Transfusion of RhD-incompatible blood components in RhD-negative blood marrow transplant recipients.

BACKGROUND: Transfusion-dependent bone marrow transplant recipients are routinely transfused with ABO group and RhD-compatible blood components. However, because of the scarcity of RhD-negative blood components, particularly platelets, a policy was developed to transfuse RhD-positive blood components to RhD-negative patients during periods of shortage. METHODS: We reviewed the records of 78 RhD-negative patients with hematologic malignancies who received RhD-negative bone marrow and/or peripheral blood stem cells, from June 1995 to August 2000. The patients transfused with RhD-incompatible blood components were screened periodically for evidence of the development of red blood cell (RBC) alloimmunization. RESULTS: Three of 78 patients (4%) developed anti-D antibodies after receiving RhD-incompatible platelet transfusions. One of the patients developed evidence of anti-RhD antibodies after receiving 42 units of RhD-positive random donor platelets; the second patient developed such evidence after receiving 6 apheresis platelets and 2 infusions of intravenous immunoglobulin G (positive for anti-RhD). The third patient received 206 RhD-positive random donor platelets and 5 apheresis units. All patients were discharged from the hospital. The overall immunization rate was 4%. Six patients received Rh-incompatible packed RBCs and showed no evidence of neither anti-RhD nor any other anti-RBC antibodies. All 78 patients had received RhD-incompatible platelets throughout their engraftment period. CONCLUSION: Transfusion of RhD-positive blood components to Rh-negative patients with hematologic cancers, who have received RhD-negative bone marrow and/or peripheral blood stem cells, are at low risk of developing RhD antibodies. These findings allow for a flexible strategy of blood component therapy support for this special patient population during periods of shortage.

Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth.

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.

Growth hormone secretion and circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3 concentrations in children with sickle cell disease.

Impaired growth involving both height and weight accompanying sickle cell disease (SCD) poses diagnostic and therapeutic problems. We undertook this study to test the hypothesis that this impaired growth is associated with abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF binding protein-3 (IGFBP-3) axis in 21 children with SCD and that SCD is associated with GH resistance. Nine of 21 children with SCD had a defective GH response to both clonidine and glucagon provocation (peak < 10 micrograms/L); these children differed from the 12 others in having slower linear growth velocity (GV and GVSDS), lower circulating concentrations of IGF-I and IGFBP-3, and either partial or complete empty sellae in computed tomographic scans of the hypothalamic-pituitary area. In this group of patients with SCD, it appears that defective GH secretion and consequent low IGF-I production are the major etiological factors causing the slow growth. The two groups with SCD did not differ significantly in dietary intake, body mass index (BMI), midarm circumferences, skinfold thickness, serum albumin concentration, or intestinal absorption of D-xylose. A single injection of GH produced a smaller increase in circulating IGF-I in children with SCD with or without defective GH secretion versus 10 age-matched children with idiopathic short stature (ISS) and 11 children with isolated GH deficiency (GHD), suggesting partial GH resistance in the SCD group. The presence of defective GH secretion, decreased IGF-I synthesis, and partial resistance to GH in short children with SCD suggests that treatment with IGF-I may be superior to GH therapy for improving growth.

Mode of presentation and progress of childhood diabetes mellitus in the Sultanate of Oman.

