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.

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.

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.

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.

Empty sella in short children with and without hypothalamic-pituitary abnormalities.

A study was conducted on growth hormone (GH) response to oral clonidine (0.15 mg/m2), GH and cortisol responses to i.m. glucagon (0.1 mg/kg), and glucose response to an oral load of glucose (1.75 g/kg). Measurements were made on the circulating concentrations of free thyroxine (FT4), thyroid stimulating hormone (TSH) and different growth parameters and CT sellar images in 25 GH deficient children (Peak GH response to clonidine and glucagon < 7 ug/ml), 15 growth retarded children (Ht < 5th percentile for age and gender) with sickle cell disease (SCD) and GH deficiency, 30 randomly selected children with normal variant short stature (NVSS) (HtSDS 2SD below the mean for age and gender with normal GH response to stimulation (> 10 ug/ml) and 20 age-matched normal children were evaluated. Out of the 25 children with GH deficiency, five had multiple pituitary hormonal deficiency (GH < TSH and/or ACTH. deficiencies), and 20 had isolated GH deficiency. Empty sella, either complete or partial, was detected in 9 out the 20 children with isolated GH deficiency (45%), 4 out of the 5 children with multiple pituitary deficiency (80%), all the children with SCD and GH deficiency (100%), 3 out of the 30 children with NVSS (10%) and in none of the normal children. The insulin-like growth factor-I (IGF-I) concentrations were significantly lower in the two groups of children with GH deficiency compared to those with NVSS. The height standard deviation scores (HTSDS) were significantly lower and the annual growth velocity was slower in children with idiopathic GH deficiency and empty sella compared to those with NVSS and those with empty sella associated with SCD. The bone age delay (yr) did not differ among the 3 groups of children with short stature. All children with isolated GH deficiency associated with empty sella had normal body mass indices (BMI), while all the children with SCD and empty sella had BMI below the 5th percentile for the corresponding age and gender. None of the children had glucose intolerance. In conclusion, children with growth retardation and abnormal hypothalamic pituitary functions have high incidence of empty sella. However, empty sella is detected in considerable number (10%) of short children with normal hypothalamic pituitary function.

Diabetes mellitus in the sultanate of Oman.

In February 1990 a World Health Organization consultancy was undertaken to assess the current impact of diabetes mellitus in Oman. Routine national health statistics suggested that diabetes was the principal diagnosis in approximately 1% of all hospital discharges in 1988. The number of 'new cases' of diabetes treated at hospitals during the same year was 4.8 per 1000 Omani population, representing almost 6000 diabetic patients. In 1989, at the Royal Hospital, Muscat, diabetes was recorded as the principal diagnosis for 2.6% of all discharges, and 6% of those in subjects aged 45 years and over. It is known that the frequency of diabetes is generally underestimated by routine health statistics. Limited ad hoc investigation during the consultancy suggested that approximately 9% of all adult hospital admissions and 12% of adult hospital bed occupancy were associated with diabetes. Thus, diabetes should be considered a priority in a national health strategy for Oman. It is recommended that emphasis be placed upon epidemiological research, education, and the provision of appropriate technology.