Showing papers in "Annales D Endocrinologie in 2022"

Covid-19, the thyroid and the pituitary — The real state of play

Abstract: Thyroid and pituitary disorders linked to the coronavirus SARS-CoV-2, responsible for the COVID-19 epidemic, are mainly due to direct infection of the endocrine glands by the virus and to cell damage induced by the immune response. The two most frequent thyroid complications of COVID-19 are low T3 syndrome, or "non-thyroidal illness syndrome" (NTIS), and thyroiditis. Studies among in-patients with COVID-19 have shown that between one out of six and half of them have a low TSH level, related to NTIS and thyroiditis, respectively, sometimes found in the same patient. In NTIS, the decrease in free T3 concentration correlates with the severity of the infection and with a poor prognosis. Assessment of thyroid function in patients after a COVID-19 infection, shows normalization of thyroid function tests. Thyroiditis linked to COVID-19 can be divided into two groups, which probably differ in their pathophysiology. One is "destructive" thyroiditis occurring early in infection with SARS-CoV-2, with a severe form of COVID-19, usually observed in men. It is often asymptomatic and associated with lymphopenia. The other is subacute thyroiditis occurring, on average, one month after the COVID-19 episode, usually in clinically symptomatic women and associated with moderate hyperleukocytosis. Post-infection, one quarter to one third of patients remain hypothyroid. An Italian study demonstrated that low TSH in patients hospitalized for COVID-19 was associated with prolonged hospitalization and a higher mortality risk. Pituitary diseases associated with SARS-CoV-2 infection are much rarer and the causal relationship more difficult to ascertain. Several cases of pituitary apoplexy and diabetes insipidus during COVID-19 infection have been reported. Hyponatremia occurs in 20-50% of patients admitted to hospital for COVID-19. The prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) amongst these hyponatremic cases is difficult to determine. These endocrine complications may influence the prognosis of infection with SARS-CoV-2. Although they rarely require specific treatment, it is important that endocrinologists recognize them to ensure appropriate management, particularly in the acute phase.

Androgens and spermatogenesis.

Abstract: Male infertility contributes to 50% of all cases of infertility. The main cause is low quality and quantity of sperm. In humans, spermatogenesis starts at the beginning of puberty and lasts lifelong. It is under the control of FSH and testicular androgens, and mainly testosterone (T), and therefore requires a normal gonadotroph axis, intratesticular T production by Leydig cells and functional androgen receptors (ARs) within testicular Sertoli cells. Various clinical cases illustrate the roles of T in human spermatogenesis. Men with complete congenital hypogonadotropic hypogonadism (HH) are usually azoospermic. Treatment by exogenous testosterone injection and FSH is not able to produce sperm. However, combined treatment with FSH and hCG is effective. This example shows that intratesticular T plays a major role in spermatogenesis. Furthermore, testicular histology of men with LH receptor mutations shows Leydig cell hypoplasia/agenesis/dysplasia with conserved Sertoli cell count. The sperm count is reduced, as in males with partial inactivating mutation of the androgen receptor. Some protocols of hormonal male contraception or exogenous androgen abuse induce negative feedback in the hypothalamic pituitary axis, decreasing FSH, LH and T levels and inducing sperm defects and testicular atrophy. The time to recovery after cessation of drug abuse is around 14 months for sperm output and 38 months for sperm motility. In summary, abnormal androgen production and/or AR signaling impairs spermatogenesis in humans. The minimal level of intratesticular T for normal sperm production is a matter of debate. Interestingly, some animal models showed that completely T-independent spermatogenesis is possible, potentially through strong FSH activation. Finally, recent data suggest important roles of prenatal life and minipuberty in adult spermatogenesis.

Consensus statement by the French Society of Endocrinology (SFE) and French Society of Pediatric Endocrinology & Diabetology (SFEDP) on diagnosis of Cushing's syndrome.

