Life-threatening amiodarone-induced thyrotoxicosis - Personalized approach to radical treatment.

Objective: Amiodarone is an iodine-rich molecule and an effective antiarrhythmic drug. It is a first-line treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk. The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition.According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases. ; however, is not always feasible in the clinical setting due to the high anesthetic risk.We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status. Methods: Retrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022. Results: An electronic database search identified 75 patients hospitalized for severe AIT. At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/L (range 0.001-0.35), fT4 63.2 pmol/L (range 9.0 - >100), and fT3 10.2 pmol/L (range 3.8-49.3). All patients received optimal conservative treatment. Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure. In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation). The median dose of 131-I used for the therapy was 784MBq (range 627-860). The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism. Conclusion: The decision regarding the optimal time and type of radical treatment of AIT refractory to pharmacotherapy is critical for patients management and should not be delayed. Urgent therapy with 131-I may be an effective therapeutic option in patients who are unsuitable for thyroidectomy due to the high risk of anesthesia.

Increased incidence of myxedema coma during the COVID-19 pandemic and in the post pandemic era: a single-center case series.

The COVID-19 pandemic was a major challenge for all health care employees, but it was also difficult for patients to gain access to health care services. Myxedema coma (MC) is an extremely rare but potentially fatal endocrine emergency. The aim of the study was to report an increased incidence of life-threatening myxedema coma that occurred in relation to the COVID-19 pandemic. In this paper, we report a cohort of 11 patients with MC who were treated at the University Hospital in Krakow, Poland, in the period from 2015 to 2023. Only 1 case of MC was recorded in the period from 2015 to 2019, and, in the same area, 10 cases of MC were recorded after the start of COVID-19 pandemic until present. Hypothyroidism was diagnosed de novo in 2 (18%) patients; the remaining patients were severely hypothyroid due to therapy non-compliance. Nine patients had primary hypothyroidism, and 2 had central hypothyroidism. Besides longstanding hypothyroidism, an additional precipitating factor for MC was identified in 4 (36%) of the patients. Due to the inaccessibility of parenteral levothyroxine, patients were treated with oral, mostly liquid, form of levothyroxine. The mortality rate in this cohort was 27.2%. In conclusion, the increase of the incidence of MC, which is a life-threatening complication of inadequately treated hypothyroidism, during the COVID-19 pandemic, when resources were limited, and in the post-pandemic era, underlines the importance of adequate communication with patients and of long-term availability of primary care for patients with thyroid disease.

Patients with Cushing's syndrome suffer from provoked venous thromboembolism and are anticoagulated in various patterns.

Objective: Cushing's syndrome (CS) is associated with an 18-fold greater risk of venous thromboembolism (VTE). We aimed to identify factors which provoke VTE among patients with CS and VTE and to describe the anticoagulant regimen used in these cases. Methods: In this retrospective observational study, patients included in the European Registry on CS (ERCUSYN) in Krakow center, Poland, were followed for the occurrence of VTE and anticoagulant treatment. We identified factors provoking VTE according to the International Society of Thrombosis and Hemostasis (ISTH), along with factors included in the Padua score and CS-VTE score. Results: Of the 128 patients followed for a median of 4.3 years, there were nine patients who experienced ten VTE episodes (prevalence of 7.8% and incidence of 13.4 per 1000 patient-years). All VTEs were classified as provoked according to the ISTH guidance, predominantly due to the transient major and minor (50% and 20%, respectively) factors, while they were less commonly due to persistent (30%) factors. In 2/9 patients, we could not identify any risk factor for VTE according to the Padua score, while in 2/6 patients according to the CS-VTE score. Patients were mostly anticoagulated with vitamin K antagonists (4/8 patients), followed by direct oral anticoagulants (3/8) and low-molecular-weight heparin (1/8). The median duration of anticoagulation was 2.75 years and exceeded beyond the primary treatment in 28% of episodes provoked by transient factors. Conclusion: Further, multicenter studies are required to create a validated thrombotic risk score and guidelines regarding VTE treatment in CS patients.

The thrombotic risk in Cushing's syndrome-questions, answers, and the algorithm to consider in its assessment: part I-thrombotic risk not related to surgery.

