Short stature is one of the most common causes for referrals to pediatric endocrinologists. However, in a majority of the children, no underlying cause can be identified and the child instead receives the unhelpful diagnosis of idiopathic short stature (ISS), often after extensive work-up and testing. Recent advances in genetic methodology have allowed for the identification of a number of different monogenic conditions within the large cohort of ISS children. Isolated short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (MIM#165800) due to heterozygous aggrecan gene mutations exemplifies how this progress is changing the way we assess, counsel and treat children with non-endocrine growth disorders.
You are looking at 1 - 10 of 20,001 items for
Mischa de Ridder, Els Nieveen van Dijkum, Anton Engelsman, Ellen Kapiteijn, Heinz-Josef Klümpen and Coen R N Rasch
To perform a nationwide population based study in ATC on incidence, treatment and survival.
Retrospective cohort study.
All patients with primary ATC between 1989 and 2016 were identified in the Netherlands Cancer Registry (NCR). Of all these patients excerpts from the pathology reports from PALGA: Dutch Pathology registry were linked to the data of the NCR. Standardized incidences were calculated, survival was estimated using Kaplan–Meier method and univariable statistically significant factors were included in a multivariable regression model.
In total, 812 patients were included. Mean standardized incidence rates were 0.18/100 000 (range 0.11–0.27/100 000) with a significant trend over the years with an estimated annual percentage change of 1.3% per year (95% CI 0.4–2.1%). Median overall survival was 2.2 months, and estimated 1-year survival was 12%. Patients without distant metastases at diagnosis had an estimated 1-year survival of 21.6%. Prognostic factors for prolonged survival were double or triple therapy, age below 65 years, M0-status and absence of bilateral lymph node metastases.
ATC is rare, but often lethal, form of thyroid cancer, with a median survival of 2 months and 1-year survival of approximately 10%. The incidence is slightly rising in the Netherlands over the past 3 decades. There appears to be a subgroup of patients that survive longer, mainly those with relatively limited disease who underwent double or triple therapy. Further research is needed to define these patients more distinctively.
Saskia le Cessie, Jelle J Goeman and Olaf M Dekkers
Rougin Khalil, Leen Antonio, Michaël R Laurent, Karel David, Na Ri Kim, Pieter Evenepoel, Anton Eisenhauer, Alexander Heuser, Etienne Cavalier, Sundeep Khosla, Frank Claessens, Dirk Vanderschueren and Brigitte Decallonne
Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover.
Prospective cohort study.
Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied.
Of 26 screened patients, 17 were included. The median age was 44 (range 20–75) years. The median time interval between baseline and first follow-up was 13 (6–27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4–12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01–0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7–35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered.
In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.
Lucie Allard, Frédérique Albarel, Jérôme Bertherat, Philippe Jean Caron, Christine Cortet, Carine Courtillot, Brigitte Delemer, Christel Jublanc, Dominique Maiter, Marie Laure Nunes, Gerald Raverot, Julie Sarfati, Sylvie Salenave, Emmanuelle Corruble, Walid Choucha and Philippe Chanson
In patients treated with antipsychotics, the rare occurrence of a macroprolactinoma represents a therapeutic challenge.
Our aim was to evaluate the efficacy and psychiatric safety of dopamine agonists (DAs) prescribed for large macroprolactinomas in patients with psychosis treated with antipsychotics.
This was a multicenter (France and Belgium) retrospective study.
Eighteen patients treated with antipsychotics were included.
Under DA, median PRL levels decreased from 1247 (117–81 132) to 42 (4–573) ng/mL (P = 0.008), from 3850 (449–38 000) to 141 (60–6000) ng/mL (P = 0.037) and from 1664 (94–9400) to 1215 (48–5640) ng/mL (P = 0.56) when given alone (n = 8), before surgery (n = 7), or after surgery (n = 6), respectively. The prolactinoma median largest diameter decreased by 28% (0–57) in patients under DAs alone (P = 0.02) but did not change when given after surgery. Optic chiasm decompression was achieved in 82% of patients. Five patients (28%) were admitted for psychotic relapse while receiving DAs (but three of them had stopped antipsychotic treatment at that time). A more severe underlying psychosis, rather than the DA treatment itself, may explain such psychiatric admissions.
Even if the DA efficacy on PRL levels and tumor volume in patients with macroprolactinoma under antipsychotic drugs is less impressive than that typically observed, it may be considered satisfactory for half of our patients, particularly in cases of optic chiasm compression. Psychotic exacerbation was unusual in these patients, occurring mostly in those with the most severe psychotic forms. DAs may therefore be used as antitumor treatment for macroprolactinoma in patients with visual involvement, severe headaches or invasion into the skull base who receive antipsychotics.
Shakila Thangaratinam, Shamil D Cooray, Nithya Sukumar, Mohammed S B Huda, Roland Devlieger, Katrien Benhalima, Fionnuala McAuliffe, Ponnusamy Saravanan and Helena J Teede
The COVID-19 pandemic has required rapid transformation and adaptation of healthcare services. Women with gestational diabetes mellitus (GDM) are one of the largest high-risk groups accessing antenatal care. In reformulating the care offered to those with GDM, there is a need to balance the sometimes competing requirement of lowering the risk of direct viral transmission against the potential adverse impact of service changes. We suggest pragmatic options for screening of GDM in a pandemic setting based on blood tests, and risk calculators applied to underlying risk factors. Alternative models for antenatal care provision for women with GDM, including targeting high-risk groups, early lifestyle interventions and remote monitoring are provided. Testing options and their timing for postpartum screening in women who had GDM are also considered. Our suggestions are only applicable in a pandemic scenario, and usual guidelines and care pathways should be re-implemented as soon as possible and appropriate.
