The etiologies of adrenal insufficiency in 73 Thai children: 20 years experience.

BACKGROUND: Adrenal insufficiency (AI) is an event caused by an inadequate secretion or action of adrenal hormones. It can be classified as primary (1 degree) and secondary (2 degree). AI may result in severe morbidity and mortality when undiagnosed or ineffectively treated. OBJECTIVE: To determine the etiologies of AI in Thai children. MATERIAL AND METHOD: Data of children with AI presented to the authors' pediatric endocrine service between 1982 and 2002 (20 years) were retrospectively collected and analyzed. RESULTS: AI was diagnosed by clinical and laboratory data in 73 children (31 boys and 42 girls). Sixty-two (84.9%) patients had 1degree AI while 11 (15.1%) had 2 degree AI. The majority of patients with 1 degree AI (87.1%) were diagnosed with congenital adrenal hyperplasia (CAH). Other causes of 1 degree AI were uncommon such as ACTH unresponsiveness (4.8%) and no definite diagnosis (8.1%). Most children with 1 degree AI presented with hyperpigmentation. Causes of 2 degree AI were as follows: panhypopituitarism (63.6%), isolated ACTH deficiency (9.1%), and low birth weight (27.3%). CONCLUSION: In the present study, CAH was the most common cause of 1 degree AI while panhypopituitarism was the most common cause of 2 degree AI. Other causes of AI were quite uncommon. Definite causes of AI have not yet been identified in some children. Further clinical observation and special tests including molecular studies in these children are warranted for diagnostic and prognostic importance.

Treatment outcome of Graves' disease in Thai children.

BACKGROUND: Graves' disease is the most common cause of thyrotoxicosis in children. Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial. OBJECTIVE: To review treatment outcome of Graves' disease in Thai children. MATERIAL AND METHOD: Retrospective review of 32 children with Graves' disease, diagnosed between Jan. 1994 and Dec. 2004, at the Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand was performed. RESULTS: All patients (median age 10.5 yrs, range 2.85-15 yrs) presented with goiter and increased serum T4 (median 18.4 mcg/dL, range 8.8-30 mcg/dL), serum T3 (median 443 ng/dL, range 206-800 ng/dL) and suppressed TSH levels (median 0.009 mU/L, range 0-0.18 mU/L). Anti-thyroglobulin and Anti-microsomal antibodies were positive in 70% and 82% respectively. All patients except two were initially treated with propylthiouracil (PTU). Two patients were initially treated with methimazole. Adverse reaction of PTU occurred in two patients (One girl had arthralgia, positive pANCA, nephritis and another girl had skin rash and arthralgia). Clinical course of 32 patients after treatment with anti-thyroid drugs mainly PTU for 3.4 (range 0.3-11.2) years is as follows: six (18.8%) underwent remission (cessation of PTU > 2 yrs), three (9.4%) relapsed, one (3.1%) underwent subtotal thyroidectomy, and seven (21.9%) had I131 treatment. All patients (6 of 7) who received I131 dose of 100 microCi/g of thyroid tissue required more than a single dose of I131 treatment. Further outcome in fifteen patients (46.9%) is yet to be followed. Among these patients PTU was just discontinued in four and eleven had never been off anti-thyroid drugs (four still had biochemical hyperthyroidism and seven were biochemically euthyroid). CONCLUSION: PTU was the most common first line therapy in the presented patients with Graves' disease. Remission rate was only 18.8% after an average 3.5 years of treatment with anti-thyroid drugs. I131 or thyroidectomy was used as second line therapy in the present study. They were offered to those who developed side effects, had poor compliance or failed medication. For those who received I131, higher dose (200 microCi/g of thyroid tissue) seemed to be more effective than the lower dose (100 microCi/g).

Preliminary data of insulin glargine use among Thai adolescents and young adults with type 1 diabetes mellitus treated at Siriraj Hospital.

