Search

A 59-year-old woman presented with flushing attacks accompanied by tachycardia and hypotension, which lasted approximately 30 to 60 minutes, underwent 18 years ago a gastrointestinal tumor resection. The histologic examination revealed a poorly differentiated mixed neuroendocrine/adenocarcinoma located in the caecum with regional metastases. Postoperatively, the patient received combined chemotherapy of 5-fluorouracil with interferon for six months and since has remained asymptomatic. Her examination revealed positivity for chromogranin A (CgA) and a-Fetoprotein (aFP) (580 ng/24 h, normal range 27–94, and 10 IU/mL, normal range 0–6, respectively). Urinary 5-hydroxy indole acetic acid excretion was remarkably high (41.8 mg/24 h, normal range 2–10 mg/24 h). An abdominal Magnetic Resonance Imaging scan revealed multiple focal loci in the liver whose histological examination revealed a carcinoid tumor confirmed by an Octreoscan. Additional uptake was noted on the right shoulder and the right sternum-clavicle joint confirmed by Tc-99m MDP scan. The patient received somatostatin analogue therapy followed by long-acting release octreotide analogue therapy (30 mg/month) showing a partial improvement of relevant biomarkers. Two years later, carcinoid syndrome symptoms reappeared and due to the tumors expression of somatostatin receptors the patient received peptide receptor radionuclide therapy with 177Lu-DOTATATE that resulted in both clinical and biochemical improvements.

Autoimmune thyroid disease (AITD) is the most common adverse effect in alemtuzumab (ALZ) treated relapsing–remitting (RR) multiple sclerosis (MS) patients. The objective of this prospective study was to analyze the occurrence, timing of onset, clinical course, and laboratory characteristics of AITD post-ALZ. We evaluated 35 RRMS patients treated with ALZ at a single academic MS center; clinical and laboratory data were collected before ALZ initiation and thereafter quarterly on follow-up with a median of 43.5 months. Seventeen out of 31 patients (54.8%) with no prior history of thyroid dysfunction developed AITD with a mean onset of 19.4 months ± 10.2 (SD) after the first ALZ cycle; Graves’ disease (GD) (n = 9); hypothyroidism with positive stimulating thyrotropin receptor antibodies (TRAb) (n = 1); Hashimoto thyroiditis (HT) (n = 6); HT with hypothyroidism (n = 1). Interestingly, seven of nine (77.7%) GD patients showed a fluctuating course. Three out of four patients with preexisting thyroid disease remained stable, whereas one with prior HT and hypothyroidism developed fluctuating GD. All patients with GD commenced antithyroid drugs (ATDs); five continued on “block and replace” treatment; one required radioactive iodine, and one total thyroidectomy. Our analysis showed earlier onset of ALZ-induced AITD in comparison to most other ALZ cohorts; overall, these patients required complex therapeutic approaches of the AITD. We observed a higher rate of fluctuating GD, with earlier onset and lower remission rate than previously reported, which in the majority of patients required prolonged “block and replace” therapy in the minimum dose of each therapeutic agent or more definitive interventions.

Obstructive sleep apnea (OSA) is a common but largely undiagnosed clinical condition, which is turning into a serious public health issue. Of note is that its prevalence is gradually increasing in parallel with the obesity and type 2 diabetes mellitus (T2DM) epidemics. The aim of this article is to comprehensively review the literature in order to evaluate the cardiovascular (CV) risk among patients with OSA and prediabetes or T2DM. OSA seems to be an independent risk factor for the development as well as the progression of T2DM, whereas it is associated with T2DM-related macrovascular and microvascular complications. OSA may also act as a potential risk factor for the presentation and development of CV disease, such as hypertension, coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation and other cardiac arrythmias, as well as stroke. OSA and T2DM also share common pathophysiological mechanisms leading to atherosclerosis. Considering that the coexistence of OSA and T2DM is an independent and cumulative risk factor for CV mortality, more so than the two diseases separately, clinicians and healthcare professionals should be aware of and screen for OSA in patients with T2DM. Notably, targeted therapy for both conditions seems to substantially improve CV prognosis.

