Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients

CONTEXT: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients. OBJECTIVE: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. DESIGN: Retrospective study. SETTING: Academic hospital. PATIENTS: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls. MEASUREMENTS: TSH, FT4 and FT3 concentrations by immunoassays. RESULTS: FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients. CONCLUSIONS: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

La monoterapia con Levotiroxina non garantisce l'eutiroidismo in tutti i pazienti atireotici

Introduzione: La terapia con levotiroxina (LT4) è, secondo le linee guida, il trattamento di scelta per i pazienti ipotiroidei, poiché si considera che la conversione periferica della T4 in T3 possa ottemperare al generale fabbisogno di ormoni tiroidei dei tessuti. In ogni caso, i pazienti in terapia con LT4 necessitano di concentrazioni maggiori di FT4 per normalizzare i livelli di TSH, esponendo così i tessuti periferici a un rapporto sbilanciato fra FT4 e FT3. Nonostante presentino livelli di TSH normali, alcuni pazienti ipotiroidei in terapia con LT4 lamentano un non perfetto benessere. Scopo dello studio: Valutare se, in pazienti atireotici in monoterapia con LT4, si ottenga la normalizzazione dei livelli di ormoni tiroidei e se la risposta dell asse ormoni tiroidei-ipofisi sia conservata. Pazienti e metodi: Abbiamo valutato retrospettivamente una numerosa serie (1811) di pazienti tiroidectomizzati per carcinoma tiroideo differenziato e trattati con LT4 ad un dosaggio stabile da almeno tre mesi, con TSH nel range di normalità (0.4-4.0 mU/L). Abbiamo paragonato questa popolazione con 3875 soggetti eutiroidei di controllo, visitati presso il nostro Centro per le Tireopatie e con TSH nel range di normalità. I soggetti con TSH <0,4 mU/L o >4,0 mU/L sono stati esclusi nel sospetto di iper- o ipotiroidismo subclinico. In entrambi i gruppi i pazienti trattati con farmaci potenzialmente interferenti con la funzione tiroidea o affetti da patologie croniche sonos stati esclusi, così come, nel gruppo degli eutiroidei, i soggetti con anticorpi AAT e/o AAM positivi o con quadro ecografico suggestivo di tiroidite cronica autoimmune. Tutti i dosaggi sono stati eseguiti presso il laboratorio centrale del nostro presidio ospedaliero. Risultati: I livelli di FT4 erano significativamente più elevate e quelli di FT3 significativamente più bassi nei pazienti atireotici trattati con LT4 rispetto ai controlli eutiroidei di pari età e sesso (p<0.001 in entrambi i casi). Tra i pazienti trattati con LT4, il 15,2% presentava FT3 inferiore alla norma, il 7,2 % mostrava livelli di FT4 superiori al range di normalità. La notevole variabilità del rapporto FT3/FT4 indicava una grande eterogeneità nella capacità di produrre T3 a livello periferico nei diversi individui. Nei pazienti in terapia con LT4, la pendenza della retta di regressione lineare tra TSH e FT4 era maggiore rispetto a quanto osservato negli eutiroidei; negli ipotiroidei si osservava, inoltre, una correlazione fra FT3 e TSH, assente nei soggetti di controllo. Ciò suggerisce che l alterato rapporto FT3/FT4 determini una differente risposta ipofisaria agli ormoni tiroidei. Conclusioni: Nei pazienti atireotici si osserva una grande eterogeneità nella capacità di produrre T3 dalla LT4 somministrata. Più del 20% di questi pazienti, nonostante livelli di TSH nei limiti della norma, non mantiene FT3 o FT4 entro il range di riferimento; è, dunque, verosimile che, in questi soggetti, la desiodazione periferica della LT4 non riesca a compensare l assenza della produzione tiroidea di T3. Gli effetti a lungo termine della esposizione ad un anomalo rapporto T3/T4 non sono noti. Inoltre, nei soggetti in monoterapia con LT4, il feedback ormoni tiroidei-ipofisi risulta alterato, per cui misurare il solo TSH potrebbe non essere sufficiente ad accertare l eutiroidismo

Hashimoto's thyroiditis: similar and dissimilar characteristics in neighboring areas. Possible implications for the epidemiology of thyroid cancer.

