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Parathyroid Hormone Levels in Thyroid-Vein Blood of
Patients Without Abnormalities of Calcium Metabolism
PETER M. SHIMKIN, M.D., and DAVID POWELL, M.D., Bridgeport, Connecticut,
and Boston, Massachusetts
Five patients without disorders known to influence
calcium metabolism were considered euparathyroid by
standard laboratory tests and normal peripheral
radioimmunoactive plasma parathyroid hormone
levels. All five had higher concentrations of parathyroid
hormone in the drainage from both sides of the thyroid
venous bed, ranging from 1.9 to 20 times the
peripheral concentration. Hyperplastic parathyroid
glands cause similar bilateral local increases in
concentration. In known cases of hyperparathyroidism
bilateral thyroid venous hormone increases indicate
hyperplasia. In equivocal cases with normal peripheral
parathyroid hormone levels, however, such localized
increases indicate the need for further investigation to
ensure the diagnosis of hyperparathyroidism.
RADIOIMMUNOASSAY of blood samples obtained by
selective catheterization of the thyroid venous bed
offers the clinician a sensitive and highly accurate
method for the preoperative localization of parathyroid tumors. Both adenomatous and hyperplastic
parathyroid glands consistently produce high concentrations of parathyroid hormone in draining thyroid veins ( 1 , 2 ) .
For comparison, we have assayed thyroid blood
samples from patients with disorders of calcium
metabolism believed to have normal parathyroid
function ( 1 , 2 ) . Most had the diagnosis of idiopathic
hypercalciuria. With increasing acceptance and re• From the Department of Radiology, Bridgeport Hospital, Bridgeport,
Connecticut, and the Endocrine Unit, Massachusetts General Hospital,
Boston, Massachusetts.
finement of the concept of normocalcemic hyperparathyroidism (3, 4 ) , the clinical diagnosis in these unoperated patients has become increasingly unsure.
Further problems in the interpretation of parathyroid function in these cases have arisen with the recognition of two separate patterns in thyroid venous
catheterization data ( 1 ) . One group of patients had
bilateral thyroid-vein values of parathyroid hormone
that were the same as normal peripheral levels; the
second group had elevated levels in blood obtained
from both sides of the thyroid venous bed. Since
surgically proved hyperparathyroid patients may have
normal peripheral hormone levels (2, 5 ) , does just
one pattern or both indicate normal function?
To provide a normal control group for hyperparathyroid cases and to clarify the cases discussed above,
we present the thyroid venous catheterization data of
five euparathyroid patients with no disorders affecting
calcium metabolism.
Patients and Methods
Incidental to venous catheterization for other purposes, bilateral inferior thyroid-vein samples were obtained in five patients with no disorders of calcium and
phosphorus metabolism. Table 1 presents the age, sex,
and final clinical diagnosis of each patient. None had a
history of kidney disease, urinary calculi, or other symptoms of hyperparathyroidism such as duodenal ulcer
or pancreatitis. None had a known malignant tumor.
None took medications that might alter calcium metabolism, including thiazide diuretics or corticosteroids. Results of complete blood count, routine urinalysis, and
protein electrophoresis and levels of serum electrolytes,
alkaline phosphatase, and blood urea nitrogen were normal in all five patients. Chest X rays and intravenous
pyelograms were also normal.
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Annals of Internal Medicine 78:714-716. 1973
Table 1 . Clinical Diagnoses and Calcium and Phosphorous Variables Establishing Normal Parathyroid Function in Five Patients
Case
Sex
Age
Diagnosis
Serum
Calcium*
Neurofibromatosis %
Soft-tissue hemangioma
Essential hypertension
Alcoholic cirrhosis and
gynecomastia§
Hirsutism and obesity||
9.6
10.0
9.0
9.9
3.1
3.8
3.6
4.2
92
133
118
240
10.1
8.6-10.8
3.4
2.4-5.0
188
100-300
Serum
Phosphate
(As Phosphorus) \
yr
1
2
3
4
5
Normal range
M
F
F
M
35
78
61
47
F
22
mg/100 ml
Urinary
Calcium
mg/24 hr
* Mean of the three normal measurements obtained in each patient. The highest single value of the group was 10.3 mg/100 ml; the lowest was
8.7 mg/100 ml.
t Mean of the three normal measurements obtained in each patient. The highest single value of the group was 4.5 mg/100 ml; the lowest was
2.9 mg/100 ml.
t Additional data in Case 1, to exclude multiple endocrine tumors: blood pressure, normal; calcitonin, undetectable in peripheral or thyroid venous samples.
