Emilio Mattar

Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome.

Abstract The hypothalamic-pituitary-gonadal system was evaluated in three siblings with the Bardet-Biedl syndrome. All patients had mental retardation, pigmentary retinopathy, obesity, polydactyly, and hypogonadism. Serum levels of luteinizing hormone (LH) were above the upper limit of normality in the elder brothers (101.6 and 62.6 ng/ml, respectively) but were within normal limits in the younger patient. Serum follicle-stimulating hormone (FSH) was within the normal range for all three patients. After 100 μg of intravenous gonadotropin-releasing hormone (LH-RH), the LH and FSH serum levels showed a response that correlated well with the respective pubertal stages of the patients. Chronic stimulation with synthetic LH-RH (500 μg for 3 days) was also followed by a marked rise in both LH and FSH. Clomiphene administration induced a marked rise in serum LH, while FSH values did not show a clear elevation. Although plasma testosterone was found to be normal for each individual patient, repeated stimulation with human chorionic gonadotrophin failed to further increase plasma testosterone in the two elder brothers. Basal levels of serum prolactin and growth hormone were within the normal range and stimulatory and supressive tests for these pituitary hormones were also normal in these patients. An oral glucose tolerance test revealed high basal levels and an exaggerated rise in plasma insulin values. Testicular biopsy performed in the three patients showed a nonuniform degenerative lesion of the seminiferous tubules with marked reduction of spermatogenic activity. Only scant groups of Leydig cells were seen in the interstitium with a clear decrease of the total number of these cells. These findings indicated a trend to an evolutive gonadal disorder possibly beginning near the onset of puberty and progressing throughout the adult life.

Effects of adrenergic stimulating and blocking agents on glucose-induced insulin responses in human thyrotoxicosis.

Abstract The effects of thyroid hormone excess on insulin responses to a constant glucose infusion ( 300 mg min/60 min ) were studied in five adult thyrotoxic patients with Graves disease before and after they had attained euthyroidism. The tests were also performed during administration of isoproterenol (0.05 μg/kg body weight/min), propranolol (0.08 mg/min) and phentolamine (0.5 mg/min). In the control experiments, to similar plasma glucose, thyroid hormone excess was accompanied by higher fasting plasma insulin, suggesting an insulin resistant state. During glucose infusion, to similar glucose increments, insulin concentration increased in both hyper and euthyroid states, differences in concentration observed in the fasting state disappearing during the infusion, suggesting either reversal of the insulin resistant state and/or decreased insulin responses in the hyperthyroid state. During isoproterenol administration, thyroid hormone excess induced disproportionally higher insulin responses to glucose, suggesting that β-stimulation and thyroid hormone exerted agonistic actions. During propranolol administration, thyroid hormone excess counteracted the β-adrenergic blockade effect in decreasing insulin secretion, suggesting that thyroid hormone and β-adrenergic blockade presented antagonistic effects. During phentolamine administration, apart from its effect by itself, no apparent action of thyroid hormone excess on insulin responses to glucose could be demonstrated. The results suggest that thyroid hormone influences on glucose-induced insulin responses are apparently agonistically interrelated to the β-adrenergic tonus of the patients.

Preparation of high-quality iodine-125-labelled pituitary human follicle-stimulating hormone (hFSH) for radioimmunoassay: Comparison of enzymatic and chloramine-T iodination

A method is described for the enzymatic radioiodination of human follicle-stimulating hormone (hFSH) by a system consisting of lactoperoxidase, hydrogen peroxide and Na125I. It was compared with the Chloramine-T modified technique. A satisfactory specific activity of the labelled hormone was obtained with the enzymatic iodination with much greater immunoreactivity was stability than after Chloramine-T.

