Impaired Na+,K+ATPase activity in red blood cells in euthyroid women treated with levothyroxine after total thyroidectomy for Graves' disease.

In patients suffering from hyperthyroidism dependent on Graves' disease, a reduction in Na+,K+ATPase activity has been demonstrated in red blood cells (RBCs), as well as an inverse correlation between this enzymatic action and free triiodothyronine (FT3) levels. The restoration of normal FT3 values also brings about a normalization of Na+,K+ATPase activity in erythrocytes. These results have made it possible to hypothesize that the thyroid hormones control Na+,K+ATPase activity and that this control is manifested by means of variations in the number of ouabain-binding sites. For this reason, the measurement of the activity of the Na/K pump can be considered as a further indicator of the peripheral effects of thyroid hormones. With a view to assess the relation between the course of treated hyperthyroidism and Na+,K+ATPase activity during antithyroid therapy and after surgical thyroidectomy followed by replacement therapy, we studied 24 patients affected by Graves' disease (group Graves [GG]). They were compared with 24 female Graves' patients who underwent total thyroidectomy for nontoxic and diffuse nodular goiter (NDNG) (group control [GC]) and with 24 normal healthy women (group normal [GN]). When Graves' hyperthyroidism was diagnosed, the Na+,K+ATPase activity in RBCs was impaired in all GG patients. Thionamide treatment restored the normal activity of the Na/K pump, accompanied by normalization of the number of ouabain-binding sites. One hundred eighty days after thyroidectomy, in conditions of clinical and biochemical euthyroidism due to replacement therapy with levothyroxine, the activity of Na+,K+ATPase in RBCs was once again reduced in GG, while appearing normal in GC and GN (1.77 +/- 0.16 mmol Pi h(-1) L(-1) RBCs v 2.09 +/- 0.26 v 2.09 +/- 0.24, P < .05). Different instrumental or biochemical parameters, such as glycemia, serum lipids, ions, serum alkaline phosphatase (AIPh), serum creatine phosphokinase (CPK), blood pressure, and heart rate, were evaluated and appeared normalized in GG and GC 180 days after surgery. We conclude that (1) in patients suffering from Graves' disease, subjected to total thyroidectomy followed by levothyroxine replacement therapy, there is a reduction in the activity of the Na+,K+ATPase on erythrocytes 6 months after the surgical approach; and (2) a similar alteration is not observed in patients subjected to thyroidectomy for NDNG. These findings allow the formulation of the hypothesis that (1) treatment with levothyroxine for 180 days after thyroidectomy in GG is not long enough to restore the normality of all the peripheral indicators of action of the thyroid hormones; and (2) levothyroxine replacement therapy is unable to guarantee euthyroidism in all the tissues in GG (eg, during hematopoiesis in the bone marrow).

Hypoglycaemia unawareness in a young boy with insulin-dependent diabetes mellitus and anti-adrenal medullary antibodies.

The main purpose of intensive insulin therapy in insulin-dependent diabetes mellitus is to prevent complications by maintaining short- and long-term euglycaemia. This therapeutic approach implies a high frequency of hypoglycaemic events which can be disturbing when hypoglycaemia unawareness is involved. Although this phenomenon can be reversed, it may lead to discontinuance of intensive insulin therapy. This paper concerns the case of a young insulin-dependent patient with early onset diabetes who had frequent severe occurrences of hypoglycaemia with convulsions, hypothermia, bradycardia and coma. These events were associated with hypoglycaemia unawareness not due to autonomic neuropathy. A defect in counterregulation was demonstrated during hypoglycaemic-hyperinsulinaemic clamp, expressed as a reduction of adrenaline response. A positive pattern of anti-adrenal medullary antibodies suggested that a functional defect of the adrenal medulla plays a role in the pathogenesis of hypoglycaemia unawareness.

Increased sodium influx and calcium uptake in erythrocytes in hyperthyroidism: role of abnormal membrane lipid levels.

The study was designed to examine the effects of thyroid hormones on red blood cell (RBC) membrane phospholipids and ion transport. We demonstrated that in untreated Graves' disease, an alteration in the phospholipid pattern is present at cellular levels, with a concomitant derangement in membrane permeability defined as (22)Na influx and (45)Ca uptake. Thionamide therapy replaced the normal membrane permeability, presumably as a consequence of restoring the normal phospholipid membrane composition. We conclude that thyroid hormones are able to induce a quick breakdown of a large number of membrane components such as membrane phospholipids.

Na+, K+ ATPase activity in red cells predicts the recurrence of hyperthyroidism in patients with Graves' disease.

