Letter: The Biochemical Prognostic Factors of Subclinical Hypothyroidism (Endocrinol Metab 2014;29:154-62, Myung Won Lee et al.)

No abstract available.

Sunitinib-induced hypothyroidism / 대한내과학회지

Sunitinib is an oral multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor. Currently, sunitinib is being investigated in multiple other tumor types including non-small cell lung cancer, breast cancer, colon cancer, and endocrine tumors. Recent studies have shown that sunitinib induces thyroid dysfunction, mainly hypothyroidism during treatment. The incidence of sunitinib-induced hypothyroidism has been reported to be 36~85%. Although several hypotheses have been suggested, the mechanisms by which sunitinib induces hypothyroidism are not clear. As considered the fairly high incidence of sunitinib-induced hypothyroidism, thyroid function should be regularly monitored in all patients treated with sunitinib.

A case of papillary thyroid cancer and pheochromocytoma with ganglioneuroma / 대한내과학회지

Composite tumors containing pheochromocytoma and ganglioneuroma are very rare. We report a 70-year-old female with papillary thyroid carcinoma and a compound adrenal medullary tumor, composed of pheochromocytoma/ ganglioneuroma. She had complained of epigastric discomfort 2 months earlier. Chest computed tomography and pancreatic magnetic resonance imaging revealed an intrathoracic goiter and pancreatic cystic tumor. She underwent an explorative laparotomy, and a left adrenalectomy was done because of an adrenal mass, not the pancreatic mass. The pathological diagnosis was a compound adrenal medullary tumor, composed of pheochromocytoma and ganglioneuroma. Although there was no evidence of thyroid cancer on fine needle aspiration cytology, a total thyroidectomy was done because of the neck discomfort. The pathological diagnosis was a papillary thyroid carcinoma, and she underwent radioactive iodine therapy.

Steroid-Responsive Recurrent Encephalopathy Associated with Subacute Thyroiditis

BACKGROUND: Steroid-responsive encephalopathy associated with subacute thyroiditis has, to our knowledge, not been reported previously. CASE REPORT: A 49-year-old woman was found collapsed and brought to our institution with decreased mentality, dysarthria, and gait disturbance. Brain magnetic resonance imaging and angiography were normal but blood tests revealed thyroid-autoantibody-negative thyrotoxicosis. Results of a (99m)technetium-pertechnetate scan were compatible with the thyrotoxic phase of subacute thyroiditis. 14-3-3 proteins were detected in cerebrospinal fluid. Her mental status began to improve from the day following steroid administration. Recurrent encephalopathy was found 2 months after the initial admission, which was also effectively treated with steroid. CONCLUSIONS:We speculate that steroid-responsive recurrent encephalopathy associated with subacute thyroiditis is a subtype of Hashimoto's encephalopathy, and consider that steroid treatment should not be delayed in suspected patients.

Overexpression of USF Increases TGF-beta1 Protein Levels, But G1 Phase Arrest was not Induced in FRTL-5 Cells

Transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of cellular growth and proliferation by G1 phase arrest or apoptosis. We investigated the association of TGF-beta1 with the anti-proliferative effect of upstream stimulatory factor (USF) in Fischer rat thyroid cell line (FRTL-5) cells. [Methyl-(3)H] thymidine uptake was measured after treatment of FRTL-5 cells with TGF-beta1 to identify its anti-proliferative effect. USF-1 and USF-2 proteins were in vitro translated, and an electrophoretic mobility shift assay was performed to identify the interaction between USF and the TGF-beta1 promoter. FRTL-5 cells were transfected with USF cDNA, and then the expression of TGF-beta1 was examined with Northern and Western blotting. The cell cycle-regulating proteins associated with TGF-beta1 were also measured. TGF-beta1 significantly inhibited [methyl-(3)H] thymidine uptake in FRTL-5 cells. Two specific binding sites for USF were found in the TGF-beta1 promoter: -1,846~-1,841 (CACATG) and -621~-616 (CATGTG). Overexpression of USF increased both the mRNA levels and protein levels of TGF-beta1. However, the expression of cyclin D1, CDK4, cyclin E, and CDK2, and the phosphorylation of retinoblastoma protein remained unchanged. Overexpression of USF in FRTL-5 cells increased the expression of TGF-beta10 through specific binding to TGF-beta1 promoter. However, the USF-induced expression of TGF-beta1 did not cause G1 arrest.

