Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association最新文献

The issue of a possible association between Shwachman-Diamond Syndrome and diabetes has been debated for many years. This review updates the Italian Shwachman-Diamond registry, confirming our previous findings that suggest that these patients might be at higher risk of developing diabetes, particularly type 1. These data are of relevance in the clinical follow-up of patients in everyday life, emphasizing the need for early diagnosis and timely intervention.

Patients with a hepatic type of glycogen storage diseases (GSDs) can manifest endocrine features such as hypoglycemia, dyslipidemia, or osteoporosis. This study aimed to investigate the long-term endocrine consequences in patients with hepatic GSDs.This study included 64 patients from 52 families with hepatic GSDs including GSD type Ia (41 patients from 37 families), Ib (3 unrelated), III (8 from 6 families), IV (1 patient), and IX (11 from 5 families). All patients were genetically confirmed. Clinical and endocrine findings were retrospectively analyzed.The median age at diagnosis and current age were 2.4 years (range, 0.1-42.4 years) and 17.6 years (range, 1.0-47.8 years), respectively. The mean height SDS at diagnosis was -3.5±1.4, and short stature was observed in 35.6% of patients. Patients diagnosed after the age of 3.4 years exhibited a high risk of short stature (OR=36.1; P-value<0.001). Among 33 patients who reached the final height, 23 (69.7%) showed delayed puberty. Hypertriglyceridemia was observed in 46 patients (71.9%), whereas 25 patients (39%) had elevated low-density lipoprotein cholesterol levels during the follow-up period. Among 24 patients who underwent dual-energy X-ray absorptiometry, 22 showed a low bone mineral density Z-score of -3.0±1.3 at the L-spine.This study described the long-term endocrine consequences in patients with hepatic GSDs. Pediatric endocrinologists should be aware of the presenting features and long-term endocrine sequelae of GSDs to provide proper management and decrease its morbidities.

Introduction: The diagnosis of adrenal insufficiency (AI) related to traumatic brain injury (TBI) remains a challenge. We investigated the basal and low-dose adrenocorticotropic hormone (ACTH)-stimulated serum cortisol and salivary cortisol (SaC) levels and the diagnostic utility of SaC levels during 28 days following TBI.

Materials and methods: Blood samples were collected for basal levels [sequentially from day 1 (D1) to D7 and on D28)] and for peak serum cortisol and SaC responses to the low-dose ACTH stimulation test (on D1, D7, and D28). After the patient enrollment period was completed, patients were retrospectively categorized as AI or AS (adrenal sufficiency) for each day separately, based on a basal serum cortisol cut-off level of 11 µg/dL, and data analysis was performed between the groups.

Results: Thirty-seven patients and 40 healthy controls were included. Median basal serum cortisol levels were higher in patients on D1 but were similar on other days. Median basal SaC levels were higher in patients on D1 and D2 but were similar on other days. Median peak serum cortisol and SaC levels were similar on D1 but were lower in patients on D7 and D28. Median basal SaC levels were higher in the AS group than in the AI group on all days.

Discussion and conclusions: When evaluating AI during the course of TBI, the cut-off for basal SaC levels is 0.5-0.6 µg/dL throughout the first week, except for 1.38 µg/dL on D2. SaC levels may serve as a surrogate marker for accurately reflecting circulating glucocorticoid activity.

Aim: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity.

Methods: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before.

Results: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population.

Conclusions: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.

Maturity-onset diabetes of the young (MODY) is the most common monogenetic form of diabetes with an autosomal dominant inheritance pattern. MODY is caused by mutations in genes important for the development and function of pancreatic beta cells, resulting in impaired insulin secretion capacity. To date, 14 different types have been described. While glucokinase (GCK)-MODY (formerly MODY-2) generally requires no drug therapy, other forms of MODY, such as hepatocyte nuclear factor-1-alpha (HNF1A)-MODY (formerly MODY-3) and HNF4A (formerly MODY-1), usually respond very well to sulfonylurea therapy. However, these MODY forms are characterised by a progressive course, meaning that insulin therapy is often required as the disease progresses. Both sulfonylurea therapy and insulin therapy are associated with an increased risk of hypoglycaemia and frequent weight gain. Newer blood glucose-lowering therapies, such as SGLT2 inhibitors (SGLT2i), DPP-4 inhibitors (DPP4i) and GLP-1 receptor agonists (GLP-1RA), have a much lower risk of hypoglycaemia and usually have a favourable effect on body weight. This review aims to provide an overview of the treatment of MODY patients with SGLT2i, DPP4i and GLP-1RA on the basis of previously published clinical studies, case series and case reports.

Introduction: This study aimed to examine the correlation between the growth response in prepubertal children with idiopathic growth hormone (GH) deficiency after 1 year of treatment with GH to the initial clinical and biochemical parameters. Additionally, the secretion dynamics of GH was also studied by analyzing the GH stimulation test profiles in relation to the GH treatment response.

Methods: This retrospective study included 84 prepubertal children (47 males and 37 females) with a definitive diagnosis of GH deficiency. The GH secretory indexes GH_max, GH secretion rate, and GH secretion volume were analyzed in relation to the response to recombinant human growth hormone (rhGH) treatment as defined by the index of responsiveness (IoR). Correlation and regression models were used to identify the best clinical and biochemical predictors to rhGH treatment. ResultsIoR was negatively correlated with the age (r=-0.607, p<0.01) and positively with the distance of child's height from its midparental height (MPH) r=0.466 (p<0.01) and pretreatment growth velocity (r=0.247, p<0.05). GH secretory indexes were correlated, and the highest association was observed between GH_max and GH secretion volume (r=0.883, p<0.01). Among the GH secretory indexes, GH_max was the best predictor of IoR (β coef. = -0.514, p<0.001) followed by the GH secretion volume (β coef. = -0.47, p<0.001) and GH secretion rate (β coef. = -0.367 p<0.001).

Conclusions: The age and the distance of child's height from its MPH are major predictors of GH treatment response in children with idiopathic GH deficiency. The calculation of the other GH secretory indexes GHSR and GHSV are not better predictors of response to GH than GH_max. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment.

Endogenous Cushing's syndrome (CS) is a rare disease characterized by a glucocorticoid excess. If inadequately treated, hypercortisolism can lead to increased morbidity and mortality. Surgical removal of the underlying tumor is the first-line treatment but is sometimes not feasible or even contraindicated. Additionally, in cases with severe CS, rapid control of hypercortisolism may be required. In these scenarios, steroidogenesis inhibitors represent a therapeutic alternative to surgery. Over the last years, the knowledge of the broad therapeutic effects of steroidogenesis inhibitors per se and the number of available drugs have increased. However, large comparative studies are still lacking. Accordingly, the decision on which drug to be used in a certain patient or clinical setting may be difficult. This review aims to summarize the main characteristics of steroidogenesis inhibitors.

The genetic landscape of corticotroph tumours of the pituitary gland has dramatically changed over the last 10 years. Somatic changes in the USP8 gene account for the most common genetic defect in corticotrophinomas, especially in females, while variants in TP53 or ATRX are associated with a subset of aggressive tumours. Germline defects have also been identified in patients with Cushing's disease: some are well-established (MEN1, CDKN1B, DICER1), while others are rare and could represent coincidences. In this review, we summarise the current knowledge on the genetic drivers of corticotroph tumorigenesis, their molecular consequences, and their impact on the clinical presentation and prognosis.