A probable case of gigantism in a fifth Dynasty skeleton from the

Transcription

International Journal of Osteoarchaeology
Int. J. Osteoarchaeol. 15: 261–275 (2005)
Published online 31 December 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/oa.781
A Probable Case of Gigantism in a
Fifth Dynasty Skeleton from the
Western Cemetery at Giza, 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 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 ß
2004 John Wiley & Sons, Ltd.
Key words: gigantism; acromegaly; pituitary; Giza; Egypt; skeletal
Introduction
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
* Correspondence to: Department of Anthropology, Smithsonian
Institution, P.O. Box 37012, NMNH, MRC 138, Washington DC
20013-7012, USA.
e-mail: [email protected]
Copyright # 2004 John Wiley & Sons, Ltd.
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
Received 20 August 2003
Revised 6 May 2004
Accepted 5 July 2004
D. M. Mulhern
262
gigantism in a female skeleton from Ostrów
Lednicki, in Lednogóra, 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 (Dostálová
et al., 2003) and Japan (Takakura & Kuroda, 1998)
was compared with differences between 2507x
and other Egyptian males using z scores.
Results
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
Gigantism in a Skeleton from Giza
263
Figure 1. Anterior view of left proximal humerus with clear epiphyseal line.
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.
Figure 2. Anterioposterior radiograph of proximal left humerus.
Metric analysis
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
D. M. Mulhern
264
Table1. Maximum long bone lengths and estimated staturea
Bone
Side
Humerus
Radius
Radius
Ulna
Ulna
Fibula
Left
Left
Right
Left
Right
Left
Max. length (cm)
Stature (cm)
39.7
33.1
32.6
34.5
34.4
47.0b
a
189.8
195.3
193.7
193.2
192.9
189.7
Stature estimates for the humerus, radii and ulnae are based on
formulae by Robins & Shute (1986); stature estimate for the fibula
is based onTrotter & Gleser (1958).
b
Maximumfibula lengthwas estimated duetopostmortem damage
to the proximal end of the bone.
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
Table 2. Postcranial measurements for 2507X
Bone
Description
Measurements (mm)
Left
Scapula
Humerus
Radius
Ulna
Innominate
Femur
Fibula
Calcaneus
First metatarsal
Second metatarsal
a
Glenoid breadth
Glenoid height
Midglenoid to inferior anglea
Maximum length
Proximal epiphyseal breadth
Maximum midshaft diameter
Minimum midshaft diameter
Maximum vertical head diameter
Epicondylar breadth
Least circumference of shaft
Maximum length
Maximum head diameter
Anterioposterior midshaft diameter
Mediolateral midshaft diameter
Maximum length
Physiological length
Maximum olecranon breadth
Minimum olecranon breadth
Maximum olecranon width
Anterioposterior shaft diameter
Mediolateral shaft diameter
Least circumference of shaft
Iliac breadth
Pubis length
Ischium length
Anterioposterior subtrochanteric diameter
Mediolateral subtrochanteric diameter
Anterioposterior midshaft diameter
Mediolateral midshaft diameter
Maximum head diameter
Minimum vertical neck diameter
Midshaft circumference
Maximum length
Maximum length
Middle breadth
Maximum length
Maximum length
33
46
170
397
57
24
20
47
75
67
331
26
14
16
345
315
33
26
31
16
14
35
185
96
109
Right
51
75
65
326
27
13
17
344
315
35
25
36
16
15
35
31
34
39
30
52
33
106
470
102
52
79
89
The inferior angle of the scapula is unfused.
42
44
16
37b
51b
idgn
ecec
dd
nb
bl
192
143a
132
59
52
128
80
108
115
58
27
42
37
107
28
111
119
33
Measurement
(mm) 2507X,
5th Dynasty
Cemetery 2500,
Giza
gop
eueu
zyzy
ecmecm
pralv
auau
npr
ftft
fmtfmt
nns
alal
dec
Landmarks
32.6***
34.4***
12.7
29.4*
41.6**
182.3*
133.0**
119.0
57.4
50.0
115.3***
70.2*
95.4*
103.0
48.0*
25.0
38.8***
32.7*
94.0***
21.8
112.9
115.8
28.2
Mean (mm)
Males,
5th
Dynasty
Cemetery
2500,
Giza
5
5
6
5
5
7
6
1
5
6
3
5
5
3
3
4
4
3
3
4
7
6
9
n
b
a
Bilateral measurements are from the left side unless otherwise indicated.
Maximum cranial breadth is affected by the presence of parietal thinning.
Measurement is from the right side.
c
Nasal height was measured from nasion to the inferior border of the nasal aperture.
*P < 0.05.
**P < 0.01.
***P < 0.001
Cranium
Maximum cranial length
Maximum cranial breadth
Bizygomatic diameter
Maxilloalveolar breadth
Maxilloalveolar length
Biauricular breadth
Upper facial height
Minimum frontal breadth
Upper facial breadth
Nasal height
Nasal breadth
Orbital breadth
Orbital height
Biorbital breadth
Interorbital breadth
Frontal chord
Parietal chord
Mastoid length
Mandible
Chin height
Mandibular body height
Mandibular body breadth
Minimum ramus breadth
Maximum ramus breadth
Description
2.3
3.0
2.1
3.5
3.2
0.29
0.67
3.63
2.09
1.83
5.6
3.0
3.5
4.7
6.9
0.0
5.0
2.2
1.0
2.1
1.0
4.7
2.4
3.8
3.8
4.09
3.20
1.57
2.17
2.94
2.00
0.91
3.20
2.05
13.00
1.32
0.79
0.84
1.26
2.26
2.38
z score
4.3
4.2
S.D.