HEREDITARY CONGENITAL GOITRE WITH THYROGLOBULIN DEFICIENCY CAUSING HYPOTHYROIDISM

The thyroid glands of two hypothyroid goitrous siblings aged 13 and 14 and of a 21‐year‐old hypothyroid goitrous female were examined. In all three patients a very high thyroid uptake of iodide was observed in the presence of a negative perchlorate discharge test. An abnormally high serum protein bound iodine (12·9–20·0 μg/dl) and low serum T4 concentration suggested the presence of increased serum levels of iodoalbumin. Surprisingly, serum T3 levels were normal or low normal (80–220 ng/dl) in several determinations. Basal serum TSH was elevated and an exaggerated TSH response was observed after TRH. Serum thyroglobulin was undetectable in one patient, low normal in another and in the normal range for the third one. Except for the patient with undetectable Tg the two other subjects slightly increased the serum Tg levels after a bovine TSH injection. Plasma chromatography after a tracer dose of 125I disclosed only minute amounts of T3+T4 and MIT+DIT. Studies performed in the homogenized thyroid tissues indicated that these goitrous glands had pronounced decrease of immunoreactive thyroglobulin. The total amount of Tg‐like proteins (RIA) in the thyroid soluble protein extract was only 16–122 μg/g (normal: 50–70 mg/g of tissue). Ultracentrifugal studies were unable to demonstrate the presence of mature (18–20S) thyroglobulin. Only one peak (3·6–4·1S) was obtained in the pooled soluble proteins supernatants. Hydrolysis of the homogenates indicated, by subsequent column chromatography, very low relative concentrations of iodotyrosines and iodothyronines and that a relatively large amount of iodide remained associated with subcellular proteins and undigested. The predominant histological pattern was of the intermediary differentiated adenoma type, microfollicular or fetal, with several atypical features and capsular invasion which may suggest malignant change. We conclude that a defective Tg export from the cell to the lumen or an anomaly in the structural gene leading to inadequate translation of Tg mRNA finally results in deficient storage of normal, mature Tg in the colloid with subsequent goitrous hypothyroidism.

ON THE MECHANISM OF INSULIN HYPERSENSITIVITY IN ADRENOCORTICAL INSUFFICIENCY.

A study of the sensitivity to a test dose of exogenous insulin was undertaken in eight patients with primary and five with secondary (Sheehans syndrome) adrenal insufficiency. The great majority showed hypersensitivity to insulin and hypoglycemia-unresponsiveness was present in all. The hypersensitivity was primarily the result of excessive peripheral insulin action as shown by the increased disappearance rate (k) of an intravenous glucose load, in the well nourished patient. A possible failure in glycogenesis and consequent reduced glucose release by the liver, which might explain the hypoglycemia-unresponsiveness, was not confirmed by the glucagon test, suggesting that if there is liver impairment it is in its rate of glucose release independent of the amount of glycogen present and related to the glucocorticoid influence on the threshold of blood glucose regulation by the liver.

Comparison of plasma progesterone assay in women by competitive protein binding (CPB) and radioimmunoassay (RIA)

Plasma progesterone levels during the follicular and luteal phases were compared when measured simultaneously by competitive protein binding (using guinea pig sera as binding agent) and radioimmunoassay (antiserum against progesterone-11-alpha-succinyl bovine serum albumin in rabbits), the values obtained were significantly different within each technique, depending on whether previous thin-layer chromatographic purification of the extracts was employed or not. No significant differences were noticed between CPB and RIA when the chromatographic step was used, but when it was omitted, CPB was greater than RIA at the follicular but not at the luteal phase.

Electrophoretic patterns of the plasma proteins in diffuse liver necrosis

It is well recognized that changes in electrophoretic patterns of serum or plasma proteins occur in various types of liver diseases.l-l0 To date, however, only a few isolated studies of these proteins have been reported in patients with diffuse hepatic necrosis.s, 9 Systematic attempt has not yet been made to evaluate the results in a large series of proved cases. * We describe in the present paper the electrophoretic pattern of the plasma proteins seen in 10 cases of diffuse liver necrosis in all of which extensive anatomico-pathologic studies of the liver were made. The exact diagnosis of such cases being frequently impossible solely on the bases of the clinical picture and usual tests, we preferred grouping them according to the anatomicopathologic features, considering three criteria: (1) Diffuse or focal, according to the extension of the lesion throughout the liver as a whole. In the present studies we will consider only the diffuse cases. (2) Massive or zonal, according to the extension of the lesion throughout the hepatic lobule.n (3) Fulminant or protracted, according to the approximate duration of the lesions. We based the distinction between fulminant and protracted forms on the absence or presence of regeneration, degree of bile duct proliferation, reticulum collapse, and widening of sinusoids. However, no one of these criteria alone allows a positive judgment concerning the length of the process. In 5 cases (1. A. P., C. C., B. C. M., A. J., and J. A. Q.) the pathologic features were suggestive of a viral etiology, according to the criteria of Lucke and Mallory.13