Normal thyroid volume in subjects evaluated in a primary ambulatory setting in Liguria.

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.

Retrospective observation of subacute thyroiditis before and during the COVID-19 vaccination campaign in a single secondary endocrine centre in the Savona district, Liguria, Italy.

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.

Evaluation of anti-Müllerian hormone in pre-menopausal women stratified according to thyroid function, autoimmunity and age.

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.

Prevalence of Lactose Intolerance in Patients with Hashimoto Thyroiditis and Impact on LT4 Replacement Dose.

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.

2-[18F]FDG PET in the Management of Radioiodine Refractory Differentiated Thyroid Cancer in the Era of Thyrosin-Kinases Inhibitors: A Real-Life Retrospective Study.

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.

Acute thyroid swelling with severe hypothyroid myxoedema after COVID-19 vaccination.

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.

Increased Creatine Kinase May Predict A Worse COVID-19 Outcome.

Early reports from Asia suggested that increased serum levels of the muscular enzyme creatine-(phospho)-kinase (CK/CPK) could be associated with a more severe prognosis in COVID-19. The aim of this single-center retrospective cohort study of 331 consecutive COVID-19 patients who were hospitalized during Italy's "first wave" was to verify this relationship, and to evaluate the role of possible confounding factors (age, body mass index, gender, and comorbidities). We subdivided our cohort in two groups, based on "severe" (n = 99) or "mild" (n = 232) outcomes. "Severe" disease is defined here as death and/or mechanical invasive ventilation, in contrast to "mild" patients, who were discharged alive with no need for invasive ventilation; this latter group could also include those patients who were treated with non-invasive ventilation. The CK levels at admission were higher in those subjects who later experienced more severe outcomes (median, 126; range, 10-1672 U/L, versus median, 82; range, 12-1499 U/L, p = 0.01), and hyperCKemia >200 U/L was associated with a worse prognosis. Regression analysis confirmed that increased CK acted as an independent predictor for a "severe" outcome. HyperCKemia was generally transient, returning to normal during hospitalization in the majority of both "severe" and "mild" patients. Although the direct infection of voluntary muscle is unproven, transient muscular dysfunction is common during the course of COVID-19. The influence of this novel coronavirus on voluntary muscle really needs to be clarified.

A comparative cross-sectional study on sleep quality in patients with a history of differentiated thyroid carcinoma and its correlation with quality of life.

PURPOSE: To evaluate sleep quality in differentiated thyroid carcinoma (DTC) patients and correlate sleep disturbances with quality of life (QoL). METHODS: 119 DTC patients were enrolled (DTC group). The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) inventories were administered. The Thyroid-specific Patient-Reported Outcome (ThyPRO) questionnaire, the Billewicz scale (BS) and an ad-hoc visual analogic scale (VAS) were used to measure QoL and subjective therapy-related complaints. The same examinations were conducted in 53 subjects (control group) who had undergone surgery for benign thyroid pathology. RESULTS: L-T4 dosages and TSH levels differed between the groups. BS and VAS scores were comparable. PSQI documented a similar percentage of poor sleepers in the DTC (74%) and control (62%) groups. ISI showed no difference in subjects without clinically significant insomnia: DTC (43%) and controls (48%). ThyPRO showed significantly worse scores in DTC than control subjects. In DTC patients, PSQI (P = 0.002) and ISI (P = 0.04) correlated significantly with age. In control subjects, TSH displayed a significant positive association with PSQI (P = 0.02) and ISI (P < 0.05). The ThyPRO general score correlated significantly with PSQI in DTC patients. In both groups, ISI correlated significantly with several ThyPRO scales and the ThyPRO general score. "Anxiety" and "emotional susceptibility" were the scales most significantly related with PSQI and ISI. CONCLUSION: In disease-free DTC patients and subjects who undergo thyroid surgery for benign pathology, abnormal sleep components and insomnia are similar. The ThyPRO questionnaire closely reflects sleep disturbances in all subjects. Recognising and treating sleep disturbances might improve QoL.

Cross-Cultural Adaptation and Validation of the Italian Version of the Observational Scale of Level of Arousal.

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.

Evaluation of Quality of Life in Patients with Differentiated Thyroid Cancer by Means of the Thyroid-Specific Patient-Reported Outcome Questionnaire: A 5-Year Longitudinal Study.

