Hormone Substitution Therapy Research Articles

Childhood craniopharyngioma: a retrospective study of children followed in Hôpital Universitaire de Bruxelles.

Craniopharyngiomas (CPs) are benign brain tumors accounting for 5 - 11% of intracranial tumors in children. These tumors often recur and can cause severe morbidity. Postoperative radiotherapy efficiently controls and prevents progression and recurrence. Despite advancements in neurosurgery, endocrinological, visual, and neuropsychological complications are common and significantly lower the quality of life of patients. We performed a retrospective study, including all patients younger than sixteen diagnosed with CP between July 1989 and August 2022 and followed up in Hôpital Universitaire de Bruxelles. Nineteen children with CP were included, with median age of 7 years at first symptoms and 7.5 at diagnosis. Common symptoms at diagnosis were increased intracranial pressure (63%), visual impairment (47%), growth failure (26%), polyuria/polydipsia (16%), and weight gain (10.5%). As clinical signs at diagnosis, growth failure was observed in 11/18 patients, starting with a median lag of 1 year and 4 months before diagnosis. On ophthalmological examination, 27% of patients had papillary edema and 79% had visual impairment. When visual disturbances were found, the average preoperative volume was higher (p=0.039). Only 6/19 patients had gross total surgical resection. After the first neurosurgery, 83% experienced tumor recurrence or progression at a median time of 22 months. Eleven patients (73%) underwent postsurgical radiotherapy. At diagnosis, growth hormone deficiency (GHD) was the most frequent endocrine deficit (8/17) and one year post surgery, AVP deficiency was the most frequent deficit (14/17). Obesity was present in 13% of patients at diagnosis, and in 40% six months after surgery. There was no significant change in body mass index over time (p=0.273) after the first six months post-surgery. CP is a challenging brain tumor that requires multimodal therapy and lifelong multidisciplinary follow-up including hormonal substitution therapy. Early recognition of symptoms is crucial for prompt surgical management. The management of long-term sequelae and morbidity are crucial parts of the clinical path of the patients. The results of this study highlight the fundamental importance of carrying out a complete assessment (ophthalmological, endocrinological, neurocognitive) at the time of diagnosis and during follow-up so that patients can benefit from the best possible care.

Horizons in Endometriosis: Proceedings of the Montreux Reproductive Summit, 14-15 July 2023.

Endometriosis is a complex and chronic gynaecological disorder that affects millions of women worldwide, leading to significant morbidity and impacting reproductive health. This condition affects up to 10% of women of reproductive age and is characterised by the presence of endometrial-like tissue outside the uterus, potentially leading to symptoms such as chronic pelvic pain, dysmenorrhoea, dyspareunia, and infertility. The Montreux summit brought a number of experts in this field together to provide a platform for discussion and exchange of ideas. These proceedings summarise the six main topics that were discussed at this summit to shed light on future directions of endometriosis classification, diagnosis, and therapeutical management. The first question addressed the possibility of preventing endometriosis in the future by identifying risk factors, genetic predispositions, and further understanding of the pathophysiology of the condition to develop targeted interventions. The clinical presentation of endometriosis is varied, and the correlation between symptoms severity and disease extent is unclear. While there is currently no universally accepted optimal classification system for endometriosis, several attempts striving towards its optimisation - each with its own advantages and limitations - were discussed. The ideal classification should be able to reconcile disease status based on the various diagnostic tools, and prognosis to guide proper patient tailored management. Regarding diagnosis, we focused on future tools and critically discussed emerging approaches aimed at reducing diagnostic delay. Preserving fertility in endometriosis patients was another debatable aspect of management that was reviewed. Moreover, besides current treatment modalities, potential novel medical therapies that can target underlying mechanisms, provide effective symptom relief, and minimise side effects in endometriotic patients were considered, including hormonal therapies, immunomodulation, and regenerative medicine. Finally, the question of hormonal substitution therapy after radical treatment for endometriosis was debated, weighing the benefits of hormone replacement.

Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma.

Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

Intelligence quotient (IQ) outcome in children with early-treated congenital hypothyroidism: a systematic review and meta-analysis

Background Congenital hypothyroidism (CH) is the most common congenital endocrine disorder in childhood and is one of the most preventable causes of intellectual disability (ID). Late initiation of thyroid hormone substitution therapy has a negative impact on intellectual abilities in CH patients.
 Objective To compare Intelligence Quotient (IQ) between children with CH who underwent early treatment among the children without CH.
 Methods We performed online literature searches of ScienceDirect, Pubmed, Cochrane Library, and Google Scholar. We included clinical studies that examined IQ scores in patients with early-treated CH and without CH. Review Manager 5.4 was used to perform the meta-analysis.
 Results Twelve studies comparing pediatric patients with and without CH were included in this meta-analysis, for a total of 808 patients. Based on data analysis, IQ levels of verbal IQ [mean difference (MD) -9.05; (95%CI -14.51 to -3.59); (P<0.00001)], performance IQ [MD -11.70; (95%CI -17.41 to -5.99); (P<0.00001)], and total IQ [MD -10.78; (95%CI -14.03 to -7.54); (P<0.00001)]. While verbal, performance, total, of the early-treated CH group were within the normal range, they were each significantly lower than those in the non-CH group.
 Conclusion This meta-analysis reveals that IQ scores in early-treated CH subjects were within normal limits, but significantly lower than that of normal controls.

Long-term clinical significance of benign endometrial cells identified on routine cervical cytology in women aged more or equal to 45 years

Within the Bethesda System, the recommendation of describing benign-appearing endometrial cells (BECs) has changed over recent years. Since the 2014 revision, their presence in cervical cytology reports has been deemed essential, beginning with age 45. Recent studies have suggested rising the reporting age to 50 years. Does the presence of these cells necessitate further assessment? This retrospective cohort study included patients aged between 45 and 65 years in whom BECs were present on cervical cytology between January 2001 and December 2010, with a follow-up at 5 and 10 years. Women who had abnormal cervical cells or atypical endometrial cells on cervical cytology were excluded, as well as women with a history of cervical or endometrial cancer, or a history of hysterectomy and incomplete follow-up data. One hundred seventy-six women were included. Of these, 31% were postmenopausal of which 65% used hormonal substitution therapy. Twenty-eight percent presented with abnormal uterine bleeding at inclusion. During the follow-up period of 10 years, 87.5% had a normal gynecological follow-up and 11.4% underwent a hysterectomy for benign pathology. One percent (2 patients) had been diagnosed with endometrial malignancy, both presenting with postmenopausal bleeding and aged over 60 years. Our study confirmed that the presence of BECs is not a reason for concern when no additional clinical indicator is recognized, especially with normal ultrasonographic examination. Further invasive exploration may be controversial. If reporting BECs in cervical cytology continues, we strongly agree on rising the reporting age to 50 years or postmenopausal state.

P-421 Return rates and outcome of fertility preservation in women with cervical cancer.

