The response to exogenous parathyroid hormone (PTH) with urinary excretion of phosphate and cyclic adenosine monophosphate (cAMP) was tested by the use of synthetic human parathyroid hormone (1-34) [hPTH-(1-34)] on 59 patients with hypocalcemia and normal or high serum inorganic phosphorus and normal renal function without a history of parathyroidectomy for differentiation between idiopathic hypoparathyroidism (IHP), pseudohypoparathyroidism (PHP) and related diseases along with 18 normal subjects.
A positive phosphaturic response to exogenous PTH was defined as the increment of 2 hours phosphate excretion (ΔP) of more than 35 mg. A positive urinary cAMP response to exogenous PTH was defined as the increment by more than 1 μmole per one hour (ΔcAMP) and the increase of 1 hour excretion by more than 10 times.
Increments of 2 hours urinary phosphate excretion in response to hPTH-(1-34) 100 units were 60.5±7.7 mg (mean±SEM) in 27 patients with IHP, 23.5±5.9 mg in 21 patients with PHP type I and 24.9±4.0 mg in 17 normal subjects. Increments of 1 hour urinary cAMP excretion in response to (1-34) 100 units were 12.0±1.5 μmole in 27 patients with IHP, 0.33±0.10 μmole in patients with PHP type I and 23.6±5.8 μmole in 15 normal subjects. Ratios of 1 hour urinary cAMP excretion were 97±10 in 27 patients with IHP, 3.6±0.5 in 21 patients with PHP type I and 54±14 in 15 normal subjects.
Positive phosphaturic and negative urinary cAMP response was encountered in 3 out of 21 patients with PHP type I in response to hPTH-(1-34). This exaggerated phosphaturic response should be considered as due to the influence of treatment with Ca or vitamin D derivatives.

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The relationship between thyroid disorders and gastric pathophysiology has been studied mainly from standpoints of gastric histology and gastric acid output capacity. Though anti-gastric antibody has been thought to play a part in this relationship, there have been no clear conclusions obtained about that. Since blood gastrin levels are easily measurable by radioimmunoassay today, the relationship between thyroid disorders and gastric pathophysiology has drawn attention again from a standpoint of gastrin levels. Seino et al. have reported about hypergastrinemia in hyperthyroidism, speculating that β-adrenergic hyperresponsiveness of gastrin-producing cells could be the mechanism of hypergastrinemia. However, there are other reports which mentioned feedback mechanism between gastrin and gastric acid or interaction of gastrointestinal hormones as the main mechanism of hypergastrinemia.
In this study, the problem of gastrin in Graves' disease and chronic thyroiditis were studied by measurement of fasting serum gastrin levels and gastric juice excretion in view of feedback mechanism between gastrin-producing cells and parietal cells which are the target cells of gastrin.
Following results were obtained.
1) Fasting serum gastrin levels in Graves' disease were 236.2±39.1 (mean±SE) pg/ml for 39 hyperthyroid patients and 126.3±23.9 pg/ml for 35 euthyroid patients. These levels were significantly higher than those of sex and age-matched control subjects with P<0.001 and P<0.05, respectively. Fasting serum gastrin levels in serial studies of 13 patients with Graves' disease were 222.3±56.7 pg/ml before treatment and 167.3±56.6 pg/ml at the time of euthyroid state after a mean observation period of 6.6±1.1 months. Fasting serum gastrin levels at the time of euthyroid state decreased significantly when compared with fasting serum gastrin levels before treatment (P<0.05).
2) Fasting serum gastrin levels in chronic thyroiditis were 160.7±51.1 pg/ml for 24 hypothyroid patients and 96.4±24.7 pg/ml for 31 euthyroid patients. Each of these levels had no significant differences when compared with sex and age-matched control subjects. Fasting serum gastrin levels in serial studies of 10 patients with chronic thyroiditis were 81.1±18.0 pg/ml at the time of hypothyroid state and 91.5±15.2 pg/ml at the time of euthyroid state after a mean observation period of 7.1±2.1 months. Fasting serum gastrin levels before treatment had no significant differences when compared with fasting serum gastrin levels in euthyroid state.
3) Fasting serum gastrin levels in hyperthyroidism did not correlate with any of serum thyroxine levels, serum triiodothyronine levels and free thyroxine indices. Fasting serum gastrin levels did not significantly correlate with any of anti-thyroid microsomal antibody and anti-thyroglobulin antibody titers in both hyperthyroid and euthyroid state.
4) Fasting serum gastrin levels correlated inversely with the maximum acid output in the study of 22 patients with Graves' disease (r=-0.44, P<0.05).
5) Two group were differentiated in serial study of 8 patients with Graves' disease. In one group, fasting serum gastrin levels were decreased and normalized immediately in response to decline and/or normalization of thyroid functions. In the other group, fasting serum gastrin levels decreased rather slowly or retained at high levels with labile fluctuation relatively independently of thyroid functions. These results suggested that Graves' disease could be associated with multiple factors to elevate fasting serum gastrin levels, ie, existence of anti-parietal cell antibody, hyperresponsiveness of β-adrenergic receptors, gastric hypoacidity, interaction of gastrointestinal hormones, etc.

