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International Journal of OsteoarchaeologyInt. J. Osteoarchaeol. 15: 261–275 (2005)Published online 31 December 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/oa.781

AProbableCaseofGigantism inaFifth Dynasty SkeletonfromtheWesternCemeteryatGiza,Egypt

D. M. MULHERN*National Museum of Natural History, Smithsonian Institution, Washington DC, USA

ABSTRACT Pituitary gigantism is a rare endocrine disorder caused by excess secretion of growthhormone during childhood. Individuals with this condition exhibit unusually tall stature dueto prolonged growth as well as associated degenerative changes. Continued secretion ofexcess growth hormone during adulthood results in acromegaly, a related condition thatresults 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 Dynastytomb (2494–2345 BC) were excavated in 2001 from Cemetery 2500 in the Western Cemeteryat Giza, Egypt, as part of the Howard University Giza Cemetery Project. This individualexhibits characteristics of pituitary gigantism, including tall but normally-proportioned stature,delayed epiphyseal union, a large sella turcica, advanced arthritis and a transepiphysealfracture of the left femoral head. Additional pathological features, including osteopenia andthinness 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 andacromegalic patients show some tendency toward acromegalic skull morphology. Differentialdiagnosis includes eunuchoid gigantism, Sotos syndrome, Beckwith-Wiedemann syndrome,Marfan syndrome, homocystinuria, Weaver syndrome and Klinefelter syndrome. In conclu-sion, the pathological features associated with this skeleton are more consistent with pituitarygigantism 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

Introduction

Pituitary gigantism is a rare disorder generallycaused by hypersecretion of growth hormone, orsomatotrophin, during childhood. Excess growthhormone causes prolonged stimulation at theendochondral growth plates, resulting in tallstature with normal body proportions. A pituitarytumour can provide the stimulus for the over-production of growth hormone. Onset of the

tumour during adulthood, or continued produc-tion of growth hormone into adulthood, resultsin acromegaly. Acromegaly is characterised byperiosteal apposition and bone overgrowth, par-ticularly of the mandible, hands and feet(Resnick, 1988). If excess growth hormone isproduced during childhood and continues intoadulthood, the features of gigantism and acrome-galy are both expressed.

Acromegaly, the more common of the twoconditions, has been reported in the palaeo-pathological literature, including cases fromEgypt, Illinois and New Mexico (Ortner, 2003).Very few cases of gigantism have been describedin prehistoric skeletons. A probable case of

Copyright # 2004 John Wiley & Sons, Ltd. Received 20 August 2003Revised 6 May 2004Accepted 5 July 2004

* Correspondence to: Department of Anthropology, SmithsonianInstitution, P.O. Box 37012, NMNH, MRC 138, Washington DC20013-7012, USA.e-mail: [email protected]

gigantism in a female skeleton from OstrowLednicki, in Lednogora, Poland, dating to aboutthe 12th to 13th century AD was described byGladykowska-Rzeczycka et al. (1998). This speci-men 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 caseof probable gigantism in a Fifth Dynasty skeleton(2494–2345 BC) from Cemetery 2500 in theWestern Cemetery at Giza, Egypt. In this paper,metric data are compared with data from ancientEgyptian populations and data reported for othercases of gigantism. The pathological features ofthis skeleton are compared with skeletal symp-toms reported in pituitary giants. Differentialdiagnosis is also discussed.

Materials and Methods

The skeletal remains of a large adult male (Burial2507X) were excavated in 2001 from a FifthDynasty mastaba tomb in Cemetery 2500 ofthe Western Cemetery at Giza, Egypt, as partof the Howard University Giza Cemetery Pro-ject. Skeletal analysis was conducted in 2002.This individual is represented by a cranium,mandible and largely complete postcranial skele-ton in fair condition. The cranial base, ribs andarticular ends of the lower long bones exhibitpostmortem fragmentation.

Analysis of sex is based on the morphology ofthe cranium and pelvis, following Buikstra &Ubelaker (1994). Age at death is based primarilyon stages of epiphyseal closure following Scheuer& Black (2000). Secondary age assessment wasbased on cranial suture closure following themethod of Meindl & Lovejoy (1985), as well asdental attrition following Smith (1984). Themorphology of the pubic symphysis and auricularsurfaces were not used for age assessment, due topathological changes.

Craniometric analysis follows Buikstra &Ubelaker (1994). Postcranial measurements areconsistent with definitions from Bass (1987),Moore-Jansen et al. (1994) and Zobeck (1983).Stature was calculated using formulae revised byRobins & Shute (1986) for ancient Egyptians,based on original formulae published by Trotter

& Gleser (1958) for blacks. Stature was calculatedusing the left humerus, both radii, both ulnae andthe left fibula. The length of the left fibula wasestimated due to slight postmortem damage.

Craniometric data for 2507X were comparedwith measurements for the other males fromCemetery 2500, as well as a sample of 26th–30th dynasty males from Giza (Howells, 1989)using z scores. Measurements from Egyptianpopulations from 4th–11th Dynasty Qau (Mor-ant, 1925), 4th–5th Dynasty Medum and 4thDynasty Sakkarah (Morant et al., 1936) were alsocompared with 2507X, but statistical analysis wasnot conducted because standard deviations werenot reported. In addition, the pattern of cranio-metric differences between normal and acrome-galic males from the Czech Republic (Dostalovaet al., 2003) and Japan (Takakura & Kuroda, 1998)was compared with differences between 2507xand other Egyptian males using z scores.

Results

Age and sex

Pelvic and cranial morphology are consistentwith male sex. Although bones are large, muscu-lature is not pronounced, except for bilateralpilastering of the femoral shafts.