We surveyed the clinical presentation, initial management and subsequent course of a prospectively registered cohort of 60 children with insulin-dependent diabetes mellitus (IDDM) diagnosed before age 15 years in the Sultanate of Oman between January 1990 and December 1993. Clinical details from the time of diagnosis were available on all the children. At diagnosis 9 (15 per cent) presented with severe ketoacidosis (DKA) with pH less than 7.1 or plasma bicarbonate less than 10 mmol/l, and 16 (27 per cent) had mild to moderate ketoacidosis with pH 7.1-7.35 or plasma bicarbonate 10-18 mmol/l. During DKA electrolyte disturbances included: hypokalemia (K < 3.5 mmol/l) 25 per cent), hyperkalemia (K > 5.5 mmol/l) (18 per cent) and hyponatremia (Na < 130 mmol/l) (40 per cent). Serum creatinine concentrations were high in 25 per cent of children with DKA. Within the first year of diagnosis, 17 of the 60 children (28 per cent) experienced symptomatic hypoglycaemia, which in six (10 per cent) led to one or more admissions. Re-admission for unstable glycaemic control, excluding acute hypoglycaemia occurred at least once in six children (10 per cent) within 1 year of diagnosis and in 10 (17 per cent) within 2 years. Statural growth velocity (GV) and GVSDS (6.9 +/- 0.85 cm/year and 0.75, respectively) were significantly higher in the group of children with good glycaemic control (HbA1C = 7.9 +/- 0.4 per cent) compared to those children (3.7 +/- 0.44 cm/ year and -1.6, respectively) with bad glycaemic control (HbA1C = 12.5 +/- 1.5 per cent). Insulin-like growth factor-I (IGF-I) concentrations were significantly higher (260 +/- 21 ng/ml) in the group with good glycemic control v. the group with bad control (149 +/- 15 ng/ml). In summary, greater public and medical awareness of the presenting features of diabetes in young children is needed to reduce the frequency of DKA at presentation, and improvement of patient and family education is necessary to reduce the incidence of DKA and hypoglycaemia in children with IDDM.

Congenital adrenal hyperplasia complicated by central precocious puberty: linear growth during infancy and treatment with gonadotropin-releasing hormone analog.

Some children with congenital adrenal hyperplasia (CAH) develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have seen six such children who had the diagnosis of CAH with late initiation of corticosteroid treatment and/or poor compliance who developed central precocious puberty (CPP). These patients were treated with standard-dose hydrocortisone and fludrocortisone. Administration of depot leuprorelin (3.75 mg subcutaneously every 28 days) for 2 years or longer was effective in arresting the manifestations of puberty, decelerating the pretreatment growth velocity ([GV] 10.8 +/- 1.5 v3.65 +/- 0.95 cm/yr), increasing the predicted adult height ([PAHT] 147.5 +/- 7.8 v 153.4 +/- 8.3 cm), and decreasing the bone age to statural age ratio (1.26 +/- 0.13 v 1.16 +/- 0.09). Analysis of auxanological data during the first 2 years of life showed that linear growth was significantly accelerated and bone age was advanced in patients who developed CPP compared with 11 age-matched patients. It appears that proper glucocorticoid replacement to achieve adequate control of hyperandrogenemia during early life might prevent development of CPP in these patients. Gonadotropin-releasing hormone agonist (GnRHa) therapy can improve the final adult height, bringing it closer to that expected from the genetic potential.

Insulin and glucagon responses to provocation with glucose and arginine in prepubertal children with thalassemia major before and after long-term blood transfusion.

Hypertransfusion therapy has dramatically increased the duration and quality of life in patients with B-thalassemia major; however, it leads to chronic iron overload, and is frequently complicated by the development of diabetes mellitus or impaired glucose tolerance. To determine the early effect of iron overload on the endocrine pancreatic function, we studied glucose, insulin, and glucagon responses to oral load of glucose and to arginine provocation in 15 children with B-thalassemia major, before and after (3.1 +/- 0.6 years) high-transfusion and iron chelation and compared them with 15 age matched normal controls. In addition, we evaluated growth hormone (GH) responses to oral clonidine and measured the circulating insulin-like growth factor-I concentration in thalassemic children on long-term transfusion and controls. After long-term high-transfusion, thalassemic children had significantly decreased serum insulin concentrations and low insulin/glucose ratios at 60 and 120 min after an oral glucose load (1.75 g/kg) in comparison with values before therapy and those for controls. None of the thalassemic children had glucose intolerance after this period of frequent blood transfusion; however, their serum glucose levels at 60 and 120 min after the oral glucose load were significantly higher compared to control children. Thirty minutes after starting arginine infusion, serum insulin concentration was significantly lower in thalassemic children compared to before therapy. Basal and arginine-stimulated glucagon secretions were significantly elevated in thalassemic children on long-term blood transfusion with significantly low serum insulin/glucagon ratios. In addition, the high basal serum glucagon concentrations were not suppressed after the oral glucose load. Despite hyperglucagonaemia in all thalassemic children, their blood glucose dropped appropriately below 50 per cent of the fasting glucose level after an intravenous insulin dose (0.1 U/kg) ruling out any significant insulin-resistance. GH responses to clonidine provocation were subnormal in thalassemic children after long-term blood transfusion compared to controls. In summary, thalassemic children on long-term blood transfusion and iron chelation have progressive and early loss of B-cell mass, manifested by decreased insulin release in response to secretagogues, before the development of significant insulin resistance or impairment of glucose tolerance.

