Biomedical subjects
Publications and source records attributed to F Maloof.
Serum thyroxine and triiodothyronine levels in 15 adult phenylketonuric patients on an unrestricted diet were normal despite reduced circulating tyrosine levels. Serum thyrotropin levels were normal in the basal state or in response to thyrotropin-releasing hormone in selected patients tested. These results support and extend previous observations of normal thyroid function in phenylketonuria.
In 60 patients with pituitary adenomas, the serum concentration of the alpha subunit of the glycoprotein hormones (serum alpha) was measured by a sensitive and specific radioimmunoassay. Five patients had markedly elevated serum alpha prior to therapy (range 14.5-23.0 ng/ml). These 5 patients included 2 hyperthyroid men with inappropriately high serum thyrotropin, one of whom also had acromegaly, a man with hyperprolactinemia and elevated cerebrospinal fluid alpha, a postmenopausal woman with low serum gonadotropins and hyperprolactinemia, and a man with central hypothyroidism and hypogonadism. Three of the 5 were restudied after therapy; serum alpha in these three decreased from19.5 to 10.6, 23.0 to 2.0, and 17.0 to 12.0 ng/ml. Alpha in these 3 patinets' serum eluted similarly to normal pituitary alpha by gel chromatography. The other 55 patinets, including twenty with acromegaly, fifteen with galactorrhea, and two with Nelson's syndrome, had serum alpha.less than 0.5-5.0 ng/ml. In addition, 22 patients with "empty sella" syndrome (no pituitary tumor) had alpha less than 0.5-5.0 ng/ml. Normal men and premenopausal women had serum alpha concentrations of less than 0.5-2.5 ng/ml; normal postmenopausal women, 1.0-7.0 ng/ml; and patients with primary hypothyroidism, 0.7-9.0 ng/ml. The decreased alpha response to thyrotropin and luteinizing hormone-releasing hormones (TRH and LHRH) implied a relative autonomy of pituitary tumor alpha secretion; the mean alpha increment in the 5 patients with elevated serum alpha was 15% after TRH administration and 10% after LHRH. Normal individuals and patients with primary hypothyroidism demonstrated greater mean per cent alpha increments after TRH or LHRH. In certain patients with an enlarged sella turcica, an elevated serum alpha with little or no increase in secretion after TRH and LHRH may suggest the presence of pituitary tumor.
In order to determine the mechanism by which glucocorticosteroids decrease the serum concentration of thyrotropin (TSH), we studied eight normal subjects before and after they received 16 mg of dexamethasone daily for 2 1/2 days. Serum levels of TSH and prolactin (PRL) were measured in the basal state and in response to the intravenous administration of 200 mug thyrotropin-releasing hormone (TRH); T4, free T4 (fT4), T3, and free T3 (fT3) were measured before TRH injection. Metabolic clearance rates of TSH corrected for body surface area (MCR-TSH/m2) were determined by the method of constant infusion to equilibrium; the production rates of TSH (PR-TSH/m2) were calculated. Dexamethasone produced a decrease in basal TSH from 2.2 to 0.8 muU/ml (P less than 0.02), a statistically insignificant elevation in MCR-TSH/m2 from 25.8 to 34.1 ml/min/m2, and a decrease in PR-TSH/m2 from 79 to 30 mU/day/m2 (P less than 0.01). Peak TSH response to TRH decreased from 16.4 to 5.8 muU/ml (P less than 0.005), as did TSH reserve from 1.58 to 0.54 mU - min/ml (P less than 0.005). Repetitive TRH testing alone did not account for these changes. Basal PRL, peak PRL after TRH, and PRL reserve did not change significantly after dexamethasone administration. Although Basal T4 and fT4 did not change significantly, dexamethasone did decrease T3 from 106 to 61 ng/dl (P less than 0.001) and fT3 from 174 to 76 pg/dl (P less than 0.05). Dexamethasone produced similar changes in patients with various thyroid disorders. In addition, when plasma cortisol was lowered by metyrapone administration in 25 euthyroid patients, the serum TSH concentration rose from 1.6 to 3.1 muU/ml (P less than 0.001). These data indicate that dexamethasone a) suppresses TSH secretion without increasing fT3 and fT4 and b) blunts the TSH, but not the PRL response, to TRH. Hence, one effect of the administration of dexamethasone in high dose is a direct suppression of pituitary TSH secretion. Furthermore, physiologic levesl of circulating cortisol also have a suppressive effect on serum TSH.