§ Additional data in Case 4, to exclude underlying neoplasm: mild increase urinary 17-hydroxysteroid and normal 17-ketosteroid levels; urinary
human chorionic gonadotropin, undetectable; bilateral adrenal venograms, normal; 6-month follow-up: spontaneous regression of gynecomastia.
|| Additional data in Case 5, to exclude multiple endocrine adenomas: both adrenal and ovarian vein testosterone levels, elevated; bilateral adrenal
venograms, normal; sella turcica, normal.
Table 1 gives the serum calcium and phosphate and
urinary calcium values for each patient. Calcium was
measured by AutoAnalyzer and phosphate by the FiskeSubbarow method. The 24-hour urinary calcium level
was measured with the patient on an unrestricted calcium diet. The adequacy of collection was assured by a
concurrent normal value for urinary creatinine. All calcium and phosphorous variables were within normal
limits.
All patients had venous sampling done while on an
unrestricted calcium diet. Dehydration was carefully
avoided. Because of the paramount importance of the
inferior thyroid veins in parathyroid venous drainage
(1), samples were obtained from these thyroid veins
only. A single sample was drawn from a thyroid vein
in all cases except Case 1. The catheter was positioned
at least 1 cm within the thyroid venous bed to prevent
dilution by innominate-vein blood. The peripheral vein
sample was taken from the right iliac vein during the
course of the catheterization procedure.
The radioimmunoassay procedure for parathyroid
hormone is described elsewhere (2). A sample was
analyzed six times; in all cases maximum variation between the six was less than 15%. The normal peripheral
hormone level (for example, from a brachial vein) is
0.4 to 0.8 ng/ml plasma, using partially purified human
parathyroid hormone as the reference standard.
Results
Table 2 presents the peripheral and thyroid-vein
parathyroid hormone values for the five patients.
Peripheral values were normal in all, confirming their
euparathyroid status (Table 1). Each patient showed
bilateral elevation of thyroid-vein hormone, as compared with the concentration of hormone in the peripheral specimen (hereafter referred to as 'local
hormone increase"). Individual local hormone increases ranged from 1.9-fold (Case 4, right inferior
thyroid vein) to 20-fold (Case 1, left inferior thyroid). Comparing sides of the thyroid venous bed,
bilateral hormone increases were approximately
equal (Case 2) or quite asymmetric (Case 5 ) .
Three hormone concentrations that varied considerably in magnitude were obtained from the right
inferior thyroid vein of the patient in Case 1. Figure
1 shows a tracing of the thyroid venous bed of this
patient with location of and corresponding hormone
values for the venous samples. Obviously the symmetry of the bilateral local hormone increases depends on which of the three right-sided samples one
chooses to compare with the single left-sided value.
Discussion
In most cases, hypercalcemia and elevation of the
peripheral parathyroid hormone level provide a definitive preoperative diagnosis of hyperparathyroidism.
As with other blood hormone assays, however, there
is an overlap between circulating hormone levels of
a few normal and hyperfunctioning patients ( 5 ) . The
Table 2. Parathyroid Hormone Concentration in Peripheral and
Selective Thyroid-Vein Samples
Peripheral
Case
<
0.60
1
2
3
4
5
Normal
range
0.63
0.55
0.69
0.48
0.4-0.8
Right
Inferior
Thyroid
Left
Inferior
Thyroid
, .
ng/ml
2.1*
11.4*
4.9*
7.8
2.5
1.3
1.2
—
12.2
6.5
3.5
2.0
9.6
—
* See Figure 1 for anatomic correlation of the individual values.
Only one sample for a thyroid vein was obtained in Cases 2 to 5.
