The Efficacy of Anastrozole and Growth Hormone Therapy on Adult Height in Six Adolescent Males with Growth Hormone Deficiency or Idiopathic Short Stature

Background. Data on adult height outcomes of the use of Anastrozole and Growth Hormone (GH) in pubertal males with Growth hormone deficiency (GHD) and Idiopathic short stature (ISS) are limited. Objective. We examined the effect of Anastrozole and GH therapy on near adult height (NAH) with pubertal males with GHD or ISS. Methods. Retrospective review of 419 charts from 2008 to 2015. The primary outcomes are NAH compared to mid-parental target height (MPTH) and predicted adult height (PAH). Results. We identified 23 patients (5 SGA/IUGR, 1 Noonan syndrome, 6 GHD, and 11 ISS). Six patients (4 GHD; 2 ISS) achieved NAH. Prior to Anastrozole treatment, the mean chronological age was 13.9±0.2 years (range 13.7–14.4), bone age was 13.6±0.6 years (range 12.5–14), mean height SDS was -1.5±0.5 (range −0.8 to −2.3), and mean PAH was 162.6±5.9 cm (range 153.5–168.6). MPTH was 173.6 cm ± 7 (range 161.8–181.6). Patients received Anastrozole for an average of 30.5 months (range 19–36 months). At NAH, the mean chronological age was 16.7±0.8 years (range 15.9–18.1 years) and height was 170±1.8 cm (range 168.5–173.4 cm). The mean height SDS improved to +0.81±0.6 (range +0.08 to +1.92, p=0.002). Net height gain was 7.3 cm compared to pretreatment PAH (p<0.01) and overall the mean adult height remained 3.5 cm below MPTH. Conclusion. Anastrozole and GH therapy can be effective in augmenting adult height without significant side effects. However, the long-term safety and efficacy of aromatase inhibitor use in pediatrics remain limited.

Evaluation of Prepubertal Patients with Suspected Neurosecretory Dysfunction of Growth Hormone Secretion: Diagnostic Steps and Treatment Response

Background and Aims. Existence and diagnostic procedures of neurosecretory dysfunction of growth hormone (NSD) are still a matter of debate. The aim of our study was (a) to find out if prediagnostic auxological and laboratory data could serve as an indicator for pathologic and normal spontaneous GH-secretion and (b) to evaluate the response to GH-therapy in NSD-patients. Methods. Of 90 children (unicentric study) with normal response to GH-stimulation tests, in whom 12-hour night profiles for GH-secretion were performed, 49 were diagnosed with NSD (NSD group). Their auxologic data, IGF-I/IGFBP3-levels as well as the night profiles, were analysed and compared to those of the non-NSD group. Additionally, follow-up auxological data of the GH-treated NSD-patients were collected. Results. Prediagnostic auxologic and laboratory data did not differ between the two groups. Instead, for all analysed criteria of spontaneous GH-secretion (number of peaks, maximal and mean secretion) a significant difference was found. Children with NSD showed a good response to GH-treatment after 1 (ΔH-SDS +0,77 ± 0,48) as well as 4 years (+1,51 ± 0,75). Conclusion. According to our results, analysing spontaneous GH-secretion remains the only method to identify NSD. Yet, as response to GH-treatment is comparable to results in idiopathic GHD, it is worth to consider this diagnosis.

The Protective Effect of Testosterone on Indomethacin Induced Gastric Ulcer in Female Sprague Dawley Rats

Gastric ulcer has shown association with changes in sex hormones, with impact exacerbated in males. Also, males are known to be more exposed to ulcer risk factors. This study investigates the effect of testosterone on indomethacin induced gastric ulcers in adult female rats. Eighteen female rats (225 ± 25 g body weight) were randomly assigned to 3 groups under standard laboratory condition. After acclimatization, animals fasted for 40 hrs but were given water ad libitum. Group A served as control while group B served as the ulcer control, in which ulcer was induced without treatment using indomethacin (40 mg/kg single orally dose). Group C was pretreated with testosterone (1 mg/kg IM) eight hours before ulcer induction. Eight hours after ulcer induction, animals were sacrificed and the stomach was harvested for analysis. Results showed a significant reduction in mucus content in groups C (0.79±0.11 g) and B (0.87±0.02 g) compared to A (1.11±0.03 g). Gastric mucus pH was significantly acidic in group B (4.40±0.55) compared to C (5.20±0.45) and A (5.80±0.45). There was a significantly higher ulcer index in group B (4.60±0.55 mm) compared to C (3.60±0.89 mm) and testosterone pretreatment resulted in a 21.74% ulcer inhibition. Although weak, the findings suggest that testosterone might protect the gastric mucosa against NSAIDs in females.