Abstract Study question What are the return rates and reproductive outcome after fertility preservation (FP) in women with cervical cancer (CC)? Summary answer Return rates after FP in women with CC seem to be comparable with those after FP for other indications. What is known already Cervical cancer is the fourth most common cancer among women. Approximately 42% of the affected women are under the age of 45, and many of them wish to preserve fertility at the time of diagnosis. Fertility sparing treatment modalities and FP with cryopreservation of oocytes, embryos or/and ovarian tissue can be offered for this purpose to carefully selected patients. These treatments are offered at Swedish academic centers within the health insurance coverage available to all citizens. To date, data on return rates, reproductive outcome and survival in women with cervical cancer undergoing FP are scarce. Study design, size, duration Prospective, single center study aiming to report long-term outcomes in women with CC who have versus have not undergone FP at Karolinska University Hospital between January 1st 1999 and September 30th 2018. Participants/materials, setting, methods During the study period, 74 women with CC received FP counseling at Karolinska University Hospital, and 52 of them women proceeded to FP. Data on return rates, reproductive outcomes and overall survival were extracted using the clinical registries. Main results and the role of chance By January 15th, 2023, 22 of 52 women with FP returned for a new fertility counselling or treatment, mean time between FP and return was 4 years (1-7 years). Among women with cryopreserved ovarian tissue (n = 40), 17 have been in contact with the clinic with fertility wish, 3 of them had re-transplantation of the tissue, but none of them achieved oocyte retrieval yet. Additionally, one woman is planned for re-transplantation in February 2023, and one woman is awaiting the decision. In two cases the decision not to re-transplant ovarian tissue was based on absence of endometrial growth following attempts of hormonal substitutive therapy. Among women with cryopreserved oocytes (n = 5), 1 returned for thawing but no pregnancy has been achieved. Among women with cryopreserved embryos (n = 5), 3 returned during follow-up, 2 proceeded to thawing and transfer, 1 got pregnant and gave birth to a child. Of two women with combination of oocytes and ovarian tissue cryopreserved, one returned for fertility treatment, but no pregnancy has been achieved after thawing and re-transplantation. Eight women died during follow-up because of recurrence of their cancer, 4 of 22 in the group without FP and 4 of 52 in the group with FP. Limitations, reasons for caution This study provides much needed data on real-world outcome in women with FP indicated by diagnosis of CC, but it has the limitations related to its descriptive character. The use of gestational carriers is not permitted in Sweden and FP program may differ from those in other countries. Wider implications of the findings The study results provide much needed data on real-world reproductive and oncologic outcome following FP in women with CC. Trial registration number NTC04602962

Bone Turnover in Relation to Thyroid-Stimulating Hormone in Hypothyroid Patients on Thyroid Hormone Substitution Therapy.

Background Bone turnover markers (BTMs) have emerged as a useful tool for monitoring bone remodeling activity in the skeleton, and their serum levels correlate with bone loss rates in osteoporotic and normal individuals. Whether the same holds for other metabolic bone diseases is still subject to discussion. Methods We analyzed the relation between levels of BTMs and TSH in 79 females on thyroid hormone substitution therapy for hypothyroidism. Based on the reference range for TSH (0.2–4.0 mU/L) in our lab, we assessed BTMs in five different groups of patients based on the following criteria: (1) hypothyroidism (TSH >4.0); (2) TSH in the high normal range (1.0–4.0); (3) TSH in the low normal range (0.2–1.0); (4) TSH below the normal range (0.01–0.2); (5) TSH undetectable (<0.01). We studied the relationship between TSH and four different bone markers: procollagen type 1 N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and bone specific alkaline phosphatase (BSAP). In a subgroup of patients, bone mineral density was assessed by a DXA scan. Results PINP emerged as the most sensitive and dynamic BTM for assessment of bone turnover in this patient group, achieving significant rho values on nonparametric correlation analysis for both TSH (rho −0.47; p=0.0001) and FT4 (rho 0.27; p=0.018). CTX and OC also revealed significant correlations to TSH, albeit with lower rho values (−0.37 and −0.24, respectively). Categorical analysis showed that bone turnover increased significantly, albeit with pronounced interindividual variability for TSH values below the lower limit of normal (0.2 mU/l), with the most severe affected being women exhibiting suppression of TSH. Further analysis of loss rates by DXA in a limited subgroup of patients showed that this was accompanied by accelerated bone loss. Conclusion PINP is the most sensitive marker of bone turnover in thyroid disorders. TSH values below the lower limit of normal are associated with increased bone turnover and accelerated bone loss, however, with pronounced interindividual variations. Assessment of PINP may be a valuable tool in cases where there is concern about possible adverse effects of thyroid hormone substitution therapy on bone.

Experience in surgical treatment of pediatric patients with adrenal tumors (monocenter study)

