GIGANTISM AND ACROMEGALY:

REPORT OF A CASE AND REVIEW

OF THE LITERATURE
Alma R. George, MD, Meer Deen, DPM, and Floyd Atkins, DPM
Detroit, Michigan

A case of focal gigantism with concomitant

acromegaly of the great hallux and second
digit is reported. A review of pertinent literature is presented.

Gigantism or acromegaly results from the excessive secretion of human growth hormone
caused by an acidophilic adenoma of the pituitary,
less'commonly by a chromophobe adenoma and,
rarely, by a histologically normal pituitary. When
the condition arises after fusion of the epiphyseal
plate, it is referred to as acromegaly.
Although by the time the diagnosis is made, the
patient almost always has a growth-hormonesecreting adenoma, the condition may arise from
prolonged stimulation by growth-hormone-release
stimulating factor(s) or a deficiency of growthhormone-release inhibitory hormone, produced by
cells of the hypothalamus. Thus, several reports
have suggested that the secretion of growth hormone is not always autonomous in patients with
acromegaly, but changes with stimuli that increase
or suppress the secretion of the hormone and are
thought to act via the hypothalamus.' More interesting, levels of growth hormones show paradoxi-

From Kirwood General Hospital, Detroit, Michigan. Requests for reprints should be addressed to Dr. Alma R.
George, Chief of Medical Staff, Kirwood General Hospital,
4059 W. Davidson, Detroit, Ml 48238.

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cal responses in acromegalics as compared with

normal subjects. For example, dopaminergic
stimulation normally results in a rise of serum
growth hormone whereas the administration of the
dopamine agonist, bromocriptine, often depresses
serum levels of growth hormone in acromegalics,2
an effect that has been utilized in medical management of this condition.
Hypersecretion of growth hormones prior to
closure of the epiphyses leads to proportional
growth of bone; both length and width of bone are
increased. Hypersecretion after closure of epiphyses leads to periosteal overgrowth and cortical
thickening. Bone overgrowth and soft tissue
thickening lead to characteristic coarsening of facial features. The hands are widened and the fingers become broad. Similar changes occur in the
feet, requiring a larger shoe size. Erosion of articular surfaces occurs and joint complaints are common. Hypertension is not uncommon. The skin is
thickened with increased sweating and females
may note hypertrichosis. Galactorrhea may also
be present.
Skull x-ray films show cortical thickening, enlargement of the frontal sinuses, and enlargement
and erosion of the sella turcica. X-ray examination
of the hands and feet shows tufting of the terminal
phalanges and soft-tissue thickening. Glucose tolerance test usually yields abnormal results. EleContinued on page 1106

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GIGANTISM AND ACROMEGALY

Continued from page 1104

vated serum inorganic phosphate has been used as

an index of active acromegaly, but is now recognized as an imprecise reflection of growth hormone. The measurement of plasma human growth
hormone concentration by radioimmunoassay is
the most direct and precise means of assessing increased secretions of growth hormone.

CASE REPORT
A 54-year-old, black, obese woman presented
to Family Health Center with the chief complaint
that her right foot had been getting larger and was
painful whenever she wore shoes. The patient further stated that the big toe and second toe of her
right foot had been exceptionally large since birth.
She had worn a special shoe until age 12 years,
when she discontinued wearing special shoes upon

departing from the South. She described purchasing a pair of shoes to fit the normal-sized left foot
and stretching or at times cutting the right shoe to
accommodate the abnormally large right foot. She
said that within the past ten years the soft tissue of
her right foot had increased in size. The patient
denied any knowledge of this condition existing in
any other family members; her medical history
included hypertension for the previous ten years
and osteoarthritis. The patient denied having infectious or systemic diseases but did have the
normal childhood illnesses. Surgical history included a hysterectomy in 1969. The patient has no
known allergies and is presently taking sulindac
(Clinoril) for an arthritic condition. Traumatic injury and family histories were unremarkable.

Physical Examination
Physical examination revealed a 54-year-old
female, height, 5 feet 7 in; weight, 241 lb; temperature, 97.80 F; pulse, 88 beats/min; and blood pressure, 150/100 mmHg left and 150/94 mmHg right.
The skin was clear with light hair growth; neurological examination revealed deep tendon reflexes
of the left extremity, within normal limits, and no
pathological reflexes were noted, bilaterally. Vascular examination revealed strong posterior tibial
pulses, bilaterally; dorsalis pedis pulse of the right
foot was nonpalpable, secondary to increase in
soft tissue. Nail beds were pink; pitting edema was
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noted at ankles and forefoot, bilaterally. Muscle

strength of lower extremity exhibited no abnormality. Range of motion was decreased in hip, knee,
ankle, subtalar, midtarsal joints, bilaterally, first
metatarsophalangeal and proximal interphalangeal
joints of right foot. The lower extremity measurements revealed circumference of left extremity to
be the following: leg, 15.5 in; midfoot, 10.5 in;
forefoot, 10 in; hallux, 3.5 in; length of foot, 9.5 in.
Right extremity circumference exhibited the following: leg, 15.6 in; midfoot, 1 1.5 in; forefoot, 12.2
in; hallux, 8 in; length of foot, 11.5 in.

Laboratory and Radiographic

Examination
Laboratory results, serology, and liver scan
were all found to be unremarkable. X-ray examination of chest, pelvis, and right extremity to the
ankle were negative. X-ray examination of the feet
revealed no significant osseous or articular abnormalities of the left foot. The right foot revealed
gigantism including bone and soft tissue proliferation of the great toe and second digit with minimal
changes at the metatarsophalangeal joint. Involvement of the second toe was considered to be due to
partial gigantism although pressure effect may also
have been a contributing factor.

