Months Of Replacement Therapy Research Articles

Personified Orthodontic Treatment of Adults with Malocclusions and Deformations in Dentition Depending on the Degree of Caries Resistance of the Dental Enamel

Background: To increase the effectiveness of orthodontic treatment in children with various degrees of dental enamel caries resistance using a personified orthodontic treatment. Materials and Methods: The present study included 108 adults (6-16 years old) with the first class of occlusion who referred for the Department of Pediatric Dentistry with orthodontics in Voronezh pediatrics’ dental clinic №2 Russian Federation. According to the study design, it can be characterized as open, prospective, and clinical. The electrometric diagnostics of dental enamel and electromyography of the masseter and temporalis were recorded. Results: Functional therapy with the proposed personified orthodontic treatment normalized the mean number of biopotential masseters and temporalis muscles and improved caries resistance of hard dental tissues. However, the examination on the group of children with a low degree caries resistance of dental enamel resulted in the decrease in the mean number of electrometric diagnostics from 4.0 (3.6; 6.0) μA-1.6 (1.5; 3.37) μA (differences are statistically significant, p˂0.05) after 18 months of replacement therapy. In turn, the mean number of bioelectric activity of masseter and temporalis muscles changed from 324.25 (303.75; 345.75) μV-332.5 (318.75; 347.25) μV, p˂0.05. Conclusion: Employing the personified orthodontic treatment depending on the degree of caries resistance of the tooth enamel, determination of the functional state of the masseter and temporalis, and electrometric diagnosis of dental hard tissues enhanced the effectiveness of orthodontic treatment.

EMPATHY: A New Tool for Identifying the Most Suitable Thyroxine Formulation in Hypothyroid Patients.

Background: Therapy of hypothyroidism is based on the administration of appropriate doses of levothyroxine (LT4). A failure to achieve the thyrotropin (TSH) target may be due to poor compliance with the LT4 therapy in about 60% of cases or to malabsorption in about 40% of cases. No tools are available for detecting malabsorption disorders before the choice of the most appropriate therapy. The aim of this study was to validate the Evaluation of Malabsorption in PATients with HYpothyroidism (EMPATHY) questionnaire and to demonstrate its usefulness in indicating the most appropriate therapy. Methods: EMPATHY consists of seven questions that allow the evaluation of several intolerances and allergies. Three hundred (100 males) newly diagnosed hypothyroid patients were enrolled and randomly assigned to complete an EMPATHY questionnaire (150 patients; group 1) or to a control group (150 patients; group 2). The choice of thyroxine formulation and dose for each group was made on the basis of the questionnaire answers or based on the history. Thyroid hormones and TSH were evaluated at enrollment and then every two months for six months; the number of the dose adjustments in the six months for each patient was recorded. Results: Of the 150 patients in each group, 21 (14%) in group 1 and 42 (28%) in group 2 (p = 0.005) needed more than two dose adjustments within six months. After six months of replacement therapy, six (4%) patients in group 1 and 17 (11%) in group 2 (p = 0.03) did not have appropriately controlled hypothyroidism (TSH ≥2.5 mIU/L). A significantly higher LT4 final dose was found in group 2 (148 ± 33 μg/day) than in group 1 (136 ± 28 μg/day; p = 0.003). Conclusions: Validation of EMPATHY provides endocrinologists with a useful tool in clinical practice, permitting a better personalization of LT4 replacement therapy, a more rapid attainment of the target TSH levels, and a decreased need for dose adjustments after initiating therapy.

Short- and long-term responsiveness to low dose growth hormone (GH) in adult GH deficiency: Role of GH receptor polymorphism.

