Chiara Cosci

Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities and is believed to be due to increased thyroid hormone synthesis and release; Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone-induced destructive process of the thyroid. Management differs in the two forms of AIT, since Type 1 usually responds to combined thionamides and potassium perchlorate therapy, while Type 2 is generally responsive to glucocorticoids. Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and destructive phenomena, may require a combination of the two therapeutic regimens. In this cross-sectional prospective study, 55 consecutive untreated patients, whose AIT was subtyped according to clinical and biochemical criteria, were evaluated to assess the specificity of color flow doppler sonography (CFDS) and thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen patients (6 men, 10 women, age 66±13 yr), who had diffuse or nodular goiter with or without circulating thyroid autoantibodies, were classified as Type 1 AIT; 39 patients (27 men, 12 women, age 65±13 yr) with apparently normal thyroids were classified as Type 2 AIT. All Type 1 patients had normal or increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal or elevated thyroidal 3-h and 24-h RAIU values (range 6–37% and 10–58%, respectively), in spite of elevated values of urinary iodine excretion; the remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had low 3-h and 24-h RAIU values (range 1.1–3.0% and 0.9–4.0%, respectively). The latter patients, who were unresponsive to the combination of methimazole and potassium perchlorate, became euthyroid after the addition of glucocorticoids. Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4–3.7% and 0.2–3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU values (6% and 13%, respectively).In conclusion, CFDS can accurately distinguish between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus, assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and help in selecting the appropriate therapy. Finally, in long standing iodine sufficient areas, such as the United States, where the thyroid RAIU is consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and available method to differentiate between Type 1 and Type 2 AIT.

Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis

Background: Two main forms of amiodarone-induced thyrotoxicosis (AIT) exist: type 1 AIT is a condition of true hyperthyroidism developing in patients with pre-existing thyroid disorders, and usually requires thyroid ablative treatment. On the other hand, type 2 AIT is a form of destructive thyroiditis occurring in normal thyroids, the management of which usually consists in glucocorticoid treatment. Aim: To assess the long-term outcome of thyroid function in a prospective study of type 2 AIT patients, as compared to patients with De Quervain’s subacute thyroiditis (SAT). Patients and Methods: Sixty consecutive patients with type 2 AIT were evaluated during oral glucocorticoid treatment (oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month period) and followed for 38±4 months (range 6–72) thereafter. Sixty consecutive patients with SAT, referred to our Institutes during the same period and treated with the same therapeutic schedule, served as controls. Results: Type 2 AIT patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1 vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3) concentrations at diagnosis were increased in both conditions, but higher in type 2 AIT than in SAT (FT4 47.6±18.8 and 29.6±8.3 pmol/l, respectively, p<0.0001; FT3 15.4±7.0 and 11.2±3.0 pmol/l, respectively, p<0.001). Correction of thyrotoxicosis was obtained in all patients in both groups, but restoration of euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid after glucocorticoid withdrawal and required levothyroxine replacement. Conclusions: A relevant proportion of type 2 AIT patients develop permanent hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of thyroid status is required after type 2 AIT.

Iopanoic acid rapidly controls Type I amiodarone-induced thyrotoxicosis prior to thyroidectomy

Amiodarone-induced thyrotoxicosis (AIT) may develop either in apparently normal thyroid glands (Type II AIT) or in the presence of sub-clinical thyroid abnormalities (either autonomous goiter or latent Graves’ disease; Type I AIT). Mixed forms also occur. While Type I AIT is due to iodine-induced excess thyroid hormone synthesis, Type II AIT is a form of amiodarone (possibly iodine) -induced destructive thyroiditis. Type I AIT is usually treated by combined thionamide and potassium perchlorate therapy, but may be resistant to therapy. On the other hand, Type II AIT often responds favorably to glucocorticoids and may not require further therapy once euthyroidism has been restored. Not infrequently, however, AIT (especially Type I) is resistant to conventional treatment, and several weeks or months may elapse before euthyroidism is restored. Thyroidectomy has been carried out in Type I AIT patients, but thyroid surgery in thyrotoxic patients, especially those with underlying cardiac problems, carries a high surgical risk. In this study we describe 3 patients with Type I AIT, who were successfully treated with a short course of iopanoic acid (IOP), an oral cholecystographic agent, which is rich in iodine and is a potent inhibitor of 5′-deiodinase, resulting in a marked decrease in the peripheral tissue conversion of T4 to T3, in preparation for thyroid surgery. Euthyroidism was rapidly restored in 7–12 days, allowing a subsequent safe and uneventful thyroidectomy in all cases. These patients were then treated with L-T4 for their hypothyroidism and amiodarone was safely re-instituted. We suggest that IOP is the drug of choice in the rapid restoration of euthyroidism prior to definitive thyroidectomy in patients with drug resistant Type I AIT.

Improvement of intrinsic myocardial contractility and cardiac fibrosis degree in acromegalic patients treated with somatostatin analogues: a prospective study

Background Acromegalic patients have increased left ventricular (LV) mass (M) and impaired diastolic function.