CONTEXT: Medical centers worldwide report an increased frequency of Hashimoto's thyroiditis (HT) and thyroid cancer (TC), two environmentally influenced diseases. In Sicily, data on HT are available for the province of Messina (1975-2005); data on TC are available for the whole island (2002-2004), with the volcanic province of Catania having the highest incidence. OBJECTIVE: To replicate in Catania, on comparable years, the HT data of Messina. DESIGN METHODS SETTING: Review of the clinical records of patients in years 1995-2005 to compare presentation and yearly changes of HT. During 1995-2005, records were computer stored in the Endocrine Divisions of the University Hospitals of Catania and Messina, two tertiary referral centers. RESULTS: Catania is outnumbered by Messina (742 vs. 3,409 HT patients). Similar were the linear increase in the yearly number of HT patients, rates of thyroid dysfunctions though with different proportions of subclinical and overt hypothyroidism, and rates of positiveness for TgAb or TPOAb. Different were age and its yearly trend; gender distribution and rates of the sonography variants, though yearly trends were similar. CONCLUSION: The HT epidemics is smaller in Catania, with changes in presentation overlapping partially those in Messina. Whatever environmental factors might be involved, they (and/or their intensity) were not necessarily the same in these provinces. Intriguingly, the expected number of TC in HT patients with thyroid nodules in Catania is congruent with that of the general population of this province, but it is far less than in the Messina province. Thus, TC and HT incidences could be influenced by distinct environmental factors

Yearly prevalence of the serum positiveness for thyroglobulin autoantibodies (TgAb, left panel) and thyroperoxidase autoantibodies (TPOAb, right panel), <i>viz.</i> proportion of patients with higher-than-normal serum levels of TgAb and TPOAb, in the two cohorts of patients with Hashimoto's thyroiditis.

<p>Yearly prevalence of the serum positiveness for thyroglobulin autoantibodies (TgAb, left panel) and thyroperoxidase autoantibodies (TPOAb, right panel), <i>viz.</i> proportion of patients with higher-than-normal serum levels of TgAb and TPOAb, in the two cohorts of patients with Hashimoto's thyroiditis.</p

Geographic location of the Catania and Messina provinces.

<p>Approximately, 14% of the Catania cohort is represented by HT patients coming from the neighboring provinces of Siracusa (6%), Ragusa (2.5%), Enna (2%), Caltanissetta (2.5%) and Agrigento (0.7%). This compares with approximately 18% of the Messina cohort of HT patients coming from Southern Calabria, particularly from the province of Reggio Calabria. Population in these provinces is approximately 1.1 million (Catania), 660,000 (Messina), 400,000 (Siracusa), 300,000 (Ragusa), 275,000 (Caltanissetta), 175,000 (Enna), 450,000 (Agrigento), and 560,000 (Reggio Calabria).</p

Yearly prevalence of the indicated variants of Hashimoto's thyroiditis (HT) based on thyroid size and nodules as assessed by thyroid ultrasonography in the two HT patients cohorts.

<p>Yearly prevalence of the indicated variants of Hashimoto's thyroiditis (HT) based on thyroid size and nodules as assessed by thyroid ultrasonography in the two HT patients cohorts.</p

Expected epidemiology of thyroid cancer in patients with the nodular variant of Hashimoto's thyroiditis (HT) from the provinces of Messina and Catania (based on data reported here for the period 1995–2005) and observed epidemiology (years 2002–2004, as reported in ref. 11).

<p>The possible scenarios assume three rates of prevalence of HT in the general population (2, 5 or 10%) and two rates of malignancy for thyroid nodules (5 or 10%). The one-fourth or one-fifth lower magnitude of the HT prevalence in the Catania province is because the 1 to 4.5 ratio observed between Catania and Messina (742 and 3,409 cases, respectively) can be rounded off to either 1.0 to 4.0 or 1.0 to 5.0. The rates of thyroid nodules in HT patients (55% for Messina or 25% for Catania) were taken from the variant “thyroid nodules regardless of goiter” in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055450#pone-0055450-t001" target="_blank">Table 1</a> of the present paper. Expected numbers do not change substantially by referring to the period 2002–2004, because cases of HT were 352 in the Catania cohort and 1,351 in the Messina cohort (ratio of 1 to 3.84), with a rate of 26.4% and 56.5% for the variant “nodules regardless of goiter”.</p

Summary of the relationships between the calendar year (1995–2005) and the indicated characteristic in the Catania or the Messina cohort of Hashimoto's thyroiditis (HT) patients.

<p>P values<0.05 are typed boldface.</p

Acute Primary Adrenal Insufficiency after Hip Replacement in a Patient with Acute Intermittent Porphyria

Adrenal insufficiency is a potentially life-threatening condition when it occurs acutely, as in adrenal hemorrhage. Generally it is not reversible and requires chronic replacement therapy. Acute intermittent porphyria (AIP) is a rare genetic disease characterized by alterations in heme biosynthesis that result in accumulation of precursors in tissues. A crisis can be triggered by many conditions such as surgery and infections. Symptoms are similar to those of acute hypoadrenalism. Moreover, both conditions are characterized by hyponatremia. We describe the case of a postmenopausal woman known to be affected by AIP who developed after surgery a primary adrenal insufficiency associated with adrenal enlargement; the latter completely reverted in six months