Smoking habits and osteoporosis in community-dwelling men subjected to dual-X-ray absorptiometry: a cross-sectional study.

BACKGROUND: Active and Environmental Tobacco Smoke (ETS) are a global cause of death. Osteoporosis (Op) is the most common metabolic bone disorder worldwide, impacting on mortality and disability, with high health and welfare costs. Active smoking is a known risk factor for Op, but there is few information regarding Op and ETS in men. PURPOSE: The study aim is to evaluate the association between smoking habits and Op in community-dwelling men that have been subjected to Dual-X-ray Absorptiometry and completed a questionnaire about their own and cohabiter's smoking habits. METHODS: We performed a cross-sectional study based on administrative data. This study is part of the SIMON protocol. The binary logistic regression analysis was used to estimate the role of ETS on the risk of Op, adjusting for age, body mass index (BMI), type 2 diabetes mellitus (T2DM) and eGFR. RESULTS: Four hundred sixteen men were selected and, based on questionnaire replies, 167 were classified as current smokers (CS), 93 as passive smokers (PS) and 156 as never smokers (NS). NS showed a lower prevalence of past fragility fracture, radiological features of osteoporosis and hypovitaminosis D compared to PS and CS (p < 0.05). NS showed a lower prevalence of Op compared to PS and CS, also after correction for age, BMI, T2DM and eGFR (p < 0.05). CONCLUSION: The study results demonstrate that PS and CS have a higher risk of Op, fragility fractures and vitamin D deficiency compared to NS.

Role of active and environmental tobacco smoke on susceptibility to osteoporosis in women undergoing dual-X-ray absorptiometry.

PURPOSE: Current smoking is a risk factor for osteoporosis (Op), but few data are available regarding the passive smoke impact on Op susceptibility. This cross-sectional study aimed to evaluate the association between the smoking habits and Op in community-dwelling women undergoing dual-energy X-ray absorptiometry (DXA). METHODS: On 01/06/2018, general practitioners from "COMEGEN" Medical Cooperative, Naples, Italy, selected the medical records from the last 10 years of women who had a measurement of bone mineral density performed and simultaneously completed a questionnaire about their smoking behaviour and their cohabiters'. The binary logistic regression analysis was used to estimate the role of passive smoke on the risk of Op, adjusting for age and body mass index (BMI). RESULTS: Among 10,616 subjects, 3942 were currently smokers [CS; mean age 69.4 ± 10.4 years; BMI 27.0 ± 4.9 kg/m2], 873 were passive smokers (PS; mean age 67.8 ± 11.6 years; BMI 27.0 ± 4.9 kg/m2) and 5781 were never smokers (NS; mean age 67.8 ± 11.6 years; body mass index (BMI) 27.0 ± 4.9 kg/m2). Of all, 8562 women (mean age 70.3 ± 10.2 yrs; BMI 27.0 ± 4.9 kg/m2) received the Op diagnosis. PS showed an increased Op risk compared to NS [odds ratio (OR) 1.38 (1.14-1.67)] and comparable to CS [OR 1.02 (0.84-1.24)]. CONCLUSION: The study results demonstrate an association between passive smoke and Op in community-dwelling women already presenting with susceptibility to Op according to Italian essential assistance levels, suggesting that passive and active smoke are equivalent Op risk factors in women.

Metabolic syndrome is not associated to an increased risk of low bone mineral density in men at risk for osteoporosis.

PURPOSE: We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. METHODS: Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to "COMEGEN" general practitioners' cooperative operating in Naples, Southern Italy. RESULTS: Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. CONCLUSION: In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.

Metabolic syndrome is associated to an increased risk of low bone mineral density in free-living women with suspected osteoporosis.

PURPOSE: Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns. This cross-sectional study was performed to evaluate if MetS and its constitutive elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. METHODS: 13,182 free-living Caucasian women referring to "COMEGEN" general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study. RESULTS: MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08-1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD. CONCLUSIONS: The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.

