Effect of Masked Hypertension on Aortic Elastic Properties

Aortic stiffness is increased in patients with sustained hypertension (SH). The aim of this study was to investigate the relationship between aortic elastic properties and masked hypertension (MH). We evaluated aortic elastic properties in 35 individuals with MH, 35 patients with SH, and 35 normotensive healthy volunteers using transthoracic Doppler echocardiography. All aortic distensibility values were carried out at the same time or immediately after the blood pressure (BP) measurement. Baseline clinical and demographic characteristics of the patients were similar in all three groups. Aortic stiffness index and elastic modulus values were higher in MH group compared to SH group and control group (8.9 ± 6.3 vs. 5.4 ± 2.2 vs. 4.2 ± 2.5, P < .001 and 9.0 ± 6.3 vs. 6.4 ± 2.5 vs. 4.1 ± 2.4, P < .001, respectively). Aortic strain values were lower in MH group compared to SH group and control group (7.4 ± 5.3 vs. 9.5 ± 4.1 vs. 14.6 ± 7.1, P < .001, respectively). Aortic distensibility values were lower in MH and SH groups compared to controls (3.1 ± 1.9 vs. 3.7 ± 1.6 vs. 6.4 ± 3.4, P < .001, respectively). Furthermore, diastolic aortic diameter, left ventricular mass index, interventricular septum, and posterior wall thickness were higher in MH and SH groups when compared to controls. This study shows that masked hypertensive patients are at higher risk of “aortic” stiffness, a risk factor for cardiovascular morbidity and mortality, than normotensive and sustained hypertensive patients.     

Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults*

OBJECTIVES The role of growth hormone in maintaining normal body composition and bone strength In adults has attracted much interest recently. We have assessed body composition and bone mass in GH deficient hypopituitary adults on conventional replacement therapy and compared them with matched controls. DESIGN AND SUBJECTS A cross-sectional Study Of 64 growth hormone deficient hypopituitary adults (29 males and 35 females) on conventional replacement therapy and a large number of healthy control subjects matched for age, sex and body mass index (BMI). MEASUREMENTS Skinfold thicknesses at two sites (triceps and subscapular), waist and hip girth circumferences were assessed by standard methods. Body composition was assessed using total body potassium (TBK), bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA). Bone mineral mass was assessed at the lumbar spine and the total body by DEXA. Not every patient and control participated In every measurement. RESULTS Obesity was common in the hypopituitary patients; BMI (mean±SD) was 27·5 ± 4·6 kg/m² and body weight was 111·8 ±185% of the maximal ideal for height (P< 0·001). The sum of subscapular and triceps skinfolds was significantly higher in hypopituitary patients than in controls (men 46+15 vs 37±14mm, P<0·05; women 55±13 vs 47±17mm, P<0·05). Waist to hip circumference ratio was significantly greater In female hypopituitary patients than in matched controls but was not significantly different in men (men 0·94± 0·07 vs 0·91 ± 0·07, NS; women 0·84±0·09 vs 0·77±0·05, P < 0·001). The difference between patients and controls in the sum of skinfolds and the waist to hip ratio were present In non-obese (BMI < 26 kg/m²) subjects (21 patients and 32 controls). TBK corrected for body weight was significantly lower In hypopituitary patients (n= 44) than in controls (n= 31) (men 43·±5.6 vs 50·1 ± 5·9 mmollkg, P < 0·003; women: 34·0 ± 3.2 vs 40·6 ± 5·3 mmol/kg, P < 0.0001). BIA-derived body water content (corrected for body weight) was significantly lower In hypopituitary patients (n= 56) than in controls (n= 57) (0·492 ± 0·064 vs 0·545 ± 0·067 1/kg, P < 0.0004). Percentage body fat derived from ail the three methods was significantly higher in hypopituitary patients than in normal controls In both sexes (from TBK men 34·7 ± 94 vs 28·8 ± 7·0%, P < 0·05; women 37·8 ± 8·7 vs 30·4 ± 9·7%, P < 0·01; from BIA men 29·3 ± 8·5 vs 23·2 ± 8·4%, P < 0·01; women 34·6 ± 8.1 vs 29·3 ± 9·1%P < 0·01; and from DEXA: men 24·8 ± 6·8 vs 20·4 ± 6·1 %, P < 0·05; women 38·9 ± 7·9 vs 32·5 ± 9·8%, P < 0·01). There was a significant difference between non-obese patients and controls in BIA-derived percentage fat in both sexes and in TBK-derived percentage fat In females only. Bone mineral density (BMD) of the lumbar spine in the L2-L4 region was lower in hypopituitary patients than in controls (men 1·116±0·129 vs 1·311 ± 0·131 g/cm², P <0·0001; women 1·001 ±0·122 vs 1·131 ±0·138g/cm², P < 0·001). Spine BMD was also reduced in hypopituitary patients compared to the young adult and age and weight matched reference data. Total body BMD was significantly lower in patients than In controls (men 1·186 ± 0·102 vs 1·250 ± 0·080 g/cm², P < 0·05; women 1·080 ± 0·077 vs 1·149 ± 0·073 g/cm², P < 0·005). CONCLUSIONS Hypopituitary adults on conventional therapy have abnormal body composition with increased fat content, reduced body water content and reduced bone mineral mass     

