
Niwayama G (eds). W.B. Saunders Company: Philadelphia,
Goodman RM, Gorlin RJ. 1983. The Malformed Infant
and Child. Oxford University Press: Oxford.
Howells WW. 1989. Skull shapes and the map:
craniometric analyses in the dispersion of modern
Homo. Papers of the Peabody Museum of Archaeology and
Ethnology. Harvard University, Vol. 79. Harvard
University Press: Cambridge, MA.
Kayath MJ, Vieira JG. 1997. Osteopenia occurs in a
minority of patients with acromegaly and is predominant
in the spine. Osteoporosis International 7(3):
Kosowicz J, Rzymski K. 1975. Radiological features of
the skull in Klinefelter’s syndrome and male hypogonadism.
Clinical Radiology 26: 371–378.
Lesse GP, Fraser WD, Farquharson R, Hipkin L, Vora
JP. 1998. Gonadal status is an important determinant
of bone density in acromegaly. Clinical Endocrinology
Lodge T. 1967. Thinning of the parietal bones in early
Egyptian populations and its aetiology in the light
of modern observations. In Diseases in Antiquity,
Brothwell D, Sandison AT (eds). CC Thomas:
Springfield, IL, 405–412.
McAlister WH. 1988. Osteochondrodysplasias, dysostoses,
chromosomal aberrations, mucopolysaccharidoses
and mucolipidoses. In Diagnosis of Bone
and Joint Disorders (Vol. 5, 2nd edn), Resnick D,
Niwayama G (eds). W.B. Saunders Company: Philadelphia,
Meindl RS, Lovejoy CO. 1985. Ectocranial suture
closure: a revised method for the determination of
skeletal age at death based on the lateral-anterior
sutures. American Journal of Physical Anthropology 68:
Melo DG, Acosta AX, Salles MA, Pina-Neto JM,
Castro JDV, Santos AC. 2002. Sotos syndrome
(cerebral gigantism): analysis of 8 cases. Arquivos de
neuro-psiquiatria 60(2-A): 234–238.
Morant GM. 1925. A study of Egyptian craniology
from Prehistoric to Roman times. Biometrika 17(1/2):
Morant GM, Collett M, Adyanthaya NK. 1936. A
biometric study of the human mandible. Biometrika
Moore-Jansen PM, Ousley S, Jantz RL. 1994. Data
Collection Procedures for Forensic Skeletal Material (3rd
edn). Report of Investigations no. 48. University of
Musa BU, Paulsen CA, Conway MJ. 1972. Pituitary
gigantism: Endocrine studies in a subject with
hypergonadotropic hypogonadism. American Journal
of Medicine 52: 399–405.
Ortner DJ. 2003. Identification of Pathological Conditions in
Human Skeletal Remains (2nd edn). Academic Press:
San Diego, CA.
Ortner DJ, Putschar WGJ. 1985. Identification of Pathological
Conditions in Human Skeletal Remains. Smithsonian
Contributions to Anthropology Number 28.
Smithsonian Institution Press: Washington, DC.
Paul LW, Juhl JH. 1962. The Essentials of Roentgen
Interpretation. Harper and Row: New York.
Podgorski M, Robinson B, Weissberger A, Stiel J,
Wang S, Brooks PM. 1988. Articular manifestations
of acromegaly. Australian and New Zealand Journal of
Medicine 18: 28–35.
Reeves GD, Gibbs M, Paulshock BZ, Rosenblum H.
1978. Gigantism with slipped capital femoral epiphysis.
American Journal of Diseases in Children 132:
Resnick D. 1988. Pituitary disorders. In Diagnosis of
Bone and Joint Disorders (Vol. 4, 2nd edn), Resnick D,
Niwayama G (eds). W.B. Saunders Company:
Philadelphia, PA; 2173–2198.
Resnick D, Goergen TG, Niwayama G. 1988. Physical
injury. In Diagnosis of Bone and Joint Disorders
(Vol. 5, 2nd edn), Resnick D, Niwayama G (eds).
W.B. Saunders Company: Philadelphia, PA; 2757–
Robins G, Shute CCD. 1986. Predynastic Egyptian
stature and physical proportions. Human Evolution
Scheithauer BW, Kovacs KT, Stefaneanu L, Horvath
E, Kane LA, Young WF Jr, Lloyd RV, Randall RV,
Davis DH. 1995. The pituitary in gigantism.
Endocrine Pathology 6(3): 173–187.
Scheuer L, Black S. 2000. Developmental Juvenile
Osteology. Academic Press: San Diego, CA.
Smith HB. 1984. Patterns of molar wear in huntergatherers
and agriculturalists. American Journal of
Physical Anthropology 63: 39–56.
Steinbach HL, Obata WG. 1957. The significance of
thinning of the parietal bones. American Journal of
Roentgenology 78(1): 39–45.
Takakura M, Kuroda T. 1998. Morphologic analysis of
dentofacial structure in patients with acromegaly.
The International Journal of Adult Orthodontics and
Orthognathic Surgery 13: 277–288.
Trabelsi M, Ben Hariz M, Monastiri K, Taktak M,
Bennaceur B. 1990. Weaver’s syndrome. Apropos of
a new case. Annales de Pediatrie 37(5): 327–330.
TrotterM, Gleser GC. 1958. A re-evaluation of estimation
of stature based on measurements of stature
taken during life and of long bones after death.
American Journal of Physical Anthropology 16: 79–123.
Whitehead EM, Shalet SM, Davies D, Enoch BA,
Price DA, Beardwell CG. 1982. Pituitary gigantism:
a disabling condition. Clinical Endocrinology 17: 271–
Zakrzewski SR. 2003. Variation in ancient Egyptian
stature and body proportions. American Journal of
Physical Anthropology 121: 219–229.
Zobeck TS. 1983. Postcraniometric Variation Among the
Arikara. Unpublished dissertation. University of
Tennessee, Knoxville, TN.
Gigantism in a Skeleton from Giza 275
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