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Introduction: Risk of malignancy for pediatric thyroid nodules classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is not well defined. Correlations between risk of malignancy and ancillary clinical data remain inconclusive. We report a single institutional experience of fine-needle aspiration (FNA) to improve upon current management paradigm of thyroid nodules. Methods: A retrospective chart review of 575 thyroid nodules was performed of 324 patients who underwent 340 FNAs between 2008 and 2018 at the Children’s Hospital of Philadelphia. Demographics, ultrasound (US) characteristics, FNA cytology, surgical pathology, and ancillary data were reviewed. Results: The rate of malignancy according to TBSRTC was 0.0% for category I, 0.8% for category II, 15.6% for category III, 54.5% for category IV, 100.0% for category V, and 100.0% for category VI. The cumulative Thyroid Imaging Reporting and Data System (TI-RADS) score was significantly correlated with benign and malignant nodules on pathology (p < 2.2e−16). Distribution of TI-RADS for cytologically indeterminate nodules with benign or malignant pathology revealed significant differences for composition (p = 3.20e−8) and echogenic foci (p = 0.005) but not for echogenicity (p = 0.445), shape (p = 0.160), margins (p = 0.220), and size (p = 0.105). Distributions of thyroid-stimulating hormone levels between benign and malignant patients was significant (p = 1.58e−3). Conclusions: Nodules with TI-RADS scores >3 should undergo FNA, irrespective of size; surgical resection is recommended for nodules classified as TBSRTC category IV and V due to high risk of malignancy. US surveillance instead of FNA can be performed for nodules with TI-RADS scores ≤3.

Introduction: We aimed to assess the mid-term type 2 diabetes mellitus recovery patterns in morbidly obese patients by comparing some relevant physiological parameters of patients of bariatric surgery between two types of surgical procedures: mixed (roux-en-Y gastric bypass and biliopancreatic diversion) and restrictive (sleeve gastrectomy). Material and methods: This is a prospective and observational study of co-morbid, type 2 diabetes mellitus evolution in 49 morbidly obese patients: 37 underwent mixed surgery procedures and 12 a restrictive surgery procedure. We recorded weight, height, body mass index, and glycaemic, lipid, and nutritional blood parameters, prior to procedure, as well as six and twelve months post-operatively. In addition, we tested for differences in patient recovery and investigated predictive factors in diabetes remission. Results: Both glycaemic and lipid profiles diminished significantly to healthy levels by 6 and 12 months post intervention. Type 2 diabetes mellitus showed remission in more than 80% of patients of both types of surgical procedures, with no difference between them. Baseline body mass index, glycated haemoglobin, and insulin intake, among others, were shown to be valuable predictors of diabetes remission one year after the intervention. Conclusions: The choice of the type of surgical procedure did not significantly affect the remission rate of type 2 diabetes mellitus in morbidly obese patients. (Endokrynol Pol 2017; 68 (1): 18–25)

We examined the prevalence of metabolic syndrome (MetS), glucose tolerance categories and risk factors of cardiovascular-disease (CVD) in the general Spanish population. We studied 3844 randomly sampled subjects (46% males) aged 35-74 years. Glucose tolerance categories were defined according to the 2003 ADA and MetS according to the Harmonized Consensus Criteria with waist circumference (WC) cut-off-points previously reported in Spanish population (≥94.5/≥89.5cm for males/females). The prevalences of normoglycemia (NG), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG and IGT considered together (IFG/IGT), and diabetes mellitus (DM) were 67.6/16.6/5.0/3.3, and 7.5%, respectively. The overall prevalence of MetS was 31.2%. In subjects with NG, IFG, IGT, IFG/IGT, and DM the MetS prevalence's were 16.3/57.1/31.5/66.1, and 74.4% (p

The prevalence of type 2 diabetes mellitus (T2DM) has risen in recent decades, and cardiovascular disease (CVD) remains the leading cause of death in this population. Several studies have shown that, in clinical practice, identifying diabetic patients at high risk for CVD is essential, since these patients benefit from aggressive strategies to achieve a greater risk reduction. In recent years, new markers of CV risk have been added to the list of those already known. These new emerging markers, such as inflammatory, bone and hormonal markers, act as new indicators of subclinical atherosclerosis and CV mortality. Therefore, we reviewed the ongoing scientific research on these new biomarkers and discuss their clinical impact on the identification of T2DM patients at high CV risk.

Resumen Objetivos Los pacientes con hiperparatiroidismo primario (HPP), incluso asintomatico, presentan un mayor riesgo cardiovascular. Sin embargo, los datos sobre la reversibilidad o mejoria de las alteraciones cardiovasculares con la cirugia son controvertidos. Los objetivos de nuestro estudio fueron evaluar la prevalencia de factores de riesgo cardiovascular clasicos en pacientes con HPP asintomatico, examinar su relacion con los niveles de calcio y PTH y analizar el efecto de la paratiroidectomia sobre los mismos. Pacientes y metodos Estudio retrospectivo observacional de 2 grupos de pacientes con HPP asintomatico: 40 pacientes en observacion y 33 pacientes intervenidos. Se recogieron datos clinicos y bioquimicos relacionados con el HPP y de diversos factores de riesgo cardiovascular en todos los pacientes de forma basal, y al ano de la cirugia en el grupo de pacientes intervenidos. Resultados Encontramos una elevada prevalencia de obesidad (59,9%), diabetes mellitus tipo 2 (25%), hipertension arterial (47,2%) y dislipidemia (44,4%) en la muestra total, sin diferencias entre los grupos de estudio. En el grupo que se mantuvo en observacion las concentraciones sericas de calcio y PTH se relacionaron positivamente con el IMC (r = 0,568, p = 0,011 y r = 0,509, p = 0,026 respectivamente). En los pacientes intervenidos, al ano de la cirugia no hubo mejoria de los factores de riesgo cardiovascular considerados. Conclusiones Nuestros resultados confirman la elevada prevalencia de obesidad, diabetes mellitus tipo 2, hipertension arterial y dislipidemia en pacientes con HPP asintomatico. Sin embargo, el tratamiento quirurgico no supuso una mejoria en estos factores de riesgo cardiovascular.

Una reciente conferencia de consenso, promovida por los National Institutes of Health y la Endocrine Society, ha establecido un conjunto de recomendaciones para el tratamiento del hiperparatiroidismo primario en la practica clinica. Sin embargo, no se conoce los grados de conocimiento y de cumplimiento de estas recomendaciones por parte de los endocrinologos espanoles. En este articulo se revisan las recomendaciones del consenso y se presenta una encuesta elaborada por el Grupo de Trabajo de Metabolismo Mineral Oseo de la SEEN.

