Familial dysalbuminaemic hyperthyroxinaemia: a review.
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Humans↗
Biomedical subjects
J Faber
Publications and source records attributed to J Faber.
Euthyroid hyperthyroxinemia due to a generalized 5'-deiodinase defect.
We studied an 11-yr-old girl with asymptomatic hyperthyroxinemia, who remained euthyroid and healthy for 5 yr of follow-up. Besides having elevated serum T4 concentrations, her serum free T4 concentrations were consistently elevated, as measured by three different methods, including equilibrium dialysis and ultrafiltration. Serum total and free T3 concentrations were in the low normal range, and serum 3,5-diiodothyronine (3,5-T2) levels were low, suggesting reduced 5'-deiodination of both T4 and T3. Serum total and free rT3 and total and free 3', 5'-T2 concentrations were all markedly elevated, whereas serum total and free 3,3'-T2 were low, suggesting unaltered 5-deiodination of T4 to rT3 and of rT3 to 3',5'-T2 in combination with reduced 5'-deiodination of rT3 and 3',5'-T2. The girl had a small diffuse goiter, her serum TSH response to TRH was exaggerated, and thyroid radioiodine uptake was elevated, suggesting slightly increased TSH secretion and, consequently, increased thyroid secretion. Both T3 and T4 administration resulted in suppressed basal as well as TRH-stimulated serum TSH concentrations, and radioiodine uptake was suppressed during T3 administration. Our data suggest reduced activity of several (all?) peripheral 5'-deiodination pathways, including possibly also thyrotroph T4 5'-deiodination. Thus, this girl seems to have a previously unrecognized syndrome of generalized 5'-deiodinase deficiency.
Child↗
Thyroid hormone turnover in patients with small cell carcinoma of the lung.
Patients with small cell carcinoma of the lung often present with symptoms suggestive of hyperthyroidism i.e. weight loss without anorexia. Consequently [125I]T4 and [131I]T3 turnover was studied using simultaneously iv bolus injection and noncompartmental analysis in 6 patients with untreated small cell carcinoma of the lung and 14 normal subjects of comparable ages. Both T4 and T3 production rates were enhanced, T4 production being in median 135 nmol.day-1.70 kg-1 (range 111-200) in patients with small cell carcinoma of the lung vs 98 nmol.day-1.70 kg-1 (range 69-134) in controls (P less than 0.01), and T3 production being 46 nmol.day-1.70 kg-1 (range 33-65) vs 31 nmol.day-1.70 kg-1 (range 24-45) (P less than 0.01). The mean transit time was shortened for both T4 and T3, T4 mean transit time being 5.9 days (3.9-8.0 days) vs 8.3 days (6.1-11.2 days) in controls (P less than 0.01), and T3 mean transit time being 0.74 days (0.36-0.98 days) vs 1.03 days (0.81-1.45 days) in controls (P less than 0.01). Serum total and free T4 and T3 levels were unchanged. Basal serum TSH levels and the TSH response to iv TRH were also normal. Thyroid-stimulating immunoglobulins were only present in the serum in 1 of 6 patients. Thus, thyroid hormone production seemed under pituitary regulation. The peripheral effect of thyroid hormones was evaluated measuring serum sex hormone binding globulin levels, which were increased to in median 270% (77-310%) (P less than 0.01) of that in controls, suggesting some degree of hyperthyroidism in liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Metabolic clearance and production of diiodotyrosine in healthy man.
Metabolic clearance rate (MCR) and daily production rate (PR) of diiodotyrosine (DIT) were estimated using a constant infusion technique of trace amounts of [125-I]-DIT followed by chromatographical isolation of tracer. Median DIT MCR was in eight healthy subjects estimated to 162 l/day x 70 kg (range 135-242), whereas PR was 52 nmol/day x 70 kg (range 25-126). The median serum DIT concentration was 0.27 nmol/l (range 0.16-0.62). In five L-thyroxine substituted subjects without endogenous thyroxine (T4) production, serum DIT concentrations were below 0.02 nmol/l, suggesting that more than 94% of daily produced DIT is secreted by the thyroid gland.
Adult↗
Histochemical study of the forelimb muscles in Rana temporaria L.
Fibre types in the 7 forelimb muscles of Rana temporaria were characterized according to actomyosin ATP-ase activity and 5 distinct fibre types were distinguished. Besides the twitch fibres of type I, IIA, IIB, and IIC, also the tonic fibres were found in the examined muscles. The metabolic profiles of these fibre types was identified on the basis of SDH activity. The scores of SDH activity of different fibre types overlapped and correlation between fibre types defined by ATP-ase activity and their metabolic profiles was not found. All investigated muscles showed the heterogenous distribution of fibre types. Caput superius m. extensoris carpi radialis and caput mediale m. anconei were composed of 4 and 3 fibre types, respectively, in the opposite to the other ones which contained all 5 types of fibres.