Age estimation was complicated by a numberof factors. Hypertrophy of the pubic symphysisand iliosacral joint surfaces obscures age estima-tion based on pelvic morphology, as thesechanges appear to be pathological and notrelated to normal ageing. Epiphyseal closureand cranial suture closure do not provide consis-tent evidence of age at death. The epiphyseallines of the distal radii and ulnae, proximalhumeri, iliac crests and ischial tuberosities arestill grossly visible, suggesting relatively recentfusion. As shown in Figures 1 and 2, the proximalleft humerus shows poor alignment of the epi-physis and diaphysis and still shows evidence ofan epiphyseal line. The inferior three sternalsegments and inferior lumbar rims also exhibitevidence of recent fusion. The rib heads arepartially fused. The left inferior scapular borderis unfused. Anterior rib ends show billowing orflat surfaces. These epiphyseal indicators suggest

262 D. M. Mulhern

Copyright # 2004 John Wiley & Sons, Ltd. Int. J. Osteoarchaeol. 15: 261–275 (2005)

an age of over 20 years, but younger than 27years. The right proximal femur, proximal radiiand ulnae and the distal tibiae and fibulae exhibitcomplete fusion, with no remnant epiphyseallines. The medial clavicles, distal femora andproximal tibiae and fibulae are unobservable dueto postmortem damage.

The sagittal and coronal sutures exhibit com-plete closure endocranially. Partial to completecranial suture closure is also present at the follow-ing landmarks: lambda, obelion, anterior sagittalsuture, bregma, midcoronal suture and pterion.Cranial suture closure suggests a mean age ofabout 45 years for the vault landmarks (age rangeabout 30–60 years) and a mean age of about 40years (age range about 27–52 years) for thelateral-anterior landmarks.

Tooth wear is moderate to pronounced and isconsistent with patterns observed in the 30–40year age range compared with 20 other adoles-cent and adult individuals from this site. Pro-nounced degenerative changes of the pelvis andspine, as well as arthritis of the long bones andgeneralised osteopenia, are present and areusually indicative of more advanced age, but inthis case appear to be part of an overall pattern ofpathological changes and therefore need to beconsidered with caution.

Metric analysis

Maximum length measurements for long bonesand the resulting statures are shown in Table 1.Values for stature range from 189.7 cm for thefibula to 195.3 cm for the left radius. Table 2shows all postcranial measurements. Table 3shows measurements of the cranium and mand-ible for 2507X as well as comparative data forother males from Cemetery 2500 and Egyptianmales from other ancient sites.

The frontal and left lateral views of the skullare shown in Figures 3 and 4, respectively. Ingeneral, cranial and mandibular measurements for2507X were larger than the mean values for

Figure 1. Anterior view of left proximal humerus with clear epiphy-

seal line.

Figure 2. Anterioposterior radiograph of proximal left humerus.

Gigantism in a Skeleton from Giza 263


ancient Egyptian males from several sites. Asshown in Table 3, 13 out of 21 measurementsshow significant differences between 2507X andthe other males from Cemetery 2500. The zscores indicate that for these measurements,2507X exhibits significantly larger values thanthe rest of the sample. Seven out of 16 measure-ments differed significantly between 2507X andthe sample of 26th–30th Dynasty males fromGiza. Measurements represented in both groupsthat are significantly different from 2507Xinclude biauricular breadth, upper facial height,nasal height, orbital height and biorbital breadth.Maximum cranial length and breadth and orbital

Table1. Maximum longbone lengthsand estimated staturea

Bone Side Max. length (cm) Stature (cm)

Humerus Left 39.7 189.8

Radius Left 33.1 195.3

Radius Right 32.6 193.7

Ulna Left 34.5 193.2

Ulna Right 34.4 192.9

Fibula Left 47.0b

189.7

aStature estimates for the humerus, radii and ulnae are based on

formulae by Robins & Shute (1986); stature estimate for the fibula

isbasedonTrotter &Gleser (1958).bMaximumfibula lengthwasestimatedduetopostmortemdamage

to theproximal endof thebone.

Table 2. Postcranialmeasurements for 2507X

Bone Description Measurements (mm)

Left Right

Scapula Glenoidbreadth 33

Glenoidheight 46

Midglenoid to inferioranglea

170

Humerus Maximum length 397

Proximal epiphyseal breadth 57

Maximummidshaftdiameter 24

Minimummidshaftdiameter 20

Maximumverticalheaddiameter 47 51

Epicondylar breadth 75 75

Leastcircumference of shaft 67 65

Radius Maximum length 331 326

Maximumheaddiameter 26 27

Anterioposteriormidshaftdiameter 14 13

Mediolateralmidshaftdiameter 16 17

Ulna Maximum length 345 344

Physiological length 315 315

Maximumolecranonbreadth 33 35

Minimumolecranonbreadth 26 25

Maximumolecranonwidth 31 36

Anterioposterior shaftdiameter 16 16

Mediolateral shaftdiameter 14 15

Leastcircumference of shaft 35 35

Innominate Iliacbreadth 185

Pubis length 96

Ischium length 109

Femur Anterioposterior subtrochanteric diameter 31

Mediolateral subtrochanteric diameter 34

Anterioposteriormidshaftdiameter 39

Mediolateralmidshaftdiameter 30

Maximumheaddiameter 52

Minimumverticalneckdiameter 33

Midshaft circumference 106

Fibula Maximum length 470

Calcaneus Maximum length 102

Middlebreadth 52

Firstmetatarsal Maximum length 79

Secondmetatarsal Maximum length 89

aThe inferiorangle of the scapula is unfused.