Abstract: Cushing's syndrome is defined by prolonged exposure to glucocorticoids, leading to excess morbidity and mortality. Diagnosis of this rare pathology is difficult due to the low specificity of the clinical signs, the variable severity of the clinical presentation, and the difficulties of interpretation associated with the diagnostic methods. The present consensus paper by 38 experts of the French Society of Endocrinology and the French Society of Pediatric Endocrinology and Diabetology aimed firstly to detail the circumstances suggesting diagnosis and the biologic diagnosis tools and their interpretation for positive diagnosis and for etiologic diagnosis according to ACTH-independent and -dependent mechanisms. Secondly, situations making diagnosis complex (pregnancy, intense hypercortisolism, fluctuating Cushing's syndrome, pediatric forms and genetically determined forms) were detailed. Lastly, methods of surveillance and diagnosis of recurrence were dealt with in the final section.

Endocrinology of bone mineralization: An update

Abstract: Throughout the world, millions of people suffer from fragilizing osteopathies such as osteomalacia and osteoporosis. Osteomalacia is a rare disorder, corresponding to mineralization abnormalities in adult bone, as opposed to rickets in children. Renal phosphate loss and hypophosphatasia are the main causes of vitamin-resistant osteomalacia. Diagnosis is based on clinical history, phosphocalcic metabolism assessment and, if necessary, molecular characterization, and must be rapid in order to initiate the most appropriate treatment and consider new treatments such as burosumab if necessary. Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fracture. Fracture-related burden is expected to increase over the coming decades linked to the aging of population and a treatment gap. In order to reduce this treatment gap, it is important to develop two strategies: improvement of screening and of treatment. Systematic screening using the FRAX® fracture risk assessment tool could be useful to increase anti-osteoporosis medical treatment and reduce fracture rates. The question of treatment sequencing in osteoporosis is another challenge, notably after denosumab cessation, complicated by a decrease in bone mineral density and increased risk of fracture. New treatments are also available, including romosozumab, a humanized monoclonal antibody, which promotes bone formation and inhibits bone resorption by inhibiting sclerostin. Romosozumab is approved in several countries, including France, for treating severe osteoporosis in postmenopausal women at high risk of fracture and free of cardiovascular comorbidity. Endocrinologists need to be aware of these fragilizing osteopathies in order to improve both diagnosis and treatment.

Characterization of a transgender population in Portugal

Abstract: Gender dysphoria (GD) is a condition in which the individual's gender identity does not correspond to their biological sex, causing significant distress. Biological males who identify as females are referred to as transgender females or as showing male-to-female GD (MtF GD) and biological females who identify as males are referred to as transgender males or as showing female-to-male GD (FtM GD). In our center, there is a multidisciplinary consultation to approach and follow patients with GD.We aimed to analyze the characteristics of the individuals who attend this consultation.Retrospective study of individuals attending the Sexual Medicine Group Consultation. Age, comorbidities, symptom onset, and hormonal and surgical treatment were analyzed.In total, 114 patients were diagnosed with GD: 68.4% FtM GD and 31.6% MtF GD. Median age was 30.2±12years. Among the patients, 63.2% reported symptom onset in childhood: 14.9% between 10 and 18years, and 4.4% later than 18years. Median age at treatment initiation was 23.1±7.1years. Several individuals had concomitant medical conditions, notably smoking (n=37; 32.5%) and depression (n=26; 22.3%). The majority of (92.3% FtM GD and 88.9% MtF GD) were under hormone treatment, and about one-third had undergone some sex reassignment surgery.We found higher prevalence of FtM than MtF, in contrast with most other studies. The reasons for this are not clear. A high percentage of our patients were self-medicated. Other characteristics were similar to those previously reported.Medical requests by individuals with GD are increasing worldwide. To our knowledge, this is the first study to portray a case series in a consultation center dedicated to the diagnosis, treatment and follow-up of individuals with GD in Portugal.

Fertility preservation for prepubertal boys: are we ready for autologous grafting of cryopreserved immature testicular tissue?