Hypoinsulinaemia has an important role in the development of oedema and hepatomegaly during malnutrition.

Various alterations in hormonal levels have been suggested to contribute to the development of nutritional oedema and fatty liver in children with kwashiorkor. We present an infant who underwent near-total pancreatectomy at the age of 4 weeks and developed kwashiorkor after 11 weeks. The sequence of events following surgery can be divided into two phases. The first phase was characterized by hyperinsulinaemia and hypoglycaemia before feeds. During this phase, although the weight gain was slow (10 g/day) serum albumin (32 g/I) and prealbumin (0.23 g/I) concentrations were maintained with no oedema or hepatomegaly. In the second phase, insulin deficiency prevailed and he was receiving the same amount of milk (protein)/day (enriched with starch). During that phase he rapidly developed hypoalbuminaemia (18 g/l), hypoprealbuminaemia (0.1 g/l), oedema, hepatomegaly, and dermatosis. This case demonstrates clearly the important role of defective insulin secretion in the development of nutritional oedema and hepatomegaly.

Empty sellae, impaired testosterone secretion, and defective hypothalamic-pituitary growth and gonadal axes in children with Bardet-Biedl syndrome.

We evaluated growth parameters and hypothalamic-pituitary-gonadal and growth functions in five children with Bardet-Biedl syndrome (BBS). Three of the five children had stature below the fifth percentile for age. Their growth hormone (GH) response to provocation was defective, and computed tomographic (CT) scanning revealed empty sellae in all of them. All the children were obese (body mass index [BMI] > 95th percentile for age). Three had hypercholesterolemia. Their basal serum testosterone concentration and testosterone response to 3-day human chorionic gonadotropin (HCG) stimulation were significantly lower than the levels in 12 age-matched obese normal children. Testosterone secretion failed to respond to HCG therapy for 4 weeks. Both basal gonadotropin levels (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and gonadotropin responses to LH-releasing hormone (LHRH) stimulation were normal and did not differ among the two study groups. It appears that primary hypogonadism is a cardinal feature of BBS, and it may be accompanied by hypothalamic and pituitary abnormalities.

Defective growth hormone secretion in children with pycnodysostosis and improved linear growth after growth hormone treatment.

Short stature is a characteristic feature of pycnodysostosis. We report defective growth hormone secretion in response to provocation and low insulin-like growth factor-I (IGF-I) concentration in five out of six patients with pycnodysostosis. Physiological replacement with growth hormone increased IGF-I concentration and improved linear growth in these children.

An assessment of the reliability of pulp testing deciduous teeth.

The aim of this study was to assess the reliability of children's responses to pulp testing of deciduous teeth. The maxillary canine was chosen as the test tooth. One hundred children aged 7-10 years were selected who had at least one non-carious maxillary canine with an intact root showing only early radiographic signs of resorption. Using a minimization sampling technique, the children were allocated to one of two groups, for pulp testing with ethyl chloride (EC) or with an electric pulp tester (EPT). True and sham tests for both pulp testing methods were applied. The tests were repeated following an application of 5% lignocaine paste to the gingival margin around the tooth to prevent gingival detection of the stimulus. Children were asked to record their responses to each of the four tests on a visual analogue scale (VAS) of 1-10. Significantly higher mean scores were obtained with true tests than with sham tests, for both EC and EPT. The application of lignocaine to the gingival margin did not significantly affect the responses to either EC or EPT. It was concluded that pulp testing of intact maxillary deciduous canines with no or only early signs of radiographic root resorption, using EC or EPT, results in reliable responses in 7-10-year-olds, suggesting that pulp testing is valid in the deciduous dentition. The VAS was a useful tool for the evaluation of the children's responses.