Determinants of low-quality warfarin anticoagulation in patients with mechanical prosthetic heart valves. The nationwide PLECTRUM study

Quality of warfarin therapy in patients with a mechanical prosthetic heart valve (MPHV) has been barely investigated. We analysed determinants of low time in the therapeutic range (TiTR <60%) in 2111 patients with MPHVs from the nationwide PLECTRUM study by the Italian Federation of Anticoagulation Clinics. Overall, 48·5% of patients had a TiTR of < 60%. At logistic regression analysis, arterial hypertension (odds ratio [OR] 1·502, P < 0·001), diabetes (OR 1·732, P < 0·001), heart failure (OR 1·484, P = 0·004), mitral site (vs. aortic) (OR 1·399, P = 0·006), international normalised ratio (INR) ranges of 2·5–3·5 (OR 2·575, P < 0·001) and 3·0–4·0 (OR 8·215, P < 0·001) associated with TiTR < 60%. TiTR is substantially suboptimal in MPHV patients, particularly in higher INR ranges.     

Dose‐dependent acute effects of recombinant human TSH (rhTSH) on thyroid size and function: comparison of 0·1, 0·3 and 0·9 mg of rhTSH

Context Recombinant human TSH (rhTSH) is used to augment the effect of radioiodine therapy for nontoxic multinodular goitre. Reports of acute thyroid swelling and hyperthyroidism warrant safety studies evaluating whether these side‐effects are dose dependent. Objective To determine the effects on thyroid size and function of various doses of rhTSH. Design In nine healthy male volunteers, the effect of placebo, 0·1, 0·3 and 0·9 mg of rhTSH was examined in a paired design including four consecutive study rounds. Main outcome measures Main outcome measures were evaluated at baseline, 24 h, 48 h, 96 h, 7 days and 28 days after rhTSH and included: Thyroid volume (TV) estimation by planimetric ultrasound, and thyroid function by serum TSH, free T3, free T4 and Tg levels. Results Following placebo or 0·1 mg rhTSH, the TV did not change significantly from baseline at any time. At 24 and 48 h after administration of 0·3 mg rhTSH, the TV increased by 37·4 ± 12·3% (SEM) (P = 0·03) and 45·3 ± 16·1% (P = 0·05) respectively. After 0·9 mg rhTSH, the TV increased by 23·3 ± 5·8% (P = 0·008) and 35·5 ± 18·4% (P = 0·02) respectively. The increase in serum FT3, FT4 and thyroglobulin (Tg) was greater when administering 0·3 mg compared with 0·1 mg (P = 0·02) and when administering 0·9 mg compared with 0·3 mg (P = 0·02). After 0·1 mg rhTSH, the increase in FT3 and Tg was not significantly different from placebo whereas the FT4 increase was significantly higher (P = 0·02 compared with placebo). Conclusions In healthy individuals, rhTSH‐induced thyroid swelling and hyperthyroidism is rapid and dose dependent. If valid for patients with goitre, our results suggest that these adverse effects are unlikely to be of clinical significance, following doses of rhTSH of 0·1 mg or less.     

Eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures

Objective Subclinical hypercortisolism (SH) is suggested to exert a deleterious effect on bone. This effect and the role of gonadal status in male subjects are not fully elucidated. We evaluated bone mineral density (BMD) and prevalence of vertebral fractures in eugonadal male subjects with adrenal incidentalomas (AI) and without SH. Design This 12‐month observational multicentre study was performed between January and December 2006 on inpatient basis in three referral Italian centres. Patients Eighty‐eight consecutive eugonadal male patients with AI and 90 matched control subjects were studied. Measurements All subjects underwent the determination of BMD by dual‐energy X‐ray absorptiometry at lumbar spine (LS) and femoral neck (FN), and spinal radiograph. In AI patients SH was diagnosed in the presence of two of the following: urinary free cortisol > 193·1 nmol/l, cortisol after 1 mg dexamethasone suppression test > 82·8 nmol/l, ACTH levels < 2·2 pmol/l. Results As compared to patients without SH (SH–, n = 66) and controls, patients with SH (SH+, n = 22) had lower BMD at LS (Z‐score: SH+, –1·04 ± 1·84; SH–, 0·19 ± 1·34, Controls 0·20 ± 1·28, P = 0·001 and FN (Z‐score: SH+, –0·63 ± 1·01; SH–, 0·01 ± 1·01, Controls 0·26 ± 1·06, P = 0·002) and higher prevalence of fractures (SH+, 72·7%; SH–, 21·2%, Controls 20·0%, P = 0·0001). Multivariable analyses showed that SH was associated to BMD at LS (β = –0·378, P = 0·0001) and vertebral fractures (OR = 7·81, 95% CI 1·96–31·17, P = 0·004). Conclusion In eugonadal male patients with AI, SH is associated with low BMD and high prevalence of vertebral fractures.     

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004–2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51–9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24–9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47–60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01–40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.     

Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese

Objective Thyroid dysfunction commonly occurs in the elderly population and overt thyroid dysfunction is associated with some liver abnormalities. This study aimed to investigate the association of thyroid function with nonalcoholic fatty liver disease (NAFLD) in euthyroid elderly Chinese. Methods A cross‐sectional study was performed among 878 euthyroid elderly Chinese who took their annual healthy examination at Zhenhai Lianhua Hospital, Ningbo, China. Results A total of 227 (25·85%) subjects fulfilled the diagnostic criteria of NAFLD. Patients with NAFLD had significantly lower levels of serum‐free thyroxine (FT4) than controls (11·12 ± 1·43 vs 11·58 ± 1·47 pmol/l; P < 0·001). The prevalence rate of NAFLD decreased along with progressively higher serum FT4 levels (P for trend < 0·001). Age, gender and smoking status–adjusted correlation analysis showed that serum FT4 level was negatively correlated with body mass index, waist circumference, triglyceride and serum uric acid levels (All with P < 0·05). Stepwise logistic regression analysis showed that serum FT4 level was significantly associated with the risk for NAFLD [odds ratio (OR): 0·847, 95% confidence interval (CI): 0·743 – 0·966; P = 0·013]. Conclusion Our findings suggest that thyroid function, even within the reference range, is associated with NAFLD in elderly Chinese.     

Glucose homeostasis in patients with acromegaly treated with surgery or somatostatin analogues

Objective Long‐acting somatostatin analogues (SSA) are widely used for the treatment of acromegaly; however, they also alter β‐cell function by inhibiting insulin secretion. In this study, we assess the effect of SSA on glucose homeostasis in patients with acromegaly treated with SSAs, compared to patients treated with surgery. Design We studied four groups of patients with acromegaly: at the time of diagnosis (group I, n = 53), after successful transsphenoidal surgery (TSS, group II, n = 30) and under successful SSA treatment (group III, n = 20); 22 patients were studied only before treatment, 19 only post‐treatment, while 31 patients (group IV) were studied before and after the treatment. Measurements Patients underwent an oral glucose tolerance test. Insulin sensitivity and β‐cell insulin secretion were estimated using appropriate mathematical models. Results Control of acromegaly with either TSS or SSA improved insulin sensitivity as evident by significantly lower fasting and postglucose insulin levels and HOMA‐IR. In addition, patients of group III compared to patients of group II demonstrated significantly lower HOMA‐β% (52·5 ± 10·9 vs 189·6 ± 86·7, P < 0·05) and lower first and second phase insulin release (443 ± 83·5 vs 1077 ± 140·8, P < 0·05 and 150 ± 18·2 vs 285 ± 33·3, P < 0·05), respectively. Also, lower fasting glucose levels and a lower prevalence of diabetes were noted in group II compared to group III (5·1 ± 0·2 vs 6·2 ± 0·2 mm , P < 0·05, and 13·3%vs 40%, P < 0·0031, respectively). Conclusions Control of acromegaly with SSA seems to exhibit a negative effect on pancreatic β‐cell function. Whether this has long‐term clinical implications remains to be established. Nevertheless, careful monitoring of glucose metabolism in patients under SSA is beneficial for their optimal management.     

