Purpose: There is a need to refine the reference intervals (RI) of normal TSH values for age and gender. Aim of this study was to construct an RI of normal TSH in subjects living in Liguria, Italy. Methods: From 2014 to 2023, 1787 medical records (1336 females, 451 males) were evaluated in order to document TSH values. The RI of TSH was set at the 2.5th and 97.5th percentiles. The population was stratified into three age-groups: 18–44, 45–64 and ≥65 years. Results: Median TSH levels were significantly (P<0.0001) higher in females (1.82 mIU/l) than in males (1.43 mIU/l). This significance was maintained in all age-groups. In females, the RI were 0.46-6.31 mIU/l, 0.45-6.70 mIU/l, and 0.34-8.80 mIU/l in the 18-44 (n=542), 45-64 (n=517) and >65 (n=277) year age-groups. In males, the RI were 0.26-7.03 mIU/l, 0.33-6.21 mIU/l, and 0.26-8.57 mIU/l in the 18-44 (n=125), 45-64 (n=188) and >65 (n=138) year age-groups. When TSH values were evaluated by means of “study population RI” instead of the “pooled RI reported by manufacturers”, a significantly higher percentage of females had sub-clinical hyperthyroidism (P=0.005), while a significantly lower percentage of both females and males (females P<0.0001; males P=0.03) had sub-clinical hypothyroidism. Conclusions: This study establishes new gender- and age-specific RI for TSH in our area. These TSH RI could be extensively employed in order to improve diagnosis and treatments. The reduced percentages of sub-clinical hypothyroidism in the elderly when the RI was derived from the study population, rather than from RI from manufacturers, redefines the need for treatment.

TSH is the first-line test of thyroid function, and the normal TSH references provided by manufacturers are generally used in diagnoses. In the age of gender medicine, however, there is a need to refine normal TSH ranges. The aim of this study was to construct a normal TSH range in women living in our district. The data were collected in a secondary-level centre located in Savona (Liguria, Italy). From 2003 to 2022, 6227 medical records from women undergoing their first endocrinological examination were anonymously evaluated. After the application of exclusion criteria, statistical analysis was anonymously performed on a sample of 2597 medical records. The pooled median 2.5th and 97.5th percentiles of TSH provided by manufacturers were 0.20 mIU/l and 5.64 mIU/l, respectively. In the study population, median (2.5th − 97.5th percentiles) TSH was 1.70 mIU/l (0.37–6.95 mIU/l). TSH and patient age did not vary significantly over the years (2003–2022). A slight negative correlation was found between TSH and age (P = 0.05). On stratifying the sample into three age-groups (18–44 years, N = 1200; 45–64 years N = 934; ≥65 years, N = 463), TSH was 1.75 mIU/l (0.49–5.94 mIU/l), 1.70 mIU/l (0.30–6.89 mIU/l) and 1.64 mIU/l (0.30–7.69 mIU/l), respectively. When TSH was evaluated according to the age-related range instead of the pooled range reported by manufacturers, the number of women aged 18–44 years considered to have sub-clinical hyperthyroidism increased slightly (P = 0.02) and the number of women in the 45-64-year and ≥ 65-year age-groups considered to have sub-clinical hypothyroidism decreased significantly (P = 0.05 and P < 0.001). This is the first study in Liguria aimed at establishing new age-specific reference values for TSH in women. Based on a large number of data, this new age-related range could be more extensively employed in order to improve diagnosis. The main result of implementing age-related normal TSH levels between the 2.5th and 97.5th percentiles seems to be both a slight increase in 18-44-year-old women and a significant reduction in > 45-year-old women in whom sub-clinical hyperthyroidism or hypothyroidism, respectively, should be promptly treated.

BACKGROUND:Ultrasonography (US) is the simplest method of evaluating thyroid volume (TV). The current normal TV in Liguria is not known. The aim of this study was to obtain normative data on TV in Liguria, Italy.METHODS:From 3552 files of endocrine evaluations registered in a primary outpatient setting, we selected 483 files on euthyroid subjects (383 females and 100 males) with a normal echoic pattern on US. The inclusion criterion was the absence of thyroperoxidase autoantibodies and drugs known to interfere with thyroid hormone secretion or metabolism. TV was calculated by means of US. Anthropometric characteristics, smoking habits and the district where subjects lived were registered.RESULTS:Less than 50% of patients were not taking any drug. The percentage of obesity was similar in both sexes. TSH levels were similar in males and females. Median TV was 8.0 mL (IQR: 6.7-9.8 mL) in females and 11.8 mL (9.3-15.6 mL) in males (P<0.0001). In females, TV was greater (P=0.01) in smokers than in non-smokers. In both sexes, the right lobe was significantly (P<0.0001) larger in volume than the left. Post-hoc analysis did not show any differences among age-groups in either females or males. In females, but not in males, TV differed significantly (P=0.0002) according to the district of residence. A significant positive correlation was found in both groups between TV and weight, height, BMI and BSA.CONCLUSIONS:Reference values of TV in the Ligurian population are now available. TV in the general population could be compared with these normative data.

