New onset type 1 diabetes mellitus is an uncommon but possible complication triggered by SARSCoV- 2 infection. Metabolic inflammation supported by cytokine storm leading to pancreatic beta cells ...destruction is the most probable link between COVID-19 and diabetes. Here, we describe the case of a 51-year-old female suffering from Hashimoto thyroiditis, who came to our attenction for new onset polyuria-polydipsia syndrome associated to hyperglycemia after a mild form of COVID- 19 recognized two months before and already recovered. Type 1 diabetes was diagnosed.
The management of patients with differentiated thyroid carcinoma (DTC) showing low levels of serum thyroglobulin autoantibodies (TgAb) and undetectable Tg after thyroidectomy is unsettled. This study ...sought to elucidate the clinical significance of low levels of TgAb and to evaluate their interference with Tg measurement in vitro.
Tg and TgAb levels were correlated with the post-thyroidectomy staging of 177 consecutive DTC patients undergoing (131)I ablation after total thyroidectomy (clinical study). Tg was measured by an immunometric assay (functional sensitivity: 0.1 ng/mL), and TgAb were evaluated by six assays (functional sensitivities: 1.2-96 IU/mL; positive cutoffs: 4-150 IU/mL). The changes in Tg concentration (Tg recovery) of diluted specimens from DTC patients were also measured after incubation with 67 sera from DTC patients with undetectable Tg and low levels of TgAb (in vitro study). DTC sera containing Tg were diluted serially (from 330 to 0.1 ng/mL) and incubated with TgAb samples; Tg was then measured.
In the clinical study: all patients had residual thyroid tissue, and 10 had metastatic disease. Depending on the TgAb assay, median Tg values were 7.0-10.9, 0.0-5.3, and 0.0-0.0 ng/mL in patients with undetectable, borderline (between functional sensitivities and positive cutoffs), and positive TgAb, respectively (p < 0.001). An undetectable Tg value was associated with borderline levels of TgAb in five assays. Only two patients with metastatic disease had undetectable Tg; both were TgAb positive by three or more assays. Conversely, no patient with undetectable Tg and undetectable or borderline TgAb by sensitive assays had metastatic disease. In the in vitro study, TgAb interfered significantly with Tg recovery (p < 0.001), but low levels of TgAb did not abolish Tg recovery.
While low levels of TgAb do not preclude Tg measurement in vitro, they can be associated with an undetectable Tg in DTC patients with residual thyroid tissue after thyroidectomy. However, the finding of low levels of TgAb by sensitive assays associated with an undetectable Tg rules out metastatic disease.
According to Rundle's curve, Graves' ophthalmopathy (GO) worsens during an initial phase up to a peak of maximum severity, then improves and reaches a static plateau, with the activity curve ...preceding the severity curve by a few months. To our knowledge, no studies have tried to replicate Rundle's curve, and very few have investigated the natural history of GO. Here, we studied GO natural history retrospectively and tried to identify factors that may affect it.
A total of 65 patients with untreated GO underwent an eye assessment after a median of seven months after the appearance of GO and then after a median of 40 months. The primary endpoints were the variation of the single GO features and of the NOSPECS score, as well as the overall outcome of GO. The secondary endpoint was the influence of several variables (age, sex, smoking, GO and thyroid disease duration, thyroid treatment, thyroid status, thyroid volume, anti-TSH receptor autoantibodies) on the outcome of GO.
The majority of patients had mild, minimally active GO, and only five had a Clinical Activity Score (CAS) >3. There was a significant reduction of CAS (p<0.0001) and NOSPECS (p=0.01) between the first and last observation, with a timing pattern resembling Rundle's curve. This difference was confirmed even when patients with a CAS >3 at first observation were excluded. At the last observation, 50.8% of patients had improved, 33.8% had remained stable, and 15.4% had worsened moderately or substantially. The overall outcome of GO was not affected by any of the variables under examination.
In confirmation of Rundle's observations, untreated GO improves spontaneously with time in the majority of patients, with an activity peak between 13 and 24 months, which may have implications in determining the proper timing of GO treatments.