Analysis of the Pharmacokinetics of Recombinant Human TSH in Patients with Thyroid Papillary Carcinoma / 대한내분비학회지

BACKGROUND: Individual variations of the pharmacokinetics of recombinant human TSH (rhTSH) might influence the efficacy of the radioactive iodine (RAI) uptake. We studied to investigate the individual pharmacokinetics of rhTSH and the effect of the anthropometric parameters on the serum TSH levels in patients with thyroid papillary carcinoma. METHODS: We selected 16 patients with conventional rhTSH administration for the preparation of RAI administration between June 2004 and May 2005. We measured serum TSH levels at 24-hour (prior to second rhTSH injection), 48-hour (peak level, prior to RAI administration) and 96-hour (prior to scanning) after the first rhTSH injection. We analyzed the correlation of each TSH levels with age, height, weight, creatinine clearance, body mass index (BMI), and body surface area (BSA). RESULTS: Peak TSH levels were negatively correlated with weight, BMI, and BSA. Among them, weight was an independent parameter by multivariate analysis. Decrement of serum TSH levels from the peak to the level at 96-hour was negatively correlated with weight, BMI, and BSA. It was positively correlated with increment of serum TSH levels from the level at 24-hour to the peak level. Serum TSH level at 96-hour was lower than 25 mU/L in nine of 16 patients. CONCLUSION: Body weight was inversely correlated with peak TSH level after rhTSH administration. rhTSH-stimulated TSH levels might be exaggerated to unwanted levels, and very rapidly degraded in lower-weighted patients. We should make up for the rhTSH regimen considering the individual variations of its pharmacokinetics.

Efficacy of Octreotide LAR in Acromegalic Patients / 대한내분비학회지

BACKGROUND: Octreotide(OC)-LAR is a long-acting preparation of octreotide which has been effectively used to suppress GH/IGF-1 hypersecretion in acromegalic patients. The clinical response, biochemical outcomes, and safety of OC-LAR were evaluated in 27 active acromegalic patients. METHOD: 27patients with an active disease status (according to the clinical picture, GH >5microgram/L and elevated age-matched IGF-1), and previously treated with bromocriptine after surgery, comprised the study population. OC-LAR was given(20mg, i.m., every 4 week for 3 injections, then the doses were titrated individually) and the acromegalic symptoms and adverse reactions recorded. The serum levels of GH and IGF-1 were evaluated every 12 week. The acromegalic symptoms including headache, fatigue and arthralgia, improved in all patients. RESULTS: Gastrointestinal side effects were transient and mild. The levels of GH significantly decreased, from 8.9+/-3.5 to 2.9+/-2.2 microgram/L at 12 weeks(P<0.001, vs. baseline), to 2.9+/-2.1microgram/L after 24 weeks(P<0.001) and to 2.5 +/-1.3microgram/L at 48 weeks(P<0.001). The levels of IGF-1 significantly decreased, from 753.7+/-213.6 to 429.7+/-253.4 microgram/L at 12 weeks(P<0.001, vs. at baseline), to 405.7+/-213.3microgram/L at 24 weeks(P <0.001) and to 348.9+/-144.7microgram/L at 48 weeks(P<0.001). The safelevel of GH is less than 2.5microgram/L and normal age-matched IGF-1 levels were achieved in 63 and 52% of the patients, respectively. CONCLUSION: Octreotide-LAR was well tolerated and effective as an adjuvant treatment in lowering the levels of GH and IGF-1 in active acromegalic patients.