The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism*

OBJECTIVE The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with blosynthetic human GH in hypopituitary adults on aspects of calcium homeostatis, bone metabolism and bone mineral mass. PATIENTS Forty hypopituitary adults (21 females and 19 males; aged 19–67 years). DESIGN A prospective randomized double-blind placebo-controlled trial lasting for 6 months. PROTOCOL Following baseline assessments, GH was given in a daily dose of 0·02–0·05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. MEASUREMENTS Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. RESULTS Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I Increased significantly on GH treatment (mean ± SD) (GH: 276 ± 197 vs P: 88 ± 50 μg/l, P < 0 0001 at 6 months). Plasma calcium increased slightly but significantly in the GH-treated group (2·23 ± 0·11–2·29 ± 0·11 mmol/l, P<0·05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2·29 ± 0·11; P, 2·26 ± 0·09 mmol/l). Plasma phosphate increased on GH (GH: 1·02±0·23–1·32±0·19; P: 0·99±0·16–0·96±0·12 mmol/l over the 6 months of treatment, P<0·001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104±32 vs P: 69±32 U/I, P<0·01, osteocalcin: GH: 17·2±8·0 vs P: 5·3±3·2 μg/l, P<0·001 and P1CP: GH: 207 ± 152 vs P: 93±31 μg/l, P<0·01). There was no difference in the intact parathyroid hormone level (GH: 31 ± 14 vs P:31 ± 15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. CONCLUSION In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.     

Alterations in thyroid function tests in aged hospitalized patients: prevalence, aetiology and clinical outcome

Background Thyroid dysfunction is common in aged people and has recently been associated to mortality. Aims Our aims have been (1) to assess the prevalence of alterations in thyroid function tests in hospitalized patients over age 60 years and (2) to study the relationship between thyroid functional status and mortality during hospitalization. Methods We studied a group of 447 patients (62% women), aged 61–101 year, hospitalized during 2005. Thyroid dysfunction was assessed by measuring serum concentrations of thyrotrophin (TSH), free thyroxine (FT4), and free thriiodothyronine (FT3). Thyroid autoimmune status was evaluated through thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies quantification. Results Twenty‐one patients (4·7%, 19 women) showed previously known thyroid dysfunction. 332 patients (74·3%) showed alterations in thyroid function tests. Euthyroid sick syndrome (ESS) was the derangement more frequently found (n = 278, 62·2%). After excluding ESS patients, 60 patients (13·4%) showed thyroid dysfunction: overt hypothyroidism, 14 (3·1%); subclinical hypothyroidism, 25 (5·6%); overt hyperthyroidism, 11 (2·5%), and subclinical hyperthyroidism, 10 patients (2·2%). Thyroid autoimmunity was positive in only 4·0% and 2·3% of patients, for TPOAb and TgAb, respectively. The presence of alterations in thyroid function tests was positively associated with the age of the patients and mortality during hospital stay (P < 0·001). Serum levels of FT3 were negatively related to death during hospitalization (OR 0·56; CI 95%, 0·38–0·81; P < 0·01). Conclusions About three quarters of patients admitted in our geriatric unit exhibited alterations in thyroid function tests. This finding was associated with elevated age and poor prognosis. The reduction of FT3 values was a powerful predictor for mortality during hospitalization in elderly patients.     

