Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy

BACKGROUND: Graves' disease (GD) is an autoimmune thyroid disorder caused by antibodies stimulating the thyrotropin (TSH) receptor. TSH receptor antibody (TRAb) measurement is useful for predicting GD relapse after antithyroid drug (ATD) treatment. However, the association of other thyroid autoantibodies with GD relapse remains obscure. METHODS: This retrospective study enrolled patients with GD who were initially treated with ATD. TRAb, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured at the initial diagnosis and at the time of ATD discontinuation. RESULTS: A total of 55 patients were enrolled. The mean age was 49.7 years, and 39 patients (70.9%) were female. Antibody positivity at diagnosis was 90.9%, 69.1%, and 61.9% for TRAb, TPOAb, TgAb, respectively. Median ATD treatment period was 15.1 months. At the time of ATD withdrawal, TRAb titers decreased uniformly overall. Conversely, TPOAb and TgAb showed various changes. After withdrawal of ATD, 19 patients (34.5%) experienced relapse. No clinical features or laboratory results were significantly related to relapse in the overall patient group. However, in the TPOAb positive group at diagnosis, increasing titer of TPOAb or TgAb after ATD treatment was significantly and independently related to relapse free survival (TPOAb: hazard ratio [HR], 17.99; 95% confidence interval [CI], 1.66 to 195.43; P=0.02) (TgAb: HR, 5.73; 95% CI, 1.21 to 27.26; P=0.03). CONCLUSION: Changes in TPOAb or TgAb titers during treatment might be useful for predicting relapse after ATD treatment in patients with positive TPOAb at diagnosis.

Emphysematous Gastritis with Concomitant Portal Venous Air and Acute Necrotizing Esophagitis in Type 1 Diabetes with Diabetic Ketoacidosis: A Case Report and Literature Review of a Rare Complication in Diabetes / 임상당뇨병

Emphysematous gastritis is a rare disorder characterized by emphysematous change of the gastric wall due to infection with a gas-forming organism. Acute necrotizing esophagitis is a rare disorder with an unknown pathogenesis. Above two disorders rarely occur together, only three global cases have been reported to date. Such a case has never been reported in Korea, we report a novel case of severe emphysematous gastritis with concomitant portal venous air and acute necrotizing esophagitis in type 1 diabetes presenting with diabetic ketoacidosis. A 24-year-old man known to have type 1 diabetes and pulmonary tuberculosis was brought to the emergency room for epigastric pain with vomiting. His body mass index was 14.7, and the laboratory findings demonstrated leukocytosis and acidosis, as well as elevated serum glucose, ketone, and C-reactive protein levels. Enhanced computed tomography showed portal vein gas and edematous wall thickening without enhancement in the stomach wall, with air density along the stomach and esophageal wall. The patient required surgical intervention of total gastrectomy and cervical esophagostomy followed by esophagocolostomy and esophageal reconstruction. Early radiologic diagnosis and clinical suspicion of this disease and prompt intervention including antibiotics, decompression, and surgery are important for a good prognosis.

Hyperinsulinemic Hypoglycemia Caused by Acute Reduction of Renal Function on an Eldery Patient Without Diabetes

In patient with renal failure, hypoglycemia may develop because of decreased caloric intake, diminished renal insulin degradation and clearance, reduced renal gluconeogenesis and hepatic glucose production, impaired release of counter-regulatory hormone such as glucagon and epinephrine. We report here on a 80-year-old female patient with hypoglycemia due to endogenous hyperinsulinemia with acute kidney injury. She had chronic kidney disease and had no history of diabetes mellitus or insulin use. She had experienced recurrent hypoglycemia despite of intravenous dextrose injection and eventually generalized tonic clonic seizure occurred as a result of hypoglycemia. As serum creatinine level decreases, serum insulin and C-peptide level decreased and hypoglycemia was not occurred. We present this case along with a review of the literature.

Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia

Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS) is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

A Case of Acute Suppurative Thyroiditis with Thyrotoxicosis in an Elderly Patient

Acute suppurative thyroiditis (AST) is a rare condition, as the thyroid gland is relatively resistant to infection. Thyroid function tests are usually normal in AST. A few cases of AST associated with thyrotoxicosis have been reported in adults. We report a case of AST that was associated with thyrotoxicosis in a 70-year-old woman. We diagnosed AST with thyroid ultrasonography and fine needle aspiration of pus. The patient improved after surgical intervention and had no anatomical abnormality. Fine needle aspiration is the best method for the difficult task of differentiating malignancy and subacute thyroiditis from AST with thyrotoxicosis. Earlier diagnosis and proper treatment for AST might improve the outcome.