Effects of USF-1, USF-2, PTEN and Thyroid Transcription Factors on the Function and Growth in FRTL-5 Cells / 대한내분비학회지

BACKGROUND: Upstream stimulatory factors (USFs) and PTEN are known to be tumor suppressants. USFs and PAX-8 were reported to be the functional competitors in sodium iodide symporter (NIS) gene expression. We investigated the effects of USF-1, USF-2, PTEN, and thyroid-specific transcription factors (TTF-1, PAX-8) on the function and growth of thyrocytes of FRTL 5 rat thyroid cells. METHODS: Complementary DNAs of the USF-1, USF-2, PTEN, TTF-1 (homeodomain), and PAX-8 were synthesized from RNA extracted from FRTL-5using an RT-PCR kit. Each of them was transiently transfected to the FRTL-5 cells using the lipofectamine after being cloned into the pcDNA3.1 vectors. Stable cell lines, which were transfected by USF-1, PTEN, TTF-1, and PAX-8, were also obtained from the FRTL-5 cells, respectively. Extracellular cAMP concentrations were measured after 24 hours of incubation with varying concentrations of bTSH (0.1~100 mIU/mL). After, [Methyl-3H] thymidine uptake or 5-bromo-2'-deoxyuridine (BrdU) assay was performed. RESULTS: USF-1 and USF-2 significantly increased cAMP levels and decreased thymidine uptake in both transiently and stably transfected cells (p<0.01). PTEN had a tendency to increase both the cAMP levels and BrdU uptake in stable cells, but had a tendency to decrease thymidine uptake in transiently transfected cells. TTF-1 significantly increased the cAMP levels and either thymidine or BrdU uptake in both transiently and stably transfected cells (p<0.05). PAX-8 significantly increased both the cAMP levels and BrdU assay in stable cells, but in transiently transfected cells, it significantly decreased cAMP concentrations (p<0.01). CONCLUSIONS: These results suggested that both the USF-1 and USF-2 play a role in suppressing the growth of thyrocytes but at the same time, they kept the ability to produce cAMP after TSH stimulation. They had opposing effects on TTF-1 and PAX-8 in terms of the proliferation of thyrocytes

Analysis of Ret Proto-oncogene Mutation in Korean Patients with Medullary Thyroid Carcinomas / 대한내분비학회지

BACKGROUND: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 ~30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. METHODS: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. RESULTS: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. CONCLUSION: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this.

Clinical and Hormonal Analysis of Five New Cases and Eight Previously Reported Cases of Isolated ACTCH Deficiency in Korea / 대한내분비학회지

Isolated ACTH deficiency is an uncommon disorder, which is defined by low cortisol production with low or normal plasma ACTH levels and no other pituitary abnormalities. We report five new cases of this disorder, and summarize the clinical and hormonal features of 8 previously reported cases in Korea plus 5 new cases. 1) The clinical manifestations of isolated ACTH deficiency are variable, non-specific and similar to those seen in adrenocortical insufficiency of any cause, the age of patients ranged from 21 to 66 years old with an average age of 46 years, and the male to female ratio was 10:3. 2) Hyponatremia and hypoglycemia were commmon laboratory findings, so the presence of unexplained hyponatremia or hypoglycemia should always warrant consideration of the diagnosis of isolated ACTH deficiency. 3) 3 of 13 patients accompanied by empty sella suggesting selective destruction of pituitary ACTH producing cells. 4) ACTH response to exogenous CRH or vasopressin was not elicited in all tested cases, suggesting pituitary disorders. 5) Most patients showed dramatic response with oral predinisone. In conclusion, when there are unexplained general weakness, fatigue, weight loss, nausea, vomiting, hypoglycemia, or hyponatremia, isolated ACTH deficiency should be excluded. Immunologic and pathologic studies, and hormonal evolution with glucocorticoid treatment are needed to understand the pathogenesis of isolated ACTH deficiency.