Background: The adequate management of thyroid dysfunction in pregnancy reduces pre-partum adverse events and improves the life of the new-born. Aim: Women managed for thyroid hypo-function during pregnancy were retrospectively identified and a survey was performed on their offspring aged from 6 months to 18 years. Methods: We selected 131 pregnancies for survey. From January to August 2022, the mothers were sent a questionnaire containing questions on the neonatal and post-natal period and questions on their children's current auxological, scholastic and pathological status and lifestyle. Eighty-two questionnaires were returned. The mothers’ replies were compared with their f-T4 and TSH levels recorded during pregnancy. Reference f-T4 and TSH values were extrapolated from 76 pregnancies managed according to current guidelines. Results: f-T4 values below the 2.5th percentile were found in less than 3% of cases, while f-T4 values above the 97.5th percentile were found in less than 4%. TSH proved more variable. Replies regarding the time of the new-born’s first postural changes were significantly inversely correlated with f-T4 concentrations in each trimester of pregnancy and positively correlated with the TSH levels observed in the 1st trimester. Conclusions: This single-centre, cross-sectional, study offers further indications for the management of thyroid hypofunction in pregnancy and suggests that the control of maternal f-T4 and TSH levels during pregnancy has improved in our district. Data from survey indicate that f-T4 influences early motor activity in new-borns more than TSH does. However, the small sample size, the wide age range of the children and the long time-lag between delivery and survey administration could impair our results.

Abstract Background AMH is a reliable index of ovarian reserve. It is not clear whether, or how much, thyroid function and/or thyroid autoimmunity can impair ovarian function and AMH secretion in the long term. Aim This retrospective cross-sectional study compared AMH levels in pre-menopausal women with/without positive thyroid autoimmunity or hypofunction. Methods From January 2019 to May 2022, AMH was evaluated in 250 pre-menopausal women not undergoing assisted fertility procedures who were referred to a secondary endocrine centre. Thyroid function and autoimmunity, sonographically measured thyroid volume, FSH and E2 in the early follicular phase, and PRL and progesterone in the luteal phase were also evaluated. Exclusion criteria were: age < 18 years, genetic hypogonadism, pregnancy and previous treatments that have potentially damaging effects on gonads. Results We evaluated 171 women (mean age ± SD: 31.5 ± 9.0 years) off L-T4 treatment and 79 women on L-T4 treatment (39.7 ± 9.5 years; P < 0.001). AMH (median, IQR, CI) was 16.1 pmol/l (7.1 – 35.7 pmol/l, 21.4 – 29.9 pmol/l) and 7.6 pmol/l (1.4 – 17.8 pmol/l, 8.6 – 14.7 pmol/l; P < 0.001), respectively. When the women were stratified according to age (18-25, 26-30, 31-35, 36-40, 41-45, > 46 years) no significant difference emerged between those on/off L-T4 treatment in groups of the same age-range. In women on- or off-L-T4 treatment, AMH was negatively related with age on univariate and multivariate analyses (P < 0.0001). In both groups, AMH was negatively related to FSH (P < 0.0001). On multivariate analysis, AMH was positively related to the age of the mother on spontaneous menopause (P = 0.006) and negatively to thyroid volume (P = 0.02) in women on L-T4. AMH levels were significantly (P = 0.03) higher in TPOAb-negative than in TPOAb-positive women, but age was significantly (P = 0.001) lower in TPOAb-negative than in TPOAb-positive women. Conclusions In our cohort of women, age proved to be a better predictor of AMH levels than any of the other factors linked to thyroid function and autoimmunity. Our data do not support the hypothesis that subclinical hypothyroidism and/or autoimmunity are associated with decreased ovarian reserve. However, a larger number of cases is needed in order to obtain conclusive data.

Purpose: to determine lactose intolerance (LI) prevalence in women with Hashimoto’s thyroiditis (HT) and assess the impact of LI on LT4 replacement dose. Methods. consecutive patients with HT underwent Lactose Breath Test and clinical/laboratory data collection. Unrelated gastrointestinal disorders were carefully ruled out. Lactose-free diet and shift to lactose-free LT4 were proposed to patients with LI. Results: we enrolled 58 females (age range, 23–72 years) with diagnosis of HT. In total, 15 patients were euthyroid without treatment, and 43 (74%) euthyroid under LT4 (30 of them with a LT4 formulation containing lactose). Gastrointestinal symptoms were present in 84.5% of patients, with a greater prevalence in change in bowel habits in lactose-intolerant patients (p < 0.0001). The cumulative LT4 dose required did not differ in patients with or without LI. No significant difference in both TSH values and LT4 dose were observed in patients shifted to lactose-free LT4 and diet at 3 and 6 months compared to baseline. Conclusion: the prevalence of LI in patients with HT was 58.6%, not different from global prevalence of LI. In the absence of other gastrointestinal disorders, LI seems not to be a major cause of LT4 malabsorption and does not affect the LT4 required dose in HT patients.