Menstrual disturbances in thyrotoxicosis *

OBJECTIVES In thyroid textbooks it is stated that hyperthyroidism in women may be associated in almost 50% of the cases with hypomenorrhoea, oligomenorrhoea or amenorrhoea and perhaps with reduced fertility. Our experience at a busy thyroid clinic has given a picture which differs from that described in the literature. Most of our female thyrotoxic patients had normal menstruation. This study was performed to define the menstrual abnormalities in hyperthyroidism. DESIGN AND PATIENTS We investigated the menstrual history, starting 6 months before the discovery of the disease, the smoking habits and the body mass index (BMI), in 214 female, premenopausal thyrotoxic patients and a similar number of normal controls matched for age and weight. MEASUREMENTS TT4 and TT3 were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m^2. RESULTS Of the 214 patients, 168 (78·5%) had regular menstrual cycles and 46 (21·5%) irregular cycles. No difference in BMI was found between the patients with or without menstrual abnormalities. Out of the 46 patients with irregular periods, 23 (50%) were smokers, while only 32 out of the 168 patients (19%) with normal periods were smokers (P < 0·001). TT4 levels were higher as a group in patients with menstrual disturbances (mean±SD 267·7 ± 66·9 nmol/1) than in those with normal periods (240·6 ± 47·6 nmol/1) (P < 0·05). The 23 smokers with irregular periods had higher TT4 levels (280·5 ± 51·8 nmol/1) than the remaining non-smokers from the same group (241·9 ± 43·7 nmol/1) (P < 0·01). No such differences were found for TT3 levels. Out of 214 normal controls, matched for age and weight, 196 (91·6%) had normal menstruation and 18 (8·4%) irregular cycles. The latter group included mainly women with oligomenorrhoea. Out of 18 normal controls with irregular periods, 6 (33·3%) were smokers, while 57 (29·1%) out of 196 with normal periods were smokers. CONCLUSIONS These data demonstrate that hyperthyroidism in women is less frequently associated with menstrual abnormalities than was previously believed. Furthermore, no patient presented with amenorrhoea. Smoking and TT4 levels are strongly associated with the occurrence of menstrual disturbances in thyrotoxicosis.     

THYROXINE AND TRIIODOTHYRONINE LEVELS IN THYROID VEIN BLOOD AND IN THYROID TISSUE OF PATIENTS WITH AUTONOMOUS ADENOMAS

Thyroxine (T4) and triiodothyronine (T3) concentrations were measured in peripheral and thyroid vein blood and in nodular and extranodular thyroid tissue from twenty-four patients with autonomous thyroid nodules (AFTN); fifteen of these patients showed clinical signs of hyperthyroidism and nine were euthyroid. Thirteen patients with solitary non-functioning thyroid adenomas who were clinically euthyroid, served as controls; samples of thyroid vein blood and normal thyroid tissue being obtained from the contralateral lobe. T4 (189·4 ± 27·2 nmol/l) and T3 (7·05 ± 2·03 nmol/l) concentrations were significantly higher in the thyroid vein blood of patients with AFTN compared with controls (T4 = 119 ± 9·1 nmol/l, P < 0·05; T3 = 2·3 ± 0·21 nmol/l, P < 0·01) whereas peripheral levels in the two groups were similar. The T3 concentrations (10·56 ± 4·12 nmol/g wet tissue) in autonomously-functioning thyroid nodular tissue were significantly higher than those of extranodular (1·9 ± 0·62 nmol/g wet tissue, P < 0·01) and normal thyroid tissue (2·63 ± 0·43 nmol/g wet tissue, P < 0·05). The T4 levels were not different in the tissues examined. The concentrations of T4 and T3 in thyroid vein blood did not show any significant correlation with the hormone levels in thyroid tissue.     

NOCTURNAL NATRIURESIS IN HYPERTHYROIDISM

We measured urine flow and the renal excretion of total solute, sodium, potassium and calcium in eleven patients with hyperthyroidism before and after treatment. Mean nocturnal sodium excretion was significantly greater (P < 0·05) during hyperthyroidism and was unaccompanied by any significant alterations in day time or 24-h values. As a result of this nocturnal natriuresis in hyperthyroidism significant changes were noted in the ratios of day/night sodium excretion (P < 0·005) and urinary flow (P < 0·05). The change in ratio of day/night sodium excretion resulting from treatment of hyperthyroidism was shown to correlate significantly with the change in plasma total triiodothyronine (r=0·73, P < 0·01). Twenty-four hour urinary calcium output was significantly greater (P < 0·02) in hyperthyroidism but there was no significant alteration in the day/night pattern of excretion.     