BACKGROUND: Patients with malignancy suffer impairment of their quality of life (QoL). QoL has been evaluated in thyroid cancer patients. Since 2010, a new inventory, the thyroid-specific patient-reported outcome (ThyPRO) measure for benign thyroid disorders, has been available. AIM: This study evaluated QoL longitudinally in patients with a history of differentiated thyroid cancer (DTC) by means of the ThyPRO questionnaire. Methods : From 2012 to 2016, QoL was evaluated yearly in 123 adult DTC patients by means of ThyPRO. The ThyPRO questionnaire consists of 13 scales on which higher scores represent greater impact on QoL in areas affected by thyroid pathology. Disease-specific morbidity due to possible inadequate L-T4 treatment was evaluated by means of the Billewicz scale (BS). The same examinations were conducted in 192 control subjects who had undergone surgery for benign thyroid pathology. RESULTS: DTC and control subjects had similar scores on all but one scale; scores on the hyperthyroid symptoms scale were significantly higher in DTC patients than in controls. Over the 5 years, scores did not change significantly in the DTC group. Overall, QoL and BS scores showed a slight, but not significant, improvement during the study period in DTC patients. BMI impacted on several ThyPRO scales. No significant differences between genders were noted in DTC. CONCLUSIONS: The ThyPRO questionnaire indicates that illness perception is similar after thyroidectomy for malign and benign pathology. Only a marginal improvement in QoL was noted in DTC subjects over the 5-year study period. In both groups, females showed a greater perception of illness than males.

Five-Year Results of Radiofrequency and Laser Ablation of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Radiofrequency ablation (RFA) and laser ablation (LA) are effective treatments for benign thyroid nodules. Due to their relatively recent introduction into clinical practice, there are limited long-term follow-up studies. This study aimed to evaluate technique efficacy, rate of regrowth, and retreatment over 5 years after RFA or LA and to identify predictive factors of outcome. Methods: In this multicenter retrospective study, the rates of technique efficacy, regrowth, and retreatment were evaluated in 406 patients treated with either RFA or LA, and followed for 5 years after initial treatment. Propensity score matching was used to compare treatments. Cumulative incidence studies with hazard models were used to describe regrowth and retreatment trends, and to identify prognostic factors. Logistic regression models and receiver operating characteristic analyses were used for risk factors and their cutoffs. Results: RFA and LA significantly reduced benign thyroid nodule volume, and this reduction was generally maintained for 5 years. Technique efficacy (defined as a reduction ≥50% after 1 year from the treatment) was achieved in 74% of patients (85% in the RFA and 63% in the LA group). Regrowth occurred in 28% of patients (20% in the RFA and 38% in the LA group). In the majority of cases, further treatment was not required as only 18% of patients were retreated (12% in the RFA and 24% in the LA group). These data were confirmed by propensity score matching. Cumulative incidence studies showed that RFA was associated with a lower risk of regrowth and a lower risk of requiring retreatment over time. Overall, technique inefficacy and regrowth were associated with low-energy delivery. Retreatments were more frequent in young patients, in large nodules, in patients with lower volume reduction at 1 year, and in cases of low-energy delivery (optimal cutoff was 918 J/mL for RFA). Conclusions: Both thermal ablation techniques result in a clinically significant and long-lasting volume reduction of benign thyroid nodules. The risk of regrowth and needing retreatment was lower after RFA. The need for retreatment was associated with young age, large baseline volume, and treatment with low-energy delivery.

Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19.

OBJECTIVES: No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. METHODS: We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6±12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to-severe adverse events attributable to TCZ were recorded. RESULTS: We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean±SD Pa02/Fi02 at admission: 152±53; at day 7: 283.73±115.9, at day 14: 302.2±126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.

Parathyroid Carcinoma: An Up-to-Date Retrospective Multicentric Analysis.

Parathyroid carcinoma (PC) is a rare disease responsible for about 1% of primary hyperparathyroidism (PHPT) cases. PC usually has an indolent course, tough to differentiate from the benign causes of PHPT, and the only certain diagnosis is histologic. The gold standard surgical treatment is the en bloc resection associated with the homolateral thyroid loboistmectomy. The aim of this study was to underline the main differences between PC and benign PHPT, along with gathering epidemiological knowledge relative to PC in our region. Data from the regional cancer network (Rete Oncologica del Piemonte e della Valle d'Aosta) since 2007 have been reported, including 21 patients from three hospitals (AO S. Croce e Carle of Cuneo, AOU Città della Salute of Turin, and ASL Città di Torino). The incidence of the disease, gender, age at time of diagnosis, presence of renal and bone symptoms, serum calcium and PTH levels, surgical technique performed, and percentage of recurrence were analysed. PC data were than compared with a series of patients affected by benign PHPT, referred to ASL Città di Torino, Maria Vittoria Hospital, from 2007 to 2019. A PC incidence of 0.05 cases per 100,000 inhabitants was found in our region. Benign forms occurred more frequently in females (p=0.0002), while PC equally occurred in males and females and affected younger patients (p=0.026). Serum calcium and PTH levels were significantly higher in PC patients; accordingly, typical PHPT symptoms were more frequently reported in PC than in benign PHPT. In the PC group, the en bloc resection shows a 13 times lower risk for relapse compared with all the other surgical techniques. PC is equally gender distributed, and the average patients' age is in the fifth decade of life. It is usually functioning, with greater biochemical activity and multiple symptoms. A not-radical surgical resection is associated with a higher recurrence rate. A meticulous presurgical evaluation of PHPT patients showing PC's evocative features is mandatory to obtain a complete disease extirpation.