Predictors of Erectile Dysfunction in Men with Type 2 Diabetes Mellitus Referred to a Tertiary Healthcare Centre

Background. The frequency of erectile dysfunction (ED) complicating diabetes mellitus (DM) is reportedly high. However, its risk factors have not been well studied. Methods. This was a cross-sectional study of 160 male type 2 DM adults, aged 30–70 years, attending a tertiary healthcare clinic. Demographic and relevant clinical information was documented. Erectile function was assessed using an abridged version of the International Index of Erectile Function (IIEF-5). All subjects were evaluated for central obesity, glycemic control, peripheral arterial disease (PAD), autonomic neuropathy, dyslipidemia, and testosterone deficiency. Results. 152 (95%) patients with a mean age of 60.3 ± 8.8 years completed the study. 71.1% had varying degrees of ED, while 58.3% suffered from a moderate-to-severe form. Independent predictors of ED [presented as adjusted odds ratio (95% confidence interval)] were longer duration of DM, 1.14 (1.02–1.28), PAD, 3.87 (1.28–11.67), autonomic neuropathy, 3.51 (1.82–6.79), poor glycemic control, 7.12 (2.49–20.37), and testosterone deficiency, 6.63 (2.61–16.83). Conclusion. The prevalence of ED and its severe forms was high in this patient population. Poor glycemic control and testosterone deficiency were the strongest risk factors for ED, making it possibly a preventable condition.

Thyroid Diseases in Omani Type 2 Diabetics: A Retrospective Cross-Sectional Study

Background. Diabetes mellitus and thyroid diseases are common endocrine disorders in the general population and found to exist simultaneously. This study aimed to establish the prevalence of thyroid dysfunction among Omani type 2 diabetics and its association with glycemic control. Methodology. A retrospective cross-sectional randomized primary and secondary care based study of 285 Omani type 2 diabetics, ≥ 30 years of age with known thyroid function. The following parameters were examined: age, sex, duration of diabetes, duration of thyroid disease, thyroid morphology, thyroid function, thyroid antibodies, and the mean glycated hemoglobin (mean HbA1C). The prevalence of thyroid dysfunction was compared to an independent control group of randomly selected healthy individuals with known thyroid function. Results. Thyroid dysfunction was found in 12.6% of the diabetic patients compared to 4.9% in the control group. The prevalence was higher among the diabetic females (86%) compared to diabetic males (14%). The commonest thyroid dysfunction among diabetics was overt hypothyroidism (4.6%). Subclinical hypothyroidism was the commonest thyroid dysfunction seen in less controlled diabetics at a mean HbA1c of 7.8 (± 0.7). Conclusion. Screening for thyroid dysfunction in patients with type 2 diabetes mellitus should be routinely performed considering the higher prevalence of thyroid diseases in this group compared to the general population.

Mean Platelet Volume in Hyperthyroid Toxic Adenoma Patients after Radioactive 131I Treatment

This study demonstrates that mean platelet volume (MPV) levels decrease after radioiodine (RAI) ablation therapy in hyperthyroid patients. Regarding the fact that large platelets are hemostatically more active, we suggest that hyperthyroid patients are at risk of cardiovascular disease despite all other cardiovascular risk factors. After RAI ablation therapy as MPV levels return to normal, cardiovascular risk for hyperthyroid patients reduces.