Objective — to determine and analyze the structure of adrenal pathology in pediatric patients operated at the Center in the years 2009 to 2020 (retrospective analysis).&#x0D; Materials and methods. A retrospective study was carried out. The analysis and investigation involved following data of 24 pediatric patients with adrenal neoplasms: age, gender, anamnesis, clinical features, preliminary diagnosis, diagnostic methods, hormonal background, radiological characteristics of tumors, surgical method of treatment, pathomorphological signs of tumors. The observation period was 2 to 11 years, on average 3 to 5 years.&#x0D; Results. A total, 980 operations in patients with the pathology of the adrenal glands were performed, from them 24 interventions (2.4 %) were carried out in pediatric patients of age group 5 to 17 years, the age 12.2 years. The proportion of boys was 8 (33.3 %), girls — 16 (66.7 %). The duration of the disease was 1 to 97 months, 13.2 months at average. The following main complaints were determined: weight gain, increased blood pressure, increased body hair, impaired puberty, pain in the abdominal cavity. Malignant tumors included adrenocortical cancer — 12.5 %, ganglioneuroblastoma — 12.5 % and pheochromoblastoma — 1 case, in total — 29.1 %. Tumors of the adrenal cortex 25 %, the adrenal medulla 12.6 %, other types of tumors amounted to 33.3 %. The long-term results of malignant neoplasms of the adrenal glands were determined. In six cases (follow-up period was up to 10 years) there was no recurrence of the disease. Additional treatment in the form of radiation and chemotherapy was not carried out. 79.1 % were operated laparoscopically, 20.9 % had lumbotomy with adrenalectomy. There were large sized malignant tumors of 4 — 17 cm, on average 8 cm. Benign tumors were between 1 — 11 cm, on average 4.3 cm. 58 % of cases were not hormonally active. In the post-operative phase, attention was paid to the prevention of adrenal insufficiency. Blood cortisol was determined on the 3rd-5th day after the operation. 29 % of patients needed hormonal substitution therapy. Two clinical cases in children of the same biological family are considered separately.&#x0D; Conclusions. Neoplasms of the adrenal glands in children, in the structure of operations performed for the pathology of the adrenal gland constituted 2.4 % of the total number of patients, the proportion of malignant neoplasms in children, according to our data was 29.1 % among pediatric patients. Malignant tumors of the adrenal glands do not have a clear age correlation. The presence of clinical manifestations associated with hormonal activity makes it possible to suspect a tumor. Hormonal activity was confirmed in 42 % of cases. At the same time, the absence of these changes does not exclude the possibility of a tumor. The disease had no clinical manifestations in 25 % of the investigated subjects.

Pituitary deficiency after brain radiation therapy in childhood

Introduction: As part of an anticancer therapy, craniospinal radiotherapy causes variable degrees of hormonal deficiencies. The onset of hormonal deficiencies depends on the dose delivered to the pituitary –hypothalamic region while their incidence and severity depends on dose fractionating and follow up duration.&#x0D; Objectives: Analyzing the long –term endocrine complications in children treated with craniospinal radiotherapy.&#x0D; Material and methods: A prospective study; including 4 medical files collected over a period of 2 years.&#x0D; Results: The study includes 4 patients with a sex ratio of 3M/1F; and a mean age of 18, 62 years. The average age at the time of irradiation was 9, 12 years. The delay between the end of radiotherapy and the first consultation varied between 1 year and 21 years. The radiotherapy was administred for medulloblastoma (n=1), Burkitt lymphoma (n=1), cavum cancer (n=1), Posterior Cranial Fossa Tumor (n=1).&#x0D; The hormonal assessment revealed: a central hypothyroidism in 3 patients, corticotropin insufficiency in 2 cases, and gonadotropin deficiency associated with micropenis in one case. No cases of diabetes insipidus have been reported. Pituitary hypothalamic MRI objectified an atrophic anterior pituitary gland in two cases. Hormonal substitutive therapy was started in all patients. Recombined human GH treatment was introduced in one case, but omitted in two others cases for bad control of the cancerous disease and for an achieved puberty in the fourth patient.&#x0D; Conclusion: The search of the hormonal deficiencies is essential for any child treated by craniospinal radiotherapy in order to institute an early hormonal substitutive therapy.&#x0D; Keywords: Craniospinal radiotherapy, hormonal deficiencies, substitutive therapy

Značaj hormonske terapije u menopauzi

Prolonging the life span has led to prolonging the menopause period, which for women brings a lot of essential changes in everyday functioning. Obtaining and recognizing health issues, together with improving quality of life, is a challenge itself to be faced not only by healthcare professionals but patients them-selves. The challenge within the challenge is to help those women that iatrogenic enter menopause (disease, post-surgically, etc.). Hormonal substitution therapy should be verified, well chosen, efficient, and safe, taken under adequate supervision, and in consultation with other healthcare specialists. Its efficiency is considerably significant for women in the first decade into menopause. Hormonal therapy could be prescribed as oral, intravaginal, intrauterine, and transdermal therapy.

