Iodine deficiency has multiple adverse effects on growth and development. Diets in many countries cannot provide adequate iodine without iodine fortification of salt. In 2020, 124 countries have legislation for mandatory salt iodization and 21 have legislation allowing voluntary iodization; as a result, 88% of the global population uses iodized salt. For population surveys, the urinary iodine concentration (UIC) should be measured and expressed as the median, in μg/L. The quality of available survey data is high: UIC surveys have been done in 152 out of 194 countries in the past 15 years; in 132 countries the studies were nationally representative. The number of countries with adequate iodine intake has nearly doubled from 67 in 2003 to 118 in 2020. However, 21 countries remain deficient, while 13 countries have excessive intakes, either due to excess groundwater iodine, or over-iodized salt. Iodine programs are reaching the poorest of the poor: of the 15 poorest countries in the world, 10 are iodine sufficient and only three (Burundi, Mozambique and Madagascar) remain mild-to-moderately deficient. Nigeria and India have unstable food systems and millions of malnourished children, but both are iodine sufficient and population coverage with iodized salt is a remarkable 93% in both. Once entrenched, iodine programs are often surprisingly durable even during national crises; for example, war-torn Afghanistan and Yemen are iodine sufficient. However, equity of iodized salt programs within countries remains an important issue. In summary, continued support of iodine programs is needed to sustain these remarkable global achievements, and to reach the remaining iodine-deficient countries.
Michael B Zimmermann and Maria Andersson
Michael B Zimmermann and Maria Andersson
Iodine deficiency has multiple adverse effects on growth and development. Diets in many countries cannot provide adequate iodine without iodine fortification of salt. In 2020, 124 countries have legislation for mandatory salt iodization and 21 have legislation allowing voluntary iodization. As a result, 88% of the global population uses iodized salt. For population surveys, the urinary iodine concentration (UIC) should be measured and expressed as the median, in μg/L. The quality of available survey data is high: UIC surveys have been done in 152 out of 194 countries in the past 15 years; in 132 countries, the studies were nationally representative. The number of countries with adequate iodine intake has nearly doubled from 67 in 2003 to 118 in 2020. However, 21 countries remain deficient, while 13 countries have excessive intakes, either due to excess groundwater iodine, or over-iodized salt. Iodine programs are reaching the poorest of the poor: of the 15 poorest countries in the world, 10 are iodine sufficient and only 3 (Burundi, Mozambique and Madagascar) remain mild-to-moderately deficient. Nigeria and India have unstable food systems and millions of malnourished children, but both are iodine-sufficient and population coverage with iodized salt is a remarkable 93% in both. Once entrenched, iodine programs are often surprisingly durable even during national crises, for example, war-torn Afghanistan and Yemen are iodine-sufficient. However, the equity of iodized salt programs within countries remains an important issue. In summary, continued support of iodine programs is needed to sustain these remarkable global achievements, and to reach the remaining iodine-deficient countries.
Anna-Maria Andersson, Hans Ørskov, Michael B Ranke, Steve Shalet, and Niels E Skakkebæk
Andersson A-M, Ørskov H, Ranke MB, Shalet B, Skakkebæk NE. Interpretation of growth hormone provocative tests: comparison of cut-off values in four European laboratories. Eur J Endocrinol 1995;132:340–3. ISSN 0804–4643
To compare interpretations of growth hormone (GH) provocative tests in laboratories using six different GH immunoassays (one enzymeimmunometric assay (EIMA, assay 1), one immunoradiometric assay (IRMA, assay 5), one time-resolved fluorimmunometric assay (TRFIA, assay 3) and three radioimmunoassays (RIAs, assays 2, 4 and 6)), aliquots of peak samples from GH provocative tests were distributed between the four participating laboratories, quantified in the respective immunoassays and interpreted according to the cut-off values for provocative tests defined for each assay method. There was a high degree of relative correlation between the different assays, but absolute GH estimates differed. Assays 2, 4, 5 and 6 yielded almost identical GH levels. Assays 1 and 3 yielded serum GH levels approximately 39% and 70%, respectively, of those of assays 2, 4, 5 and 6. Although the absolute GH level measured in the various assay methods varied, there was good agreement between the interpretation of a given sample among the participating laboratories. This indicates that the differences in estimates of serum GH concentration by different immunoassay systems can be compensated for when cut-off values are defined for each method.
Anna-Maria Andersson, Dept. of Growth and Reproduction, University Hospital of Copenhagen, Ward GR5064, 9 Blegdamsvej, DK-2100 Copenhagen Ø, Denmark
Kaspar Sørensen, Lise Aksglaede, Jørgen Holm Petersen, Anna-Maria Andersson, and Anders Juul
IGF1 plays an important role in growth and metabolism during puberty. IGF1 levels are increased in girls with central precocious puberty (CPP). However, the relationship with insulin before and during gonadal suppression is unknown. In addition, the influence of the exon 3-deleted GH receptor gene (GHRd3) on IGF1 levels was evaluated.
