Different FT3/TSH correlation in acquired and congenital hypothyroid patients reveals a different hypothalamic set-point.

OBJECTIVE: To understand differences in thyroid hormone replacement therapy with levo-thyroxine (l-T4) between acquired and congenital hypothyroid (CH) patients. DESIGN: We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy. PATIENTS AND MEASUREMENTS: A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18-58). Serum TSH, FT3, FT4, l-T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups. RESULTS: The daily weight-based l-T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p = .03). FT3/FT4 ratio was significantly higher in the EU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in the TP group, but not in the EU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects. CONCLUSIONS: Adult CH patients require a higher daily l-T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic-pituitary-thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH.

Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster-Randomized FADOI TIAMO Study.

Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05314790.

Ten-year estimated risk of bone fracture in women with differentiated thyroid cancer under TSH-suppressive levothyroxine therapy.

INTRODUCTION: After thyroidectomy and radioiodine therapy, patients with differentiated thyroid cancer (DTC) are indefinitely treated with levothyroxine (L-T4). Osteoporosis is a debated consequence of hypothyroxinaemia. The aim of this study was to evaluate bone mineral density (BMD) and fracture risk assessed by FRAX in a cohort of DTC women. MATERIAL AND METHODS: Seventy-four women with DTC (aged 56.5 ± 9.9 years) treated at the mean age of 51.9 ± 12.0 years were studied. Baseline BMD and FRAX were evaluated after 3.0 years (median). BMD and FRAX were further evaluated 5.5 years (median) after the baseline evaluation. A cohort of 120 euthyroid women, matched for age, BMI, and menopausal status, were evaluated as controls. RESULTS: L-T4 dosages were 813.6 ± 208.8 µg/week and 782.1 ± 184.4 µg/week at the baseline and second evaluation, respectively. The risks of major osteoporotic fracture (MOF) and hip fracture (HF) were similar in DTC patients and in controls. In DTC women, significant changes in FRAX were found, with a higher increase in the probability of HF than of MOF. A similar change was found in controls. A significant inverse correlation (P < 0.001) between L-T4 dosage and HF/MOF probability on both first and second evaluations was found. A significant inverse correlation (P = 0.05) was found between fT4, TSH and duration of therapy and HF/MOF probability only on the second evaluation. CONCLUSIONS: FRAX increase is a multi-factorial, age-related phenomenon. The absence of correlations between L-T4 dosage, length of therapy or fT4 levels and FRAX does not enable us to attribute an increased fracture risk to DTC women with well-controlled disease on therapy. (Endokrynol Pol 2016; 67 (4): 350-358).