Methodological approach to the assessment of the obesogenic environment in children and adolescents: A review of the literature.

AIMS: Childhood and adolescent obesity has been defined as a planetary epidemic by WHO "globesity". The obesogenic environment, defined as a life environment promoting a high-energy intake and a sedentary lifestyle, significantly contributes to the genesis and the diffusion of the globesity. In the last decades, several authors and working groups tried to develop methodological instruments in order to guarantee a reliable analysis of an obesogenic environment. Their efforts have led to the production of a relatively large number of questionnaires with different characteristics. The general aim of these questionnaires is to identify the factors that significantly contribute to the creation of an obesogenic environment around children and adolescents. As a result of this work, a number of studies were carried out using such questionnaires. Aim of this review is to evaluate ad hoc questionnaires useful to identify and analyze obesogenic environment. DATA SYNTHESIS: The search was carried out in February-March 2017 using the PubMed-Medline and Scopus databases (time interval: the last 10 years). After the selection and verification phases, a total of 14 studies were selected and therefore included in the present review. CONCLUSIONS: The questionnaires constructed and validated to analyze multiple constitutive elements of an obesogenic environment at the same time are complex and must be administered by qualified and trained staff. On the other hand, when two or more questionnaires are used to analyze different factors, the questionnaires used are generally shorter, self-administered, and generally easier to understand and interpret.

Laparoscopy or retroperitoneoscopy for pediatric patients with adrenal masses?

Minimally invasive approach to the adrenal gland was first reported in 1992. Since then, the experience with the laparoscopic technique for adrenal disease in children has been limited. We report our experience with minimally invasive adrenal surgery in children. Two young girls (2 and 4 years old) with a left adrenal mass were operated using minimally invasive surgery (MIS) in our Unit. Ultrasonography and MRI showed in the oldest a 2 x 3 cm adrenal mass, while in the youngest a 5.5 x 5 cm adrenal tumor was found. According to the pre-existing literature, we approached the smallest lesion via retroperitoneoscopy, and the largest one laparoscopically. The operating time was 110 minutes for retroperitoneoscopy and 75 minutes for laparoscopy. No major intra or postoperative complications occurred. There were no conversions to open surgery. Postoperative hospital stay was 5 days for both patients. In both cases, the anatomo-pathological result was an adenoma. Minimally invasive adrenalectomy is a safe and feasible procedure in children with good results. For lesions smaller than 3-4 cm retroperitonescopy is feasible, while for tumors larger than 5 cm, due to malignancy risk, the laparoscopic approach is indicated. To keep oncologic criteria it is important to avoid tumor rupture and to extract the specimen in an endobag.

Prevalence of simple nodular goiter and Hashimoto's thyroiditis in current, previous, and never smokers in a geographical area with mild iodine deficiency.

Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

Interleukin-6, soluble interleukin-6 receptor/interleukin-6 complex and insulin resistance in obese children and adolescents.

BACKGROUND/AIM: To study the characteristics of interleukin 6 (IL6), soluble form of interleukin 6 receptor (sILR)/IL6 complex in obese children and adolescents and its relationship with insulin resistance (IR). SUBJECTS AND METHODS: 66 obese children and adolescents [34 boys, mean age 10.3 ± 2.9 years, z-score of body mass index (BMI) 4.76 ± 1.36] and 24 non-obese healthy sex- and age-matched controls. Fasting levels of glucose, insulin, IL6, sIL6, sgp130 were measured. IR was assessed by homeostasis model assessment of IR (HOMA-IR). RESULTS: Obese subjects showed increased levels of insulin and IL-6 and higher HOMA-IR compared to controls (117.67 ± 50.9 vs. 62.42 ± 29.4 pmol/L, 2.73 ± 0.98 vs. 1.07 ± 0.41 pg/ml and 4.03 ± 2.16 vs. 1.83 ± 1.05 for insulin, IL-6 and HOMA-IR, respectively, p < 0.01 in all cases). sIL-6R levels were significantly lower in obese subjects (34.7 ± 14.2 vs. 55.6 ± 15.2 ng/ml in controls, p = 0.005), whereas sgp130 levels were not significantly different. In obese subjects, IL-6 directly correlated with z-score BMI (r = 0.481, p = 0.009) and with waist-to-height ratio (r = 0.494, p = 0.007), while sIL6-R was inversely related to HOMA-IR (r = -0.522, p = 0.002). Insulin resistant subjects showed higher levels of IL6 and lower levels of sIL6R (3.31 ± 0.72 vs. 2.25 ± 0.64 pg/ml, p = 0.020 and 25.3 ± 9.3 vs. 42.5 ± 10.4 ng/ml, p = 0.013, respectively). CONCLUSIONS: In obese children and adolescents, IR is associated with elevated levels of IL-6 and diminished values of sIL-6R.