In patients with growth hormone (GH) deficiency (GHD), low doses of recombinant human GH (rhGH) have a similar or better long-term clinical effect than higher doses. Pharmacogenetic studies suggest that GH receptor (GHR) polymorphism only influences some metabolic parameters. Nonetheless, there is no clear scientific evidence proving the effects of lower rhGH dose regimens on metabolic parameters. The aim of our prospective study was to evaluate the effects of GHR polymorphism in adult GHD patients treated with low rhGH dose during short- (6 and 12months) and long-term (5years) follow-up. Sixty-nine GHD adult patients were studied, before and during treatment with rhGH, using a standardised low-dose protocol calculated on the basis of body weight (0.01-0.03mgkg-1 week-1 ) and monitored by an insulin-like growth factor (IGF)-I plasma assay, as well as anthropometric and metabolic parameters. The GHR genotype (flfl, fld3 or d3d3) was determined from the peripheral blood. d3-GHR carriers showed a more effective short- and long-term response to low rhGH dose with respect to low-density lipoprotein reduction, body composition and blood pressure (homozygous patients only); d3-GHR homozygosity is related to a significant IGF-I increase during short-term follow-up. Regression analysis demonstrated that rhGH dose, age at diagnosis and GHR genotype are the major determinants of IGF-I increase at 6 and 12months of replacement therapy. The d3d3-GHR genotype may influence some metabolic effects during the short- and long-term follow-up of low rhGH dose and could be an independent determinant of the increase of IGF- I during short-term follow-up.

Cholecalciferol improves glycemic control in type 2 diabetic patients: a 6-month prospective interventional study.

Background and purposeTo investigate the effects of vitamin D supplementation on glucose homeostasis and lipid profile in type 2 diabetic patients who have vitamin D deficiency.Patients and methodsOne hundred twenty-five type 2 diabetic patients taking oral hypoglycemic agents as mono- or combination therapy were recruited from the diabetes and endocrinology clinic. Subject demographics, duration of diabetes, antidiabetic medication, body mass index (BMI), pulse, and blood pressure (BP) were assessed. Laboratory measurements of serum vitamin D3 level, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and lipid profile were measured. Homeostatic model assessment-insulin resistance (HOMA-IR) was calculated whenever fasting insulin (FI) was available. Forty-one patients (27 males and 14 females) were started on cholecalciferol replacement–45,000 units once weekly for 8 weeks and then 22,500 units once weekly for 16 weeks. Calcium carbonate tablets 500 mg once daily were also prescribed for the initial 2 months of treatment. Measured variables were reassessed after 6 months of replacement therapy. During the trial, subjects were instructed not to change their diabetes drugs or lifestyle.ResultsNo significant association was found between vitamin D3 level and any of the measured variables apart from a significant positive correlation with blood urea nitrogen. Vitamin D3 replacement was associated with a significant increase in its level (14.0±4.0 vs 31.0 vs 7.9 ng/mL, P<0.001). This was associated with a significant reduction of HbA1c (7.9±1.7 vs 7.4%±1.2%, P=0.001) and FPG (9.1±4.3 vs 7.9±2.4 mmol/L, P=0.034). Mean reduction of HbA1c was 0.54% and that of FPG was 1.22 mmol/L. FI, c-peptide and insulin resistance (IR) were reduced but this was statistically insignificant (P=0.069, 0.376, 0.058, respectively). FI decreased by 22%, HOMA-IR by 27.6%, and c-peptide by 1.83%. Total cholesterol, low-density lipoprotein cholesterol, parathyroid hormone, alkaline phosphatase, serum creatinine, and pulse rate significantly decreased (4.3±0.9 vs 4.0±0.9 mmol/L, P=0.036; 2.5±0.8 vs 2.2±0.8 mmol/L, P=0.018; 4.6±2.1 vs 3.5±1.8 pmol/L, P=0.001; 82.1±26.2 vs 66.2±19.5 U/L, P<0.001; 74.6±15.6 vs 70.7±14.7 μmol/L, P=0.047; and 81.6±11.9 vs 77.5±12.0 bpm, P=0.045, respectively). Triglycerides and high-density lipoprotein cholesterol, both systolic and diastolic BP, and BMI did not show significant change.ConclusionCholecalciferol helps improve blood glucose control and cholesterol profile in vitamin D3-deficient type 2 diabetic patients.

Autonomic nervous system and cardiovascular risk assessment during one year of growth hormone replacement therapy in adults with growth hormone deficiency.