Cross-sectional and prospective study on anti-Müllerian hormone changes in a cohort of pre-menopausal women with a history of differentiated thyroid cancer.

BACKGROUND: Anti-Müllerian hormone (AMH) decreases acutely after post-surgical radioactive iodine (RAI) ablation in females with differentiated thyroid cancer (DTC). AIM: We performed a cross-sectional and prospective study on AMH levels in pre-menopausal females with a history of DTC. METHODS: Fifty-nine females after surgery and RAI (group 1) and 30 females after surgery alone (group 2) were studied. The control group consisted of 141 healthy women (group 3). The prospective study was performed in 43 and 14 females from groups 1 and 2, respectively. RESULTS: On first evaluation, AMH levels were similar in groups 1 and 2, but lower than in group 3. In all groups, AMH was negatively related with chronological age and FSH levels. When subjects were stratified according to age, AMH levels were not different between groups. When AMH was evaluated up to 2 years after the baseline evaluation, no changes emerged in either group of women with DTC. In the prospective study, the incidence of abnormal menstrual cycles and the onset of menopause were observed in similar percentages of women with a history of RAI-treated DTC and of those treated with surgery alone. CONCLUSIONS: AMH can be considered a reliable index of ovarian reserve in women with DTC. Chronological age is the main factor influencing AMH levels in both DTC patients and controls. After age-related stratification, AMH levels are similar in women with DTC treated with RAI and those treated with surgery alone.

RETRACTED ARTICLE: Can baseline endocrinological examination and thyroid ultrasound predict the development of thyroid disease in immunotherapy-treated patients? Results from a prospective, single-center, open-label study.

The authors are retracting this article [1] because they do not have permission to publish the data from the study reported. As the data are confidential, the content of this article has been removed from the journal website. All authors agree with this retraction.

Urinary Iodine Concentration in a Cohort of Adult Outpatients with Thyroid Diseases in Liguria 14 Years after the Law on Salt Iodization.

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.

Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma.

We report a case of an elderly woman presenting with a huge cervical mass invading the tracheal lumen. Diagnosed as invasive poorly differentiated thyroid cancer, after an endotracheal biopsy, stenting and radiotherapy, it was judged eligible for total thyroidectomy, but surgery was delayed due to pulmonary thromboembolism. The patient was therefore treated with lenvatinib with a neoadjuvant intent until hemodynamic stability was obtained. Thyroidectomy and radioiodine therapy were then performed and the postdose scan revealed an area of modest uptake in the anterior part of the neck. The patient is now in a good clinical status and she continues her follow-up program without any adjuvant therapy.

An H-TERT Mutated Skin Metastasis as First Occurrence in a Case of Follicular Thyroid Carcinoma.

Differentiated thyroid cancer arising from thyroid follicular epithelial cells is the most frequent endocrine malignancy, and skin metastases are very rare. We describe a case of a 70-year-old women with a history of an indeterminate thyroid nodule on cytology. A painless, erythematous skin nodule of about 7 mm diameter was removed from the scalp and diagnosed as a metastasis from thyroid cancer. After total thyroidectomy, a histological diagnosis of follicular thyroid cancer was made. Two cycles of radioactive iodine were performed. Both the follicular thyroid carcinoma (FTC) and the metastasis were investigated for the presence of BRAF/RAS and TERT promoter mutations. The results showed that the cutaneous metastasis was BRAF wild-type and TERT promoter-mutated (position g.1,295,228 C>T); in contrast, the primary thyroid lesion was negative for both molecular markers.

Current perspectives on the impact of clinical disease and biochemical control on comorbidities and quality of life in acromegaly.

Acromegaly is a rare chronic, systemic disorder caused by excessive growth hormone (GH) secretion from a somatotroph pituitary adenoma. GH hypersecretion leads to overproduction of insulin-like growth factor-1 (IGF-1), which contributes to the somatic overgrowth, physical disfigurement, onset of multiple systemic comorbidities, reduced quality of life (QoL) and premature mortality of uncontrolled patients. Somatostatin receptor ligands, dopamine agonists and a GH receptor antagonist are currently available for medical therapy of acromegaly. The main aim of treatment is biochemical normalisation, defined as age-normalised serum IGF-1 values and random GH levels <1.0 µg/L. However, there is an increasing evidence suggesting that achieving biochemical control does not always decrease the burden of disease-related comorbidities and/or improve patients' QoL. This lack of correlation between biochemical and clinical control can be due to both disease duration (late diagnosis) or to the peculiarity of a given comorbidity. Herein we conducted ad hoc literature searches in order to find the most recent and relevant reports on biochemical and clinical disease control during medical treatment of acromegaly. Particularly, we analyse and describe the relationship between biochemical, as well as clinical disease control in patients with acromegaly receiving medical therapy, with a focus on comorbidities and QoL. In conclusion, we found that current literature data seem to indicate that clinical disease control (besides biochemical control), encompassing clinical signs and symptoms, comorbidities and QoL, emerge as a primary focus of acromegaly patient management.