5-Fluorouracil-associated severe hypertriglyceridaemia with positive rechallenge.

Chemotherapy-induced hypertriglyceridaemia (HTG) is a potential serious adverse event. Severe HTG with triglycerides (TG) >11.3 mmol/L (1000 mg/dL) can cause acute pancreatitis in addition to cardiovascular diseases such as coronary artery disease. While the association of capecitabine (5-fluorouracil (5-FU) prodrug) with clinically relevant HTG is a well-known adverse reaction, 5-FU is not typically associated with HTG. We here report the case of a patient who developed 5-FU-associated grade 4 HTG with TG level raising up to 37.1 mmol/L (3286 mg/dL) occurring after the ninth cycle of adjuvant FOLFOX (Fluorouracil and Oxaliplatin) chemotherapy. Fenofibrate treatment and diet were started. Chemotherapy was postponed and then resumed for two additional cycles. However, severe HTG recurred shortly after. Chemotherapy was therefore permanently stopped. Approximately 8 weeks after chemotherapy discontinuation, TG fell back to range at 2.1 mmol/L (189 mg/dL) allowing interruption of fenofibrate without HTG recurrence at 3 months.

Relapse of Human Chorionic Gonadotropin-Induced Hyperthyroidism and Severe Hyperemesis Gravidarum Secondary to Twin-Twin Transfusion Syndrome, With Rapid Recovery Following Fetoscopic Laser Coagulation: Case Report.

Background: Limited data have shown that, compared to uncomplicated twin pregnancies, pregnancies complicated by twin-twin transfusion syndrome (TTTS), a life-threatening condition, are associated with higher maternal serum levels of both human chorionic gonadotropin (hCG) and thyroid hormones. With the continuing expansion of assisted reproductive technologies, the rate of twin pregnancies, including those complicated by TTTS and associated hyperemesis gravidarum, is expected to increase further. Therefore, detailed descriptions of the maternal and fetal clinical outcomes of maternal thyrotoxicosis linked to TTTS can be useful for timely diagnosis and management. However, such descriptions are currently lacking in the literature. Case Presentation: We report the case of a 30-year-old woman carrying a monochorionic twin pregnancy complicated by TTTS that induced a relapse of severe hyperemesis gravidarum with overt non-autoimmune hyperthyroidism at 17 weeks of gestation. Following fetoscopic laser coagulation (FLC), both hyperemesis and hyperthyroidism improved within 1 week. Conclusions: The present experience contributes to the knowledge base on maternal thyrotoxicosis linked to TTTS and can be useful in the diagnosis and treatment of future cases; it also emphasizes the need for a high degree of clinical suspicion and for close collaboration between endocrinologists and obstetricians. Another key point is that TTTS-associated hyperemesis gravidarum and maternal hyperthyroidism should be considered in the differential diagnosis of refractory or relapsing hyperemesis gravidarum in women with monochorionic twin pregnancy, because this condition may require more stringent supportive treatment before and during the FLC procedure when the mother is overtly hyperthyroid.

Interprofessional Medication Adherence Program for Patients With Diabetic Kidney Disease: Protocol for a Randomized Controlled and Qualitative Study (PANDIA-IRIS).

BACKGROUND: Despite effective treatments, more than 30% of patients with diabetes will present with diabetic kidney disease (DKD) at some point. Patients with DKD are among the most complex as their care is multifactorial and involves different groups of health care providers. Suboptimal adherence to polypharmacy is frequent and contributes to poor outcomes. As self-management is one of the keys to clinical success, structured medication adherence programs are crucial. The PANDIA-IRIS (patients diabétiques et insuffisants rénaux: un programme interdisciplinaire de soutien à l'adhésion thérapeutique) study is based on a routine medication adherence program led by pharmacists. OBJECTIVE: The aim of this study is to define the impact of the duration of this medication adherence program on long-term adherence and clinical outcomes in patients with DKD. METHODS: This monocentric adherence program consists of short, repeated motivational interviews focused on patients' medication behaviors combined with the use of electronic monitors containing patients' medications. When patients open the electronic monitor cap to take their medication, the date and hour at each opening are registered. In total, 73 patients are randomized as 1:1 in 2 parallel groups; the adherence program will last 6 months in the first group versus 12 months in the second group. After the intervention phases, patients continue using their electronic monitors for a total of 24 months but without receiving feedback. Electronic monitors and pill counts are used to assess medication adherence. Persistence and implementation will be described using Kaplan-Meier curves and generalized estimating equation multimodeling, respectively. Longitudinal adherence will be presented as the product of persistence and implementation and modelized by generalized estimating equation multimodeling. The evolution of the ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified-Release Controlled Evaluation) and UKPDS (United Kingdom Prospective Diabetes Study) clinical scores based on medication adherence will be analyzed with generalized estimating equation multimodeling. Patients' satisfaction with this study will be assessed through qualitative interviews, which will be transcribed verbatim, coded, and analyzed for the main themes. RESULTS: This study was approved by the local ethics committee (Vaud, Switzerland) in November 2015. Since then, 2 amendments to the protocol have been approved in June 2017 and October 2019. Patients' recruitment began in April 2016 and ended in October 2020. This study was introduced to all consecutive eligible patients (n=275). Among them, 73 accepted to participate (26.5%) and 202 (73.5%) refused. Data collection is ongoing and data analysis is planned for 2022. CONCLUSIONS: The PANDIA-IRIS study will provide crucial information about the impact of the medication adherence program on the adherence and clinical outcomes of patients with DKD. Monitoring medication adherence during the postintervention phase is innovative and will shed light on the duration of the intervention on medication adherence. TRIAL REGISTRATION: Clinicaltrials.gov NCT04190251_PANDIA IRIS; https://clinicaltrials.gov/ct2/show/NCT04190251. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25966.

Combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab causing acute-onset type 1 diabetes mellitus following a single administration: two case reports.

BACKGROUND: The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. CASES PRESENTATION: We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. CONCLUSIONS: Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

Thyrotropin-secreting pituitary adenomas: a systematic review and meta-analysis of postoperative outcomes and management.

PURPOSE: TSH-secreting pituitary adenomas are rare pituitary tumors. An efficient treatment is essential to limit the mortality and morbidity in untreated patients. The aim of this study is to summarize the evidence about the postoperative outcomes and management of this rare pathology. METHODS: A systematic search and meta-analysis of surgical series was performed. RESULTS: Our analysis included 23 articles (536 patients). No sex difference was observed and mean age at diagnosis was 45 years. Hyperthyroidism was reportedly clinical in 67% and biochemical in 90% of patients. Co-secretion of other pituitary hormones was present in 42% of cases. Macroadenomas were found in 79% of patients, showing in 44% and 30% of cases respectively extrasellar extension and cavernous sinus invasion. The pooled rate of postoperative biochemical remission was 69.7% and a gross total resection (GTR) was observed in 54% of patients. The extent of resection was significantly increased in microadenomas (p < 0.001) and cavernous sinus invasion was predictive of lower GTR rate (p < 0.001). A biochemical remission was achieved in 66% of patients after adjuvant radiation therapy and in 76% after adjuvant medical treatment. The combination of both allowed remission in 67% of cases. At final follow-up the overall biochemical remission rate was significantly improved (85.8%) when compared to the postoperative biochemical remission (p < 0.001). CONCLUSION: When compared to the early postoperative period, at last follow-up biochemical remission was significantly greater (p < 0.001). GTR was achieved in half of patients; the size of tumor and cavernous sinus invasion determined the extent of resection.

The Bethesda System for Reporting Thyroid Cytopathology Explained for Practitioners: Frequently Asked Questions.

BACKGROUND: The recent update of The Bethesda System for Reporting Thyroid Cytology (TBSRTC) is a very important development in the evaluation of thyroid nodules. Clinical experience and scientific literature both show that practitioners performing thyroid fine-needle aspiration are accustomed to basing the clinical management of patients on reports using TBSRTC. Specifically, clinicians are familiar with the percent risk of malignancy corresponding to each TBSRTC diagnostic category (DC), as well as with the respective recommendation for clinical management. However, most clinicians are much less familiar with the specific considerations that lie between a given DC, on the one end, and the respective risk of malignancy and associated management recommendation, on the other end. SUMMARY: A deeper understanding of the system can enlighten the clinician's thinking about the specific nodule under examination and can guide the decision-making process in a more meaningful way. Such an understanding can only be developed via close two-way communication between cytopathologists and clinicians. Through this type of interaction in the authors' tertiary medical center, recurring issues of particular importance for clinical practice were identified, which are reported here in the form of 16 frequently asked questions posed by the clinician to the cytopathologist. CONCLUSIONS: For each frequently asked question, an answer is provided based on the literature, the authors' experience, the new version of TBSRTC, and the new World Health Organization classification of tumors of endocrine organs.

Bone Mineral Density in Sheehan's Syndrome; Prevalence of Low Bone Mass and Associated Factors.

