Pituitary-thyroid feedback hypersensitivity as a novel cause of hypothyroidism in children.

Recognition and treatment of childhood hypothyroidism is essential to prevent serious developmental abnormalities, and neonatal screening based on detection of raised thyrotropin concentrations is routine. We investigated an adolescent who had developmental retardation because of an undiagnosed and novel cause of childhood hypothyroidism associated with normal circulating thyrotropin concentrations. Dynamic testing showed a hypersensitive pituitary-thyroid feedback axis with no evidence of other pituitary or hypothalamic disease, and sequence analysis of four candidate causative genes was negative. A high index of suspicion is required to diagnose and treat this disorder to prevent the consequences of long-term hypothyroidism on development.

Serum creatine kinase levels in overt and subclinical hypothyroidism.

Overt hypothyroidism is known to be associated with increased serum creatine kinase (CK) levels. However, there is little information on CK levels in subclinical hypothyroidism. The aim of the study was to assess the relationship between CK levels and thyroid function in overt and subclinical hypothyroidism. Thyroid function tests (thyrotropin [TSH], free thyroxine [FT4], free triiodothyronine [FT3]) and the serum levels of CK were obtained from 23 patients admitted to a general hospital for illnesses other than thyroid or muscular diseases, myocardial ischemia, or brain damage. Overt hypothyroidism, based on thyroid function tests, was present in 10 patients, whereas hypothyroidism could be classified as subclinical in the other 13. A positive correlation was observed between CK and thyrotropin, and to a lesser extent between CK and thyroid hormones. Moreover, the correlation between CK and TSH and between CK and FT4 was detectable in subclinical hypothyroidism. Our data suggest that even in subclinical hypothyroidism there is some degree of dysfunction in skeletal muscle metabolism.

[Biological aspects of treatment of hyperthyroidism]. / Aspects biologiques du traitement de l'hyperthyroïdie.

A woman treated for hyperthyroidism is described. This case illustrates two aspects of the laboratory follow-up of hyperthyroidism: sequential measurements of sensitive TSH and of the parameters of calcium metabolism.

Hypocalcemia after thyroidectomy.

Serum calcium, sodium, potassium, chloride, magnesium, phosphorus, osmolarity, total protein, albumin, parathyroid hormone, and calcitonin values were systematically surveyed in 135 patients who underwent thyroidectomy and in 104 control surgical patients. A transient and moderate hypocalcemia developed after operation in thyroidectomized and control patients. Concentrations of other electrolytes, osmolarity, proteins, and albumin followed the same pattern of evolution. After thyroidectomy, the degree and duration of hypocalcemia increased with the extent of thyroid resection. A profound hypocalcemia (less than 2.0 mmol/L) and a marked reduction of the parathyroid hormone concentration (below normal) were present in 12% and 8% of cases after subtotal thyroidectomy and in 22% after total thyroidectomy. Calcitonin values did not increase after thyroidectomy. A slight correlation was observed between the preoperative serum alkaline phosphatase level and the minimal postoperative serum calcium level. It is concluded that post-thyroidectomy hypocalcemia is a multifactorial phenomenon. It is due, at least in part, to hemodilution. A temporary parathyroid insufficiency after subtotal and total thyroidectomy, and an avidity of the skeleton for calcium in hyperthyroid patients, may aggravate the hypocalcemia.

Calcitonin and bone mass status in congenital hypothyroidism.

Calcitonin (CT) deficiency and its possible repercussions on bone mass were studied in a group of 9 adult patients (7 females, 2 males) with congenital hypothyroidism of dysgenetic origin. Using a new extraction method (exCT) which considerably improves the sensitivity and the specificity of the assay for CT-monomer, we measured CT levels before and after a short calcium (Ca) stimulation test (2 mg Ca/kg over 5 minutes) to evaluate C-cell secretory reserve. Mean basal plasma CT concentrations were lower in the hypothyroid women (mean +/- SEM: 0.6 +/- 0.1 pg/ml) than in 30 normal female controls (1.7 +/- 0.2 pg/ml, P less than 0.001). Serum calcium increased similarly in the two groups, but postinfusion CT levels were lower in the hypothyroid women, (1.7 +/- 0.2 pg/ml) than in normal women (16.8 +/- 2.9 pg/ml), P less than 0.001. Hypothyroid women showed a 10% reduction in bone mineral content at the diaphyseal site in the radius, 0.840 +/- 0.037 g/cm, compared with normal age-matched controls, 0.930 +/- 0.020 g/cm, (P less than 0.05). Our study demonstrates the existence of a profound CT-monomer deficiency in adult patients with thyroid agenesis or dysgenesis. Both calcitonin deficiency and thyroid hormone treatment could play a role in the observed bone loss. Attention should therefore be paid to bone metabolism during treatment of congenital hypothyroidism to avoid further bone loss.