This prospective study aimed to evaluate the impact of growth hormone deficiency (GHD) on cardiac autonomic tone and on cardiovascular risk and the changes after 12 months of GH replacement therapy (GHRT). GHD is associated with increased cardiovascular morbidity and mortality. This has been attributed to increased markers of cardiovascular risk and to abnormalities of both the cardiac and peripheral autonomic nervous systems. The autonomic cardiac nervous system (ACNS) can be indirectly evaluated by analysis of heart rate variability (HRV) in clinostatism and orthostatism. We compared 14 GHD patients at baseline and after 12 months of GHRT and 17 healthy controls. We analyzed a number of cardiovascular risk factors and we used analysis of HRV during the Tilt Test that identified high frequency (HF) and low frequency (LF), representing parasympathetic and sympathetic activity, respectively. Compared with the control group, in either clinostatism or in orthostatism our patients showed a significantly lower value of LF (P=0.047; P=0.004, respectively), whereas HF was significantly reduced in orthostatism (P=0.037), and indicatively in clinostatism (P=0.065). These values remained unchanged after 12 months of GHRT. No statistically significant differences were found between the LF/HF ratio in untreated and treated patients. In GHD patients, there was a significant reduction of cardiovascular risk in 12 months of replacement therapy (P=0.002). Our study highlights the absence of sympathovagal imbalance in GHD patients; GHRT does not change ACNS during the first year of GH treatment but it reduces the absolute cardiovascular risk in these patients.

Chronic dialysis discontinuation: a systematic narrative review of the literature in the new millennium.

Renal function recovery (RFR), defined as the discontinuation of dialysis after 3 months of replacement therapy, is an uncommon occurrence. At a time when the "too early" start of dialysis is in discussion, a systematic review of the literature for cases in which patients recovered renal function after starting dialysis with chronic indications, including single cases and large series, may lead to attention being focused on this interesting issue. The search strategy was built in Medline on Pubmed, in EMBASE and in the Cochrane Collaboration (August 2013) combining Mesh, Emtree and free terms: dialysis or hemodialysis, kidney function, renal function and recovery (publication date 2000-2013). The following tasks were performed in duplicate: titles and abstracts were manually screened, the data were extracted: title, author, objective, year, journal, period of study, multi-center, country, type of study. The systematic review retrieved 1,894 titles; 58 full papers were retrieved and the final selection included 24 papers: 11 case series or Registry data (4 from ANZdata) and 13 case reports. In spite of the high heterogeneity of the studies, overall they suggest that RFR occurs in about 1% of patients, without differences between PD and HD. RFR appears to be more frequent in elderly patients with renal vascular disease (up to 10% RFR in cholesterol emboli or scleroderma), but is reported in all types of primary and secondary kidney diseases. RFR is a clinical event that should be looked for, particularly in elderly patients with vascular comorbidity.

Effects of L-Thyroxine Therapy on Circulating Leptin and Adiponectin Levels in Subclinical Hypothyroidism: A Prospective Study

Subclinical hypothyroidism (SCH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) levels. Controversial data are available regarding the effects of SCH on adipose tissue. Adiponectin and leptin are two major adipokines secreted from adipose tissue. We aimed to determine the levels of adiponectin and leptin in women with SCH and potential effects of L-thyroxine therapy on those levels. Forty three women with SCH and 53 age- and BMI-matched healthy euthyroid control women were included. Adiponectin and leptin levels, total cholesterol (TC), triglycerides (TG), HDL-, and LDL cholesterol, fat mass (FM) and fat-free mass (FFM) were determined in all participants. Patients received L-thyroxine treatment for 6 months after which all measurements were repeated. Patients with SCH and controls had similar baseline values for adiponectin, leptin, lipids, FM and FFM. All patients reached euthyroid status after 6 months of replacement therapy. Treatment resulted in an increase in adiponectin (p <0.01) and a decrease in leptin levels (p <0.05). Lipid levels, FM and FFM did not show a significant change. Achievement of euthyroid status by replacement therapy increases adiponectin and decreases leptin levels in women with SCH in this prospective study independent of a change in body fat mass.