Hypopituitarism is a known cause of bone mineral loss. This study aimed to evaluate the frequency of osteopenia and osteoporosis in patients with Sheehan's syndrome (SS) and to determine the risk factors. This is a retrospective study of 60 cases of SS that have had a bone mineral density (BMD) measurement. Clinical, biological, and therapeutic data were collected. The parameters of osteodensitometry at the femoral neck and the lumbar spine of 60 patients with SS were compared with those of 60 age-, height-, and weight-matched control women. The mean age at BMD measurement was 49.4 ± 9.9 yr (range: 25-76 yr). The mean duration of SS was 19.3 ± 8.5 yr (range: 3-41 yr). All patients had corticotropin deficiency and were treated with hydrocortisone at a mean daily dose of 26.3 ± 4.1 mg. Fifty-seven patients (95%) had thyrotropin deficiency and were treated with thyroxine at a mean daily dose of 124.3 ± 47.4 µg. Thirty-five of the 49 patients, aged less than 50 yr at diagnosis and having gonadotropin deficiency (71.4%), had estrogen-progesterone substitution. Osteopenia was present in 25 patients (41.7%) and osteoporosis in 21 (35.0%). The BMD was significantly lower in the group with SS than in the control group (p < 0.001). The odds ratio of osteopenia-osteoporosis was 3.1 (95% confidence interval: 1.4-6.8) at the femoral neck and 3.7 (95% confidence interval: 1.7-7.8) at the lumbar spine. The lumbar spine was more frequently affected by low bone mineral mass (p < 0.05). The duration of the disease and the daily dose of hydrocortisone were independently and inversely associated with BMD at the femoral neck. The daily dose of thyroxine was independently and inversely associated with BMD at the lumbar spine. Estrogen-progesterone replacement therapy was not associated with BMD. Low bone mineral mass was very common in patients with SS. The lumbar spine was more frequently affected. The duration of the disease and the doses of hydrocortisone and thyroxine were involved in bone mineral loss.

Determination of catecholamines in plasma and urine.

For more than 20 years, measurement of catecholamines in plasma and urine in clinical chemistry laboratories has been the cornerstone of the diagnosis of neuroendocrine tumors deriving from the neural crest such as pheochromocytoma (PHEO) and neuroblastoma (NB), and is still used to assess sympathetic stress function in man and animals. Although assay of catecholamines in urine are still considered the biochemical standard for the diagnosis of NB, they have been progressively abandoned for excluding/confirming PHEOs to the advantage of metanephrines (MNs). Nevertheless, catecholamine determinations are still of interest to improve the biochemical diagnosis of PHEO in difficult cases that usually require a clonidine-suppression test, or to establish whether a patient with PHEO secretes high concentrations of catecholamines in addition to metanephrines. The aim of this chapter is to provide an update about the catecholamine assays in plasma and urine and to show the most common pre-analytical and analytical pitfalls associated with their determination.

[Blood pressure and type 2 diabetes mellitus: impact of the insulin therapy]. / Pression arterielle et diabete de type 2: impact de la mise sous insuline.

BACKGROUND: The incidence of arterial hypertension is by 2-3 times with diabetics than with non-diabetics. Etiopathogenesis of arterial hypertension in type 2 diabetes is multifactorial insulin-resistance, obesity, hyperlipoproteinemia, age, smoking and probably method of treatment (insulin therapy). The aim of this retrospective study is to evaluate, over 5 years period, the level of blood pressure and the frequency's progression of arterial hypertension in 35 type 2 diabetes patients treated with insulin METHODS: comparison of 35 type 2 diabetes patients treated with insulin to 35 controls treated with oral hypoglycemic agents. RESULTS: No significant differences were found over 5 years period in mean systolic blood pressure, mean diastolic blood pressure and frequency of arterial hypertension. However, frequency of arterial hypertension was correlated with mean dose of insulin. CONCLUSION: Our study confirms the long-term results found in the literature reading effects of insulin therapy on blood pressure in diabetic patients.

Food intake and high density lipoprotein cholesterol levels changes during ramadan fasting in healthy young subjects.

During the holy month of Ramadan, it is obligatory for all adult healthy Muslims to abstain from food, drink and smoking each day from dawn to sunset. The aims of our study were to evaluate the effects of Ramadan fasting on plasma lipids, lipoproteins and the change of food consumption in healthy subjects. Thirty young healthy and normal weighted adults (9 males and 21 females) were evaluated during three periods: 3 weeks before Ramadan (T0); the 4th week of Ramadan (T1) and 3 weeks after the end of Ramadan (T2). Main Clinical and biological parameters investigated were: body weight, blood glucose, plasma triglycerides (TG), plasma total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and. low density lipoprotein cholesterol (LDL-c) Body weight, and blood glucose were unchanged. There was a significant increase of the mean daily caloric intake, the lipids intake particularly mono-unsaturated and poly-unsaturated fatty acids (p < 0.001) and cholesterol intake (p < 0.001) during Ramadan with a decrease of the meal frequency. There was also a significant increase of plasma total cholesterol and HDL-cholesterol. The most striking finding was a significant increase in the HDL-Cholesterol during Ramadan +20% (p < 0.02). This increase was lost after Ramadan. Fasting Ramadan affects beneficially serum lipoprotein metabolism in young adult healthy subjects with an increase of HDL-cholesterol.

[Graves' ophthalmopathy: diagnosis and highlights on etiopathogenesis and treatment]. / L'exophtalmie basedowienne: diagnostic et mise au point etiopathogeniques et therapeutiques.

It's due to extraocular tissues enlargement: extraocular muscles. Thyroid stimulating receptor antibodies were first incriminated. However, Graves' proptosis can appear several months or years before development of goiter or thyrotoxicosis. Different treatment are possible: glucocorticoids, radiotherapy, surgical orbitary decompression, classical surgery. Treatment of hyperthyroidism has to be undertaken similarly. Classically, surgical or medical treatment with antithyroid drugs were indicated.