Differentiating pathologic parathyroid glands from thyroid nodules on neck ultrasound: the PARATH-US cross-sectional study.

Background: Neck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs). However, thyroid nodules may sometimes be confused with PPGs. PARATH-US study aims at identifying US characteristics to differentiate PPGs from thyroid nodules, as there is no study, at present, which directly compares the US features of these two common neoplasms. Methods: PARATH-US is a single-center study that was conducted at a tertiary referral center, including consecutive lesions from patients undergoing neck US examination from 2016 to 2022. Findings: 176 PPGs (158 patients: serum calcium levels 2.91 [IQR 2.74-3.05] mmol/L, PTH levels 173 [112-296] ng/L) were compared to 232 size- and volume-matched thyroid nodules (204 age- and sex-matched patients). The morphologic patterns, echoic content and vascular status were all different between PPGs and thyroid neoplasms (p < 0.01 for all comparisons). The combined parameters maximally discriminated PPGs from thyroid nodules (OR, 7.6; 95% CI: 3.4, 17.1, p < 0.0001). When applying risk stratification systems developed for thyroid malignancies, 58-63% of PPGs were classified as high-risk lesions. Parathyroid adenomas had larger sizes and volumes than hyperplasias (p = 0.013 and p = 0.029). Serum calcium and PTH levels were significantly correlated with PPG size and volume (p < 0.0001 for all comparisons). Interpretation: We demonstrate the presence of distinct US characteristics in PPGs, which help differentiate them from thyroid nodules. When mistaken for thyroid nodules, PPGs bear high-risk US features. When dealing with high-risk cervical lesions detected on US, a PPG should be suspected, and an assessment of calcium levels recommended to avoid unnecessary invasive procedures. Funding: CYTO-TRAIN, C2022DOSRH053, funded by the French Regional Health Agency.

Impact of Cushing's syndrome on the gonadotrope axis and testicular functions in men.

STUDY QUESTION: Does Cushing's syndrome (CS) differently affect the gonadotrope axis and testicular functions (GA/TF) according to the hypercortisolism intensity and underlying etiology? SUMMARY ANSWER: Endogenous cortisol excess caused by CS leads to varying degrees of hypogonadotropic hypogonadism (HH) with more severe GA/TF impairment and altered spermatogenesis in men with intense hypercortisolism associated with paraneoplastic/ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS). WHAT IS KNOWN ALREADY: CS is very rarely studied in men due to its lower prevalence in men than in women. In a few old reports focusing exclusively on a limited number of men with Cushing's disease (CD), the occurrence of hypogonadism was reported. However, a detailed assessment of the impact of CS on the GA/TF in a significant series of patients has not been performed. Yet, hypogonadism could worsen CS-associated comorbidities such as osteoporosis and myopathy. To date, the full spectrum of GA/TF impairment in men with CS of different etiologies and intensity remains unknown. STUDY DESIGN, SIZE, DURATION: In this monocentric study, 89 men with CS diagnosed at a tertiary endocrine university center (Bicêtre, Paris Saclay) between January 1990 and July 2021 were evaluated and compared to 40 normal men of similar age. PARTICIPANTS/MATERIALS, SETTING, METHODS: The CS patient cohort of 89 men included 51 with CD, 29 with EAS and 9 with CS of adrenal origin i.e. (ACTH-independent CS (AI-CS)). They all had frank hypercortisolism, with increased 24 h-urinary-free cortisol (24 h-UFC) in two separate samples. A case-control study was performed focusing on pituitary gonadotrope function and testicular sex steroids and peptides. An additional set of six CS men had an evaluation including semen analysis. In a subgroup of 20 men with available data after CS remission, a longitudinal analysis was conducted to assess the reversibility of GA/TF defects. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to controls, men with CS had significantly lower total testosterone (TT), bioavailable TT, and free TT (P < 0.0001). Hypogonadism, defined as serum TT levels <3.0 ng/ml, was present in 83% of men with EAS, in 61% of men with CD, and in 33% of men with AI-CS. Low-normal LH concentrations in the included men with hypercortisolism indicated HH. Serum sex hormone-binding globulin levels were moderately decreased in men with CD (P = 0.01 vs controls). Among the CS men, those with EAS had significantly lower TT, LH, and FSH levels than those with CD or AI-CS. When compared to controls, patients with EAS were the only group exhibiting a significant decrease in both serum FSH (P = 0.002) and the testicular peptides inhibin B (P < 0.0001) and anti-Müllerian hormone (P = 0.003). Serum INSL3 levels were significantly lower in men with CD than in the controls (P = 0.03). Of note, 24 h-UFC and ACTH were inversely and significantly associated with the majority of reproductive hormones including LH, FSH, TT, and inhibin B. Following successful curative therapy, reproductive assessment at a mean of 6.0 ± 4.3 years showed a significant increase in serum TT (P < 0.0001) and plasma LH (P = 0.02) levels, indicating a reversal of HH in 75% of the affected males. Among the six patients with available semen analysis, the two EAS cases exhibited a decrease in Sertoli cell peptides associated with a severe oligozoospermia, which completely normalized following removal of the source of hypercortisolism. LIMITATIONS, REASONS FOR CAUTION: The potential bias due to the retrospective design is counteracted by the analysis of the largest male CS cohort to date as well as the use of stringent inclusion and exclusion criteria. Due to the low number of patients with semen analysis in this study, further research is needed to unravel the full spectrum of spermatogenesis defects in men with CS. WIDER IMPLICATIONS OF THE FINDINGS: This work reveals the variable spectrum of reproductive impact in men with CS. We demonstrate that GA/TF impairment depends on the intensity of hypercortisolism which in turn is related to the underlying etiology. The causal link between hypercortisolism and GA/TF impairment was attested by its reversibility in most patients after CS remission. The wider implications of our findings lie in the potential generalization to a much commoner entity, iatrogenic CS due to chronic exposure to exogenous glucocorticoids. STUDY FUNDING/COMPETING INTEREST(S): Several research grants were attributed to J.Y.: (i) a grant from Programme Hospitalier de Recherche Clinique (PHRC # P081212 HYPOPROTEO); (ii) a grant from the French Association of Patients with Adrenal Diseases ('Association surrénales'); and (iii) independent Investigator Research Grants from HRA Pharma, Novartis and Recordati Pharma. A SICPA Foundation grant (Lausanne, Switzerland) allowed protected research time for G.E.P. The above sponsors were not involved in any part of the study. The authors have no competing or other conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Parathyroid hormone in situ measurement in patients with hyperparathyroidism: single-centre experience of 179 patients.