Background Clinicians should be aware that subacute thyroiditis (SAT) might be an under-reported adverse effect of COVID-19 vaccines. Aim In records from endocrinological examinations, we reviewed the incidence of diagnoses of SAT from 2000 to 2020 and during the 2021 COVID-19 vaccination campaign. Methods Review of electronic records from June to December in each year from 2000 to 2021. Results From 2000 to 2020, 51 patients in our centre had SAT (0.6%). From June to December 2021, 7 females were diagnosed with SAT after vaccination. The percentage of SAT in 2021 medical files was 1.5%. SAT diagnoses significantly (P = 0.03) increased in 2021 in comparison with the 2000–2020 period. The median age of SAT patients in 2021 (51 years; IQR 35–66 years) was higher than in the 2000–2020 period (45 years, IQR 38–52 years; P = 0.05). Conclusion To date, few cases of SAT after COVID-19 vaccinations have been described in the literature, with sub-clinical, normal or increased thyroid function during 1-3-month follow-up. Our findings indicate that SAT after COVID-19 vaccination occurs more frequently than in other virus-related cases and at a greater age. Our observation of a local increase in SAT during the 2021 COVID-19 vaccination campaign indicates that physicians should be aware of this infrequent side effect, which must be considered and monitored after COVID-19 vaccination.

Purpose To evaluate the role of 2-[18F]FDGPET/CT in the follow-up of radioiodine refractory thyroid cancer (RR-TC). Methods Forty-six 2-[18F]FDGPET/CT scans from 14 RR-TC patients were considered. Thyroid function tests: thyroglobulin (Tg), levothyroxine (LT4), and tyrosine-kinases inhibitors (TKIs) assumptions were recorded. Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from each scan and correlated with clinical parameters and the overall survival (OS). Results Baseline TLG and MTV predicted OS (p = 0.027 and p = 0.035), and negative correlation with OS was also confirmed when the same parameters were measured in follow-up scans (p = 0.015 and p = 0.021). Tg also correlated with the OS; (p = 0.014; p = 0.019 and p = 0.009). However, TLG and MTV were not significantly correlated with Tg levels. MTV and TLG variation in time were reduced during TKI therapy (p = 0.045 and p = 0.013). Conclusions 2-[18F]FDGPET/CT confirmed its prognostic role at the first assessment and during the follow-up of RR-TC patients. 2-[18F]FDGPET/CT parameters seem at least partially independent from Tg. TKI therapy resulted in a measurable effect on the variation of 2-[18F]FDGPET/CT parameters over time.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Objectives: Along with deficit of attention, level of arousal is a primary criterion for the diagnosis of delirium. The Observational Scale of Level of Arousal (OSLA) is a quick, simple, and observational instrument used to evaluate the variation of arousal for rapid screening of delirium in clinical practice. The current study aims to perform a cross-cultural adaption of and to validate the Italian version of the OSLA scale to detect delirium in older aged, hospitalized patients. Design: Longitudinal study. Setting and Participants: In hospital and transitional care setting. Old age patients. Methods: A cross-cultural adaptation of the OSLA from English into Italian was conducted, including back-translation. The validation of the OSLA was assessed in 116 older patients (age >65 years) admitted to geriatric, internal medicine, and transitional care wards. The 4 "A"s Test serves as the gold standard for the measurement of delirium. Results: Incident delirium was assessed longitudinally at different time points during hospitalization. The Italian version of OSLA demonstrated adequate internal consistency, specificity, sensitivity, agreement, test-retest reliability, and sensitivity to change, indicating adequate its clinometric properties in the detection of delirium in a real world hospitalized cohort of older adults. Conclusions and Implications: The current study is among the few studies to assess arousal as a core feature of delirium by virtue of a longitudinal assessment of delirium, moving a step forward in the implementation of a brief and easy to use delirium-screening tool for the measurement of important clinical outcomes in a frail, old aged hospitalized population. (C) 2020 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Background: After surgery, clinical approach to thyroid neoplasms often involves TSH suppression. An increased cardiovascular (CV) risk due to thyroid hormones excess has already been proved. Aim of the study was to evaluate the role of CV assessment in preventing new events and optimizing the follow-up of these patients. Methods: After thyroidectomy for low risk thyroid neoplasms, a cohort of 108 women was retrospectively evaluated. A first examination (V1) at the end of primary treatments and a second one (V2) five years later were considered. Clinical and echocardiographic evaluations were performed in each examination. Patients were divided into 3 subclasses depending on TSH-suppression degree in the study period. New cardiovascular events, initiation of new therapies and cardiovascular deaths were recorded. Results: The incidence of CV events was 7,4%. Patients age (p=0.032), previous CV events (p=0.001), use of lipid-lowering (p=0.002) and antiplatelet (p=0.027) drugs and diabetes mellitus (p=0,049) were associated with total CV events; interventricular septum thickness, BMI and tryglicerides value with ischaemic events (sensitivity 66,6%, 100%, 80%; specificity 91,1%, 55,1%, 77,2%, respectively; p<0.001); TSH-suppression class with arrhythmic events (p=0.035); an increased left ventricular mass index ratio between V2 and V1 with both total (p=0.001) and ischaemic (p=0.002) CV events. Conclusions: After primary treatments for thyroid neoplasm, a complete CV assessment is advisable in defining TSH-suppression target. Ultrasound parameters appear useful in evaluating CV risk both at baseline and during the follow-up. A periodic revaluation of those parameters may allow the prevention or early diagnosis of new events and complications.

