Stephen F. Kemp

American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update.

The American Association of Clinical Endocrinologists Medical Guidelines for Growth Hormone use in Growth Hormone Deficient Adults and Transition Patients – 2009 Update are systematically developed statements to assist health care providers in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual circumstances.

Effect of long-term recombinant growth hormone therapy in children--the National Cooperative Growth Study, USA, 1985-1994.

Over a 9-year period (1985-1994) approximately 20,000 children received recombinant human growth hormone (rhGH) while enrolled in the National Cooperative Growth Study (NCGS), an observational, longitudinal study designed to monitor the long term efficacy and safety of rhGH administered to children in North America. Forty-four percent of the patients had idiopathic growth hormone deficiency (IGHD), 13.8% organic GHD (OGHD), 25% idiopathic short stature (ISS), 9.9% Turners syndrome (TS), and 7.3% miscellaneous disorders. Eighty-five percent of the patients enrolled were Caucasian, and approximately two-thirds of the non-Turner patients were male. For the subset of patients treated for at least 4 years and who were prepubertal throughout this period (IGHD N=308, OGHD N=93, ISS N=169, TS N=82), mean growth rates increased in all patient categories and remained at or above pretreatment growth rates through 4 consecutive years of therapy with rhGH. Growth rates during administration of rhGH were greater in children in whom the pretreatment maximum stimulated GH concentration was < or =3 microg/l. Patients treated with 6 or 7 doses of rhGH each week grew more rapidly than did those receiving thrice weekly dosages, although the ratios of the increment in bone age to the increment in height age after two years of therapy were similar in the two treatment regimens. For patients treated with rhGH for 7 consecutive years, the mean height standard deviation scores increased by 2.5 in IGHD (N=169), 2.0 in OGHD (N=50), 1.9 in ISS (N=69), and 1.3 in TS (N=19), but remained below target heights in all categories. It is concluded that administration of rhGH increases growth rates in patients with IGHD, OGHD, ISS, and TS, and that this stimulatory effect can persist for at least 4 years.

Renal structural-functional relationships in early diabetes mellitus

Abstract.u2003 To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5u200a–u200a12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: “glomerular size” correlated with patient age, CCr, and UAE; “peripheral capillary decrease” correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; “mesangial increase” correlated with UAE; and “interstitial scarring” correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.

Isolation of a biotin receptor from hepatic plasma membranes.

Biotin, one of the growth promoting members of the B complex vitamin family, was found in the present investigation to have a specific receptor on isolated plasma membranes. Biotin bound to its receptor in a linear manner at 20 degrees C with some binding as early as 30 minutes and full equilibrium binding being present at 20 hours. The best binding was found at 0.6 mg/ml of protein, but significant binding was still present at 0.6 microgram/ml. The saturation of ligand binding sites was at 10(-7)M. Half maximal saturation of binding was between 10(-9) and 10(-10)M. These results demonstrate that a receptor for biotin does exist on purified plasma membranes.

Twenty Years of Recombinant Human Growth Hormone in Children: Relevance to Pediatric Care Providers

Recombinant human growth hormone has revolutionized the management of children and adolescents with growth hormone deficiency and other growth disorders, but clinical and ethical controversies remain regarding diagnostic approach, optimal recombinant human growth hormone dose and duration, and expected outcomes. Management of pubertal and transitioning patients with growth hormone deficiency has also commanded increased attention. Recent clinical studies that demonstrate the positive health benefits of recombinant human growth hormone in children with cystic fibrosis, inflammatory bowel disease, and juvenile rheumatoid arthritis have not yet clarified issues about patient selection and appropriate long-term use. An understanding of current recombinant human growth hormone indications and controversies can facilitate patient evaluation and expedite referral for potential treatment. This review summarizes current indications for recombinant human growth hormone use, discusses clinical challenges, and provides recommendations for pediatricians caring for children who may be appropriate candidates for recombinant human growth hormone therapy.

Hypertrophy of clitoral hood : presenting sign of neurofibromatosis in female child

Although clitoral involvement with neurofibromatosis is rare, all cases previously reported have described clitoral hypertrophy due to neurofibromas of the clitoral corpora. We report on a patient who had localized enlargement of the prepuce only, with no evidence of neurofibromatous infiltration. In all cases, diagnosis of clitoromegaly requires basic chromosomal and endocrinologic evaluation. However, recognition of its association with neurofibromatosis due to either neurofibromas of the genitalia or localized genital hypertrophy may spare the patient an unnecessary or invasive evaluation. Because of an association with urinary tract neurofibromas, the patient with genital involvement should have cystoscopy. Clitoroplasty with sparing of the neurovascular bundle and glans is the preferred method of management of the enlarged clitoris.