Abstract: Fertility preservation in prepubertal boys is a matter that has been gaining ground fast during the past 20 years. As the life expectancy for childhood cancer survivors continues to increase (5-year survival rate>80%), and as the risk of permanent infertility in adulthood is still high with current treatment options, offering a testicular biopsy to cryopreserve immature testicular tissue (ITT) containing spermatogonial stem cells is now recommended as an experimental option for fertility preservation. Transplantation of cryopreserved testicular prepubertal tissue fragments back to the cured patient appears to be one of the most feasible and promising techniques for fertility restoration. In 2019, the birth of a healthy female baby rhesus monkey after intracytoplasmic sperm injection using spermatozoa recovered from frozen-thawed ITT autografts fueled the hopes of translating the technique to humans. While gonadal tissue autotransplantation has already been successfully achieved in clinical practice for females, it has never been attempted in males to date. In this work, we review acquired knowledge on ITT transplantation in animal models and share our vision on the remaining challenges to autograft currently banked human ITT within pilot clinical trials in the near future.

What an endocrinologist should know for patients receiving lithium therapy.

Abstract: Lithium is an efficient treatment of bipolar disorder. Besides renal insufficiency, many endocrine side effects are described such as the occurrence of thyroid disorders, hypercalcaemia and nephrogenic diabetes insipidus. Lithium inhibits the secretion of thyroid hormones. The prevalence of goiter is 4 times more common in Lithium-treated patients compared as to the general population. Hypothyroidism (8-20%) is more frequent in women and in case of pre-existing thyroid autoimmunity. Grave's disease and other hyperthyroidisms are sometimes reported. Lithium stimulates the proliferation of parathyroid cells by activating the Wnt pathway. An increase in serum calcium and PTH is described in patients treated with Lithium with a 4 to 6-fold higher risk of primary hyperparathyroidism than in the general population. Nevertheless, 24-hour urine calcium is not often increased, and the phenotype can mimic a hypercalcemia-hypocalciuria syndrome that may regress with Lithium discontinuation. Surgery should be cautious since parathyroid hyperplasia is more common than parathyroid adenoma. Nephrogenic diabetes insipidus is frequently reported and may be debilitating, sometimes intricated with severe dehydration, hypernatremia, and acute renal insufficiency. Nephrogenic diabetes insipidus is not generally reversible after Lithium discontinuation, especially in patients who have chronic kidney disease due to interstitial tubule nephritis. In conclusion, clinical assessment (goiter, diuresis) and biological monitoring of serum calcium, sodium creatinine, TSH and lithium are recommended in patients receiving Lithium therapy. The risk of Lithium discontinuation in case of side effects should be weighed against the psychological risk, and must be discussed with the psychiatrist.

Impact of intra-uterine life on future health

Abstract: Since the emergence of the concept of developmental origins of health and disease (DOHaD), suggested by Barker in the 1980s, numerous epidemiological studies in humans have confirmed the relationship between maternal obesity during pregnancy and the risk of offspring developing various chronic adult illnesses. These effects of intrauterine life are independent of inheritance of disease susceptibility genes and/or socio-economic factors. Regarding potential mechanisms, recent data from animal models suggests a role of insulin resistance early in development. Another potential mechanism, in the case of maternal obesity, is increased placental nutrient transfer. The DOHaD concept also includes fetal exposure to environmental endocrine disruptors (EEDs). A Danish group for the first time recently analyzed EED passage across the placenta in humans throughout pregnancy. This study showed different levels of bioaccumulation depending on the fetal organ, with greater vulnerability in male than female fetuses. Recent clinical studies suggested an association between fetal exposure to particular EEDs and precocious puberty, increased incidence of cryptorchidism and impaired sperm quality in adulthood. These modifications of the in-utero environment also appear to be responsible for epigenetic changes that are transmittable over several generations. A recent example of this is the demonstration of the transmission of polycystic ovary syndrome (PCOS) in mice. In summary, an increasing number of examples of the impact of intrauterine life on the health of offspring have appeared in recent years, illustrating the important role that endocrinologists can play in preventing particular pathologies in future generations.

Introduction to the consensus.

Abstract: The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This introductory text explains the reasons for this choice and the methodology used, and gives an overview of the current consensus on the management of the thyroid.

L'impact du syndrome de Cushing sur la fertilité et la grossesse.