A Case of Cushing's Disease due to Large Pituitary Adenoma Treated by Surgery in Combination with Radiotherapy / 대한내분비학회지

Large pituitary adenomas causing Cushings disease are uncommon, and usually present with mild manifestations of Cushings syndrome. Large adenomas may have rapid growth and quickly reach a size large enough to become clinically apparent. These tumors are more frequently invasive than microadenomas, their widespread extensions make radical surgical removal difficult and the ultimate clinical course malignant. We report a case of 37 year-old women presenting amenorrhea, weight gain, and moon face. Sellar magnetic resonance imaging(MRI) demonstrated a large lobulating tumor measuring 3.5cm in diameter, arising from sella turcica, extending up to suprasellar area and invading the cavernous sinuses. Transfrontal adenectomy was performed to remove a mass, but residual mass was remained after surgery. Subsequent external brain radiotherapy(total dose 5400cGy) was performed. Histology revealed an adrenocorticotrophin(ACTH) secreting pituitary adenoma. After treatment, her menstration was started, body weight was reduced, and moon face was disappeared.

A Case of Acromegaly with Graves' Disease / 대한내분비학회지

Goiter is present in 25-50% of patients with acromegaly, which probably results from IGF- I stimulation of thyroid cell growth. These goiters are usually non-toxic but there have been well documented cases of co-existent hyperthyroidism and acromegaly. Graves disease with acromegaly has been rarely reported compared with the other type of hyperthyroidism due to increased tumoral secretion of TSH. We experienced a 44-year-old woman who presented with Graves disease and acromegaly. Basal serum GH and IGF-I concentrations were 10.8 pg/L and 571.82 ng/mL, respectively (reference value: (5 mg/L and 130-354 ng/mL, respectively). GH was not suppressed less than 2 pg/L during oral glucose loading test. GH was stimulated by TRH. Postcontrast sellar MRI demonstrated ovoid-shaped low signal intensity nodule measuring O.8 cm in diameter in left side of pituitary gland. Thyroid scan(131I) showed enlarged thyroid with increased radioiodine uptake (61.3%). Histologic examination showed acidophilic adenoma. GH and prolactin were positive on immunohistochemical staining. GH was suppressed less than 2.26 mg/L by oral glucose loading following operation. The patient has been followed with antithyroid drug(PTU) medication after operation(TSA).

Minimal Change Disease and Focal Segmental Glomerulosclerosis in Identical Twin Brothers / 대한신장학회잡지

The simultaneous occurrence of primary glomerulonephritis in identical twins has been rarely reported previously. It has suggested that genetic factors may play an important role in the pathogenesis of primary glomerulonephritis. We describe a pair of 17-year-old identical twin brothers with asymptomatic proteinuria, one with histologically proven minimal change disease and the other with focal segmental glomerulosclerosis. HLA typing in twin brothers revealed an identical phenotype consisting of A25, A33, B44, B54, Cwl, Cw7, DR7 and DRB1. To our knowledge, this is the first case of glomerulonephritis in identical twins in Korea.

A Case of Cyclosporine Induced Reversible Cortical Blindness / 대한혈액학회지

The immunosuppressive agent, cyclosporine (CSA), has improved the success rate of organ transplantation due to its effectiveness in treating graft versus host diseases. However, as its use has increased, so has the variety of toxicities associated with it, including in the kidney, liver, and central nervous system. The spectrum of neurotoxcity ranges from mild tremor and blurred vision to seizures, ataxia, mental status changes, peripheral neuropathy, and paraparesis. Cortical blindness, an extremely rare form of CSA neurotoxicity, has previously been described in only 15 patients after a bone marrow transplant (BMT). We have experienced a rare case of CSA induced cortical blindness in a 15 year-old girl receiving a bone marrow transplantation for aplastic anemia. Tests showed a high cyclosporine level, a low serum magnesium level, and a low cholesterol. In a brain MRI, we found a diffuse high signal intensity in the parieto-occipital lobe on T2-weighted images. In an awake EEG, there were diffuse slowing waves. A visual evoked potential, performed at the time of initial evaluation, when patient was cortical blind, showed no wave formation in the left occipital recording. After discontinuation of CSA, there was significant improvement of cortical blindness, much improvement in the brain MRI, the brain EEG, and the visual evoked potential.