Congenital Hypothyroidism: An Audit and Study of Different Cord Blood Screening TSH Values in a Tertiary Medical Centre in Malaysia

Mothers are often discharged within 24 hours in most Asian countries. Therefore, our screening programs for congenital hypothyroidism (CH) must consider the value of cord blood TSH. Our objectives were to compare the incidence of CH, positive predictive values, and recall rates using different cord blood TSH values. We also reviewed the results of the second-screening program for premature babies. 99.7% (n=25,757) of all newborns were screened from 1st January 2009 to 31st December 2013. Babies with cord blood TSH > 25 mIU/L or 20–25 mIU/L and FT4<20 pmol/L were recalled for a repeat venous TSH and FT4 on days 3–5 of life to confirm CH. Twenty-two babies were confirmed to have CH, an incidence of 1:1170. Five were premature. Eleven term babies had cord blood TSH>30 mIU/L and six had values 25.1–30 mIU/L. Lowering the recall cut-off value to 20 mIU/L would double the recall rate from 0.63% (n=163) to 1.3% (n=340) with no additional cases detected, whereas using 30 mIU/L would have missed 35% of cases. The incidence of CH was similar, 1:1515, when using either cut-off 20 mIU/L or cut-off 25 mIU/L but lower, 1:2380, when using 30 mIU/L. We recommend the screening cord blood TSH cut-off should be 25 mIU/L and screening for premature babies should be continued.

Effects of Low-Dose Pioglitazone on Serum Levels of Adiponectin, Dehydroepiandrosterone, Amyloid Beta Peptide, and Lipid Profile in Elderly Japanese People with Type 2 Diabetes

This study was performed to see how pioglitazone at low doses could affect blood biomarkers related to atherosclerosis and aging. The effects of an add-on treatment with pioglitazone (15 mg for males and 7.5 mg for females) for 6 months were assessed in 24 outpatients (12 males, 12 females) with type 2 diabetes aged ≥ 70 years. As doses of sulfonylurea were reduced in 10 patients, no significant differences in HbA1c and glucose levels were seen. After the treatment, serum levels of HDL cholesterol, arachidonic acid (predominant in males), and high-molecular-weight adiponectin significantly increased. The level of dehydroepiandrosterone sulfate significantly decreased. No significant changes were seen in those of small dense LDL cholesterol, high-sensitivity C-reactive protein, and amyloid beta peptides 1–40 and 1–42. There was a slight but significant increase in body weight, but apparent adverse effects were not observed. In conclusion, pioglitazone at low doses increased serum adiponectin, HDL cholesterol, and arachidonic acid levels but decreased serum dehydroepiandrosterone level, not associated with glycemia, in elderly Japanese people with type 2 diabetes. An optimal dose of pioglitazone should be sought for to minimize its adverse effects and to fully exert its pleiotropic effects such as antiatherosclerotic and antiaging effects.

Overview of Cellular Transplantation in Diabetes Mellitus: Focus on the Metabolic Outcome

Diabetes mellitus is a metabolic disease possible to treat via several different therapeutic approaches. Since the advent of insulin in 1922, type 1 diabetes mellitus has become a chronic treatable disease. Nonetheless, type 1 diabetes mellitus can be a devastating disease when the macro- and microangiopathic complications take place after several years of illness. Starting from the eighties, pancreas/islet transplantation has become a potential innovative treatment of diabetes mellitus. The major advantage of pancreas/islet transplantation is the restoration of c-peptide cosecretion along with insulin; the major disadvantage is the need to administer immunosuppressive drugs which are diabetogenic themselves. Islet transplantation is the progenitor of more recent forms of cellular and stem cell therapies which will be reviewed herein. Cellular therapies for diabetes mellitus are still an experimental procedure. Herein we present the actual current achievements and an outlook of close future possible advancements in the area of cellular transplantation for the cure of diabetes mellitus.

Cystatin C and Its Role in Patients with Type 1 and Type 2 Diabetes Mellitus

Diabetes mellitus is the commonest cause of CKD. It is the leading cause of new patients requiring renal replacement therapy, accounting for 40%, 34%, and 30% of cases in United States, Germany, and Australia, respectively. Recent studies have shown that a low-molecular weight protein, cystatin C, freely filtered by the kidneys is a novel biomarker that may be used for detection of early renal dysfunction in patients with type 1 or type 2 diabetes. Cystatin C has also been shown to detect cardiovascular disease in patients with diabetes and it may also be linked with incident type 2 diabetes in obese patients. We aim to review current evidence based literature on use of cystatin C for early detection of diabetic nephropathy due to type 1 and type 2 diabetes in comparison to conventional methods and explore its association with other comorbidities.