Abstract: Cushing's syndrome is defined by an endogenous or exogenous hypercortisolism. Increased cortisol, as well as increased androgens will have a negative impact on the pulsatile secretion of GnRH, thus leading to an increased risk of infertility. However, pregnancy can occur in a woman with Cushing's syndrome: it is a challenging situation, because of the numerous consequences which can be observed in the mother (increased risk of gestational diabetes, hypertension, eclampsia… in addition to the specific complications of hypercortisolism) and in the fetus (intrauterine growth retardation, prematurity). In contrast, Cushing's syndrome can also appear during pregnancy. It is a very rare situation: the diagnosis is challenging because of the numerous hormonal changes induced by pregnancy on cortisol levels. The objective of this brief review will be to detail the mechanisms of infertility due to hypercortisolism, the diagnostic methods of Cushing's syndrome during pregnancy, the maternal and fetal consequences of hypercortisolism during pregnancy, and finally the potential means of contraception that can be proposed.

Section 7 Surgical treatment.

Abstract: The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French-speaking Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the surgical management of thyroid nodules.

Thyroid pathology and female fertility: myth or reality?

Abstract: The relationship between thyroid state and female fertility is an area of particular interest for both clinicians and researchers worldwide. This is partially due to the increasing prevalence of infertility and to the understanding of its complex and multifactorial aetiology. Studies conducted in variable forms of female infertility (e.g., recurrent miscarriages or polycystic ovarian syndrome) together with the worldwide rising use of assisted reproduction technologies (ART) contributed the uncovering of the potential role of thyroid conditions in relation to ovarian function and fertility. However, as the title of this short review suggests, several aspects are yet to be elucidated and several questions are still awaiting an answer. This short review is mainly focusing on the distinct roles of thyroid dysfunction and thyroid autoimmunity in infertile women undergoing ART procedures.

Role of insulin resistance on fertility-focus on polycystic ovary syndrome.

Abstract: Several lines of evidence show that gonadal functions and insulin sensitivity display multifaceted relationships, which extend far beyond the well-known association between polycystic ovary syndrome (PCOS), obesity, and metabolic syndrome. In this brief review, we will summarize the main findings showing the pathophysiological role of insulin resistance in impairing reproductive functions. Extreme phenotypes of severe insulin resistance, due to primary defects in insulin receptor or to lipodystrophy syndromes, provide unique opportunities for the modeling of interactions between insulin signaling and ovarian endocrine functions. In addition, recent studies further suggest that common forms of dysfunctional adiposity, as well as altered production of adipokines, could underlie important pathophysiological links between metabolic syndrome and infertility.

MANAGEMENT OF THYROTOXICOSIS AND PREGNANCY: Review of the current literature and an update of the care pathway.

Abstract: Pregnancy can be complicated by hyperthyroidism or thyrotoxicosis. Diagnosis is founded on an increase in free thyroid hormones and low TSH. The most frequent etiologies are Graves' disease, an autoimmune disease linked to stimulatory anti-TSH receptor antibodies, and non-autoimmune gestational hyperthyroidism linked to the TSH-like activity of the chorionic growth hormone (hCG). During pregnancy, thyrotoxicosis can entail maternal, obstetrical and fetal or neonatal complications. Graves' hyperthyroidism may be responsible for fetal and neonatal hyperthyroidism due to placental transfer of stimulatory anti-TSH receptor antibodies. During pregnancy, treatment of thyrotoxicosis must restore normal thyroid function in the mother without affecting fetal thyroid function. The recent reassessment of the prevalence of teratogenic effects in children of women treated with antithyroid drugs in the first weeks of gestation should orient the care pathway before and during pregnancy for women of child-bearing age with hyperthyroidism linked to Graves' disease.