[Value of echography for measuring the volume of the thyroid and its lesions]. / Valeur de l'échographie pour la mesure des volumes de la glande thyroïde et de ses lésions.

The sizes of thyroid lobes and lesions estimated by ultrasonography have been compared to surgical specimens in 92 cases of thyroid pathology. Volumes can be calculated with a reasonable accuracy for parenchymatous and cystic lesions from measurements of their diameters when considered as ellipsoids. This easy method, currently used by ultrasonographers, is however unsatisfactory for estimation of the volumes of thyroid lobes. More reliable results are obtained by computation of volumes from planimetry of cross-sections through the gland.

Pathogenesis of autonomous thyroid nodules: in vitro study of iodine and adenosine 3',5'-monophosphate metabolism.

The in vitro characteristics of iodide and cAMP metabolism have been compared in tissues from autonomously functioning thyroid nodules and their quiescent counterpart to test the hypothesis that autonomy may result from constitutive activation of the tissue's TSH, cAMP, and protein phosphorylation regulatory axis, as in vivo nodular tissue took up more iodide. This effect was entirely due to increased transport capacity, the affinity of iodide transport, and the fractional binding of iodide to protein remaining unchanged. However, at high concentrations total iodide binding to protein was similar in quiescent and nodular tissue. In both tissues, this metabolic step was enhanced by phorbol esters and the ionophore A23187. As evaluated by autoradiography of two-dimensional gel protein electrophoregrams, no differences in the patterns of protein synthesis or phosphorylation between quiescent and nodular tissue were found. Basal cAMP levels were similar in quiescent and nodular tissue. The cAMP response to TSH was lower in nodular tissue, with no change in sensitivity or kinetics; both tissues responded to forskolin. No systematic suppression of iodide inhibition or abnormal responses to other hormones or neurotransmitters were found. Three proteins (24K-1, 24K-2, and 26K) were phosphorylated only in the presence of TSH or forskolin in both quiescent and nodular tissue. One protein substrate (20K) was phosphorylated in the presence of TSH in the quiescent, but not in the nodular, tissue. In conclusion, 1) slices from autonomous thyroid nodules reproduce the in vivo characteristics of the lesion and are, therefore, a suitable in vitro experimental model for biochemical studies; 2) taken together with data from transplantation experiments, the reproduction in vitro or its in vivo characteristics suggest an inherent defect in the nodule; 3) the homogeneity of biochemical findings within each nodule is compatible with the clonality of the lesion; 4) the autonomous nodule is a minimal deviation tumor; and 5) the characteristics of the TSH, cAMP, protein phosphorylation cascade are qualitatively normal, and autonomy does not result from constitutive activation of this system; and 6) a 20K protein, not phosphorylated in response to TSH in the nodule, could represent an absent negative controlling element.

Calcitonin deficiency in primary hypothyroidism.