264 D. M. Mulhern


Table3.Cranialandmandibularmeasurementsfor2507XandEgyptiancomparativedata

Description

Landmarks

Measurement

Mean(m

m)

nS.D.

zscore

Mean(m

m)

S.D.

zscore

Mean(m

m)

Mean(mm)

Mean(m

m)

(mm)2507X,

Males,

Males(mm)

Males,

Males

Males

5thDynasty

5th

(n¼58)

4th

11th

(n¼54)

(n¼31)

Cemetery2500,

Dynasty

26th^30th

Dynasty

4th^5th

4th

Giza

Cemetery

Dynasty,

Qau

Dynasty

Dynasty

2500,

Giza

Deshasheh,

Sakkarah

Giza

Medum

Cranium

Maximumcraniallength

g�op

192

182.3*

74.3

2.26

185.6

6.2

1.03

185

185

Maximumcranialbreadth

eu�eu

143a

133.0**

64.2

2.38

139.2

5.0

0.76

139

141

Bizygomaticdiameter

zy�zy

132

119.0

1128.8

4.2

0.76

127.1

(n¼16)

131

Maxillo�alveolarbreadth

ecm�ecm

59

57.4

55.6

0.29

62.8

3.1

�1.23

Maxillo�alveolarlength

pr�

alv

52

50.0

63.0

0.67

Biauricularbreadth

au�au

128

115.3***

33.5

3.63

118.6**

4.0

2.35

Upperfacialheight

n�pr

80

70.2*

54.7

2.09

68.4***

3.0

3.87

Minimumfrontalbreadth

ft�ft

108

95.4*

56.9

1.83

2.9

Upperfacialbreadth

fmt�

fmt

115

103.0

30.0

96.1***

2.7

6.52

Nasalheight

n�ns

58

48.0*

35.0

2.00

51.7c**

1.7

2.33

Nasalbreadth

al�al

27

25.0

42.2

0.91

24.8

1.8

1.29

Orbitalbreadth

d�ec

42

38.8***

41.0

3.20

39.5

2.0

1.39

Orbitalheight

37

32.7*

32.1

2.05

33.0

2.7

2.00

Biorbitalbreadth

ec�ec

107

94.0***

31.0

13.00

95.8***

1.7

4.15

Interorbitalbreadth

d�d

28

21.8

44.7

1.32

20.9***

1.8

3.94

Frontalchord

n�b

111

112.9

72.4

�0.79

111.9

5.5

�0.16

Parietalchord

b�l

119

115.8

63.8

0.84

115.7

6.2

0.53

Mastoidlength

33

28.2

93.8

1.26

35.7

2.4

�1.13

Man

dible

Chinheight

id�gn

42

32.6***

52.3

4.09

33.8(n¼67)

Mandibularbodyheight

44

34.4***

53.0

3.20

Mandibularbodybreadth

1612.7

62.1

1.57

32.2(n¼73)

Minimumramusbreadth

37b

29.4*

53.5

2.17

Maximumramusbreadth

51b

41.6**

53.2

2.94

Bilateralm

easurementsarefromtheleftsideunless

otherwiseindicated.

aMaximumcranialbreadthisaffectedbythepresenceofparietalthinning.

bMeasurementisfromtherightside.

cNasalheightwasmeasuredfromnasiontotheinferiorborderofthenasalaperture.

*P<0.05.

**P<0.01.

***P

<0.001



breadth are significantly different between 2507Xand the Cemetery 2500 males, but not between2507X and the 26th–30th Dynasty males. Inter-orbital breadth is significantly different between2507X and the 26th–30th Dynasty males, but notbetween 2507X and the Cemetery 2500 males.Minimum frontal breadth, chin height, mandib-ular body height, minimum ramus breadth andmaximum ramus breadth are significantly differ-ent between 2507X and the Cemetery 2500males. These measurements were not reportedin the 26th–30th Dynasty sample. Finally, upperfacial breadth is significantly different between2507X and the 26th–30th Dynasty sample; onlyone comparative individual was available for theCemetery 2500 sample, so a z score was notcalculated.

Description of pathological changes

The cranium exhibits a small, lytic lesion on theendocranial surface of the clivus. The lesion is5 mm (anterioposterior) by 3 mm (mediolateral)with slightly raised edges. A spicule of bonebisects the inside of the lesion. The pituitaryarea appears grossly and radiologically normalwith no lytic destruction, but the dorsum sellae isporous. Gross observation was possible due tosome postmortem damage to the cranial base.The anterioposterior diameter of the sella turcicais 15 mm.

Pronounced degenerative changes are presentthroughout the skeleton. Both shoulder jointsexhibit arthritic lipping and erosive lesions.Both elbow joints show lipping and complete

Figure 3. Frontal viewof skull.

266 D. M. Mulhern


subchondral destruction of the radiocapitularjoints as well as the lateral half of the ulnar andtrochlear articular surfaces. Wrist joints, carpo-metacarpal joints and metacarpophalangeal jointsalso show moderate to severe arthritic lippingand erosion. The left hip joint shows lipping andcomplete subchondral destruction of the femoralhead. Arthritic erosion and porosity cover theposterior surface of the left patella, which alsoexhibits atrophy of the medial half of the bone.Pronounced arthritic changes, including profuselipping and some erosion, also affect the left andright tarsals.

Vertebral apophyseal joints show lipping, por-osity and erosion. Advanced degenerative jointdisease is present in the spine. Vertebral osteo-phytes with curved spicules and marginal porosityare present on the superior rims of C4–C6, thesuperior and inferior rims of T5–T11 and L3–L5.Porosity is also present on the superior end platesof C4–C6 and the superior and inferior rims of T5–T11 and L3–L5. Porosity and erosion of the super-ior L4 and L5 end plates are shown in Figure 5.

