GIGANTISM AND ACROMEGALY:REPORT OF A CASE AND REVIEWOF THE LITERATUREAlma R. George, MD, Meer Deen, DPM, and Floyd Atkins, DPMDetroit, Michigan

A case of focal gigantism with concomitantacromegaly of the great hallux and seconddigit is reported. A review of pertinent litera-ture is presented.

Gigantism or acromegaly results from the ex-cessive secretion of human growth hormonecaused by an acidophilic adenoma of the pituitary,less'commonly by a chromophobe adenoma and,rarely, by a histologically normal pituitary. Whenthe condition arises after fusion of the epiphysealplate, it is referred to as acromegaly.

Although by the time the diagnosis is made, thepatient almost always has a growth-hormone-secreting adenoma, the condition may arise fromprolonged stimulation by growth-hormone-releasestimulating factor(s) or a deficiency of growth-hormone-release inhibitory hormone, produced bycells of the hypothalamus. Thus, several reportshave suggested that the secretion of growth hor-mone is not always autonomous in patients withacromegaly, but changes with stimuli that increaseor suppress the secretion of the hormone and arethought to act via the hypothalamus.' More inter-esting, levels of growth hormones show paradoxi-

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

cal responses in acromegalics as compared withnormal subjects. For example, dopaminergicstimulation normally results in a rise of serumgrowth hormone whereas the administration of thedopamine agonist, bromocriptine, often depressesserum levels of growth hormone in acromegalics,2an effect that has been utilized in medical man-agement of this condition.

Hypersecretion of growth hormones prior toclosure of the epiphyses leads to proportionalgrowth of bone; both length and width of bone areincreased. Hypersecretion after closure of epiphy-ses leads to periosteal overgrowth and corticalthickening. Bone overgrowth and soft tissuethickening lead to characteristic coarsening of fa-cial features. The hands are widened and the fin-gers become broad. Similar changes occur in thefeet, requiring a larger shoe size. Erosion of articu-lar surfaces occurs and joint complaints are com-mon. Hypertension is not uncommon. The skin isthickened with increased sweating and femalesmay note hypertrichosis. Galactorrhea may alsobe present.

Skull x-ray films show cortical thickening, en-largement of the frontal sinuses, and enlargementand erosion of the sella turcica. X-ray examinationof the hands and feet shows tufting of the terminalphalanges and soft-tissue thickening. Glucose tol-erance test usually yields abnormal results. Ele-

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vated serum inorganic phosphate has been used asan index of active acromegaly, but is now recog-nized as an imprecise reflection of growth hor-mone. The measurement of plasma human growthhormone concentration by radioimmunoassay isthe most direct and precise means of assessing in-creased secretions of growth hormone.

CASE REPORTA 54-year-old, black, obese woman presented

to Family Health Center with the chief complaintthat her right foot had been getting larger and waspainful whenever she wore shoes. The patient fur-ther stated that the big toe and second toe of herright foot had been exceptionally large since birth.She had worn a special shoe until age 12 years,when she discontinued wearing special shoes upondeparting from the South. She described purchas-ing a pair of shoes to fit the normal-sized left footand stretching or at times cutting the right shoe toaccommodate the abnormally large right foot. Shesaid that within the past ten years the soft tissue ofher right foot had increased in size. The patientdenied any knowledge of this condition existing inany other family members; her medical historyincluded hypertension for the previous ten yearsand osteoarthritis. The patient denied having in-fectious or systemic diseases but did have thenormal childhood illnesses. Surgical history in-cluded a hysterectomy in 1969. The patient has noknown allergies and is presently taking sulindac(Clinoril) for an arthritic condition. Traumatic in-jury and family histories were unremarkable.

Physical ExaminationPhysical examination revealed a 54-year-old

female, height, 5 feet 7 in; weight, 241 lb; tempera-ture, 97.80 F; pulse, 88 beats/min; and blood pres-sure, 150/100 mmHg left and 150/94 mmHg right.The skin was clear with light hair growth; neuro-logical examination revealed deep tendon reflexesof the left extremity, within normal limits, and nopathological reflexes were noted, bilaterally. Vas-cular examination revealed strong posterior tibialpulses, bilaterally; dorsalis pedis pulse of the rightfoot was nonpalpable, secondary to increase insoft tissue. Nail beds were pink; pitting edema was

noted at ankles and forefoot, bilaterally. Musclestrength of lower extremity exhibited no abnormal-ity. Range of motion was decreased in hip, knee,ankle, subtalar, midtarsal joints, bilaterally, firstmetatarsophalangeal and proximal interphalangealjoints of right foot. The lower extremity measure-ments revealed circumference of left extremity tobe 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 fol-lowing: leg, 15.6 in; midfoot, 1 1.5 in; forefoot, 12.2in; hallux, 8 in; length of foot, 11.5 in.