Pembrolizumab-induced cyclic ACTH-dependent Cushing's syndrome treated by a block-and-replace approach with osilodrostat

Abstract: Community-Directed Treatment with Ivermectin (CDTI) is the strategy of choice to fight onchocerciasis in Africa. In areas where loiasis is endemic, onchocerciasis control and/or elimination is hindered by severe adverse events (SAEs) occurring after ivermectin mass treatments. This study aimed at (i) investigating the impact of two decades of CDTI on L. loa clinical and parasitological indicators in the Ndikinimeki Health District, and (ii) assessing the risk of SAEs after this long-term preventive chemotherapy. A cluster-based cross-sectional survey was conducted in the six Health Areas of the Ndikinimeki Health District. All volunteers underwent day-time calibrated thick blood smears to search for L. loa microfilariae, as well as an interview to assess the history of migration of eye worm and Calabar swelling. The overall prevalence of L. loa microfilaraemia was 2.2 % (95% CI: 1.3–3.7%), and the proportions of individuals who had already experienced eye worm and/or Calabar swelling were 1.0% and 0.5%, respectively. The mean microfilarial density was 63.55 (SD: 559.17; maximum: 9220.0) mf/mL. These findings indicate that (i) the long-term ivermectin-based preventive chemotherapy against onchocerciasis significantly reduced L. loa clinical and parasitological indicators, and (ii) the risk of developing neurologic and potentially fatal SAE after ivermectin mass treatment is zero in the Ndikinimeki Health District.

Mise en évidence par LC-MS/MS du pseudohyperaldostéronisme par intoxication à la glycyrrhizine

Abstract: La présentation clinique du pseudohyperaldostéronisme par intoxication à la glycyrrhizine associe hypertension artérielle et hypokaliémie. Il existe de nombreux aliments contenant ce toxique, et l’interrogatoire ne permet pas toujours de les déceler induisant souvent une recherche inutile d’autres causes d’hypertension artérielle hypokaliémique. Le but de ce travail est de trouver un paramètre biologique permettant d’authentifier le diagnostic. Onze volontaires sains ont consommé un produit à base de réglisse (confiseries ou boissons disponibles sur le marché). Les prélèvements sanguins ont été réalisés avant (T0) puis 6, 10 et 24 heures après (T + 6, T + 10 et T + 24). La natrémie, kaliémie, la glycyrrhizine, son métabolite actif l’acide glycyrrhétinique, cortisol et cortisone ont été dosés, et le rapport cortisol/cortisone (RCC) a été calculé. Trois patients ayant une hypertension artérielle hypokaliémique (deux patients consommant régulièrement de la réglisse, et un hyperaldostéronisme primaire avéré) ont aussi bénéficié de ces dosages. Un pic d’acide glycyrrhétinique (8,2–180,8 ng/mL) a été observé chez les volontaires à T + 6 ou T + 10. Pour les volontaires, le RCC moyen à T0 était à 6,1 et s’élevait à T + 6 pour trois d’entre eux (5,4 (T0) → 6,8 ; 3,9 → 4,9 ; 3,2→5,5). Les RCC des patients intoxiqués étaient à 16,5 et 8,8 (RCC de l’hyperaldostéronisme primaire : 3,2). Le dosage de l’acide glycyrrhétinique ne permettrait pas de distinguer une consommation régulière d’une consommation ponctuelle de réglisse mais l’élévation du rapport cortisol/cortisone pourrait orienter plus aisément vers un pseudohyperaldostéronisme. Déterminer un cut-off évocateur d’une intoxication chronique constituerait une aide au diagnostic dans les suspicions d’intoxication à la glycyrrhizine.

Fertility in men with Klinefelter's syndrome.

Abstract: Patients with a Klinefelter syndrome (KS), defined by a 47 XXY karyotype, were long considered infertile. Testicular sperm extraction (TESE) now allows them to access fatherhood. We will present the data of studies since first experiment of TESE. Several factors influencing TESE outcome were proposed in these different studies. Among them, clinical and hormonal parameters have reported by few studies, age has been one of the most discussed prognostic factor of positive sperm retrieval rate. Data seems to show that TESE carried out before an age greater than 30 has a poorer prognosis for positive sperm retrieval. In few studies performed in younger patient, before 20 years, SRR was closed to result for 20 to 30 year old patients. Offering a TESE before 16 years old does not improve positive sperm extraction rate. In fact, the few studies carried out before the age of 16 were of poorer prognosis, most often linked to insufficient maturation of the residual gametes. In addition, androgen therapy, frequently prescribed in case of Klinefelter syndrome, did not seem to show any effect on sperm retrieval but only few studies were interested in the possible impact of this treatment. In conclusion, further studies are necessary to determine the interest of new markers to predict the chance of sperm retrieval, taking into account age, hormonal therapy.