Increased oxidized low density lipoprotein associated with high ceruloplasmin activity in patients with active acromegaly

Objective Active acromegaly is associated with increased mortality from cardiovascular causes. Several studies have shown increased atherogenic risk factors and biomarkers of inflammation and atherosclerosis in association with growth hormone excess. The aim of this study was to evaluate oxidized low density lipoprotein (oxLDL) levels and some modulators of LDL oxidative modification in patients with acromegaly. Design Open transversal study. Patients Fifteen patients with active acromegaly and 15 controls were studied. Measurements We evaluated the levels of oxLDL, thiobarbituric acid reactive substances (TBARS), ceruloplasmin, bilirubin, uric acid and total reactive antioxidant potential, and the activities of ceruloplasmin, myeloperoxidase, superoxide distmutase, paraoxonase 1, and platelet activating factor acethylhydrolase. Statistical analysis was performed including body mass index as a covariate or as a fixed variable. Results Patients with acromegaly showed significantly higher levels of oxLDL (120 ± 19 vs. 86 ± 20 U/l, P < 0·001) and endothelin (P < 0·05), increased ceruloplasmin activity (P < 0·01) and a trend towards higher values in TBARS concentration (P = 0·07) in comparison to healthy controls. OxLDL was positively associated with GH, IGF‐I and its binding protein 3 (r = 0·63, P < 0·001; r = 0·53, P < 0·01; and r = 0·56, P < 0·01; respectively). OxLDL showed direct associations with endothelin‐1 (r = 0·53, P < 0·01) and ceruloplasmin activity (r = 0·43, P < 0·05). The other parameters evaluated were similar in both groups. Conclusions The increase in plasma oxLDL levels, a direct marker of the plaque formation, could constitute a link between atherosclerosis and active acromegaly. LDL oxidation would not be the consequence of diminished antioxidant defences, but of an enhancement in prooxidant factors like ceruloplasmin.     

Plasma soluble tumour necrosis factor‐α receptor 2 is elevated in obesity: specific contribution of visceral adiposity

Objective We examined the obesity phenotype most strongly associated with increased plasma concentrations of sTNFR2, and compared which of the two markers, TNF‐α or sTNFR2, better predicts indices of plasma glucose‐insulin homeostasis. Design, patients and measurements Plasma sTNFR2 levels were measured in a sample of 287 healthy nondiabetic men [age: 43·9 ± 8·0 years (mean ± SD)], covering a wide range of adiposity values (BMI: 29·0 ± 4·4 kg/m²; waist girth: 100·0 ± 11·7 cm). Results Plasma sTNFR2 levels correlated positively and significantly with BMI (r = 0·36; P < 0·0001), fat mass (r = 0·42; P < 0·0001), waist girth (r = 0·38; P < 0·0001) as well as with visceral (r = 0·37; P < 0·0001) and subcutaneous adipose tissue (AT) (r = 0·40; P < 0·0001) areas measured by computed tomography. Two subgroups (n = 27 in each group) of overweight men (BMI ≥25 kg/m²) were individually matched for similar BMI values, but with markedly different levels of visceral AT (< or ≥130 cm²) and then compared with a control group of 46 lean subjects (with both BMI <25 kg/m² and visceral AT <130 cm²). This analysis revealed that men characterized by high levels of visceral AT had significantly higher concentrations of sTNFR2 compared with obese men with low visceral AT (1861 ± 457 pg/ml vs. 1722 ± 400; P < 0·05) and with lean controls (1570 ± 291 pg/ml; P < 0·001). Whereas subjects classified across tertiles of TNF‐α levels showed no difference in glucose tolerance and insulin levels, subjects in the upper tertile of plasma sTNFR2 levels were characterized with the highest plasma insulin concentrations during the OGTT and had the highest area under the curve of insulin concentrations. Conclusions These results indicate that sTNFR2 levels are more closely related to abdominal AT accumulation than to total adiposity. Furthermore, plasma concentrations of sTNFR2 are independently related to plasma glucose‐insulin homeostasis beyond the known contribution of visceral adiposity.     