Purpose. The objective of this retrospective study was to compare glycemic control, pregnancy outcome, as well as fetal/neonatal outcomes, between women with gestational diabetes mellitus (GDM) treated with (a) insulin detemir and (b) insulin neutral protamine Hagedorn (NPH). Methods. A total of 192 women with GDM were included. 98 women received detemir, while 94 women received NPH. Data regarding medical history, glycemic control, time and mode of delivery, as well as neonatal outcomes were recorded. Results. Baseline characteristics were comparable between the two groups. There were no differences with respect to the week of insulin initiation, total insulin dose, duration of insulin therapy, daily insulin dose/weight in early and late pregnancy, as well as the number of insulin injections per day. Maternal overall weight gain during pregnancy, and weight gain per week did not differ either. The detemir group had slightly lower HbA1c level at the end of gestation [median: Det 5.2% (33 mmol/mol) vs NPH 5.4% (36 mmol/mol), p = 0.035). There were no hypoglycemias or allergic reactions in both groups. There were also no differences regarding neonatal outcomes Conclusion. The use of insulin detemir for glucose control was found to be equally effective and safe compared with NPH.

Context: Association of central diabetes insipidus (CDI) and pituitary stalk thickening (PST) may have several etiologies (including malignancies) and differential diagnosis remains often difficult. Objective: The purpose of this study was to identify which clinical, biochemical or radiological features could help clinicians to make an etiological diagnosis, especially distinguishing neoplastic from non-neoplastic pituitary stalk lesions. Design and methods: We retrospectively analyzed clinical, biochemical, radiological and histological data of 38 adult patients diagnosed with CDI and PST of proven etiology. Results: Of the 38 pituitary stalk lesions included, 11 (29%) were neoplastic. A histopathological diagnosis was obtained in 22/38 (58%) patients. The three most frequently observed etiologies of PST were neuroinfundibulitis (34%), germinoma (21%) and histiocytosis (18%). Pituitary stalk thickness was larger for neoplastic lesions, particularly germinomas. Male gender and a very young age were statistically associated with a risk of germinoma. At least one anterior pituitary deficit was observed in nearly 60% of patients. Patients with neoplastic PST were more affected by multiple anterior pituitary dysfunction than patients with benign PST. A high serum prolactin level was individually the best predictor of a neoplastic origin (90% sensitivity and 60% specificity for a serum prolactin level 1.27-fold above the normal upper limit (ULN)). Conclusion: We confirm a relatively high risk of malignancy in adult patients presenting with the association of CDI and PST. Young age, male gender, a very large thickening of the stalk, multiple anterior pituitary deficits and prolactin above 1.3× ULN increase the likelihood of a neoplastic origin., SCOPUS: ar.j, info:eu-repo/semantics/published

Summary Medullary thyroid carcinoma (MTC) has a varying clinical course; distant metastases are frequently present even at diagnosis. We present two MTC cases with unusual metastatic sites. Two female patients are presented with slow progressive MTC. The first case developed distant metastases 23 years after diagnosis and underwent locoregional therapies. At the same time a breast mass developed representing MTC metastasis. Treatment with vandetanib led to long-term disease stabilization. The second patient is presented with metastases in the pancreas 13 years after diagnosis. Shortly, a painful mass developed in the mandible and metastasis of MTC was diagnosed. Disease progression was recorded 20 months after the initiation of local and systemic therapy. Such cases have only rarely been reported in the literature and highlight the need for prompt recognition of unexpected MTC metastases. Learning points Unusual sites of metastasis may appear in patients with medullary thyroid carcinoma (MTC) years after the initial diagnosis. Although rare, unexpected MTC metastases highlight the need for prompt recognition and appropriate treatment. Local recurrences accompanied by inappropriately low calcitonin levels should prompt further investigation for possible distant metastatic disease. Systemic treatment with tyrosine kinase inhibitors may be effective even in patients with unusual metastases from MTC.