The relative lack of sensitivity and specificity of current assays for plasma calcitonin (CT) have made it difficult to study possible CT deficiency conditions. Using a new extraction method that considerably improves the sensitivity of the assay for CT monomer, CT levels were measured before and after a short calcium (Ca) stimulation test (2 mg Ca/kg over 5 min) to determine C-cell secretory reserve in women with autoimmune primary hypothyroidism and normal women. Mean basal plasma CT concentrations were lower in the hypothyroid women [0.9 +/- 0.1 (+/- SEM) pg/ml] than in the normal women (1.5 +/- 0.2 pg/ml; P less than 0.01). Serum Ca increased similarly in both groups, but postinfusion CT levels were lower in the women with primary hypothyroidism (3.8 +/- 1.3 pg/ml) than in normal women (15.9 +/- 3.0 pg/ml; P less than 0.001). The functional thyroid status at the time of the study did not influence CT levels; both hypothyroid patients (n = 10) and patients who were euthyroid during T4 treatment (n = 11) were CT deficient to the same extent. Unlike that in primary hypothyroidism, CT secretion was normal in four patients with hypothyroidism of pituitary origin. We conclude that the process that causes hypothyroidism in patients with autoimmune thyroid disease can also cause marked CT deficiency. This first demonstration of spontaneous CT deficiency in adults should contribute to the understanding of CT physiology; it also suggests that bone metabolism should be closely monitored during the treatment of primary hypothyroidism.

Iodide organification defect in a cold thyroid nodule: absence of iodide effect on cyclic AMP accumulation.

A follicular adenoma of the thyroid was 'hot' one hour after 99mTc pertechnetate administration, but 'cold' 24 h after 131I iodide administration. Incubation of the tissue in vitro demonstrated a defect in iodide binding to proteins that was abolished by addition of an H2O2 generating system. In this tissue iodide failed to inhibit TSH-induced cyclic AMP accumulation. The results show that iodide oxidation is required for its inhibitory action on cyclic AMP accumulation in human thyroid.

Ultrasound examination of the thyroid.

Ultrasound examination of the thyroid offers an accurate morphological picture and the possibility of comparing objectively the size of lobes and lesions over long periods. Cysts and calcifications, mostly benign, are readily recognized. Neoplastic lesions in our series were all less reflective than normal thyroid tissue. But so were the majority of benign nodules. In hyperthyroidism, subacute thyroiditis and Hashimoto's thyroiditis, the thyroid tissue is much less echogenic than in the normal gland.

Alterations in circulating thyroid hormones and thyroxine binding globulin in chronic alcoholism.

The present study concerns eighteen chronic alcoholics with minimal liver damage. A significant reduction in total serum T4 with an accompanying drop in circulating TBG was observed in these otherwise euthyroid patients. During alcohol withdrawal, we observed a rapid increase in T4 and TBG into the normal range. We suggest that the fall in the level of circulating thyroxine-binding globulin is related to a defect in its synthesis or secretion by the liver due to ethanol consumption. Caution is recommended in the interpretation of thyroid function tests in chronic alcoholics.

Thyroid status in elderly sick patients.

Thyroid investigations were performed on 55 euthyroid patients hospitalized for chronic disease or recovering from acute illness. Three age groups were considered. Abnormalities were found only in patients over 75 years: 1) in the TRH test the maximum increase in serum TSH (delta TSHmax) was less marked and frequently delayed to 60 min, whereas the increase in T3 in 120 min (delta T3) was maintained; basal TSH was normal; 2) in 15 out of 28 cases, the pattern of circulating thyronines was abnormal showing an increase in reverse T3 a normal or decreased T3, and a rise in free T4 index beyond the normal range in 3 cases. In all cases but one, the combination of delta TSHmax, and delta T3 differentiated these patients from hyperthyroids.

The effect of 131I for diagnostic purposes on serum thyroglobulin (hTg) levels in subjects with thyroidal disorders.

The concentration of serum thyroglobulin was measured in sera of subjects with various thyroid disorders, before and after the administration of tracer doses of 131I. The mean serum human thyroglobulin (hTg) concentration before administration of the isotope was 35.2 ng/ml +/- 7.8 (SE) in 13 subjects and 36.3 ng/ml +/- 7.9 (SE) 24 h after the administration of 131I. The data indicate that no significant release of thyroglobulin occurs 24 h after the administration of tracer doses of 131I. In 2 of the 3 subjects, however, in whom samples were obtained at 4 and 8 h after diagnostic administration of 131I, a modest rise in serum Tg levels was observed. Determinations of serum thyroglobulin levels within 24 h after the administration of a tracer dose of 131I are nevertheless valid providing one allows sufficient time to elapse for tracer decay.