Certain preparations of human serum albumin have been found to decrease the apparent titer of antisera to alpha subunit of human TSH (hTSH-alpha) and the sensitivity of the resultant radioimmunoassay for the immunologically common alpha subunit of the human glycoprotein hormones. Utilizing bovine serum albumin as the carrier protein, antisera to hTSH-alpha had 20-fold higher titers, and the resultant radioimmunoassay demonstrated 20-fold greater sensitivity for alpha subunit. Interference in the alpha immunoassay was not caused by protease since protease inhibitors did not eliminate it. Gel chromatography of human serum albumin revealed alph immunoactivity in an elution position identical to that of standard alpha subunit. Only certain human serum albumin preparations demonstrated interference in the radioimmunoassay because of the species specificity of the alpha subunit.A possible explanation for the alpha subunit contamination of human albumin preparations may be contamination of the serum source with placental blood, which contains large quantities of the alpha subunit of human chorionic gonadotropin.
A 33 year old woman with persistent galactorrhoea developed breast cancer six years after pituitary radiation for a pituitary adenoma (Forbes-Albright syndrome). The possible role of prolactin in human mammary cacinoma is discussed.
As with any specialized diagnostic technique, the degree of success and safety of needle biopsy of the thyroid are largely based on experience. While an adequate core of tissue for examination is imperative, the interpretation by the pathologist is equally important. A close liaison of the latter with his clinical colleagues is necessary for optimal pathologic evaluation. A review of this experience during a 20 year period shows that needle biopsy is a reliable diagnostic procedure in more than 90 per cent of the patients. It is unlikely to disseminate the disease or compromise the prognosis, and it is a safe office procedure.
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The molecular size of microsomal membrane proteins from frozen porcine thyroids before and after solubilization by proteolytic and non-proteolytic techniques has been investigated by means of polyacrylamide-gel electrophoresis in the presence of 1% sodium dodecylsulfate. When thyroid microsomal membrane proteins are solubilized by non-proteolytic methods such as high pH, n-butanol, or deoxycholate, no major change in the electrophoretic pattern compared to untreated microsomes has been observed, thereby suggesting that these non-proteolytic methods are capable of extracting membrane proteins from thyroid microsomes without altering their molecular size. However, treatment of microsomes with protein-solubilizing levels of trypsin (1-5 mug trypsin per mg thyroid protein) results in degradation of all major proteins with a molecular weight greater than 30 000. The high-molecular-weight proteins are particularly susceptible to attack by trypsin. Thus, these experiments indicate that the use of trypsin to solubilize thyroid microsomal membrane proteins, particularly thyroid peroxidase, will result in fragmented proteins and should be avoided if intact membrane proteins are desired.
Nontoxic goiters are very common. A single hyperfunctioning nodule is never malignant. Treatment is required only if the patient is hyperthyroid. Most single hypofunctioning thyroid nodules are cool and most are benign; however, it is important to rule out malignancy. The presence of microcalcification is consistent with psammoma bodies and the presence of papillary cancer of the thyroid. An elevated plasma calcitonin level with a further increase in calcitonin after calcium infusion is usually characteristic of medullary cancer of the thyroid. Needle biopsy of the thyroid is recommended when an experienced surgeon and pathologist are available. The treatment of benign thyroid lesions may include a trial of fully suppressive doses of thyroxine.
Between 1000 and 1200 hr on any given morning, female rats displaying regular 4-day estrous cycles were bled by decapitation. Plasma TSH concentrations were determined by homologous radioimmunoassay (RIA), in terms of NIAMDD-Rat-TSH-I-1 standards. Mean plasma TSH concentrations plus or minus SE were 1.2 plus or minus 0.1, 1.5 plus or minus 0.2, 2.3 plus or minus 0.6, and 1.1 plus or minus 0.1 ng/ml for rats killed at proestrus, estrus, diestrus-1, and diestrus-2, respectively. Statistical analysis revealed no significant differences among the TSH levels, except for the elevation at diestrus-1, which is of borderline significance at the 0.05 probability level. Our findings, based on RIA, are in contrast to previous reports, based on bioassays, of an elevation of plasma TSH at estrus.