Primary pituitary abscess: case report and suggested management algorithm

Purpose To describe a case of successful treatment of a patient with a rare primary pituitary abscess (PA) and propose a management algorithm. Summary of background data PA is an infrequent entity that can be life-threatening if not promptly diagnosed and treated. PAs can be primary or secondary, the latter in the presence of sellar anomalies, risk factors or a systemic or local infection. Symptoms are nonspecific, making clinical suspicion imperative. Magnetic Resonance Imaging (MRI) is the radiological tool of choice. Despite some characteristic radiographic signs, oftentimes the diagnosis is not suspected until surgical exploration. Treatment includes transsphenoidal decompression surgery with sampling of purulent material and abscess wall for appropriate microbiological staining and cultures (bacteria, mycobacteria and fungus) and prolonged antibiotic treatment. Pituitary hormonal deficiencies must be addressed as well. Methods and results We describe a case of a female patient who presented with headaches, anorexia and bitemporal hemianopsia. MRI revealed a peripherally enhancing sellar mass. Transsphenoidal surgery was performed, with intra-operative finding of purulent material. Cytology confirmed the presence of abundant leucocytes, but no pathogen was isolated. Patient completed three weeks of antibiotic therapy, with good clinical and radiological response. Headaches and visual deficits resolved. Hormonal substitution therapy was needed for six months after surgery. Conclusion This report highlights the importance of early recognition and treatment of PAs. The diagnosis is commonly very difficult before surgery, due to overlapping clinical, radiological and laboratorial findings with various other pathologies. Prompt management, with surgical decompression and appropriate antibiotic treatment, typically results in a low mortality rate and higher chance of full recovery of pituitary function. We propose a management algorithm for sellar masses suspected of being PAs.

Chapter 2 - Pituitary stalk interruption syndrome

Pituitary stalk interruption syndrome (PSIS) is a distinct developmental defect of the pituitary gland identified by magnetic resonance imaging and characterized by a thin, interrupted, attenuated or absent pituitary stalk, hypoplasia or aplasia of the adenohypophysis, and an ectopic posterior pituitary. The precise etiology of PSIS still remains elusive or incompletely confirmed in most cases. Adverse perinatal events, including breech delivery and hypoxia, were initially proposed as the underlying mechanism affecting the hypothalamic-pituitary axis. Nevertheless, recent findings have uncovered a wide variety of PSIS-associated molecular defects in genes involved in pituitary development, holoprosencephaly (HPE), neural development, and other important cellular processes such as cilia function. The application of whole exome sequencing (WES) in relatively large cohorts has identified an expanded pool of potential candidate genes, mostly related to the Wnt, Notch, and sonic hedgehog signaling pathways that regulate pituitary growth and development during embryogenesis. Importantly, WES has revealed coexisting pathogenic variants in a significant number of patients; therefore, pointing to a multigenic origin and inheritance pattern of PSIS. The disorder is characterized by inter- and intrafamilial variability and incomplete or variable penetrance. Overall, PSIS is currently viewed as a mild form of an expanded HPE spectrum. The wide and complex clinical manifestations include evolving pituitary hormone deficiencies (with variable timing of onset and progression) and extrapituitary malformations. Severe and life-threatening symptomatology is observed in a subset of patients with complete pituitary hormone deficiency during the neonatal period. Nevertheless, most patients are referred later in childhood for growth retardation. Prompt and appropriate hormone substitution therapy constitutes the cornerstone of treatment. Further studies are needed to uncover the etiopathogenesis of PSIS.