Although previous studies have established the importance of genetic, hormonal and lifestyle factors separately, the integral role of these factors on bone mass in postmenopausal women is still controversial. We examined the association of the collagen 1-alpha-1 gene (COLIA1) and vitamin D receptor gene (VDR) polymorphisms, s-IGF-I, s-25OHD and lifestyle factors with bone mineral density (BMD) in postmenopausal women. We determined anthropometric parameters, lifestyle factors, serum levels of IGF-I and 25OHD, the COLIA1 Sp1 (Mscl) and VDR (Bsml, Taql) polymorphisms by PCR and BMD by dual X-ray absorptiometry in 141 ambulatory postmenopausal Spanish women. There were significant linear correlations between S-25OHD and BMD and between s-IGF-I and BMD. BMD was statistically higher in active subjects. Of the three different polymorphisms, only the COLIA1 Sp1 polymorphism was significantly associated with BMD. In the logistic regression model, the COLIA1 Sp1 polymorphism, S-25OHD, s-IGF-I and physical activity variables were independently associated with osteoporosis. Our study shows that COLIA1 Sp1 polymorphism, S-25OHD and s-IGF-I serum levels and physical activity are independently associated with BMD in postmenopausal Spanish women.

Hoy dia se considera que la osteoporosis es un problema de salud publica que justifica la implementacion de medidas preventivas y terapeuticas eficaces. El objetivo primario debe ser prevenir la primera fractura y preservar la integridad osea, aumentando la masa osea y mejorando la calidad del hueso. Los suplementos de calcio y vitamina D deben recomendarse en todos los individuos de riesgo, y cuando esten indicados deben administrarse farmacos antiosteoporoticos. La evidencia aporta resultados satisfactorios con los farmacos antirresortivos usados actualmente; ademas, futuros agentes anabolicos permitiran establecer pautas combinadas de tratamiento. Osteoporosis is a worldwide public health issue and effective preventive and therapeutic strategies should be implemented. The primary aim should be to prevent the first fracture by increasing bone mass and improving bone quality. Calcium and vitamin D supplementation should be recommended to all at-risk patients in addition to antiosteoporotic drugs, when indicated. There is strong evidence of the antifracture efficacy of the antiresorptive drugs that are currently used and in future we will be able to use combined therapies with anabolic agents.

Some studies have suggested that bone turnover markers (BTM) and collagen type I alpha 1 gene (COLIA1) may be useful in the prediction of rates of future bone loss, and may therefore provide information about fracture risk. Our study aimed to examine the association of the COLIA1 genotype with the risk of vertebral fracture and to investigate the predictive value of this genetic factor in comparison with bone mineral density (BMD) and BTM, in ambulatory postmenopausal Spanish women. We determined the COLIA1 polymorphism by polymerase chain reaction, BMD by dual-energy X-ray absorptiometry and BTM in 43 postmenopausal women with prevalent vertebral fracture and a control group of 101 postmenopausal women without fracture. There was a significant overrepresentation of the 'T' allele in fractured women ( p = 0.029). BTM exhibited no differences between women with or without fractures or COLIA1 genotype groups. After adjusting for all other variables, the osteoporosis densitometric criteria variable was the most strongly associated with fracture (OR = 5 [1.8-13.3]) followed by COLIA1 (OR = 2.1 [1-4.3] per copy of the 'T' allele). Our study shows that COLIA1 is associated with prevalent vertebral fracture independently of bone mass, and the performance of this genetic factor to assess prevalent vertebral fracture is better than bone turnover markers.

Summary objective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test. patients and design Seventy-three patients with adult GH deficiency and organic hypothalamic-pituitary disease were recruited, along with 46 controls. The patients were divided into five groups according to the number of associated hormone deficiencies present. measurements Hypopituitary subjects underwent assessment of GH secretory status by the ITT, the glucagon test and measurement of serum IGF-I concentration. Controls underwent the glucagon test. After the ITT, glucose and GH levels were measured at baseline, 30, 60 and 90 minutes, and after glucagon at baseline, 90, 120, 150, 180, 210 and 240 minutes. results The highest GH value after the ITT in the patient group was 3 µg/l (0·76 ± 0·82 µg/l), and after the glucagon test the highest GH peak value was 2·9 µg/l (0·64 ± 0·79 µg/l). A correlation was found between the GH peak and the progressive number of hormone deficiencies. After the glucagon test, the GH peak obtained in the controls at 180 minutes was 9·8 ± 4·6 µg/l and, on an individual basis, none of the 46 controls failed to achieve peak GH levels higher than 3 µg/l. In the controls, a negative correlation was observed between the GH response to glucagon and age (r = –0·389, P = 0·0075) and body mass index (r = –0·329, P = 0·0254). The accuracy of the glucagon test for differentiating patients from controls, estimated by receiver operating characteristics (ROC) curve methodology, showed that the cut-off of 3 µg/l for the GH peak provides 100% sensitivity and 100% specificity and is a reliable decision threshold. conclusions The glucagon GH test is reliable and provides a clear separation between GH-deficient and normal adults. A single glucagon test with a cut-off of 3 µg/l for the GH peak is diagnostic of GH deficiency in adults and could be considered and studied as an alternative to the ITT.

The aim of the present study was to assess the relationship between serum concentrations of several persistent organic pollutants and insulin resistance markers in a cohort of women with a history of gestational diabetes mellitus. ∑POPs was computed as the sum of individual serum POP concentrations. No statistically significant associations were found between levels of any POP and fasting glucose. However, polychlorinated biphenyl (PCB) congeners 138 and 180 were positively associated with 2-h glucose levels and PCB 180 also with fasting immunoreactive insulin (IRI). We also found a positive association of p,p′- dichlorodiphenyldichloroethylene (p,p′- DDE), PCBs (138, 153, and 180), hexachlorobenzene, and ∑POPs with 2-h IRI. Serum concentrations of PCBs (138, 153, and 180), hexachlorobenzene, and ∑POPs were also positively associated with homeostasis model assessment (HOMA2-IR) levels. Moreover, p,p′- DDE, PCBs (138, 153 and 180), hexachlorobenzene, and ∑POPs were negatively associated with Insulin Sensitivity Index (ISI-gly) levels. No significant association was found between glycated hemoglobin and the concentrations of any POP. The removal of women under blood glucose lowering treatment from the models strengthened most of the associations previously found for the whole population. Our findings suggest that exposure to certain POPs is a modifiable risk factor contributing to insulin resistance.

