Two cases of Klinefelter syndrome with precocious puberty due to mediastinal germ cell tumor.

Background: Klinefelter syndrome may present as precocious puberty, which can be either central precocious puberty or peripheral precocious puberty, caused by an extragonadal germ cell tumor. Objective: Report two cases of Klinefelter syndrome that presented with precocious puberty due to a ?-hCG producing mediastinal tumor. Method: Review of the clinical history, physical examination, and laboratory investigations. Results: Pseudo-precocity developed some years before diagnosis of -hCG producing tumor. The patients did not have typical physical features of this syndrome. The testes were small and had loose consistency. Conclusion: Klinefelter syndrome must be excluded in all boys presenting with precocious puberty due to a ?-hCG producing tumor. Conversely, patients with Klinefelter syndrome should be regularly checked for ?-hCG and ?-fetoprotein levels. In those cases, the patients can be diagnosed and treated early. With the early treatment, they will be able to attain normal adult height and have fewer complications from the tumor.

Bone mineral density and body composition in prepubertal and adolescent patients with the classical form of 21-hydroxylase deficiency.

OBJECTIVES: To evaluate bone mineral density (BMD) and body composition in prepubertal and adolescent patients with the classical form of 21-hydroxylase deficiency. MATERIAL AND METHOD: The authors measured height, weight and used dual energy x-ray absorptiometry (DEXA) to evaluate lumbar spine, whole body BMD and body composition in 10 prepubertal and adolescent patients with the classical form of 21-hydroxylase deficiency. Serum hormone concentrations (17-hydroxyprogesterone, dehydroepiandrosterone sulfate) were also measured. Results were compared with those of age- and sex-matched controls. RESULTS: Seven patients were adolescent (4 girls and 3 boys; age range, 9.0-19.6 years) and three patients were prepubertal. (2 girls and 1 boy; age range, 6.5-8.6 years). There were no significant differences in age, height z-score, weight z-score and body mass index between the patients with congenital adrenal hyperplasia (CAH) and controls. DEXA showed no differences between each group in whole body BMD, but showed significantly elevated areal regional BMD at the lumbar spine (L1-L4) in CAH patients. However four of the 10 CAH patients and 6 of the 10 controls had osteopenia. The BMD z-score at the lumbar spine was significantly correlated with increasing weight z-score in both CAH patients and controls. When CAH patients with osteopenia were compared with those with normal BMD, there was a trend toward lower weight z-score, higher dose of glucocorticoids and longer duration of treatment among the osteopenic patients, but it did not reach statistical significance. CONCLUSION: Classical 21-hydroxylase deficiency patients treated with long-term glucocorticoids did not have impaired bone mineral density compared with healthy, age and sex-matched controls. However, the reference data for BMD in the Thai pediatric population is lacking and the number of studied participants was limited so we need further studies.

Diagnosis and growth hormone (GH) therapy in children with GH deficiency: experience in King Chulalongkorn Memorial Hospital, Thailand.

