ACTA ENDOCRINOLOGICA (BUC)

Background. Hip fractures are a major issue of public health as they are responsible for high morbidity, excess mortality and costs. There are differences in Europe and worldwide in the incidence rates of hip fractures and time trends, in the context of the population aging. Ten years ago, we characterized the incidence of hip fracture in Romania using data from the national hospital discharge register. Objective. This is the first Romanian study to assess the hip fracture incidence rates over a period of 11 years, between 2008 and 2018. Subjects and Methods. This analysis is a nationwide retrospective study on hospitals reporting primary DRG data on hip fracture, using a rigorous definition with both diagnostic and surgical procedure codes. The population aged 40+ was stratified in 5-year intervals and both the crude incidence rates and the adjusted incidence rates of hip fracture using standardization on age for the 2018 reference population were calculated in women and men. Results. From 2008 to 2018, the number of hip fractures rose by 53 % in women (from 7513 to 11512) and 22.4 % in men (from 4266 to 5220). Meanwhile, the Romanian population over 40 years increased by 12.5% in women and 14.2% in men. The crude incidence rate rose by 36.2% in women and 7.2% in men and the age-standardized incidence rates by 27.4% in women and 6% in men. These increases are mostly based on 85+ age populations’ changes. Conclusions. In Romania, the hip fractures incidence continues to grow throughout an 11-year-period, especially in women, representing an increasing burden for our society.

Hypothyroidism is a common endocrine disease with characteristic symptoms and signs such as fatigue, weight gain, intolerance of cold, constipation, depression, mental slowdown and muscle cramps. Myopathic changes are observed in 30-80% of patients with hypothyroidism, but muscular hypertrophy with muscle stiffness has been reported in less than 10% of patients. Hoffmann’s syndrome is a specific form of the hypothyroid-associated myopathy, rarely seen. Symptoms of this syndrome include proximal muscle weakness, hypertrophies in extremities, stiffness, muscle cramps, spontaneous muscle pain; and are associated with increased muscle enzymes. These findings can be seen at any time during hypothyroidism. Hofmann’s syndrome has a very good prognosis. Its response to hormone replacement therapy is very good. Therefore, in patients with myopathylike symptoms, considering in the differential diagnosis that the myopathy may be a reflection of hypothyroidism will facilitate the diagnosis and treatment. In this case, we aimed to present together Hashimoto thyroiditis and muscular hypertrophy, which is an atypical presentation of hypothyroidism and rarely seen in the literature, namely Hoffmann’s syndrome.

Context. Amiodarone use has been associated with Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH) with only 12 cases reported from its first description in 1996. Objective. The clinical use of the antiarrhythmogenic drug amiodarone is frequently complicated by a very broad spectrum of side effects: cardiac toxicity, hypo- and hyper-thyroidism, pulmonary fibrosis and liver function abnormalities. We report the case of a patient with amiodarone-induced SIADH with the particularity of a very late onset of these adverse effects. Case. A 78 years old man on amiodarone therapy for a history of complex ventricular arrhythmia after a myocardial infarction, comes to the Emergency Department of our Hospital for pre-syncopal symptoms. Laboratory test showed a hypo-osmotic hyponatremia (sodium 110 mEq/L, serum osmolality 233 mOsm/kg) associated with liver enzymes increases. A not suppressed urinary osmolality with high urinary sodium excretion associated with normal thyroid and adrenal functions led to the diagnosis of SIADH. Known associated disorders (neoplasms, lung diseases and central nervous system disorders) were suspected and excluded. A pharmacologic aetiology was suspected and, in the absence of diuretics and neurological drugs, amiodarone seemed the most probable cause of the SIADH. Hypertonic saline solution and fluid restriction were initiated and amiodarone discontinued with a gradual normalization of plasma sodium levels and liver enzymes. Conclusion. The clinical case underlines the importance of monitoring amiodarone-related SIADH with frequent electrolytes biochemical assessment not only in relation to an early but also to a late clinical onset.

Context. Subacute thyroiditis (SAT) is an inflammatory disease of the thyroid gland and commonly affects females. Despite adequate treatment, the recurrence of SAT can be seen in some patients. Although there is insufficient data about the reasons for recurrences, HLA predisposition is one of the reasons thought to be responsible and is a current issue for clinicians. Objective. This case report presented the management of 7 SAT attacks of a patient who had HLA-B35:01 and B41:02 alleles in the genotype analysis. Case Report. A 37-year-old male patient who had consecutive 7 SAT attacks was presented in this report. Corticosteroid or non-steroidal anti-inflammatory drugs were initiated at each recurrence depending on the severity of clinical symptoms and laboratory findings. The genotype analysis showed the positivity for HLA-B35:01 and B41:02 alleles. The anti-thyroglobulin antibody was detected positive after the last attack. The patient was followed up as asymptomatic and euthyroid in the third month after the last attack. Results. The management of some SAT cases may be challenging for clinicians. Although recurrence can be seen despite adequate treatment, repetitive seven attacks are extraordinary in SAT. HLA genotyping showed cooccurrence of HLA-B35:01 and B41:02 alleles in our patient. The co-occurrence of these alleles has been described firstly in this case. Explaining high recurrence rates of SAT with these HLA alleles is difficult, though the present case may shed light on further studies.