Vertebral osteophytes with elevated rims are pre-sent on the superior and inferior rims of T12–L2.Schmorl’s nodes are present on T12–L5. Thefourth and fifth thoracic vertebrae exhibit superiorend plate depressions without wedging, and T10and T11 show superior end plate depressions withwedging, resulting in slight kyphosis.

The entire skeleton exhibits general osteopeniawith cortical thinning. This is illustrated in theradiograph of the proximal humerus (Figure 2).The maximum thickness of the left humeral mid-shaft cortex is 2.2 mm. The maximum thickness ofthe left tibial midshaft is 1.5 mm. As shown inFigure 6, the cranium exhibits biparietal thinning.A large depression is present on the superiopos-terior aspect of the left parietal that measuresabout 58 mm in diameter. Three or four smallerdepressions are present on the superioposterioraspect of the right parietal that cover an areaabout 51 mm (anterioposterior) by 72 mm(mediolateral). The morphology, location andsize of the lesions is consistent with parietalthinning, as opposed to healed trauma. The outer

Figure 4. Left lateral viewof skull.



table and diploe are involved and the inner table isspared.

The left femur exhibits a subcapital fracturewith non-union (Figure 7). The femoral head isnormal in shape, but is completely separated fromthe rest of the femur. The fractured surface of thefemoral head shows some sclerosis. The subchon-dral surface of the femoral head shows completedestruction due to arthritic erosion. The neck isno longer present and the shaft shows extensivehealing in the location of the neck base. Theproximal shaft is deformed, including probabledisplacement of the lesser trochanter. The extentof healing and deformation suggests that thiscondition existed for some time. It is likely thatthis represents a transepiphyseal fracture thatoccurred prior to full closure of the growth plate.

Healed fractures of the anterior third of the leftsixth and seventh ribs are also present. The left

third and right second metatarsal shafts exhibitprobable healed fractures. All of the left meta-tarsal shafts, the right second, third and fourthmetatarsal shafts and the dorsal surfaces of thefirst to third proximal toe phalanges also showperiostitis. Periostitis covers the middle and distalthirds of the left fibular shaft and the medialaspect of the left middle and distal tibial shaft.

A large osteoma is present on the left zygo-matic arch (Figure 4). The radiograph shows thatthe structure comprises of uniform, dense bone. Itis 13 mm in diameter and is raised 10 mm abovethe normal bone surface.

Dental pathology includes several cariouslesions and abscesses. The mesial half of the rightmandibular first molar crown shows a large car-ious lesion and is associated with a periapicalabscess with facial drainage. The mandibularright lateral incisor shows complete cariousdestruction of the crown and is associated witha periapical abscess with facial and lingual drai-nage. The mandibular left second molar shows anabscess exposing the buccal aspect of the distalroot. The mandibular right canine exhibits

Figure 5. Superior view of lumbar vertebrae 4 and 5 showing de-

generative changes.

Figure 6. Superior view of the cranium showing thinness of the

parietal bones.

268 D. M. Mulhern


unaligned hypoplastic pits in a band between2.9 mm and 5.3 mm from the cervico-enameljunction. Slight calculus formation is present onthe mandibular teeth.

The maxillary dentition shows antemortemloss of the left second premolar, both first molarsand the right second molar. Using Smith’s (1984)eight stage system for dental attrition, dentalwear is moderate for the right third molar(score 4) and advanced for the anterior dentitionand premolars (scores 6–7). Antemortem loss ofthe left first mandibular molar is present. Dentalwear is moderate to advanced for the anteriorteeth and premolars (scores 4–6) and slight for

the mandibular second and third molars (scores2–3).

Discussion

Skeleton 2507X has an unusual suite of patholo-gical features, a number of which are related to acondition that resulted in abnormal skeletalgrowth. The combination of an apparent delayin epiphyseal fusion, tall stature with normalproportions and superimposed degenerativechanges is indicative of a growth-related dysfunc-tion such as pituitary gigantism.

Pituitary gigantism is caused by overproduc-tion of growth hormone, which stimulates carti-laginous growth at the growth plates, ultimatelyresulting in increased linear growth. The normalperiod of epiphyseal fusion is extended due tothe suppression of gonadotropin production(Aegerter & Kirkpatrick, 1975; Aufderheide &Rodrıguez-Martın, 1998), resulting in increasedgrowth and immature skeletal age compared tochronological age. Excess growth hormone canbe caused by a pituitary tumour, usually a benignadenoma, but occasionally by diffuse hyperplasia(Aegerter & Kirkpatrick, 1975). A study of 19cases of gigantism by Scheithauer et al. (1995)included 18 adenomas, 22% of which weregrossly invasive, and one case of pure hyperplasia.

If a tumour causes the condition, the sellaturcica may show evidence of enlargement andlytic destruction (Ortner & Putschar, 1985).Gross observation and radiographic examinationshowed a large anterioposterior sella turcica dia-meter (15 mm) and porosity of the dorsum sellae.Gross observation was possible due to postmor-tem damage to the cranial base. The normalrange of anterioposterior diameter measurementsfor the sella turcica is 8 to 12 mm (Paul & Juhl,1962). The sella turcica of 2507X is slightly largerthan normal, but no lytic destruction is present.Although clear evidence of a pituitary lesionwould facilitate diagnosis, the size and morphol-ogy of the sella turcica can be normal in cases ofpituitary hyperplasia (Ortner, 2003). It isunknown whether the lytic lesion observed onthe clivus is related to this condition. No refer-ence to any similar lesions was found in theliterature.

Figure 7. Anterior viewof the left femur with non-union fracture.