Alopecia in preexisting autoimmune thyroid disease in family medicine practice: can hyperprolactinemia induce hair loss? A case report

Management of hair loss in women presents several challenges for general practitioners, who are the first in identifying its cause and consequences in everyday clinical practice. It is usually associated with multiple secondary factors, including endocrine disorders, drug side effects, and physical or emotional stress. We report a possible pathophysiological link between hyperprolactinemia and alopecia in a patient with preexisting autoimmune thyroid disease, which has not been documented in a significant number in the literature. A 27-year-old female patient with a previous history of an autoimmune thyroid disease on hormone substitution therapy presented to a family doctor with signs of frontal alopecia that had started several months previously. On examination, frontal alopecia was confirmed. Laboratory results and thyroid ultrasound confirmed autoimmune thyroid disease, with reduced parathyroid hormone and elevated prolactin. Her female sex hormones were in the normal range. Due to elevated prolactin levels, computed tomography of the pituitary gland was performed, which excluded any brain pathology. Based on available data, there is no published systematic analysis on hyperprolactinemia-induced alopecia in previous autoimmune diseases (large cohort studies). This report indicates that, due to moderately elevated prolactin values, consideration of alternative causes and further diagnostics are necessary to exclude a prolactin-producing tumor of the pituitary gland.

Laron Syndrome—Possibilities of Diagnoses, Treatment, and Outcome

Background&#x0D; Laron syndrome (growth hormone insensitivity) is a rare autosomal recessive condition characterized by severe short stature with postnatal onset usually (1), particular facial features and hypoglycemia in childhood, and type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, and obesity in adulthood (2), caused by growth hormone receptor (GHR) anomalies (insensitivity). It is estimated that there are 350 people with this condition worldwide (3). The growth hormone receptor mutation prevents the stimulating effects of growth hormone, inducing insulin-like growth factor-1 (IGF1) deficiency. Treatment with recombinant IGF1, the only treatment option which can improve final height (4), is not available for all patients. &#x0D; Aim&#x0D; Present the clinical outcomes of a Laron syndrome patient untreated and on hormonal substitution treatment.&#x0D; Case Report&#x0D; A 18-year-old girl with Laron syndrome diagnosed at the age of 2 years and 10 months, based on the clinical feature of severe short stature (height—63 cm; −8.24 SDS, standard deviation score), particular facial features (protruding forehead, saddle nose, large eyes, sparse and thin silky hair, and high-pitched voice), small hands and feet, and sweating and hypotonic episodes, especially in the morning. The endocrine growth axis assessment revealed an elevated growth hormone concentration (&gt;40 ng/mL; 0–8 ng/mL) and very low serum IGF-1 levels ( A L141X) in the 6 exon of the GHR gene. The growth velocity without hormonal substitution was low at 0.23 cm/month (14.5 cm/63 months). After 15 months (between 8 years 1 month and 9 years 4 months) of IGF1 (mecasermin) treatment, the growth velocity increased to 0.53 cm/month, the girl’s height increased from 77.5 cm (−8.55 SDS) to 85.6 cm (−7.94 SDS). After IGF1 treatment discontinuation, height velocity fell to 0.22 cm/month. At the age of 17 years and 2 months, hormone replacement therapy with mecasermin was resumed up to 18 years. The patient also had associated pubertal delay; thelarche started at the age of 15 and progressed slowly. The final height of the patient was 117 cm. In addition, she has developed focal epilepsy, obesity, and depression.&#x0D; Conclusions&#x0D; Early diagnosis and hormone substitution therapy may reduce the clinical consequences of complications, improving the prognosis.

Порівняння ефективності різних фіксованих комбінацій антигіпертензивних препаратів у хворих з артеріальною гіпертензією та гіпотиреозом

