A novel germline mutation, IVS4+1G>A, of the POU1F1 gene underlying combined pituitary hormone deficiency.

BACKGROUND: POU1F1 is a pituitary transcription factor that plays a pivotal role in pituitary development and expression of the GH, PRL and TSH beta genes. Therefore, abnormalities of the POU1F1 gene are known to be responsible for a phenotype causing combined pituitary hormone deficiency (CPHD) involving growth hormone, prolactin and thyrotropin. METHODS: We described an 18-year-old Thai man, from a consanguineous family, who presented with short stature and cognitive deficit. He underwent endocrinological and molecular investigations. RESULTS: Hormonal studies showed that the patient had GH deficiency and secondary hypothyroidism, consistent with CPHD. Direct DNA sequencing revealed a novel homozygous mutation at the splice site of exon 4, IVS4+1G>A. It is the first splice site mutation in the POU1F1 gene described to date. Of the 7 other family members studied for this mutation by restriction enzyme digestions, 5 were heterozygous. They were all unaffected, suggesting a recessive pattern of inheritance. CONCLUSIONS: We described a novel POU1F1 splice site mutation, IVS4+1G>A, the first of its kind, in a Thai patient with CPHD. Recessive inheritance is suggested. We also noted preventable morbidities which resulted from delay in diagnosis of concomitant pituitary hormone defects in newborns suspected of CPHD.

Adrenal hemorrhage as the first presentation of hepatocellular carcinoma.

We report a 67-year-old man who presented with sudden onset of pain in the left flank in association with anemia and hypotension. Imaging studies revealed hepatocellular carcinoma (HCC) at the right lobe of the liver with bilateral adrenal metastases and recent hemorrhage in the left adrenal gland. His serology for hepatitis C was positive. Abdominal exploration with left adrenalectomy was performed. The postoperative course of the patient was uneventful and three cycles of transarterial chemoembolization (TACE) were administered. His general condition gradually deteriorated, and he died 6 months after surgery. Spontaneous massive AH due to metastatic HCC is unusual. Considering the high incidence of HCC in Asia, clinicians should be aware of this atypical and fatal presentation.

Asymptomatic bilateral giant adrenal myelolipomas: case report and review of literature.

OBJECTIVE: To describe an unusual case of bilateral giant adrenal masses caused by a primary adrenal myelolipoma. METHODS: We present the clinical, laboratory, and pathologic findings in a 32-year-old man with bilateral adrenal masses. The previous reports of bilateral myelolipomas also were reviewed. RESULTS: During a routine examination, a 32-year-old Thai man was found to have an asymptomatic abdominal mass. A computed tomographic scan of the abdomen disclosed bilateral adrenal masses; the one on the left was approximately 27 by 24 by 12 cm, and the one on the right side was 9 by 5 by 5 cm. The computed tomographic scan characteristics showed that both masses consisted mainly of low-density tissues (-30 to -90 Hounsfield units), suggestive of fatty component. An endocrinologic evaluation revealed no evidence of adrenal cortical or medullary functional abnormalities. Bilateral adrenalectomy was performed because of the large size of the lesions and the inability to rule out malignant involvement. CONCLUSION: Myelolipoma is a relatively rare benign tumor of the adrenal glands composed of adipose cells and mature hematopoietic elements. Most such lesions are small, asymptomatic, and unilateral; giant or bilateral myelolipomas are quite rare. To our knowledge, our current case may represent the largest bilateral lesions in the literature.