Skeletal age of this individual is between 20–26 years based on epiphyseal fusion. This agerange is not consistent with cranial suture closureand tooth wear, which suggest an age over 30years. This discrepancy suggests the presence ofa growth abnormality, where epiphyseal fusion isdelayed, so this individual is probably at least inhis middle to late 20s, or possibly as old as early30s, with an age range of 25–35 years. Irregularepiphyseal closure can also lead to asymmetricgrowth (Aufderheide & Rodrıguez-Martın, 1998).The radii and ulnae were the only long boneswith measurable maximum lengths from bothsides. The ulnae did not exhibit asymmetry.The maximum lengths of the radii were 331 mmand 326 mm for the left and right sides, respec-tively.

Stature estimates for individual 2507X rangefrom 189.7 to 195.3 cm, with an average of192.4 cm (Table 1). Statures of pituitary giantswho lived during the 1700s–1900s were reportedby Gladykowska-Rzeczycka et al. (1998) andWhitehead et al. (1982). Adult male stature varieswidely, ranging from 185 cm to 272 cm for 16individuals. Stature for individual 2507X is at thelower end of this range, but also must be con-sidered in the context of ancient Egyptian stature.Robins & Shute (1986) reported average malestature of 168.7 cm using the femur and 169.4 cmusing the humerus in a sample of predynasticskeletons from Naqada. Zakrzewski (2003) pro-vided stature estimates for Egyptians from varioustime periods using the formulae revised forancient Egyptians presented by Robins & Shute(1986). Early Dynastic, Old Kingdom and Mid-dle Kingdom males had mean statures of169.6� 5.1 cm (n¼ 11), 168.8� 3.6 cm (n¼ 16)and 166.4� 5.1 cm (n¼ 13), respectively, basedon femoral and tibial length. Aufderheide &Rodrıguez-Martın (1998) defined gigantic statureas three or more standard deviations above themean stature of the population. The stature of192.4 cm for skeleton 2507X is greater than threestandard deviations above the mean staturesreported by Zakrzewski (2003) for ancientEgyptian groups. Stature comparisons between2507X and each of these population means arehighly significantly different (P< 0.001), with zscores of 4.47, 6.56 and 5.10 for the EarlyDynastic, Old and Middle Kingdoms, respectively.

It is also important to note that the amount ofskeletal overgrowth in gigantism depends on theage of onset of the condition. If the conditionbegins at a young age, growth is extreme, but ifonset is closer to puberty, increased growth is notas pronounced (Resnick, 1988). Skeleton 2507Xshows skeletal growth at the lower end of therange for modern giants, suggesting onset in laterchildhood.

Persistence of growth hormone excess intoadulthood can result in acromegaly. The skeletaleffects of acromegaly include bone overgrowth inthe skull, hands, feet and vertebral bodies(Resnick, 1988). This leads to exaggerated fea-tures, particularly the protrusion of the mandibleand supraorbital area. Individual 2507X doesexhibit a large skull, but more detailed compara-tive data are needed to determine whether apattern typical of acromegaly is present.

In a comparative cephalometric study includ-ing 26 acromegalic males and 50 normal malesfrom the Czech Republic, Dostalova et al. (2003)found that acromegalic patients showedincreased facial height, neurocranial length, man-dibular ramus and mandibular body lengths.They also found increased anterioposterior sellaturcica length. Mandibular ramus and bodylengths were not measured for 2507X due topostmortem damage, but other measurementsare compared below between 2507X and clinicaldata using z scores.

Anterior upper face height, measured fromnasion (N) to the anterior nasal spine (ANS)was reported by Dostalova et al. (2003) as52.56� 3.47 mm for the normal group and57.80� 5.65 mm for the acromegalic group(z¼ 1.51, ns). Nasal height (n-ns), which iscomparable to N-ANS, is 58 mm for 2507X,48.0� 5.0 mm for the other males from Ceme-tery 2500, and 51.7� 2.7 mm for the 26th–30thDynasty males from Giza (Table 3). Nasalheight differs significantly (z¼ 2.00; P< 0.05)between 2507X and the Cemetery 2500 malesand also between 2507X and the 26th–30thDynasty males (z¼ 2.33; p< 0.01). Upper facialheight (n-pr) was 80 mm for 2507X, 70.2�4.7 mm for other males from Cemetery 2500,and 68.4� 3.0 mm for 26th–30th Dynastymales. Differences are significant between2507X and the Cemetery 2500 males (z¼ 2.09;

270 D. M. Mulhern


P< 0.05) and the 26th–30th Dynasty sample(z¼ 3.87; P< 0.001).

Dostalova et al. (2003) found that neurocraniallength, measured from nasion (N) to opisthocra-nion (OP) was 176.32� 4.96 mm for the normalgroup and 187.49� 7.68 mm for the acromegalicgroup (z¼ 2.25; P< 0.05). Maxiumum craniallength (g-op), a slightly shorter measurementthan neurocranial length, was 192 mm for2507X, 182.3� 4.3 mm for the other malesfrom Cemetery 2500 (z¼ 2.26; P< 0.05) andabout 185–186 mm for other ancient Egyptianmales (Table 3). No significant differences wereobserved between 2507X and the 26th–30thDynasty Egyptian males in maximum craniallength.

Dostalova et al. (2003) found that meansella turcica diameter was 9.54� 1.27 mm forthe normal sample and 12.34� 3.74 mm for theacromegalic sample (z¼ 2.20; P< 0.05). Thesella turcica diameter of 2507X is 15 mm. Com-parative data for other Egyptian males was notavailable, so comparisons were made with thenormal and acromegalic values reported byDostalova et al. (2003). Sella turcica diameterdiffered significantly between 2507X and normalmales (z¼ 4.30; P< 0.001), but no significantdifference was found between 2507X andacromegalic males.

