Carbohydrate metabolism in children receiving growth hormone for 5 years

Carbohydrate metabolism was evaluated by fasting and postprandial glucose, insulin, and hemoglobin (Hb)A_1c levels in children with chronic renal insufficiency and various other growth disorders treated with growth hormone. Mean fasting and postprandial glucose remained unchanged throughout the 5-year study period in all four study groups. Median fasting insulin levels rose from lownormal levels into the normal range after 5 years of growth hormone. Average fasting insulin level after 5 years was 10 mU/l. Median postprandial insulin values also rose, yet remained within the normal range at the 5-year mark. Mean Hb A_1c levels remained within low to middle end of the normal range in the patients with growth hormone deficiency, Turner syndrome, and idiopathic short stature. Mean Hb A_1c levels at the 5 years were slightly elevated to 6.3% for the patients with chronic renal insufficiency.     

Reversibility of deficient sleep entrained growth hormone secretion in a boy with achondroplasia and obstructive sleep apnea

Obstructive sleep apnea may lead to disordered sleep architecture and impair the physiologic slow wave sleep related growth hormone release. Obstructive sleep apnea occurs with craniofacial syndromes and in children with airway narrowing, pharyngeal hypoplasia, tonsillar adenoidal hypertrophy, micrognathia and achondroplasia. To examine the relationship between disordered sleep and growth hormone release we studied a 9 year old male with achondroplasia, growth failure (3 cm/year) and obstructive sleep apnea. Polysomnography data and a 20 min sampling for sleep entrained growth hormone showed before therapeutic tracheostomy numerous apneic episodes, absent slow wave sleep and abnormal low growth hormone secretion during sleep. Normalized slow wave sleep entrained growth hormone secretion after tracheostomy led to a sustained increase in growth rate. Normal growth rate (greater than 5 cm/year) continues 2 years after tracheostomy. We conclude that obstructive sleep apnea may impair sleep related growth hormone release. Obstructive sleep apnea may be a useful model for other diseases in which growth failure and sleep disturbances are linked.     

The use of biomarkers for the evaluation and treatment of patients with acute coronary syndromes

The advent of inexpensive, highly accurate, and predictive markers of myocardial injury, inflammation, and hemodynamic stability has revolutionized the evaluation and treatment of patients who have acute coronary syndromes (ACSs). These blood biomarkers require small sample volumes, can be run expeditiously, and provide important information concerning the diagnosis, risk stratification, and treatment of these patients. To understand the use of these markers, one must have some knowledge about what elevations in these markers imply, how they have to be collected and measured to provide reliable information, when to suspect analytic confounds, and what the key values are that impart the diagnostic, prognostic, and therapeutic information. This article discusses these issues, emphasizing what clinicians must know for optimal test use, and then addresses the practical use of these markers in patients who have ACS.     

Evidence for an unidentified ACTH-induced steroid hormone causing hypertension.

The hypothesis that hyperaldosteronism is not the sole cause of hypertension in dexamethasone-suppressible hyperaldosteronsim was tested in an 18-year-old male. After six years of little or no treatment, the hypertension and mild hyperaldosteronism were promptly decreased by a small dose of dexamethasone. During dexamethasone treatment, when aldosterone secretion was suppressed to less than normal and he was normotensive, steroids were given by constant infusion in an attempt to reproduce the hypertension of the dexamethasone-free state. Neither five days of aldosterone or 18-hydroxydesoxycorticosterone (18-OH-DOC) at 1 mg/day, nor desoxycorticosterone (DOC) at 30 mg/day caused hypertension. However, sodium retention and potassium loss was observed during aldosterone and DOC infusion. Hypertension was produced within five days during infusion with ACTH or oral metyrapone. The hypertensive effect of the latter was abolished by addition of aminoglutethimide treatment. These studies suggest that a steroid other than aldosterone, 18-OH-DOC, or DOC may be the cause of the ACTH-induced hypertension in this patient. The aminoglutethimide data suggest that the ACTH effect on blood pressure is due to a steroid, and the metyrapone studies suggest that the steroid may be an 11-desoxysteroid. Urine and blood collected under ACTH stimulation and metyrapone treatment may be a rich source from which we may characterize this hormone.     

Partial growth hormone insensitivity--idiopathic short stature is not always idiopathic

Heterozygous growth hormone receptor (GHR) gene defects are not a common cause of idiopathic short stature. Although some of these GHR mutations may result in relative insensitivity to growth hormone (GH) in other studies, obligate heterozygotes did not present any clinical manifestations. Although patients with GH insensitivity and elevated GH binding protein (GHBP) levels have been described, it may be a reasonable approach to screen children who have growth failure, low levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3, and low levels of GHBP. Whether the sensitivity of this screening approach can be increased by administering pharmacological doses of GH for a few days and measuring the resultant increase in serum IGF-I concentration remains to be determined by ongoing studies.     

Ductus-dependent fetal cardiac defects contraindicate indomethacin tocolysis.

The hemodynamics of critical aortic stenosis in the fetus make it a ductus-dependent cardiac defect because the ductus arteriosus supplies blood not only to the descending aorta but also to the aortic arch and coronary vessels. In utero closure of the ductus arteriosus has been reported in association with tetralogy of Fallot, truncus arteriosus, maternal use of prostaglandin inhibitors, and as idiopathic events. This is the first report of a ductus-dependent congenital heart defect (critical aortic stenosis) where treatment with indomethacin, a prostaglandin synthetase inhibitor, precipitated premature closure of the ductus and hydrops fetalis. Review of reported cases of premature closure of the ductus show that acute, in utero closure of the ductus in a fetus with limited cardiopulmonary reserves has a worse prognosis than with previously reported cardiac anomalies. This study strongly supports published concerns of increased perinatal morbidity and mortality when fetuses are exposed to prostaglandin inhibitors in utero, and shows that ductus-dependent fetal cardiac defects are contraindications to the maternal use of prostaglandin inhibitors during pregnancy.