Growth hormone response to standard provocative stimuli and combined tests in very young children with Prader-Willi syndrome.

BACKGROUND: In Prader-Willi syndrome (PWS) a reduced growth hormone (GH) response to several stimulators has been documented in many studies, but none have focused on very young children. We evaluated the pattern of GH secretion in very young PWS patients. PATIENTS AND METHODS: Twenty-seven genetically confirmed PWS children (10 females, aged 0.4-5 years, mean: 2.2 ± 1.4 years) were included. All subjects underwent standard provocative tests (clonidine, CLO; and arginine, ARG) and one combined test [growth hormone-releasing hormone (GHRH) plus pyridostigmine (13 patients) or GHRH plus arginine (14 patients)]. Insulin-like growth factor-1 (IGF-1) levels were also measured. RESULTS: While standard tests (CLO and ARG) showed low GH peak in 85.2 and 70.4% of the patients, respectively, the combined test was found to be normal in 85.2%. IGF-1 was low in 66.7% of patients. Out of 27 patients, 3 (11%) showed a normal GH peak with both standard tests (group A), 6 (22%) to one of the standard tests (group B) and 18 (67%) presented a low response to both standard tests (group C). Four subjects showed low response to both the combined and standard tests and reduced IGF-1. CONCLUSION: Our data suggest that very young PWS children seem to have impaired hypothalamic GHRH secretion with a normal GH pituitary reserve.

Central precocious puberty and growth hormone deficiency in a boy with Prader-Willi syndrome.

In Prader-Willi syndrome (PWS) hypothalamic dysfunction is the cause of hormonal disturbances, such as growth hormone deficiency (GHD), hypogonadism, and delayed or incomplete puberty. Only a few cases of central precocious puberty (CPP) have been reported. We describe an 8.8-year-old PWS boy, with microdeletion of chromosome 15q, who developed CPP. On admission, height was 131.1 cm (+0.17 SD), BMI 26.2 kg/m(2), pubic hair (Ph) 2, and testis 4.5 ml. We found increased growth velocity (7 cm/year), high testosterone levels, pubertal response to GnRH test, and advanced bone age (10.6 years). An evaluation of growth hormone (GH) secretion revealed a deficiency. Pituitary MRI was normal. LHRH analogue therapy (Leuproreline 3.75 mg/28 days i.m.) was started at 8.9 years and discontinued at 11.3 years, when the patient had bone age of 13 years. During therapy, growth velocity, testosterone, FSH, and LH peak decreased significantly, with no pubertal progression. Growth hormone therapy (0.24 mg/kg/week) was started at 9.5 years and discontinued at 15.3 years because the patient had bone age of 17 years. After interrupting LHRH therapy the patient demonstrated spontaneous pubertal progression with pubertal gonadotropin and testosterone. At 16.3 years, height was 170 cm (-0.48 SDS), BMI 36.3 kg/m(2), Ph 4, testis volume 10 ml and there was a combined hypothalamic and peripheral hypogonadism hormonal pattern (normal LH even with low testosterone and undetectable inhibin B with high FSH). To our knowledge this is the fourth male patient with genetically-confirmed PWS demonstrating CPP and GHD and the first with a long follow-up to young adulthood.

Sudden death in Prader-Willi syndrome during growth hormone therapy.

We describe a child with Prader-Willi syndrome (PWS) aged 3 years and 11 months who suddenly died 7 months after the initiation of GH therapy. The child never showed respiratory problems, but suffered from severe obesity. This case raises the question about the association between sudden death in children with PWS (with or without respiratory problems) and GH therapy, as already suspected in the recent past. We suggest that further epidemiological studies are required in order to determine more accurately the frequency of this causal connection and better understand its pathogenesis.

Multiple myeloma diagnosed during early pregnancy: a case report.

Only five pregnant women with multiple myeloma have been reported in literature. We present the case of one woman with multiple myeloma diagnosed in early pregnancy, who decided to postpone therapy until after delivery. A cesarean section was performed at the 34th week due to the progression of the disease and a normal healthy baby was delivered.