ABSTRACT
Objective:To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1(MEN1) through analyzing the clinical diagnosis and treatment process, as well as outcomes in one case of this disorder.Methods:The clinical manifestations, biochemical and hormone levels, imaging presentations, medical and surgical treatments, and post-operational pathologic findings in the process of diagnosis and treatment of a patient with thyrotropin-secreting adenoma in MEN1 were analyzed. The next generation sequencing followed by Sanger method was used for analyzing MEN1 and related genes. The results were evaluated with online PolyPhen2 and PROVEAN for variation hazard.Results:One 19-year old male patient was diagnosed with hyperthyroidism due to thyrotoxicosis and high level of thyroid hormones(THs) with measurable TSH(2.78 mIU/L) and negative thyrotropin receptor antibody(TRAb). Meanwhile, primary hyperparathyroidism was suggested by hypercalcemia, hypophosphatemia, and elevated intact parathyroid hormone(PTH) level, all the parameters were returned to normal after surgical resection of the mass which was below the left thyroid lobe indicated by ultrasound and 99mTc scan. Thyrotoxicosis remained in spite of one year treatment with antithyroid drug, thyrotropinoma was then suspected, and subsequent MRI scan found a macroadenoma at right pituitary. TSH and THs returned to normal 1 month after transsphenoidal removal of the adenoma. As expected, immunohistochemical staining revealed TSH positive. In addition, a pancreatic mass was found by both CT and MRI scan, which was considered as a silent neuroendocrine tumor. Gene analysis revealed a missense mutation of MEN1 as c. 415C>T and p. His139Tyr(H139Y), which was predicted highly hazard. Only five cases of thyrotropinoma in MEN1 were previously reported. Conclusion:Thyrotropinoma should be cautiously identified from hyperthyroidism to avoid misdiagnosis and mistreatment, and it should keep in mind that thyrotropinoma may be associated with MEN1 though it would be very rare.
ABSTRACT
Objective@#To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1(MEN1) through analyzing the clinical diagnosis and treatment process, as well as outcomes in one case of this disorder.@*Methods@#The clinical manifestations, biochemical and hormone levels, imaging presentations, medical and surgical treatments, and post-operational pathologic findings in the process of diagnosis and treatment of a patient with thyrotropin-secreting adenoma in MEN1 were analyzed. The next generation sequencing followed by Sanger method was used for analyzing MEN1 and related genes. The results were evaluated with online PolyPhen2 and PROVEAN for variation hazard.@*Results@#One 19-year old male patient was diagnosed with hyperthyroidism due to thyrotoxicosis and high level of thyroid hormones(THs) with measurable TSH(2.78 mIU/L) and negative thyrotropin receptor antibody(TRAb). Meanwhile, primary hyperparathyroidism was suggested by hypercalcemia, hypophosphatemia, and elevated intact parathyroid hormone(PTH) level, all the parameters were returned to normal after surgical resection of the mass which was below the left thyroid lobe indicated by ultrasound and 99mTc scan. Thyrotoxicosis remained in spite of one year treatment with antithyroid drug, thyrotropinoma was then suspected, and subsequent MRI scan found a macroadenoma at right pituitary. TSH and THs returned to normal 1 month after transsphenoidal removal of the adenoma. As expected, immunohistochemical staining revealed TSH positive. In addition, a pancreatic mass was found by both CT and MRI scan, which was considered as a silent neuroendocrine tumor. Gene analysis revealed a missense mutation of MEN1 as c. 415C>T and p. His139Tyr(H139Y), which was predicted highly hazard. Only five cases of thyrotropinoma in MEN1 were previously reported.@*Conclusion@#Thyrotropinoma should be cautiously identified from hyperthyroidism to avoid misdiagnosis and mistreatment, and it should keep in mind that thyrotropinoma may be associated with MEN1 though it would be very rare.
ABSTRACT
OBJECTIVE@#To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations.@*METHODS@#Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production.@*RESULTS@#Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous.@*CONCLUSION@#The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
Subject(s)
Humans , Male , Adrenal Insufficiency , DAX-1 Orphan Nuclear Receptor , Genetics , Hypoadrenocorticism, Familial , Genetics , Mutation , Mutation, Missense , Pedigree , Repressor ProteinsABSTRACT
[Summary] Sixty-one patients suffering from pituitary apoplexy( PA) were mainly diagnosed according to pathologic findings, and were collected from case record, pathology, and MRI databases. They were classified into 4 types according to the clinical condition: the insidious type was characterized with only positive pathological findings;the asymptomatic type had both positive pathologic and MRI findings; the subacute type had PA associated symptoms longer than 2 weeks; and the acute type had PA associated symptoms for 2 weeks or less. The latter 2 types had positive pathological and MRI findings additionally. The basic lesions, acute or chronic symptoms, endocrinopathies and MRI findings were compared among 4 types. Results showed as followed. In all patients, there were headache(60. 7% ), blurred vision(55. 7% ), vomiting(21. 3% ), and dizziness(14. 8% ). Apoplexy associated symptoms comprised severe headache (24. 6% ), rapid vision loss (29. 5% ), and blepharopotosis or diplopia (9. 83% ). Insidious, asymptomatic, subacute, and acute types were composed of 15 (24. 6% ), 9 (14. 8% ), 19 (31. 1% ), and 18 (29. 5% ) cases, respectively. Aging and intracranial space-occupying symptoms as first complaint showed increasing trend from mild to severe types(both P<0. 05), while in chronic course it showed decreasing trend(P<0. 05). Acute massive symptoms(P<0. 01), and non-functional tumor(P<0. 01) in the 2 clinical types were much more frequent than in the two mild types. Half or more pituitary-target glands showed impaired functions in each type, and the impairment showed increasing trend through mild to severe types(P<0. 01). The present study provided a brief typing system in order to expand PA concept to a wider span covering various conditions. Some differences in tumor composition and endocrinopathies existed among the four types.
ABSTRACT
Normal function of growth hormone-insulin-like growth factor Ⅰaxis is essential for linear growth after birth. A case of continuous growth with undetectable growth hormone level even under insulinhypoglycemia stimulation was reported. The growth hormone deficiency was due to pituitary stalk interruption combined with deficiency of multiple pituitary hormones. Taken together with reviewed literature, this so-called nongrowth hormone-dependent linear growth was preconditioned by other hormones, especially gonadotropin deficiency,and the unclosed epiphysis.