Unlocking the Genetic Secrets of Acromegaly: Exploring the Role of Genetics in a Rare Disorder.

Acromegaly is a rare endocrine disorder characterized by the excessive production of growth hormone (GH) in adulthood. Currently, it is understood that certain pituitary neuroendocrine tumors (PitNETs) exhibit a hereditary predisposition. These tumors' genetic patterns fall into two categories: isolated and syndromic tumors. The isolated forms are characterized by molecular defects that predispose exclusively to PitNETs, including familial isolated pituitary adenomas (FIPAs) and sporadic genetic defects not characterized by hereditary predisposition. All the categories involve either germline or somatic mutations, or both, each associated with varying levels of penetrance and different phenotypes. This highlights the importance of genetic testing and the need for a more comprehensive view of the whole disease. Despite the availability of multiple treatment options, diagnosis often occurs after several years, and management is still difficult. Early detection and intervention are crucial for preventing complications and enhancing the quality of life for affected individuals. This review aims to elucidate the molecular, clinical, and histological characteristics of GH-secreting PitNETs, providing insights into their prevalence, treatment nuances, and the benefits of genetic testing for each type of genetic disorder associated with acromegaly.

Bone mineral density predictors in long-standing type 1 and type 2 diabetes mellitus.

BACKGROUND: Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. METHODS: Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) - matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. RESULTS: T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration - but not HbA1c- negatively predicted femoral neck BMD in T1D (ß= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (ß = 0.46, p = 0.006) and femoral neck BMD (ß = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. CONCLUSIONS: Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.

Changes in body composition, adipokines, ghrelin, and FGF23 in growth hormone-deficient children during rhGH therapy.

INTRODUCTION: Beyond growth acceleration, growth hormone (GH) therapy improves body composition of GH-deficient (GHD) children due to the interaction of GH with lipid and carbohydrate metabolism, possibly mediated by adipokines secreted by adipose tissue and ghrelin. To promote linear growth, it is essential to have normal phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is a known regulator of serum phosphorus and may be responsible for the increased renal phosphorus reabsorption observed during GH therapy. This study aimed to assess the impact of one-year GH therapy on body composition, adipokines, acylated/unacylated ghrelin (AG/UAG), and FGF23 in GHD children. MATERIAL AND METHODS: A prospective observational study of 42 prepubertal, non-obese GHD children followed up in the first year of GH replacement therapy, investigating changes in adipokine profiles, AG/UAG, FGF23, and body composition. Data before therapy onset were compared with measurements obtained after 6 and 12 months of GH therapy. RESULTS: All children with a mean age of 9.2 ± 2.6 years grew at an accelerated pace. Total body fat decreased significantly, while the lipid profile improved, and total bone mineral density (BMD) significantly increased over the 12 months of treatment. Leptin and UAG levels decreased significantly, whereas adiponectin and AG values increased. A significant increase in plasma FGF23 and insulin growth factor 1 (IGF1) was accompanied by increased serum phosphate. Changes in FGF23 concentration did not have an impact on BMD. The strong association of FGF23 with IGF1 and height standard deviation (SD) could reveal a role of FGF23 in linear growth. In regression analysis models, GH therapy influences the changes of leptin and adiponectin, but not ghrelin, independently of body composition - lean or fat mass. CONCLUSIONS: GH replacement therapy improves body composition and adipokine profile in GHD children and directly impacts leptin and adiponectin concentrations independently of body composition. Also, GHD children have increased serum phosphate, correlated with upregulation rather than with suppression of FGF23, an unexpected observation given the phosphaturic role of FGF23. Further research is needed to identify the molecular mechanisms by which the GH/IGF1 axis influences adipokines secretion and plasma changes of FGF23.

Coincidence or Causality: Parathyroid Carcinoma in Chronic Kidney Disease-Case Report and Literature Review.

Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) are, however, scarce. Most features that raise the suspicion of PC in PHPT are part of the usual SHPT evolution in CKD, mirroring the natural changes undergone by the parathyroid glands. Therefore, pre-surgically establishing the malignant or benign character of the lesions is cumbersome. We present two cases of PC in end-stage renal disease, one of which was bilateral, diagnosed after total parathyroidectomy in a high-volume parathyroid surgery center. A literature review of the data was also performed. A systematic search of the PubMed/MEDLINE database until January 2024 identified 42 cases of PC associated with SHPT. Understanding the PC features in CKD might improve associated bone and mineral disease management, and reduce the risk of metastasis, parathyromatosis, or recurrence. Irradiation, prolonged immunosuppression, long dialysis vintage, and genotype may predispose to the malignant transformation of chronically stimulated parathyroids. Despite postsurgical diagnosis, favorable outcomes occurred when distant metastases were absent, even without "en bloc" resection. Further research is warranted to delineate specific diagnostic and therapeutic approaches tailored to this particular patient subpopulation.

Preptin: A New Bone Metabolic Parameter?

Preptin is a 34-aminoacid peptide derived from the E-peptide of pro-insulin-like growth factor 2 (pro-IGF2) that is co-secreted with insulin and upregulates glucose-mediated insulin secretion. High serum preptin levels were described in conditions associated with insulin resistance, such as polycystic ovary syndrome and type 2 diabetes mellitus (T2M). Insulin and also IGF2 are known to be anabolic bone hormones. The "sweet bone" in T2M usually associates increased density, but altered microarchitecture. Therefore, preptin was proposed to be one of the energy regulatory hormones that positively impacts bone health. Experimental data demonstrate a beneficial impact of preptin upon the osteoblasts. Preptin also appears to regulate osteocalcin secretion, which in turn regulates insulin sensitivity. Preptin is greatly influenced by the glucose tolerance status and the level of physical exercise, both influencing the bone mass. Clinical studies describe low serum preptin concentrations in osteoporosis in both men and women, therefore opening the way towards considering preptin a potential bone anabolic therapy. The current review addresses the relationship between preptin and bone mass and metabolism in the experimental and clinical setting, also considering the effects of preptin on carbohydrate metabolism and the pancreatic-bone loop.

Thyroid, Gonadal and Adrenal Dysfunction in Kidney Transplant Recipients: A Review for the Clinician.

While chronic kidney disease-associated mineral and bone disorders (CKD-MBD) prevail in the endocrinological assessment of CKD patients, other endocrine abnormalities are usually overlooked. CKD is associated with significant thyroid, adrenal and gonadal dysfunction, while persistent and de novo endocrinological abnormalities are frequent among kidney transplant recipients (KTR). Low T3 levels prior to transplantation may help identify those at risk for delayed graft function and are often found in KTR. Thyroid surveillance after kidney transplantation should be considered due to structural anomalies that may occur. Despite the rapid recovery of gonadal hormonal secretion after renal transplantation, fertility is not completely restored. Testosterone may improve anemia and general symptoms in KTR with persistent hypogonadism. Female KTR may still experience abnormal uterine bleeding, for which estroprogestative administration may be beneficial. Glucocorticoid administration suppresses the hypothalamic-pituitary-adrenal axis in KTR, leading to metabolic syndrome. Patients should be informed about signs and symptoms of hypoadrenalism that may occur after glucocorticoid withdrawal, prompting adrenal function assessment. Clinicians should be more aware of the endocrine abnormalities experienced by their KTR patients, as these may significantly impact the quality of life. In clinical practice, awareness of the specific endocrine dysfunctions experienced by KTR patients ensures the correct management of these complications in a multidisciplinary team, while avoiding unnecessary treatment.

SHOX Deletion and Idiopathic Short Stature: What Does the Clinician Need to Know? Case Series Report.