Takakura & Kuroda (1998) reported similarresults in a sample of 28 acromegalic males and23 normal males from Japan. They observedincreased facial height, mandibular length andmandibular ramus length as well as mandibularheight in acromegalic patients compared with anormal sample. Mandibular height was measuredfrom supramentale (B) to menton (ME). This is aslightly shorter measurement than chin height(id-gn), but generally measures the height of theanterior mandible. In the Japanese study, themean value for mandibular height (B-ME) inacromegalic males was 30.8� 4.7 mm and themean value for normal males was 24.6� 2.8 mm(z¼ 2.21; P< 0.05). Chin height (id-gn) was42 mm for 2507X, 32.6� 2.3 mm for males fromCemetery 2500 (z¼ 4.09; P< 0.001), and33.8 mm for Egyptian males from Qau (Table 3).Values for 2507X and the Qau males were notcompared statistically because standard devia-tions were not provided.

Although the cranium and mandible of 2507Xdo not exhibit the exaggerated characteristicsassociated with advanced acromegaly, compara-tive measurements reveal a pattern suggestingacromegalic morphology. Facial height, craniallength and mandibular height are increased in2507X compared with normal Egyptian males.Also, the anterioposterior diameter of sella tur-cica is long compared with the range for normalindividuals, a characteristic found in acromegalicindividuals.

Prolonged linear growth coupled with in-creased muscular weakness leads to degenerativechanges in gigantism (Aufderheide & Rodrıguez-Martın, 1998). In addition, excess secretion ofgrowth hormone increases the risk of osteoar-thritis (Boullion, 1991). Peripheral and axial jointabnormalities have been observed in many casesof gigantism (Whitehead et al., 1982; Podgorskiet al., 1988; Gladykowska-Rzeczycka et al., 1998).Individual 2507X exhibits pronounced degenera-tive changes throughout the postcranial skeleton,including osteoarthritis of all major joints andadvanced degenerative joint disease of the spine.The pubic symphysis and iliosacral joints showdegenerative changes superimposed on hypertro-phy of the joint surfaces.

Conditions characterised by increased growthhormone, such as gigantism and acromegaly, areusually associated with increased bone mass(Frost, 1998). This could be due to stimulationof bone turnover which results in a net positivebone balance, despite the fact that high remodel-ling rates usually result in bone loss over time(Boullion, 1991). It is also possible that biome-chanical factors are important. For example,increased bone mass could result indirectly fromthe stimulation of bone growth and increasedbody weight caused by growth hormone (Frost,1998).

In some cases of gigantism and acromegaly,osteopenia results from a decrease in oestrogensand androgens due to deficient basophilic cellfunction (Aegerter & Kirkpatrick, 1975). Disor-ders such as eunuchoidism, a type of male hypo-gonadism, are sometimes found in individualswith gigantism or acromegaly (Musa et al.,1972). Lower bone mineral density in the spineand femur has been observed in hypogonadalacromegalic patients compared with eugonadal



acromegalic patients (Kayath & Vieira, 1997;Lesse et al., 1998). Individual 2507X shows pro-nounced osteopenia of the axial and appendicularskeleton, possibly indicating insufficient sex hor-mone production.

The aetiology of thinness of the parietal boneshas been a matter of some debate. It is unclearwhether this condition is progressive and due toage-related bone loss or whether it is static andcaused by a developmental abnormality.Steinbach & Obata (1957) suggested that bothsituations may exist based on several case studies,including one case of documented thinning overtime in an elderly female and two cases of parietalthinning in males diagnosed with gonadal insuf-ficiency. Biparietal thinning has been describedin a number of ancient Egyptian crania, includingfive by Lodge (1967), one by Ortner & Putschar(1985) and one by Barnes (1994) dating from theNinth and Twelfth Dynasties as well as the NewEmpire Period.

The non-union fracture of the left femoralhead may have occurred during growth, since aprolonged growth period increases joint vulner-ability. The capital femoral epiphyseal plate ismore susceptible to shearing stress duringgrowth, when a shortage of sex hormone com-pared with growth hormone causes a widening ofthe growth plate. Slipped femoral capital epiphy-sis has been associated with endocrine diseasesincluding gigantism and acromegaly (Reeves et al.,1978; Resnick et al., 1988; Feydy et al., 1997).

A large osteoma of the zygomatic arch wasobserved on skeleton 2507X. This is not a patho-logical feature commonly associated with growthabnormalities like gigantism, but Gladykowska-Rzeczycka et al. (1998) observed an osteoma thatobliterated the external auditory meatus of aprobable giant from Ostrow Lednicki.

The possible healed metatarsal fractures andperiostitis are probably indirectly related to theoverall observed condition. The metatarsals showsevere osteopenia and were probably susceptibleto trauma and related infection.

Differential diagnosis

Differential diagnosis includes eunuchoid gigant-ism, which is caused by gonadal failure before

puberty. In males, this condition results inincreased stature due to delayed epiphysealfusion, although not as extreme as that observedin pituitary gigantism. In addition, the lower halfof the body shows greater growth than the upperhalf (Aegerter & Kirkpatrick, 1975). Bones arelong and tubular and the condition may beassociated with osteoporosis and lack of normalmuscle development (Chew, 1991).

The stature of skeleton 2507X is not extremecompared with modern pituitary giants, althoughstature is very tall compared with other ancientEgyptians. The lower half of the body does notexhibit more pronounced growth compared withthe upper half based on stature estimates of thefibula compared with the humerus, radius andulna. In general, bones show less muscular devel-opment than expected for an individual of thissize, except for the femora. Osteopenia is presentthroughout the skeleton. Thinness of the parietalbones, which was noted in two cases of hypogo-nadism by Steinbach & Obata (1957), is alsopresent. In a study of 30 males with eunuchoid-ism, radiographic analysis showed normal skullshape, small sella turcica dimensions, small mas-toid processes and thin cranial bones (Kosowicz& Rzymski, 1975). Skull 2507X does exhibit thinparietal bones, but does not have a small mastoidprocess or sella turcica. Mastoid process lengthfor 2507X is 33 mm, within the range of 24–37 mm observed for the nine other adult malesfrom Cemetery 2500. The length of the sellaturcica is slightly higher than the normal range.In summary, some of the features of this skeletonare also consistent with eunuchoid gigantism.Hypogonadism can exist along with gigantism,so it is possible that both conditions werepresent.