Adenosine Triphosphatases↗
Thalamocortical reverberation circuit simulation using the simula language.
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Arousal↗
Sensitive serum thyrotropin assay assessed for efficiency of screening hospital patients.
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Hospitalization↗
Immunoradiometric assay of serum thyroid stimulating hormone (TSH) as a first-line test in a mixed hospital population.
An immunoradiometric assay of thyroid stimulating hormone (TSH-IRMA) was evaluated as a first-line test for the diagnosis of thyroid disease in a prospective study of 318 consecutive patients in a major city hospital. The results of TSH-IRMA were compared with the diagnoses made by means of our usual diagnostic methods. Based on previous studies a serum TSH level of 0.15 mU/l was chosen as cutoff limit for calculation of diagnostic performance. For patients with serum TSH greater than 5.0 mU/l the results of TSH-IRMA were in accordance with the results of our routine radioimmunoassay. Patients with serum TSH levels between 0.15 mU/l and 5.0 mU/l were euthyroid (the diagnostic sensitivity was 100%). Consequently, the final diagnosis could be made with one test and within two days for 88% of patients. Patients with serum TSH less than 0.15 mU/l needed supplementary tests since only 32% of these patients had thyrotoxicosis, 32% had a non-toxic goiter, and 36% had no thyroid disease.
Adolescent↗
[The electroencephalogram and stereo-electroencephalogram in epileptic and psychotic patients].
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Adolescent↗
From DNA transcription to visible structure: what the development of multicellular animals teaches us.
This article is concerned with the problem of the relation between the genetic information contained in the DNA and the emergence of visible structure in multicellular animals. The answer is sought in a reappraisal of the data of experimental embryology, considering molecular, cellular and organismal aspects. The presence of specific molecules only confers a tissue identity on the cells when their concentration exceeds the 'threshold of differentiation'. When this condition is not fulfilled the activity of the genes that code for the specific molecules in question only confers on them a histogenetic potency, i.e. the capacity to form the corresponding tissue in further development (or to trans-differentiate to that tissue). The progressive restriction of histogenetic potencies during development reflects the irreversible repression of more and more genes. The establishment of a given tissue identity under the influence of an inducing tissue (or a morphogenetic hormone) is only possible when the cells have acquired the competence to respond. Tissue differentiation proceeds progressively during development thanks to the cytoplasmic 'memory' that cells retain collectively (or sometimes individually) of the items of information successively registered by their ancestors cells. The increasing complexity of visible structure emerging during development results only from the progression of tissue differentiation. This involves continual exchange of information among the cells and leads to (1) cell displacements and rearrangements, particularly during organogenesis and (2) extreme diversification of cell individualities within tissues, particularly during postembryonic growth. A mutation (just as a teratogenic factor) evokes an anomaly that is localized in both space and time because it alters a certain aspect of cell behaviour (particularly cell surface adhesiveness or mitotic activity) at the time when this is involved in the establishment of a particular structural trait. Neither the organization of the adult nor the modalities of development are encoded in the DNA. The automatic concatenation of cell interactions in the embryo and the structural amplification it entails is conditioned by the specific biochemical composition of the cytoplasm of the egg and by the heterogeneous distribution of its inclusions.
Animals↗
Familial intestinal pseudoobstruction dominated by a progressive neurologic disease at a young age.
Chronic neuropathic intestinal pseudoobstruction is a rare entity, characterized by recurrent episodes of bowel obstruction without a mechanical obstructive cause. We report five members of two Jewish-Iranian families in whom chronic neuropathic intestinal pseudoobstruction was associated with an identical and unique progressive severe neuronal disease. It appeared within the first two decades of life. The disease consisted of external ophthalmoplegia, ptosis, and severe sensory and motor peripheral neuropathy. Three patients also had neuronal hearing loss. There was no evidence of central nervous system involvement and all patients were mentally intact. The combined disease was confirmed by radiologic, electrophysiologic, and histologic studies. Specific nutritional deficiencies, toxic elements, and systemic diseases affecting both the gastrointestinal tract and the nervous system were ruled out. It seems that these patients suffer from an autosomal recessive, presently unrecognized variant, of chronic neuropathic intestinal pseudoobstruction. In a patient with severe peripheral neuropathy of unknown etiology associated with symptoms suggestive of intestinal obstruction, the possibility of chronic neuropathic intestinal pseudoobstruction has to be considered.