Objective To study bone mineral density (BMD) and bone remodeling factors at the time of diagnosis of adult-onset type 1 diabetes mellitus (DM). Methods In 22 men and 10 women, who ranged in age from 20 to 39 years, a study was undertaken promptly after diagnosis of type 1 DM (on the basis of criteria established by the World Health Organization). Before any treatment, the clinical history, glycemia, ketonuria, basal and glucagon-stimulated C-peptide levels, islet cell antibodies (ICA), glutamic acid decarboxylase autoanti-bodies (GADA), and bone remodeling variables were recorded for all the study subjects. Dual-energy x-ray absorptiometry (Hologic QDR1000) was performed to measure BMD in the lumbar spine (LS), femoral neck (FN), and Ward's triangle. Results Of the 32 patients, 24 (75%) showed positive levels of ICA or GADA (or both), whereas 8 (25%) tested negative. The BMD values--Z-scores (standard deviation [SD] adjusted for age and sex)--were lower among the patients with DM than in a matched healthy population in both the LS (-0.61 ± 1.23 SD; P = 0.008) and the FN (-0.38 ± 1.00 SD; P = 0.003). Twelve patients had a T-score between -2.5 SD and -1 SD in the LS, and 14 had the same scores in the FN and were classified as having osteopenia. A correlation was found between BMD values and C-peptide levels in the LS (r = 0.231; P = 0.02) and the FN (r = 0.27; P = 0.01). The BMD values did not correlate with bone remodeling markers, hemoglobin A1c, or immunologic variables. Conclusion We found reduced bone mass in patients with type 1 DM at the time of the clinical diagnosis. A high percentage of patients with DM have osteopenia, which may not, therefore, be a late complication of type 1 DM. These findings need to be confirmed in larger studies. (Endocr Pract. 2001;7:346-351)

A questionnaire describing a typical clinical case of Graves' disease and 10 variations on it was mailed to 70 Spanish units of endocrinology with the aim of assessing the new diagnostic and therapeutic trends for hyperthyroidism caused by Graves' disease in Spain and to compare the results obtained from previous studies carried out in Europe and Spain 10 years previously. Responses indicated that thyrotrophin (98%) and free thyroxine (88%) were the most used tests in the in vitro diagnosis of Graves' disease with a significant decrease in the use of total thyroxine, total triiodothyronine, and thyroglobulin in comparison with the surveys conducted 10 years previously in Europe and Spain. The presence of antibodies against the thyrotrophin receptor was the most frequently used immune marker in the diagnosis (78%) and the new use of antithyroperoxidase antibodies (36%) in diagnosis is noteworthy. Antithyroid drugs remain the treatment of choice (98%). Surgery was used mainly for large size goitres (33%) and radioiodine for recurrences after medical (61%) or surgical (80%) treatment. In conclusion, the responses obtained from this questionnaire provide insight into current specialist diagnostic and therapeutic practices with respect to Graves' disease and which could be of value to non-specialist units of endocrinology.

In order to determine the prevalence of microalbuminuria in people with Type 1 diabetes mellitus (Type 1 DM) and identify factors associated with microalbuminuria, we studied 312 Type 1 DM patients attending in three hospitals in two Spanish regions over 6 months. Clinical characteristics, micro- and macro-vascular complications, blood pressure, 24-h urine albumin excretion, lipid profile, HbA1(c) levels, smoking habits, and family history of hypertension and diabetic nephropathy were recorded. Univariate analysis and multiple logistic regression were used to examine associations between these variables and the prevalence of microalbuminuria. We detected microalbuminuria in 29% of the patients. The prevalence of microalbuminuria was high during the second decade of diabetes and declined thereafter. Univariate analysis showed dyslipidaemia (P

The major adverse reactions of antithyroid drugs are hematologic; aplastic anemia (AA) is one of the rarest and most severe complications. Use of recombinant human hemopoietic colony-stimulating factor was reported to be of benefit in patients who developed agranulocytosis, although there is still some doubt regarding the efficacy in AA. We present a case of a 58-year-old female patient with Graves' disease who developed AA in the third exposure to methimazole (MMI). The withdrawal of MMI and early treatment with 5 microg/kg per day recombinant human granulocyte colony-stimulating factor (G-CSF) for 9 days, allowed a favorable recovery of peripheral blood cell count. We conclude that the use of hemopoietic colony stimulating factors might be a suitable means to achieve the correction of severe thionamide-induced hematologic adverse reactions.

OBJECTIVE To study whether the presence of antithyroid peroxidase antibodies (TPO-Abs) before gestation in IDDM affects thyroid function and metabolic control during pregnancy and early postpartum as well as neonatal outcome. RESEARCH DESIGN AND METHODS A prospective study at an outpatient endocrine-obstetric unit was carried out in 20 pregnant IDDM women. Free T4 (thyroxine), thyroid-stimulating hormone (TSH), TPO-Abs, and HbA1c were assayed before gestation; during the first, second, and third trimester of pregnancy; and 3 months postpartum. RESULTS HbA1c was significantly higher in TPO-Ab+ women than in those who were TPO-Ab− during the second (P < 0.01) and third (P < 0.05) trimesters. HbA1c levels significantly decreased in TPO-Ab− patients when the second (P < 0.01) and third (P < 0.05) trimesters were compared with before the pregnancy and the first trimester. There was a significant increase in the dosage of insulin for TPO-Ab+ versus TPO-Ab− patients during the second (P < 0.05) and third (P < 0.01) trimesters and 3 months postpartum (P < 0.05). TSH was significantly increased in the second (P < 0.001) and third (P < 0.05) trimesters and 3 months postpartum (P < 0.01) when compared with TPO-Ab− patients; 7.6% of the TPO-Ab− group and 29% in the TPO-Ab+ group presented postpartum thyroid dysfunction, and 42% of the TPO-Ab+ women required thyroid treatment. CONCLUSIONS Pregnant women with IDDM who have a positive test for TPO-Abs before gestation have poorer glucose control and a high prevalence of hypothyroidism. Therefore we recommend that prepregnant IDDM patients be screened for anti-TPO-Abs. Those with a positive result should be followed with serial monitoring of free T4 and TSH levels during each trimester as well as the postpartum period.