BACKGROUND: Diagnosis of growth hormone deficiency (GHD) needs both clinical and biological aspects such as auxological data and GHprovocative tests, and active metabolites of GH including IGF-I and IGFBP-3. In GHD children, rhGH has been used worldwide with minimal serious side effects. The aims of the present study were to describe the experience in King Chulalongkorn Memorial Hospital regarding diagnosis and treatment with rhGH in GHD children. MATERIAL AND METHOD: Clinical data of 173 short children was retrospectively reviewed. Two GH provocative tests used in the present study were insulin tolerance test (ITT) and clonidine test. To make the diagnosis of GHD, the children had to fail both GH provocative tests (peak GH < 10 ng/ml). Baseline clinical data, IGF-I, and IGFBP-3 were compared between the group with true positive test and the group with false positive test. Thirty-five children with GHD, who had been treated with rhGH, were evaluated in terms of growth response, changes of IGF-I SDS and the relationship between these parameters. RESULTS: From the present study, ITT could diagnose GHD with true positive 57% and false positive 43% and clonidine could diagnose with true positive 67% and false positive 33%. Clinical data including chronological age, bone age, HtSDS, WtSDS, IGF-I SDS, and IGFBP-3 SDS were not different between the true positive and false positive group. rhGH with a mean dose of 29.3 +/- 4.6 microg/kg/day increased height velocity (HV) from 3.9 +/- 2.5 to 9.3 +/- 2.5, 8.1 +/- 1.5, 7.2 +/- 2.2, 6.8 +/- 2.2, 7.6 +/- 2.4, and 6.5 +/- 1.8 cm/yr after 6 months, 1, 2, 3, 4, and 5 years after treatment, respectively. This also improved HtSDS during treatment and brought the HtSDS into the target range after 3 years of treatment. At the end of the first year of treatment, the difference of IGF-I SDS (DeltaIGF-I SDS) > or = 1 could predict a good response (DeltaHtSDS > or = 0.5) with sensitivity of 88.9% and specificity of 60% respectively. At the end of the second year, DeltaIGF-I SDS > or = 1 could predict a good response with sensitivity and specificity of 100% and 29%, respectively. CONCLUSION: From the present study, the authors demonstrated the investigation and treatment practices of short children with GHD. The growth response is satisfactory even with a lower dose than suggested. In addition, measurement of IGF-I and IGFBP-3 cannot be used in diagnosing GHD but can predict the height outcome at least by the first 2 years of the treatment. However long-term outcome need to be clarified.

Final adult height in "early normal pubertal girls" treated with gonadotropin releasing hormone agonists.

Gonadotropin releasing hormone (GnRH) agonist has been used worldwide for the treatment of central precocious puberty. However, the results on final adult height (FAH) are discrepant in various studies especially in girls with normal early puberty. Fourteen girls with normal early puberty who were treated with depot GnRH agonists 3.75 mg intramuscular (i.m.) monthly for a mean period of 1.5 +/- 0.4 yr were retrospectively studied. The chronological age and bone age at the beginning of treatment were 9.9 +/- 0.7 yr and 12.6 +/- 0.9 yr, respectively. When the treatment was stopped, all the girls were followed-up until they reached their final adult heights. The results showed that the mean FAH was 154.0 +/- 6.9 cm, which was not significantly different from the predicted adult height (PAH) at start of treatment, 153.1 +/- 6.2 m. All the girls were divided into 2 groups. Group A was girls who had FAH-PAH at the start of treatment > or = 1.5 cm and group B, FAH-PAH at the start of treatment < 1.5 cm. The authors found that only the duration of treatment was different between these 2 groups, 1.7 +/- 0.3 yr in group A and 1.3 +/- 0.3 yr in group B (p = 0.015). In conclusion, GnRH agonist cannot improve the final height outcome in girls with normal early puberty. However, a longer period of treatment may improve the height prognosis.

Basal luteinizing hormone/follicle stimulating hormone ratio in diagnosis of central precocious puberty.

BACKGROUND: Precocious puberty is characterized by breast development in girls prior to 8 years old and may have acne, adult odor, growth spurt and menstruation. Conventionally, gonadotropin releasing hormone (GnRH) stimulation test is a gold standard for diagnosis of central precocious puberty but it is a time-comsuming procedure that is not practical on an out patient basis. OBJECTIVE: To evaluate the basal luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in diagnosis of central precocious puberty in order to save time and cost. SUBJECTS AND METHOD: The GnRH stimulation tests were performed on 51 girls with breast development before 8 years old. The 51 girls were divided into 2 groups, 24 girls with central precocious puberty (CPP) and 27 girls with premature thelarche (PT), and the clinical data and GnRH stimulation tests data were compared between the 2 groups. The authors also compared the clinical data and GnRH stimulation tests data between 13 girls with PT and 12 girls with thelarche variants (TV) who developed puberty approximately 1 year later as confirmed by GnRH stimulation test. RESULTS: Girls with CPP had a large bone age and chronological age ratio and advancement of breast staging. Girls with TV had a greater level of basal luteinizing hormone (LH), peak LH and 120 min estradiol than girls with PT. Basal luteinizing hormone and follicle stimulating hormone (FSH) ratio greater than 0.2 can be used to diagnose CPP with 75 per cent sensitivity, 85 per cent specificity, 82 per cent positive predictive value (PPV) and 82 per cent negative predictive value (NPV). CONCLUSION: Girls with CPP have a basal LH/FSH ratio greater than 0.2 and this can be used as a cut-off point for the diagnosis CPP.