Endocrine system plays a vital role in controlling human homeostasis. Understanding the possible effects of COVID-19 on endocrine glands is crucial to prevent and manage endocrine disorders before and during hospitalization in COVID-19-infected patients as well as to follow them up properly upon recovery. Many endocrine glands such as pancreas, hypothalamus and pituitary, thyroid, adrenal glands, testes, and ovaries have been found to express angiotensin-converting enzyme 2 receptors, the main binding site of the virus. Since the pandemic outbreak, various publications focus on the aggravation of preexisting endocrine diseases by COVID-19 infection or the adverse prognosis of the disease in endocrine patients. However, data on endocrine disorders both during the phase of the infection (early complications) and upon recovery (late complications) are scarce. The aim of this review is to identify and discuss early and late endocrine complications of COVID-19. The majority of the available data refer to glucose dysregulation and its reciprocal effect on COVID-19 infection with the main interest focusing on the presentation of new onset of diabetes mellitus. Thyroid dysfunction with low triiodothyronine, low thyroid stimulating hormone, or subacute thyroiditis has been reported. Adrenal dysregulation and impaired spermatogenesis in affected men have been also reported. Complications of other endocrine glands are still not clear. Considering the recent onset of COVID-19 infection, the available follow-up data are limited, and therefore, long-term studies are required to evaluate certain effects of COVID-19 on the endocrine glands.

We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highest IgG4-levels were more prone to thyroid-related autoimmune manifestations and specific autoimmune adverse events such as Crohn's disease, Graves' disease, and hemolytic anemia. Compared to baseline, total IgG-levels showed a trend towards reduced levels following two-courses of Alemtuzumab, but no significant change of C3 and/or C4-levels was observed. In conclusion, monitoring of IgG4-levels can serve as a marker for secondary autoimmunity risk in multiple sclerosis patients treated with Alemtuzumab.

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of highly active relapsing-remitting multiple sclerosis (MS). The principal adverse effect is the development of secondary autoimmune disorders during the immune reconstitution period after alemtuzumab, with autoimmune thyroid disease (AITD) being the most common. To define the type, timing and course of AITD after alemtuzumab treatment for MS we analyzed clinical and serologic data from 31 patients (follow-up range 8 to 58 months). Hashimoto thyroiditis (HT) with positive anti-TPO and/or anti-Tg antibodies was present at baseline in four patients. Of note, one of them 13 months after the first dose developed mild hyperthyroidism [stimulating TRAbs: 1,8U/L, normal range:40 U/L) as well as anti-Tg antibodies. Seven cases of HT with positive anti-TPO/anti-Tg antibodies were documented, of which one developed hypothyroidism. During follow-up, two successful pregnancies were recorded. The first, a 32-year-old woman, developed HT with hypothyroidism 12 months after the first cycle of alemtuzumab and gave birth to a healthy boy 22 months following last dose. The second, a 31-year-old woman, developed GD hyperthyroidism during the first trimester of pregnancy and was started on PTU that was stopped in the beginning of the second trimester. TRAbs titer declined and a healthy girl was delivered. Contrary to published literature, we recorded frequent occurrence of GD with fluctuating and unpredictable course requiring block and replace ATD regimen. This is suggestive of alternating stimulating and inhibitory TRAbs, while further studies are needed to understand the underlying mechanisms responsible for Th1-Th2 balance and cytokine pathways towards AITD. Pretreatment screening and careful follow-up allow for early diagnosis and treatment. Finally, concerning future pregnancies post-alemtuzumab it is important to address the risk for secondary AITD in women of childbearing age in conjunction with their treating obstetrician.

A 33-year-old Caucasian woman was referred at 24 + 3 weeks of gestation due to fetal tachycardia and hydrops. She had an uncomplicated pregnancy 16 years previously and was on levothyroxine after total thyroidectomy for Graves' disease 6 years previously, when she developed moderate exophthalmos. Laboratory evaluation revealed appropriate thyroid function for this time of gestation: thyroid stimulating hormone (TSH) 1.7 μU/ml (1–3), fT4 18.53 pmol/l (12−22), with positive antibodies: anti-TPO 157 U/ml (, Highlights • Fetal hyperthyroidism occurs in 1–5% of pregnancies with Graves' disease. • The risk correlates with the maternal TRAb titer. • Mothers even after a definitive treatment (thyroidectomy or ablative therapy) are at risk. • A multidisciplinary teamwork is needed. • Early diagnosis and treatment are crucial.