Purpose
The aim of this study was to assess whether oral liquid levothyroxine would correct tablet levothyroxine malabsorption induced by calcium or iron, two sequestrants of levothyroxine.
Methods
...Nineteen adult hypothyroid patients with tablet levothyroxine malabsorption caused by calcium and/or iron supplements were switched from tablet to liquid levothyroxine at the same dose. Primary outcomes were: (1) significantly lower mean serum thyroid-stimulating hormone with the liquid compared with the tablet formulation, and (2) significantly greater rate of serum thyroid-stimulating hormone less than or equal to 4.12 or 2.5 mU/L.The mean follow-up was 25.2 ± 16.5 weeks.
Results
TSH was lower with liquid levothyroxine compared with tablet levothyroxine (7.48 ± 5.8 vs. 1.95 ± 1.3 mU/L,
P
< 0.001), both in the calcium group (8.74 ± 7.2 vs. 2.15 ± 1.4,
P
< 0.001) and iron group (8.74 ± 7.2 vs. 1.68 ± 0.9,
P
< 0.001). Thyroid-stimulating hormone levels ≤4.12 mU/L in all patients, calcium group and iron group were more frequent post-switch (95, 87 and 100%) compared to pre-switch (26, 22 and 29%,
P
< 0.001), and so were thyroid-stimulating hormone levels ≤2.50 mU/L (66, 59 and 76% compared to 5, 9 and 0%,
P
< 0.001). The pattern held comparing the first liquid levothyroxine thyroid-stimulating hormone levels and the first tablet levothyroxine thyroid-stimulating hormone levels or the corresponding rates of thyroid-stimulating hormone levels below the target.
Conclusions
Liquid levothyroxine is resistant to the sequestration by calcium or iron. The high rate of thyroid-stimulating hormone normalization already at the first check (6–8 weeks) should avoid frequent adjustments in levothyroxine doses and assays of thyroid-stimulating hormone, with consequent financial savings.
The significance and impact of the coexistence of chronic lymphocytic thyroiditis (CLT) with thyroid cancer is still debated. To verify the influence of CLT on papillary thyroid cancer (PTC), we ...retrospectively collected 505 PTC cases and analyzed age at diagnosis, sex, size, lymph node status, and staging. We found that CLT was present in 168 PTC (33.3%). Compared with the 337 patients without CLT (non-CLT), CLT patients were younger (44.42 ± 13.72 vs. 47.21 ± 13.76 years,
= 0.03), had smaller tumors (9.39 ± 6.10 vs. 12 ± 9.71 mm,
= 0.002), and lower rate of lymph node metastases (12.5 vs. 21.96%,
= 0.01, OR = 0.508). Tumor-node-metastasis (TNM) staging (T1a through T4) was more favorable for the CLT group compared to the non-CLT group (for instance, T1a = 65.5 vs. 49.8%, T3 = 4.8 vs. 23.4%). This study shows that one in three patients with PTC harbors CLT, which is associated with a more favorable TNM staging, consistently with a favorable outlook of PTC.
Thyroid Autoimmunity and Lichen Guarneri, Fabrizio; Giuffrida, Roberta; Di Bari, Flavia ...
Frontiers in endocrinology (Lausanne),
06/2017, Letnik:
8
Journal Article
Recenzirano
Odprti dostop
Lichen planus (LP) and lichen sclerosus (LS) are cutaneous-mucous diseases with uncertain epidemiology. Current data, which are likely to be underestimated, suggest a prevalence in the general ...population of 0.1-4% for cutaneous LP, 1.27-2.0% for oral LP, and 0.1-3.3% for LS. While etiology of lichen is still unknown, clinical and histological evidence show an (auto)immune pathogenesis. Association of lichen with autoimmune thyroid disease (AITD) has been investigated in few studies. This association appears better defined in the case of LS, while is more controversial for LP. In both situations, the frequency of the association is higher in females. We review the available literature on the correlation between the different types of lichen and AITD, and the literature on the genetic risk factors which are shared by both conditions. Such data suggest that a common pathogenic mechanism could be the cause for co-occurrence of lichen and AITD, at least in some patients. Additionally, analyzing literature data and in continuity with our previous work on other autoimmune diseases, we suggest that molecular mimicry could trigger both diseases, and thus explain their co-occurrence.
