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Biomedical subjects

H Landau

Publications and source records attributed to H Landau.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cross-sectional and longitudinal study of the pituitary-thyroid axis in patients with thalassaemia major.

OBJECTIVE AND DESIGN: Thyroid dysfunction is known to occur frequently in thalassaemia major, but its prevalence and severity varies in different cohorts, and the long-term natural history is poorly described. We evaluated the pituitary/thyroid axis in thalassaemia major patients in a cross-sectional study and correlated abnormalities with indices of iron overload. Furthermore, the course of thyroid disease in thalassaemia major patients was assessed in a 15-year longitudinal study. PATIENTS AND MEASUREMENTS: Cross-sectional study: pituitary-thyroid axis function was examined in 37 patients (22 F, 15 M; aged 10-39 years, mean +/- SE = 21 +/- 1.4) out of a total of 43 who attended the Haematology and Endocrinology Clinics of Hadassah Hospital on a regular basis. The mean pretransfusion Hb level was 85 +/- 20 g/l, and all patients except one were treated with desferrioxamine (DF, mean +/- SE dose 20.2 +/- 2.6 mg/kg/day). Twenty-two had hypogonadotrophic hypogonadism (HH). Longitudinal study: 21 thalassaemia major patients were evaluated with TRH tests in 1976 and again in 1985. Fourteen of these and another eight were evaluated in both 1985 and 1991. RESULTS: Cross-sectional study: no patient had any clinical signs or symptoms of hypothyroidism; however, one had abnormally low T4, borderline low FT4 and normal T3 levels associated with an exaggerated TSH response to TRH consistent with mild hypothyroidism. This patient did not have a previous TRH test, but serial basal determinations over 7 years revealed a progressive decrease in thyroid function. Thirty-six patients had thyroid hormone levels within the normal range. Nine of these (24.3%) had only an exaggerated TSH response to TRH whereas seven others (19%) also had borderline elevated basal TSH levels. TSH response to TRH was not correlated with age, serum ferritin or liver function tests (ALT or GGT). Longitudinal study: mean TSH response to TRH decreased (P < 0.002), and mean T3 levels increased (P < 0.001) between 1975 and 1985. These findings are probably related to the initiation of DF treatment in 1981. During the last 6 years, four patients with previously normal TSH responses to TRH developed elevated peak TSH levels. Mean T3 concentrations decreased and TSH response to TRH increased significantly (P < 0.001 for both). CONCLUSIONS: (1) In this patient group the thyroid pituitary axis is less sensitive than the gonadal axis to iron-induced damage; only one out of 37 patients developed mild uncompensated hypothyroidism. (2) As opposed to the gonadal axis, the thyroid gland appears to fail before the central components of the axis. (3) Abnormal thyroid function may be reversible in the early stages. (4) Progression is variable, and it may take years to progress from normal to uncompensated hypothyroidism.

Adolescent↗
PubMed1993

Effect of timing of growth hormone administration on plasma growth-hormone-binding activity, insulin-like growth factor-I and growth in children with a subnormal spontaneous secretion of growth hormone.

Since normal pulsatile growth-hormone (GH) secretion displays a major and consistent surge during sleep, we studied the effect of timing of GH supplementation on plasma GH-binding protein activity (GH-BP), insulin-like growth factor-I (IGF-I) and growth. 34 prepubertal subjects (28 boys, 6 girls) aged 8-11 years, of short stature (< 2 SD for age), with a GH response to provocative test > 10 micrograms/l and a subnormal 24-hour GH secretion (< 3 micrograms/l), were randomly allocated to receive Bio-Tropin (recombinant GH, Bio-Technology, Israel) 0.81 IU/kg/week in 3 equally divided doses. GH was administered either at 8.00-10.00 h (M group), 14.00-16.00 h (AN group) or 19.00-21.00 h (NT group). Height velocity, IGF-I and GH-BP were determined prior to and after 6 and 12 months on GH therapy in the three groups. There was no significant difference between the three groups in the growth response, IGF-I and GH-BP increase, all of which increased significantly during GH therapy. Although GH levels after the injection decline to preinjection levels after 10 h, the changes induced by GH therapy, as reflected in IGF-I and GH-BP, last in the circulation long enough to prevent fluctuations in its action. The similarity of IGF-I and of GH-BP levels in the three treatment groups might explain the similar growth effects of the 3 protocols.

