Iodine nutritional status of pregnant women in an urban area of northern Taiwan in 2018.

Pregnant women are considered as one of the most vulnerable groups for iodine deficiency. The Nutrition and Health Survey in Taiwan 2013 revealed that the median urinary iodine concentration (UIC) of non-pregnant women of child-bearing age of 15-44 years was 124 µg/L, which was adequate in general, but insufficient according to pregnancy criteria. The aim of this study was to determine the iodine nutritional status of pregnant women in an urban area of Northern Taiwan. A hospital-based cross-sectional survey was conducted in Taipei Veterans General Hospital. Random spot urine samples were collected from January to October, 2018 and UIC was determined by inductively coupled plasma mass-spectrometry. A food frequency questionnaire was also delivered to the participants. The overall median UIC was 225.3 µg/L (IQR: 109.1-514.2 µg/L) for 257 pregnant women ranging from 21-47 years-old. The distribution of UIC was as follows: 35.4% with UIC <150 µg/L, 17.1% with UIC within 150-249 µg/L, 21.8% with UIC within 250-499 µg/L, and 25.7% with UIC ≥500 µg/L. The use of prenatal multivitamin was very common among the participants: 79.4% (n = 204) took multivitamin either every day or less frequently, with 52.5% (n = 135) taking one pill every day, and only 20.6% (n = 53) never took multivitamin during their pregnancy. Other commonly consumed iodine-containing foods were dairy products and fish. Our results indicate that the iodine status in the studied women is adequate. However, efforts are still needed to avoid iodine deficiency as well as iodine excess.

Iodine Status of Taiwanese Population in 2013: 10 Years After Changing From Mandatory to Voluntary Salt Iodization.

BACKGROUND: In 2003, Taiwan's iodine policy changed from mandatory to voluntary. The Nutrition and Health Survey in Taiwan (NAHSIT) 2001-2002 for schoolchildren showed adequate iodine nutrition, while NAHSIT 2005-2008 for adults showed the iodine status was at borderline adequacy. OBJECTIVE: To investigate the iodine status of the Taiwanese population from schoolchildren to adulthood 10 years after the change of the salt iodization policy. METHOD: Urinary iodine was measured in samples from subjects in NAHSIT 2013. RESULTS: The median urinary iodine concentration (UIC) of the Taiwanese population aged 6 years and above in 2013 was 96 µg/L, indicating mild iodine deficiency. The median UIC of 6- to 12-year-old schoolchildren was 124 µg/L (interquartile range [IQR]: 92-213 µg/L), and 115 µg/L (IQR: 80-166 µg/L), 125 µg/L (IQR: 74-161 µg/L), 73 µg/L (IQR: 52-131 µg/L), and 78 µg/L (IQR: 52-132 µg/L) in populations aged 13 to 18 years, 19 to 44 years, 45 to 64 years, and ≥65 years, respectively. Declining iodine nutrition in age groups ≥45 years old was noted that the median UIC of populations aged 45 to 64 years and ≥65 years was 99 and 88 µg/L, respectively, in NAHSIT 2005-2008. The median UIC of schoolchildren was not lower than that during the mandatory salt fortification period, but the distribution of urinary iodine levels signified a dietary pattern change. CONCLUSION: Wide-ranging variation in iodine nutrition levels was observed in different age groups. Universal salt iodization, as suggested by the World Health Organization, should be the best strategy to achieve adequate iodine nutrition.

Unusual visualization of an adrenal carcinoma on NP-59 scintiscan.

[Iodine-131]6-beta-iodomethylnorcholesterol (NP-59) visualization of adrenocortical carcinoma is unusual. We describe a 17-year-old female with virilization and elevated plasma testosterone, dehydroepiandrosterone sulfate (DHEAS) and aldosterone. Magnetic resonance imaging disclosed a 9-cm right adrenal mass. NP-59 adrenal scanning displayed unilateral uptake of tracer and no visualization of the contralateral adrenal gland. Exploratory laparotomy revealed adrenocortical carcinoma. Subsequent immunohistochemical studies confirmed that the tumor was capable of producing a mixture of steroids, including testosterone, DHEAS and aldosterone. Visualization of an adrenal tumor on NP-59 scintiscan is an unusual finding, which cannot exclude the possibility of malignancy.

A case of adrenal Cushing's syndrome with bilateral adrenal masses.