Graves' disease is an autoimmune disorder characterized by a course of remission and relapse. Several parameters have been evaluated for their abilities to predict the clinical course of Graves' disease in patients treated with antithyroid drugs. We recently demonstrated in patients with hyperthyroidism dependent by Graves' disease, an impaired Na+, K+ ATPase activity in red cells and a correlation between ATPase and free T3. With the aim to clarify the relationship between the course of hyperthyroidism and the Na+, K+ ATPase activity during and after discontinuing the antithyroid therapy, we followed up 24 patients for two years. In our previous work by restoring a normal level of free T3, we obtained a normalization of Na+, K+ ATPase activity in the red cells of all the patients. However, in eight subjects after a period of 150 days following the suspension of therapy, we observed a new reduction of ATPase activity in a clinical condition of euthyroidism. The same subjects, newly evaluated after 150 days, developed a clinical and biochemical relapse of hyperthyroidism. We believe that the determination of Na+, K+ ATPase activity is able to predict the recurrence of hyperthyroidism in patients with Graves' disease.

Na+K+ATPase activity and ouabain binding sites in erythrocytes in hyperthyroidism before and after treatment.

Erythrocyte sodium pump is decreased in hyperthyroid patients. We described the effect of untreated hyperthyroidism on Na+K+ATPase activity, ouabain binding sites and intracellular sodium concentration. We found a reduction in Na+K+ATPase activity and in number of ouabain binding sites with a concomitant increase in intracellular sodium. B-blockade therapy failed to restore normal pump activity and sodium concentration, where only thionamide treatment was successful when it was able to decrease free T3.

Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats.

The relative contribution of atrial natriuretic peptide (ANP) and vasodilatory prostaglandins to hyperfiltration in Wistar rats with experimental diabetes was studied 6-8 wk after streptozocin injection. Plasma levels of immunoreactive ANP were significantly higher (P less than 0.01) in hyperglycemic diabetic (72.9 +/- 11.7 pg/ml) than in normoglycemic diabetic (44.8 +/- 8.6 pg/ml) or nondiabetic (40.0 +/- 6.8 pg/ml) rats. Blocking endogenous ANP by specific ANP-antiserum infusion reduced significantly (P less than 0.01) glomerular filtration rate (GFR) and renal plasma flow (RPF) of hyperglycemic rats compared with preinfusion values (1.23 +/- 0.06-1.02 +/- 0.04; 2.87 +/- 0.25-2.40 +/- 0.10 ml.min-1.100 g-1, respectively). However, correction of hyperfiltration and hyperperfusion was only partial (nondiabetic rats GFR 0.85 +/- 0.07; RPF 2.27 +/- 0.13 ml.min-1.100 g-1). Because diabetic rats with hyperglycemia also had an increased urinary excretion of prostacyclin metabolite 6-keto-prostaglandin F1 alpha (220.6 +/- 62.8 ng/24 h) compared with nondiabetic rats (51.2 +/- 2.7 ng/24 h), we wondered whether excessive prostacyclin formation contributed to hyperfiltration and hyperperfusion in this setting. Indomethacin infusion partially reduced GFR (1.25 +/- 0.07 to 1.06 +/- 0.07 ml.min-1.100 g-1, P less than 0.05) and RPF (2.85 +/- 0.11 to 2.46 +/- 0.12 ml.min-1.100 g-1, P less than 0.01) in diabetic rats. The combined infusion of ANP antiserum and indomethacin normalized GFR and RPF in diabetic rats with hyperglycemia (1.27 +/- 0.05 to 0.88 +/- 0.05 and 2.84 +/- 0.10 to 2.22 +/- 0.06 ml.min-1.100 g-1, respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[XYY syndrome. Report of a case]. / Sindrome XYY. Segnalazione di un caso.

A sixteen year old boy was admitted to our department for delayed puberty. The personal history was not significant and physical examination revealed only a genital hypogonadism. The endocrinology study of the patient showed a hypogonadotropic hypogonadism. The IQ was low. The personality showed infantilism and aggressive impulses. A karyotype revealed 47,XYY. We discuss here the clinical implications of the case.

Type I insulin-dependent diabetic patients show an impaired renal hemodynamic response to protein intake.