Carrier Proteins↗
PubMed1992

Predictors of growth response to growth hormone in otherwise normal short children.

Sixty prepubertal short children (39 boys) with heights less than 2 SD for age and gender were treated daily for 1 year with recombinant human growth hormone (GH), either 0.1 IU/kg (group 0.1, n = 32) or 0.05 IU/kg (group 0.05, n = 28). Reserve of GH was determined by at least one GH provocative stimulus and 24-hour continuous blood withdrawal to determine the integrated concentration of GH (IC-GH). All participants had a GH response to provocative tests greater than 10 micrograms/L. The height velocity (mean +/- SD) of the group as a whole increased from 4.46 +/- 1.02 to 7.59 +/- 1.65 cm/yr (p less than 0.001). The growth velocity of group 0.1 was significantly greater than that of group 0.05 (8.1 +/- 1.5 vs 7.0 +/- 1.65 cm/yr; p less than 0.01). Bone age did not advance more than 1 year during the treatment period. Growth velocity after 1 year of GH therapy was inversely correlated with the IC-GH in both groups, as was the pretreatment height velocity. We found no correlation of growth velocity during GH therapy with other measures such as parental heights, bone age/chronologic age ratio, maximal GH response to provocative tests, chronologic age, or pretreatment insulin-like growth factor I levels. We conclude that the best predictors for the 1-year growth outcome of short children with a normal GH response to provocative tests are the pretreatment growth velocity and the IC-GH. The short-term benefit from GH therapy in children with a normal growth velocity and a normal IC-GH is poor, whereas marked growth acceleration is noted in children with a low growth velocity and a low 24-hour IC-GH.

Age Determination by Skeleton↗
PubMed1992

Detection of albumin binding abnormalities in sera of patients with familial dysalbuminaemic hyperthyroxinaemia using isoelectric focusing.

Definitive diagnosis of familial dysalbuminaemic hyperthyroxinaemia (FDH) requires finding a high concentration of [125I]T4 bound to albumin. We used isoelectric focusing (IEF) in agarose gels to study the sera of three members of a family with FDH and compared the distribution of [125I]T4 obtained by IEF with that obtained by conventional agarose gel electrophoresis (AGE). Both IEF and AGE confirmed the diagnoses of FDH. In case #1, the % [125I]T4 bound to albumin was 15.2 and 20.0, with IEF and AGE, respectively, in case #2 23.6 and 26.5, and in case #3, 22.1 and 23.0, compared to normal controls of 5.9 and 7.4, respectively. IEF has not previously been used to diagnose FDH, to our knowledge. IEF has the advantage of eliminating TBG interference with albumin migration, which can potentially complicate the diagnosis of FDH when the AGE method is used. To date, reverse flow electrophoresis, a more cumbersome method with poorer resolution than IEF, has been utilized to eliminate TBG interference. IEF, in agarose gels, is a relatively simple and accurate method to diagnose FDH, and avoids artifacts which may be encountered with AGE.

Adult↗
PubMed1992

Final height after growth hormone therapy in peripubertal boys with a subnormal integrated concentration of growth hormone.

The aim of this study was to test the effect of growth hormone (GH) therapy on final height in peripubertal boys with idiopathic short stature in whom a subnormal integrated concentration of GH (< 3.2 micrograms/l) was found. Twenty-eight peripubertal children were studied. Height was below 2 SD for age, growth velocity was < 4.5 cm/year, bone age was more than 2 SD below mean for age and GH response to provocative tests was more than 10 micrograms/l. Eleven subjects (group B) were treated with recombinant GH 0.75 unit/kg/week, divided into 3 weekly doses for 2 years, and then the same weekly dose divided into daily injections was administered until final height was attained. Seventeen untreated children (group A) who were followed until cessation of growth served as controls. The GH-treated patients reached their target heights (-2.1 +/- 0.5, mean +/- SD in SDS) and predicted heights (-1.8 +/- 0.8) determined by the Bayley and Pinneau method, while the final heights of the untreated patients were significantly lower than their target heights and their predicted final heights (-2.7 +/- 0.7, -1.8 +/- 1.0 and -2.7 +/- 0.7, respectively). The main effect of GH was observed during the 1st year of treatment when height velocity was significantly higher in the GH-treated group than in the untreated one (9.3 +/- 2.1 vs. 5.3 +/- 1.1, respectively, p < 0.001). The high cost of the treatment in this specific age group should be weighed against the results.