Impaired gonadal function in a woman with multiple symmetric lipomatosis.

Multiple symmetric lipomatosis (MSL, OMIM 151800), is a rare disease characterised by the growth of uncapsulated masses of abnormal adipose tissue around the neck, shoulders or other parts of the trunk and typically associated with high ethanol intake. We describe the case of a 33 year-old woman with MSL and secondary amenorrhea. Despite the presence of an ovarian failure confirmed by undetectable serum levels of inhibin B and anti-Müllerian hormone, the patient had normal serum levels of estrone and gonadotropins coexisting with a biological adrenal hyperandrogenism. We suggest that the adrenal hyperandrogenism observed in our patient could be attributed to an impairment of the cytochrome p450 function, inducing a relative 21-hydroxylase deficiency/insufficiency, related to alcohol abuse and that the increased peripheral aromatization of androgens in estrogens lead to normal circulating levels of estrone. The result is the absence of gonadotropin elevation despite primary ovarian failure. The peculiar functional pattern of brown adipocytes in patients with MSL may contribute to this biological phenomenon with an additive effect related to alcohol consumption. Altogether, these data could help to better define the peculiar pituitary-gonadal profile observed in this rare syndrome and in some cases of women with heavy alcohol consumption.

Relationship between metabolic syndrome and multinodular non-toxic goiter in an inpatient population from a geographic area with moderate iodine deficiency.

BACKGROUND: Obesity and insulin resistance predispose individuals to the development of both metabolic syndrome and non-toxic nodular thyroid diseases. AIM: The aim of this observational, cross-sectional study is to evaluate the relationship between metabolic syndrome and multinodular nontoxic goiter in an inpatient population from a geographic area with moderate iodine deficiency. SUBJECTS AND METHODS: We examined 1422 Caucasian euthyroid inpatients. Thyroid volume was determined by ultrasound of the neck. A fine-needle aspiration biopsy was performed to evaluate single thyroid nodules and dominant nodules ≥15 mm in euthyroid multinodular goiter. The diagnosis of metabolic syndrome was made according to the criteria of the American Heart Association/ National Heart, Lung, and Blood Institute. RESULTS: Of the sample, 277 patients had clinical evidence of multinodular nontoxic goiter, 461 met the criteria for the diagnosis of metabolic syndrome, and 132 were found to have both conditions. After adjusting for age, gender, body mass index, nicotinism, parity, alcohol intake, thyroid function, and metabolic syndrome- related pharmacological treatment, metabolic syndrome was found to be an independent risk factor for the occurrence of multinodular non-toxic goiter. The relationship between metabolic syndrome and multi nodular non-toxic goiter was apparent in both men and women. CONCLUSIONS: In this study of euthyroid inpatients, we demonstrate that metabolic syndrome is an independent risk factor for the occurrence of multinodular non-toxic goiter in a geographic area with moderate iodine deficiency. We propose that patients meeting the criteria for metabolic syndrome should be screened for the presence of multinodular non-toxic goiter.

Should vitamin D status be assessed in patients with congestive heart failure?