Мета роботи – оцінити ефективність різних фіксованих подвійних комбінацій антигіпертензивних препаратів та проаналізувати їх вплив на ремоделювання серця у хворих з артеріальною гіпертензією (АГ) та гіпотиреозом.Матеріали і методи. У дослідження увійшло 50 хворих з АГ та гіпотиреозом, яких розділили на дві групи методом сліпих конвертів по 25 осіб у кожній. Хворим 1-ї групи була призначена фіксована комбінація периндоприлу з індапамідом, хворим 2-ї групи – фіксована комбінація периндоприлу з амлодипіном. Групи статистично значуще не відрізнялися за віком хворих, тривалістю замісної гормональної терапії, тривалістю АГ, рівнем офісного систолічного і діастолічного артеріального тиску (АТ) при залученні в дослідження. За індексом маси тіла досліджувані групи були порівнянні, проте кількість пацієнтів з ожирінням була більшою у 2-й групі (p=0,05). Спостереження за хворими тривало 12 міс.Результати та обговорення. Отримані дані показали, що у хворих з АГ та гіпотиреозом досягнення еутиреоїдного стану сприяє зниженню рівня АТ, проте вимагає подальшого призначення антигіпертензивної терапії. Вивчені фіксовані комбінації антигіпертензивних препаратів, а саме периндоприлу з індапамідом та периндоприлу з амлодипіном, у хворих із АГ та супутнім гіпотиреозом забезпечують статистично значуще зниження АТ за результатами амбулаторного моніторування (р&lt;0,05). При порівнянні ефективності комбінацій у хворих з АГ та гіпотиреозом залежно від індексу маси тіла встановлено, що комбінація периндоприлу з амлодипіном має більш виразний вплив на АТ у хворих з ожирінням.Висновки. Фіксована комбінація периндоприлу з амлодипіном порівняно з фіксованою комбінацією периндоприлу з індапамідом забезпечує статистично значуще більший вплив на регрес гіпертрофії міокарда лівого шлуночка, а саме зменшення індексу маси міокарда за зростом у степені 2,7 у хворих з ожирінням (р&lt;0,01).

Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy.

Although the overall risk of cancer is not increased in Turner syndrome, the pattern of cancer occurrence differs from the general population. We aim to describe the cancer morbidity pattern in Turner syndrome and evaluate the effect of long-term hormone replacement therapy (HRT). Nationwide epidemiological study. 1156 females with Turner syndrome diagnosed during 1960-2014, were linked with data from the Danish National Patient Registry. Statistics Denmark randomly identified 115 578 female controls. Stratified Cox regression was used to analyze cancer morbidity, mortality and effect of HRT. Overall risk of cancer was not elevated (hazard ratio 1.04 (95% CI: 0.80-1.36)). The risk of skin cancer and benign skin neoplasms was two-fold increased, while the risk of breast cancer was decreased (hazard ratio 0.4 (0.2-0.9)). Turner syndrome (45,X) had a two- to five-fold increased risk of benign CNS tumors, colon and rectal cancers, benign skin neoplasms and skin cancer. Turner syndrome women with a 45,X/46,XX karyotype had an increased risk of tongue cancer. HRT had no impact on the risk of any cancer investigated in this study. The lack of one X chromosome might play a role in skin neoplasms, CNS tumors, colon and rectal cancers. The risk of breast cancer is lower than in the general population. Long-term HRT during the premenopausal age range seems not to exert a cancerous effect in Turner syndrome. Increased vigilance concerning specific types of cancer in Tuner syndrome harboring a 45,X karyotype is needed.

Incidental lingual thyroid with subclinical hypothyroidism: case report

BackgroundLingual thyroid is a very rare pathological finding and is usually incidentally discovered. It occurs when a defect in embryogenesis gives rise to ectopic thyroid as tongue base mass. Majority of patients are asymptomatic. This clinical case highlights the importance of performing thyroid function tests for all lingual thyroid patients regardless of symptoms or clinical presentation.Case presentationWe present a 25-year-old lady who presented with sub-mental abscess. A CT scan was performed to confirm the diagnosis. The CT scan confirmed submental abcess and incidentally discovered lingual thyroid along with absence of thyroid tissue in its normal pretracheal position. The patient denied any symptoms of hypothyroidism. But subsequent investigations revealed clinical hypothyroidism. She was started on substitutive hormone therapy and remains asymptomatic.ConclusionLingual thyroid patients may remain asymptomatic with subclinical hypothyroidism. Hormone therapy needs to be initiated in these patients.

Female gender and exogenous progesterone exposition as risk factors for spheno-orbital meningiomas.

