Background: Analysis of insulin-like growth factor I in serum (S-IGF-I) is an integral component in the diagnosis of GH-related disorders and is going to be of interest in the diagnosis and follow-up of many disorders. The objective of the present study was to develop cross-sectional reference values for S-IGF-I measured by an automated chemiluminescence immunoassay (Nichols Advantage®). Methods: The study included samples from 3,961 healthy subjects (2,201 males, 1,760 females) aged 1 month to 88 years. Six laboratories were involved in this study and the samples were analyzed by one of seven automated immunoassay systems run in these laboratories. For data analysis, polynomial age and sex-specific models were fitted after transformation of S-IGF-I values. Results: The results show the well-known age dependency of S-IGF-I levels. At ages <20, higher S-IGF-I levels were seen in girls with an estimated mean peak of 410 µg/l at age 14 and an estimated mean peak of 382 µg/l at age 16 in boys. Thereafter, a rapid decrease was seen to approximately 25 years of age, followed by a slow age-dependent decrease. In adulthood, S-IGF-I in males were slightly, but significantly higher than in females. It could be shown that the mean values of some reference sample subgroups differed significantly from the total mean. However, the multicenter approach used in this study reduces the impact of systematic population, sample handling and laboratory differences on the calculated reference mean. Conclusion: The present study establishes age- and sex-specific reference values for a fully automated immunoassay system based on a large population of healthy subjects. The established reference values may be used for this immunoassay system in different laboratories provided that the systematic difference between systems is low.
Our data, drawn from a large population of hypopituitary adults treated with GH for a total of more than 800 patient years, confirm previous reports that untreated GHD in hypopituitary adults is associated with a number of important clinical problems. In addition, the results suggest that there has been a shift in recent years from determination of GH dose on the basis of body weight to dose titration of individual patients, and indicate that the latter technique has important advantages. The data provide further evidence that GH replacement therapy is well-tolerated in adults. However, it is possible that some adverse events may not become evident over the time scale covered by the present analysis, and continued surveillance therefore remains mandatory.
Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609→620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.
Objective: To compare baseline characteristics in adult patients with growth hormone (GH) deficiency (GHD) who had previously been treated for Cushing's disease or acromegaly with data from patients with GHD of other aetiologies. To study the effects of GH therapy in those patients who had completed at least 6 months of GH replacement. Design: Data from a large outcomes research database (KIMS (Pharmacia International Metabolic Database)). Methods: 135 patients were identified with previous Cushing's disease, 40 had had acromegaly, and 1392 had GHD of other aetiologies. The number of additional hormone deficiencies, and the mean age of the patients were similar in the three groups. Similar proportions of patients in each group were treated using surgery, but radiotherapy was used more often in patients with acromegaly than those with other diagnoses. Results: At baseline, the prevalence of diabetes mellitus and hypertension were significantly higher in the group treated for Cushing's disease, and the prevalence of stroke was significantly higher in the group treated for acromegaly. The incidence of coronary heart disease and claudication were similar in all three groups. Patients treated for Cushing's disease had lower bone mineral density and suffered fractures more often than other GHD adults. Body mass index, waist-hip ratio, serum concentrations of lipids and standard deviation scores of serum concentrations of insulin-like-growth factor-I were similar in the three groups. The dose of GH administered was comparable in the three groups and the effects of GH replacement on waist circumference, blood pressure and quality of life were also similar across the groups. The numbers and types of adverse events reported were not different between the groups. Conclusions: These data suggest that the characteristics of patients in these diagnostic groups depend on the primary disease which resulted in GHD, and that the clinical expression of GHD does not differ between the groups. Patients with previous hypercortisolism showed more long-term effects of their disease, such as diabetes mellitus, hypertension and fractures. A benefit from GH replacement was evident in patients previously treated for acromegaly and Cushing's disease particularly in relation to quality of life.
Data from 665 adults with GH deficiency (GHD; 332 women; 169 childhood-onset GHD; mean age, 44 yr) were analyzed to determine the efficacy of and individual responsiveness to GH replacement therapy. GH replacement was started at enrolment into KIMS (Pharmacia & Upjohn, Inc. International Metabolic Database). Mean maintenance doses of GH after 6 and 12 months were 0.43 and 0.53 mg/day (1.3 and 1.6 IU/day) for men and women, respectively. Serum insulin-like growth factor I (IGF-I) SD score increased from -2.2 and -4.2 in men and women, respectively, to 1.8 and -0.9 at 6 months and 0.8 and -0.7 at 12 months. The waist/hip ratio decreased after 6 and 12 months, with the changes more pronounced in men. The waist/hip ratio was not influenced by age of onset of GHD, severity of hypopituitarism, or gonadal status. Total cholesterol decreased significantly in men, and high density lipoprotein cholesterol increased in women. Systolic blood pressure was unchanged during GH therapy, but diastolic blood pressure decreased in women. Quality of life, determined by a specific questionnaire for assessment of GHD in adults, improved after 6 and 12 months of GH therapy; this was more pronounced in adult-onset than in childhood-onset GHD, but was not influenced by gender, severity of hypopituitarism, or gonadal status. In 80% of patients, the starting dose of GH was 0.27 mg/day or less. This and the absence of a correlation between body weight and change in IGF-I were consistent with a dose-titration approach, which would tend to obscure individual variations in responses (determined by IGF-I levels). Nonetheless, the increase in IGF-I was significantly higher in men than in women on similar mean GH doses. Weak correlations were observed between the maintenance dose of GH and the change in IGF-I in men and women receiving sex steroid replacement, but not in patients with untreated hypogonadism or an intact gonadotropin reserve. Similarly, the increment in IGF-I was not related to the severity of GHD, as determined by the number of additional pituitary hormone deficiencies. Differences in IGF-I generation may partly explain the gender differences in reduction of central adiposity. These data highlight the value of large longitudinal surveillance databases in defining the optimum dose regimen for GH replacement and indicate that women may need a higher replacement dose of GH than men.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.