Primary hyperparathyroidism (PHPT) is rare in pregnancy. PHPT and hypercalcemia are associated with negative maternofetal outcomes. Therefore, an early diagnosis and adequate treatment are essential.
...We described the case of a pregnant woman complaining of nausea, vomiting and weight loss. Diagnosis of gestational PHPT (GPHPT) was made based on elevated serum calcium and parathyroid hormone levels (3.4 mmol/L and 41.6 pmol/L). Neck ultrasound documented a nodule suggestive of enlarged parathyroid, whereas the abdomen ultrasound revealed renal microlithiasis. Conservative treatment was started with oral hydration and a low-calcium diet. Clinical and biochemical monitoring was weekly and multidisciplinary. Despite our suggestion, the patient refused parathyroidectomy in the second trimester. Additional intravenous fluid rehydration from the 15th to the 25th week of gestation ameliorated the symptoms rapidly, and reduced calcium levels progressively from the 23rd week. At week 40, the woman gave birth to a healthy girl. At month 8 postpartum, calcemia and PTH were still elevated, and accompanied by osteoporosis and nephrocalcinosis. Surgery was accepted, and a parathyroid adenoma was removed.
In the absence of guidelines for GPHPT management, its treatment should be individualized. In our case, despite high calcium levels, conservative treatment with strict monitoring led to a positive outcome of pregnancy.
Purpose
To verify the prevalence of autoimmune thyroiditis (AIT) and the ultrasound characteristics (composition and volume) of thyroid nodules with respect to the area of residence in the province ...of Messina, some areas having environmental issues.
Methods
Fine-needle aspiration-interrogated nodules (
n
= 902) of 809 patients were evaluated upon stratification into 8 areas of residence.
Results
Overall, women were younger than men (55.3 ± 14.0 vs. 58.6 ± 12.6 years,
P
= 0.0083). Patients residing in three areas (one hosting two garbage dumps, one hosting a petrochemical complex and a thermoelectrical power plant, and one hosting several ceramic factories CFA) were younger than those residing in the city of Messina (MEA) (52.9 ± 13.4 vs. 57.7 ± 13.6 years,
P
< 0.0001). Also, patients residing in those three areas had a greater rate of AIT, diagnosed either ultrasonographically/serologically (22.2% of patients) or cytologically (26.3% of nodules), compared with MEA (11.7% of patients,
P
= 0.0007 or 20.2% of nodules,
P
= 0.0815). Rates of AIT ranged 12.5–28.6% in the remaining four areas. Overall, nodules in women were smaller than in men (3.6 ± 5.7 vs. 6.1 ± 9.4 ml,
P
= 0.0006). Compared with the other seven areas, patients living in CFA had the largest nodules (6.8 ± 6.8 ml,
P
= 0.0040–0.0291), with the nodule volume being inversely correlated to patient’s age (
r
= −0.4955,
P
= 0.0431).
Conclusion
Rates of AIT and associated ultrasound features of thyroid nodules vary in different areas of our province. Further studies correlating these rates and features with exposure to specific toxicants are warranted.
Graves' is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of thyroid stimulating hormone (TSH) ...and stimulates the thyroid hormone receptor (TSHR), which results in hyperthyroidism (overactive thyroid gland) and goiter. Methimazole (MMI) is used for hyperthyroidism treatment for patients with Graves' disease.
We have developed a model using a system of ordinary differential equations for hyperthyroidism treatment with MMI. The model has four state variables, namely concentration of MMI (in mg/L), concentration of free thyroxine - FT4 (in pg/mL), and concentration of TRAb (in U/mL) and the functional size of the thyroid gland (in mL) with thirteen parameters. With a treatment parameter, we simulate the time-course of patients' progression from hyperthyroidism to euthyroidism (normal condition). We validated the model predictions with data from four patients.
When there is no MMI treatment, there is a unique asymptotically stable hyperthyroid state. After the initiation of MMI treatment, the hyperthyroid state moves towards subclinical hyperthyroidism and then euthyroidism.
We can use the model to describe or test and predict patient treatment schedules. More specifically, we can fit the model to individual patients' data including loading and maintenance doses and describe the mechanism, hyperthyroidism→euthyroidism. The model can be used to predict when to discontinue the treatment based on FT4 levels within the physiological range, which in turn help maintain the remittance of euthyroidism and avoid relapses of hyperthyroidism. Basically, the model can guide with decision-making on oral intake of MMI based on FT4 levels.