Defective growth hormone secretion and hypogonadism in the new syndrome of congenital hypoparathyroidism, growth failure and dysmorphic features.

A child with extreme growth failure, dysmorphic features, hypoparathyroidism, and abnormal skeletal survey was studied. He was a product of first degree consaguineous marriage who had intrauterine growth retardation and presented at 14 days of age with hypocalcemic tetany with normal cardiovascular system and immune function. Endocrine evaluation after infancy revealed defective growth hormone (GH) secretion in 2 provocation tests and lack of clinical and testosterone response to human chorionic gonadotrophin (HCG) therapy.

Growth parameters, growth hormone (GH) response to clonidine and circulating insulin-like growth factor-I (IGF-I), free thyroxine (FT4) and cortisol concentrations in relation to glycaemic control in children with insulin-dependent diabetes mellitus.

The objective of this paper was to determine the effect of glycaemic control and endocrine functions on linear growth in children with IDDM. We studied 45 prepubertal children with IDDM (30 males, 15 females) over 1 year period. The mean +/- SD for age of onset and duration of IDDM were 6.2 +/- 2.3 years and 3.5 +/- 1.3 years, respectively. At each clinic visit (every 3 months), glycaemic control was assessed by measuring glycosylated haemoglobin (HbA1C). Growth hormone and cortisol responses to high dose clonidine (0.15 mg/m2) and ACTH, respectively, were evaluated and circulating concentrations of free thyroxine (FT4) and TSH estimated. The average insulin dose (unit/kg/day) during this period was calculated for each patient. Growth was assessed by determining both height standard deviation score (HtSDS) and growth velocity standard deviation scores (GVSDS) and bone age determined according to the atlas of Greulich and Pyle. Two-hundred-and-fifty age- and sex-matched normal children served as controls for growth data, and 20 normal age-matched children and 20 normal children with short stature (NVSS) served as controls for the hormonal studies. Growth velocity (GV) (cm/year) and GVSDS were significantly lower in children with IDDM compared to normal children, and significantly lower in children with poorly controlled diabetes compared to those with good glycaemic control. GV and GVSDS were inversely correlated to HbA1C (r = -0.356, P < 0.01 and r = 0.335, P < 0.01 respectively). GVSDS was correlated with serum IGF-I (r = 0.22, P < 0.01), FT4 (r = 0.321, P < 0.01) and inversely with basal GH (r = -0.362, P < 0.01) concentrations, but was not correlated with cortisol levels or peak GH concentrations in response to clonidine. GVSDS was correlated with HtSDS (r = 0.222, P < 0.01) and inversely with age (r = -0.43, P < 0.05). There was no significant correlation between GVSDS on the one hand and weight gain or body mass index (BMI) on the other hand. Peak GH response to clonidine was correlated with BMI (r = 0.68, P < 0.001) and insulin dose/kg/day (r = 0.602, P < 0.01). This study confirms that in children with IDDM linear growth velocity is dependent on the age of the child and the degree of glycaemic control, as well as on growth promoting hormones such as IGF-I and FT4. High BMI is associated with more GH secretion in response to clonidine, this might explain the higher requirements of insulin/kg in children with IDDM and high BMI.

Prevalence and significance of Acanthosis nigricans in children and adolescents.