An atypical alpelisib-induced hyperglycemic hyperosmolar and diabetic ketoacidosis state: A case report and critical analysis of alpelisib-induced hyperglycemia management guidelines.

Abstract: Percutaneous intervention in the context of coronary artery ectasia (CAE) is penalized with no-reflow phenomenon. The glycoprotein-IIb/IIIa-inhibitor abciximab was the most accepted method for pharmacology thrombus resolution in this scenario, nevertheless, this agent was recently withdrawn. We describe 5 patients treated with local intracoronary fibrinolysis administrated through predesigned catheters in the setting of AMI and CAE.

Section 8: Thermal ablation.

Abstract: The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with thermal ablation, which may constitute an alternative to thyroid surgery in selected patients.

Feasibility and therapeutic potential of the 68Ga/177Lu-DOTATATE theranostic pair in patients with metastatic medullary thyroid carcinoma.

Abstract: This study assessed: 1) the clinical efficacy of imaging with 68Ga-DOTATATE PET/CT (SSTR (somatostatin receptor)-PET) to detect medullary thyroid carcinoma (MTC); and 2) the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in MTC patients.Patients with histologically proven MTC and suspected recurrence following thyroidectomy, based on raised serum calcitonin levels, underwent SSTR-PET. In addition, to evaluate the clinical efficacy and safety of PRRT, the patients with intense uptake on SSTR-PET or 99mTc-octreotide scintigraphy underwent PRRT. The Common Terminology Criteria for Adverse Events (version 4.03) was used to grade adverse events after PRRT. Treatment response was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).Twenty MTC patients (10 male, 10 female) with a median age of 48.5 years underwent SSTR-PET. SSTR-PET was positive in 17/20 patients (85%). Four of the 17 patients with positive SSTR-PET were scheduled for PRRT. In addition, 2 patients had positive 99mTc-octreotide scintigraphy results (Krenning score ≥ 2) and were scheduled for PRRT. Two of the 6 patients who underwent PRRT showed PR, 2 SD and 2 PD. Two patients died during the follow-up period. Median overall survival was 19 months (95% CI: 5.52-29.48). There were no cases of significant toxicity.Radiolabeled somatostatin analogs are contributive for the management of recurrent MTC. 68Ga-DOTATAE PET-CT showed a relatively high detection rate in recurrent MTC. In addition, PRRT with 177Lu-DOTATATE was found to be a safe alternative therapeutic option for MTC.

Calcium homeostasis pathologies in hyperparathyroidism: nephrologic and endocrinologic points of view.

Abstract: Parathyroid hormone (PTH) is a hypercalcemic hormone acting on kidneys, bone and intestine. PTH promotes calcium release from the bone, renal calcium reabsorption and phosphate excretion, and conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D-3. Hyperparathyroidism consists in PTH elevation, which may be adapted (secondary hyperparathyroidism) or non-adapted to calcemia levels (primary hyperparathyroidism, familial hypercalcemia/hypocalciuria, tertiary hyperparathyroidism). Primary hyperparathyroidism (PHP) features hypercalcemia and elevated or inappropriate PTH elevation. PHP may be revealed by biological abnormalities such as hypercalcemia and can be accompanied by renal complications (hypercalciuria, nephrolithiasis, nephrocalcinosis) and/or osteoporosis. However, it can also be normocalcemic and calcium loading will be necessary to diagnosis it. The differential diagnosis of PHP is familial hypocalciuric hypercalcemia (FHH), a dominant autosomal disease implicating a calcium sensing receptor-inactivating mutation. It impairs parathyroid cell sensitivity to calcemia elevation and thus induces excessive PTH stimulation, leading to hypercalcemia. Secondary HP (SHP) consists in PTH elevation secondary to a stimulus that needs to be corrected. 25 OHvitD deficiency, kidney failure, renal hypercalciuria, malabsorption and some drugs can induce SHP. Tertiary HP (THP) consists in autonomous PTH secretion by the parathyroid glands after prolonged stimulation under SHP, of whatever cause. This parathyroid autonomy results from the polyclonal hyperplasia observed in SHP progressing toward monoclonal nodular proliferation, leading to nodular hyperplasia or parathyroid adenoma (or, exceptionally, carcinoma), with reduced expression of CaSR and vitamin D receptor. In patients under dialysis, the frontier between SHP and THP is a matter of debate. This review will focus on the pathophysiology of calcium, diagnosis, and management of hyperparathyroidism.