Purpose
In 236 pregnant women, we showed that selective or predominant consumption of swordfish (group A) was associated with high rates of positivity for serum thyroid autoantibodies (TPOAb and ...TgAb) throughout day 4 postpartum. In contrast, selective or predominant consumption of oily fish (group B) was associated with TPOAb and TgAb negativity. Rates were intermediate in group C (scanty consumption of swordfish) and group D (consumption of fish other than swordfish and oily fish). Gestational TPOAb positivity is a risk factor for postpartum thyroiditis (PPT), which evolves into permanent hypothyroidism (PH) in about 50% of cases. Purpose of this study was to verify that the different rates of thyroid autoantibodies in the four groups translated into different PPT rates.
Methods
We expanded our previous cohort (
n
= 412) and duration of follow-up (month 12 postpartum), and measured frequency of PPT and PH.
Results
At first timester of gestation, we confirmed the different Ab positivity rates in group A vs. group B (TPOAb = 21.7% vs. 4.7%,
P
< 0.0001; TgAb = 14.1% vs. 2.4%,
P
< 0.05). Overall, PPT prevalence was 63/412 (15.3%), but 22/92 in group A (23.9%), 4/85 in group B (4.7%;
P
< 0.0001 vs. group A), 17/108 (15.7%) in group C, and 16/117 (13.7%) in group D. Approximately half of the PPT women had PH, regardless of fish group.
Conclusions
In conclusion, stable consumption of oily fish (which is enriched in polyunsaturated omega-3 fatty acids) protects from PPT, while stable consumption of swordfish (which is enriched in pollutants) favors PPT. Thus, a dietary prophylaxis of PPT is possible.
Cabozantinib in Thyroid Cancer Fallahi, Poupak; Ferrari, Silvia M; Di Bari, Flavia ...
Recent patents on anti-cancer drug discovery,
01/2015, Letnik:
10, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Cabozantinib is an oral once-daily multitarget tyrosine kinase inhibitor of MET, VEGFR2, RET, acting against KIT, AXL, FLT3 and Tie-2. Cabozantinib has shown anti-cancer effects in preclinical and ...clinical models of cancers derived from both epithelial and mesenchymal origins prostate cancer, non small lung cancer, medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC), renal cell carcinoma, etc.. In a Phase III clinical study, cabozantinib improved PFS (11.2 months versus 4.0 months in the placebo group) of patients with MTC (independently of age, bone metastases, RET status and prior treatment). Cabozantinib was approved in 2012 by FDA for metastatic MTC and in 2013 by EMA. Cabozantinib has been also evaluated in metastatic DTC patients, because they have activation on tyrosine kinases, including MET, VEGFR2 and RET, suggesting the possible use of cabozantinib in metastatic DTC. Actually, two Phase II trials of cabozantinib in DTC patients resistant to RAI are ongoing. To increase the antineoplastic effect of cabozantinib, and to overcome the occurrence of drug resistance, combination studies with other anticancer agents are ongoing. In conclusion, cabozantinib has shown to exert an important therapeutic effect in patients with MTC improving PFS. In DTC patients, cabozantinib has shown promising results.
Patients with idiopathic gynaecomastia have greater BMI and an unfavourable lipid profile compared with age‐matched controls. Twenty‐five adult eugonadal patients with idiopathic gynaecomastia and 50 ...age‐ and BMI‐matched controls were selected. Clinical and biochemical parameters and ultrasound testis volume were reviewed retrospectively. Patients and controls differed for no biochemical parameter, except for LH levels, which were 31% higher in patients (p = 0.019), although within the normal range. Compared with controls, patients had a threefold greater rate of elevated LDL‐c (p = 0.025). Patients ≥ 25 years had higher levels of serum LDL‐c compared with either patients < 25 years (p = 0.006) or controls ≥ 25 years (p = 0.012). In patients, both at bivariate analysis and at linear regression, age correlated positively with total cholesterol and LDL‐c, the latter correlated inversely with total testosterone. Negative interactions were found for age and total testosterone with LDL‐c, for LH and estradiol to testosterone ratio (E2:T) with LDL‐c, and for age and E2:T with total cholesterol. Our data suggest inadequate local androgen action in patients with idiopathic gynaecomastia. This partial androgen resistance might blunt the beneficial effects of testosterone on lipid metabolism. Further studies are needed to verify whether this metabolic derangement impacts the cardiovascular health of these patients.
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