Adolescent↗
Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine.
Cholecystokinin has previously been shown to produce a rise in immunoglobulin A (IgA) antibodies in the intestinal fluid of human volunteers. Whether the source of these antibodies was pancreatic, biliary, or mucosal had not been defined. The object of the present investigation was to study factors involved in regulating the release of IgA and IgG antibodies from the intestinal mucosa. Hooded-Lister rats were sensitized to ovalbumin. After the sensitization protocol, which lasted 21 days, the rats were anesthetized and a segment of intestine 10 cm long was isolated and perfused in vivo. This segment was flushed with normal saline for 30 min to remove all pancreatic, biliary, and other secretions. It was found in this model that after the intravenous injection of cholecystokinin-octapeptide there was a rise of IgA and IgG antibodies within 2.5 min. Significantly increased secretion of IgA lasted for 10 min, and increased secretion of IgG lasted for 20 min. The cholecystokinin antagonist proglumide reduced the secretions of both immunoglobulins. Atropine reduced baseline IgA secretion by one-half. Intragastric protein hydrolysate, which left the body through the severed end of the duodenum, also raised IgA and IgG levels significantly in the perfused intestine. Control animals receiving intragastric normal saline did not have an elevation of IgA or IgG levels. The phenomena described here demonstrate that the rate of IgA release from the mucosa is influenced by endocrine and nervous stimuli. The rate of IgG release is, as far as could be ascertained, only under endocrine control and not significantly influenced by the cholinergic antagonist atropine.
Animals↗
Familial dysalbuminemic hyperthyroxinemia.
A family with familial dysalbuminemic hyperthyroxinemia is described. The syndrome is inherited as an autosomal dominant trait and is characterized by marked elevation of serum thyroxine, due to increased binding of thyroxine to albumin, whereas serum triiodothyronine is normal. Serum free thyroxine is normal when measured with ultrafiltration or equilibrium dialysis, but artefactually high when measured with an analogue assay. The importance of the condition, which is harmless, lies in the misinterpretation of values with subsequent erroneous treatment of thyrotoxicosis. By using an ultrasensitive TSH method it is possible to discriminate between euthyroid and hyperthyroid patients and thereby to avoid incorrect diagnosis in subjects with euthyroid hyperthyroxinemia.
Adolescent↗
Relationships between serum thyrotropin, serum free thyroxine (T4), and 3,5,3'-triiodothyronine (T3) and the daily T4 and T3 production rates in euthyroid patients with multinodular goiter.
Serum TSH, as measured by a sensitive assay, and serum free T4 and T3, as measured by an ultrafiltration technique, were compared in 14 euthyroid patients with multinodular goiter and 14 normal subjects. T4 and T3 turnover studies also were performed, using the single injection, noncompartmental approach. The goitrous patients had serum free T3 levels within the normal range, but their median serum T3 level was increased compared to that in the normal subjects [goitrous patients, 5.48 pmol/L (range, 4.41-9.03); normal subjects, 4.12 pmol/L (range, 2.58-5.78); P less than 0.01]. The T3 production rate (PR) also was elevated in the patients (median, 39.4 nmol/day X 70 kg; range, 28.7-70.5) compared to that in the normal subjects 31.1 nmol/day X 70 kg; range, 24.4-45.2); P less than 0.05). No differences were found between the two groups with regard to serum free T4 levels or T4 PRs. Serum TSH levels in the patients were reduced (median, 0.20 mU/L; range, less than 0.05-1.6) compared to those in normal subjects (1.8 mU/L; range, 0.36-5.1; P less than 0.01). A significant inverse correlation was found between serum TSH levels and free T3 levels (r = 0.70; P less than 0.001), whereas serum TSH did not correlate with serum free T4 or the PR of T4 or T3. Our data suggest that clinically and biochemically euthyroid patients with multinodular goiter have slight T3 hyperproduction, and TSH secretion in the patients studied was more closely related to serum free T3 levels than to serum free T4 levels or the T3 or T4 PR.
Adult↗
Pituitary-thyroid axis in critical illness.
