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Reviews in Endocrine & Metabolic... Jun 2024The results of many studies in recent years indicate a significant impact of pituitary function on bone health. The proper function of the pituitary gland has a... (Review)
Review
The results of many studies in recent years indicate a significant impact of pituitary function on bone health. The proper function of the pituitary gland has a significant impact on the growth of the skeleton and the appearance of sexual dimorphism. It is also responsible for achieving peak bone mass, which protects against the development of osteoporosis and fractures later in life. It is also liable for the proper remodeling of the skeleton, which is a physiological mechanism managing the proper mechanical resistance of bones and the possibility of its regeneration after injuries. Pituitary diseases causing hypofunction and deficiency of tropic hormones, and thus deficiency of key hormones of effector organs, have a negative impact on the skeleton, resulting in reduced bone mass and susceptibility to pathological fractures. The early appearance of pituitary dysfunction, i.e. in the pre-pubertal period, is responsible for failure to achieve peak bone mass, and thus the risk of developing osteoporosis in later years. This argues for the need for a thorough assessment of patients with hypopituitarism, not only in terms of metabolic disorders, but also in terms of bone disorders. Early and properly performed treatment may prevent patients from developing the bone complications that are so common in this pathology. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary disease.
Topics: Humans; Hypopituitarism; Osteoporosis; Bone and Bones; Bone Density
PubMed: 38565758
DOI: 10.1007/s11154-024-09878-w -
Molecular Genetics and Metabolism... Mar 2024Galactosemia type I is an autosomal recessive disorder of galactose metabolism due to galactose-1-phosphate uridyltransferase deficiency, encoded by . To investigate the...
BACKGROUND
Galactosemia type I is an autosomal recessive disorder of galactose metabolism due to galactose-1-phosphate uridyltransferase deficiency, encoded by . To investigate the phenotypes, genotypes and long-term outcomes of galactosemia, we performed a retrospective cohort study in our center.
METHODS
All individuals with galactosemia type I were included. We divided individuals into two groups to compare the outcomes of those treated symptomatically (SymX) and asymptomatically (AsymX). We reviewed electronic patient charts for clinical features, biochemical investigations, molecular genetic investigations, treatments, and outcomes.
RESULTS
There were 25 individuals including classic ( = 17), clinical variant ( = 4), and biochemical variant (Duarte) galactosemia ( = 4). Twelve individuals were diagnosed symptomatically (SymX), and 9 individuals were diagnosed asymptomatically (AsymX). We did not include individuals with biochemical variant (Duarte) galactosemia into any of these groups. At the time of the diagnosis, conjugated hyperbilirubinemia was present in 83.3% of SymX group, whereas only 22% of AsymX group. SymX group had hepatomegaly (25%), failure to thrive (33.3%), cataract (16.7%) and sepsis (25%), whereas none of the individuals in the AsymX group had these clinical features. Fourteen variants in were identified including pathogenic/likely pathogenic ( = 12), and likely benign/benign ( = 2) variants. The vast majority of individuals with classic and clinical variant galactosemia were treated with a galactose-lactose-free diet for life ( = 20/21). Intellectual disability was present in 54.5% of the SymX group, and in 37.5% of the AsymX group as a long-term outcome. Tremors were present 50% of the SymX group, and in 22% of the AsymX group as a long-term outcome. Although, intellectual disability and tremors seem to be less common in the AsymX group, there was no statistically significant difference between both groups. Primary ovarian insufficiency was present 50% of the SymX group, whereas in 20% of the AsymX group in post-pubertal females. We report a novel hypomorphic variant (p.Ala303Ser) in one individual with clinical variant galactosemia. We also report an individual with clinical variant galactosemia with normal urine galactitol levels on a normal diet.
CONCLUSION
It seems that newborn screening and early administration of a galactose-lactose-free diet decreases the long-term galactosemia-associated complications but does not prevent them completely. It may be that not all individuals with clinical variant galactosemia may need a galactose-lactose-free diet. It is timely to find new therapeutic strategies that can reduce the frequency of late-onset complications in galactosemia.
PubMed: 38469090
DOI: 10.1016/j.ymgmr.2024.101055 -
Children (Basel, Switzerland) Feb 2024Possible therapeutic failure of pediatric obesity is influenced by the high dropout rate. The aim of this study was to evaluate the rate of dropout and the rate of...