Context Large variations in thyroid volume (TV) have been reported in Hashimoto's thyroiditis (HT). The need for long-term levo-thyroxine (L-T4) administration in order to control TV, as well as to normalise thyroid function, has not been well defined. Subjects and Methods Retrospective data on TV in 94 adult women with HT were analysed in an ambulatory setting in Liguria, an area of moderate iodine sufficiency. TV was evaluated by means of ultrasonography (US). Thyroid function, anthropometric data, smoking habits and pharmaceutical drugs were registered at each examination. Results At the baseline, an atrophic gland was noted in 16% of the women, and goitre in 13%. The women were evaluated 56 and 102 months after the baseline examination. At the time of each examination, 50%, 78% and 83% of women, respectively, were on L-T4 treatment. Baseline TV was not significantly different in women on/off L-T4 treatment. However, in those on L-T4, TV decreased significantly over the period of follow-up, while in those without L-T4 treatment, it did not change. By the end of the study, the percentage of L-T4-treated women with an atrophic gland had increased to 27%, and that of women with goitre had dropped to 6%; in untreated women, only minor changes were noted. There was a significant negative correlation between TV% change and baseline TSH levels in HT women on L-T4 treatment. Conclusion The majority of HT women living in an area of moderate iodine sufficiency have normal TV. Moreover, long-term L-T4 treatment can be used to control TV, as well as to maintain normal thyroid parameters.

The use of recombinant human PTH (1-84) [rhPTH(1-84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. The objective of this study was to investigate the effects of 12 months of rhPTH (1-84) treatment in a cohort of patients selected according to the indications of recent hypoparathyroidism guidelines. It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers were involved. Fourteen adult subjects with chronic hypoparathyroidism treated with rhPTH (1-84) for 12 months were enrolled. Main outcome measures included serum and urinary parameters of mineral metabolism, renal function, oral calcium and vitamin D doses, and clinical manifestations. At 12 months, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean serum calcium levels quickly normalized after initiation of rhPTH (1-84) treatment compared to baseline (p=0.009). Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p= 0.014). No severe adverse events were described. In conclusion, this study confirm the efficacy and safety of rhPTH (1-84) therapy.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The SARS-CoV-2 virus can trigger thyroid dysfunction. Thyroid dysfunctions after COVID-19 vaccination have been rarely reported. We report the case of overt hypothyroidism in a 61-year-old woman seen after BNT162b2-mRNA vaccination. This case underlines the fact that thyroid function should also be monitored after COVID-19 vaccination, especially in at-risk subjects.

Italy is considered a mildly iodine-deficient country. The aim of this study was to evaluate the iodine status of a cohort of adults living in Liguria after the 2005 salt iodization program. We searched all medical records of patients examined in two endocrine outpatient clinics in Genoa and Savona for data on urinary iodine. Subjects were under evaluation for thyroid diseases. Information on the type of salt used was found in few clinical records. Iodized salt use was reported in 29%, 20%, and 13% of records of people living in Genoa districts, the Savona district and nearby districts, respectively. The average urinary iodine concentration was 112.9 ± 62.3 µg/L (n = 415, median 101.0 µg/L). Non-significant differences (P > 0.05) were found between subjects with (median 103.5 µg/L) and without (median 97.5 µg/L) a thyroid gland, between the periods 2009–2013 (median 105.0 µg/L) and 2014–2018 (median 97.5 µg/L), and between Genoa (median 94.0 µg/L), Savona (median 105.0 µg/L) and the other districts (median 114.5 µg/L). No correlation with age, body mass index, creatinine, free thyroxine, thyroglobulin, levo-thyroxine dosage, or thyroid volume was observed. These data suggest a borderline status of iodine sufficiency in this cohort.