Previous studies suggest that low bone mass is a potential complication of insulin-dependent diabetes mellitus. Nevertheless, the factors that influence diabetic osteopenia are not well established. In order to evaluate the prevalence and magnitude of diabetic osteopenia and its association with clinical and metabolic variables, we studied 94 consecutive patients with insulin-dependent diabetes mellitus. Their age ranged from 20 to 56 years and duration of diabetes varied from 1 to 35 years. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at lumbar spine and proximal femur and the values were expressed as z-score. The presence and extent of microvascular complications, degree of metabolic control, and other risk factors for osteoporosis were recorded and some biochemical markers of bone metabolism were assessed. Diabetic patients showed reduced BMD in all sites (lumbar spine: -0.89 +/- 1.21; femoral neck: -0.99 +/- 1.24; Ward triangle: -1.05 +/- 1.24; P0.0001). Of the 94 patients 19.1% met diagnostic criteria for osteoporosis. BMD correlated with body mass index in all sites and with the duration of disease in Ward's triangle. Presence and extent of diabetic complications were associated with lower BMD, as was smoking. No correlation was found between BMD and biochemical markers. In conclusion, osteopenia is a common complication in patients with insulin-dependent diabetes mellitus. Microvascular complications are a critical point in the progression of diabetic osteopenia. Other risk factors for osteoporosis (nutritional status and smoking) must be taken into account.

Silent myocardial ischemia in non-insulin-dependent diabetic patients occurs frequently in association with autonomic dysfunction, suggesting that diabetic neuropathy may be involved in the development of this disorder. Repeated episodes of silent myocardial ischemia can induce myocardial necrosis. Recently, actin was detected with Western blotting in the serum of patients with acute myocardial infarction and angina pectoris. We found that a large proportion of non-insulin-dependent diabetic patients with neuropathy also have detectable circulating concentrations of alpha-actin, and therefore suggest that the determination by immunoblotting of serum alpha-actin in such patients is an effective method to detect myocardial cell suffering and to identify patients that may need special consideration.

Pancreastatin (PST), a 49 amino acid peptide originally isolated from porcine pancreas, is derived from chromogranin A (Cg A), an acidic protein co-released with catecholamines from sympathetic nerve terminals and chromaffin cells. Extracellular processing of Cg A yields PST as well as other biological active peptides. Measurement of Cg A and PST-like immunoreactivity (PST-LI) has been used to investigate patients with pheochromocytoma and other neuroendocrine neoplasia. Some studies have found increased plasma norepinephrine (NE) levels in essential hypertension. We therefore measured venous plasma PST-LI and catecholamines in patients with essential hypertension. We employed a radioimmunoassay developed with commercially available reagents for measuring plasma PST-like immunoreactivity, and HPLC with electrochemical detection for measurement of plasma catecholamines. The correlation of PST-LI with epinephrine (E) was very weak. However, its correlation with NE was highly significant. Thus, venous plasma PST-LI immunoreactivity may reflect sympathetic nerve activity in essential hypertension.

The efficacy of miglitol in improving postprandial glucose levels and its relationship to carbohydrate metabolism and absorption has been shown in several in vivo and in vitro studies. A multicenter (10 centers), randomized, double-blind, parallel-group study was designed to evaluate long-term efficacy and tolerability of miglitol versus placebo in patients with non—insulin-dependent diabetes mellitus (NIDDM). A total of 102 patients were recruited and randomized (89 assessable patients); after a run-in placebo period of 4 weeks, patients received miglitol or placebo 100 mg thrice daily for 18 weeks. Fasting blood glucose, cholesterol, and triglyceride levels were determined every 6 weeks; glycosylated hemoglobin HbA 1c levels were determined at the beginning and at the end of the study. No significant differences appeared in baseline values of efficacy variables. The primary efficacy analysis showed that miglitol was significantly more effective in reducing HbA 1c levels that placebo ( P = 0.0158). Miglitol was also significantly more effective in reducing fasting blood glucose levels ( P = 0.0012). No statistically significant differences were found in cholesterol or triglyceride levels. Meteorism, diarrhea, and flatulence were the most common adverse events and occurred more frequently in the miglitol group (49.0% of miglitol patients vs 36.7% of placebo patients). Hypoglycemic episodes occurred in 7 patients (2 in the miglitol group and 5 in the placebo group). Miglitol appears to be useful in the treatment of patients with NIDDM as it significantly reduces HbA 1c and fasting blood glucose levels.

Several different strategies were used to investigate the relationship between hyperandrogenism and hyperinsulinemia associated with polycystic ovary syndrome. Ketoconazole was given orally (400 mg/day) for 9 months to evaluate the effect of reduction in ovarian and adrenal androgens on insulin response (oral glucose tolerance test) in 35 women with polycystic ovary syndrome. Androgenic steroids (testosterone, androstenedione, dehydroepiandrosterone sulphate, and free testosterone index) decreased (p < 0.01), but basal insulinemia, maximum peak insulin, and insulin/glucose ratio showed no significant changes. One month after treatment was stopped, free testosterone index, and serum concentrations of androstenedione and testosterone, increased (p < 0.05), but no alterations were noted in insulin parameters. Body mass index was stable throughout the ten-month study period. Our findings suggest that endogenous androgens, no matter whether they are of ovarian or adrenal origin, do not play a major role in the modulation of hyperinsulinemia in patients with polycystic ovary syndrome.

The aim of this study was to evaluate the effect of thyroid functional state on cortical and trabecular bone mineral density (BMD) (g/cm2) in premenopausal and postmenopausal women. Control subjects were used as a reference population to calculate Z-scores from patient data. In patients with active hyperthyroidism, BMD was reduced in lumbar spine (LS; P0.01), femoral neck (FN; P0.01) and Ward triangle (WT; P0.0001) in comparison with reference standards. In premenopausal women treated in the past for hyperthyroidism or treated at the time of study with L-thyroxine in non-TSH-suppressive doses, there was no significant decrease in BMD. In postmenopausal women with hyperthyroidism in remission, we found a significant decrease in BMD in LS (P0.01), FN (P0.05) and WT (P0.0001). In postmenopausal women treated with L-thyroxine (L-T4), there was a significant decrease in BMD in LS (P0.01) and WT (P0.01). There was a significant negative correlation between the cumulative dose of L-T4 and BMD in FN (r = -0.688, P0.05) and WT (r = -0.657, P0.05) in postmenopausal women. Our findings suggest that the deleterious effects of thyroid hormones on BMD are accentuated in areas consisting predominantly of trabecular bone, e.g., the LS and WT. Postmenopausal women subjected to excess thyroid hormone represent a population at greater risk for osteoporosis.