For decades the vitamin D biological system has been considered almost exclusively as the master integrator of calcium-phosphate homeostasis and bone metabolism. More recently, the discovery that many human tissues and cells, which do not directly participate in mineral ion homeostasis, express the vitamin D receptor (VDR) and are able to convert the circulating pro-hormone 25-hydroxyvitamin D in its active form, 1,25-dihydroxyvitamin D, has provided new insights into the biological function of this peculiar endocrine system. Several reports have highlighted a variety of human diseases possibly related to vitamin D insufficiency or deficiency (respectively defined as 25-hydroxyvitamin D serum levels lower than 30 or lower than 20 ng/ml). In particular, experimental and observational studies, including those published in this journal issue, support the concept that vitamin D deficiency is involved in the pathogenesis of congestive heart failure, a disabling condition affecting over 15 million of patients worldwide. Considering that circulating levels of 25-hydroxyvitamin D represent the accepted clinical indicator of individual vitamin D status, the measurement of this pro-hormone can be regarded as an appropriate and cost-effective screening tool in patients with chronic heart failure.

Epidemiological, clinical, and genetic characteristics of Paget's disease of bone in a rural area of Calabria, Southern Italy.

BACKGROUND: The prevalence of Paget's disease of bone (PDB) is unknown in peninsular Southern Italy, although an elevated clinical severity of the disease was reported in patients from Campania. AIM: This study was performed to evaluate the epidemiological and genetic characteristics of PDB in a rural area of Calabria, the southernmost region in the Italian peninsula. SUBJECTS AND METHODS: We examined 1068 consecutive pelvic radiographs of patients older than 40 yr referred for any reason to the "Spinelli" Hospital, Belvedere Marittimo, from January 1st 2004 to December 31st 2006. In subjects with radiological findings of pelvic PDB, a 99m Technetium methylene diphosphonate bone scan and the sequence analysis of the sequestosome 1 (SQSTM1) gene were subsequently performed. RESULTS: In the examined geographic area, the crude radiographic prevalence of pelvic PDB was 0.74% (8/1068; male:female 5:3, mean age 71.6 ± 13.1 yr) whereas the estimated overall prevalence of PDB between 0.82% and 1.21%. PDB patients from Calabria showed clinical characteristics similar to those reported in patients from Campania. The disease was also frequently complicated by osteoarthritis and the right side of the body was more affected than the left. The SQSTM1 gene analysis revealed the presence of a novel missense mutation (M401V) in exon 8 in one subject with a familial and aggressive form of PDB. CONCLUSION: The study results confirmed that patients with PDB from rural districts of Southern Italy show an earlier onset and an increased clinical severity of the disease that appears mostly independent from the presence of germinal SQSTM1 mutations.

[Phosphatonins: novel insights and clinical perspectives]. / Le fosfatine: recenti acquisizioni e possibili evoluzioni nella clinica.

Phosphate plays a vital role in several biological processes including energy and nucleic acid metabolism, cell signaling and bone mineralization. Several endocrine factors coordinately act on the intestine, kidney and bone to maintain their physiological homeostasis. A number of peptides, collectively known as phosphatonins, have recently been identified as regulators of phosphate metabolism in physiological and pathological conditions. These factors--fibroblast growth factors (FGF) 23 and 7, secreted frizzled related protein 4 (sFRP-4), and matrix extracellular phosphoglycoprotein (MEPE)--primarily regulate tubular phosphate reabsorption by acting on the transmembrane expression of SLC34 sodium-phosphate cotransporters. FGF- 23, FGF-7 and sFRP-4 also inhibit the biosynthesis of 1,25(OH)2D3, leading to decreased intestinal phosphate absorption. In this review, we discuss the biological properties of these peptides, their physiological roles, and the alterations in their concentrations in various hypophosphatemic and hyperphosphatemic clinical disorders.

Interleukin (IL)-6 and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) are increased in the serum of a patient with primary pachydermoperiostosis.