Utilizing sensitive and specific radioimmunoassays, serum concentrations of human thyrotropin (hTSH), the immunologically common alpha subunit of the glycoprotein hormones, and the specific beta subunit of hTSH ( hTSH-beta) have been measured in normal individuals, in patients with primary hypothyroidism, and in patients with other disorders of thyroid function before and after intravenous administration of thyrotropin releasing hormone (TRH). In 29 normal individuals hTSH-beta was not detectable in serum (smaller than 0.5 ng/ml) before or after TRH; alpha was smaller than 0.5-2.0 ng/ml in men and premenopausal women and 1.0-5.0 ng/ml in postmenopausal women and did not increase after TRH. In 20 patients with primary hypothyroidism mean serum hTSH-beta was 1.3 ng/ml and increased to a peak value of 3.7 ng/ml after TRH; mean alpha was 4.3 ng/ml and increased to 6.3 ng/ml after TRH. None of the patients with Graves' disease, a hyperfunctioning thyroid nodule, or hypothyrotropic hypothyroidism had detectable serum hTSH-beta concentrations or alpha concentrations higher than the normals before or after TRH. In 3 patients with primary hypothyroidism given an intravenous bolus of labeled hTSH, no dissociation of hTSH into subunits was detectable for at least 3 h, indicating that the increment in serum alpha and hTSH-beta after TRH represented secretion of free subunits from the pituitary. In addition, L-thyroxine (L-T4) administered to 2 hypothyroid patients decreased the serum concentrations of alpha and hTSH-beta before and after TRH. Serum hTSH-beta was fully suppressed with 100-300 mug L-T4 daily, but there was a residual serum alpha component, which could not be suppressed with thyroid hormone and probably represented alpha subunits arising from gonadotropin-secreting pituitary cells. Normal pituitary glands also contained a predominance of free alpha subunit relative to hTSH-beta, in addition to hTSH. The secretion of free subunits in hypothyroidism may represent only a quantitative difference from the normal state, and subunits of hTSH appear to respond to the same control mechanisms as complete hTSH.
The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.
Ten patients (8 women, 2 men) with the "empty sella syndrome" were studied to evaluate the pituitary reserve of human thyrotropin (hTSH) and prolactin (hPRL). None of the patients had signs or symptoms of hypopituitarism or primary hypothyroidism. All patients had normal baseline thyroid function tests except for 2 patients with mild elevations in total triiodothyronine as measured by competitive protein displacement assay (T3D). Eight of ten patients had normal hTSH responses to thyrotropin releasing hormone (TRH), whereas the 2 patients with elevated T3D had blunted TRH responses. In the 4 patients studied, the metabolic clearance (MCR) and production rates (PR) of hTSH were normal. In 9 of 10 patients normal baseline serum hPRL levels were detected, and each responded to TRH. In one case serum hPRL was undetectable and failed to respond to TRH. The assessment of other anterior pituitary function revealed few minor abnormalities. In summary, like other anterior pituitary hormones, the pituitary reserve in "empty sella syndrome" of hTSH and hPRL is usually normal. When abnormalities do occur, they are attributable to other co-existent endocrine pathology.
A euthyroid woman with ophthalmic Graves disease developed endogenous hyperthyroidism coincident with T3 suppression test. There is a putative role of liothyronine administration in precipitating or activating hyperthyroidism. Aberrancies in T3 suppression testing in graves disease occur.
1. The treatment of Graves' Disease by Potassium Iodide (like thyroidectomy, radioiodine, and antithyroid drugs) is followed by rate failure of thyroid function. 2. These findings suggest that the natural history of Graves' Disease may be one of progression from hyperthyroidism towards a decreased thyroid functional state. This progression may be accelerated by ablative methods of treatment. 3. Certainly, all patients with Graves' Disease, no matter what the treatment may be, should be followed carefully for the rest of their lives. 4. In certain patients, Potassium Iodide appears to be an effective means of controlling the hyperthyroidism of Graves' Disease.
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