Long-Term Effects of Growth Hormone Replacement Therapy on Thyroid Function in Adults with Growth Hormone Deficiency

Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient

We report detailed genetic and immunologic studies in a patient diagnosed with adenosine deaminase (ADA) deficiency and combined immune deficiency at age 5 years. At the time of diagnosis, although all other lymphocyte subsets were depleted, circulating CD8 + T cells with a terminally differentiated phenotype were abundant and expressed normal ADA activity due to a reversion mutation in a CD8 + T cell or precursor. Over the first 9 months of replacement therapy with PEG-ADA, the patient steadily accumulated mature naïve CD4 + and CD8 + T cells, as well as CD4 +/FOXP3 + regulatory T cells, consistent with restoration of a functional cellular immune system. While CD19 + naïve B cells also accumulated in response to PEG-ADA therapy, a high proportion of these B cells exhibited an immature surface marker phenotype even after 9 months, and immunization with neoantigen bacteriophage ϕX174 demonstrated a markedly subnormal humoral immune response. Our observations in this single patient have important implications for gene therapy of human ADA deficiency, as they indicate that ADA expression within even a large circulating lymphocyte population may not be sufficient to support adequate immune reconstitution. They also suggest that an immature surface marker phenotype of the peripheral B cell compartment may be a useful surrogate marker for incomplete humoral immune reconstitution during enzyme replacement, and possibly other forms of hematopoietic cell therapies.

Neural response to transcranial magnetic stimulation in adult hypothyroidism and effect of replacement treatment

Purpose Despite clinical evidences that hypothyroidism is often associated with cognitive dysfunction, affective disorders and psychosis, the effects of thyroid hormone deficiency on the adult brain have been largely unexplored. We investigated the hypothesis that hypothyroidism might affect cortical excitability and modulates inhibitory and excitatory cortical circuits by using Transcranial Magnetic Stimulation. Materials and methods Cortical excitability was probed in 10 patients with overt hypothyroidism and 10 age-matched healthy controls. We tested motor thresholds and corticospinal excitability, cortical silent period and peripheral silent period, short interval intracortical inhibition, intracortical facilitation. Patients were evaluated at the time of diagnosis, as well as after 3 and 6 months replacement therapy with l-thyroxin. Results At baseline, patients showed decreased cortical excitability, with increased resting and active motor threshold and decreased steepness of the motor evoked potential recruitment curves. These changes were paralleled by longer cortical silent period and decreased short interval intracortical inhibition. After 3 months replacement therapy, all the parameters but short interval intracortical inhibition were restored to normal values. Short interval intracortical inhibition returned to normal values only after 6 months of replacement therapy. Conclusions Thyroid hormones are needed to modulate cortical excitability and cortical inhibitory circuits in adults.

Effects of levothyroxine therapy on left and right ventricular function in neonates with congenital hypothyroidism: a tissue Doppler echocardiography study

Cardiac function is impaired in adults or children with hypothyroidism and it can be reversed by levothyroxine (L-T(4)) substitution therapy. However, only a few studies are available on left and right ventricular function in neonates with congenital hypothyroidism (CH), most of which were performed with standard echocardiography. The aim of this study was to investigate the effects of L-T(4) substitution therapy on left and right ventricular function in neonates with CH, measured with tissue Doppler echocardiography (TDE) and conventional echocardiography. Fifty neonates (27 females and 23 males) with CH and 35 normal neonates (19 females and 16 males) underwent conventional echocardiography and TDE. On TDE, peak mitral and tricuspid annular systolic (Sa) velocity, peak early (Ea) and late (Aa) mitral and tricuspid annular diastolic velocity were measured, and the Ea/Aa ratio was calculated. All the biochemical tests and echocardiographic evaluations were reevaluated after 1 month of replacement therapy. In CH neonates, TDE showed that CH neonates had significantly lower Sa, Ea, and Ea/Aa of both left and right ventricles (P<0.001, respectively). However, Aa of left and right ventricles did not differ significantly. After 1 month of substitutive therapy, CH neonates showed a significant increase of Sa and Ea and a subsequent increase of the Ea/Aa ratio (P<0.001, respectively). Our findings suggest that neonates with CH suffer from right ventricular subclinical systolic and diastolic dysfunction in addition to left ventricular dysfunction. Early L-T(4) substitution therapy is able to reverse the impairment of cardiac function.