Primary pachydermoperiostosis (PDP) is a rare syndrome, characterized by digital clubbing, periostosis, and pachydermia. We have evaluated biochemical bone turnover markers, including components of interleukin-6 (IL-6) and osteoprotegerin/receptor activator of nuclear factor (NF)-kappaB ligand (OPG/RANKL) systems, in an 18-year-old man affected by primary PDP. The acute phase of the disease was characterized in our patient by high serum levels of IL-6 and RANKL. The observed high serum levels of these parameters are associated with increased values in markers of bone resorption (degradation products of C-terminal telopeptides of type-I collagen and urinary hydroxyproline/creatinine ratio) and reduced serum levels of bone alkaline phosphatase, a marker of bone formation. Serum levels of osteotrophic hormones were in the normal range. Our data suggest that, despite the radiographic findings, the acute phase of primary PDP is characterized by increased bone resorption, probably mediated by IL-6 and RANKL.

WNT4 deficiency--a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report.

The pathways leading to female sexual determination in mammals are incompletely defined. Loss-of-function mutations in the WNT4 gene appear to cause developmental abnormalities of sexual differentiation in women and mice. We recruited six patients with different degrees of Müllerian abnormalities, with or without renal aberrations and a normal female 46,XX karyotype. A clear androgen excess was found only in one patient. This 19-year-old woman was affected by primary amenorrhoea, absence of Müllerian ducts derivatives, clinical (acne and hirsutism) and biochemical (repeatedly high levels of testosterone) signs of androgen excess. Direct sequencing of her WNT4 gene followed by functional studies in human ovarian cells (OVCAR3) was performed. This patient carried the novel R83C loss-of-function dominant negative mutation in her WNT4, confirming the role of WNT4 in the development and maintenance of the female phenotype in women. Our study can also help refine the phenotype of WNT4 deficiency in humans. In fact, it appears that at least in this limited casuistic small group of patients, the absence of a uterus (and not other Müllerian abnormalities) and the androgen excess are the pathognomonic signs of WNT4 defects, suggesting that this might be a clinical entity distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome.

Liver regeneration in response to partial hepatectomy in rats treated with retrorsine: a kinetic study.

BACKGROUND/AIM: We have designed an experimental model in which transplantation of normal hepatocytes into rats previously treated with retrorsine (a naturally-occurring pyrrolizidine alkaloid) results in near-complete replacement of the recipient liver by donor-derived cells. Two/thirds partial hepatectomy was found to be essential for this process to occur. To probe this finding, in the present study we describe the kinetics of liver regeneration in response to partial hepatectomy in rats given retrorsine. METHODS: Six-weeks-old male Fisher 344 rats received retrorsine (2 injections of 30 mg/kg each, i.p., 2 weeks apart), or the vehicle. Four weeks after the last injection, partial hepatectomy was performed and rats were killed at 1, 2, 3, 6, and 15 days thereafter. RESULTS: At time zero, i.e. prior to partial hepatectomy, liver weight and total liver DNA content were significantly lower in retrorsine-treated animals compared to controls (DNA content: 19.2+/-1.7 vs. 25.7+/-1.1 mg/liver). Diffuse megalocytosis (enlarged hepatocytes) was present in the group exposed to retrorsine. By day 3 post-partial hepatectomy liver DNA content in control animals had more than doubled compared to day 1 values (20.2+/-1.5 vs. 8.8+/-1.2), while very little increase was seen in retrorsine-treated rats at the same time points (7.6+/-0.4 vs. 6.1+/-0.2). At 2 weeks after partial hepatectomy, total DNA content returned close to normal levels in the control group (26.9+/-1.0 mg/liver); however, the value was still very low in animals receiving retrorsine (9.1+/-0.7). Data on BrdU labeling were consistent with this pattern and indicated that DNA synthesis following partial hepatectomy was largely inhibited in the retrorsine group. Similarly, no mitotic response was observed in hepatocytes following partial hepatectomy in animals exposed to retrorsine. CONCLUSIONS: These results clearly indicate that retrorsine exerts a strong and persistent cell cycle block on hepatocyte proliferation. Further, these results are in agreement with the hypothesis that selective proliferation of transplanted hepatocytes in retrorsine-treated animals is dependent, at least in part, on the persistent cell cycle block imposed by the alkaloid on endogenous parenchymal cells.