Introduction: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing's syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients. Methods: The four relevant topics and questions on thrombotic risk in CS were identified. The current guidelines on prevention and diagnosis of venous thromboembolism (VTE) were reviewed for the answers. An algorithm to consider in the assessment of the thrombotic risk in patients with CS was proposed. Results: To address both generic and CS-specific risk factors for VTE, the algorithm includes the stepwise approach consisting of Padua Score, urine free cortisol, and CS-VTE score, with no indication for routine thrombophilia testing in the prediction of an index VTE episode. Having confirmed VTE, selected patients require thrombophilia testing to aid the duration of anticoagulant treatment. The separate part of the algorithm is devoted to patients with ectopic adrenocorticotropic hormone syndrome in whom exclusion of VTE precedes introducing routine thromboprophylaxis to prevent VTE. The cancer-related VTE also prompts thromboprophylaxis, with the possible vessel invasion. The algorithm presents a unifactorial and multifactorial approach to exclude high-bleeding risks and safely introduce thromboprophylaxis with low-molecular-weight heparin. Summary: Our article is the first to present an algorithm to consider in the thrombotic risk assessment among patients with Cushing's syndrome as a starting point for a broader discussion in the environment. A plethora of factors affect the VTE risk in patients with CS, but no studies have conclusively evaluated the best thromboprophylaxis strategy so far. Future studies are needed to set standards of care.

Tall stature and gigantism in adult patients with acromegaly.

OBJECTIVES: Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. METHODS: This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess. We established three categories for height for patients with acromegaly: normal stature, tall stature (TS, height above the 97th percentile (1.88 standard deviations (SD)) to <3 SD for gender- and country-specific data or as a height which was greater than 1.5 SD but less than 2 SD above the MPH) and gigantism (height which was greater than 3 SD) above the gender- and country-specific mean or greater than 2 SD above MPH). RESULTS: Thirteen percent (17/135) of patients (53% females) met the criteria for gigantism, 10% (14/135) fulfilled the criteria for TS (57% females). Parents and adult siblings were not taller than the population mean. CONCLUSION: In a group of 135 consecutive adult patients with acromegaly, 23% had increased height based on country-specific and MPH data: 13% presented with gigantism while 10% had TS. The frequency of gigantism and TS in patients diagnosed with GH excess as adults is not higher in males than in females. Patients with acromegaly come from normal-stature families.

Comparison of clinical characteristics of a pediatric cohort with combined pituitary hormone deficiency caused by mutation of the PROP1 gene or of other origins.

The most commonly identified genetic cause of combined pituitary hormone deficiency (CPHD) is PROP1 gene mutations. The aim of the study was to compare selected clinical features of patients with CPHD caused by variants of the PROP1 gene (CPHD-PROP1) and patients with inborn CPHD of other etiology (CPHD-nonPROP1). MATERIAL AND METHODS: The retrospective analysis included childhood medical records of 74 patients (32 female) with CPHD, including 43 patients (23 female) with the mutation in the PROP1 gene. RESULTS: Patients with CPHD-PROP1 compared to the CPHD-nonPROP1 presented with the following: significantly higher median birth weight (0.21 vs. - 0.29 SDS, p = 0.019), lower growth velocity within 3 years preceding growth hormone administration (- 2.7 vs. - 0.8 SDS, p < 0.001), higher mean maximal blood concentration of growth hormone within the stimulation process (1.2 vs. 1.08 ng/mL, p = 0.003), lower TSH (1.8 vs. 2.4 µIU/mL, p < 0.001), significantly lower prolactin concentrations (128 vs. 416.3 µIU/mL, p < 0.001), and less frequent typical signs of hypogonadism at birth in boys (n = 6; 30% vs. n = 12, 54%, p < 0.001). Secondary adrenal insufficiency was less frequent in CPHD-PROP1 (20 vs. 25 cases, p = 0.006) and occurred at a later age (13.4 vs. 10.4 years). MRI of the pituitary gland in CPHD-PROP1 revealed a small pituitary gland (21 cases), pituitary gland enlargement (eight cases), and one pituitary stalk interruption and posterior lobe ectopy, while it was normal in nine cases. CONCLUSION: Patients with the PROP1 mutations present a clinical picture significantly different from that of other forms of congenital hypopituitarism. Certain specific clinical results may lead to the successful identification of children requiring diagnostics for the PROP1 gene mutation.

Differences in clinical characteristics, treatment, and outcomes of sporadic and MEN-1-related insulinomas.