Nine hundred and eleven healthy and 23 early pubertal girls (15 with CPP) participated and were evaluated by dual-energy X-ray absorptiometry (DXA) scans, fasting and oral glucose-stimulated insulin levels, IGF1 levels, and GHR genotyping. Fifteen girls with early puberty (13 with CPP) were treated with GNRH agonists and reevaluated after 3 and 12 months.
IGF1 and insulin levels were higher in girls with CPP compared with healthy controls after adjustment for age, bone age, and breast development (all P≤0.02). IGF1 levels were only significantly positively correlated with insulin levels in girls with CPP at baseline (P≤0.03). During gonadal suppression, changes in IGF1 levels were inversely associated with changes in insulin levels (P=0.04). The GHRd3/d3 genotype was associated with significantly higher IGF1 levels (P=0.01) but not with earlier pubertal timing in healthy girls. The distribution of the GHRd3 genotypes among girls with CPP did not differ significantly from healthy girls (P=0.2).
The increased IGF1 and insulin levels in girls with CPP may be causally interrelated. In addition, the GHRd3 allele positively influences IGF1 levels in a copy number–response relationship but not pubertal timing in healthy girls.
Mikkel G Mieritz, Kaspar Sorensen, Lise Aksglaede, Annette Mouritsen, Casper P Hagen, Linda Hilsted, Anna-Maria Andersson, and Anders Juul
Pubertal gynaecomastia is a frequent phenomenon occurring in 20–40% of otherwise healthy adolescent boys. Little is known about the aetiology of pubertal gynaecomastia. Markedly elevated thyroid hormone levels in adults with hyperthyroidism are associated with gynaecomastia.
A cross-sectional examination of 444 healthy boys with and without pubertal gynaecomastia.
We evaluated TSH, triiodothyronine (T3), thyroxine (T4), free T4 and free T3 in a cohort of healthy boys with and without pubertal gynaecomastia.
Boys with gynaecomastia had significantly higher serum free T3, even after correction for age, BMI and pubertal stage. After inclusion of IGF1 in the model the differences disappeared. TSH, T4, free T4 and T3 did not differ between the groups.
We speculate that the GH/IGF1 axis and thyroid hormones interact and influence the development of pubertal gynaecomastia.
A Kirstine Bang, Loa Nordkap, Kristian Almstrup, Lærke Priskorn, Jørgen Holm Petersen, Ewa Rajpert-De Meyts, Anna-Maria Andersson, Anders Juul, and Niels Jørgensen
Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after GnRH and hCG stimulation in healthy men and assess the impact of six single nucleotide polymorphisms on the responses.
GnRH and hCG stimulation tests were performed on 77 healthy men, 18–40 years (reference group) at a specialized andrology referral center at a university hospital. The potential influence of the tests was illustrated by results from 45 patients suspected of disordered hypothalamic–pituitary–gonadal axis.
Baseline, stimulated, relative and absolute changes in serum FSH and LH were determined by ultrasensitive TRIFMA, and testosterone was determined by LC–MS/MS.
For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. Testosterone increased approximately 110% (range: 18.7–67.6 nmol/L) during hCG testing. None of the polymorphisms had any major impact on the test results. Results from GnRH and hCG tests in patients compared with the reference group showed that the stimulated level and absolute increase in LH showed superior identification of patients compared with the relative increase, and the absolute change in testosterone was superior in identifying men with Leydig cell insufficiency, compared with the relative increase.
We provide novel reference ranges for GnRH and hCG test in healthy men, which allows future diagnostic evaluation of hypothalamic–pituitary–gonadal disorders in men.
Stine A Holmboe, Niels E Skakkebæk, Anders Juul, Thomas Scheike, Tina K Jensen, Allan Linneberg, Betina H Thuesen, and Anna-Maria Andersson
Male aging is characterized by a decline in testosterone (TS) levels with a substantial variability between subjects. However, it is unclear whether differences in age-related changes in TS are associated with general health. We investigated associations between mortality and intra-individual changes in serum levels of total TS, SHBG, free TS and LH during a ten-year period with up to 18 years of registry follow-up.
1167 men aged 30–60 years participating in the Danish Monitoring Trends and Determinants of Cardiovascular Disease (MONICA1) study and who had a follow-up examination ten years later (MONICA10) were included. From MONICA10, the men were followed up to 18 years (mean: 15.2 years) based on the information from national mortality registries via their unique personal ID numbers.
Cox proportional hazard models were used to investigate the association between intra-individual hormone changes and all-cause, CVD and cancer mortalities.
A total of 421 men (36.1%) died during the follow-up period. Men with most pronounced decline in total TS (<10th percentile) had a higher all-cause mortality risk compared to men within the 10th to 90th percentile (hazard ratio (HR): 1.60; 95% confidence interval (CI): 1.08–2.36). No consistent associations were seen in cause-specific mortality analyses.
Our study showed that higher mortality rates were seen among the men who had the most pronounced age-related decline in TS, independent of their baseline TS levels.