Prevalence of HNPCC in a series of consecutive patients on the first endoscopic diagnosis of colorectal cancer: a multicenter study. The Italian Collaborative Group.

BACKGROUND AND STUDY AIMS: It is difficult to measure the prevalence of hereditary non-polyposis colorectal cancer (HNPCC) in geographical areas that do not have tumor registers, as is the case in the present study, and it was therefore decided to assess the prevalence in Italy using different methods. PATIENTS AND METHODS: The pedigree was established for 485 of 501 colorectal cancer patients diagnosed with colorectal carcinomas. Patients were included consecutively in 13 gastroenterology centers; they had not taken part in prevention examinations. Information was collected regarding the neoplastic pathology observed in the families, confirmed in 90% of cases among 3515 first-degree relatives and in 79.5% of cases among 7068 second-degree relatives. RESULTS: In the 3515 first-degree relatives (1002 parents, 1560 siblings and 953 children), 61 colorectal carcinomas, 29 carcinomas in the digestive tract outside the colon, and 99 carcinomas in other locations were reported. Only five of the 485 patients (1%) satisfied the Amsterdam criteria (three cancers, two of which were in first-degree relatives in different generations and one in a relative younger than 50). When broadening the criteria that we are proposing (satisfying only two of the three Amsterdam criteria), the prevalence would increase to 3% (15 cases). CONCLUSIONS: Modifying the criteria makes it easier to identify new mutations or confirm the existence of those already known, as well as allowing preventative treatment in relatives who are apparently healthy.

Pubertal growth, sexual maturation, and final height in children with IDDM. Effects of age at onset and metabolic control.

OBJECTIVE: To evaluate growth and pubertal development in children with IDDM and the influence of the age at onset of IDDM and the degree of metabolic control on final height. RESEARCH DESIGN AND METHODS: We conducted a retrospective evaluation of 62 subjects followed longitudinally both clinically and metabolically from the onset of IDDM until final height was reached. RESULTS: Height at diagnosis was within the normal percentiles in boys (0.5 +/- 1.0 standard deviation score [SDS]) and girls (0.4 +/- 1.0 SDS), but above the genetic target height (-1.0 +/- 0.9 SDS in boys and -1.1 +/- 0.6 SDS in girls; P = 0.0001 for both comparisons). Although a lesser height gain was observed during the ensuing years, the final height reached by boys (-0.4 +/- 1.1 SDS) and girls (-0.4 +/- 0.9 SDS) was higher than the genetic target height. Blunted total pubertal growth was observed both in boys (24.5 +/- 3.6 cm) and girls (20.1 +/- 4.2 cm). The decrease in height gain was independent of the duration of IDDM, the degree of metabolic control, or the insulin requirement. The greater the height at diagnosis, with respect to the genetic target height, the lesser was the subsequent height gain to reach final adult height (r = 0.34, p < 0.01). BMI increased with age as normally occurs in healthy children, independent of the duration of disease and the degree of metabolic control. Pubertal development began and progressed normally both in boys and girls. In boys, a testicular volume of 4 ml was reached at a mean age of 12.1 +/- 0.9 years. In girls, breast enlargement occurred at a mean age of 10.4 +/- 1.2 years and the mean age of menarche was 12.8 +/- 1.4 years. Pubertal development and progression occurred independent of the age at onset of IDDM, the glycemic control, or the insulin requirement during the pubertal period. CONCLUSIONS: Children with IDDM have normal onset of puberty and normal sexual maturation. Even though final height falls within the normal percentiles, the diminished height gain after diagnosis requires further investigation.