Shimkin and Powell • Parathyroid Hormone Levels
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Figure 1 . Parathyroid hormone levels (in ng/ml plasma) In thyroid venous blood of Case 1 .
diagnosis of hyperparathyroidism may thus remain
uncertain in asymptomatic patients with equivocal
hypercalcemia and a peripheral hormone level within
normal limits. A parathyroid adenoma produces only
a unilateral increase in thyroid-vein parathyroid hormone levels, presumably because normal contralateral glands are suppressed. Detection of this adenoma pattern by venous sampling may thus provide
the diagnosis of hyperparathyroidism, besides localizing the tumor in problem cases (1, 2). However,
because both hyperplastic and normal glands cause
bilateral increases in local hormone levels, thyroidvein sampling cannot differentiate between them.
In our experience, many cases of hyperplasia have
had quite asymmetrical local increases in parathyroid
hormone in comparisons of the two sides of the thyroid venous bed. The average local increase in all
cases of hyperplasia has been 10 times the peripheral
level (1). One might reason that normal cases would
have no increase at all or only small, equal elevations
on both sides of the thyroid venous bed; either pattern would allow differentiation from many cases of
hyperplasia. The results of this investigation have not
supported these expectations.
We do not intend that this paper should discourage
the use of thyroid-vein sampling for localizing tumors
responsible for known cases of hyperparathyroidism.
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We have never failed to find bilateral local hormone
increases in previously unoperated patients with hyperplasia. In only 1 of 20 cases, including the 10 in
our initial report (2), have we failed to localize a
surgically proved adenoma. We present the results of
this investigation to temper the use of venous sampling for the support of the diagnosis of hyperparathyroidism in equivocal cases with normal peripheral
parathyroid hormone levels.
Case 1 shows the influence of the catheterization
procedure on the magnitude of a local increase in
thyroid-vein hormone levels. Such a consideration
must be invoked to accept with equanimity the
marked difference between the two thyroid-vein values of Case 5. One would expect reasonably equal
output of hormone from normal glands. We can provide no facile explanation for the three different increases in right inferior thyroid-vein hormone levels
in Case 1 (Figure 1). Possible reasons include very
rapid fluctuations in the secretory rate of normal
glands, stimulation of secretion by venography, inconstant rates of blood aspiration, and differing positions of the sampling catheter. The sample with the
highest concentration may have been obtained closest
to the discharge site of the inferior parathyroid gland
(6). We are currently investigating the other possibilities.
This investigation establishes that, in fasting adult
humans without disorders affecting calcium and phosphorus metabolism, the parathyroid glands vigorously
secrete hormone to maintain the normal circulating
concentration. Whether catheterization studies could
ever find resting glands in normal patients remains
unanswered.
ACKNOWLEDGMENTS: Received 13 December 1972; accepted
5 January 1973.
• Requests for reprints should be addressed to Peter M. Shimkin,
M.D., Department of Radiology, Bridgeport Hospital, 267 Grant
St., Bridgeport, CT 06602.
References
1. SHIMKIN PM, POWELL D, DOPPMAN JL, et al: Parathyroid
venous sampling. Radiology 104:571-574, 1972
2. POWELL D, SHIMKIN PM, DOPPMAN JL, et al: Primary hyper-
parathyroidism. Preoperative tumor localization and differentiation between adenoma and hyperplasia. N Engl J Med 286:
1169-1175, 1972
3. WILLS MR, PAK CYC, HAMMOND WG, et al: Normocalcemic
primary hyperparathyroidism. Am J Med 47:384-391, 1969
4. FRAME B, FOROOZANFAR F, PATTON RB: Normocalcemic pri-
mary hyperparathyroidism with osteitis fibrosa. Ann Intern
Med 73:253-257, 1970
5. BERSON SA, YALLOW RS: Clinical applications of radioim-
munoassay of plasma parathyroid hormone. Am J Med 50:623629, 1971
6. SHIMKIN PM, DOPPMAN JL, PEARSON KD, et al: Anatomic
considerations in parathyroid venous sampling. Am J Roentgenol Radium Ther Nucl Med. In press, 1973
May 1973 • Annals of Internal Medicine • Volume 78 • Number 5
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