In addition to endocrine abnormalities, anumber of syndromes are associated with accel-erated growth and tall stature, including Sotossyndrome, Beckwith-Wiedemann syndrome,Marfan syndrome, homocystinuria, Weaver syn-drome and Klinefelter syndrome (Eugster &Pescovitz, 1999). The clinical features of thesesyndromes differ from those associated withendocrine disorders. For example, several areassociated with advanced skeletal age, asopposed to delayed skeletal maturation, includ-ing Sotos, Beckwith-Wiedemann and Weaver

272 D. M. Mulhern


syndromes (Goodman & Gorlin, 1983; Trabelsiet al., 1990; Melo et al., 2002). Marfan syndromeis characterised by overgrowth of the lower halfof the skeleton compared with the upper half,and elongated limbs compared with the trunk(Goodman & Gorlin, 1983; Goldman, 1988).Homocystinuria can be characterised by anincreased or decreased rate of skeletal maturationand is also associated with osteoporosis, codfishvertebrae and calcified spicules in the distalradius and ulna (Goodman & Gorlin, 1983;Goldman, 1988). Klinefelter syndrome, a formof male hypogonadism caused by a chromosomalabnormality, can be associated with delayedskeletal maturation as well as decreased craniallength and breadth, short metacarpals, radio-ulnar synostosis and accessory epiphyses(Kosowicz & Rzymski, 1975; McAlister, 1988).It is unlikely that the pathological features of2507X were caused by any of these syndromes.

Conclusion

This study describes a Fifth Dynasty skeleton of alarge male from the Western Cemetery at Giza,Egypt, probably in his late 20s or early 30s, withmetric and pathological features consistent withpituitary gigantism. The combination of tall sta-ture, proportional growth, delayed epiphysealunion and a large sella turcica are consistentwith a pituitary growth abnormality. Pathologicalchanges superimposed on the skeleton, includingadvanced arthritis and a transepiphyseal fractureof the left proximal femur, further support thisdiagnosis. Additional pathological features,including osteopenia and thinness of the parietalbones, may be related to hypogonadism, a con-dition sometimes associated with gigantism.Comparative measurements of the cranium andmandible show that a tendency toward acrome-galic morphology was also present, which meansthat the effects of excess growth hormone experi-enced during growth persisted into adulthood.

Pituitary gigantism is a rare condition that hasnot been widely documented in ancient skeletalremains. The rarity of this disorder combinedwith the great antiquity of skeleton 2507X makethis case an important contribution to the palaeo-pathological literature.

Acknowledgements

I would like to thank Dr Ann Macy Roth, thedirector of the Howard University Giza Ceme-tery Project, as well as Dr William B. Hafford andDr Pia-Kristina Anderson, the archaeologistswho conducted the excavation of tomb 2507X.I also thank Nicole Moss, for her assistanceduring the skeletal examination. I am grateful toDr Azza Sarry el-Din and her staff for providingaccess to the laboratory facility at Giza and forconducting the radiographic documentation.Finally, I am indebted to Dr Zahi Hawass andthe Permanent Committee of the Supreme Coun-cil for Antiquities for arranging permission tostudy the human remains from Cemetery 2500at Giza. The skeletal analysis of the remains fromCemetery 2500 at Giza was funded by theInstitute for Bioarchaeology.

References

Aegerter E, Kirkpatrick JA. 1975. Orthopedic Diseases.Physiology, Pathology, Radiology (4th edn). WBSaunders: Philadelphia, PA.

Aufderheide AC, Rodrıguez-Martın C. 1998. TheCambridge Encyclopedia of Human Paleopathology.Cambridge University Press: Cambridge.

Barnes E. 1994. Developmental Defects of the Axial Skeleton inPaleopathology. University Press of Colorado: Niwot,CO.

Bass WM. 1987. Human Osteology: A Laboratory and FieldManual (3rd edn). Special Publication No. 2. Mis-souri Archaeological Society, Inc.: Columbia, MO.

Boullion R. 1991. Growth hormone and bone. HormoneResearch 36(Suppl. 1): 49–55.

Buikstra JE, Ubelaker DH. 1994. Standards for DataCollection from Human Skeletal Remains. ArkansasArchaeological Survey Research Series No. 44:Fayetteville, AR.

Chew FS. 1991. Radiologic manifestations in themusculoskeletal system of miscellaneous endocrinedisorders. Radiological Clinics of North America 29(1):135–147.

Dostalova S, Sonka K, Smahel Z, Weiss V, Marek J.2003. Cephalometric assessment of cranial abnorm-alities in patients with acromegaly. Journal of Cranio-Maxillofacial Surgery 31: 80–87.

Eugster EA, Pescovitz OH. 1999. Commentary: Gi-gantism. Journal of Clinical Endocrinology and Metabolism84(12): 4379–4384.



Feydy A, Carlier RY, Mompoint D, Rougereau G, PatelA, Valee C. 1997. Bilateral slipped capital femoralepiphysis occurring in an adult with acromegalicgigantism. Skeletal Radiology 26: 188–190.

Frost HM. 1998. Could some biomechanical effectsof growth hormone help to explain its effects onbone formation and resorption? Bone 23(5): 395–398.

