Long-term hypothyroidism in patients started on levothyroxine during pregnancy.

Background: Current guidelines recommend different postpartum approaches for patients started on levothyroxine (LT4) during pregnancy. Objective: We studied the postpartum management of these patients and determined factors associated with long-term hypothyroidism. Methods: A retrospective study was conducted at a tertiary center between 2014 and 2020, with LT4 initiation according to 2014 ETA recommendations. We performed multivariate logistic regression (MVR) and a receiver operating characteristic curve analysis to determine variables associated with long-term hypothyroidism and their optimal cutoffs. Results: LT4 was initiated in 177 pregnant women, and 106/177 (60%) were followed at long-term (at least 6 months post partum) (28.5 (9.0-81.9) months). LT4 could have been stopped in 45% of patients who continued it immediately after delivery. Thirty-six out of 106 (34%) patients were long-term hypothyroid. In them, LT4 was initiated earlier during pregnancy than in euthyroid women (11.7 ± 4.7 vs 13.7 ± 6.5 weeks, P = 0.077), at a higher thyroid-stimulating hormone (TSH) level (4.1 (2.2-10.1) vs 3.5 (0.9-6.9) mU/L, P = 0.005), and reached a higher dose during pregnancy (62.8 ± 22.2 vs 50.7 ± 13.9 µg/day, P = 0.005). In the MVR, only the maximal LT4 dose during pregnancy was associated with long-term hypothyroidism (odds ratio (OR) = 1.03, 95% CI: 1.00-1.05, P = 0.003). The optimal cutoffs for predicting long-term hypothyroidism were an LT4 dose of 68.75 µg/day (87% specificity, 42% sensitivity; P = 0.013) and a TSH level ≥ 3.8 mU/L (68.5% specificity, 77% sensitivity; P = 0.019). Conclusion: One-third of the patients who started on LT4 during pregnancy had long-term hypothyroidism. The TSH level at treatment initiation and the LT4 dose during pregnancy could guide the decision for continuing long-term LT4.

How often should we perform magnetic resonance imaging (MRI) for the follow-up of pituitary adenoma?

Magnetic resonance imaging (MRI) is the examination of choice for diagnosing and monitoring pituitary adenoma (also known as pituitary neuroendocrine tumor or PitNET), whether treated or not. However, repeating the examination too often (and sometimes unnecessarily) is costly, and worrying data on tissue accumulation (brain, bone, etc.) of gadolinium atoms dissociated from their carrier molecule (chelator) have led European authorities to ban contrast agents based on linear chelators of gadolinium, which are particularly susceptible to rapid dissociation, in favor of chemically more stable macrocyclic chelators. It is therefore important to determine the optimal frequency for pituitary MRI monitoring in order to safely assess the natural history or therapeutic response of pituitary adenomas. The aim of this article is to summarize the most recent data on optimal follow-up intervals depending on the type, size and location of the pituitary tumor and the clinical situation in general, in order to generate monitoring algorithms to guide clinicians.

Significance of thyroperoxidase and thyroglobulin antibodies in medically treated Graves' disease.

Background: Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves' disease (GD), but their significance is controversial. Methods: We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. Results: At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034). Conclusion: In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.

Pituitary incidentaloma.

Pituitary incidentalomas (PI) are lesions of the pituitary region discovered fortuitously by imaging for reasons unrelated to pituitary disease. They range from small cysts to large invasive adenomas. All over the world, improvements in the quality and availability of radiological examinations are leading to an increase in the discovery of PI. In the last four decades, significant advances have been made in the understanding of PI. Autopsy studies have shown that about 10% of deceased individuals harbour a PI, most often a non-functioning microadenoma. In contrast, modern patient series showed that among PIs that come to endocrinological attention, a significant proportion are macroadenomas, and many patients suffer from asymptomatic or pauci-symptomatic endocrine or ophthalmologic disturbances. Other than adenomas, empty sella, Rathke's cleft cyst, craniopharyngioma and meningioma are the most frequent types of PIs. About 10% of micro-incidentalomas and 25% of macro-incidentalomas grow over time. Most cases can be managed conservatively by mere surveillance. Follow-up is necessary in all patients with macroadenoma, but uncertainty remains for microadenomas as to the extent of endocrinological work-up as well as the necessity and duration of follow-up. Visual and endocrine anomalies constitute the most common indications for surgery. When needed, surgery yields better outcome in PIs than in symptomatic pituitary lesions.

Chronic dialysis, NAT2 polymorphisms, and the risk of isoniazid-induced encephalopathy - case report and literature review.

BACKGROUND: Isoniazid is the most widely used anti-tuberculosis agent, yet it may lead to life-threatening complications. CASE PRESENTATION: Here we report the case of a chronic hemodialysis patient who developed severe encephalopathy after the start of isoniazid. Blood levels of isoniazid were elevated, and acetyl-isoniazid over isoniazid ratio was decreased 3 h after intake of the medication, suggesting that a slow acetylator phenotype may have contributed to drug toxicity, in addition to pyridoxal phosphate removal by dialysis. This hypothesis was confirmed by sequencing of NAT2, the gene responsible for isoniazid elimination, and identification of NAT2 polymorphisms compatible with a slow acetylator phenotype. Isoniazid withdrawal along with supplementation using high doses of pyridoxine successfully reversed the drug toxicity. Isoniazid toxicity occurs in populations at risk, including patients with chronic kidney failure or NAT2 polymorphisms, who have a disturbed metabolism of pyridoxine or isoniazid, respectively, and those on renal replacement therapies, in whom pyridoxal phosphate - the active metabolite of pyridoxine - is inadvertently removed by dialysis. CONCLUSIONS: Physicians should be aware of the increased risk of isoniazid toxicity in patients on dialysis and in those with a slow acetylator phenotype conferred by NAT2 polymorphisms. Adaptation of prescription - either with higher doses of pyridoxine or decreased doses of isoniazid, respectively - has been suggested to reduce the risk of potentially life-threatening toxicity of isoniazid.