Acquired Ichthyosis and Hypertrichosis due to Autoimmune Thyroiditis: Therapeutic Response to Thyroxine Replacement

Thyroid diseases may be associated with a wide variety of dermatologic disorders. We report a 15-year-old girl with acquired ichthyosis and hypertrichosis associated with hypothyroidism resulting from autoimmune thyroiditis. Her skin lesions progressively resolved after 8 months of replacement therapy with L-thyroxine. This result supports the hypothesis that hypothyroidism in our patient can be directly related to the pathogenesis of acquired ichthyosis and hypertrichosis.

The effect of growth hormone (GH) replacement therapy on sympathetic nerve hyperactivity in hypopituitary adults

Objective To test whether sympathetic nerve hyperactivity associated with adult hypopituitarism and untreated growth hormone (GH) deficiency is affected by GH treatment. Design and methods Sympathetic nerve activity to the muscle vascular bed (MSA) expressed as burst frequency (bursts/min) and incidence (bursts/100 heartbeats) was recorded in 10 hypopituitary patients (aged 48–69 years), before and after acute (1 week) randomized, double-blind, crossover treatment with a 1-month washout period and chronic (1 year) GH replacement treatment. Results MSA burst frequency and incidence remained unchanged from baseline values after the short-term treatment, but exhibited decreases in median values [from 53 to 47 bursts/min (P = 0.02) and from 85 to 70 bursts/100 heartbeats (P = 0.03), respectively] after 12 months of replacement therapy. Twenty-four-hour urinary excretion of nitrate increased after the short-term cross-over treatment and the long-term treatment (P = 0.04). Diastolic blood pressure and waist circumference decreased after the 12-month treatment (P = 0.02 and P = 0.04, respectively). No correlation was found between the reduction in MSA and the increase in 24-h urinary nitrate excretion, the decrease in diastolic blood pressure and waist circumference. Conclusions The sympathoexcitation in adult GH deficiency and the modest decline in MSA seen after long-term GH replacement treatment may suggest that the somatotropic axis is involved in the regulation of central sympathetic outflow.

Magnetic Resonance Imaging–Assessed Adipose Tissue and Serum Lipid and Insulin Concentrations in Growth Hormone–Deficient Adults

The visceral and subcutaneous abdominal adipose tissue (AT) areas and the subcutaneous hip AT area were assessed by magnetic resonance imaging (MRI) in relation to serum lipid and plasma insulin levels in 12 growth hormone-deficient (GHD) adults before and after 6 months of replacement therapy with recombinant human growth hormone (rhGH) and in 12 healthy control subjects. Compared with control subjects, GHD patients had a significantly increased amount of visceral AT, which was inversely related with plasma HDL cholesterol and positively correlated with plasma triglyceride levels. Visceral AT was not associated with plasma total and LDL cholesterol or plasma insulin concentrations. GHD patients also had elevated serum total cholesterol, LDL cholesterol, and triglyceride levels compared with control subjects. After 6 months of rhGH replacement therapy the mean visceral, subcutaneous abdominal, and subcutaneous hip AT areas and serum concentration of total cholesterol decreased significantly, whereas serum HDL cholesterol concentration increased significantly. No significant correlations were found between changes in the amount of AT and changes in serum lipid and plasma insulin levels.