Objective: To report on 2 patients with moderate to severe Graves ophthalmopathy (GO) who developed dysthyroid optic neuropathy following levothyroxine (LT4) withdrawal in preparation for 131I ...treatment for thyroid carcinoma.Methods: Two patients referred to a center for the treatment of thyroid diseases were evaluated.Results: Patient 1, a 55-year-old woman, had active (clinical activity score CAS, 5 out of 7 moderate to severe GO. After LT4 withdrawal, her left eye visual acuity decreased from 10/10 to 1/10, and her omolateral visual field was impaired. Euthyroidism was rapidly restored and GO was treated with intravenous glucocorticoids. Nevertheless, as the patient's visual acuity was still impaired, orbital decompression was performed. Patient 2, a 50-year-old man, had active (CAS, 3 out of 7) moderate to severe GO. After LT4 withdrawal, the patient developed a right dysthyroid optic neuropathy. His visual acuity decreased from 10/10 to 4/10, and his omolateral visual field was impaired. After prompt restoration of euthyroidism and treatment with intravenous glucocorticoids, normalization of his visual acuity was achieved.Conclusion: In moderate to severe GO, dysthyroid optic neuropathy may be precipitated in thyroidectomized patients following LT4 withdrawal, even if triiodothyronine at doses that do not prevent elevated serum thyroid-stimulating hormone concentrations are administered, suggesting that hypothyroidism should be carefully avoided in patients with such grades of GO.Abbreviations: CAS clinical activity score DON dysthyroid optic neuropathy GD Graves disease GO Graves ophthalmopathy LE left eye LT4 levothyroxine RE right eye rhTSH recombinant human thyroid-stimulating hormone T3 triiodothyronine TRAb thyroid-stimulating hormone receptor autoantibody TSH thyroid-stimulating hormone TTA total thyroid ablation
Clinically overt Graves' orbitopathy (GO) is associated with Graves' disease (GD) in approximately 95% of cases, whereas the remaining 5% is observed in patients with hypothyroid autoimmune ...thyroiditis (AT) or without overt thyroid dysfunction (euthyroid GO). However, it is not known whether there is a difference in terms of GO phenotype between patients with GD and those with hypothyroid AT or without thyroid dysfunction, and hence this is investigated here.
The study design was to evaluate retrospectively all consecutive patients with a recent manifestation of GO, seen at their first visit to a tertiary referral center over a period of 10 years. In total, 358 GO patients were studied, and all of them underwent GO assessment.
Of the 358 patients studied, 341 had hyperthyroid GD, 10 had AT with hypothyroidism, and seven had euthyroid GO. Age, sex, and smoking habits were similar in the three groups, as was the time since GO was first noticed (GO duration). The vast majority of patients had moderate to severe, active GO, as expected in a tertiary referral center. Exophthalmometry, eyelid width, clinical activity score (CAS), diplopia, and visual acuity did not differ between patients with GD and those with AT or euthyroid GO, suggesting that the GO phenotype was similar. Accordingly, the NOSPECS score did not differ between the three groups.
The phenotype of GO is similar regardless of the underlying thyroid disease. Because this study was performed in a tertiary referral center, this conclusion can be restricted only to patients who develop moderate to severe GO.
Context:
Serum thyroglobulin (Tg), the marker of residual tumor in papillary thyroid carcinoma, can be underestimated in patients with Tg autoantibodies (TgAb). TgAb are due to a coexistent ...lymphocytic thyroiditis (LT) or the papillary thyroid carcinoma per se. TgAb assays are highly discordant.
Design:
We evaluated 141 patients with a clinical diagnosis of nodular thyroid disease, 32 of Hashimoto's thyroiditis, and four of Graves' disease, who underwent total thyroidectomy for an associated papillary thyroid carcinoma. Patients were classified as papillary thyroid carcinoma-lymphocytic thyroiditis (PTC-T) and papillary thyroid carcinoma (PTC) according to the presence or absence of LT on histology. Tg was measured before thyroid remnant ablation, when it is expectedly detectable, by an immunometric assay (IMA) and TgAb by three noncompetitive IMA and three competitive radioimmunoassays (RIA). The number of lymphocytes was compared with TgAb concentration.
Results:
Seventy-two of 177 patients (40.7%) were classified as PTC-T and 105 (59.3%) as PTC. Although the tumor stage was similar in the two groups, Tg was undetectable in more PTC-T (37 of 72) than PTC (12 of 105) (P < 0.01), and Tg values were lower in the former (0; 0–4.7 ng/ml) (median; 25th to 75th percentiles) than in the latter group (9.7; 2.7–24.2) (P < 0.01). Accordingly, the percent of positive TgAb by the six assays resulted in higher PTC-T (29.2–50.0%) than PTC (1.9–6.7%) (P < 0.01). Among 49 patients with undetectable Tg, TgAb were more frequently positive by IMA (57.1–63.3%) than RIA (30.6–42.9%). The number of lymphocytes correlated with TgAb concentration in all six assays (0.34 < Rho < 0.46) (all P < 0.01).
Conclusions:
In papillary thyroid carcinoma, LT on histology must be carefully searched for because it is frequently associated with TgAb and therefore mistakenly low or undetectable Tg. TgAb can be missed by some assays. In absence of LT, TgAb are rare.