Context: The measurement of parathyroid hormone(PTH) in situ (PTHis) by fine-needle aspiration (FNA) has been proposed as a tool to preoperatively help localize parathyroid glands detected on ultrasound. However, the accuracy of PTHis is highly variable according to the few available studies. Aim: We aimed to develop and validate the PTHis procedure and assessed the performance of PTHis in a large series of patients with hyperparathyroidism and/or undetermined cervical lesions. Patients and methods: The technique set-up consisted of PTHis measurement in thyroid samples from patients with thyroid nodules and patients with high circulating PTH levels (tertiary hyperparathyroidism). Consecutive patients were recruited at one tertiary referral centre from 2017 to 2020 and submitted to ultrasound-guided FNA-PTHis determination. Results: During the method set-up, we obtained undetectable PTHis levels in all non-parathyroid tissues after sample dilutions. PTHis was higher in patients with hyperparathyroidism (n = 145; 1817 ± 3739 ng/L; range: <4.6-31 140) than in those with thyroid or undetermined cervical lesions (n= 34; <4.6 ng/mL; P < 0.0001). When evaluating PTHis performance in histologically proven samples (158 lesions from 121 patients), PTHis was detectable in 85/97 parathyroid lesions (87%; range: 22-31;140 ng/L) and undetectable in all non-parathyroid lesions (n = 61; P < 0.0001). The specificity and positive predictive value were 100%, and the sensitivity was 87.6%. False-negative lesions (n= 12) were smaller (9.4 ± 5.9 mm) and more often consisted of hyperplasias (75%) than true-positive lesions (16.1 ± 8.4 mm and 33%, P = 0.009 and P = 0.0089, respectively). The method was safe and well tolerated. Four educational cases are also provided. Conclusions: PTHis determination is a safe and well-tolerated procedure that enhances the specificity of ultrasound-detected lesions. If accurately set-up, it confirms the parathyroid origin of uncharacterized cervical lesions.

Solitary Breast Metastasis From Thyroid Papillary Carcinoma Revealed on Whole-Body Radioactive 131I Scan.

Breast metastasis from thyroid papillary carcinoma is an exceptional situation. Here, we present the diagnostic approach and the management of a 19-year-old woman with single breast metastasis from thyroid carcinoma. There was no extra thyroidal extension, neoplastic emboli, or lymph node invasion. The metastasis was revealed by whole-body radioactive I scan, explored by a fine-needle aspiration, and confirmed by elevated thyroglobulin in situ.

Prevalence of hepatitis B and anti-hepatitis C virus antibody among people who inject drugs in the Lebanese population.

BACKGROUND: People who inject drugs (PWIDs) are prone to a number of blood-borne viral infections. Hepatitis B virus (HBV) and hepatitis C virus (HCV) constitute an important public health concern in this high risk group. AIMS: We aimed to determine the prevalence of HBV and HCV antibody among PWIDs in Lebanon. METHODS: We conducted a prospective cross-sectional study between June 2015 and June 2016 on PWIDs recruited through Lebanese nongovernmental organizations in collaboration with the Lebanese Ministry of Public Health. The participants were tested for HBs antigen and HCV antibody using rapid test kits. The prevalence of each virus was then calculated. The correlation between both infections and other possible risk factors was also analysed. RESULTS: A total of 250 people were included in our study, of whom 98% were males. Mean age was 31.9 (standard deviation 8.7) years. The prevalence of HBsAg and anti-HCV among PWIDs was 1.2% and 15.6%, respectively. Older age, longer duration of drug use and lack of awareness were significantly correlated with a higher rate of HCV infection (P < 0.01). The high rate of needle sharing among our PWIDs significantly affected the prevalence of anti-HCVAb. CONCLUSION: PWIDs remain the subpopulation most affected with chronic HCV in Lebanon.

