Objective:To report the diagnosis, treatment, and follow-up of a 21-hydroxylase deficiency boy with central precocious puberty caused by complex heterozygous mutation of CYP21A2 gene.Methods:The child was symptomatic of rapid growth and secondary sexual characteristics at the age of 6. The diagnosis of central precocious puberty was confirmed by serum testosterone, gonadotropin levels, and gonadotropin-releasing hormone (GnRH) stimulation test. 21-hydroxylase deficiency was diagnosed clinically based on the serum adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone levels, and images on the computed comography (CT) of the adrenal glands.Results:The CYP21A2 gene was detected to have a compound heterozygous mutation by Sanger sequencing and multiplex ligation-dependent probe amplification. During the 3 years follow-up, the effects of glucocorticoids, GnRH analogs, and recombinant human growth hormone were regularly monitored and evaluated.Conclusions:Glucocorticoid replacement followed the principle of the lowest effective dose. GnRH analogs showed an effective inhibition of the hypothalamus-pituitary-gonadal axis, while recombinant human growth hormone had no such growth-promoting effect.

Three cases of Langerhans cell histiocytosis (LCH)with central diabetes insipidus as the first manifestation were reported, with the summary of their clinical manifestations, laboratory examinations, imaging examinations, pathological results, diagnosis process, and treatment response. All three patients presented with central diabetes insipidus in the early stage. The pituitary magnetic resonance imaging (MRI)showed thickened pituitary stalks, and all lost the normal high signal of the posterior pituitary. Two patients showed isolated hypothalamic-pituitary lesions, while one case showed pituitary and thyroid systems involvement. Pathological findings showed typical Langerhans cells, immunohistochemistry showed positive for S-100, CD1a, Langerin. The clinical manifestations of LCH manifested distinct heterogeneity, which is easy to be misdiagnosed and left out. The diagnosis should be confirmed by pathological examination. The biopsy of isolated hypothalamic-pituitary lesions is difficult. It is recommended to actively screen other organs to increase the probability of biopsy. LCH-induced neurohypophysis requires life-long hormone replacement therapy.

Objective:To investigate the correlation between the level of thyrotropin receptor antibody(TRAb) and bone turnover markers(BTMs) in the patients with newly-diagnosed Graves′ disease(GD).Methods:The clinical data of GD patients who were newly-diagnosed in the First Affiliated Hospital of Zhengzhou University from October 2016 to June 2021 were collected, including free triiodothyronine(FT 3), free thyroxine(FT 4), thyroid stimulating hormone, thyroid related antibodies, N-terminal procollagen of type I collagen(PINP), N-terminal osteocalcin(N-MID), β-cross-linked C-telopeptide of type I(β-CTX), blood lipid and renal function, etc. Results:There were 618 GD patients with an average age of(43.7±13.2) years(male∶female=1∶1.99). The PINP and β-CTX level in male GD patients were significantly higher than those in female(all P<0.05). Spearman correlation analysis showed that PINP, N-MID and β-CTX were positively correlated with FT 3, FT 4, TRAb, serum calcium and serum phosphorus; and negatively correlated with body mass index and low density lipoprotein cholesterol(all P<0.05). Linear regression analysis showed that TRAb was positively correlated with lg-PINP, lg-N-MID and sqrt-β-CTX in the univariate model of total GD patients( β were 0.006, 0.005, and 0.006, respectively; all P<0.001); positive correlation remained after adjusting for thyroid function(all β=0.004, all P<0.001); and for multiple confounding factors(model 3 and 4, all P<0.05). Results of univariate and adjusted thyroid function models with GD in different genders were consistent with the total patients(all P<0.05). Conclusion:TRAb is a risk factor for accelerated bone turnover in GD patients which is independent of thyroid function.

Objective:To compare the spermatogenes response of human chorionic gonadotropin(HCG)combined with human menopausal gonadotropin(HMG)in patients with idiopathic hypogonadotropic hypogonadism(IHH)and congenital combined pituitary hormone deficiency(CCPHD), and to explore related factors.Methods:Clinical data of 90 IHH patients and 61 CCPHD patients from January, 2014 to November, 2018 were retrospectively analyzed. Spermatogenesis was compared between the two groups receiving combined gonadotropin therapy. The patients were then divided into two subgroups: spermatogenesis subgroup and nonspermatogenesis subgroup. Related factors of spermatogenesis after the combined gonadotropin therapy were investigated.Results:After the combined treatment of HCG/HMG for 3, 6, and 9 months, the patients with CCPHD revealed lower testicular sizes than those with IHH( P=0.004, 0.021 and 0.032, respectively). Compared with IHH patients, CCPHD patients had larger testicular volume increments( P<0.001), higher spermatogenesis rates( P=0.048), and shorter initial time for sperm appearance( P<0.001)after 24-month treatment. Multivariate logistic regression analysis showed that lower total cholesterol(TC)(IHH group: OR=5.508, 95% CI 1.110-27.326, P=0.037; CCPHD group: OR=4.068, 95% CI 1.077-15.371, P=0.039)was an independent risk factor of poorer spermatogenesis in patients with IHH and CCPHD. Conclusions:The patients with CCPHD demonstrate a better response to combined gonadotropin treatment than those with IHH. Lower TC is an independent risk factor for poor spermatogenesis of combined HCG/HMG therapy in patients with IHH or CCPHD.