Insulin glargine is a new long-acting insulin analog with a duration of action of 24 hours and can be given once a day as the only basal insulin combined with short or rapid-acting insulin as bolus insulin for each meal. The goals of this study were to evaluate short term result of treatment with insulin glargine compared to NPH and to determine the initial dosage of insulin glargine in Thai adolescents with type 1 diabetes. We reviewed charts of 10 adolescents (median age 20.8 years, range 12.3-22.7 years) with type 1 diabetes who had received insulin glargine for > or = 4 months (median 16.5 months, range 4-25 months). Before switching to insulin glargine, all patients received NPH. Seventy percent of subjects had improvement of HbA1c from 10.4% (range 8.2-12.6) to 8% (range 6.7-10.6). The total amount of insulin dosage was significantly decreased from 1.2 (range 0.9-2.4) to 0.9 (range 0.4-1.5) units/kg/day as well as the percentage of basal insulin which was decreased from 70% (range 67-81) to 47% (range 38-56) of the total daily insulin. Insulin glargine did not cause severe hypoglycemia in this study. Conclusion: Insulin glargine is another promising therapy for adolescents with type 1 diabetes. We recommend the starting total daily insulin dosage to be decreased to 70-80% of previous dosage. Insulin glargine should be started at 50% of the new total daily insulin dosage.

Improved glycemic control among Thai children and young adults with type 1 diabetes participating in the diabetes camp.

Diabetes Education Program, Faculty of Medicine Siriraj Hospital has provided summer camps for Thai children with type 1 diabetes since 1990. The objective of this study was to evaluate the effectiveness of the diabetes camp in glycemic control. Twenty male and forty-two female patients participated in the 5-day diabetes camp held in Karnchanaburi, Thailand in 2003. The mean age was 14.1 +/- 4.3 years and the mean duration of disease was 4.5 +/- 3.5 years. Fifty out of sixty-two patients returned for a 3-month-postcamp visit. The glycemic control improved significantly. The mean precamp and postcamp HbA1c levels were 10.0 +/- 3.1% and 9.0 +/- 2.6% (p = 0.008) respectively. The diabetes camp is a valuable program for patients to learn diabetes-self management skills, especially in countries where the diabetes education programs are not always available.

Clinical pictures of type 2 diabetes in Thai children and adolescents is highly related to features of metabolic syndrome.

Prevalence of type 2 diabetes (T2DM) in children and adolescents has increased, parallelled to the increased prevalence of obesity around the world. The objectives of this study are (1) to identify the clinical presenting features of T2DM in Thai children and adolescents, and (2) to identify evidence of feature of metabolic syndrome in these affected. We analyzed 26 T2DM patients who were treated by Pediatric endocrinologists in our hospital. The study showed that their mean ages (+/- SD) at diagnosis was 12.1 +/- 2.3 years, all were obese and 96% had acanthosis nigricans. Fifty three percents (53%) presented with clinical signs and symptoms which included DKA (19.2%), clinical triad of polyuria, polydipsia and weight loss (15.4%), only polyuria, polydipsia (11.5%) and abnormal menstruation (7%). The rest of 46.2% had no clinical symptoms. The initial fasting or random plasma glucose found above diagnostic range in 84.5%, the rest of 15.5% were diagnosed by using oral glucose tolerance test. Dyslipidemia was found in 75%. Fifteen percents had no family history. Eighty percents had three or more than three features of metabolic syndrome. In conclusions, clinical picture of type 2 diabetes in Thai youth varied from asymptomatic to severe illness (DKA). Almost all had clinical features of metabolic syndrome. Childhood obesity has become epidemic in our population. Such clinical picture should alert all pediatricians to be aware of chronic diseases and for making an early diagnosis and preventing long-term complications in the future.

Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS.

The prevalence of obesity in Thai children is increasing. These individuals are at increased risks of metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS), dyslipidemia and hypertension. PCOS has been known to be associated with insulin resistance. OBJECTIVES: To compare the insulin sensitivity between obese adolescent girls with PCOS and those without PCOS. MATERIAL AND METHOD: We reviewed demographic and hormonal data of 6 obese adolescent girls with PCOS and compared with 6 age, weight and BMI-matched non-PCOS controls. Each subject underwent an oral glucose tolerance test. RESULTS: Homeostasis model assessment of insulin resistance score (HOMA-IR score) in obese adolescent girls with PCOS was significantly higher than in girls without PCOS with median and range as follows (16.5 [3.8, 21.8] vs. 4.1 [3.3, 6.9], p = 0.04). Our study demonstrates that obese adolescent girls with PCOS have more severe insulin resistance measured by HOMA-IR score than girls without PCOS independent of the degree of obesity. Since insulin resistance is a metabolic precursor of future cardiovascular diseases, obese adolescent girls with PCOS might be at greater risk of developing cardiovascular disease in later adulthood than their non-PCOS counterparts.