Cathepsin K is a member of the cysteine protease family that cleaves both helical and telopeptide regions of collagen I, the major type of collagen in bone. Measurement of circulating levels of cathepsin K may be useful to assay the number or function of osteoclasts.The aim of the study was to evaluate the role of serum cathepsin K as a biochemical marker of bone metabolism in patients with postmenopausal osteoporosis before and after treatment with alendronate.The study was a case-control and prospective study with postmenopausal osteoporotic women including a total number of 86 subjects. Serum cathepsin K was determined in 46 women with postmenopausal osteoporosis before and after 3, 6 and 12 months of treatment with alendronate. Basal serum cathepsin K levels were also compared between premenopausal healthy women (n=20), postmenopausal women without osteoporosis (n=20) and osteoporotic women. In addition, serum carboxyterminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) and bone-specific alkaline phosphatase (bALP) were measured.Changes in cathepsin K serum levels after alendronate treatment.Serum cathepsin K levels were higher in postmenopausal women with osteoporosis (9.4+/-11pmol/L) compared with healthy postmenopausal women (6.8+/-8.1pmol/L; p0.01) and premenopausal women (6.3+/-5.0pmol/L, p0.01). Serum cathepsin K decreases gradually after alendronate treatment (17% at 3 months, 22% at 6 months and 41% at 12 months, p0.01). In contrast, the treatment resulted in early and sustained reductions in serum CTX.We conclude that serum cathepsin K seems to provide additional information on bone metabolism in postmenopausal women treated with alendronate.

Resistance to the conventional treatment of hyperthyroidism with antithyroid drugs is not commonly found in clinical practice, and only few other treatment options have been reported on in detail. For example, surgery or radioiodine ablation are well-accepted interventions that must be always considered. The euthyroid state is strongly recommended before both of these as this might reduce complications. There are few studies indicating that bile acid sequestrants, when added to antithyroid drugs, produce a more rapid decline in serum thyroid hormone levels and that this effect is maintained for at least 4 weeks. Complete normalization of serum thyroid hormone levels is generally not expected, however.We report a patient whose thyrotoxicosis failed to respond to conventional treatment. The patient remained persistently hyperthyroid, both clinically and biochemically, despite several months of methimazole and propranolol and the addition of iodine. Cholestyramine, a bile acid sequestrant, was then added, and a dramatic improvement was observed.We report a patient who was resistant to conventional antithyroid drugs in whom thyroid hormone levels completely normalized after 1 week of additional treatment with cholestyramine.

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.

Regulation of osteoclastic activity is critical for understanding bone loss associated with the postmenopausal period. In vitro and animal studies have revealed the role of OPG as a decoy receptor that neutralizes the effect of RANKL on the differentiation and activation of osteoclasts. However, the role of the OPG-RANKL system in postmenopausal osteoporosis is controversial. Thus, the aim of this study was to investigate the relationship among circulating levels of OPG, RANKL, bone turnover markers (BTM), bone mineral density (BMD) and vertebral fractures in postmenopausal women. We determined anthropometric parameters, circulating OPG and RANKL, BTM, estradiol, BMD by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN), and pre-existing vertebral fractures in 206 ambulatory postmenopausal women of a mean age of 62 years (SD 7). Circulating OPG was significantly related to age ( r =0.158; P =0.023), years since menopause ( r =0.167; P =0.016) and BMD (LS Z-score: r =0.240; P =0.001, FN Z-score: r =0.156; P =0.025). Over half of the women had undetectable RANKL ( n =113; 54.9%). There were no significant differences in clinical variables, BTM or BMD among women with detectable vs. undetectable RANKL. OPG was found to be independently associated with osteoporosis (OR: 2.9, 1.4–5.9) and prevalent vertebral fractures (OR: 2.5, 1.2–5.4). We conclude that serum OPG levels are independently associated with bone mass and prevalent vertebral fractures in postmenopausal women.

Objective To review various aspects of thyroid function during and early after pregnancy. Methods We discuss biochemical and potential pathologic changes in the thyroid associated with the gestational and postpartum periods. Results Urinary iodine excretion during the last trimester of gestation in healthy euthyroid women shows that, in areas with mild iodine intake, iodine supplementation is necessary during pregnancy and the postpartum period. This measure should be considered in iodine-sufficient areas as well. Thyroglobulin is the main biochemical marker of persistent thyroidal stimulation. Alterations in thyroid volume during pregnancy can persist after delivery, especially in breast-feeding mothers. In most patients, the goitrogenic stimulus of pregnancy can be suppressed with iodine supplementation. Autoimmune thyroid disease during pregnancy and the postpartum period is reflected by monitoring of thyroid peroxidase antibodies (TPO-Ab). Women with positive test results for TPO-Ab early in gestation showed a highly significant decrease in free thyroxine and increased thyroid-stimulating hormone levels late in gestation. The main marker of Graves’ disease during pregnancy is thyroid-stimulating antibodies. Nonautoimmune gestational hyperthyroidism differs from Graves’ disease in that thyroid-stimulating antibodies are not detectable. Conclusion Clinicians should be alert to the fact that pregnancy can induce thyroidal pathologic conditions. (Endocr Pract. 1998;4:97-105)

Aims: The aims of the study were to evaluate the prevalence of increased urinary albumin excretion (UAE) and associated cardiovascular risk factors and vascular diabetes complications in patients with type 2 diabetes mellitus (DM). Methods: We studied 975 patients in a cross-sectional design from 1998 to 2000. Frequency of micro- and macroalbuminuria, and their associations with cardiovascular risk factors and vascular DM complications, were examined. Results: Prevalence of increased UAE was 28.5% (18.3% micro- and 10.2% macroalbuminuria). Body mass index (BMI) (only females) and hemoglobin (Hb)A1c significantly correlated with macroalbuminuria (p = 0.034, p = 0.027, respectively), while high blood pressure (diastolic) was associated with microalbuminuria (p = 0.008). Diabetes duration, high systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides were significantly correlated with both micro- and macroalbuminuria. Increased UAE was associated with neuropathy (relative risk (RR) 2.12, confidence interval (CI) 1.07–4.19), retinopathy (RR 2.19, CI 1.76–2.74) and hypertension (RR 2.91, CI 1.77–4.78), but not with cardiovascular disease, high cholesterol and peripheral vascular disease. In the multiple logistic regression analysis, a significant association of albuminuria was found with diabetes duration (odds ratio (OR) 1.59, CI 0.98–2.58; p < 0062), hypertension (OR 3.42, CI 2.22–5.27; p < 0.0001), low HDL cholesterol (OR 1.78, CI 1.31–2.43; p < 0.0003), current smoking status (OR 2.19, CI 1.32–3.64; p < 0.0024), and increased serum creatinine (OR 11.16, CI 5.7–21.7; p < 0.0001). Conclusion: Prevalence of increased UAE was similar to that described in other geographically close populations. The stronger association found with microvascular diabetes complications suggests that increased UAE is a better predictor for renal damage than for cardiovascular disease in this type 2 DM population.