Hypothyroidism With Acute Renal Failure and Heart Failure

Here we report a 65-year-old male patient initially presented with dyspnea and chest discomfort. This patient was finally diagnosed with severe hypothyroidism accompanied by heart failure, pericardial effusion and acute renal failure. We suspected that heart failure, pericardial effusion and acute kidney injury were induced by severe hypothyroidism. Thus, we began thyroid hormone replacement therapy. After the therapy, the patient's dyspnea and chest discomfort were improved. Hypothyroidism has many complications, such as myxedema, dyslipidemia, and depression. In contrast, heart failure, pericardial effusion, and acute kidney injury are very rare complications of hypothyroidism. Only a few cases of heart failure or renal failure combined with hypothyroidism have been reported. Our case suggests that severe hypothyroidism can lead to multiorgan failure, such as heart failure as well as renal failure. Moreover, congestive heart failure induced by severe hypothyroidism can be reversed by thyroid hormone replacement therapy.

A Case of Metformin-Induced Acute Kidney Injury without Lactic Acidosis: A Case Report / 대한구급학회지

Metformin is an oral antidiabetic drug in the biguanide class, which is used for type 2 diabetes. The side effects of metformin are mostly limited to digestive tract symptoms, such as diarrhea, flatulence and abdominal discomfort. The most serious potential adverse effect of metformin is lactic acidosis. A 51-year-old man was admitted due to hypoglycemia as a result of an overdose of antidiabetic drugs. He took massive dose of metformin. Conservative treatment failed for metabolic acidosis without lactic acidosis accompanied by acute kidney injury. Hemodialysis was executed to correct the high anion gap metabolic acidosis and acute kidney injury, and the patient recovered fully from metabolic acidosis. This case illustrates that the presence of clinical conditions, such as metformin-induced acute kidney injury and metabolic acidosis, can be developed without lactic acidosis. Prompt recognition of metabolic acidosis and early intervention with hemodialysis can result in a successful clinical outcome.

Changes of Central Obesity is the Major Determinant of Influences of Weight Reduction on Bone Mineral Density / 대한골다공증학회지

OBJECTIVES: Obesity and osteoporosis have been increasing for decades but their relationship to bone mineral density (BMD) and fat mass has not been defined. The aim of this study was to investigate how changes in body composition affect BMD after a weight reduction. MATERIALS AND METHODS: We reviewed 48 middle-aged obese women who had participated in our diet program and succeeded in reducing their weight. Body composition was measured by the dual-energy X-ray absorptiometry method, and metabolic syndrome was defined as described in the ATP-III guidelines. All differences between baseline and 12 weeks later were expressed as [{12th week data-baseline data}/baseline datax100]. RESULTS: The mean age of the participants was 38.29+/-10.89 years, and the mean follow-up time was 85 days. The mean body mass index was 31.50+/-5.19 kg/m2. Basal BMD decreased with age and increased with weight and appendicular lean mass. In a regression analysis, appendicular lean mass was positively correlated with leg BMD (R2=0.235, B=0.015, P<0.001) and age (B=-0.002, P=0.046), and appendicular lean mass (B=0.019, P=0.049) was the main determinant of total BMD (R2=0.272). After weight reduction, the total body BMD change ratio (R2=0.281) was negatively related to the change of fat mass, trunk fat mass (B=-0.042, P=0.087) and waist circumference (B=-0.108, P=0.014). CONCLUSIONS: Our findings suggest that BMD is determined by muscle mass, and that changes in central obesity may also affect BMD.

A Case of Demyelinating Peripheral Neuropathy Associated with Hashimoto's Thyroiditis

Peripheral neuropathy is somewhat common in hypothyroidism. But, demyelinating peripheral neuropathy in Hashimoto's thyroiditis is extremely rare. The pathophysiology of demyelinating peripheral neuropathy associated with Hashimoto's thyroiditis is unclear and complex and various mechanisms including the cell mediated and antibody mediated responses may be operative. We report a 68-year-old woman who presented with paresthesia and gait disturbance. She was diagnosed with hypothyroidism 7 years prior and has been on thyroid hormone. Serum antithyroglobulin antibody was significantly elevated. Nerve conduction studies revealed sensory-motor demyelinating polyneuropathy with prolonged distal latencies and reduced conduction velocities. She was under the suspicion of the lymphoma of thyroid. Surgery was performed which turned up to be Hashimoto's thyroiditis. With the impression of rare demyelinating peripheral neuropathy associated with Hashimoto's thyroiditis after other causes were excluded, she was treated with steroid which ameliorated rapidly her neurological symptoms.

