The Association between Lymphocytic Thyroiditis and Papillary Thyroid Cancer Harboring Mutant BRAF: A Systematic Review and Meta-Analysis.

Background: Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harboring BRAFV600E (PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC. Objective: We compared the prevalence of PTC-BRAF with and without LT. The risk of adverse pathological features in (i) PTC in the presence and absence of BRAF mutation, irrespective of LT status, was compared to (ii) PTC in the presence and absence of LT, irrespective of BRAF status. Methods: We searched PubMed, Embase, and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features, and the quality assessment tool were extracted by two reviewers. The study was registered with PROSPERO (CRD42023437492). Results: Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated that the odds of PTC-BRAF were significantly lower in the presence of LT compared to its absence (odds ratio [OR] 0.53, 95% confidence interval [CI]: 0.48-0.58, p < 0.00001). In PTC-BRAF patients, there was a positive association of central neck nodal disease (CNND), PTC > 1 cm, extra-thyroidal extension, American Joint Committee on Cancer (AJCC) Stage 3-4, and multifocality with pooled ORs of 1.54 (95% CI: 1.16-2.04), 1.14 (95% CI: 0.82-1.58), 1.66 (95% CI: 1.40-1.97), 1.53 (95% CI: 1.35-1.75), and 1.24 (95% CI: 1.11-1.40) respectively, compared to wild-type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled ORs of 0.64 (95% CI: 0.51-0.81) for CNND, 0.83 (95% CI: 0.73-0.95) for PTC > 1 cm, 0.71 (95% CI: 0.58-0.86) for ETE, 0.84 (95% CI: 0.75-0.94) for AJCC Stage 3-4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT, with pooled ORs of 1.12 (95% CI: 0.66-1.90, p = 0.67) and 0.60 (95% CI: 0.28-1.30, p = 0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set. Conclusion: The odds of PTC-BRAF are significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and whether this is relevant to the role of immunotherapy in advanced thyroid cancer.

PD-L1 expression in papillary thyroid cancer with and without lymphocytic thyroiditis: a cross sectional study.

The impact of concurrent autoimmune thyroid disease on the tumour microenvironment and disease progression in papillary thyroid cancer (PTC) is not well understood. Studies evaluating the programmed cell death ligand 1 (PD-L1) tumour expression in PTC have shown variable results, and the effect of lymphocytic thyroiditis (LT) on tumour PD-L1 expression has not been adequately assessed. The main aim of this study was to determine expression of PD-L1 in PTC with and without LT. We examined 81 PTC cases; 28.5% of all reviewed PTC had presence of LT. In PTC specimens without LT, tumour PD-L1 expression was significantly lower compared to PD-L1 expression in PTC with LT, 6.9% vs 39.1%, respectively. Expression of PD-L1 did not differ with PTC stage, even when sub-categorised according to the presence and absence of LT. Utility of PD- L1 expression as a prognostic marker in thyroid cancer needs to be interpreted with caution.

A case of Klinefelter syndrome with hypersexual desire.

Klinefelter syndrome (KS) is a chromosomal disorder affecting males, with the typical karyotype of 47,XXY due to a supernumerary X chromosome, which causes progressive testicular failure resulting in androgen deficiency and infertility. Despite it being the most common sex chromosomal disorder, its diagnosis is easily missed. In addition to its classical clinical features of tall stature, gynaecomastia, small testes, and symptoms and signs of hypogonadism including infertility, KS is also often associated with neurocognitive, behavioural and psychiatric disorders. We present a 44-year-old man with KS who, despite having erectile dysfunction, paradoxically had increased libido. He used sildenafil to overcome his erectile dysfunction. Hypersexuality was manifested by very frequent masturbation, multiple sexual partners most of whom were casual, and a sexual offence conviction at the age of 17 years. Discussion focuses on the frequent failure of clinicians to diagnose KS, the neurocognitive, behavioural and psychiatric aspects of KS, this unusual presentation of hypersexuality in a man with KS, and the challenges of medical management of hypogonadism in a man with a history of a sexual offence. LEARNING POINTS: Klinefelter syndrome (KS) is common in men (about 1 in 600 males), but the diagnosis is very often missed.In addition to classic features of hypogonadism, patients with KS can often have associated neurocognitive, behavioural and/or psychiatric disorders.More awareness of the association between KS and difficulties related to verbal skills in boys could improve rates of early diagnosis and prevent longer-term psychosocial disability.Hypersexuality in the context of hypogonadism raises the possibility of sex steroid independent mechanistic pathways for libido.Testosterone replacement therapy in KS with hypersexuality should be undertaken with caution using a multidisciplinary team approach.

Vitamin D status and its predictive factors in pregnancy in 2 Australian populations.

BACKGROUND: High prevalence rates of suboptimal vitamin D levels have been observed in women who are not considered 'at risk'. The effect of behavioural factors such as sun exposure, attire, sunscreen use and vitamin D supplementation on vitamin D levels in pregnancy is unknown. AIM: To determine prevalence and predictive factors of suboptimal vitamin D levels in 2 antenatal clinics in Australia--Campbelltown, NSW and Canberra, ACT. METHODS: A cross-sectional study of pregnant women was performed with a survey of demographic and behavioural factors and a mid-pregnancy determination of maternal vitamin D levels. RESULTS: The prevalence of vitamin D deficiency (≤25 nmol/L) and insufficiency (26-50 nmol/L) was 35% in Canberra (n=100) and 25.7% in Campbelltown (n=101). The majority of participants with suboptimal D levels had vitamin D insufficiency. Among the vitamin D-deficient women, 38% were Caucasian. Skin exposure was the main behavioural determinant of vitamin D level in pregnancy in univariate analysis. Using pooled data ethnicity, season, BMI and use of vitamin D supplements were the main predictive factors of suboptimal vitamin D. Vitamin D supplementation at 500 IU/day was inadequate to prevent insufficiency. CONCLUSIONS: Behavioural factors were not as predictive as ethnicity, season and BMI. As most participants had one of the predictive risk factors for suboptimal vitamin D, a case could be made for universal supplementation with a higher dose of vitamin D in pregnancy and continued targeted screening of the women at highest risk of vitamin D deficiency.