Neil J Gittoes, Sherwin Criseno, Natasha M Appelman-Dijkstra, Jens Bollerslev, Ernesto Canalis, Lars Rejnmark and Zaki Hassan-Smith
Endocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the management of commonly encountered calcium metabolic problems and osteoporosis. Non-urgent elective appointments should be postponed, and remote consultations and digital health solutions promoted. Patients should be empowered to self-manage their conditions safely. Patients, their caregivers and healthcare providers should be directed to assured national or international online resources and specific patient groups. For patients in acute hospital settings, existing emergency guidance on the management of hyper- and hypo-calcaemia should be followed. An approach to osteoporosis management is outlined. IV zoledronic acid infusions can be delayed for 6–9 months during the pandemic. Patients established on denosumab, teriparatide and abaloparatide should continue planned therapy. In the event of supply issues with teriparatide or abaloparatide, pausing this treatment in the short term is likely to be relatively harmless, whereas delaying denosumab may cause an immediate increased risk of fracture. The challenge of this pandemic will act as a catalyst to innovate within our management of metabolic bone and mineral disorders to ensure best use of resources and resilience of healthcare systems in its aftermath.
Stefan M Constantinescu, Natacha Driessens, Aurélie Lefebvre, Raluca M Furnica, Bernard Corvilain and Dominique Maiter
Intravenous etomidate infusion is effective to rapidly lower cortisol levels in severe Cushing’s syndrome (CS) in the intensive care unit (ICU). Recently, etomidate treatment has also been proposed at lower doses in non-ICU wards, but it is not yet clear how this approach compares to ICU treatment.
We compared data from patients with severe CS treated with high starting doses of etomidate (median: 0.30 mg/kg BW/day) in ICU or with lower starting doses (median: 0.025 mg/kg BW/day) in non-ICU medical wards.
Fourteen patients were included, among which ten were treated with low starting doses (LD) and four with high starting doses etomidate (HD). All patients had severe and complicated CS related to adrenal carcinoma (n = 8) or ectopic ACTH secretion (n = 6). Etomidate was effective in reducing cortisol levels below 500 nmol/L in a median of 1 day in the HD group compared to 3 days in the LD group (P = 0.013). However, all patients of the HD group had etomidate-induced cortisol insufficiency and needed frequent monitoring, while no patient from the LD group required hydrocortisone supplementation. No patient in either group died from complications of CS or etomidate treatment, but final outcome was poor as six patients in the LD group and all four patients in the HD group died from their cancer during follow-up.
Our study suggests that, for patients with severe CS who do not require intensive organ-supporting therapy, the use of very low doses of etomidate in medical wards should be considered.
Daniel G Bichet
For an endocrinologist, nephrogenic diabetes insipidus (NDI) is an end-organ disease, that is the antidiuretic hormone, arginine-vasopressin (AVP) is normally produced but not recognized by the kidney with an inability to concentrate urine despite elevated plasma concentrations of AVP. Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. For a geneticist, hereditary NDI is a rare disease with a prevalence of five per million males secondary to loss of function of the vasopressin V2 receptor, an X-linked gene, or loss of function of the water channel AQP2. These are small genes, easily sequenced, with a number of both recurrent and private mutations described as disease causing. Other inherited disorders with mild, moderate or severe inability to concentrate urine include Bartter’s syndrome and cystinosis. MAGED2 mutations are responsible for a transient form of Bartter’s syndrome with severe polyhydramnios. The purpose of this review is to describe classical phenotype findings that will help physicians to identify early, before dehydration episodes with hypernatremia, patients with familial NDI. A number of patients are still diagnosed late with repeated dehydration episodes and large dilations of the urinary tract leading to a flow obstructive nephropathy with progressive deterioration of glomerular function. Families with ancestral X-linked AVPR2 mutations could be reconstructed and all female heterozygote patients identified with subsequent perinatal genetic testing to recognize affected males within 2 weeks of birth. Prevention of dehydration episodes is of critical importance in early life and beyond and decreasing solute intake will diminish total urine output.
Mariacarolina Salerno, Nicola Improda and Donatella Capalbo
Subclinical hypothyroidism (SH) is biochemically defined as serum TSH levels above the upper limit of the reference range in the presence of normal free T4 (FT4) concentrations. While there is a general agreement to treat subjects with serum TSH levels above 10 mU/L, the management of mild form (TSH concentrations between 4.5 and 10 mU/L) is still a matter of debate. In children, mild SH is often a benign and remitting condition and the risk of progression to overt thyroid dysfunction depends on the underlying condition, being higher in the autoimmune forms. The major concern is to establish whether SH in children should always be considered an expression of mild thyroid dysfunction and may deserve treatment. Current data indicate that children with mild SH have normal linear growth, bone health and intellectual outcome. However, slight metabolic abnormalities and subtle deficits in specific cognitive domains have been reported in children with modest elevation of TSH concentration. Although these findings are not sufficient to recommend levothyroxine treatment for all children with mild SH, they indicate the need for regular monitoring to ensure early identification of children who may benefit from treatment. In the meanwhile, the decision to initiate therapy in children with mild SH should be based on individual factors.