Children diagnosticated with idiopathic short stature (ISS) are probably, in most cases, underdiagnosticated. The genetic causes of ISS may be mutations of genes involved in local regulation of the growth plate or genes involved in the GH-IGF1 axis physiology. We present a kindred of five children evaluated for short stature or low normal stature, initially diagnosticated as idiopathic short stature, familial short stature, or being small for gestational age. Clinical signs suggestive of SHOX deletion screening in a child with short stature are low arm span/height ratio, increased sitting height/height ratio, BMI > 50% percentile, Madelung deformity, cubitus valgus, bowing and shortening of the forearm, dislocation of the ulna (at the elbow), and the appearance of muscular hypertrophy. Radiological characteristics suggestive of SHOX deficiency are triangularisation of the distal radial epiphysis, an enlarged diaphysis of the radius plus bowing of the radius, the convexity of the distal radial metaphysis, short fourth and fifth metacarpals, pyramidalization of the carpal row. Treatment with rGH is approved for children with SHOX gene deficiency and short stature. This kindred is an example that familial short stature, idiopathic short stature, and short stature due to a small gestational age are not final diagnoses. Complex investigations are necessary to identify the precise cause, leading to optimal clinical management. Treatment with rGH is an option for some of them; for others, it has no therapeutic response and, in some cases, is even harmful.

Personalized Diagnosis in Differentiated Thyroid Cancers by Molecular and Functional Imaging Biomarkers: Present and Future.

Personalized diagnosis can save unnecessary thyroid surgeries, in cases of indeterminate thyroid nodules, when clinicians tend to aggressively treat all these patients. Personalized diagnosis benefits from a combination of imagery and molecular biomarkers, as well as artificial intelligence algorithms, which are used more and more in our timeline. Functional imaging diagnosis such as SPECT, PET, or fused images (SPECT/CT, PET/CT, PET/MRI), is exploited at maximum in thyroid nodules, with a long history in the past and a bright future with many suitable radiotracers that could properly contribute to diagnosing malignancy in thyroid nodules. In this way, patients will be spared surgery complications, and apparently more expensive diagnostic workouts will financially compensate each patient and also the healthcare system. In this review we will summarize essential available diagnostic tools for malignant and benignant thyroid nodules, beginning with functional imaging, molecular analysis, and combinations of these two and other future strategies, including AI or NIS targeted gene therapy for thyroid carcinoma diagnosis and treatment as well.

Pathogenic Connections in Post-COVID Conditions: What Do We Know in the Large Unknown? A Narrative Review.

The coronavirus 2019 (COVID-19) disease has long-term effects, known as post-COVID conditions (PCC) or long-COVID. Post-COVID-19 syndrome is defined by signs and symptoms that occur during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which persist for more than 12 weeks and cannot be supported by an alternative diagnosis. The cardiovascular damage caused by COVID-19 in the severe forms of the disease is induced by severe systemic inflammation, considered to be one of the causes of myocardial lesions, with increased levels of circulating cytokines and toxic response mediators. We have focused on conditions that can induce long-COVID-19, or multisystem inflammatory syndrome in adults or children (MIS-C/MIS-A), with an emphasis on endocrinological and metabolic disorders. Although described less frequently in children than in adults, long-COVID syndrome should not be confused with MIS-C, which is an acute condition characterized by multisystem involvement and paraclinical evidence of inflammation in a pediatric patient who tested positive for SARS-CoV-2. At the same time, we mention that the MIS-A symptoms remit within a few weeks, while the duration of long-COVID is measured in months. Long-COVID syndrome, along with its complications, MIS-A and MIS-C, represents an important challenge in the medical community. Underlying comorbidities can expose both COVID-19 adult and pediatric patients to a higher risk of negative outcomes not only during, but in the aftermath of the SARS-CoV-2 infection as well.

Updated Incidence of Thyroid Cancer in the North East Region of Romania after 35 Years of Chernobyl Fallout. Is There a Link between?

Thyroid cancer (TC) represents a worldwide problem, the consistent growth of the incidence increment issues about management of risk factors and curative treatment. Updated statistical data are not complete in the North East region of Romania and need to be improved. Therefore, through this study, we aim to renew the existing data on thyroid cancer. We conducted a retrospective study covering a period of 10 years. Data were collected from a hospital information system (InfoWorld) between 2009 and 2019. Patients' age groups were stratified in relation with the age at the moment of the Chernobyl event. A database was obtained (Microsoft Excel) and statistical correlations were applied. In the studied period, 1159 patients were diagnosed: 968 females and 191 males, distributed by region, with the highest addressability in Iasi (529), followed by neighboring counties. Age distribution displayed that most of the thyroid cancers were in the range 4060 years old (50.94%), followed by 60-80 years old (32.41%). Most patients were diagnosed with papillary carcinoma 63.10%, then follicular 14.7%, medullary 6.74% and undifferentiated 1.02%. Romania was in the vicinity of the radioactive cloud at Chernobyl fallout, so we must deliberate whether the increased incidence of thyroid cancer in the age group 40-60 years is associated with radiogenicity (iodine 131) given the fact that over has 35 years and the half-life of other radioisotopes like Caesium-137 and Strontium -90 is completed.