ObjectiveIntravenous glucocorticoid (i.v.GC) pulse therapy for Graves' ophthalmopathy (GO) can be associated with acute liver damage (ALD), which was roughly estimated to occur in ∼1% of patients, ...with an overall mortality of 0.4%. The aim of this study was to evaluate the frequency of ALD after the introduction of a series of exclusion criteria and preventive measures.DesignRetrospective evaluation of all consecutive patients candidate to i.v.GC over a period of 5 years.MethodsThe study includes 376 GO patients candidate to i.v.GC. Several liver tests were performed before, during, and after i.v.GC. To prevent ALD morbidity and mortality, the following measures were applied: i) exclusion of patients with active viral hepatitis and/or severe liver steatosis; ii) reduction in the GC dose, frequency, and number of pulses; and iii) administration of oral GC after i.v.GC, and also during i.v.GC in patients positive for nonorgan-specific autoantibodies (to prevent autoimmune hepatitis due to immune rebound). ALD was defined as an increase in alanine aminotransferase ≥300 U/l.ResultsA total of 353 patients were given i.v.GC and 23 were excluded for various conditions. ALD was detected in 4/376 patients candidate to i.v.GC, resulting in a morbidity of 1.06%. One patient recovered spontaneously and three after additional treatment with oral GC, given to re-establish immune suppression in the suspect of an autoimmune hepatitis.ConclusionsALD related to i.v.GC is a relatively rare adverse event. Provided an accurate selection of patients and a series of preventive measures are applied, i.v.GC is a safe treatment for the liver.
High-dose intravenous glucocorticoid (ivGC) pulse therapy, which is commonly used for Graves' orbitopathy (GO), has been associated with acute liver damage (ALD), resulting in a fatal outcome in a ...few cases. No certain risk factors for ALD have been established. Consequently, a large retrospective cohort study was performed.
The relationship between ALD and several potential risk factors was assessed in 1076 consecutive patients with GO given ivGC. ALD was defined as an increase of alanine aminotransferase ≥300 IU/L.
Fourteen cases of ALD were recorded, resulting in a morbidity of 1.3%. Thirteen patients recovered and one died, resulting in a mortality of 0.09%. There was a significant, positive correlation of ALD with age and methylprednisolone acetate (MPA) cumulative dose, and ALD was more common (relative risk RR=2.8; p=0.05) in patients aged ≥53 years (9/420; 2.14%) than in those aged <53 years (5/656; 0.76%). In patients aged ≥53 years, there was a significant positive correlation of ALD with MPA cumulative dose, and with MPA dose per infusion. Thus, the frequency of ALD in this age group was greater (RR=3.48; p=0.04) in patients with a MPA dose per infusion ≥0.7 g (5/111, 4.5% vs. 4/308, 1.29%). Regardless of age, no cases of ALD were observed for MPA doses per infusion <0.57 g.
Age and MPA dose are significant risk factors for ALD, with the following practical implications. First, the total MPA cumulative dose should not exceed 8.5 g (the average dose in patients without ALD). Second, in patients aged ≥53 years, selection and observation should be quite strict. However, being aged ≥53 years should not be seen as an absolute contraindication to ivGC, especially in patients with severe GO, considering that the risk of ALD, although statistically significant, was relatively low. Third, the MPA dose should not exceed 0.57 g per infusion, a measure to be applied regardless of age.
Context:
In a previous study, we found that total thyroid ablation (thyroidectomy plus 131I) is associated with a better outcome of Graves' orbitopathy (GO) compared with thyroidectomy alone, as ...observed shortly (9 months) after glucocorticoid (GC) treatment.
Objective:
The objective of the study was to evaluate the outcome of GO in the same patients of the previous study over a longer period of time.
Design:
This was a follow-up of a randomized study.
Setting:
The study was conducted at a referral center.
Patients:
Fifty-two of 60 original patients with mild to moderate GO participated in the study.
Interventions:
Patients randomized into thyroidectomy (TX) or total thyroid ablation and treated with GC were reevaluated in 2010, namely 88.0 ± 17.7 months after GC, having undergone an ophthalmological follow-up in the intermediate period.
Main Outcome Measures:
The main outcome measures included the following: 1) GO outcome; 2) time to GO best possible outcome and to GO improvement; and 3) additional treatments.
Results:
GO outcome at the end of the follow-up was similar in the two groups. However, the time required for the best possible outcome to be achieved was longer in the TX group (24 vs. 3 months, P = 0.0436), as was the time required for GO to improve (60 vs. 3 months, P = 0.0344). Additional treatments were given to a similar proportion of patients in each group (TX, 28%, total thyroid ablation, 25.9%), but they affected GO beneficially more often in the TX group (28 vs. 3.7%, P: 0.0412).
Conclusions:
Compared with thyroidectomy alone, total thyroid ablation allows the achievement of the best possible outcome and an improvement of GO within a shorter period of time.
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