BACKGROUND
Possible therapeutic failure of pediatric obesity is influenced by the high dropout rate. The aim of this study was to evaluate the rate of dropout and the rate of weight loss over the 24 months of follow-up.
METHODS
The retrospective, single-center study, involved 489 patients followed for obesity in the period 2016-2020. Patients' auxological data and blood samples were collected during the first (V1) and last visit (V2). Dropout was defined as a follow-up of less than 12 months and/or including less than one visit every 6 months. Patients were divided into two groups and compared: Group A of dropout (297 patients) and Group B of non-dropout (192 patients).
RESULTS
In the follow-up period, which had a mean duration of 24 months, the dropout rate was 60.7%. In Group A, the percentage of patients with BMI ≥ 3 SD at V2 was significantly higher than that in Group B. In Group B, the percentage of patients with pathological HOMA-IR and with fasting glucose >100 mg/dL was higher than group A. The probability of dropout was positively associated with pubertal stage and negatively with impaired fasting glycemia and pathological insulinemia at V1.
CONCLUSION
The study demonstrated a high dropout rate during follow-up, mainly among adolescents and patients with no glucometabolic alterations.
PubMed: 38397317
DOI: 10.3390/children11020205 -
International Urology and Nephrology Jul 2024Cryptorchidism is a well-defined risk factor for testicular germ cell tumors, whereas the underlying mechanisms have not been fully elucidated. Surgical procedures to...
PURPOSE
Cryptorchidism is a well-defined risk factor for testicular germ cell tumors, whereas the underlying mechanisms have not been fully elucidated. Surgical procedures to reposition undescended testicles into the scrotum (orchidopexy) in early childhood are recommended both to increase fertility potential and to reduce the risk of developing testicular tumors. However, treatment in the post-pubertal period is controversial. The aim of this study is to review the histopathology of orchiectomy specimens and determination of spermatogenesis in post-pubertal patients with non-treated cryptorchidism.
METHODS
Retrospective chart review was performed to assess the occurrence of TGCTs and determine spermatogenesis in post-pubertal individuals who underwent inguinal orchiectomy for undescended testis between January 2010 and December 2019. Age at the time of surgery, laterality, location of the undescended testis and pathology results were evaluated. All pathology specimens were reviewed by a blinded pathologist.
RESULTS
There were 23 patients in the cohort with a mean age of 21 years (range 13-46 years). All testes were in the inguinal canal. Our results indicated that 1 patient had seminoma. In the histological evaluation of the remaining 22 patients in whom no tumor was detected, normal spermatogenesis was not observed in any patient. Further, seminiferous tubules were not found in 19 patients. Maturation arrest was detected in the remaining 3 patients.
CONCLUSION
Testicular germ cell carcinoma was found in 4% of the patients who underwent post-pubertal orchiectomy. In addition, none of the undescended testes had normal spermatogenetic activity. Thus, orchiectomy should be considered in post-pubertal males with unilateral undescended testis that do not need the endocrinological activity of the testis.
Topics: Humans; Male; Cryptorchidism; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Retrospective Studies; Adolescent; Spermatogenesis; Adult; Young Adult; Middle Aged; Risk Factors; Orchiectomy; Risk Assessment
PubMed: 38349599
DOI: 10.1007/s11255-024-03963-4 -
Journal of Clinical Medicine Jan 2024Paediatric and adolescent shoulder instability is caused by a unique combination of traumatic factors, ligamentous laxity, and pattern of muscle contractility. The... (Review)
Review
Paediatric and adolescent shoulder instability is caused by a unique combination of traumatic factors, ligamentous laxity, and pattern of muscle contractility. The multifactorial nature of its aetiology makes interpretation of the literature difficult as nomenclature is also highly variable. The purpose of this review is to summarize the existing literature and shed light on the nuances of paediatric and adolescent shoulder instability. The epidemiology, clinical features, imaging, and management of all forms of paediatric shoulder instability are presented. The main findings of this review are that structural abnormalities following a dislocation are uncommon in pre-pubertal paediatric patients. Young post-pubertal adolescents are at the highest risk of failure of non-operative management in the setting of traumatic instability with structural abnormality, and early stabilisation should be considered for these patients. Remplissage and the Latarjet procedure are safe treatment options for adolescents at high risk of recurrence, but the side-effect profile should be carefully considered. Patients who suffer from instability due to generalized ligamentous laxity benefit from a structured, long-term physiotherapy regimen, with surgery in the form of arthroscopic plication as a viable last resort. Those who suffer from a predominantly muscle patterning pathology do not benefit from surgery and require focus on regaining neuromuscular control.
