Volume 55, No.

6 IOOI
December 1961 CASE REPORTS

Cortisone Responsive Hypercalcemia in Proved

Hyperparathyroidism
GRANT G W I N U P , M.D., and BETTYE SAYLE, M.D.

Galveston, Texas

T HERE is NO AVAILABLE ASSAY for parathyroid

hormone in the serum. I n the absence of
such a specific determination, it is necessary to
Received February 27, 1961; accepted for publi-
cation May 22, 1961.
From the Department of Internal Medicine, The
University of Texas—Medical Branch, Galveston,
Texas.
Requests for reprints should be addressed to
Grant Gwinup, M.D., Department of Internal Medi-
cine, Division of Endocrinology, Ohio State Uni-
versity Hospital, Columbus, Ohio.
rely o n nonspecific procedures to differentiate
hyperparathyroidism from the other hypercal-
cemic states. T h e effect of the administration of
corticosteroids o n the elevated serum calcium
levels is o n e such procedure currently applied
in difficult problems of differential diagnosis.
It is the purpose of this report to present an
exception to previous experience with this pro-
cedure in a patient with proved hyperpara-
thyroidism.
T h e hypercalcemia of sarcoidosis has con-

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1002 G. GWINUP AND B. SAYLE
sistently responded to steroid administration
(1-4). In one case of proved sarcoidosis in
which the elevated serum calcium did not re-
turn to normal when steroids were given a
parathyroid adenoma was subsequently found
when the neck was explored (5). Vitamin D
intoxication has also regularly responded even
when the administration of vitamin D has been
continued (6). The hypercalcemia associated
with neoplasm with or without bony metastasis
may or may not be affected by corticosteroid
administration. This appears to be the case
also in multiple myeloma and lymphoma (7-9).
Hyperparathyroidism, on the other hand, has
been found to present a hypercalcemia which
is consistently unresponsive to steroids, and no
case is yet reported in which an effect on the
elevated calcium levels was observed (5, 6). The
following case presents an example of hyper-
parathyroidism in which the persistently ele-
vated serum calcium levels became normal with
the administration of hydrocortisone.
CASE REPORT
A 40-year-old Latin American female presented
with a chief complaint of left lower quadrant pain
of 17 years' duration which had been present almost
constantly and could not be related to bladder,
bowel, or menstrual function. Six months pre-
viously a nephrectomy had been done for a stag
horn calculus of the right renal pelvis discovered
during investigation of the chief complaint. There
was mild constipation but no dyspepsia, no poly-
uria, and only questionable generalized weakness.
FIGURE 1. Elevated serum calcium levels fell to
within the normal range with hydrocortisone ad-
ministration. Following parathyroidectomy, tempo-
rary hypocalcemia was followed by a return to
normal levels.
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Annals of
Internal Medicine
FIGURE 2. Tumor attached to the inferior portion of
the right lower pole of the thyroid gland.
There was no history of vitamin D ingestion and
no symptoms suggesting sarcoidosis.
The patient was a mildly obese Latin American
female in no distress. Blood pressure was 140/90
mm Hg, pulse 72, respirations 16. Examination of
the head, eyes, ears, nose, and throat was com-
pletely negative. The thyroid gland could be felt
but was not unusual, and there was no neck
mass. The chest was clear. The only positive physi-
cal findings were vague left lower quadrant tender-
ness and a well-healed right nephrectomy scar.
X ray revealed the chest examination, barium
swallow, upper gastrointestinal examination, chole-
cystogram, and complete skeletal survey to be nega-
tive. Hemoglobin was 13.3 g/100 ml, white blood cell
count, 4,800/mm8, with a normal differential. The
urinalysis was negative with a specific gravity of
1.010 on a random specimen. On the fourth and
fifth days of a diet containing 125 mg calcium, the
urine contained 285 and 209 mg of calcium, re-
spectively. Fasting blood sugar was 89 mg/100 ml,
blood urea nitrogen was 9 mg/100 ml, phenol-
sulfonphthalein excretion was 30% in 15 minutes,
and total serum protein was 7.2 g/100 ml, with a
normal electrophoretic pattern.
Serum calcium levels were consistently above the
normal range of 9.2 to 10.5 of our laboratory (Fig-
ure 1), and serum phosphorus levels ranged from
slightly low to normal with no significant change
throughout the period of observation. Following
the administration of 50 mg of hydrocortisone every
eight hours for five days, the serum calcium levels
were consistently normal. At operation a 2.5 by 1
cm pedunculated tumor was found attached to the
inferior portion of the right lower pole of the
thyroid gland (Figure 2). On microscopic examina-
tion this proved to be a parathyroid adenoma
(Figure 3). Following operation the serum calcium
levels remained at subnormal levels for several
days but then returned to normal.
 Volume 55, No. 6
December 1961 CASE REPORTS
FIGURE 3. Microscopic picture of parathyroid ade-
noma showing predominant chief cells with no
prominent fat.
DISCUSSION
In this case of proved parathyroid adenoma
there was a most significant change in the serum
calcium levels following five days of hydrocorti-
sone administration. There was no clinical or
laboratory evidence to suggest an additional
cause of the hypercalcemia.
It is felt that variation in the laboratory
determination was excluded by carefully control-
ling the procedure. The serum calcium values
were determined by the method of Williams
and Moser using the autoanalyzer (10). The
serum was dialyzed into an aqueous ammonium
purpurate solution following the addition of
hiamine reagent and the color was measured
at 550 millimicrons using a flow cuvette and a
6 millimeter light patch. Calcium carbonate
standards remained the same throughout the
observation period. The patient's serum calcium
levels were also compared at each determina-
tion with duplicate samples from the same pool
of normal serum with a predetermined calcium
level of 10.1 milligrams per 100 milliliters.
It is known that the elevated calcium levels
of hyperparathyroidism may occasionally show
appreciable variation, and a spontaneous return
to normal levels coincident with the period of
hydrocortisone administration cannot be ruled
out in this case; however, there was remarkable
constancy of the elevated calcium before hydro-
cortisone was given and a suggestion of return
toward those levels after hydrocortisone was
discontinued.
In sarcoidosis and vitamin D intoxication,
it is felt that the steroids act primarily by modi-
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I003
fying the gastrointestinal absorption of calcium
(5, 11). In malignancies, a direct action upon
the neoplastic cells has been presumed (7). The
mechanism by which hypercalcemia was re-
stored to normal levels in this case of hyper-
parathyroidism must remain speculative; how-
ever, there is evidence implicating the influence
of adrenal steroids on the action of parathyroid
hormone both on the bone and at the renal
level (12, 13). The question why this case re-
sponded to the calcium lowering effect of
steroids, while other cases of hyperparathyroid-
ism reported have not responded, must remain
unanswered.
The purpose of this report is not to imply
that no additional information can be obtained
by the administration of steroids in the various
hypercalcemic states, but rather to point out
that as with most other diagnostic procedures
there may be exceptions to the expected result.
Only continued experience with this particular
procedure will determine how statistically im-
portant such exceptions will prove to be.
SUMMARY
A report is presented in which the hyper-
calcemia secondary to a proved parathyroid
adenoma promptly fell to within normal limits
with the administration of therapeutic doses of
hydrocortisone. This case represents an excep-
tion to previous experience in which no instance
of hypercalcemia due to hyperparathyroidism
has been reported to fall with steroid adminis-
tration.
SUMMARIO IN INTERLINGUA
Le responsa del elevate nivellos serai de cal-
cium al administration de corticosteroides ha
essite usate como adjuta in le differentiation
de hyperparathyroidism© ab altere statos de
hypercalciemia. Le hypercalciemia de sarcoi-
dosis e de intoxication per vitamina D ha res-
pondite uniformemente. In casos de neoplasma
metastatic, myeloma multiple, e lymphoma, le
responsa ha essite variabile. Tamen, se trova
reportate nulle caso de hyperparathyroidism©
in que le elevate nivellos serai de calcium
respondeva al administration de steroide.
In le presente studio, un patiente—in qui il
esseva demonstrate subsequentemente que ille
habeva un adenoma parathyroidic—manifestava
un prompte renormalisation del elevate nivello