Hormonal agents used in lowering lipoprotein(a)

Lipoprotein(a) (Lp(a)) plasma concentrations in Caucasian populations are classified as a quantitative genetic trait. Although the prevailing view has been that Lp(a) levels are affected by age and gender, recent data are beginning to indicate otherwise. Lp(a) levels change throughout life especially in females after menopause. Lp(a) levels decrease in women treated with anabolic steroids such as stanozolol and danazol. The Lp(a) plasma concentration is also profoundly affected by sex hormone variations during pregnancy. In men with prostatic cancer Lp(a) levels are reduced about 50% by estrogen therapy, and increased 20% by orchidectomy. We have evaluated the changes in Lp(a) and lipid levels in postmenopausal women following estrogen/progestogen replacement therapy. The mean level of Lp(a) in treated women was about 50% lower after 6 and 12 months of replacement therapy. A significant correlation between basal Lp(a) levels and the changes at either 6 or 12 months was observed, suggesting that therapy was particularly efficacious in those women with high basal Lp(a) levels. One year after therapy cessation, Lp(a) concentrations tended to return to pre-therapy values. In addition estrogen-progestogen treatment significantly lowered total-cholesterol (12%) and LDL-cholesterol (28%), and increased HDL-cholesterol (18%). From these studies it appears that sex hormones are actively involved in the modulation of plasma Lp(a) levels and that both female and male sex hormones possess a lowering effect. The results confirm a direct effect of sex hormones on Lp(a) metabolism and suggest that estrogen-progestogen treatment of postmenopausal women can improve the lipid profile not only by lowering total- and LDL-cholesterol and raising HDL cholesterol, but also by lowering plasma Lp(a).

Effects of transdermal 17β‐oestradiol combined with oral progestogen on lipids and lipoproteins in hypercholesterolaemic postmenopausal women

The purpose of the study was to evaluate the effect of transdermal 17 beta-oestradiol with oral progestogen on the plasma levels of lipids, lipoproteins and apolipoproteins in hypercholesterolaemic postmenopausal women. During 6 months of replacement therapy with transdermal 17 beta-oestradiol combined with oral progestogen, plasma lipids, lipoproteins and apolipoproteins after 3 and 6 months were measured and compared with pretreatment values by Student's t-test. From January 1992 until September 1992 patients were diagnosed and treated in an out-patient clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw. The patients studied were 11 non-obese postmenopausal women with hypercholesterolaemia based on the World Health Organization criteria. Venous blood samples were obtained before and 3 and 6 months after the beginning of cyclic replacement therapy with transdermal 17 beta-oestradiol (E2 100 micrograms day-1 combined with oral chlormadinone acetate (2 mg day-1 for 7 days in each cycle). The antiatherogenic effect of transdermal oestrogen replacement therapy exerted by increased levels of high-density lipoprotein subfraction 2 cholesterol (HDL2-C) leading to the decrease of the total cholesterol level was anticipated. After 6 months of the treatment the concentrations of HDL2 cholesterol (HDL2-C) increased from 0.45 +/- 0.07 mmol l-1 to 0.73 +/- 0.03 mol l-1 (P < 0.05) but the levels of HDL3 cholesterol (HDL3-C) decreased from 1.15 +/- 0.06 mmol l-1 to 0.89 +/- 0.07 mmol l-1 (P < 0.05). The concentrations of total cholesterol decreased from 6.9 +/- 0.13 mmol l-1 to 6.2 +/- 0.2 mmol l-1 (P < 0.05). No changes were observed in the plasma levels of total triglycerides, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, apolipoproteins A-I and B. In hypercholesterolaemic postmenopausal women, transdermally administered 17 beta-oestradiol 100 micrograms daily in combination with oral chlormadinone acetate has a beneficial effect through raising the level of the antiatherogenic HDL2-C subfraction and decreasing the level of total cholesterol.