PubMed: 38337418
DOI: 10.3390/jcm13030724 -
Clinical Pediatric Endocrinology : Case... 2024Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects... (Review)
Review
Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects of inflammation and negative effects of glucocorticoids (used as therapeutic option) on the growth hormone axis and locally on the growth plate and bone metabolism. In the last decade, the introduction of biologics has changed the disease course regarding consequences and outcomes. Anyway in some cases, treatment with biologics has failed in restoring normal growth in patients with juvenile idiopathic arthritis; in contrast, several studies have reported improved height velocity and growth rate in patients with juvenile idiopathic arthritis treated with growth hormone. This study aimed to evaluate the impact of growth hormone treatment on the growth and pubertal development in juvenile idiopathic arthritis patients through a narrative review of the literature over the last four decades.
PubMed: 38299178
DOI: 10.1297/cpe.2023-0036 -
Euroasian Journal of... 2023Autoimmune hepatitis (AIH) accounts for cases of chronic liver disease with greater incidence in females than males. It has a bimodal distribution in the age group...
UNLABELLED
Autoimmune hepatitis (AIH) accounts for cases of chronic liver disease with greater incidence in females than males. It has a bimodal distribution in the age group peaking around pubertal periods and later in the fourth to sixth decade of life. It is characterized by continual hepatocellular inflammation and necrosis which bears the potential to progress to fibrosis and cirrhosis. Approximately a third of the patients manifest with features of acute hepatitis while some patients may progress to chronic liver disease with acute liver failure manifesting in the form of jaundice and coagulopathy. Management has long involved administration of corticosteroids alone or in association with other immunosuppressants like azathioprine to achieve long-term remission. Response to therapy is significantly variable as few patients achieve remission while some may relapse, thereby becoming candidates requiring lifelong therapy. It can either present as insidious onset or acute with manifestations ranging broadly from fatigue malaise, lethargy right upper quadrant pain weight loss anorexia, and jaundice, where up to one-third of patients may have progressed to frank cirrhosis at the time of diagnosis. A 62-year female presented with complaints of facial puffiness more around the eyes, associated with profoundly reduced appetite, yellowish discoloration of the skin, conjunctiva since 1 month, and sudden onset generalized itching not associated with fever, joint pains, weight loss, vomiting, loose stools, rash, or bleeding manifestations. She was admitted for further evaluation and workup. Liver function test revealed predominant unconjugated hyperbilirubinemia with direct bilirubin of 0.7 mg/dL and indirect bilirubin of 1.6 mg/day and transaminitis. Further investigations showed significantly elevated immunoglobulin G (IgG) and 1:80 titer of antinuclear antibodies (ANAs). In view of the high suspicion of autoimmune etiologies, the patient was subjected to a liver biopsy that confirmed cirrhosis with moderate interface hepatitis in the background of negative viral serologies and substance abuse history. She was started on a steroid course on a monthly follow-up basis to ensure biochemical remission.
HOW TO CITE THIS ARTICLE
Fatima R, Mohammed V, Fatima A, . Case of Autoimmune Hepatitis. Euroasian J Hepatogastroenterol 2023;13(2):166-168.
PubMed: 38222952
DOI: 10.5005/jp-journals-10018-1413 -
Medicine Dec 202317α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to...
RATIONALE
17α-Hydroxylase/17, 20-lyase deficiency (17OHD) is a recessively inherited autosomal disease caused by CYP17A1 gene mutations. It is characterized by failure to synthesize cortisol, adrenal androgens and gonadal steroids. However, it is rare in clinic combining with type 2 diabetes mellitus (T2DM).
