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Background Diurnal variation in serum growth hormone (s-GH) levels after exogenous GH delivery has previously been reported in patients with no endogenous GH secretion. Changes in postural position or physical activity, leading to changes in blood flow and/or lymphatic drainage may be underlying explanations. Primary objectives The primary aim of this study is to study a possible impact of exercise and supine rest on pharmacokinetics (PK) and day-to-day variation of subcutaneously (sc) administered GH in adult GH deficient (AGHD) patients. Secondary objective The secondary aim of this study is to compare s-IGF-I, s-insulin, and plasma (p)-glucose profiles after a carbohydrate rich breakfast following sc GH injection vs. continuous infusion. Design and methods During supine rest eight AGHD males (59.8 ± 8 years, BMI 29.7 ± 4.9 kg/m 2 ) were treated with one daily sc GH injections of 3 mg/24 h for 48 h (treatment sessions A, B) or a continuous sc GH infusion of 3 mg/24 h for 60 h (treatment sessions C, D). Exercise comprised 1 h bicycling with 50 W load on two consecutive days during treatment sessions B and D. Results Administration of GH as a bolus injection, but not as a continuous GH infusion, resulted in about 32% higher s-GH levels during exercise (60 min) as well as 30 min after (s-GH logAUC (B-A) difference was 0.28; 95% CI: 0.14–0.4; p < 0.001). However, the total s-GH AUC 0–24 h ( p = 0.75) and s-IGF-I AUC 0–48 h levels ( p = 0.51) remained unchanged between the two occasions. P-glucose and insulin profiles were significantly higher after carbohydrate rich breakfast before first and second dosing both following sc GH injection and continuous infusion ( p < 0.05). Conclusions Moderate exercise intermittently increased s-GH levels. These changes seem to have no clinical short-term relevance, since total s-GH 24 h and s-IGF-I 48 h levels were unaffected. [ABSTRACT FROM AUTHOR]

Abstract: Background: Previous studies in growth hormone (GH)-deficient (GHD) patients have indicated a possible diurnal variation in the pharmacokinetics (PK) of GH after subcutaneous (sc) GH administration. Thus, higher GH levels were observed during the night with continuous sc infusion, and increased GH bioavailability was reported following daily sc injections in the evening compared to morning. Objective: The aim was to study whether diurnal variability in the PK of sc administered exogenous GH can be reproduced under standard conditions for all study participants, e.g. supine rest. Design and methods: Eight male GHD patients (59.8±8years, body mass index 29.7±4.9kg/m2) received a continuous sc infusion of GH (3mg/24h) for 60h on two different occasions. Diurnal variation in PK of GH was studied during steady state in the last 24h of the infusion period. Results: Median GH levels were higher at night time (23:00h–07:00h) than during the day (10:00h–18:00h) for visit 1 [5.1 (4.5–7.2ng/ml/0.5h) vs. 4.6 (3.7–5.7ng/ml/0.5h); p<0.05], and reproducible results of diurnal GH variation were obtained during visit 2 [5.7 (4.6–7.4) ng/ml/0.5h vs. 4.6 (3.8–6.0) ng/ml/0.5h, p<0.05]. Reproducible results between days 1 and 2 were also obtained during 08:30h–20:30h and 20:30h–08:30h, respectively. Conclusions: Previous findings of higher nocturnal GH levels were confirmed during steady state continuous sc GH infusion under standard conditions. The underlying mechanisms, e.g. whether GH absorption, distribution or elimination is primarily affected need to be further elucidated. [Copyright &y& Elsevier]

Growth Hormone (GH) deficiency incidence in infants is reported to be 1 in 3800 live births, and although adequate data are missing, it is thought to be rising among older children due to increased survival after childhood malignancies. The main effect of GH deficiency in childhood is growth failure and it is treated with exogenous growth hormone replacement. Treatment with GH in childhood is generally without serious complications and the most common side effects reported are listed as headache, joint/muscle pains, fluid retention, mild hypertension, visual problems, nausea/vomiting, paresthesia, antibody formation, reactions at injection site and rarely, being intracranial hypertension. Here, we report a case of mood disorder with mixed features in a pre-pubertal child, which was possibly related with exogenous GH replacement. The patient was an 11-year-old male, who was brought to our department with complaints of "insomnia, talkativeness, increased energy and spending". Upon questioning, it was learnt that the complaints were present for the last 3 months. He was inattentive, hyperactive, euphoric and it was reported that "he felt he could do anything". His grades suffered and within the last month he verbalized suicidal ideations to his teachers. Mental status examination revealed auditory hallucinations, grandiose delusions alternating with depressive ruminations and limited insight. The medical and psychiatric history was unremarkable except growth failure, which led to a referral to the pediatrics department 4 months ago. The patient was diagnosed with GH deficiency and GH injections were commenced 3 months ago. Apart from mild memory problems and irritability, no depressive episode was reported prior to treatment with GH. Family history was negative for psychopathology. A neurological examination ruled out papillary edema and no signs or symptoms of intracranial hypertension were reported. Psychometric evaluation with the Childhood Mania Scale as completed by the parents revealed a score of 35 (chief complaints: auditory hallucinations, paranoid ideations, impulsivity, grandiosity, pressured speech, insomnia, increased energy, euphoria and irritability). The baseline evaluation with Young Mania Rating Scale yielded a score of 38. Childhood Depression Inventory and other measures could not be completed due to excessive hyperactivity. The patient was moderately impaired due to his symptoms as rated with Children's Global Assessment Scale (CGAS) revealing a score of 45. Consequently, the patient was diagnosed to have Mood Disorder with Mixed Features due to Exogenous GH, according to DSM-IV criteria and treatment was started with risperidone 0.5 mg/day, later titrated to 1 mg/day. A follow-up visit after 2 weeks revealed a YMRS score of 24 and a CGAS score of 55 (Variable functioning). Because of persisting grandiose delusions and depressive ruminations, valproate 200 mg/day was added on and a follow- up visit is planned. Here we report a case of mood disorder with mixed features in a pre-pubertal child. An evaluation with the Naranjo Algorithm yielded a score of 4 (Possible Adverse Drug Reaction, 3) and the patient responded partially to a trial of antipsychotics and mood-stabilizers. As a result, it can be said that exogenous GH in children may lead to secondary mood disorders. Our results should be confirmed with future studies. [ABSTRACT FROM AUTHOR]