Severe nonthyroidal illness has been claimed to cause secondary hypothyroidism. We reevaluated this concept measuring serum free T4 and free T3 by an ultrafiltration method and serum TSH by an ultrasensitive technique (detection limit, and serum TSH by an ultrasensitive technique (detection limit, 0.05 mU/L). Forty-five critically ill patients suffering from hepatic coma (n = 10), terminal cancer (n = 9), stroke (n = 8), and respiratory insufficiency not treated (n = 7) and treated (n = 11) with dopamine were studied. The mortality rate was 80%. No patients received glucocorticoids, and only patients in the last group received dopamine. Serum total as well as free thyroid hormone index values were grossly reduced in the majority of the patients. The 34 patients not receiving dopamine in general had normal values of serum free T4 (32 of 34) and free T3 (31 of 34), measurable TSH (33 of 34), and detectable TSH responses to iv TRH (33 of 34). In contrast, the dopamine-treated patients had reduced serum free T4 and TSH levels compared to normal subjects (P less than 0.05), as well as reduced TSH responses to TRH (P less than 0.01). Serum free T4 and free T3 were below the normal range in 3 patients and 1 patient, respectively, and serum TSH was below the detection limit in 2 patients. We conclude that critically ill patients with nonthyroidal illness not receiving dopamine have normal pituitary-thyroid function, whereas dopamine induces some degree of secondary hypothyroidism.
Adult↗
Familial progressive neuronal disease and chronic idiopathic intestinal pseudo-obstruction.
Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterized by recurrent episodes of bowel obstruction without mechanical cause. In five members of two Jewish-Iranian families, CIIP was associated with progressive neuronal disease, starting before age 30, with ophthalmoplegia, sensorimotor peripheral neuropathy, and hearing loss. There was no evidence of CNS involvement. The pattern suggested autosomal recessive inheritance.
Adolescent↗
Renal handling of thyroxine, 3,5,3'- and 3,3',5'-triiodothyronine, 3,3'- and 3',5'-diiodothyronine in man.
The 24-h urinary excretion and renal clearance of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), and 3',5'-diiodothyronine (3',5'-T2) were measured in 17 healthy subjects. The median urinary excretion was (pmol/24h) T4: 1242, T3: 828, rT3: 12.9, 3,3'-T2: 331, and 3',5'-T2: 5.8. The corresponding renal clearances were in median (ml/min) T4: 31, T3: 133, rT3: 15, 3,3'-T2: 683, and 3',5'-T2: 4.5. The clearances differed mutually (P less than 0.01) as well as from the creatinine clearance (P less than 0.01) which was in median 87 ml/min. Thus, all iodothyronines studied were subject to tubular transport mechanisms besides glomerular filtration. The 3 iodothyronines with 2 iodine atoms in the phenolic ring of the thyronine molecule, T4, rT3 and 3',5'-T2, were mainly tubularly reabsorbed, whereas those with only one iodine atom in the phenolic ring, T3 and 3,3'-T2, were mainly tubularly secreted. It might be hypothesized that the number of iodine atoms in the phenolic ring determines the direction of the tubular transport (presence of 2 iodine atoms is associated with tubular reabsorption, and of one iodine atom with secretion), whereas the rate of tubular transport decreases with decreasing number of iodine atoms in the tyrosylic ring.
Adult↗
The influence of free fatty acids on the free fraction of thyroid hormones in serum as estimated by ultrafiltration.
Thyroid hormones are displaced from their binding proteins in serum during nonthyroidal somatic illness, and FFA have been claimed to contribute. It seems mandatory to evaluate this effect using techniques for the measurements of serum free thyroid hormones in which serum remains undiluted. We measured the effect of 7 common human FFA on the free fraction of T4, T3 and rT3 in serum from healthy subjects using an ultrafiltration technique by which serum is diluted only minimally. In addition we measured the effect of oleic acid on the free fractions of the iodothyronines in pooled serum from healthy subjects and in pooled serum from patients with nonthyroidal illness. All FFA tested were able to displace both T4, T3 and rT3, but to a varying degree, arachidonic and linoleic acid being the most potent ones. A 20% increase in the free fractions of T4, T3 and rT3, respectively, was obtained by adding between 1.7-3.3 mmol/l, 1.3-4.6 mmol/l and 1.0-2.4 mmol/l of the different FFA. A serum pool obtained from patients with nonthyroidal somatic illness was more sensitive to oleic acid than a serum pool obtained from healthy subjects, since 2-3 times less oleic acid was necessary to induce a 20% increase in the free fractions of thyroid hormones. It is concluded that FFA are able to displace both T4, T3 and rT3 from their serum binding proteins in healthy subjects as well as in patients with nonthyroidal illness. However, serum from patients with nonthyroidal illness was more sensitive to the displacing activity of oleic acid than serum from healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Cerebrovascular Disorders↗