Adolescent↗
PubMed1992

Assessment of growth hormone (GH) axis in Turner's syndrome using 24-hour integrated concentrations of GH, insulin-like growth factor-I, plasma GH-binding activity, GH binding to IM9 cells, and GH response to pharmacological stimulation.

The GH axis was studied in Turner's syndrome (TS) patients. Thirty-seven prepubertal TS patients and 42 normally growing girls (NGG; 5.5-16.3 yr old), of whom 13 were prepubertal, were studied by 24-h continuous blood withdrawal and provocative tests. The 24-h integrated concentrations of GH (IC-GH), FSH (IC-FSH), and insulin-like growth factor-I (IC-IGF-I) as well as the IC-IGF-I/IC-GH ratio were determined. An increase in IC-GH with age and progression of puberty was found in NGG, but not in TS. IC-GH in the NGG was significantly higher than that in age-matched TS patients. Estrogen replacement therapy normalized IC-GH levels in 6 TS patients in whom these levels were subnormal for age. A positive correlation between IC-GH and IC-FSH or IC-estradiol was found in NGG (r = 0.462; P less than 0.01), but not in TS patients. The IC-IGF-I/IC-GH ratio was significantly higher in the TS than in the NGG group. Serum GH-binding activity and serum GH binding to IM9 cells in the TS group did not differ from those in the normal group. We hypothesize that the growth retardation of TS results from a combination of insufficient GH secretion, mainly due to sex steroid deficiency, and an end-organ resistance to IGF-I. IGF-I receptor studies are needed to test this speculation about IGF-I resistance.

Adolescent↗
PubMed1991

Age-related patterns of thyroid-stimulating hormone response to thyrotropin-releasing hormone stimulation in Down syndrome.

Thyroid function in subjects with Down syndrome was studied using the thyrotropin-releasing hormone test. Forty-seven infants and children with Down syndrome were investigated. Ages ranged from 1 month to 7 years; there were 26 boys and 21 girls. Fourteen of the subjects with Down syndrome who had an exaggerated thyroid-stimulating hormone response to thyrotropin-releasing hormone stimulation had two or more annual follow-up tests. The remaining 33 subjects who only underwent one thyrotropin-releasing hormone test were compared with 22 age-matched controls (11 boys and 11 girls). Mean basal thyroxine 4 and triiodothyronine 3 values were in the normal ranges. All thyroid antibody titers were negative. Mean basal thyroid-stimulating hormone levels of subjects with Down syndrome were significantly higher than those of controls for all ages, even though there was a decline in thyroid-stimulating hormone levels in both groups. Peak thyroid-stimulating hormone response levels were significantly greater in the subjects with Down syndrome than in the controls. Longitudinal study of the 14 children with Down syndrome with an exaggerated thyroid-stimulating hormone response showed that the response remained exaggerated until the third year of life, when it declined to normal levels. Thyroid dysfunction during the growth spurt of infancy or delayed maturation of the hypothalamic pituitary thyroid axis are proposed mechanisms.

Analysis of Variance↗
PubMed1990

Persistent hyperinsulinemic hypoglycemia of infancy ("nesidioblastosis"): autosomal recessive inheritance in 7 pedigrees.

Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) is a rare disease characterized clinically by persistent hypoglycemia with inappropriately elevated circulating insulin concentrations. Here we report on 7 pedigrees including 21 cases. The pedigrees are derived from 3 distinct ethnic groups, and include a very large Bedouin family, and Arab family, and 5 smaller pedigrees of Jewish families all of Eastern European origin. Data obtained from these families and from other families reported in the literature strongly suggest that PHHI is inherited as an autosomal recessive disorder.

Female↗
PubMed1990

Regulation of insulin release in persistent hyperinsulinaemic hypoglycaemia of infancy studied in long-term culture of pancreatic tissue.