American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update: executive summary of recommendations.

The American Association of Clinical Endocrinologists Medical Guidelines for Growth Hormone use in Growth Hormone Deficient Adults and Transition Patients – 2009 Update are systematically developed statements to assist health care providers in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual circumstances.

Alteration of Phenytoin Binding by Glycosylation of Albumin in IDDM

We measured glycosylated albumin and hemoglobin and serum protein binding of phenytoin in 57 children and adolescents with insulin-dependent diabetes mellitus (IDDM). Serum was incubated with phenytoin to yield concentrations of 15 and 25 mg/L, and a serum ultrafiltrate was prepared from an aliquot of each sample. We observed a linear correlation between glycosylated albumin and the free fraction of phenytoin at serum phenytoin concentrations of 15 mg/L (r = .35, P = .03) and 25 mg/L (r = .40, P = .003). A better correlation existed between the free fraction of phenytoin and total albumin concentrations for both serum concentrations (r = .45, P = .005 for 15 mg/L; r = .56, P = 10−5 for 25 mg/L), whereas the best linear correlation resided between the free fraction of phenytoin and the concentration of nonglycosylated albumin (r = .54, P = .0005for 15 mg/L; r = .63, P < 10−6 for 25 mg/L). There was no correlation between the free fraction of phenytoin and the concentration of glycosylated albumin. Incubation of solutions of glycosylated and nonglycosylated albumin demonstrated significantly lower binding to the glycosylated fraction (P = 8.1 × 10−6). These results indicate that glycosylation of albumin diminishes the affinity of the phenytoin binding site on albumin. This alteration may have clinical significance in that it may alter the disposition of phenytoin in patients with IDDM and produce free phenytoin serum concentrations that are not accurately reflected by total serum phenytoin concentrations.

Effects of Recombinant Human Growth Hormone on Height and Skeletal Maturation in Growth Hormone-Deficient Children with and without Severe Pretreatment Bone Age Delay

The relative effects of growth hormone (GH) on GH-deficient (GHD) children with and without severely delayed skeletal maturation prior to treatment are unclear. Methods: Pre-pubertal GHD children enrolled in the National Cooperative Growth Study were divided into two groups: severe pretreatment BA delay (BA Z-score ≤–2, group 1) and mild to moderate delay (BA Z-score between –2 and 0, group 2). BA Z-scores (BAZ), height Z-scores and predicted adult height (PAH) Z-scores at pubertal onset were determined after initiation of recombinant human GH (rhGH) therapy. Results: Height Z-scores increased from baseline to the start of puberty in both groups (group 1: mean difference of +0.99, males and +1.02, females; group 2: +0.68, males and +0.75, females). Mean BAZ also increased in all group 1 children (+1.62, males and +1.08, females) with no corresponding change in mean BAZ in group 2. PAH Z-scores increased in both groups. There was no evidence of undue advance in BA since mean BAZ remained well below zero in group 1 and was unchanged in group 2. Conclusion: rhGH has a beneficial effect on growth in prepubertal GHD children at all levels of pretreatment BA delay.

Glyburide Protein Binding and the Effect of Albumin Glycation in Children, Young Adults, and Older Adults with Diabetes

Because glyburide is a weak acid that is more than 98% bound to albumin, the authors evaluated the binding in vitro and the influence of albumin glycation in children, young adults, and older adults with diabetes mellitus. Glyburide binding to non‐glycated albumin was greater than 98%, and remained constant over a total concentration range of 50 to 1000 ng/mL. Increasing the albumin concentration from 0.5 to 5.0 g/dL was logarithmically related to the free fraction of glyburide. After the in vitro glycation of albumin (range, 5.7–15.6%), mean (±SD) glyburide binding was 99.05 ± 0.082%, a value in agreement with that obtained from control serum. Serum samples from 57 subjects with type I and 16 patients with type II diabetes were incubated with 300 ng/mL of unlabeled glyburide and 200 ng/mL of 14C‐glyburide. The extent of albumin glycation varied from 5 to 22% for the type I subjects and 5 to 14% for the type II subjects. The free fraction from these groups ranged from 1.07 to 1.75% and 0.66 to 0.88% for the type I and type II subjects, respectively. Although these values did not differ significantly from those of the control samples, the glyburide free fraction in patients with type I diabetes (1.39 ± 0.85%) was significantly greater than that found for the 16 elderly patients with type II diabetes (0.78 ± 0.05%). A significant linear relationship was not found between glyburide free fraction and the degree of albumin glycation for either group. Glyburide protein binding did not appear to be influenced by the extent of albumin glycation.