Novel compound heterozygous variants in the LHX3 gene caused combined pituitary hormone deficiency: A case report

BACKGROUND Combined pituitary hormone deficiency 3(CPHD3;OMIM:221750)is caused by mutations within the LHX3 gene(OMIM:600577),which located on the subtelomeric region of chromosome 9 at band 9q34.3,has seven coding exons and six introns.LIM homeobox(LHX)3 protein is the key regulator of pituitary development in fetal life.CASE SUMMARY We have diagnosed and treate an 11-year-old boy with combined pituitary hormone deficiency(CPHD).The main clinical manifestations were pituitary hormone deficiency,hydrocele of the tunica vaginalis,pituitary dwarfism,gonadal dysplasia,micropenis,clonic convulsion,and mild facial dysmorphic features.We collected peripheral blood from the patient,the patient's older brother,as well as their parents,and sequenced them by using high-throughput whole-exosome sequencing,which was verified by Sanger sequencing.The results showed that there were two compound heterozygous variants of c.613G>C(p.V205L)and c.220T>C(p.C74R)in the LHX3 gene.c.613G>C(p.V205L)was inherited from his mother and c.220T>C(p.C74R)from his father.His brother also has both variants and symptoms.CONCLUSION This study reported ununreported genetic mutations of LHX3,and recorded the treatment process of the patients,providing data for the diagnosis and treatment of CPHD.

Clinical and Biochemical Characteristics of Growth Hormone-Secreting Pituitary Tumors

To investigate the difference of biochemical characteristics on gsp positive and gsp negative growth hormone (GH) secreting pituitary tumors, 18 GH secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp positive and gsp negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp positive patients were higher than those in gsp negative patients ( P <0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp positive and gsp negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp positive with gsp negative GH secreting pituitary tumors.

Pituitary Suppression before Frozen Embryo Transfer Is Beneficial for Patients Suffering from Idiopathic Repeated Implantation Failure

Long-term gonadotropin-releasing hormone agonist（Gn RHa） administration before in vitro fertilization（IVF）/intracytoplasmic sperm injection（ICSI） in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term Gn RHa treatment might also be beneficial for the idiopathic repeated implantation failure（RIF） patients. In the 21 patients receiving Gn RHa and hormone replacement therapy（G-HRT） protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone（previous protocols）. Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior Gn RHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients.

Postoperative pituitary hormonal disturbances and hormone replacement therapy time and dosage in children with craniopharyngiomas

Background The proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas （CP） often make radical resection difficult. Therefore, complete resection of CP often results in permanent multiple pituitary hormone deficiency （MPHD）. This study aimed to elucidate the postoperative pituitary hormonal disturbances, and hormone replacement therapy （HRT） time and dosage in children with CP. Methods Twenty patients with growth retardation and CP after resection, comprising 14 boys and 6 girls, with a mean age of （10.63±3.18） years （Group A） and 10 male patients of group A aged 〉10 years （Group B） were entolled. Thirty age-, sex- and Tanner stage-matched normal children （control Group A）, and 44 male older children 〉10 years （control Group B） served as controls. The serum concentrations of insulin-like growth factor-1 （IGF-1）, growth hormone （GH）, free thyroxine （FT4）, thyroid-stimulating hormone （TSH）, adrenocorticortropic hormone （ACTH）, cortisol （COR）, follicle stimulating hormone （FSH）, luteinizing hormone （LH）, prolactin （PRL）, testosterone （T） and estradiol （E2） were measured in the CP patients after resection and in controls. The appropriate time and dosage of HRT were investigated. Linear correlation analysis was made between levothyroxine （L-T4） dosage and primary FT4 in CP patients after resection. Results All cases had MPHD. The serum peak GH, IGF-1, FT4 and COR levels of Group A were significantly lower than that of the control Group A. The serum IGF-1 concentration increased to the normal level after 3 months of rhGH therapy; the serum FSH, LH, and T levels were significantly decreased （P 〈0.001）; however, E2 and PRL were significantly increased （P 〈0.001） in Group B compared with the control Group B; 18 cases were found to have central diabetes insipidus （DI） by water deprivation test and MRI. There was a significant negative linear regression （r=-0.8, P 〈0.001） between L-T4 and primary FT4 in Group A patients with CP after resection, giving a regression equation of L-T4 dosage （μg·kg^-1·d^-1） = 3.5-0.2×FT4 （μg·kg^-1·d^-1）. The time and corresponding dosage of HRT for CP after resection were： rhGH started 1 year after resection and no recurrence of CP on MRI, when IGF-1 reached the normal range, the rhGH dosage was （0.13±0.04） U·kg-1·d-1; hydrocortisone （H-C） was started as soon as possible, and was kept in the lower normal range, at a dosage of （12.6±4.8） mg/m^2; levothyroxine started after H-C or at the same time to maintain FT4 in the higher normal range, at a dosage of （1.65±0.70） μg·kg^-1·d^-1; Minirin （DDAVP） was started as soon as possible, elicited no symptoms, and maintained normal electrolyte levels; the dosage was （0.16±0.04） mg/m^2. Conclusion Patients with CP after resection often displayed MPHD, and needed total HRT at appropriate time and dosage to improve the quality of life and normal growth.

Efficacy of the long-acting octreotide formulation in patients with thyroid-stimulating hormone-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure

Background Little information about the current management of patients with thyroid-stimulating hormone （TSH）-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. Methods Fifteen patients with TSH-secreting pituitary adenomas （8 men and 7 women）, who previously underwent incomplete surgical resection and/or adjuvant radiotherapy （n=12） and failure of octreotide treatment （n=15）, followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables. Results After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine （FT4） （（16.02±1.72） pmol/L） and free triiodothyronine （FT3） （（2.87±0.43） pmol/L） levels of 15 patients significantly decreased compared with those after octreotide-treatment （FT4, （35.36±7.42） pmol/L, P 〈0.001; FT3, （17.85±7.22） pmol/L, P 〈0.001）. Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment （（0.72±0.21） mUlL） and were significantly lower than the pretreatment value （（5.27±1.04） mUlL, P 〈0.001）, post-surgery value （（3.37±0.31） mU/L, P 〈0.001） and post-octreotide-treatment value （（4.52±0.41） mU/L, P 〈0.001）. In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis. Conclusion The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.