Pancreatic tissue was obtained during therapeutic subtotal pancreatectomy from five infants with persistent hyperinsulinaemic hypoglycaemia of infancy (so-called nesidioblastosis). Collagenase digests of the specimens were cultured in RPMI 1640 medium on extracellular matrix-coated plates. Acute insulin secretion showed minimal sensitivity to changes in glucose concentration. Sensitivity to other nutrient secretagogues such as glyceraldehyde, leucine, alpha-ketoisocaproic acid and arginine was variable, showing either diminished or absent response. On the other hand, stimulators of Beta cell cAMP and modulators of the phosphoinositide-protein kinase C pathway were effective inducers of insulin release. The response to cAMP stimulators was independent of the glucose concentration. Although insulin output was high in the absence of glucose, this was not due to passive leak of hormone, since both removal of calcium and addition of somatostatin and epinephrine inhibited the secretion. Beta cells were more sensitive to somatostatin than epinephrine; however, both agents failed to completely suppress the release even at suprapharmacological concentrations. Although it cannot be excluded that the culture conditions affected Beta cell function, the present findings may suggest that cultured Beta cells in persistent hyperinsulinaemic hypoglycaemia of infancy behave like fetal Beta cells at early developmental stages.

Cells, Cultured↗
PubMed1989

Persistent hyperinsulinaemic hypoglycaemia of infancy: long-term treatment with the somatostatin analogue Sandostatin.

Six infants with severe, persistent hyperinsulinaemic hypoglycaemia were treated with the long-acting somatostatin analogue SMS 201-995 (Sandostatin, Sandoz, Basle, Switzerland). Effective control of hypoglycaemia without the need for parenteral glucose was achieved in five of the six cases with doses ranging from 10 to 40 micrograms/kg day given either by four s.c. injections per day, or by continuous subcutaneous infusion (CSI). One has been well controlled on SMS 10 micrograms/kg day for 17 months as an out-patient without requiring surgery, while the five others underwent sub-total pancreatectomy after receiving short courses of the drug. In two patients where hypoglycaemia persisted after sub-total pancreatectomy SMS was effective in inhibiting insulin secretion and preventing hypoglycaemia. Plasma somatomedin concentrations and linear growth were not suppressed in any patient. It is concluded that Sandostatin is useful in the pre and post-operative management of most infants with this syndrome. In selected cases this analogue of somatostatin may also be a long-term treatment option in place of pancreatectomy.

Blood Glucose↗
PubMed1989

Age and seasonal factors in the incidence of premature sexual development in girls in the Jerusalem area.

We conducted a retrospective epidemiologic study on girls with signs of precocious sexual development followed-up in our clinic over a ten-year period. Of a total of 66 girls, 36 had premature thelarche, 11 had premature pubarche, and 19 had idiopathic complete precocious puberty. We noted a steady increase in the number of girls with premature sexual development over this period. Furthermore, the incidence of premature development of pubertal signs during spring months was significantly higher than in other seasons. Environmental influence on premature pubarche seems to be of lesser significance than on premature thelarche and complete precocious puberty.

Age Factors↗
PubMed1988

Raw cornstarch as an additional therapy in nesidioblastosis.

We report the successful use of raw cornstarch to maintain normoglycemia in two children with nesidioblastosis. Despite subtotal distal pancreatectomy both children required frequent daytime feedings and continuous nocturnal intragastric polycose administration to prevent symptomatic hypoglycemia. Raw cornstarch administration consistently maintained blood glucose levels in the normal range. Both children still need frequent daily feedings but no hypoglycemic episodes are reported. They have normal development and have maintained satisfactory growth during the 22 mo since initiation of treatment.

Blood Glucose↗
PubMed1988

Nephrogenic diabetes insipidus, cystinosis, and vitamin D.

We describe a patient with early diagnosed cystinosis who presented with nephrogenic diabetes insipidus in addition to proximal tubular dysfunction. Another feature in this patient was abnormally low serum concentration of 24,25 dihydroxy vitamin D3 (24,25(OH)2D3) with normal 25 hydroxy vitamin D3 (25(OH)D3) and relatively low 1,25 dihydroxy vitamin D3 (1,25(OH)2D3).

Child, Preschool↗