Vidal-Puig AJ, Muñoz-Torres M, Jódar-Gimeno E, García-Calvente CJ, Lardelli P, Ruiz-Requena ME, Escobar-Jiménez F. Ketoconazole therapy: hormonal and clinical effects in non-tumoral hyperandrogenism. Eur J Endocrinol 1994;130:333–8. ISSN 0804–4643. The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome. The study group comprised 37 women with signs of hyperandrogenism (hirsutism, acne) and oligomenorrhea. A low dose (400 mg/day) of ketoconazole was tested in a 9-month prospective clinical study. Clinical response (Ferriman & Gallway score, acne) and modifications in hormone pattern (luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, prolactin, 17-hydroxy-progesterone, androstenedione, steroid hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, adrenocorticotropin (ACTH) and free testosterone index) were measured, and ACTH stimulation tests were performed. Tolerance and side-effects also were assessed. After 9 months of ketoconazole treatment, the patients' Ferriman & Gallway scores (18.26 ± 4.6 vs 12.4 ± 4.1; p < 0.001) and acne had improved markedly. Hormone patterns also became more favorable, with decreases in androgenic steroids (testosterone, androstenedione, free testosterone index and dehydroepiandrosterone sulfate; p < 0.01) and increases in estradiol (p < 0.01). Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly, remaining within the reference range. Increases in ACTH were observed only in the 3rd month (p < 0.01). Initial levels of androgenic steroids were correlated inversely with their percentage decrease in successive samplings. Decreases in adrenal androgenic steroids were associated with an increase in steroid hormone-binding globulin. The side-effects of treatment, although not severe, caused some discomfort and led to a high drop-out rate (30%). Our results suggest that low doses of ketoconazole (400 mg/day) are an alternative therapy for non-tumoral hyperandrogenism, although the bothersome side-effects, which require close monitoring and maximal patient compliance, make this treatment advisable only in selected patients. Manuel Muñoz-Torres, Plaza Isabel la Católica no. 2, E-18009, Granada, Spain

The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA(1c)), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia.Patients with type 2 diabetes mellitus (HbA(1c)/=6.5% and/=9.8%) who had not previously received insulin or oral antihyperglycemic medications (OAMs) were randomized to treatment with placebo, pioglitazone 30 mg QD, or pioglitazone 45 mg QD in double-blind fashion for 16 weeks at 41 centers in Canada and Spain.A total of 297 patients were randomized (99 in each group). Overall, 286 (96.3%) were white. Mean (SD) age was 58.4 (10.9) years (range, 24-85 years), mean (SD) body mass index was 31.4 (4.8) kg/m(2), mean (SD) duration of type 2 diabetes mellitus was 20.0 (37.4) months, and 30.6% of patients were receiving medication for dyslipidemia. Treatment with pioglitazone 30 or 45 mg QD for 16 weeks reduced mean HbA(1c) by 0.8% and 0.9% from baseline, respectively (both P0.001 vs baseline and placebo). A reduction in HbA(1c) of 0.2% was observed in the placebo group (P = 0.025). In patients with medium (/=7% to8%) or high (/=8% to/=9.8%) baseline HbA(1c), both doses of pioglitazone significantly reduced HbA(1c) (both P0.001 vs placebo). Pioglitazone 30 and 45 mg significantly reduced fasting serum insulin versus placebo (P = 0.008 and P = 0.006, respectively) and increased insulin sensitivity by Homeostasis Model Assessment versus placebo (P = 0.039 and P = 0.001, respectively). Relative to placebo, pioglitazone 30 and 45 mg significantly increased high-density lipoprotein cholesterol (HDL-C [P = 0.028 and P0.001, respectively]) and lowered the atherogenic index of plasma (P = 0.018 and P0.001, respectively). Pioglitazone 45 mg also significantly reduced serum triglycerides, apolipoprotein B, and total cholesterol:HDL-C ratio versus placebo (P = 0.007, P = 0.015, and P = 0.005, respectively). Pioglitazone 30 and 45 mg were associated with a significant reduction in serum alanine aminotransferase relative to placebo (P = 0.036 and P = 0.005, respectively). Pioglitazone appeared to be safe and was well tolerated.In the present study, pioglitazone 30 and 45 mg produced significant improvements in HbA(1c), insulin sensitivity, and lipid profile in OAM-naive patients with type 2 diabetes mellitus with suboptimal glycemic control and mild dyslipidemia.

OBJECTIVE—Metabolic factors such as glycemic control, hyperlipidemia, and hyperkalemia are important considerations in the treatment of patients with type 2 diabetes and nephropathy. In the RENAAL (Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan) study, losartan reduced renal outcomes in the patient population. This post hoc analysis of the RENAAL study reports the effects of losartan on selected metabolic parameters and assesses the relationship between baseline values of metabolic parameters and the primary composite end point or end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS—Glycemic control (HbA1c) and serum lipid, uric acid, and potassium levels were compared between the losartan and placebo groups over time, and baseline levels were correlated with the risk of reaching the primary composite end point (doubling of serum creatinine, ESRD, or death) or ESRD alone. RESULTS—Losartan did not adversely affect glycemic control or serum lipid levels. Losartan-treated patients had lower total (227.4 vs. 195.4 mg/dl) and LDL (142.2 vs. 111.7 mg/dl) cholesterol. Losartan was associated with a mean increase of up to 0.3 mEq/l in serum potassium levels; however, the rate of hyperkalemia-related discontinuation was similar between the placebo and losartan groups. Univariate analysis revealed that baseline total and LDL cholesterol and triglyceride levels were associated with increased risk of developing the primary composite end point. Similarly, total and LDL cholesterol were also associated with increased risk of developing ESRD. CONCLUSIONS—Overall, losartan was well tolerated by patients with type 2 diabetes and nephropathy and was associated with a favorable effect on the metabolic profile of this population.