UNLABELLED: A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6ß-iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2µg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and (131)I-NP-59 scintigraphy are good diagnostic methods for Cushing's syndrome presenting with bilateral adrenal masses. LEARNING POINTS: The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein-wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses.

Iodine Nutritional Status of School Children in Nauru 2015.

Little is known about iodine nutritional status in island countries in the Pacific Ocean. The primary objective of this study was to report for the first time the iodine nutritional status of people in Nauru. In addition, sources of iodine nutrition (i.e., water and salt) were investigated. A school-based cross-sectional survey of children aged 6-12 years was conducted in three primary schools of Nauru. Urinary iodine concentration (UIC) was determined by spot urine samples. Available water and salt samples in Nauru were collected for the measurement of iodine content. A food frequency questionnaire was conducted. The median UIC was 142 µg/L, and 25.2% and 7.4% of the population had median UIC below 100 µg/L and 50 µg/L, respectively. Natural iodine-containing foods such as seaweeds and agar were rare. Iodine was undetectable in Nauruan tank water, filtered tap water, and raindrops. Of the analyzed salt products, five kinds were non-iodized, and three were iodized (iodine content: 15 ppm, 65 ppm, and 68 ppm, respectively). The results indicate that the iodine status in Nauruan school children is adequate. Iodized salt may serve as an important source of iodine nutrition in Nauru.

Primary hypothalamic lymphoma with panhypopituitarism presenting as stiff-man syndrome.

We report an unusual case of primary hypothalamic lymphoma with hypopituitarism presenting as Stiff-man syndrome (SMS). A 64-year-old man was hospitalized due to a 3-week history of general weakness, anorexia, vomiting, weight loss, and muscle pain and spasms precipitated by motion and tactile stimuli resulting in muscle stiffness and difficulty in mobility. Physical examination revealed normal sensorimotor function and reflexes, except for bitemporal visual field defect. Routine laboratory and gastrointestinal examinations provided no remarkable clues. Endocrine assessment revealed low levels of morning cortisol, thyroxine, and anterior pituitary hormones but an increase in prolactin level. The patient's muscle pain and stiffness improved dramatically within 2 days after hydrocortisone therapy and thyroxine replacement. Magnetic resonance imaging (MRI) of the brain confirmed an 18-mm enhancing hypothalamic tumor with optic chiasm involvement, which proved to be a B-cell lymphoma. The results of the extensive studies for systemic lymphoma were negative, suggesting a primary hypothalamic lymphoma. The tumor regressed completely and was invisible on MRI scan after adjuvant radiotherapy. The patient's condition was satisfactory and there was no recurrence of SMS during the 2-year follow-up period. This case demonstrated that primary hypothalamic lymphoma complicated with adrenal insufficiency may manifest as SMS. Early diagnosis and prompt intervention can lead to a favorable outcome and reduce morbidity.

Primary adrenal lymphoma manifestating as adrenal incidentaloma.

Although involvement of the adrenals by malignant lymphoma is common, primary adrenal lymphoma is extremely rare. Herein, we report a case of a 59-year-old woman with bilateral adrenal glands enlargement found incidentally on abdominal imaging. Despite of the huge size of the tumor, her adrenal function was intact. Ultrasound-guided biopsy disclosed a picture of malignant lymphoma, diffuse large B cell type. The patient received bilateral adrenalectomy and adjuvant chemotherapy, but succumbed 6 months later. We suggest that, although rare, primary adrenal lymphoma should be considered as a possible cause of bilateral adrenal incidentalomas.

Adrenocortical carcinoma initially presenting with hypokalemia and hypertension mimicking hyperaldosteronism: a case report.

BACKGROUND: Adrenocortical carcinoma is a rare malignancy and rare cause of Cushing's syndrome. CASE PRESENTATION: A 65-year-old seemingly well male patient was referred to our clinic under the suspicion of hyperaldosteronism due to hypertension combined with hypokalemia. However, his serum aldosterone and plasma renin activity were within normal limits. Instead, Cushing's syndrome was diagnosed by elevated urine free cortisol and a non-suppressible dexamethasone test. Abdominal computed tomography showed a 7.8 × 4.8 cm mass lesion at the right adrenal gland with liver invasion. Etomidate infusion was performed to reduce his cortisol level before the patient received a right adrenalectomy and liver wedge resection. The pathology report showed adrenocortical carcinoma with liver and lymph node metastasis. According to the European Network for the Study of Adrenal Tumors (ENSAT) staging system, the tumor was classified as T4N1M1, stage IV. Recurrent hypercortisolism was found shortly after surgery. The patient died of Fournier's gangrene with septic shock on the 59th day after diagnosis. CONCLUSIONS: We report a case of rapidly progressive stage IV adrenocortical carcinoma with initial presentations of hypokaelmia and hypertension, mimicking hyperaldosteronism.