MYTHS AND CONTROVERSIES IN HYPOGONADISM TREATMENT OF AGING MALES.

Low T is an independent risk factor for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) development; patients with these clinical conditions should be screened for hypogonadism. Testosterone replacement therapy (TRT) ameliorates libido, improves bone mass, improves insulin resistance, reduces fat mass and increases lean body mass with no change in body weight. There are no evidences that testosterone therapy increases the risk of prostate cancer but it is certain that testosterone stimulates growth of metastatic prostate cancer. TRT has an antiarrhythmic and a vasodilator effect, independent of the nitric oxide effect. Patients with heart failure have low levels of testosterone, and TRT improves exercise capacity. Men with low testosterone have risk for premature death. Cardiovascular adverse effects of testosterone therapy are under discussion. We need large prospective placebo-controlled randomized trials to determine definitively the cardiovascular risks of TRT.

Jod-Basedow effect due to prolonged use of lugol solution-case report.

Graves' disease is the most common form of hyperthyroidism, accounting for 60-80% of all cases of thyrotoxicosis. If left untreated, it may lead to severe thyrotoxicosis with cardiovascular, ocular, psychiatric complication, and in extreme cases thyrotoxic crisis with a high mortality rate. We present the case of a 50-years-old woman diagnosed in another service with Graves' disease and treated for many years with antithyroid drugs (ATDs), admitted to our service for a relapse due to treatment discontinuation. The surgical treatment was planned and the preoperative preparation with Lugol solution was initiated. Due to a misunderstanding, the administration of iodine solution was extended for a period of about 30 days, thus generating the so-called Jod-Basedow effect, with the exacerbation of the manifestations of thyrotoxicosis and risk of thyroid storm. The patient received treatment with high ATDs doses, glucocorticoids, and beta-blockers, resulting in the progressive improvement of symptoms. She was discharged from hospital and given the risk of thyrotoxic crisis the surgery was postponed. After a month, the patient underwent thyroidectomy without preoperative preparation with iodine solution. The operative and postoperative courses were uneventful.

[Thyroid ultrasonography. Interobserver and intraobserver variations]. / Ecografia tiroidiana. Variatii interobservator si intraobservator.

UNLABELLED: Thyroid ultrasonography is a simple diagnostic method for assessing the prevalence of goitre in children, parameter useful in the estimation of iodine supply. The normal limits recommended by WHO and ICCIDD (following the ThyroMobil study) have been debated by studies which found smaller values, even in regions included in the ThyroMobil study. AIM: To assess the importance of the inter- and intra-observer differences in the determination of thyroid volume in children. MATERIAL AND METHODS: Thyroid volume in 30 children was estimated using the rotating ellipsoid formula by 3 different observers. One of them determined twice the volume in 25 children. RESULTS: Mean interobserver variations were 9.51 +/- 8.8%. More important differences were between observer 1 and 3. The differences between every diameter were between 12 and 16%, more important for the longitudinal one. The intraobserver differences were 6.29 +/- 6.12%. We did not find a relation between the value of the thyroid volume and the interobserver (r2 = 0.13, p > 0.05) or intraobserver (r2 = 0.15, p > 0.05) differences. CONCLUSIONS: Interobserver variation may be important, and can partially explain the disagreements on thyroid volume in children. Intraobserver differences, although present, are less calculated. It is important to establish standards for each geographical area and, as much as possible, by the same person. In order to obtain comparable data the techniques of the ultrasound volume evaluation should be harmonized.