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A sensitive and specific radioimmunoassay (RIA) for arginine vasopressin (AVP) has been developed and validated. Synthetic AVP was coupled to bovine serum albumin (BSA) with glutalaldehyde. Antisera against AVP were raised in three rabbits immunized with AVP-BSA complex. After 6 months, at the 16th injection, one of the antisera had a titer high enough to be utilizable for RIA at a final dilution of 1 : 400,000.
The labeling of AVP with ¹²⁵I Na was performed with the modified chloramine T method, and the purification of iodinated AVP was done with gel filtration chromatography on a Sephadex G-25 fine column (1×20 cm) with an elution buffer of 0.01 M acetic acid containing 0.1% BSA. Radioactivities from the Sephadex G-25 were eluted in three peaks. ¹²⁵I-AVP, which was reactive to the antiserum, was contained in the third peak, and ¹²⁵I-AVP in the fractions on the down slope of the peak was used for the radioligand in the amount of 1000 cpm. The specific activity of purified ¹²⁵I-AVP was about 400 μCi/μg.
Diluted antiserum and samples, unlabeled AVP or related peptides were preincubated at 4°C for 24 hr, and then ¹²⁵I-AVP was added to the mixture and incubated for a further 72 hr. Separation of B and F was done with polyethyleneglycol.
The minimal detection limit of AVP, which was 95% of the confidence limit of the mean value of Bo, was 0.4 pg/tube. The cross-reactivities with lysine vasopressin, arginine vasotocin, DDAVP and oxytocin were 0.1%, 30%, 1% and 0%, respectively.
AVP in plasma was extracted with cold acetone and petroleum ether. The recoveries of synthetic AVP from plasma which was added (2-16 pg) were more than 94%. The intra and inter-assay coefficients of variation determined by plasma of AVP concentration of about 4.8 pg/ml were 8.7% and 11.3%, respectively. The RIA detected AVP of concentration as low as 1 pg/ml following the extraction procedure.
AVP immunoreactivity was detected without extraction in urine, and the lyophylized cerebrospinal fluid and acid extract of tissues of the central nervous system, and the reactivities in these samples were demonstrated to be immunologically identical to that of synthetic AVP when diluted serially.
The changes of plasma and urinary AVP concentration on water intake, water deprivation and smoking in humans were clearly demonstrated.
Water deprivation for 3 days in rats caused a marked decrease of AVP concentration in the neurointermediate lobe and a marked elevation of plasma AVP (one-third and twice the value of normally hydrated rats, respectively) without the changes of AVP concentration in the hypothalamus.
In conclusion, the RIA for AVP described here was sensitive and specific, and the applications of the RIA to various kinds of samples were thought to be valid in the investigation of AVP.