ioo4 G. GW1NUP AND B. SAYLE
serai de calcium in coincidentia con le admi-
nistration de hydrocortisona in u n dosage de
15 mg a intervallos de octo horas durante un
periodo de cinque dies.
Ante le administration de hydrocortisona,
le nivellos serai de calcium variava inter 10,5
e 11 m g per 100 ml. (In nostre laboratorio,
10,5 mg per 100 ml es reguardate como le
maximo ancora normal.) Subsequentemente le
nivellos serai de calcium variava inter 9,4 e 9,9
mg per 100 ml, usque post le ablation del
adenoma parathyroide, quando illos esseva 8,0
mg per 100 ml le prime die post-operatori e
retornava al norma intra cinque dies.
Le valores del calcium serai esseva deter-
minate secundo le methodo de Williams e
Moser. Le standards de carbonato de calcium
remaneva le mesmes durante le integre periodo
de observation. Le sero del patiente esseva com-
parate a omne determination con duplicate
specimens ab reservoirs multidonatori de sero
normal.
Nulle evidentia clinic o laboratorial esseva
detegite que poteva suggerer un causa pro le
hypercalciemia altere q u e le hyperparathy-
roidism©. B e n que un spontanee retorno del
elevate nivello serai de calcium al region nor-
mal, occurrente in coincidentia con le admi-
nistration de hydrocortisona, n o n pote esser
excludite, le presente caso es exceptional in
tanto que passate experientias poteva esser
interpretate como indication que un renorma-
lisation de elevate nivellos serai de calcium sub
le effecto de un administration de steroides non
pote occurrer in casos de hyperparathyroidism©.
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