A rare case of hypercalcemia-induced pancreatitis in a first trimester pregnant woman.

The objective of the study is to report a case of acute pancreatitis secondary to hypercalcemia induced by primary hyperparathyroidism in a pregnant woman at the end of the first trimester. The case included a 32-year-old woman who was diagnosed with acute pancreatitis and severe hypercalcemia refractory to many regimens of medical therapy in the first trimester of pregnancy. She was successfully treated with parathyroidectomy in the early second trimester with complete resolution of hypercalcemia and pancreatitis. Neonatal course was unremarkable. To our best knowledge, this is a rare case when primary hyperparathyroidism and its complications are diagnosed in the first trimester of pregnancy. In conclusion, primary hyperparathyroidism is a rare life-threatening condition to the fetus and mother especially when associated with complications such as pancreatitis. Early therapeutic intervention is important to reduce the morbidity and mortality. Parathyroidectomy performed in the second trimester can be the only solution. LEARNING POINTS: Learning how to make diagnosis of primary hyperparathyroidism in a woman during the first trimester of pregnancy.Understanding the complications of hypercalcemia and be aware of the high mortality and sequelae in both fetus and mother.Providing the adequate treatment in such complicated cases with coordinated care between endocrinologists and obstetricians to ensure optimal outcomes.

Case-series of paraneoplastic Cushing syndrome in small-cell lung cancer.

The objective of this study is to report three cases of paraneoplastic or ectopic Cushing syndrome, which is a rare phenomenon of the adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. Three cases are reported in respect of clinical presentation, diagnosis and treatment in addition to relevant literature review. The results showed that ectopic ACTH secretion can be associated with different types of neoplasm most common of which are bronchial carcinoid tumors, which are slow-growing, well-differentiated neoplasms with a favorable prognosis and small-cell lung cancer, which are poorly differentiated tumors with a poor outcome. The latter is present in two out of three cases and in the remaining one, primary tumor could not be localized, representing a small fraction of patients with paraneoplastic Cushing. Diagnosis is established in the setting of high clinical suspicion by documenting an elevated cortisol level, ACTH and doing dexamethasone suppression test. Treatment options include management of the primary tumor by surgery and chemotherapy and treating Cushing syndrome. Prognosis is poor in SCLC. We concluded that in front of a high clinical suspicion, ectopic Cushing syndrome diagnosis should be considered, and identification of the primary tumor is essential. LEARNING POINTS: Learning how to suspect ectopic Cushing syndrome and confirm it among all the causes of excess cortisol.Distinguish between occult and severe ectopic Cushing syndrome and etiology.Providing the adequate treatment of the primary tumor as well as for the cortisol excess.Prognosis depends on the differentiation and type of the primary malignancy.

Idiopathic Hypoparathyroidism and Severe Hypocalcemia in Pregnancy.

The objective of this study is to report a case of severe hypocalcemia secondary to hypoparathyroidism in a pregnant woman. We report a case of a 45-year-old woman who presented for tonico-clonic seizure in the third trimester of gestation. She was diagnosed with idiopathic hypoparathyroidism for the first time during pregnancy. She was successfully treated with calcium and calcitriol in the rest of her pregnancy with resolution of symptoms but her infant was born with hypercalcemia and secondary hyperparathyroidism due to the late maternal presentation. To the best of our knowledge, hypoparathyroidism is a disorder rarely observed during pregnancy, resulting in most cases from surgical thyroidectomy.

Prevalence of hepatitis B and hepatitis C among intravenous drug abusers in the Lebanese population.

INTRODUCTION: Injection drug users (IVDU) are prone to many blood born viral infections. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) constitute an important public health concern in this high-risk group. The aim of the study is to calculate the prevalence of hepatitis B and C viruses among people who inject drugs (PWID) in Lebanon. METHODOLOGY: We conducted a prospective cross-sectional study between June 2015 and June 2016 on PWIDs recruited through the Lebanese non-governmental organizations in collaboration with the Lebanese ministry of public health. The participants were tested for HBs Antigen and HCV antibody using rapid test kits. The prevalence of each virus was then calculated. The correlation between both infections and other possible risk factors was also analyzed. RESULTS: A total of 250 people were included in our study. 98% were males. Mean age was 31.9-year-old. The prevalence of HBV and HCV among PWID was 1.2% and 15.6%, respectively. Older age, longer duration of drug use, and the lack of awareness were found to be significantly correlated with higher rate of HCV infection. We noted a relatively high rate of sharing needles among PWIDs without significantly affecting the prevalence of both viruses. CONCLUSION: IVDU remains a major public health concern in Lebanon, being one of the most prevalent subpopulations for chronic viral hepatitis namely the HCV. Appropriate screening strategies, targeted educational programs and adequate HBV vaccination are of extreme importance for further viral prevention among this high-risk group.