Pattern of C-peptide response to oral glucose tolerance test: interest and cut-off values.

Abstract: The oral glucose tolerance test (OGTT) classifies subjects as normal, glucose intolerant or diabetic depending on glycemia at 120 min (T120) post-test. Five insulin profiles associated with different incidences of diabetes over 10 years' follow-up were previously described following OGTT. However, insulin measurement is sensitive to hemolysis, and can be replaced by C-peptide assay on hemolyzed samples. However, little is known about patterns of C-peptide response to OGTT.In total, 128 patients were included, to establish preliminary baseline C-peptide values and to evaluate C-peptide response to OGTT in comparison to insulin response, using the Liaison XL immunoanalyzer.Hundred patients had a normal glycemic response, 19 were classified as glucose intolerant and 9 as diabetic. In normal subjects, median C-peptide values (nmol/L, with 5-95 percentiles) were 0.53 (0.23-1.37) at baseline, peaking at 2.36 (0.94-1.83) at T60, and decreasing to 2.09 (1.13-4.36) at T120. The C-peptide response pattern was similar but flatter than the insulin pattern because of different catabolism pathways. Nevertheless, C-peptide and insulin response profiles were discordant in only 9.4% of cases. Profile 3 (C-peptide peaking at T60) was the most prevalent in normal patients whereas profile 4 (peak at 120 min and lower level at T30 than at T60) was the most prevalent in glucose intolerant and diabetic patients.In OGTT, C-peptide could replace insulin determination on hemolyzed blood samples to predict the risk of type 2 diabetes.

Quality of life, mood and sleep quality in patients with primary hyperparathyroidism. Impact of socio-personal and clinical profile.

Abstract: Quality of life (QoL) in patients with primary hyperparathyroidism (PHPT) can be negatively affected by the disease, and it is important to identify risk factors. The objectives of the present study were to analyze QoL, mood and quality of sleep in patients with PHPT and to determine the impact of socio-personal and clinical variables.The study group included patients diagnosed with PHPT, and the control group was taken from general population, paired by age and gender. QoL was analyzed using the SF-36 and the PHPQoL questionnaires. The Beck-II and Pittsburg questionnaires were used to assess depression and sleep quality. Socio-personal and clinical variables were analyzed. Statistical analysis on SPSS software v.28 used the Student t-test, ANOVA, Pearson's rank correlation, Mann-Whitney test, Kruskal-Wallis test and Spearman's rank correlation. A multiple linear regression model of the QoL was constructed.Sixty-five patients with PHPT were analyzed. A greater negative effect on QoL, mood and sleep quality were observed in patients with PHPT than in controls (P<0.05), with a good correlation between the various questionnaires. Several socio-personal variables had an effect on QoL and mood (P<0.05). QoL in patients with PHPT was affected by educational level, having offspring, and psychological symptoms (P<0.05).Patients with PHPT had poorer QoL and greater neurocognitive disorder than the general population. Socio-personal profile should be taken into account in the clinical assessment of these patients, together with psychological symptoms.

Section 11: Synthesis and algorithms.

Abstract: The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid with benign and non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies, the French Society of Endocrinology (SFE), the French Association of Endocrine Surgery (AFCE) and the French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This specific text is a summary chapter taking up the recommendations from specific sections and presenting algorithms for the exploration and management of thyroid nodules.

Mild hyperprolactinemia in a couple: what impact on fertility?