Carotid intima‐media thickness is increased in Turner syndrome: multifactorial pathogenesis depending on age,blood pressure,cholesterol and oestrogen treatment

Objective Carotid intima‐media thickness (IMT) may potentially supplement cardiovascular risk assessment in Turner syndrome (TS), where cardiovascular risk is high and appropriate risk stratification difficult. Knowledge of IMT in TS is scarce, and this study aimed to enhance insight into the cardiovascular risk marker. Design, Patients and Measurements IMT was cross‐sectionally assessed by ultrasonography of the common carotid artery (cIMT) and carotid bulb (bIMT) in TS (n = 69, age 40 ± 10 years) and age‐matched, healthy female controls (n = 67). Additional prospective IMT assessment was performed in TS over 2·4 ± 0·3 years. Metabolic biomarkers and 24‐h ambulatory blood pressure were also assessed. Results cIMT and bIMT (body surface area indexed) were increased in TS (P < 0·05) with 17–18% having IMTs that exceeded the 95th percentile of the controls (P < 0·05). Blood pressure, heart rate, glycosylated haemoglobin A1c and high‐density lipoprotein cholesterol were increased in TS, where 43% received antihypertensive treatment. cIMT decreased during follow‐up, coinciding with intensified cardiovascular risk prophylaxis, whereas bIMT was unchanged. In multiple regression analyses (R = 0·52–0·69, P < 0·05), baseline IMT in TS increased with age, blood pressure and cholesterol as well as in the presence of diabetes whilst IMT was inversely associated with duration of oestrogen replacement. In an analogue analysis, the prospective changes in cIMT (R = 0·37, P < 0·05) were beneficially influenced by antihypertensive treatment and oestrogen therapy and adversely by the presence of diabetes. Conclusion Carotid IMT was abnormal in TS and negatively influenced by age, metabolic biomarkers, blood pressure and short duration of oestrogen treatment. Attention to common cardiovascular and endocrine risk markers over more than 2 years appeared to influence IMT beneficially.     

Benefit of short‐term iodide supplementation to antithyroid drug treatment of thyrotoxicosis due to Graves’ disease

Objective Combined treatment with anti‐thyroid drugs (ATDs) and potassium iodide (KI) has been used only for severe thyrotoxicosis or as a pretreatment before urgent thyroidectomy in patients with Graves’ disease. We compared methimazole (MMI) treatment with MMI + KI treatment in terms of rapid normalization of thyroid hormones during the early phase and examined the later induction of disease remission. Design and patients A total of 134 untreated patients with Graves’ disease were randomly assigned to one of four regimens: Group 1, MMI 30 mg; Group 2, MMI 30 mg + KI; Group 3, MMI 15 mg and Group 4, MMI 15 mg + KI. For easy handling, KI tablets were used instead of saturated solution of KI. KI was discontinued when patients showed normal free thyroxine (FT4) levels but MMI was continued with a tapering dosage until remission. Remission rate was examined during a 4‐ to 5‐year observation. Measurements Serum FT4, FT3 and TSH were measured by chemiluminescent immunoassays. TSH receptor antibody (TRAb) was assayed with TRAb‐ELISA. Goitre size was estimated by ultrasonography. Results After 2 weeks of treatment, normal FT4 was observed in 29% of patients in Group 1 and 59% (P < 0·05) of patients in Group 2. Furthermore, normal FT4 after 2 weeks of treatment was observed in 27% of patients in Group 3 and 54% (P < 0·05) of patients in Group 4. Similarly, FT3 normalized more rapidly in Groups 2 and 4 than in Groups 1 and 3. None of the patients showed an increase in thyroid hormones or aggravation of disease during combined treatment with MMI and KI. The remission rates in Groups 1, 2, 3 and 4 were 34%, 44%, 33% and 51%, respectively, and were higher in the groups receiving combined therapy but differences among four groups did not reach significance. Conclusions Combined treatment with MMI and KI improved the short‐term control of Graves’ hyperthyroidism and was not associated with worsening hyperthyroidism or induction of thionamide resistance.     