PATIENT CONCERNS
A 21-year-old woman was transferred to an endocrinology clinic because of paroxysmal paralysis. In addition, she presented with hypertension, primary amenorrhea and lack of pubertal development. Blood evaluation revealed hypokalemia, and a low cortisol level with an increased adrenocorticotropic hormone concentration. The renin activity and testosterone and estrogen levels were suppressed, and the gonadotropin levels were high. CT scan showed bilateral adrenal hyperplasia. Besides, this patient had hyperglycemia, hyperinsulinism and negative diabetes type 1 related antibodies. A homozygous mutation c. 985 to 987delinsAA in exon 6 was found in the patient which caused the missense mutation (p.Y329fs).
DIAGNOSES
17α-hydroxylase/17, 20-lyase deficiency combined with T2DM was considered.
INTERVENTIONS
The patient received dexamethasone, estradiol valerate, metformin, amlodipine besylate and D3 calcium carbonate tablets. The doses of dexamethasone was changed according to her blood potassium levels.
OUTCOMES
After treatment, the blood pressure, blood potassium and blood glucose returned to normal range. Besides, she had restored her menstrual cycle.
LESSONS
For patients with hypertension, hypokalemia and lack of pubertal development, the possibility of 17OHD should be considered. The subsequent treatment would be challenging in patients with combined 17OHD and T2DM, considering the potential contribution of glucocorticoids to diabetic balance and osteoporosis.
Topics: Female; Humans; Young Adult; Adrenal Hyperplasia, Congenital; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone; Hypertension; Hypokalemia; Lyases; Mixed Function Oxygenases; Mutation; Potassium; Steroid 17-alpha-Hydroxylase
PubMed: 38206738
DOI: 10.1097/MD.0000000000036727 -
Frontiers in Endocrinology 2023Impaired testosterone secretion is a frequent following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical...
INTRODUCTION
Impaired testosterone secretion is a frequent following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.
METHODS
Monocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 years after HSCT and showing, upon enrollment, clinical and biochemical signs consistent with pubertal onset and progression were included. Clinical and biochemical data collected every 6-12 months were recorded.
RESULTS
Of 130 patients enrolled, 56% were prepubertal, while 44% were peri-/postpubertal upon HSCT. Overall, 44% showed spontaneous progression into puberty and normal gonadal profile, while the remaining experienced pubertal arrest (1%), isolated increase of FSH (19%), compensated (23%) or overt (13%) hypergonadotropic hypogonadism. Post-pubertal testicular volume (TV) was statistically smaller among patients still pre-pubertal upon HSCT ( 0.049), whereas no differences were recorded in adult testosterone levels. LH and testosterone levels showed a specular trend between 20 and 30 years, as a progressive decrease in sexual steroids was associated with a compensatory increase of the luteinizing hormone. A variable degree of gonadal dysfunction was reported in 85%, 51%, 32% and 0% of patients following total body irradiation- (TBI), busulfan-, cyclophosphamide- and treosulfan-based regimens, respectively. TBI and busulfan cohorts were associated with the lowest probability of gonadal event-free course (<0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan ( 0.024). Chemo-only regimens were associated with statistically larger TV (0.001), higher testosterone ( 0.008) and lower gonadotropin levels (0.001) than TBI. Accordingly, the latter was associated with a 2-fold increase in the risk of gonadal failure compared to busulfan (OR 2.34, CI 1.08-8.40), whereas being pre-pubertal upon HSCT was associated with a reduced risk (OR 0.15, CI 0.08-0.30).
CONCLUSIONS
a) patients pre-pubertal upon HSCT showed a reduced risk of testicular endocrine dysfunction, despite smaller adult TV; b) patients showed downwards trend in testosterone levels after full pubertal attainment, despite a compensatory increase in LH; c) treosulfan was associated to a statistically lower occurrence of hypogonadism than busulfan, with a trend towards larger TV, higher testosterone levels and lower gonadotropins.
Topics: Adult; Child; Humans; Male; Busulfan; Leydig Cells; Retrospective Studies; Hypogonadism; Hematopoietic Stem Cell Transplantation; Testosterone
PubMed: 38152128
DOI: 10.3389/fendo.2023.1292683 -
Human Reproduction (Oxford, England) Feb 2024Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent...
Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.
Topics: Adult; Humans; Male; Child; Testis; Semen; Spermatozoa; Spermatogonia; Sertoli Cells; Azoospermia; Sperm Retrieval
PubMed: 38140699
DOI: 10.1093/humrep/dead243