[Basal metabolic rate as a thyroid function test].
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Biomedical subjects
Publications and source records attributed to Y Shishiba.
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The significance of PTH-radioimmunoassay was assessed in 63 surgically proven cases of primary hyperparathyroidism. To detect hyperparathyroidism, an increase in the free serum Ca index, [1-(8 X Alb + 2 X Glb + 3)/100] X Ca, has the highest predictive value (100%) for a positive test but a low predictive value (11.8%) for a negative test. It was necessary to improve the criteria to rule out the diagnosis of hyperparathyroidism. We therefore carried out a PTH radioimmunoassay employing kits made by CIS. The criteria for ruling out the diagnosis of hyperparathyroidism were that free serum Ca index was lower than 3 and PTH was lower than 4 mU/ml. The predictive value of these criteria for ruling out the diagnosis was 83.3%, significantly greater than the previously described criteria. Furthermore, the PTH concentration was significantly correlated to the weight of pathological parathyroid tissue surgically excised and to the free serum Ca index, although to a lesser extent than the latter. Thus, PTH-RIA is of value in improving diagnostic accuracy and in determining the severity of the disease.
Suppression of TSH and thyroid radioiodine uptake by doses of either T4 or T3 were compared in 33 patients in whom Graves' thyrotoxicosis had been treated with thioamide drugs and the medication was discontinued for at least 4 months. Thyroidal radiodine uptake was suppressed in 19 patients and was not suppressed in the remaining 14 patients. Basal TSH levels before suppression were 2.07 microU/ml in the former, significantly exceeding those of the latter (0.91 microU/ml). A TSH level of at least 1.2 microU/ml before suppression is a good predictor of positive thyroid radioiodine suppression with a predictive value of 76%. A level lower than 0.7 microU/ml before suppression is a good predictor of negative thyroid radioiodine uptake suppression with a predictive value of 89%. The determination of TSH levels before the thyroid suppression test was helpful in predicting the result, but there were limitations. In the thyroid suppression test positive group, circulating T4 was depressed by doses of T3. In them, the magnitude of T4 depression correlated with the levels of thyroid radioiodine uptake before suppression. The levels of TSH correlated neither to changes in T4 nor to those in thyroid radioiodine uptake. This indicates that the thyroid glands which show high radioiodine uptake are sensitive to TSH and are also sensitive to suppression. The elevated sensitivity to TSH probably warrants the disappearance of abnormal thyroid stimulation more precisely.
As there has been no data available on the variation of RIA through a year, we assessed within kit and component of between assay variation of TSH, LH, FSH, C-peptide and PRL kit through a year (more than 12 sequential assays). The average of within kit variation was 6.9% (ranged from 4.7 to 9.8%) and that of component of between assay variation was 11.2% (ranged from 8.9 to 14.5%). These values were almost similar to those obtained for the within kit variation and component of between assay variation employing single lot of kit. These results warrant that quality of kits produced by manufacturers was homogeneous throughout the observation period.
From three patients with pretibial myxedema (PTM) of Graves' disease, a portion of the skin involved was biopsied, analyzed for proteoglycans and the results were compared with those obtained with euthyroid and hyperthyroid subjects without PTM. The tissue specimen was extracted with 4 M guanidine HCl and subjected to subsequent CsCl density gradient centrifugation. Glycosaminoglycan and protein were recovered in the heaviest density fraction in the three specimens obtained from patients with PTM and not from subjects without PTM. From the analysis by Sepharose CL-6B column, glycosaminoglycan was present as a form of proteoglycan because alkaline borohydride treatment released single chain glycosaminoglycan with a molecular weight of 77,000 or 66,000. The digestion with chondroitin ABC lyase revealed that the majority of proteoglycan in the skin tissue was chondroitin sulfate or dermatan sulfate, and heparan sulfate comprised the minor component (14-34%). The rate of proteoglycan biosynthesis was examined by 35S incorporation into glycosaminoglycan's by cultured fibroblasts from PTM and normal skin. Incorporation of 35S into both proteoglycan and single chain glycosaminoglycan was observed in the fibroblasts of PTM patients as well as of those of subjects without PTM, although the rate of synthesis was more pronounced in the former. The rate of synthesis was influenced neither by normal serum or serum from a pretibial myxedema patient. Since proteoglycan accumulation was detected only in the affected skin of PTM patients, the impairment of local degradation and the proteoglycan clearance mechanism may also be involved.