Water and sodium disorders in children undergoing surgical treatment of brain tumors.

BACKGROUND: Many children with brain tumors have abnormalities in water and sodium homeostasis, such as diabetes insipidus (DI), the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSW), either pre-operatively or post-operatively. But little data have been published on the incidence, time of onset and clinical course of water and sodium disorders in children with brain tumors. OBJECTIVES: To characterize the water and sodium disorders in children undergoing surgical treatment for brain tumors. PATIENTS AND METHOD: The medical records of children with brain tumors admitted for surgery at King Chulalongkorn Memorial Hospital from January 1997 to December 2002 were retrospectively reviewed. RESULTS: There were 79 patients, 46 males and 33 females included in this study. Water and sodium disorders occurred in 36 patients (45.57%), 23 patients had DI, 12 patients had SIADH and 1 patient had cerebral salt wasting syndrome (CSW). Nine of the 36 patients had pre-operative onset of water and sodium disorders (8 DI and 1 SIADH). The development of DI and SIADH was associated with the location of the brain tumors. Patients with sellar and suprasellar tumors had the highest incidence of DI (75.86%). Patients with tumors of the cerebral hemispheres had the highest incidence of SIADH (44.44%). Onset of post-operative DI ranged from 2 to 19 hours (mean 9.68 hours) and most patients developed SIADH within 24 hours post-operatively. CONCLUSIONS: DI and SIADH are common problems in children with brain tumors, especially after surgical treatment and the onset usually occurs within 24 hours after surgery. Patients with sellar and suprasellar tumors are more likely to have DI, patients with tumors of cerebral hemispheres and posterior fossa tumors are more likely to have SIADH.

Adrenal functions in children with adrenoleukodystrophy.

BACKGROUND: Adrenoleukodystrophy refers to an inherited disorder that mainly affects the adrenal gland, and the nervous system. The most common type is X-linked adrenoleukodystrophy (XALD). The main presenting symptoms are behavioral changes. However, endocrinological manifestations are also important and need to be clarified especially adrenal insufficiency which is a lifethreatening condition that can be prevented. OBJECTIVE: To review the endocrinological and the adrenal functions in X-linked ALD. SUBJECTS AND METHOD: The medical records of four patients diagnosed with ALD at the Endocrinology and Metabolic Unit, Department of Pediatrics, King Chulalongkorn Memorial Hospital between 1998 and 2000 were reviewed. The diagnoses were confirmed by elevated very long chain fatty acid (VLCFA) levels and the typical changes seen on magnetic resonance imaging (MRI) of the brain. The adrenal functions in these patients were studied. RESULTS: All patients presented between 7-11 years of age with learning problems and behavioral changes, without symptoms of adrenal insufficiency such as nausea, vomiting and abdominal pain. However, the physical signs of adrenal insufficiency such as generalized hyperpigmentation particularly on the nipples, skin creases and genitalia were present. The laboratory investigations revealed normal blood sugar and serum electrolytes. The adrenal functions were revealed as follows. Basal ACTH levels were high in 2 cases (290, > 1,250 pg/mL). Basal cortisol level was low in 1 case. ACTH stimulation tests revealed subnormal responses in 3 cases. Magnetic Resonance Imaging of the brain showed white matter degeneration in the occipital area in 2 cases and frontal area in 2 cases. CONCLUSION: Adrenal insufficiency can be detected by laboratory evaluation despite the lack of symptoms, therefore, the adrenal function should be evaluated in X-ALD at diagnosis for proper management.