Endocrine Abstracts

Introduction: The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors, such as PROP1, POUF1, HESX1/RPX, LHX3, LHX4, PITX2, T-PIT, SOX2 and SOX 3. Gene mutations of these pituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamic–pituitary region.Mate...

Introduction: Despite extensive research into IQ scores in congenital hypothyroidism (CH) during childhood there is little information on adult outcome in terms of pragmatic measures such as educational achievement, employment, residency and relationships.Patients and methods: We present the results of a questionnaire-based study examining these outcome measures in Scottish adults with permanent CH born between 1979 and 1991. The unaffected siblings of o...

Context: Kallmann syndrome (KS) is a developmental disease associating congenital hypogonadotropic hypogonadism (CHH) and sense of smell impairment owing to olfactory structures (OS) aplasia/hypoplasia. Although rhinencephalic MRI allows to detect specific KS OS abnormalities useful to discriminate KS from normosmic CHH (nCHH), this technique is not efficient enough to study anterior skull bone structures.Objectives: To search for specific anterior skull...

Introduction: TAC3/TACR3 mutations have been reported in normosmic congenital hypogonadotropic hypogonadism (nCHH). In the absence of animal models, studies of human neuroendocrine phenotypes associated with neurokinin B and NK3R receptor dysfunction can help to decipher the pathophysiology of this signaling pathway. Our objective was to characterize novel TACR3 mutations and to analyze neuroendocrine profiles in nCHH patients with TAC3/TACR3 biallelic mut...

A 20 yr old woman was referred for primary amenorrhea. At examination BMI was 19 and displayed a pubertal development at S4P4. Hormonal evaluation showed normal prolactin, low estradiol (18 pg/ml) and gonadotropins (LH=1.5IU; FSH=1.9 IU/L). Testosterone was normal (0.25 ng/ml) but curiously plasma progesterone (P) was increased (from 3.9 to 5 ng/ml). Initial ovarian sonography and adrenal CT scan didn’t show any abnormal mass. ACTH stimulation tests showed normal response...

Mitotane (o,p’DDD) represents the most effective treatment of adrenocortical carcinoma (ACC). However, molecular mechanisms of mitotane action remain poorly understood. Mitochondrial (mt) impact of mitotane has previously been suggested but not yet fully validated. We investigated functional consequences of mitotane exposure on mitochondrial steroidogenesis, respiratory chain activity and biogenesis, using human adrenocortical secreting H295R and non-secreting SW13 cells....

Context: The effects of cabergoline on cardiac valves have been extensively studied in Parkinson’s disease and hyperprolactinemia but not in acromegaly, a condition at risk of cardiac valve abnormalities.Objective: We examined the prevalence of heart valve disease and regurgitation in a series of patients with acromegaly treated with cabergoline, by comparison with matched patients who had never received this drug.Design and s...

PTTG transforms cells in vitro, is tumourigenic in vivo and regulates secretion of fibroblast growth factor-2 (FGF-2). Critical to transactivation of FGF-2 is PTTG's SH3 interacting domain which encodes the gene's sole phosphorylation site. We explored the mechanisms through which PTTG stimulates FGF-2 expression and cell transformation using specific mutations resulting in unphosphorylated PTTG (phos-), a mimic of constitutive phosphorylation (phos+), and a disr...

Hyperprolactinemia is the most common cause of hypogonadotropic anovulation in women. It is related to an alteration of pulsatile GnRH secretion. This gonadotropic deficiency has been proposed to result from direct suppression of prolactin (PRL) on GnRH release but its mechanism remains unknown. Because GnRH neurons do not express unequivocally the PRL receptor, and are stimulated by kisspeptin (Kp) neurons which do express PRL receptors, we hypothesized that GnRH deficiency i...

Malignant pheochromocytoma and paraganglioma (PPGLs) are rare diseases with a heterogeneous behaviour. 131I-MIBG therapy and the cyclophosphamide-dacarbazine-vincristine chemotherapy regimen (CVD) constitute the most popular options in the metastatic setting. We have investigated the antitumor effect of temozolomide (TMZ), in patients with metastatic PPGLs. Efficacy was primary endpoint, safety and identification for prognosis factors of response were secondary endpoints.<...