Abstract: Mild-to-moderate hyperprolactinemia is a frequent finding in young women presenting with infertility. Prolactin (PRL) concentration should be determined accurately, whether or not the patient has other symptoms suggestive of excess PRL such as galactorrhea or menstrual cycle disorder. After confirmation of persistent hyperprolactinemia on a second blood sample (avoiding conditions known to raise prolactin) and exclusion of macroprolactinemia, prolactinoma and other identifiable non-tumoral causes of hyperprolactinemia must be ruled out. Mildly elevated PRL levels may cause luteal insufficiency in cycling women and are associated with recurrent miscarriage. Any confirmed hyperprolactinemia should be treated in a woman who wishes or fails to become pregnant. Preference is given to cabergoline at the lowest possible dose that normalizes PRL, restoring fertility in the vast majority of cases. Evidence is much less robust in men, in whom PRL concentrations are less prone to increase and the reproductive system is less sensitive to the negative effects of hyperprolactinemia. Nevertheless, chronic and significant hyperprolactinemia in men may impair fertility or cause infertility (with or without hypogonadism) and must be treated, as in women. However, more clinical studies are clearly needed concerning male reproductive function. The significance of mild but persistent hyperprolactinemia in either member of a couple incidentally discovered during assisted reproductive technology (ART) procedures is unclear, and future evidence-based studies are needed to determine whether normalizing prolactin can improve ART outcome.

Expression of functional thyroid-stimulating hormone receptor in microglia

Abstract: The purpose of the present study was to clarify the expression of thyroid-stimulating hormone receptor (TSHR) in microglial cells, and to explore its function.Expression of TSHR in microglia was determined by Western blot, immunocytofluorescence and double immunohistofluorescence. Cyclic adenosine 3',5'-monophosphate (cAMP) production was measured after thyrotropin receptor stimulating antibody (TSAb) treatment.Results showed that TSHR protein was expressed and mainly located in the mouse microglia membrane. Moreover, TSAb stimulated cAMP production in mouse microglia (P<0.05).This study demonstrated the presence of TSHR in microglial cells. Brain TSHR was able to respond specifically to TSAb stimulation, suggesting that TSHR expression is functional. As microglia are innate immune cells that maintain environmental stability in the central nervous system and play a key role in many neuroimmune diseases, expression of functional TSHR in microglia has important pathophysiological implications.

Lysine demethylase KDM1A et expression ectopique du récepteur du GIP dans les adénomes hypophysaires somatotropes

Abstract: La réponse paradoxale de la GH à l’hyperglycémie provoquée orale (HGPO) observée chez environs 10-30 % de patients acromégales est liée à l’expression ectopique du récepteur du GIP (GIPR) dans les adénomes somatotropes. Dans l’hyperplasie bilatérale macronodulaire des surrénales GIP-dépendante, l’expression ectopique du GIPR est due à la perte fonctionnelle de l’histone demethylase KDM1A dans les lésions surrénaliennes. Notre objectif était d’étudier l’implication de KDM1A dans l’expression ectopique du GIPR dans les adénomes somatotropes. Dans cette étude rétrospective multicentrique, nous avons analysé l’ADN issu des adénomes hypophysaires de patients opérés pour une acromégalie par exome ciblé et par CGH-array. L’expression du GIPR dans ces tumeurs a été quantifiée par RT-qPCR. Nous avons analysé 72 adénomes somatotropes, et poursuivrons les analyses sur une collection tissulaire supplémentaire de 50 échantillons. L’expression du GIPR est plus élevée dans les adénomes issus de 18 (25 %) patients présentant une réponse paradoxale de la GH à l’HGPO que dans les 54 (75 %) échantillons des patients sans réponse paradoxale (p < 0,0001). Nous n’avons pas observé de variant pathogène de KDM1A. Nous avons identifié une délétion somatique du locus de KDM1A dans 21 échantillons. Ces échantillons hémizygotes pour KDM1A présentaient une élévation de l’expression tumorale du GIPR (p < 0,0001). Contrairement à l’hyperplasie surrénalienne GIP-dépendante, aucun variant pathogène de KDM1A n’a été retrouvé dans les adénomes somatotropes. Cependant, l’hémizygotie de KDM1A pourrait avoir pour conséquence un déverrouillage transcriptionnel partiel aboutissant à l’expression ectopique du GIPR dans les adénomes somatotropes.