Gladykowska-Rzeczycka JJ, Smiszkiewicz-SkwarskaA, Sokol A. 1998. A giant from Ostrow Lednicki(XII–XIII c), Dist. Lednogora, Poland. MankindQuarterly 39: 147–172.

Goldman AB. 1988. Collagen diseases, epiphysealdysplasias, and related conditions. In Diagnosis ofBone and Joint Disorders (Vol. 5, 2nd edn), Resnick D,Niwayama G (eds). W.B. Saunders Company: Phi-ladelphia, PA; 3374–3441.

Goodman RM, Gorlin RJ. 1983. The Malformed Infantand Child. Oxford University Press: Oxford.

Howells WW. 1989. Skull shapes and the map:craniometric analyses in the dispersion of modernHomo. Papers of the Peabody Museum of Archaeology andEthnology. Harvard University, Vol. 79. HarvardUniversity Press: Cambridge, MA.

Kayath MJ, Vieira JG. 1997. Osteopenia occurs in aminority of patients with acromegaly and is pre-dominant in the spine. Osteoporosis International 7(3):226–230.

Kosowicz J, Rzymski K. 1975. Radiological features ofthe skull in Klinefelter’s syndrome and male hypo-gonadism. Clinical Radiology 26: 371–378.

Lesse GP, Fraser WD, Farquharson R, Hipkin L, VoraJP. 1998. Gonadal status is an important determi-nant of bone density in acromegaly. Clinical Endo-crinology 48: 59–65.

Lodge T. 1967. Thinning of the parietal bones in earlyEgyptian populations and its aetiology in the lightof modern observations. In Diseases in Antiquity,Brothwell D, Sandison AT (eds). CC Thomas:Springfield, IL, 405–412.

McAlister WH. 1988. Osteochondrodysplasias, dys-ostoses, chromosomal aberrations, mucopolysac-charidoses and mucolipidoses. In Diagnosis of Boneand Joint Disorders (Vol. 5, 2nd edn), Resnick D,Niwayama G (eds). W.B. Saunders Company: Phi-ladelphia, PA; 3442–3515.

Meindl RS, Lovejoy CO. 1985. Ectocranial sutureclosure: a revised method for the determination ofskeletal age at death based on the lateral-anteriorsutures. American Journal of Physical Anthropology 68:57–66.

Melo DG, Acosta AX, Salles MA, Pina-Neto JM,Castro JDV, Santos AC. 2002. Sotos syndrome

(cerebral gigantism): analysis of 8 cases. Arquivos deneuro-psiquiatria 60(2-A): 234–238.

Morant GM. 1925. A study of Egyptian craniologyfrom Prehistoric to Roman times. Biometrika 17(1/2):1–52.

Morant GM, Collett M, Adyanthaya NK. 1936. Abiometric study of the human mandible. Biometrika28(1/2): 84–122.

Moore-Jansen PM, Ousley S, Jantz RL. 1994. DataCollection Procedures for Forensic Skeletal Material (3rdedn). Report of Investigations no. 48. University ofTennessee: Knoxville.

Musa BU, Paulsen CA, Conway MJ. 1972. Pituitarygigantism: Endocrine studies in a subject withhypergonadotropic hypogonadism. American Journalof Medicine 52: 399–405.

Ortner DJ. 2003. Identification of Pathological Conditions inHuman Skeletal Remains (2nd edn). Academic Press:San Diego, CA.

Ortner DJ, Putschar WGJ. 1985. Identification of Patho-logical Conditions in Human Skeletal Remains. Smithso-nian Contributions to Anthropology Number 28.Smithsonian Institution Press: Washington, DC.

Paul LW, Juhl JH. 1962. The Essentials of RoentgenInterpretation. Harper and Row: New York.

Podgorski M, Robinson B, Weissberger A, Stiel J,Wang S, Brooks PM. 1988. Articular manifestationsof acromegaly. Australian and New Zealand Journal ofMedicine 18: 28–35.

Reeves GD, Gibbs M, Paulshock BZ, Rosenblum H.1978. Gigantism with slipped capital femoral epi-physis. American Journal of Diseases in Children 132:529–530.

Resnick D. 1988. Pituitary disorders. In Diagnosis ofBone 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. Physi-cal injury. In Diagnosis of Bone and Joint Disorders(Vol. 5, 2nd edn), Resnick D, Niwayama G (eds).W.B. Saunders Company: Philadelphia, PA; 2757–3008.

Robins G, Shute CCD. 1986. Predynastic Egyptianstature and physical proportions. Human Evolution1(4): 313–324.

Scheithauer BW, Kovacs KT, Stefaneanu L, HorvathE, 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 JuvenileOsteology. Academic Press: San Diego, CA.

Smith HB. 1984. Patterns of molar wear in hunter-gatherers and agriculturalists. American Journal ofPhysical Anthropology 63: 39–56.

274 D. M. Mulhern


Steinbach HL, Obata WG. 1957. The significance ofthinning of the parietal bones. American Journal ofRoentgenology 78(1): 39–45.

Takakura M, Kuroda T. 1998. Morphologic analysis ofdentofacial structure in patients with acromegaly.The International Journal of Adult Orthodontics andOrthognathic Surgery 13: 277–288.

Trabelsi M, Ben Hariz M, Monastiri K, Taktak M,Bennaceur B. 1990. Weaver’s syndrome. Apropos ofa new case. Annales de Pediatrie 37(5): 327–330.

Trotter M, Gleser GC. 1958. A re-evaluation of estima-tion 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: 271–277.

Zakrzewski SR. 2003. Variation in ancient Egyptianstature and body proportions. American Journal ofPhysical Anthropology 121: 219–229.

Zobeck TS. 1983. Postcraniometric Variation Among theArikara. Unpublished dissertation. University ofTennessee, Knoxville, TN.



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