Use of long non-coding RNAs for the molecular diagnosis of papillary thyroid cancer.

Objective: Improved molecular testing for common somatic mutations and the identification of mRNA and microRNA expression classifiers are promising approaches for the diagnosis of thyroid nodules. However, there is a need to improve the diagnostic accuracy of such tests for identifying thyroid cancer. Recent findings have revealed a crucial role of long non-coding RNAs (lncRNAs) in gene modulation. Thus, we aimed to evaluate the diagnostic value of selected lncRNAs from The Atlas of Noncoding RNAs in Cancer (TANRIC) thyroid cancer dataset. Methods: LncRNAs in TANRIC thyroid cancer dataset that have significantly increased or decreased expression in papillary thyroid cancer (PTC) tissues were selected as candidates for PTC diagnosis. Surgical specimens from patients who underwent thyroidectomy were used to determine the separation capability of candidate lncRNAs between malignant and benign nodules. Fine needle aspiration samples were obtained and screened for candidate lncRNAs to verify their diagnostic value. Results: LRRC52-AS1, LINC02471, LINC02082, UNC5B-AS1, LINC02408, MPPED2-AS1, LNCNEF, LOC642484, ATP6V0E2-AS1, and LOC100129129 were selected as the candidate lncRNAs. LRRC52-AS1, LINC02082, UNC5B-AS1, MPPED2-AS1, LNCNEF, and LOC100129129 expression levels were significantly increased or decreased in malignant nodules compared to those in benign nodules and paired normal thyroid tissues. The combination of LRRC52-AS1, LINC02082, and UNC5B-AS1 showed favorable results for the diagnosis of PTC from fine needle aspirates, with 88.9% sensitivity and 100.0% specificity. Conclusions: LncRNA expression analysis is a promising approach for advancing the molecular diagnosis of PTC. Further studies are needed to identify lncRNAs of additional diagnostic value.

Revisiting growth hormone nadir cut-offs for remission in patients with acromegaly.

Objective: Over the past decade, the growth hormone (GH) nadir cut-off during the oral glucose tolerance test for remission in patients with acromegaly was changed from 0.4 to 1.0 µg/L due to the limited use of ultrasensitive detection kits to measure GH levels. However, the optimal cut-off level for GH nadir remains unclear. This retrospective study aimed to investigate the association between different GH nadir cut-offs and prognosis in patients with acromegaly. Design and methods: A total of 285 patients with acromegaly with a glucose-suppressed GH nadir <1 µg/L at 3-6 months after trans-sphenoidal adenomectomy were divided into two groups according to the glucose-suppressed GH nadir levels at 3-6 months post-operatively (group A: <0.4 µg/L; group B: 0.4-1.0 µg/L). GH levels were measured using an ultrasensitive IRMA. The clinical, hormonal, metabolic, and neuroradiological data of the two groups were compared. Results: Female sex, as well as confirmed macroadenomas, was significantly overrepresented in group B. The 5-year rate of patients who achieved nadir GH < 1.0 µg/L and age- and sex-matched normal IGF-1 was significantly higher in group A than that in group B. However, there was no significant difference between the two groups in metabolic parameters at 12 months post-operatively. Conclusion: Different GH nadir cut-offs were associated with different 5-year rates of patients who achieved nadir GH <1.0 µg/L and age- and sex-matched normal IGF-1, suggesting that a strict GH nadir threshold of 0.4 µg/L correlates better with remission.

Positive association between nonalcoholic fatty liver disease and growth hormone deficiency in patients with nonfunctioning pituitary adenoma.

Objective: Non-alcoholic fatty liver disease (NAFLD) is characterized by growth hormone deficiency (GHd). We investigated the association between NAFLD and GHd in patients with nonfunctioning pituitary adenomas (NFPA). Design and methods: We recruited patients with NFPA who underwent transsphenoidal adenectomy between January 2005 and December 2018. Pituitary function was determined by the insulin tolerance test, thyroid hormone assay, and gonadal hormone levels. NAFLD was defined as a hepatic steatosis index greater than 36. Results: Among 278 patients (mean age, 44.2 years; 58.6% [n=163] female), 103 (37.0%) had GHd, 139 (50.0%) had hypogonadism, and 75 (27.0%) had NAFLD. The prevalence of NAFLD was significantly higher in patients with GHd than in those without (36.9% vs. 21.1%, p=0.01). Even after adjusting for age, total cholesterol level, gonadal function, and prolactin level, patients with GHd had approximately two-fold higher prevalence of NALFD than those without GHd (adjusted odds ratio [OR]=1.85, 95% confidence interval [CI]=1.05-3.28, p=0.03). Among female patients, the prevalence of NALFD was significantly higher in those with GHd than in those without (adjusted OR=2.39, 95% CI=1.03-5.55, p=0.04); whereas, among male patients, the prevalence of NAFLD was statistically similar between those with and without GHd (p>0.05). In addition, gonadal function did not affect the prevalence of NAFLD in patients with NFPA (29.3% with eugonadism vs. 47.8% with hypogonadism, p=0.14). Conclusion: Among patients with NFPA, the prevalence of NAFLD was two-fold higher in patients with GHd than that in those without GHd. Thus, screening for NAFLD might be required in NFPA patients with GHd.