Human kidney responds to a meat meal with an increase in glomerular filtration rate (GFR), but the mechanisms regulating kidney hemodynamics following protein intake are poorly understood in Type I insulin-dependent diabetes. In the present study we investigated GFR response to protein intake (600 gr/1.73 m2 meat meal) in nine normal subjects and 21 Type I insulin-dependent diabetic patients with normal albumin excretion rates as well as proximal tubular sodium reabsorption rates and distal sodium delivery (PRNa and DDNa). The same study was reperformed in normal subjects and diabetic patients, with less than a 5 year diabetes duration, following one week of indomethacin treatment. Normal subjects showed a 38% increase in GFR following protein intake, whereas diabetic patients showed a significantly lower response (18%, p less than 0.01). The response of GFR to protein challenge was negatively related to diabetes duration but not to baseline glomerular filtration rate. Indomethacin treatment completely prevented the protein induced GFR increase in normal subjects but not in diabetic patients. Sodium reabsorption rate was increased following protein challenge both at the proximal and distal tubular level, as was net natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diabetic cardiomyopathy: preclinical pathology disclosed by the increase in ventricular afterload]. / Cardiomiopatia diabetica: patologia preclinica evidenziabile con l'incremento dell'afterload ventricolare.

In order to test the importance of the association of diabetes mellitus and arterial hypertension in generating morphological and functional changes of the left ventricle (LV) consistent with a cardiomyopathy, 37 patients, aged 27 +/- 6.7 years, were studied by standard and digitized M-Mode echo: eighteen of them were affected by diabetes mellitus, 11 by arterial hypertension, 8 by diabetes and hypertension. Each group was compared to the others and with a group of 14 normal subjects. In order to verify the importance of increased ventricular after-load in modifying ventricular performance of diabetic patients, changes of the peak rate of systolic and diastolic variation of LV diameter and changes of the peak rate of interventricular septum and posterior wall excursion (IVSE, PWE) were evaluated after methoxamine hydrochloride infusion in 8 diabetic and 6 normal subjects. In diabetics the ratio between ventricular thickness and diameter (h/r) was greater than normal subjects (p less than 0.02); this ratio resulted higher in patients with diabetic rhinopathy who also exhibited an isovolumic diastolic period longer than normal (p less than 0.02). Both h/r ratio and isovolumic diastolic period (IDP) were higher in diabetic-hypertensive group as compared to normals (p less than 0.001), strictly diabetic (p less than 0.01 and p less than 0.001) or hypertensive subjects (p less than 0.01). Diabetic-hypertensive group, exhibited a lowering of the systolic and diastolic peak rate of IVSE (p less than 0.01) as well as of systolic peak rate of PWE as compared to the other three groups (p less than 0.05).

Glomerular filtration rate is increased in man by the infusion of both D,L-3-hydroxybutyric acid and sodium D,L-3-hydroxybutyrate.

A high glomerular filtration rate (GFR) is often found early in insulin-dependent diabetes mellitus (IDDM). It has been suggested that high circulating glucose, glucagon, and GH levels could play a role in this increase in GFR. On the other hand, patients with IDDM in poor metabolic control also have high circulating ketone body levels. This study was undertaken to determine whether exogenous D,L-3-hydroxybutyric acid at two infusion rates (40 and 30 mumol kg-1 min-1) for 180 min altered renal plasma flow (RPF), GFR, and the excretion rate of total protein, beta 2-microglobulin, and albumin in 11 normal (N) subjects and 11 IDDM patients in whom euglycemia was achieved and maintained using the insulin-glucose clamp technique. RPF and GFR were measured by a priming-continuous infusion of [125I]hippurate and [51Cr]EDTA, respectively. The 40 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR in both N and IDDM subjects. Mean RPF increased from 588 +/- 78 (+/- SD) to 706 +/- 129 mL min-1 1.73 m-2 in N and from 671 +/- 101 to 781 +/- 99 in IDDM. GFR increased from 121 +/- 11 to 151 +/- 15 ml min-1 1.73 m-2 in N and from 136 +/- 11 to 191 +/- 16 in IDDM. The filtration fraction also was significantly higher in IDDM than in N during the D,L-3-hydroxybutyric acid infusion. The 30 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR to a somewhat lesser extent in both groups. D,L-3-hydroxybutyric acid infusions increased the tubular reabsorption rate of ketone bodies and sodium. The increase in tubular sodium reabsorption rate was correlated significantly to that in the tubular ketone body reabsorption rate. A significant decrease in urinary pH was found during the D,L-3-hydroxybutyric acid infusion. D,L-3-Hydroxybutyrate sodium salt (30 mumol kg-1 min-1) also was infused in 5 of the 11 diabetic patients. A similar increase in GFR and RPF occurred. Both total protein and beta 2-microglobulin, but not albumin, excretion rates increased during D,L-3-hydroxybutyric acid (40 mumol kg-1 min-1) infusion in N and IDDM subjects. D,L-3-Hydroxybutyric acid infusion did not change plasma glucagon, GH, or renin activity.(ABSTRACT TRUNCATED AT 400 WORDS)