Acanthosis nigricans (AN) develops commonly in obese adults, yet its prevalence and metabolic significance in children and adolescents have not been determined. To address these issues, 100 obese children and adolescents enrolled in the obesity clinic at the Royal Hospital, Muscat, Oman, were chosen at random and examined. AN was observed in 43 of the study children (43%). The frequency and severity of AN increases and significantly with increasing body mass index (BMI) in these children. Twenty patients with obesity and AN and 20 age-matched nonacanthotic obese children, randomly selected from the study children, were investigated. Their oral glucose tolerance and serum C-peptide responses to IV glucagon were evaluated. Circulating concentrations of free thyroxine (FT4), TSH, basal and ACTH-stimulated cortisol, testosterone, leutinizing hormone, (LH), follicle-stimulating hormone (FSH), and prolactin were measured by radioimmunoassay (RIA). Children with AN exhibited higher basal and glucagon-stimulated C-peptide concentrations than the nonacanthotic obese group. Two hours after the oral load of glucose (1.75 g/kg), serum glucose concentration (6.3 +/- 1.4 mmol/L) was higher in the acanthotic group versus the nonacanthotic group (5.2 +/- 0.8 mmol/L). Impaired glucose tolerance was detected in two children with AN (10%), and in none of the nonacanthotic controls. Hypothyroidism was diagnosed in two (10%) children with AN (TSH = 109 and 18 mIU/mL and FT4 = 4.6 and 13.5 pmol/L respectively), while all the nonacanthotic children were euthyroid. Serum testosterone concentration was insignificantly lower in the acanthotic group (6.5 +/- 3.9 ng/dL) versus the nonacanthotic children (8.3 +/- 4.5 ng/dL). Basal serum LH, FSH and prolactin concentrations and basal and ACTH-stimulated cortisol levels did not differ between the two study groups. Plasma triglyceride concentration was significantly higher in the acanthotic group (1.43 +/- 0.5 mmol/L) versus the nonacanthotic group (1.05 +/- 0.45 mmol/L), and was correlated significantly with BMI (r = 0.446, P < 0.05). In conclusion, obesity is a significant risk factor for the development of AN in children. AN is a reliable skin marker of hyperinsulinemia in obese children and adolescents. The prevalence of impaired glucose tolerance (10%) and primary hypothyroidism (10%) appears to be higher in obese acanthotic children than in those without AN.

Epidemiology of childhood insulin-dependent diabetes mellitus in the Sultanate of Oman.

This study assessed the updated incidence of IDDM in 0 to 14-year-old children in the Sultanate of Oman, which is located in the southern-eastern part of the Arabian peninsula. Incident cases were recorded prospectively from January 1993 to the end of December 1994. Incidence rates were standardized on the basis of the National Population Census. The degree of ascertainment was above 96% from the primary source. During two full calendar years, 31 new cases of IDDM in children were diagnosed in Oman (10 health regions). The standardized incidence rates were 2.45 and 2.62/100,000 per year during 1993 and 1994, respectively. The sex-specific rates among males and females were 3.23 and 1.99/100,000, respectively, in 1993 and 2.91 and 1.95/100,000, respectively in 1994. The age-specific incidence rates during the 2 years were higher in the 10-14 age group (3.69 and 4.22/100,000, respectively) vs those in the 5-9 age group (2.32 and 2.79/100,000, respectively) and 0.4 age group (1.54 and 0.97/100,000 respectively). The number of new cases/month was markedly higher in the relatively cooler months (September through March) of the year. The incidence rate of IDDM in children under the age of 15 years in Oman was lower than the reported incidence in Kuwait (another gulf country located north-west to Oman) which might reflect the north-south gradient reported in several previous studies. However this incidence rate was higher than those reported for many countries in Asia.

Growth and endocrine function after near total pancreatectomy for hyperinsulinaemic hypoglycaemia.

Seven children, with a mean (SD) age of 4.6 (2.1) years, who as infants (21 (7.5) days) underwent near total (95-98%) pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) were studied. At birth all the infants were macrosomic. Four infants had been born after a difficult labour, of whom three had moderate birth asphyxia and respiratory distress. All had normal thyroid function. After surgery transient hyperglycaemia was manifest in six of the children and required insulin treatment for 5.8 (3.8) weeks, and transient hypoglycaemia was encountered in one child and responded well to increased carbohydrate intake and diazoxide for three weeks. Six of the children rapidly crossed down their length and weight centiles during the first year after surgery. At the end of the first year these children were at or below the 5th centile of height and weight for their age and gender. After a period of 4.6 (2.1) years, their mean (SD) height score was -2.57 (0.5), growth velocity 3.9 (0.75) cm/year, and growth velocity SD score -2.1 (0.55)l these were significantly low and denoted significant growth retardation. The growth hormone peak responses to provocation with clonidine were normal (13.5 (2.8) micrograms/l). However, the circulating insulin-like growth factor-I (IGF-I) concentrations were significantly decreased (79 (34) ng/ml). Three of the children developed diabetes at two and a half, five, and seven years after surgery, two others had impaired oral glucose tolerance and six out of the seven children had an impaired C peptide response to glucagon. Defective insulin secretion in these children might directly inhibit IGF-I synthesis in the liver. The body mass index of the pancreatectomised children was 14.9 (0.5) and was normal for age and gender; they had a normal 72 hour faecal fat content and normal serum albumin concentration. These data indicated grossly adequate exocrine pancreatic function. It appears that children requiring near total pancreatectomy for PHHI have normal developmental milestones but defective linear growth with impaired insulin secretion and low IGF-I production despite normal growth hormone response to provocation.