INTRODUCTION: Although in most cases insulinomas are small, benign, sporadic tumours, they can also be associated with hereditary syndromes, most commonly multiple endocrine neoplasia type 1 (MEN-1). Such a diagnosis significantly affects patient management. The objective was to elucidate the clinical differences between sporadic and MEN-1-linked insulinoma. MATERIAL AND METHODS: Comparison of clinical and histopathological characteristics, types of surgery, and outcomes of patients with sporadic and MEN-1-related insulinoma diagnosed between 2015 and 2022. RESULTS: There were 17 cases of insulinomas that underwent MEN-1 genetic testing (10 women and 7 men). In 7 cases, the mutation in the menin gene was confirmed. The median age at the time of diagnosis of sporadic insulinoma related to MEN-1 was 69 years (range 29-87) and 31.5 years (16-47), respectively. Primary hyperparathyroidism (PHP) was found in 6 of 7 patients with MEN-1-related insulinoma, while in none of the patients without MEN-1 mutations. Multifocal pancreatic NETs were found in 3 patients with MEN-1 syndrome, while in all sporadic cases there was a single pancreatic tumour. Two patients with insulinoma related to MEN-1 had a positive familial history of MEN-1-related diseases, while none with sporadic form. Dissemination at diagnosis was found in 4 cases, including 3 patients with insulinoma related to MEN-1-related insulinoma. Patients with sporadic and MEN-1-related insulinoma did not differ in tumour size, Ki-67 proliferation index, and outcome. CONCLUSIONS: Of all the features evaluated, only the multifocal nature of pancreatic neuroendocrine tumour (PanNET) lesions and a positive family history differentiated between patients with sporadic and MEN-1-related insulinomas. An age of insulinoma diagnosis of less than 30 years may be a strong indicator of an increased risk of MEN-1 syndrome.

COVID-19 infection in a patient with Cushing's disease on osilodrostat treatment.

Not required for Clinical Vignette.

Liquid levothyroxine in the treatment of myxoedema coma.

Not required for Clinical Vignette.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. METHODS: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 µSiemens) and estimated glomerular filtration rate (eGFR). RESULTS: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). CONCLUSIONS: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

Basics of prevention and management of iodine-based contrast media-induced thyroid dysfunction - position paper by the Polish Society of Endocrinology.

Medical practice involves a high number of radiological examinations using iodinated contrast media (ICM). Therefore, it is crucial for doctors of different specialties to be aware of possible adverse effects associated with ICM use. The most common and well characterized adverse effect is contrast-induced nephropathy, whereas thyroidal adverse reactions remain a diagnostic and therapeutic dilemma. ICM-induced thyroid dysfunction represents a highly heterogenous group of thyroid disorders. Due to supraphysiological iodine concentration, ICM can induce both hyper- and hypothyroidism. In most cases, the ICM-induced thyroid dysfunction is oligo- or asymptomatic, mild, and transient. In rare cases, however, the ICM-induced thyroid dysfunction may be severe and life threatening. Recently, the European Thyroid Association (ETA) Guidelines for the Management of Iodine-Based Contrast Media-Induced Thyroid Dysfunction were published. The authors advise an individualized approach to prevention and treatment of ICM-induced thyroid dysfunction, based on patient's age, clinical symptoms, pre-existing thyroid diseases, coexisting morbidities, and iodine intake. There is a geographic variation of ICM-induced thyroid dysfunction prevalence, which is linked to iodine intake. The prevalence of ICM-induced hyperthyroidism, which may pose a serious therapeutic challenge, is greater in countries with iodine deficiency. Poland is a region with a history of iodine deficiency, contributing to an increased prevalence of nodular thyroid disease, especially in the elderly. Therefore, the Polish Society of Endocrinology has proposed national, simplified principles of ICM-induced thyroid dysfunction prevention and treatment.

Individualized medical treatment options in Cushing disease.

Cushing disease (CD) is caused by a pituitary tumor which oversecretes adrenocorticotropic hormone (ACTH). It is a serious endocrine disease associated with increased mortality and impaired quality of life. The management of CD remains challenging. Although transsphenoidal surgery is the treatment of choice in most cases, in approximately half of CD patients, second or third-line treatment options are needed. Currently, new medical therapies are available which target adrenal steroidogenesis, pituitary somatostatin and dopamine receptors, and glucocorticoid receptors. Selection of which medication to use should be individualized and is determined by many factors including severity of the disease, possible side effects, patients preferences and local availability. The aim of this article is to describe currently available medical therapy to help clinicians individualize the treatment options in the context of recently updated Pituitary Society recommendations.