Table 3. Cranial and mandibular measurements for 2507X and Egyptian comparative data
4.0
3.0
2.9
2.7
1.7
1.8
2.0
2.7
1.7
1.8
5.5
6.2
2.4
118.6**
68.4***
96.1***
51.7c**
24.8
39.5
33.0
95.8***
20.9***
111.9
115.7
35.7
6.2
5.0
4.2
3.1
S.D.
185.6
139.2
128.8
62.8
Mean (mm)
Males (mm)
(n ¼ 58)
26th^30th
Dynasty,
Giza
6.52
2.33
1.29
1.39
2.00
4.15
3.94
0.16
0.53
1.13
2.35
3.87
1.03
0.76
0.76
1.23
z score
Mean (mm)
Males
(n ¼ 54)
4th^5th
Dynasty
Deshasheh,
Medum
185
139
127.1 (n ¼16)
32.2 (n ¼ 73)
33.8 (n ¼ 67)
Mean (mm)
Males,
4th^11th
Dynasty
Qau
185
141
131
Mean (mm)
Males
(n ¼ 31)
4th
Dynasty
Sakkarah
265
266
D. M. Mulhern
Figure 3. Frontal view of skull.
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
5 mm (anterioposterior) by 3 mm (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
267
Figure 4. Left lateral 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 2.2 mm. The maximum thickness of
the left tibial midshaft is 1.5 mm. 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 58 mm in diameter. Three or four smaller
depressions are present on the superioposterior
aspect of the right parietal that cover an area
about 51 mm (anterioposterior) by 72 mm
(mediolateral). The morphology, location and
size of the lesions is consistent with parietal
thinning, as opposed to healed trauma. The outer
268
D. M. Mulhern
Figure 6. Superior view of the cranium showing thinness of the
parietal bones.
Figure 5. Superior view of lumbar vertebrae 4 and 5 showing degenerative changes.
table and diploë 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 13 mm in diameter and is raised 10 mm 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
269
the mandibular second and third molars (scores
2–3).
Discussion
Figure 7. Anterior view of the left femur with non-union fracture.
unaligned hypoplastic pits in a band between
2.9 mm and 5.3 mm 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
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 &
Rodrı́guez-Martı́n, 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 12 mm (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.
270
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 & Rodrı́guez-Martı́n, 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 331 mm
and 326 mm 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 (n ¼ 11), 168.8 3.6 cm (n ¼ 16)
and 166.4 5.1 cm (n ¼ 13), respectively, based
on femoral and tibial length. Aufderheide &
Rodrı́guez-Martı́n (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 and Middle Kingdoms, respectively.
D. M. Mulhern
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, Dostálová 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 Dostálová et al. (2003) as
52.56 3.47 mm for the normal group and
57.80 5.65 mm for the acromegalic group
(z ¼ 1.51, ns). Nasal height (n-ns), which is
comparable to N-ANS, is 58 mm for 2507X,
48.0 5.0 mm for the other males from Cemetery 2500, and 51.7 2.7 mm for the 26th–30th
Dynasty males from Giza (Table 3). Nasal
height differs significantly (z ¼ 2.00; P < 0.05)
between 2507X and the Cemetery 2500 males
and also between 2507X and the 26th–30th
Dynasty males (z ¼ 2.33; p < 0.01). Upper facial
height (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 Dynasty
males. Differences are significant between
2507X and the Cemetery 2500 males (z ¼ 2.09;
P < 0.05) and the 26th–30th Dynasty sample
(z ¼ 3.87; P < 0.001).
Dostálová et al. (2003) found that neurocranial
length, measured from nasion (N) to opisthocranion (OP) was 176.32 4.96 mm for the normal
group and 187.49 7.68 mm for the acromegalic
group (z ¼ 2.25; P < 0.05). Maxiumum cranial
length (g-op), a slightly shorter measurement
than neurocranial length, was 192 mm for
2507X, 182.3 4.3 mm for the other males
from Cemetery 2500 (z ¼ 2.26; P < 0.05) and
about 185–186 mm 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.
Dostálová et al. (2003) found that mean
sella turcica diameter was 9.54 1.27 mm for
the normal sample and 12.34 3.74 mm for the
acromegalic sample (z ¼ 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
Dostálová et al. (2003). Sella turcica diameter
differed significantly between 2507X and normal
males (z ¼ 4.30; 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 30.8 4.7 mm and the
mean value for normal males was 24.6 2.8 mm
(z ¼ 2.21; P < 0.05). Chin height (id-gn) was
42 mm for 2507X, 32.6 2.3 mm for males from
Cemetery 2500 (z ¼ 4.09; P < 0.001), and
33.8 mm for Egyptian males from Qau (Table 3).
Values for 2507X and the Qau males were not
compared statistically because standard deviations were not provided.
271
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 & Rodrı́guezMartı́n, 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
272
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 GladykowskaRzeczycka et al. (1998) observed an osteoma that
obliterated the external auditory meatus of a
probable giant from Ostrów 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
Differential diagnosis includes eunuchoid gigantism, which is caused by gonadal failure before
D. M. Mulhern
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–
37 mm 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.
Conclusion
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.
273
Acknowledgements
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.
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