Control of breathing in patients with severe hypothyroidism

purpose: Hypothyroid patients have been reported to have a blunted ventilatory response to carbon dioxide stimulation. However, previous data did not clarify the localization of abnormalities responsible for that disorder. The present investigation was aimed at evaluating to what extent central (neural) and/or peripheral (muscular) factors are involved in the abnormalities of the ventilatory control system in hypothyroid patients. patients and methods: We studied 13 patients with severe hypothyroidism before and after 6 to 9 months of replacement therapy, 7 age- and sex-matched normal subjects were also studied as a control. In each subject, we assessed (1) inspiratory muscle strength by measuring maximal inspiratory pressure (MIP), and (2) respiratory control system during a carbon dioxide rebreathing test by measuring minute ventilation (V e), tidal volume (V t), mean inspiratory flow (V t/T i), and electromyographic (EMG) activity of the diaphragm (E di) and intercostal (E int) muscles. results: Compared with the normal control group (Group C), patients exhibited similar MIP, and similar V e and EMG response slopes to carbon dioxide. However, evaluating individual V e response slopes, we were able to identify two subsets of patients: Group A (six patients) with low V e response (less than mean -SD-1.65 of Group C) and Group B (seven patients) with normal V e response. Compared with both Groups B and C, Group A exhibited significantly lower V t/T i, E di, and E int response slopes, the difference between Groups B and C was not significant. Six patients (two from Group A and four from Group B) exhibited low MIP values compared with that in Group C. After replacement therapy, (1) V e, V t/T i, and E di response slopes increased significantly in Group A, and (2) MIP increased, but not significantly in patients with low MIP. conclusions: We conclude that: (1) In patients with severe hypothyroidism, the ventilatory control system may be altered at the neural level, as indicated by a blunted chemosensitivity, (2) Impaired respiratory muscle function does not seem to play a major role in the decreased ventilatory response to carbon dioxide stimulation, (3) Replacement therapy appears to normalize the response to hypercapnic stimulation, but not respiratory muscle strength.

Psychologic and psychoeducational consequences of thyroxine therapy for juvenile acquired hypothyroidism

The observation of severe behavioral reactions or learning problems in three teenagers treated with L-thyroxine for juvenile acquired hypothyroidism prompted us to conduct a prospective study of achievement and behavioral characteristics of patients with newly diagnosed juvenile acquired hypothyroidism. On diagnosis of juvenile acquired hypothyroidism and before treatment with L-thyroxine, 23 children and adolescents underwent a comprehensive battery of psychoeducational tests, which was repeated after 3, 12, and 24 months of replacement therapy. Results revealed that adverse behavioral reactions and learning problems were relatively rare in these children, although symptoms of juvenile acquired hypothyroidism were associated with increased distractibility, hyperactivity, and poorer achievement. The least gain in achievement was made by children with more severe hypothyroidism at diagnosis; children with the best psychologic outcome were those who achieved euthyroidism more slowly. We conclude that severe behavioral manifestations of L-thyroxine therapy for juvenile acquired hypothyroidism are uncommon, but mild behavioral symptoms and poorer school achievement may occur in about 25% of patients, who represent the most severe cases at diagnosis.

Alterations of serum high-density lipoproteins and hepatic lipase activity in congenital hypothyroidism.

Fourteen term newborns and infants with congenital hypothyroidism were studied before (T0) and after (T1) 1 month of replacement therapy. From T0 to T1 serum total cholesterol and high-density-lipoprotein cholesterol remained constant and at normal levels whereas low-density-lipoprotein apolipoprotein B and triacyglycerol concentrations increased slightly. The proportion of large-size high-density-lipoprotein subfraction was high at T0 and decreased very significantly at T1. Conversely, postheparin serum hepatic lipase activity was low before treatment and increased after thyroxine therapy. Lipoprotein lipase activity remained low throughout the study. These results suggest that, in contrast to adult hypothyroidism, low-density-lipoprotein catabolism is not altered in congenital hypothyroidism. However, as in adults, a defect of lipolytic enzyme activities is present and can induce an impairment of the elimination of cholesterol via the high-density-lipoprotein route and, potentially, of the catabolism of triglyceride-rich lipoproteins. Beyond the scope of congenital hypothyroidism, one should keep in mind these results when attending infants with transient low thyroid hormone levels and lipid intolerance.

GONADOTROPHIN, GROWTH HORMONE AND PROLACTIN SECRETORY DYSFUNCTION IN PRIMARY HYPOTHYROIDISM

We have studied 5 prepubertal girls (age 6.7 - 12.3 yr) and 2 boys (age 13.3 and 14.2 yr) in early puberty (stage 2 genitalia) with primary hypothyroidism. Overnight serum hormone profiles (15-minute sampling) were performed at diagnosis and after 3 and 6 months of replacement therapy (Thyroxine 100μg/m2/day).