Persistent hyperinsulinemic hypoglycemia of infancy: experience at Siriraj Hospital.

BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of recurrent or persistent hypoglycemia in early childhood. Conventionally, pancreatectomy (Px) has often been recommended to control hypoglycemia. However, PHHI can be managed successfully by intensive medical treatment to avoid pancreatectomy. METHOD: Data from 10 infants (8M, 2F) with PHHI were retrospectively analyzed. RESULTS: Eight patients (80%) developed symptoms within 72 hours after birth (early-onset). Six patients (60%) underwent 85 per cent-95 per cent Px due to failure of medical treatment. Two patients who underwent less than 95 per cent Px required second Px (97% and 99%). One patient developed permanent diabetes mellitus and malabsorption. Hypoglycemia could be successfully managed by medication alone in four patients (40%). Of these, three patients had early-onset neonatal hypoglycemia. Medication could be discontinued in three patients (75%). Three of ten patients (30%) had delayed development. Pancreatectomies and/or the diagnosis of PHHI were made late for these patients. One of these three children also developed epilepsy. CONCLUSIONS: Patients with PHHI frequently require pancreatectomy which commonly results in long-term complications especially diabetes mellitus and malabsorption. Our data suggest that PHHI can be managed successfully with an intensive medical regimen even in patients with early-onset hypoglycemia. Although medical management is very laborious for the family and physician, it should be applied until euglycemia is accomplished. Moreover, the early diagnosis of PHHI and the successful hypoglycemic control are very necessary to prevent permanent neurologic sequelae.

Ambiguous genitalia: an overview of 22 years experience and the diagnostic approach in the Pediatric Department, Siriraj Hospital.

The newborn with abnormal genital development presents a difficult diagnostic and treatment challenge for the pediatrician providing care. It is important that a definitive diagnosis be determined as quickly as possible so that the appropriate treatment plan can be established to minimize medical, psychological and social complications. The purpose of this study was to provide an extensive review of the clinical characteristics of a patient cohort with ambiguous genitalia, from 22 years' experience in the Division of Endocrinology and Metabolism, Department of Pediatrics, Siriraj Hospital, and to classify them into diagnostic categories. Moreover, a cascade of diagnostic tools in approaching sexual ambiguity in the authors' institution, starting with history and physical examination and leading to further radiographic and laboratory investigations is demonstrated and can be adopted as a guideline for the clinical management of these disorders. From 1979 to 2001, care was provided to a total of 109 patients with ambiguous genitalia, of whom 104 patients were reviewed. Among these individuals, 52 patients (50.0%) belonged to the diagnosis of female pseudohermaphroditism, 5 patients (4.8%) were in the true hermaphroditism group and the remaining 47 patients (45.2%) were in the male pseudohermaphroditism group. All female pseudohermaphrodites carried a diagnosis of congenital adrenal hyperplasia (CAH) and were reared as girls. 21 hydroxylase deficiency CAH accounted for all except one (98%) in this group. Among the 47 male pseudohermaphrodites, 9 (19.1%) had dysgenetic male pseudohermaphroditism, 7 (14.9%) had either testosterone biosynthetic defects or hCG unresponsiveness, 22 (46.8%) had either androgen insensitivity syndrome or 5 alpha-reductase deficiency, 4 (8.5%) had ambiguous genitalia in a 46,XY male associated with multiple anomalies and 5 (10.6%) had an unidentifiable cause. Sex reassignment occurred, not uncommonly, in 4 cases of female pseudohermaphrodites (7.7%) and at least 2 cases (3.9%) in the combined group of male pseudohermaphrodites and true hermaphrodites. The scope of the ambiguous genitalia problem is definitely not minor. An inappropriate approach to this problem poses an undue risk to the integrity of the physical and psychosexual health in the future for these children.