A Case of Pseudohypoparathyroidism with Graves' Disease

Pseudohypoparathyroidism is a rare disease that is characterized by target cell resistance to the effects of parathyroid hormone and this disease is classified into various types depending on the phenotypic and biochemical findings. The patients with pseudohypoparathyroidism present with the clinical and biochemical features of hypoparathyroidism, but they have an increased serum level of parathyroid hormone. We experienced a case of pseudohypoparathyroidism in a 24 years old woman who had Graves' disease at that time. She had hypocalcemia, hyperphosphatemia, an elevated serum parathyroid hormone level and a normal urinary basal cyclic AMP(adenosine monophosphate) level. She also had a normal phenotypic appearance. Therefore, she was classified as suffering with pseudohypoparathyroidism type II. The clinical and laboratory abnormalities were improved by calcium supplementation in addition to vitamin D. To the best of our knowledge, this is the first case of pseudohypoparathyroidism combined with Graves' disease in Korea.

A case of diabetes mellitus associated with Klinefelter's syndrome / 대한내과학회지

An increased frequency of diabetes or impaired glucose tolerance in Klinefelter's syndrome has been previously reported. Insulin resistance is considered to be the cause of this phenomenon in Klinefelter's syndrome, which is associated with low serum SHBG and sex hormone deficiency. Sex hormone deficiencies also result in dyslipidemia and metabolic syndrome. The interrelationship between diabetes, metabolic syndrome, and androgen deficiency is complex. Here we report a case of an 18-year-old man first diagnosed with diabetes mellitus 3 years ago. Upon physical examination the patient showed characteristic phenotypes compatible with primary hypogonadism. Subsequently, tests aimed at determining the cause of hypogonadism, including a chromosomal analysis, suggested Klinefelter's syndrome. The patient's HOMA-IR score was compatible with insulin resistance. Therefore, when diabetes mellitus develops at a young age with characteristic phenotypes, a careful history and physical examination may be needed to determine whether the patient might have primary hypogonadism caused by Klinefelter's syndrome.

Two cases of acute human immunodeficiency virus sndrome presenting as an acute febrile disease / 대한내과학회지

Acute Human immunodeficiency virus (HIV) syndrome should be considered in any patient with possible HIV exposure who presents with acute febrile disease. The diagnosis of acute HIV syndrome is difficult because symptoms are those of common illness. A high index of suspicion and possibility of HIV exposure are important diagnostic clue. Early diagnosis during primary infection permit patient education and treatment that may delay disease progression and improve immune preservation and reconstitution. We report two cases of acute HIV syndrome presenting as an acute febrile disease. The first case had severe illness presenting as acute severe hepatitis and disseminated intravascular coagulation, and the second had relatively mild form of disease. Two cases started the treatment with highly active anti-retroviral therapy (HAART) and have been well now with no other complications.

A Case of Candida Parapsilosis Ankle Arthritis after Intra-articular Steroid Injection

Candida species are uncommon cause of infectious arthritis. The increasing use of potent antibiotics, immunosuppressives, artificial joints, and especially the injection of steroid into the joints predispose to the fungal arthritis. Candida arthritis occurs by hematogenous dissemination or by direct inoculation of fungus into the joint cavity. Fifty three-year-old diabetic patient, who received intra-articular steroid injection into right ankle joint several times, was hospitalized because of aggravating ankle pain and swelling. Candida parapsilosis was isolated from the joint aspiration fluid and MRI findings were compatible with septic arthritis with osteomyelitis of distal tibia, distal fibula, talus, and calcaneus. The patient was successfully treated with 3 weeks of amphotericin B and 7 months of oral fluconazole. We report this case with review of pertinent literatures, emphasizing a high index of suspicion for the fungal infection in patients with predisposing risk factors.