The great heterogeneity of meningiomas is challenging and we need to distinguish relevant subgroups. Spheno-orbital osteomeningiomas (SOOM) constitute a clinically specific entity, with slow-growing benign osteo-meningiomatous tumors, which recur after surgery in one fourth of cases. Neurosurgical daily practice, supported by the literature, shows that the vast majority of patients with SOOM are women, and we explored whether their epidemiological and hormonal profiles suggest a progesterone influence. We retrospectively documented all radiologically and histologically confirmed cases of SOOM operated in 2005-2019 in our institution. We completed the clinical and hormone history by systematic telephone interviews. In the literature, SOOM occur significantly more often in women than other meningiomas (749/847, 86.4% versus 73.8%, p = 0.002). Among 175 cases, we included 124 patients, 93.5% were women, younger than men (51 ± 5 versus63 ± 8, p = 0.02). Women' meningiomas showed more progesterone receptors (96.4% versus 50%, p < 0.001). Exogenous hormonal intake, reliable in 82 cases, concerned 83.3% (64/78) of women, with frequent progesterone intake: 13 oestroprogestogenic treatment only, with old-generation progesterone analogs, 41 progesterone analogs (cyproterone acetate, nomegestrol acetate, chlormadinone, promegestone, etonogestrel, levonogestrel), 7 substitutive hormonal therapy for menopause, 3 others. Duration of treatment was 2-40years, median 10years. SOOM develop preferentially in women in their fifties, who often received progesterone analogs, and show progesterone receptors. Progesterone analogs are incriminated in skull base meningiomas, and this is the first report on the prevalence of exogenous hormone therapy specifically in SOOM. Whether SOOM reduce after treatment discontinuation, in particular the osteoma part, needs to be explored. Anti-progesterone treatments may represent an avenue for future research in soom.

Organ of hearing and balance in peri- and postmenopausal women. Effects of hormone replacement therapy on hearing and balance in peri- and post-menopausal women: The current state of knowledge.

Sensory-neural hearing loss in people over 50 - senile deafness - is currently an increasing problem due to the growing proportion of the elderly people in the population. We can find a number of worldwide publications on hearing loss and dizziness in peri-menopausal women, but the data is inconsistent. Reports describing the influence of sex hormones on the ear and its aging are similarly controversial. This review attempts to summarize the current state of knowledge regarding hearing and balance in women during menopause, based on recent studies in this field. It describes the possible causes of hearing and balance impairment in post-menopausal women other than the mere physiological aging of the ear. The review concludes that impairment of hearing and balance is significantly related to osteoporosis, which results from estrogen deficiency during menopause. It also presents the results of studies on the impact of hormone replacement therapy (HRT) and of particular hormonal components of HRT on hearing and balance. The European population is aging, so accurate knowledge about the effects of HRT on hearing and balance is crucial in the context of improving the quality of life of elderly women through appropriate qualification for hormone substitution therapy. Further detailed and extensive study is necessary to verify the impact of sex hormones on hearing in post-menopausal women, taking into account the type of HRT used, serum hormone levels and the presence or absence of osteoporosis.

NR5A1 Gene Variants: Variable Phenotypes, New Variants, Different Outcomes

NR5A1 (nuclear receptor subfamily 5 group A member 1) is a transcriptional regulator of adrenal and gonadal development and function. Heterozygous and homozygous NR5A1 mutations have been described in people with 46,XY disorders of sex development (DSD). The clinical, endocrine, and genetic features of four 46,XY subjects with NR5A1 genetic variants (2 sisters, 2 boys) from 3 unrelated families are reported. All subjects presented with hypergonadotropic hypogonadism and abnormal pubertal progression. Markers of Sertoli cell function were more affected than those of Leydig cell function. Genetic investigation demonstrated the presence of different heterozygous NR5A1 genetic variants. In the boys, pathogenetic NR5A1 gene variants were found that had been previously reported. The 2 sisters carried a new genetic variant in exon 4, and in silico analysis and ACMG classification indicated its pathogenicity. The data confirmed that NR5A1 gene mutations may present with variable genital phenotypes. Anyway, reproductive function was always impaired. Any clinical or endocrine data seem to be unable to differentiate these patients from other 46,XY DSD cases, suggesting that molecular analysis must be warranted. In subjects with NR5A1 mutations, different decisions in sex assignment may permit satisfying somatic and psychological outcome, but any option requires hormonal substitutive therapy from adolescence onward.