Short- and long-term changes of quality of life in patients with acromegaly: Results from a prospective study

Quality of life (QoL) may be affected in acromegalic patients, although the role of disease activity is still unsettled. The aim of the study was to assess the QoL of acromegalic patients with a specific questionnaire (ACROQOL). ACROQOL was evaluated in a prospective study (at baseline, at 6 and 24 months) in 23 active untreated acromegalic patients. Control of acromegaly was defined by normal age-matched serum IGF-I concentrations. Patient groups were defined as controlled or uncontrolled at 6 months and at 24 months: controlled or uncontrolled during the entire study period (ACROCC or ACRONC, respectively) or uncontrolled at 6 months and controlled thereafter (ACROC). At 6 months, ACROQOL scores improved globally (from 54.3±21 to 65.1±19, p=0.04) as did subdomains and were inversely related to IGF-I variation (r=−0.50, p=0.052). At 24 months, ACROQOL improved globally (from 54.3±21 to 65.7±18.0, p=0.04) and this was also seen in the appearance subdomains; however, no correlation was revealed between variation of serum IGF-I concentrations and changes in ACROQOL total score (r=0.008, p=0.87). ACROQOL scores did not significantly change in ACRONC (p=0.310) and in ACROC (p=0.583), whereas it improved globally (from 42.1±22.1 to 58.8±16.04, p=0.021) and in psychological subdomains in ACROCC; however, it reflected the improvement occurred within the first 6 months of disease control. In conclusion, successful treatment, which normalizes disease activity, improves QoL in acromegaly in the short term. However, the lack of correlation between the ACROQOL score in the long term might suggest that factors other than serum IGF-I participate in the well-being of acromegalic patients; however, due to the small sample size, our results need to be confirmed in larger studies.

A novel mutation in the pendrin gene associated with Pendred's syndrome

Pendreds syndrome is an autosomal recessive disorder characterized by goitre, sensorineural deafness and iodide organification defect. It is one of the most frequent causes of congenital deafness, accounting for about 10% of hereditary hearing loss. It is caused by mutations in the pendrin (PDS) gene, a 21 exon gene located on chromosome 7. The aim of this study was to examine an Italian family affected with Pendreds syndrome at the molecular level.

High prevalence of cardiac hypertophy without detectable signs of fibrosis in patients with untreated active acromegaly: an in vivo study using magnetic resonance imaging

Objective  Left ventricular (LV) hypertrophy and myocardial fibrosis are considered the main pathological features of acromegalic cardiomyopathy. The aim of the study was to evaluate the proportion of LV hypertrophy and the presence of fibrosis in acromegalic cardiomyopathy in vivo using cardiac magnetic resonance (CMR).

Peroxisome proliferator-activated receptor (PPAR)γ is highly expressed in normal human pituitary gland

Objective: Expression of peroxisome proliferator-activated receptor (PPAR)γ in normal pituitary seems to be restricted to ACTH-secreting cells. The aim of the study was to evaluate the expression of PPARγ in normal human pituitary tissue and to study its localization in the pituitary secreting cells. Materials and methods: Normal pituitary tissue samples were obtained form 11 patients with non-secreting adenoma who underwent surgical excision of the tumor. Expression of PPAR? was evaluated by immunostaining and western blotting; localization of PPAR? in each pituitary secreting cell lineage was evaluated by double immunofluorescence using confocal microscopy. Pituitary non-functioning adenomas served as Controls. Results: PPARγ was highly expressed in all pituitary samples with a (mean±SD) 81±6.5% of stained cells; expression of PPARγ was confirmed by western blotting. Non-functioning pituitary adenomas had 74±11% PPAR? positive cells. Expression of PPARγ was either in cytoplasm or nuclei. In addition, treatment of GH3 cells, with a PPARγ ligand was associated with traslocation of the receptor from cytoplasm into the nucleus. Double immunostaining revealed that every pituitary secreting cell (GH, TSH, LH, FSH, PRL and ACTH) had PPARγ expressed. Discussion: The present study demonstrated that PPARγ is highly expressed in every normal pituitary secreting cell lineage. It can translocate into the nucleus by ligand binding; however, its role in pituitary hormone regulation remains to be elucidated.

Apoptosis is reduced in the colonic mucosa of patients with acromegaly.

Background  Patients with acromegaly have an increased risk of developing colonic tumours; reduced apoptosis is considered a leading mechanism in tumorigenesis. GH and IGF‐1 decrease apoptosis in several cell lines including human colonic adenocarcinoma, but it is unknown whether epithelial cells of colonic mucosa of patients with acromegaly have reduced apoptosis.

Effects of somatostatin analogues on acromegalic cardiomyopathy: Results from a prospective study using cardiac magnetic resonance

Objective: Left ventricular (LV) hypertrophy is the main finding of patients with active acromegaly at cardiac magnetic resonance (CMR). The aim of the study was to evaluate heart changes in acromegalic patients treated with somatostatin analogues (SMSA) using CMR. Design and patients: This was a prospective study. Fourteen consecutive patients (8 women, mean age 46±10 yr) with untreated active acromegaly were submitted to CMR and 2D-color Doppler echocardiography before and after a 6-month SMSA course. Measurements: LV volume, mass (LVM) and wall thickness. Results: CMR: Mean LVM and LVM index (i) decreased from 151±17 g and 77±9 g/m2, to 144±24 g and 70±12 g/m2, respectively (p=0.047 and p<0.0001, respectively); LV hypertrophy reverted in 6 out of 10 patients (p=0.016). Systolic function, evaluated by measuring LV ejection fraction remained normal in all patients (67±11%). There was not a correlation between changes in LVMi and changes in serum IGF-I concentrations. However, patients with controlled disease had higher reduction of LVMi than those with uncontrolled acromegaly (ΔLV-Mi, −8.2±4.2 vs 4.0±5.3 p<0.05). 2D-echocardiography: Mean LVMi decreased from 110±24 g/m2 to 100±20 g/m2 (p=0.026); hypertrophy, revealed in 5 patients (36%) at baseline, reversed in 2 patients (p=0.500) after SMSA; abnormal diastolic function [evaluated by isovolumic relaxation time or early (E) to late of atrial (A) peak velocities ratio] found in 4 patients (29%) at the study entry, improved in a patient. Systolic function remained within the normal range in all patients during the study period. Conclusions: CMR detects changes in LVMi in most patients with acromegaly treated with SMSA, which are more evident if the disease is controlled.