A Case of Candida Parapsilosis Ankle Arthritis after Intra-articular Steroid Injection

Candida species are uncommon cause of infectious arthritis. The increasing use of potent antibiotics, immunosuppressives, artificial joints, and especially the injection of steroid into the joints predispose to the fungal arthritis. Candida arthritis occurs by hematogenous dissemination or by direct inoculation of fungus into the joint cavity. Fifty three-year-old diabetic patient, who received intra-articular steroid injection into right ankle joint several times, was hospitalized because of aggravating ankle pain and swelling. Candida parapsilosis was isolated from the joint aspiration fluid and MRI findings were compatible with septic arthritis with osteomyelitis of distal tibia, distal fibula, talus, and calcaneus. The patient was successfully treated with 3 weeks of amphotericin B and 7 months of oral fluconazole. We report this case with review of pertinent literatures, emphasizing a high index of suspicion for the fungal infection in patients with predisposing risk factors.

Association of posttransplantation proteinuria with allograft loss in transplant kidney biopsy-proven recipients / 대한내과학회지

BACKGROUND: Previous studies reported a poor prognosis in patients with persistent proteinuria later in the posttransplantation course, suggesting that posttransplantation proteinuria is a marker for graft failure. This study was undertaken to elucidate the role of proteinuria after renal transplantation in the pathogenesis and outcome of allograft dysfunction in transplant biopsy-proven recipients. METHODS: We retrospectively analyzed the data from 55 patients who underwent transplant renal biopsy for proteinuria and/or azotemia occurring beyond 1 year after transplantation. Proteinuria was considered as significant when >or=30 mg/dL, and the results of transplant biopsy were categorized according to the Banff 97 classification. Logistic regression was used to estimate odds ratios (OR) for graft loss associated with proteinuria and transplant pathology. RESULTS: The patients were followed for 86.0 +/- 32.8 (mean +/- SD) months after transplantation, and transplant biopsy was performed at 54.1 +/- 31.0 months. Proteinuria at 1 year after transplantation was noted in 29.1% of the patients, and it was not significantly associated with graft loss (OR=1.94, 95% CI 0.59-6.41). In addition, proteinuria at the time of transplant biopsy was not significantly associated with graft loss, and none of each category of transplant pathology was significantly associated with graft loss. Chronic allograft nephropathy was the most frequent transplant pathology, and only glomerulonephritis was significantly associated with proteinuria at the time of transplant biopsy. On the other hand, graft loss was significantly associated with the presence of proteinuria both at 1 year after transplant biopsy and at the final follow-up. CONCLUSION: These results suggest that posttransplantation proteinuria is an important marker of graft dysfunction but may not be predictive of graft loss in biopsy-proven cases. Appropriate management guided by the results of transplant biopsy may improve the outcome.

Outbreak of Hepatitis by Orientia tsutsugamushi in the Early Years of the New Millenium / 대한간학회지

BACKGROUND/AIMS: Orientia -tsutsugamushi infection is an acute febrile disease due to the accidental transmission through human skin of forest dwelling vector Leptotrombidium larva. The authors observed liver dysfunctions in patients diagnosed with tsutsugamushi disease (Scrub typhus) in the past 3 years and report the data in the hope of bringing attention to this disease in the differential diagnosis of autumn-season hepatitis, especially of non-A, non-B and non-C hepatitis. METHODS: Medical records of 22 patients diagnosed with tsutsugamushi disease by the hemagglutinin method between October 2000 and November 2002 were reviewed. RESULTS: Female gender was dominant in the ratio of 3.4:1. Mean age was 56.4 +/- 2.6. Admission was between 23rd September and 15th November with the peak between mid October and early November. Fever, being the most common symptom, was observed in 21 cases, myalgia in 13, arthralgia in 12, chills in 6, and skin rash in 6. An incubation period of 7-9 days was most common (10 cases), 13-15 days (4), 10-12 days (3), within 3 days (3), and 4-6 days (2). Average ALT, AST and GGTP were increased to 93.2 +/- 17.3 IU/L (18 +/- 345 IU/L), 92.5 +/- 11.7 IU/L (34-255 IU/L) and 132.2 +/- 14.5 IU/L (19-251 IU/L), respectively, but total bilirubin was normal. All the patients improved with doxycycline therapy. CONCLUSIONS: Since it usually shows liver dysfunction, it is important to take Orientia tsutsugamushi into consideration in differential diagnosis of autumn-season, febrile hepatic disease.