The role of intra-arterial calcium stimulation test with hepatic venous sampling (IACS) in the management of occult insulinomas.

BACKGROUND: Occult insulinomas remain a clinical challenge. Specifically designed protocols are necessary to aid detection and facilitate a focused pancreatic exploration. METHODS: Seventeen non-multiple endocrine neoplasia (non-MEN) patients referred to this medical center in the past 10 years because of equivocal diagnosis, failure of previous operation or difficulty in localization for insulinomas were studied. A routine intra-arterial calcium stimulation test with venous sampling (IACS test) was done for lesion localization. An exploratory laparotomy with intraoperative ultrasound (IOUS) examinations was performed. RESULTS: Preoperative imaging (sonography, high-resolution computed tomography scan, and magnetic resonance imaging) found six insulinomas, and IOUS found an additional six in the pancreatic regions; all were compatibly indicated by the IACS test. The remaining five patients with occult lesions by IOUS were treated by 40% (1) or 60-70% (4) distal pancreatectomies when insulin gradients were demonstrated on calcium stimulation to the splenic or to the superior mesenteric artery, respectively, and nesidioblastosis was found in each pathology examination. There were no complications related to the arterial stimulation and venous sampling (ASVS) test. No patient had recurrent hyperinsulinism, permanent morbidity, or mortality from surgery. CONCLUSIONS: IACS test helps in the diagnosis of equivocal pancreatogenous hypoglycemia, indicating the pancreatic region of priority exploration and guiding a pancreatic resection.

Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1.

OBJECTIVE: To identify MEN1 gene mutations and characterize clinical manifestations in Chinese kindred with multiple endocrine neoplasia type 1 (MEN1) in Taiwan. PATIENTS AND METHODS: Eight unrelated subjects (one male and seven females, age range 26-70 years) with clinical manifestations of MEN1 were analysed. In addition, 45 relatives that included 10 affected (three males and seven females, age range 32-53 years) and 35 unaffected (17 males and 18 females, age range 15-80 years) subjects were evaluated. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis were performed according to standard procedures. RESULTS: We identified heterozygous MEN1 gene mutations in all eight probands and 10 affected subjects as well as in 13 clinically asymptomatic relatives. Novel mutations included a missense mutation in a heterozygous mutation in exon 9 (GAC --> CAC) resulting in a substitution of aspartic acid by histidine at codon 418 (family 1); a nonsense mutation at codon 556 of exon 10 (GAG --> TAG) resulting in a stop codon and termination (family 2); a missense mutation in exon 2 (GGG --> GAG) causing the substitution of glycine by glutamic acid at codon 110 (family 3); and a deletion/insertion mutation in nucleotide 1200 of exon 8 resulting in frameshift and early termination (family 4). Affected subjects in families 5-7 shared the same C insertion at nucleotide 1650 of exon 10, similar to that previously described as a hotspot for mutation, and proband 8 had a previously described mutation in intron 4 of the MEN1 gene (IVS4-9 G --> A). We also found that 18 (58%) of our 31 MEN1 mutant carriers had clinical symptoms, whereas four (13%) had biochemical abnormalities without clinical symptoms, and nine (29%) were unaffected both clinically and biochemically. CONCLUSIONS: We have identified four novel mutations in the MEN1 gene in patients with MEN1 in Taiwan.

Two novel mutations in the gene encoding thyroxine-binding globulin (TBG) as a cause of complete TBG deficiency in Taiwan.