Nocturnal growth hormone (GH) secretion and GH response to clonidine provocation in children before and after long-term prednisone therapy.

Glucocorticoids reduce growth hormone (GH) response to the majority of exogenously administered stimuli and can variably inhibit growth in man and animals. Recently, however, glucocorticoids have been shown to have varying effects on GH secretion depending on the time of administration and, furthermore, to be potent secretagogues. We evaluated growth parameters, GH response to high-dose clonidine and integrated (12-h) nocturnal and mean (12-h) nocturnal GH secretion in 10 prepubertal children before and after long-term alternate-day prednisone therapy (LTPT). Height standard deviation scores (HtSDS) and growth velocity standard deviation scores (GVSDS) decreased significantly after LTPT. GH response to clonidine as well as integrated and mean nocturnal GH secretion were significantly after LTPT. GH response to clonidine as well as integrated and mean nocturnal GH secretion were significantly depressed after LTPT v. before treatment. We compared growth parameters and GH data of two groups of children before and after LTPT. Group 1 had low GH peak response to clonidine after LTPT, and group 2 had normal GH response to clonidine. Group 1 children had significantly more impairment of their statural growth and nocturnal GH secretion. Growth parameters (HtSDS and GVSDS) during LTPT correlated significantly with the peak GH response to clonidine (r=0.69 and 0.78, respectively) as well as to the growth parameters before therapy (r > 0.9). It appears that LTPT impairs both physiologic and pharmacologically provoked GH secretion and consequently retards growth in children. However, this effect is variable and is affected by the attained statural growth before therapy.

High prevalence of diabetes mellitus and impaired glucose tolerance in the Sultanate of Oman: results of the 1991 national survey.

A national survey of glucose intolerance and cardiovascular disease risk factors in Oman has demonstrated a high prevalence of diabetes (10%) and impaired glucose tolerance (IGT, 13% in females and 8% in males). Prevalence of diabetes rose with age to a maximum of over 30% in both sexes. Prevalence of total glucose intolerance (diabetes and IGT combined) exceeded 50% in the seventh (females) and eighth (males) decade of life.

Circulating growth hormone (GH), insulin-like growth factor-I (IGF-I) and free thyroxine, GH response to clonidine provocation and CT scanning of the hypothalamic-pituitary area in children with sickle cell disease.

Serum growth hormone (GH), cortisol, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and insulin like growth factor I (IGF-I) concentrations were measured in 15 children with sickle cell disease (SCD) together with their heights < 5th percentile for age and gender, and in 15 healthy age-matched children who had normal variant short stature (NVSS). GH response to an oral dose of clonidine (0.15 mg/m2) and cortisol response to ACTH stimulation were determined in the two groups. Children with SCD had significantly lower serum concentrations of IGF-I and decreased GH response to stimulation. Eight out of the 15 children with SCD did not mount an appropriate GH response to clonidine provocation (> 10 micrograms/l). CT scanning of the hypothalamic-pituitary area in those eight children with SCD revealed a partial or complete empty sella in all of them. It appears that defective GH release, and consequently low IGF-I production and slow growth velocity in children with SCD might be secondary to hypoxic-vascular insults to their hypothalamic-pituitary axis during one or more of the sickling episodes.

Growth hormone deficiency and empty sella in DIDMOAD syndrome: an endocrine study.

Two girls with DIDMOAD syndrome are presented. One also had severe megaloblastic-sideroblastic anaemia and the other several neurological manifestations. Both were short with defective growth hormone secretion. Computed tomography revealed empty sella in both girls; one had widespread atrophic cortical and cerebellar changes. High doses of thiamine improved the anaemia in the first case, increased C peptide secretion in both, but had no effect on the neurological abnormalities.