Although only few postmenopausal women exhibit biochemical signs of hypovitaminosis D, vitamin D insufficiency has been shown to have adverse effects on bone metabolism and could be an important risk factor for osteoporosis and fracture. We determined serum levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), bone turnover markers, dietary calcium intake, and bone mineral density (BMD; measured by dual X-ray absorptiometry) in 161 consecutive ambulatory women, healthy except for osteoporosis, referred to a bone metabolic unit. The prevalence of vitamin D insufficiency [25(OH)D < or = 15 ng/ml] was 39.1%. 25(OH)D was lower in the osteoporotic subjects (15.7 +/- 5.3 ng/ml vs. 21.8 +/- 9.7 ng/ml; p < 0.001). After controlling for all other variables, lumbar spine (LS) BMD was found to be significantly associated with 25(OH)D, body mass index (BMI), and years after menopause (YSM) (R2 = 0.253; p < 0.001). For femoral neck (FN), significant independent predictors of BMD were YSM, BMI, iPTH, and 25(OH)D (R2 = 0.368; p < 0.001). The probability of meeting osteoporosis densitometric criteria was higher in the vitamin D insufficiency group (odds ratio [OR], 4.17, 1.83-9.48) after adjusting by YSM, BMI, iPTH, and dietary calcium intake. Our study shows that vitamin D insufficiency in an otherwise healthy postmenopausal population is a common risk factor for osteoporosis associated with increased bone remodeling and low bone mass.

To determine the effect of metabolic control on bone mineral density (BMD) in type 1 diabetes mellitus (type 1 DM), we studied BMD (by dual-energy X-ray energy absorptiometry) and bone remodeling parameters in 62 patients with type 1 DM both before and 7 years after commencement of intensive insulin therapy. Overall outcomes after the 7-year treatment included the stabilization of BMD at all sites, as well as a significant decrease in tartrate-resistant acid phosphatase (TRAP) (4.302 +/- 2.62 vs 2.65 +/- 0.97 IU/I; p=0.0001) and increase in intact parathyroid hormone (PTHi) (28.05 +/- 15.7 vs 39.78 +/- 22.41 ng/l; p=0.005). Presence of diabetic retinopathy (RTP) versus its absence (non-RTP) was associated with lower BMD in femoral neck (FN) (0.831 +/- 0.142 vs 0.756 +/- 0.153 mg/ cm2; p = 0.03) and Ward's triangle (WT) (0.736 +/- 0.165 vs 0.632 +/- 0.172 mg/cm2; p=0.03), and with a lower T-score in FN (-0.93 +/- 1.34 vs -1.70 +/- 1.46; p = 0.04) and WT (-0.72 +/- 1.42 vs -1.540 +/- 1.55; p = 0.04) and Z-score in FN (-0.591 +/- 1.23 vs -1.132 +/- 1.46; p=0.01). The percentage of patients with osteopenia or osteoporosis in the RTP group was significantly higher than in the non-RTP group (72% vs 53%, p=0.05; RR= 3.2) and the glycosylated hemoglobin (HbA1c) levels of the RTP group were also higher (8.53 +/- 1.6% vs 7.1+/- 1.1%; p=0.05). The improvement in metabolic control, increase in body mass index and decrease in resorption parameters could contribute to the stabilization of bone mass in type I DM but the presence of retinopathy is a critical factor in the progression of diabetic osteopenia.

OBJECTIVE: To investigate plasma pancreastatin (a chromogranin A-derived peptide) and catecholamine levels (counterregulatory hormones) in subjects with gestational diabetes compared with normal pregnant subjects. RESEARCH DESIGN AND METHODS: Fasting blood samples were obtained from 11 normal pregnant and 12 nonobese gestational diabetic subjects at late pregnancy (30+/-1 weeks). Selection criteria were those recommended by the National Diabetes Data Group (modified from O'Sullivan original criteria). Plasma glucose, insulin, glucagon, pancreastatin-like, epinephrine, and norepinephrine were measured. RESULTS: Gestational diabetic subjects had significantly higher insulin levels than control pregnant subjects (18+/-1 vs. 15+/-1 microU/ml), whereas glucose and glucagon levels where comparable in the two groups. However, increased catecholamine levels (epinephrine and norepinephrine) were found in the gestational diabetic group. We also found increased pancreastatin-like levels in these patients compared with the pregnant control group (46+/-2 vs. 30+/-2 pmol/l). Actually, pancreastatin levels positively correlated with both epinephrine (r = 0.34) and norepinephrine (r = 0.80) levels. CONCLUSIONS: Catecholamine and pancreastatin-like levels were found elevated in gestational diabetic subjects. These counterregulatory hormones may play a role in the insulin resistance syndrome of gestational diabetes.

Three further cases of mature benign cystic teratomas of the ovary associated with virilization are added to the three previously reported in the literature. They were found in postmenopausal, obese, diabetic women aged 52, 61, and 67 years. The patients presented with hirsutism and voice changes and clitoromegaly was present in one. Testosterone and androstenedione levels were elevated but promptly regressed after removal of the tumours. Histologically, sheets of stromal luteinized cells were found peripherally at the interface between the neoplasm and ovarian tissue. Luteinization of ovarian stroma induced by an unknown factor related to diabetes mellitus is the origin of the virilization.

The response of bone mass to long-term treatment with estrogen and progesterone in patients with complete androgen-insensitivity syndrome (AIS) is unknown. We report a 17-year-old female patient (karyotype 46 X, Y) with AIS studied during a 4-year period. Bone mineral density (BMD) measured by dual X-ray absorptiometry in lumbar spine and proximal femur was sharply reduced at the initial visit, and remained unchanged during long-term follow-up on hormone replacement therapy with estrogens and progestin. Bone metabolism markers were all in the normal range. The lack of significant increase in BMD highlights the importance of androgens on bone physiology that cannot be balanced in spite of an appropriate estrogenic milieu.

We analyzed the association between hyperandrogenism and hyperinsulinemia, and their relationship to body mass index, in a large series of patients with polycystic ovary syndrome (PCOS). A characteristic hormonal profile was sought in women with marked hyperinsulinemia. The patient group consisted of 73 women with PCOS, ranging in age from 16 to 29 years. The control group consisted of 34 healthy women with no evidence of hyperandrogenism, aged 19–30 years. None of the patients or control women had a body mass index above 27 kg/m2. Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, sex hormone binding globulin, 17-hydroxyprogesterone, and free cortisol were determined by radioimmunoassay. The free testosterone index was calculated. The oral glucose tolerance test was used to analyze basal insulinemia, maximum insulin peak, and the insulinemia/glycemia index. In the group with PCOS body mass index was greater, free testosterone index was higher, and levels of dehydroepiandrosterone sulfate, testosterone, 17-hydroxyprogesterone (P < 0.001) and androstenedione (P < 0.05) were higher than in the control group. Of the insulin parameters, basal insulinemia, maximum insulin peak, and insulinemia/glycemia index were higher in the patient group (P < 0.001). In patients with marked insulinemia, free testosterone index was more markedly elevated, and gonadotrophin levels were normal. Our data confirm that a characteristic pattern of hyperinsulinemia is associated with PCOS. We found no causal relationship between hyperinsulinemia and androgen levels. A characteristic hormonal pattern was found in patients with marked hyperinsulinemia.