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Background. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. Antibodies directed against programmed cell death receptor 1 (PD-1) interrupt the ability of the cancerous cell to depress the immune system. Methods and results. We report three patients who developed different endocrine abnormalities after treatment with nivolumab, a monoclonal antibody directed against PD-1. First, we report a 76-year-old male presenting with generalized fat loss after treatment with nivolumab which predominantly affected his face and trunk. Second, we described the development of thyroiditis that presented with thyrotoxicosis and the expression of thyroid-stimulating hormone receptor antibodies (TRAb). Finally, we observed the emergence of adrenal insufficiency due to hypophysitis in another case. Conclusion. Although immune checkpoint inhibitors are an effective anticancer treatment modality, adverse effects are evident that can affect the endocrine system. These adverse events may relate to different endocrine systems that include the thyroid and pituitary glands. Also, acquired generalized lipodystrophy should be suspected in patients developing unusual fat loss after treatment with ICIs.

Background. Glycogen synthase kinase.3β (GSK.3β) has an important role in several signaling pathway including Wnt signaling pathway. Recent evidence has shown that this pathway is involved in follicle development, ovulation and Corpus luteum formation. Aim. In this study we have investigated the effect of LiCl (as a GSK.3β inhibitor) on the ovulation and corpus luteum formation in rat. Materials and methods. Immature 23-day female rats were injected with PMSG (15 IU) to induce follicular development, followed 48h later by HCG (15IU) to induce ovulation. To inhibit GSK3β activity 250 mg/kg LiCl were administerted at the time of LiCl injection. The ovaries were removed at 1,4,8,12,24 h after LiCl treatment and prepared for histological studies. Results. Our results show that the number of preovulatory follicle in LiCl treatment rats was not increased compared with control group. The number of corpus luteum blood vessels were decreased in comparison with control group (p<0.05). Conclusions. These findings show that although LiCl does not inhibit ovulation, it disrupts blood vessel formation in the corpus luteum.

Background. Mosaic karyotype 45,X/46,XY related mixed gonadal dysgenesis. Aim. To report a case of mosaic karyotype and petroclival meningioma. Methods. Presentation of a clinical case with comments. Results. The case of a 37-year-old woman mosaic karyotype - 45,X/46,XY, infertility, virilisation, Turner syndrome-like phenotype, primary amenorrhea, the absence of labia majora and petroclival meningioma. Concentrations of dehydroepiandrosterone sulphate (DHEAS), testosterone, luteinizing hormone (LH) and follicular stimulating hormone (FSH) were increased indicating hypergonadotropic hypogonadism. Low and high dose dexamethasone suppression tests demonstrated incomplete suppression of DHEAS concentration without connection between pulses of LH/FSH and DHEAS. Response to adrenocorticotropic hormone (ACTH) was normal. The morning/evening concentration ratio of DHEAS was very low in comparison with cortisol, ACTH and testosterone. Head magnetic resonance imaging (MRI) demonstrated petroclival meningioma without any adrenal or ovary abnormality. Menstruation started after treatment with 2 mg of estradiol. At control visit 1.5 years later she had no complaints. MRI did not demonstrate any signs of tumour progression. Conclusions. The main lesson learned from this case is that in searching the DHEAS secreting tumours one can find unusual cases with sustained high DHEAS and lack of confirmations of polycystic ovary syndrome, adrenal or ovary tumours using available ultrasound, CT and MRI.

Context. Mealtime insulin bolus is traditionally administered before meals in children with type 1 diabetes (T1D). Controlled studies on the use of pre-and postprandial insulin bolus have shown variable results. There are no realworld studies on postprandial bolusing of insulin in young children with T1D. Methods. Children with T1D aged <7 years were grouped into preprandial (Group 1) or postprandial (Group 2) groups according to the practice of prandial insulin use. Their retrospective data on mean glycosylated hemoglobin (HbA1c), hypoglycemic events, and diabetic ketoacidosis (DKA) episodes were compared. Results. Forty-four children (mean age 4.1±1.3 years, range 2-7 years) with mean diabetes duration of 2.0±0.7 years (range, 1-4 years) were identified; 23 (52.3%) belonged to Group 1 and 21 (47.7%) to Group 2. There were no differences in the mean HbA1c levels, mean hypoglycemic events, and DKA episodes between the two groups during a mean follow-up duration of two years. Conclusion. Young children with T1D administered insulin bolus during or immediately after meals showed similar long-term glycemic control and diabetesrelated adverse event profile compared to the premeal timing of insulin bolus. Larger real-world studies are needed on flexible insulin bolus timing in young children with T1D.

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