R. Wolter

Treatment Strategy and Long Term Follow Up of Congenital Hypothyroidism

Congenital hypothyroidism is one of the most common endocrine disorders in childhood (1). Since it became possible to establish mass screening programs for this condition, its outlook has changed dramatically: early diagnosis and treatment have led to the disappearance of mental retardation (2), which was the most dramatic long-term sequella of congenital hypothyroidism (3). Whether the physical and neuropsychological development of children diagnosed as having congenital hypothyroidism by neonatal screening is entirely normal remains controversial (2, 4–11).

Enhanced ACTH and blunted cortisol responses to corticotropin-releasing factor in idiopathic panhypopituitarism

ADM IN 1STRATION of corticotropin-reteasing factor has been shown to stimulate the release of ACTH and cortisol in normal humans? -4 In one patient with hypothalamic anterior pituitary failure, Miiller et al? found a normal ACTH response without cortisol elevation. The purpose of our study was to assess the characteristics of the pituitaryadrenal responsiveness to CRF in a group of six patients with nontumoral idiopathic panhypopituitarism. METHODS Six patients (five males) with nontumoral idiopathic panhypopituitarism, aged 12 to 29 years, were examined, with informed consent. All patients had delayed growth and bone maturation. All were shown to have blunted responses of hGH and of cortisol to both insulin intravenously and glucagon intramuscularly 5 and absence of an increase of plasma l l-deoxycortisol or urinary 17hydroxysteroids after metyrapone. Serum dehydroepiandrosterone sulfate concentration ~was <100 ng/ml in all patients. All had tertiary hypothyroidism as assessed by TSH response to TRH, and gonadotropin deficiency as assessed by lowered LH and FSH responses to LH-RH and absence of spontaneous pubertal development. Skull radiographs were normal. All patients had been receiving hormonal substitutive therapy for several years. The two oldest patients (patients 4 and 5) were not receiving growth hormone treatment at the time of the study. Corticoid treatment had been stopped for 2 years in patient 4 and at

3 EFFECT OF GROWTH HORMONE RELEASING FACTOR (GRF) ON PLASMA GROWTH HORMONE (GH) AND PROLACTIN (PRL) LEVELS IN OBESE CHILDREN

Obese children have a blunted GH response to conventional pharmacological stimuli. To assess whether this blunted response has a hypothalamic or pituitary origin, the response of plasma GH to a glucagon stimulation test (0.1 mg/kg IM) and to a single IV bolus of 0.5 μg/kg of GRF was studied in 13 obese children [145 ± 7% (SEM) of ideal body weight (IBW)] and compared to that of 19 lean (93 ± 4% of IBW) short children with normal pituitary function (N). Peak GH response to glucagon was lower in obese than in N children (16.0 ± 2.0 vs 29.2 ± 4.5 ng/ml, p < 0.001) as was the GH response to GRF (12.4 ± 2.6 vs 39.2 ± 5.1 ng/ml, p < 0.001); the GH response to GRF tended to be more prolonged in obese than in N children. In neither group was there a correlation between peak GH after GRF and percentage of IBW or age. There were no acute changes in PRL levels after GRF in neither group : a normal decrease was observed between 9 and 11 AM (from 201 ± 48 and 211 ± 49 μU/ml to 146 ± 31 and 108 ± 27 μU/ml in the obese and N group, respectively).Conclusion: obese children have a blunted and prolonged GH response to GRF; this blunting is not correlated with age and is not associated with an acute increase in PRL levels, as seen in children with hypothalamic hypopituitarism (Ped Res 18 : 1216, 1984) and thus probably results from a different mechanism, perhaps at the pituitary level.

Effect of growth hormone releasing factor (GRF) on serum growth hormone (GH) and prolactin (PRL) in hypopituitary children

GRF may be of value in investigating growth disorders. An IV bolus of 0.5 μg/kg of GRF-44-NH2 (Peninsula Labs, USA) was given to 12 short normal children (N) and 24 children with documented GH deficiency (GHD). Serum GH and PRL were measured by RIA. In the N group. GRF induced a rapid and ample GH response :In the GHD group, mean peak GH after GRF was lower than in the N group (8.0±2.5 vs 39.2±5.1 ng/ml, p<0.001) but peaks within the normal range were seen in the youngest GHD patients. In the N group, PRL decreased continuously over the 3 hours of the test, a reflection of its normal circadian rythm (222±54 at 9 AM vs 108±27 μU/ml at 12 AM, p<0.05). In 7 GHD patients, PRL peaked 15 minutes after GRF (366±73 at 0 min vs 494±85 μU/ml at 15 min, p<0.05); in 2 patients with genetic GHD, PRL decreased to a nadir at 60 min, followed by a rebound; in the remainder of the GHD group there was no change in PRL. Conclusion : 1) GRF at a dose of 0.5 μg/kg is a potent GH secretagogue in children; 2) Some GHD children have GH responses to GRF within the normal range; 3) The PRL response to GRF in GHD is heterogeneous.