Coexistence of Autoimmune Hyper- and Hypothyroidism in a Kindred with Reduced Sensitivity to Thyroid Hormone.

INTRODUCTION: Resistance to thyroid hormone beta (RTHß) is a rare disease with an autosomal dominant transmission. Diagnosis may be challenging especially in patients with hyper- or hypothyroidism. CASE PRESENTATION: A 31-year-old male patient with suppressed thyroid-stimulating hormone (TSH), elevated free thyroxine and free triiodothyronine, along with high thyroid receptor antibodies was diagnosed with Graves' disease. Benzylthiouracil was started. One month later, reduced sensitivity to thyroid hormones was suspected because of persistently high thyroid hormone levels contrasting with high TSH level. Molecular analysis highlighted a 10c.1357C>T p.P453S mutation in the thyroid hormone receptor beta gene (THRB). RTHß was diagnosed. Several relatives also had RTHß (the mother, the young son, and 2 out of 3 siblings). Autoimmune hypothyroidism was present in the mother, whereas 2 out of 3 siblings had asymptomatic autoimmunity. DISCUSSION/CONCLUSION: Both Graves' disease and autoimmune hypothyroidism were described in patients with RTHß. We show here for the first time that autoimmune hypo- and hyperthyroidism may coexist in kindred with RTHß. Seven previously published cases of Graves' disease and RTHß were retrieved and analyzed. Treatments and thyroid hormone level targets are discussed as well as the possible link between RTHß and autoimmune thyroid diseases.

Foetal exposure to mitotane/Op'DDD: Post-natal study of four children.

OBJECTIVE: Mitotane/Op'DDD is used in the treatment of adrenocortical carcinoma and for other causes of hypercortisolism. Mitotane inhibits cortisol secretion and displays adrenolytic and antitumor actions. This compound is a metabolite of the pesticide and endocrine disruptor DDT (dichlorodiphenyltrichloroethane) and is classified among teratogenic compounds worldwide. However, little is known about its effects on human development. DESIGN: The outcome of four children exposed to mitotane during their intrauterine life was examined. PATIENTS: Patients having conceived while taking mitotane, or with detectable mitotane plasma levels, were retrospectively recruited via the French COMETE and FIRENDO networks. MEASUREMENTS: Mitotane in maternal plasma, adrenocortical hormones in children. RESULTS: Three women treated with mitotane gave birth to four children. During early pregnancy, all patients had detectable mitotane plasma levels (0.9, 2.4 and 6.7 mg/L, respectively). During pregnancy, no foetal malformations were detected. The four exposed newborns presented at birth with apparently normal adrenal function and genitalia. One twin female had a low birthweight. Evaluation at birth and after 3 months, 2 years and 7 years of follow-up showed no significant neurological abnormality. Evaluation of adrenocortical functions showed no cortisol deficiency. CONCLUSIONS: Unexpectedly, exposure of these four children to mitotane during foetal life seemed to have no clear teratogenic effect. However, considering the sub-therapeutic mitotane concentrations used here, the small number of cases, and because long-term follow-up is unknown, we strongly advise not to take mitotane during pregnancy and still recommend avoiding pregnancy, at least as long as mitotane plasma levels remain detectable.

Antidiabetic treatment, stroke severity and outcome.

Ischemic stroke is a leading cause of mortality and long-term disability worldwide. Given the detrimental effects of acute stroke, several neuroprotective agents have been evaluated in these patients. However, the benefits of the evaluated agents appear to be limited and none is currently recommended for clinical use. On the other hand, prior treatment with agents that are used for the primary and secondary prevention of stroke, including statins and antiplatelets, has been associated with better outcome in patients who experience an acute stroke. In contrast, there are limited data as to whether prior treatment with antidiabetic agents is beneficial in diabetic patients who suffer a stroke. In this context, the findings of a recent study that showed reduced stroke size following pretreatment with linagliptin, a dipeptidyl peptidase-4 (DDP-4) inhibitor, compared with glimepiride, in both diabetic and non-diabetic mice, appear promising. Despite these preclinical findings suggesting neuroprotective effects of DPP-4 inhibitors in acute stroke, it is still unclear whether these actions will also be observed in humans. Of note, two recent large randomized, placebo-controlled studies did not show any effect of DPP-4 inhibitors on cardiovascular events, including stroke. Several other ongoing trials are evaluating the effects of DPP-4 inhibitors on cardiovascular morbidity and mortality. These studies also provide a major opportunity to assess whether patients treated with this class of antidiabetic agents will suffer from less severe strokes and whether their outcome after stroke will be more favorable.

Sex-specific differences in cardiovascular risk factors and blood pressure control in hypertensive patients.

Cardiovascular disease (CVD) and cardiovascular risk factors are frequently undertreated in women. However, it is unclear whether the prevalence of additional cardiovascular risk factors and the total cardiovascular risk differ between hypertensive men and women. There are also limited data regarding rates of blood pressure control in the two sexes outside the United States. The authors aimed to compare the cardiovascular risk profile between sexes. A total of 1810 hypertensive patients (40.4% men, age 56.5±13.5 years) attending the hypertension outpatient clinic of our department were studied. Men were more frequently smokers than women and were more heavy smokers than the latter. Serum high-density lipoprotein cholesterol levels were lower and serum triglyceride levels were higher in men. On the other hand, abdominal obesity and chronic kidney disease were more prevalent in women. The estimated cardiovascular risk was higher in men than in women but the prevalence of established CVD did not differ between the sexes. The percentage of patients with controlled hypertension and the number of antihypertensive medications were similar in men and women. In conclusion, hypertensive men have more adverse cardiovascular risk factor profile and greater estimated cardiovascular risk than women. However, the prevalence of established CVD does not differ between sexes. These findings further reinforce current guidelines that recommend that management of hypertension and of other cardiovascular risk factors should be as aggressive in women as in men in order to prevent cardiovascular events.

Prevalence of resistant hypertension in 1810 patients followed up in a specialized outpatient clinic and its association with the metabolic syndrome.

UNLABELLED: We aimed to assess the prevalence of resistant hypertension (RH) in patients attending hypertension outpatient clinics and to identify risk factors for RH. We studied the medical records of the last visit of all patients (n = 1810; 40.4% males, age 56.5 ± 13.5 years) who attended at least once our hypertension outpatient clinic during the last decade. RH was defined as blood pressure (BP) > 140/90 mmHg in patients without diabetes or chronic kidney disease (or BP > 130/80 mmHg in patients with the latter diseases) despite treatment with full doses of three antihypertensive agents from different classes or controlled BP on four or more different antihypertensive agents. The prevalence of RH was 12.3%, whereas 22.2% of the patients had well-controlled hypertension and 65.5% had uncontrolled hypertension but were on less than three antihypertensive agents. Independent predictors of RH were age (risk ratio, RR = 1.08, 95% confidence interval, CI 1.05-1.12, p < 0.001), body mass index (RR = 1.06, 95% CI 1.00-1.13, p < 0.05) and the presence of the metabolic syndrome (MetS) (RR = 2.01, 95% CI 1.03-3.91, p < 0.05). CONCLUSIONS: RH is frequent in patients followed up in hypertension outpatient clinics. In addition to age and obesity, MetS appears to be associated with increased risk for RH. Clarification of the mechanisms underpinning the association between MetS and hypertension might reduce the prevalence of RH.