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A family of multiple endocrine neoplasia type I with five confirmed cases in three generations is described. All of them have primary hyperparathyroidism in common. The propositus is 51 year-old male. After a year of symptoms of gastroduodenal ulcer, he was found to have elevated levels of serum gastrin and PTH. The serial imaging studies revealed a tumor in pancreatic head, and Zollinger-Ellison syndrome was diagnosed. The gastrin level was reduced into normal range after extirpation of the tumor, but post surgical elevation of Calcium put the patient under parathyroidectomy, which normalized serum PTH and Calcium levels. His two sisters (I and II), the mother of them, and the daughter of sister I, had neither signs nor symptoms until family study showed hypercalcemia in all. Sister I is a 54 year-old female with enlarged parathyroid. The hyperparathyroidism is of chemical type, but no other endocrinological abnormality is found. The Calcium level decreased after parathyroidectomy. Sister II is a 56 year-old female. The only sign was galactorrhea. Serum PTH and Calcium decreased after parathyroidectomy. The prolactinoma was diagnosed by the increased prolactin levels and enhanced mass lesion in sella turcica. Her serum prolactin levels is now within normal range since she is on bromocryptine. The mother of the above three siblings and the daughter of the sister I are now under further study.
To evaluate the clinical significance of human growth hormone (HGH) dynamics during transsphenoidal microsurgery for acromegaly, serial HGH levels during the surgery were compared with the post-operative basal HGH levels in 15 acromegalic patients, retrospectively. In all patients, in whom the HGH level immediately after tumor resection was reduced below 5 ng/ml or the decreasing rate which stood for the magnitude of decrease of HGH during resection procedure was above 80%, postoperative permanent HGH levels fell to below 5 ng/ml, namely, within the normal range. The rapid radioimmunoassay (RIA) of HGH was developed by the use of high affinity antibody in order to inform the surgeons of plasma HGH levels quickly during the surgery. It is now possible to know HGH levels about 1 hour after submitting the samples. It was verified that HGH levels measured in the rapid RIA correlated well with those obtained in the conventional way. The rapid RIA method was applied to 6 patients and the correlation between HGH levels during the surgery and post operative levels was also studied prospectively. The results were essentially identical to those in a retrospective study. It was suggested that the HGH level immediately after tumor resection and the extent of the decrease in HGH during the resection procedure were good indicators of the prognosis of surgical results in acromegaly and the rapid RIA method was useful in order to judge HGH levels quickly during the surgery.
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The heterogeneity of hPRL in the serum of a patient with a giant prolactinoma (hPRL 27 micrograms/ml) was studied employing gel chromatography, RIA and lymphoma cell bioassay. After gel filtration of serum sample on Sephadex G-100 (superfine) column, a few hPRL peaks were detected by RIA. Rechromatography of the second peak, which eluted between the void volume and the small third peak, revealed four hPRL peaks designated big-big hPRL, medium-big hPRL, big hPRL and little hPRL, with BA/RIA ratio 1.3 approximately 2.6, 0.8 approximately 1.2, 0.3 approximately 0.7 and 0.7 approximately 1.5, respectively. The molecular weight of medium-big hPRL was estimated as 80K approximately 90K daltons. Most of big-big, medium-big and big hPRL were converted to little hPRL after mercaptoethanol treatment. These data suggest that most of big-big, medium-big and big hPRL are aggregates of little hPRL.
The case presented is a prolactin producing tumor originated in the sphenoid sinus of a 40-year-old woman. Histologically this tumor is a typical chromophobe adenoma of the pituitary gland. Human prolactin was immunohistochemically detected in the cytoplasm of most tumor cells. The tumor invaded around the pituitary gland and in the nasal cavity without distant metastasis. Clinically the patient showed hyperprolactinemia and amenorrhea.