We measured parathyrin (PTH) in peripheral venous blood samples and in thyroid veins (both homolateral and contralateral to the lesion) in 13 patients with surgically confirmed parathyroid adenomas. Two different RIAs were used, one specific to the mid-region of the molecule (44-68, M-PTH), the other specific to the carboxy-terminal region (65-84, C-PTH). With the M-PTH assay we established a statistically significant multiple correlation (P less than 0.05) between the PTH concentrations in blood from the peripheral and thyroid veins; no significant correlation was found when we used the C-PTH assay. Our results confirm the superiority of the M-PTH RIA over the C-PTH RIA for study of hormonal secretion in primary hyperparathyroidism.

DESIGN Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolytic effect, and is present in many endocrine and chromaffin cells. Both the plasma insulin levels and the adrenergic activity accompanying insulin resistance have been shown to be increased in hypertensive subjects. Our working hypothesis was that pancreastatin might play a role in these pathological phenomena. METHODS We studied the plasma pancreastatin level in non-obese essential hypertensive patients in response to an intravenous glucose load. We further measured the responses to the glucose challenge of insulin, glucagon, catecholamines and free fatty acids, as well as other factors related to insulin resistance (i.e. lipoproteins and apolipoproteins). We separated the hypertensive patients into three groups according to their response to an oral glucose-tolerance test: normoinsulinaemic, hyperinsulinaemic and glucose-intolerant. Matched normotensive control subjects were also studied. RESULTS Pancreastatin levels did not change in the control group after the glucose challenge. However, all hypertensive patients showed an increase in plasma pancreastatin levels after glucose loading. The normoinsulinaemic hypertensive patients also had elevated basal pancreastatin levels. The increase in pancreastatin levels was in the ranking: normoinsulinaemic > hyperinsulinaemic > glucose-intolerant. The pancreastatin: insulin ratio showed that the secretion of pancreastatin and insulin may be regulated differently. Basal free fatty acid and glucagon levels were found to be elevated both in the hyperinsulinaemic and in the glucose-intolerant group. Fasting triglycerides levels were increased in all of the hypertensive patients. Other risk factors for coronary artery disease were also found to be altered: elevated very low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol, with ranking: normoinsulinaemic < hyperinsulinaemic < glucose-intolerant. CONCLUSIONS These results show an increase in pancreastatin levels in hypertensive patients, suggesting that pancreastatin might play a role in the pathophysiology of essential hypertension.

We herein describe a family with thyroid hormone resistance. Thyroid hormones and basal TSH were elevated. Pituitary tumor or abnormality in thyroid hormone binding proteins were ruled out by appropriate tests. Mother and sister of the propositus presented similar abnormal hormonal features but no hyperthyroidism. Initially the patient was treated with carbimazole (30 mg/day): three months later a dramatic increase in the size of the thyroid gland and in TSH levels (12.5 to 28 mU/l) were noted. Thereafter, dextrothyroxine (D-T4) and 3, 5, 3'-triiodothyroacetic acid (TRIAC) were given consecutively and treatment was accompanied by a decrease of TSH levels (2 mU/l) but thyroid hormone remained elevated. The symptoms and signs of hyperthyroidism improved with the addition of propranolol (30-60 mg/day). In conclusion, the present report describes a new family with the syndrome of THR and variable degrees of involvement among relatives. We suggest the usefulness of TRIAC therapy to decrease TSH levels and propranolol to improve thyrotoxicosis due to pituitary resistance to thyroid hormone.

The effect of antiresorptive therapy with nasal calcitonin (CT) in recently diagnosed hyperthyroid patients on conventional medical therapy as well as the evolution of bone metabolism were assessed. Forty-five patients with recent-onset hyperthyroidism ( These results indicate that the euthyroid state partially reduces hyperthyroidism-associated osteopenia, with a bone mass recovery period during the 6–9 early months of effective treatment. This recovery phase is characterized by raised bone formation markers and reduced bone resorption markers. The treatment with nasal CT at the doses assayed has no additional effect over that of attainment of the euthyroid state.

OBJECTIVE The effect of hyperthyroidism on osteoporosis risk and its reversal after control of hyperthyroidism remains somewhat controversial. We assessed the values of bone mineral density in hyperthyroid patients and in former hyperthyroid patients euthyroid on medical therapy, as well as the influence of aetiology and menopause upon bone mass. DESIGN The values of bone mineral density in hyperthyroid patients (active) and former hyperthyroid patients euthyroid on medical therapy (controlled), were compared, together with data from our control group and from the Spanish reference population. We also compared the values of bone mineral density in patients with Graves' disease with those in patients with toxic nodular goitre and assessed the influence of the menopause. PATIENTS We studied 127 consecutive hyperthyroid patients (age 41 ± 16 years; 110 females, 17 males; 102 Graves' disease and 25 toxic nodular goitre); 78 were active (group A) and 49 controlled on medical therapy (carbimazole, mean time of euthyroidism 7.5 ± 9.1 months; group B). We also studied 43 healthy subjects (age 40 ± 14 years; 41 females, two males; group C). MEASUREMENTS Bone mineral density was assessed by dual X-ray absorptiometry at lumbar spine (L2–L4), femoral neck and Ward's triangle. Data were expressed as g/cm2 and as a Z score (SD vs Spanish reference population adjusted by age and sex). Blood was obtained to measure the levels of free T4, TSH and TSH receptor antibody. RESULTS Patients with active hyperthyroidism showed a generalized reduction in axial bone mineral density in comparison with both the control group and the reference population, whereas former hyperthyroid patients showed partial recovery of bone mass in lumbar spine and Ward's triangle. Mean Z scores at lumbar spine, femoral neck and Ward's triangle were: −0.92, −0.79 and −0.89 in group A; −0.74, −0.23 and −0.44 in group B and 0.18, 0.09 and 0.36 in group C, respectively. No differences were found between bone mineral density values from patients with Graves' disease and those with toxic nodular goitre, nor between pre- and postmenopausal hyperthyroid women once adjusted by age and sex. CONCLUSIONS Our data suggest that hyperthyroid patients show a generalized reduction of bone mass in the axial skeleton and that only partial recovery is present in former hyperthyroid patients after a mean of 7.5 months of biochemical euthyroidism. This recovery is insufficient to normalize the bone density in lumbar spine and Ward's triangle, although femoral bone mass was not different from that of the control group. The extent and degree of hyperthyroid bone disease surpass the effects of the menopause on the bone mass. The aetiology of hyperthyroidism does not seem to play any role in the severity of hyperthyroid bone disease.