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In order to clarify the conversion of thyroxine (T₄) to triiodothyronine (T₃) or to reverse T₃ (rT₃), serum concentrations of T₄, T₃, rT₃, thyrotropin (TSH), thyroxine-binding globulin (TBG) and values of T₃ uptake (T₃ U) were measured in 61 hyperthyroid and 31 hypothyroid patients, 8 patients with subacute thyroiditis, and 40 normal subjects. Then, free T₄ index (FT₄ I), T₃ /T₄, rT₃ /T₄, and rT₃ /T₃ ratio were calculated.
The rT₃ /T₃ ratio was high in the hyperthyroid patients and low in the hypothyroid patients compared with that in the normal subjects. The ratio was positively related to serum T₄, T₃, rT₃ levels, and FT₄ I in the patients and normal subjects. The regression equation was represented by rT₃ /T₃ = 0.015 [T₄] + 0.083. No influences of serum TBG and age on the rT₃ /T₃ ratio were observed. Our results indicated that thyroid hormones themselves could regulate the conversion of T₄ to T₃ or rT₃ by activating 5-monodeiodinase in hyperthyroidism and by activating 5'-monodeiodinase and suppressing 5-monodeiodinase in hypothyroidism. Serum rT₃ level was a more sensitive parameter than serum T₄ or T₃ for evaluating thyroid dysfunction. During the treatment with methimazole (MMI) or Lthyroxine and the natural course of subacute thyroiditis, serum T₄ levels and rT₃ /T₃ ratios changed parallel to the regression line. However, once adverse effects of MMI occurred, those changed out of the line.
From these results, we concluded that the relationship between serum T₄ level and rT₃ /T₃ ratio should be examined for adequate information concerning the peripheral conversion of thyroid hormones under various thyroid diseases.

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While patients of chronic renal failure can survive today for a long period thanks to the spread of hemodialysis, establishment of criteria for the treatment of renal hyperparathyroidism is an important problem. In the 15 cases of renal hyperparathyroidism previously operated by the author, preoperative examinations and findings at the time of operation, and technique of operation and postoperative examinations were analyzed together with the effects of operation, and the indications and technique of operation were discussed.
1. Surgical indication
Since the histological findings of resected parathyroids presented chief cell hyperplasia in the whole gland and coexistence of fat tissues was hardly recognized, it was estimated that the weight of parathyroid glands directly reflected the secretory function of the parathyroid glands. Accordingly, the relation between the preoperative findings and weight of parathyroid glands was analyzed. As a result, a significant correlation was noted between the preoperative c-PTH and the weight of parathyroid glands. Hence it was proved possible to predict the approximate weight of parathyroid glands from the preoperative level of c-PTH. Further investigations were made on s-Al-P, s-CT, RMC, roentgenographic findings, ca-infusion test, iliac bone biopsy, subjective symptoms, and weight of parathyroid glands, and the following conclusions were obtained with respect to the surgical indication.
1) When the weight of parathyroid glands was estimated to be above 2000 mg, the operation would be an absolute indication.
2) If the weight is estimated between 1000 and 2000 mg, the operation should be preferred because the improvement by conservative treatment may not be expected.
3) In the case of slight swelling of less than 1000 mg, the first choice of treatment should be conservative. However the operation in the early stage would be essential in the case of calcification of the blood vessel wall.
2. Surgical technique
In 10 of the 15 cases operated, subtotal parathyroidectomy was performed. For longer period than 6 months after surgery clinical study was performed with respect to the changes in c-PTH, s-Al-P, CT, RMC, bone roentgenographic findings, s-Ca, s-P, iliac bone biopsy, and subjective symptoms. As a result, the postoperative course was good in patients in whom the subtotal parathyroidectomy was performed with 20 to 50 mg of the remaining parathyroid tissue. The value of c-PTH was stabilized in 3 months after the operation, and was thereafter controlled within normal ranges. In view of the possibility of the recurrence, the desirable weight of the remaining parathyroid tissue would be 20 to 30 mg. Meanwhile, total parathyroidectomy and auto-transplantation were attempted in 3 cases, and the clinical course looked good although the observation period after operation was rather short.

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