The size of the parathyroid gland was evaluated at different functional levels of the gland (control: 216 glands in 54 autopsy cases, chronic renal failure: 74 glands in 21 autopsy cases, hypercalcemia: 16 glands in 15 patients with primary hyperparathyroidism). This study is based on the fact that chronic renal failure causes a hypersecretory state of parathyroid hormone (PTH), and that hypercalcemia suppresses PTH secretion. The size of the parathyroid gland was represented by the largest area cut through the hilum of the gland. Interstitial and fatty tissues were excluded from the measuring. The lower parathyroid glands are larger than the upper glands in the control. Both the upper and the lower glands enlarge with a predominance of the lower glands in size in chronic renal failure. These results suggest that the functional level of the lower glands is higher than that of the upper glands not only in the normal but in a hypersecretory state of PTH. Hypercalcemia has been shown to cause a decrease in size of the lower glands, while the upper glands scarcely decrease in size. This result indicates that the lower glands play a major role in reducing PTH secretion when PTH secretion is suppressed. It is concluded that the lower parathyroid glands play a more important role than the upper glands in the maintenance and regulation of PTH secretion.
The heterogeneity of hGH in the sera, culture media of tumor cells and tumor extract from acromegalic patients was studied employing gel chromatography, RIA and lymphoma cell bioassay. The chromatographic profile of the sera on Sephadex G-100 (superfine) column showed three peaks: the major peak eluted with 125I-hGH (little hGH), the less retarded small peak (big hGH) and the peak at void volume (big-big hGH). Bioassay to radioimmunoassay ratio of big-big, big and little hGH were 1.07-5.75, 0.25-0.70 and 0.70-1.56, respectively. These ratios were not significantly different among the acromegalic sera obtained before and after TRH test. The longer duration sera were kept for, the higher percent of big-big hGH and the lower percent of little hGH the sera contained by RIA. The percentage of big-big hGH was less in the culture media of tumor cells than that in acromegalic sera, and the least in tumor extract by RIA. Rechromatography of big-big hGH fraction of tumor extract showed the conversion of big-big hGH to big and little hGHs. These data suggest that big-big hGH was artificially made from little and big hGH during storage. Rechromatography of fractions between big-big hGH and big hGH produced another peak (medium-big hGH) with approximately 80 K-90 K daltons of molecular weight. This peak was converted to almost a little hGH peak after mercaptoethanol treatment and was supposed to be a tetramer of little hGH.
Glycosaminoglycan (GAG) was extracted from thyroid tissue obtained at surgery for thyroid adenoma and adenocarcinoma and compared with that extracted from the thyroid tissue obtained at autopsy of non-thyroid disease. The amount of GAG was almost doubled in thyroid adenoma and increased from 6 to 15 fold in adenocarcinoma when compared with that of apparently normal thyroid tissue. Analysis by Sepharose 2B or 6B column chromatography revealed that at least a part of the GAG in thyroid carcinoma tissue was present in macromolecule form and the molecular size became smaller when treated with papain or alkaline borohydride. The results indicated that those fractions of GAG were present as proteoglycans. The GAG was composed of a mixture of heparan sulfate and chondroitin sulfate or dermatan sulfate in one carcinoma tissue and mainly composed of chondroitin sulfate or dermatan sulfate in the other. The mechanism of the increase in proteoglycan and GAG remains to be elucidated.
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Free T4 calculation was performed based on the equation of the law of mass action between T4 and TBG assessed by routine radioimmunoassay. To examine the validity of this calculation, sera from normal subjects, from hypo- and hyperthyroid patients, from subjects with hereditary deficiency or increase in TBG, and those from uncomplicated pregnancy were included in the assay and the results were compared with those directly measured by radioimmunoassay with encapsulated antibody. Free T4 calculation on the sera described above was almost equal to the free T4 concentration measured directly and reflected clinical thyroid states. Thus, the proposed equation for the calculation of free T4 from total T4 and TBG radioimmunoassay is useful for clinical purposes as well as direct free T4 radioimmunoassay.
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