Laboratory and RadiographicExamination

Laboratory results, serology, and liver scanwere all found to be unremarkable. X-ray exami-nation of chest, pelvis, and right extremity to theankle were negative. X-ray examination of the feetrevealed no significant osseous or articular ab-normalities of the left foot. The right foot revealedgigantism including bone and soft tissue prolifera-tion of the great toe and second digit with minimalchanges at the metatarsophalangeal joint. Involve-ment of the second toe was considered to be due topartial gigantism although pressure effect may alsohave been a contributing factor.

Evaluation and TreatmentThe patient underwent a complete history and

physical examination at Kirwood General Hospi-tal Family Health Center and was diagnosed ashaving focal gigantism with concomitant acro-megaly of the right great hallux and second digit.The patient firmly refused any treatment thatwould not effectively reduce the size of her foot,as well as surgical correction.

METHODS OF MANAGEMENTAND PROGNOSIS

Transsphenoidal MicrosurgeryIn an analysis of 132 surgically treated acro-

megalics, 65 men and 67 women, ranging in agefrom 21 to 66 and 20 to 67 years, respectively, allsubjects exhibited a varying degree of acromegalicdysmorphism. For each patient the blood level

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of growth hormone was determined within threemonths before surgery and at least once during themonth after surgery. The determination of growthhormone (and prolactin) was done followingstandard radioimmunoassay procedures at theradionuclear laboratory of the hospital. Levelsbelow 5 ng/mL for growth hormone and below 30ng/mL for prolactin were considered normal.

The overall cure rates were 58 percent (growthhormone, 5 ng/mL) and 78 percent (growth hor-mone, 10 ng/mL). Endocrinological evidence ofcure consisted of observed hormone values below10 ng/mL.3 These results were compatible withthose obtained by other neurosurgeons. In the se-ries of Atkinson et al,4 16 patients were treatedby a transsphenoidal approach, and postoperativegrowth hormone levels below 5 ng/mL wereachieved in 62 percent of the patients. Ditullio andRand5 treated 54 patients with transsphenoidalcryohypophysectomy, obtaining a normalizationof growth hormone levels in 56 percent of theirpatients; in an additional 21 percent, the postop-erative growth hormone levels were between 5 and10 ng/mL. Laws et al6 achieved overall reductionof growth hormone to below 10 ng/mL in 66 per-cent of their 80 cases treated by transsphenoidal-adenomectomy; in patients with noninvasive tu-mors, this improvement rate was 73 percent.Hardy obtained a postoperative reduction ofgrowth hormone values to below 10 ng/mL in 70percent of40 patients treated with transsphenoidalmicrosurgery,' and in a later series postoperativegrowth hormone values below 5 ng/mL wereachieved in 80 percent of 57 patients.8

Estradiol Treatment of AcromegalyAdministration of estrogens to acromegalic pa-

tients has been shown to reduce the serum concen-trations of bioassayable somatomedin and to causeimprovement in clinical status. These results ap-pear not to be due to effect on the secretion ofgrowth hormone, as growth hormone concentra-tions are not consistently reduced.

The study indicates that the reduction of im-munoreactive somatomedin-c correlates withestrogen-induced improvement in the metabolicactivity of acromegalic patients and suggests thatmeasurements of somatomedin-c may be useful inmonitoring the effects of other drugs on thisdisease."

Bromocriptine Treatment

Eleven patients with active acromegaly resist-ant to conventional therapy were treated withbromocriptine for 15 (12 to 22) months by increas-ing the daily dose stepwise from 5 to between 10and 60 mg. A satisfactory response was achievedin all but one of eight patients in whom the meandiurnal levels of serum growth hormone were lessthan 50 ng/mL. Patients with grossly elevatedserum growth hormone levels, however, respondedpoorly. In the long term, no overall effects of glu-cose tolerance or plasma insulin (IRI) levels wereobserved, but the chemical diabetes of three pa-tients ameliorated in two. On the other hand,a dose-dependent active suppressive effect ofbromocriptine on plasma IRS response to oral glu-cose was observed, suggesting a direct effect ofbromocriptine on the release of insulin from /3cells. Bromocriptine seems to be a good alterna-tive in the treatment of patients with acromegalywho have not responded to conventional therapy. "'

Literature Cited1. Daughaday WH, Cryer PE, Jacobs LS. Diagnosis and

Treatment of Pituitary Tumors. Amsterdam: ExcerptaMedica, 1973, p26.

2. Liuzzi A, Chiodini PG, Botalla L, et al. Decreasedplasma growth hormone. J Clin Endocrinol 1974; 38:910-912.

3. Balagura S, Dermoe P, Guiot G. Acromegaly: Anal-ysis 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 cryohypophy-sectomy 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 82patients treated between 1972 and 1977. J Neurosurg 1979;50:454-461.

7. Hardy J. Transsphenoidal microsurgery of the nor-mal and pathological pituitary. Clin Neurosurg 1969; 16:185-217.

8. Hardy J, Somma M, Vezina JL. Treatment of Acro-megaly. Radiation or Surgery? In Morley T (ed): CurrentControversies 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. Bromocriptinetreatment of patients with acromegaly resistant to conven-tional therapy. Clin Endocrinol (Oxf) 1980; 12(3):219.224.

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