Evaluation and Treatment

The patient underwent a complete history and
physical examination at Kirwood General Hospital Family Health Center and was diagnosed as
having focal gigantism with concomitant acromegaly of the right great hallux and second digit.
The patient firmly refused any treatment that
would not effectively reduce the size of her foot,
as well as surgical correction.

METHODS OF MANAGEMENT
AND PROGNOSIS

Transsphenoidal Microsurgery
In an analysis of 132 surgically treated acromegalics, 65 men and 67 women, ranging in age
from 21 to 66 and 20 to 67 years, respectively, all
subjects exhibited a varying degree of acromegalic
dysmorphism. For each patient the blood level

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GIGANTISM AND ACROMEGALY

of growth hormone was determined within three

months before surgery and at least once during the
month after surgery. The determination of growth
hormone (and prolactin) was done following
standard radioimmunoassay procedures at the
radionuclear laboratory of the hospital. Levels
below 5 ng/mL for growth hormone and below 30
ng/mL for prolactin were considered normal.
The overall cure rates were 58 percent (growth
hormone, 5 ng/mL) and 78 percent (growth hormone, 10 ng/mL). Endocrinological evidence of
cure consisted of observed hormone values below
10 ng/mL.3 These results were compatible with
those obtained by other neurosurgeons. In the series of Atkinson et al,4 16 patients were treated
by a transsphenoidal approach, and postoperative
growth hormone levels below 5 ng/mL were
achieved in 62 percent of the patients. Ditullio and
Rand5 treated 54 patients with transsphenoidal
cryohypophysectomy, obtaining a normalization
of growth hormone levels in 56 percent of their
patients; in an additional 21 percent, the postoperative growth hormone levels were between 5 and
10 ng/mL. Laws et al6 achieved overall reduction
of growth hormone to below 10 ng/mL in 66 percent of their 80 cases treated by transsphenoidaladenomectomy; in patients with noninvasive tumors, this improvement rate was 73 percent.
Hardy obtained a postoperative reduction of
growth hormone values to below 10 ng/mL in 70
percent of 40 patients treated with transsphenoidal
microsurgery,' and in a later series postoperative
growth hormone values below 5 ng/mL were
achieved in 80 percent of 57 patients.8

Estradiol Treatment of Acromegaly

Administration of estrogens to acromegalic patients has been shown to reduce the serum concentrations of bioassayable somatomedin and to cause
improvement in clinical status. These results appear not to be due to effect on the secretion of
growth hormone, as growth hormone concentrations are not consistently reduced.
The study indicates that the reduction of immunoreactive somatomedin-c correlates with
estrogen-induced improvement in the metabolic
activity of acromegalic patients and suggests that
measurements of somatomedin-c may be useful in
monitoring the effects of other drugs on this
disease."

Bromocriptine Treatment
Eleven patients with active acromegaly resistant to conventional therapy were treated with
bromocriptine for 15 (12 to 22) months by increasing the daily dose stepwise from 5 to between 10
and 60 mg. A satisfactory response was achieved
in all but one of eight patients in whom the mean
diurnal levels of serum growth hormone were less
than 50 ng/mL. Patients with grossly elevated
serum growth hormone levels, however, responded
poorly. In the long term, no overall effects of glucose tolerance or plasma insulin (IRI) levels were
observed, but the chemical diabetes of three patients ameliorated in two. On the other hand,
a dose-dependent active suppressive effect of
bromocriptine on plasma IRS response to oral glucose was observed, suggesting a direct effect of
bromocriptine on the release of insulin from /3
cells. Bromocriptine seems to be a good alternative in the treatment of patients with acromegaly
who have not responded to conventional therapy. "'

Literature Cited
1. Daughaday WH, Cryer PE, Jacobs LS. Diagnosis and
Treatment of Pituitary Tumors. Amsterdam: Excerpta
Medica, 1973, p26.
2. Liuzzi A, Chiodini PG, Botalla L, et al. Decreased
plasma growth hormone. J Clin Endocrinol 1974; 38:910912.
3. Balagura S, Dermoe P, Guiot G. Acromegaly: Analysis of 132 cases treated surgically. Neurosurgery 1981;
8:413-416.
4. Atkinson R, Becker D, Martin A, et al. Acromegaly,
treatment by transsphenoidal microsurgery. JAMA 1975;
233:1279-1283.
5. Ditullio MV Jr, Rand RW. Efficacy of cryohypophysectomy in treatment of acromegaly. Evaluation of 54 cases.
J Neurosurg 1977; 46:1-11.
6. Laws ER Jr, Piepgras DG, Randall RV, Abbold CF.
Neurosurgical management of acromegaly. Results in 82
patients treated between 1972 and 1977. J Neurosurg 1979;
50:454-461.
7. Hardy J. Transsphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 1969; 16:
185-217.
8. Hardy J, Somma M, Vezina JL. Treatment of Acromegaly. Radiation or Surgery? In Morley T (ed): Current
Controversies in Neurosurgery. New York: WB Saunders,
1976, pp 377-391.
9. Clemmons DR, Underwood LE, Ridgway EC, et al.
Estradiol treatment of acromegaly. Am J Med 1980; 69(4):
571-575.
10. Pelkonen R, Yukahri R, Karonen SL. Bromocriptine
treatment of patients with acromegaly resistant to conventional therapy. Clin Endocrinol (Oxf) 1980; 12(3):219.224.

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