A randomized placebo‐controlled clinical trial of the effectiveness of thyroxine and triiodothyronine and short‐term exposure to bright light in prevention of decrements in cognitive performance and mood during prolonged Antarctic residence

Objective We examined the effects of a combined levothyroxine/liothyronine supplement and exposure to bright (10,000 lux) light in euthyroid men and women who spent the austral summer (n = 43) and/or winter (n = 42) in Antarctica. Methods Subjects were randomized to receive 64 nmol of levothyroxine and 16 nmol of liothyronine supplement or a placebo capsule for 93·2 ± 3·0 days in summer and/or 149·5 ± 2·2 days in winter. Subjects were further randomized to receive 10,000 lux bright white light or 50 lux dim red light for 14 days at the end of summer and/or winter. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric – Isolated and Confined Environments. Results In winter, bright light exposure was associated with a significantly greater reduction in TSH and anger (P < 0·05), a significantly greater increase in fT₃ (P < 0·05), and a significantly smaller increase in depressive symptoms (P < 0·001), when compared with dim light. The T4/T3 supplement also led to a significantly greater reduction in TSH (P < 0·05), but a greater reduction in cognitive task efficiency (P < 0·05) as well, when compared with placebo. Conclusion Administration of bright light leads to a significant reduction in serum TSH and prevents increases in anger and depressive symptoms in winter. However, these associations were not observed in summer, suggesting a seasonal influence of photoperiod over temperature upon this intervention in the polar environment.     

ENDEMIC INFANTILE HYPOTHYROIDISM IN A SEVERE ENDEMIC GOITRE AREA OF CENTRAL AFRICA

Thyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goitre area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 ± 4 nmol/1) and stayed at that level during the first year of life (123 ± 9) (NS), but decreased to 75 ± 8 (P < 0·001) at 2–4 years and to 62 ± 6 (P < 0·001) at 5–7 years of age. Mean serum FT4 decreased from 10·4 ± 0·9 pmol/1 during the first year to 8·2 ± 1·0 (NS) at 2–4 years (NS) and to 7·7 ± 0·9 (P < 0·05) at 5–7 years. Mean serum TSH was 10·4 (8·4-12·9) m U/1 (geometric mean ± 1 SEM) during the first year, 10·1 (7·5-13·7) (NS) at 2–4 years and 24·3 (18·5–31·9) (P < 0·05) at 5–7 years. Mean serum T3 was 3·23 ± 0·12 nmol/1 during the first year and remained stable thereafter. The frequencies of low T4 (T4 < 77 nmol/1), high TSH TSH (TSH > 50 mU/1), and low T4 and T3 (T3 < 1·69 nmol/l) were twice as high at 5–7 years as in the first year (respectively 65%, 42% and 15%). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 ± 5 ?mol/1) decreased to normal values between 3 and 12 months of age and increased again during and after weaning (1 to 3 years of age) to reach a value of 138 ?mol/l which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 ± 7 ?mol/l) in the mothers' serum but low in the mothers' milk (57 ± 3 ?mol/1) (P < 0·01). Multivariate analysis     

How should we treat patients with low serum thyrotropin concentrations?

Subclinical hyperthyroidism (SH) is defined by a low serum thyrotropin (TSH) concentration in the presence of normal levels of free thyroxine (FT4) and free triiodothyronine (FT3). However, it is helpful to distinguish between those with a detectable but low TSH value (in the 0·1–0·4 mU/l range) and those with a fully suppressed TSH (<0·1 mU/l), and we suggest the designation of grade I and grade II SH, respectively. Together, these patterns of thyroid function tests are found in 1–3% of the elderly population, and are associated with significant morbidity and mortality in longitudinal epidemiological surveys. There are a number of causes for this picture, which include endogenous thyroid disease, drug effects and concomitant nonthyroidal illness. Treatments commonly employed in the management of thyrotoxicosis are effective at correcting the biochemical abnormalities of SH but have not been shown to improve clinical outcome or symptoms. There is little good quality evidence available to guide the assessment or management of these patients. This review summarizes the clinical significance of SH and aims to provide guidance about whether we should treat patients with low serum TSH concentrations.