OBJECTIVE: Thyroxine-binding globulin (TBG) encoded by the TBG gene on chromosome Xq22 is the major transport protein, carrying approximately 75% of circulating T4. Inherited defects in TBG are associated with three phenotypes based on the level of TBG in serum of affected hemizygous males: complete TBG deficiency (TBG-CD), partial TBG deficiency (TBG-PD) and TBG excess (TBG-E). In this study, we report two unrelated Han Chinese males with complete TBG deficiency who carry different mutations in the TBG gene. PATIENTS: Two index cases of Han males who were diagnosed as having TBG deficiency on the basis of undetectable serum TBG and an additional 75 (50 males and 25 females) normal Han Chinese. MEASUREMENT: Serum thyroid hormones were measured by chemiluminescent immunoassay, thyroid autoantibodies by an agglutination test, and TSH receptor antibody and TBG by radioimmunoassay. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis of the TBG gene were performed with standard methods. RESULTS: One index case had one missense mutation in his copy of the gene, a G --> A transition in codon 52 that results in the replacement of serine by asparagine, and a known polymorphism in codon 283 (TTG --> TTt) that results in the replacement of leucine by phenylalanine. The allelic frequency of TBG-Poly allele in 75 normal Han Chinese (100 chromosomes) was 31%. A second index case was hemizygous for a nonsense mutation in codon 280 of exon 3 (TGG --> TGa). This mutation, located in the C-terminal of TBG, predicts a markedly truncated protein. CONCLUSIONS: This is the first report of complete thyroxine-binding globulin deficiency (TBG-CDT1 and TBG-CDT2) due to TBG gene mutations in Taiwan.

Evaluation of secondary adrenal insufficiency: findings by corticotropin-releasing hormone test and magnetic resonance imaging in parallel.

BACKGROUND: The corticotropin-releasing hormone (CRH) stimulation test is reliable for diagnosing pituitary or hypothalamic adrenal insufficiency. In the present study, we evaluated secondary adrenal insufficiency in patients with pituitary disease by CRH test and magnetic resonance imaging (MRI). METHODS: A total of 12 healthy persons and 20 patients with pituitary disorder were recruited, including 6 with Sheehan's syndrome, 6 with idiopathic panhypopituitarism, 3 with isolated ACTH deficiency, 2 with pituitary apoplexy, 2 with empty sella syndrome and I with postoperative suprasellar tumor. Blood ACTH and cortisol levels were measured after 100 microg ovine CRH (oCRH) intravenous bolus infusion. RESULTS: In patients, basal ACTH was 15.9+/-17.3 pg/ml and basal cortisol was 4.8+/-4.6 microg/dl. These values were significantly lower than those in controls (p = 0.02). In 11 of 20 patients (3 with Sheehan's syndrome, 3 with panhypopituitarism, 2 with empty sella, 2 with isolated ACTH deficiency and 1 with pituitary apoplexy), a delayed and prolonged ACTH response was observed. In the other 9 patients, ACTH showed little change. In all patients, there was no apparent increase in cortisol value. Moreover this value was significantly lower than in healthy persons (6.2+/-5.4 vs. 21.1+/-6.0 microg/dl; p <0.0001). Sellar MRI showed complete empty change in all Sheehan's syndrome, apoplexy and empty sella syndrome patients. The six patients with panhypopituitarism had variable hypoplastic adenohypophysis with or without visible pituitary stalk. The three isolated ACTH deficiency cases demonstrated a normal anatomy. CONCLUSIONS: Our study showed that patients with pituitary disease had significantly lower plasma cortisol response after oCRH than controls. Thus, CRH testing appears useful for the diagnosis of central adrenal insufficiency. The two different functional ACTH responses to CRH observed in each pituitary disorder did not correlate with damage levels shown on MRI.

The relationship between morning serum cortisol and the short ACTH test in the evaluation of adrenal insufficiency.

BACKGROUND: Morning serum cortisol examinations and short corticotropin (ACTH) tests are popular screening tests for unstressed patients suspected of having adrenal insufficiency. However, the correlation between morning serum cortisol and the peak cortisol response in the short ACTH test after intravenous injection of ACTH has not been studied before. This retrospective study examined the relationship among the mean basal morning cortisol level, the single random morning cortisol level and the peak cortisol level in the short ACTH test in evaluation of adrenal insufficiency. METHODS: In this retrospective study, we examined the relationship among the mean basal morning cortisol level and the peak cortisol level stimulated by intravenous injection of 250 microg synthetic ACTH in 106 unstressed patients with proven or suspected hypothalamic-pituitary-adrenal disease. Plasma cortisol levels were determined by radioimmunoassay. The correlation of the basal morning cortisol to the short ACTH test was determined by linear regression analysis. The ACTH test was analyzed using the receiver operating characteristic (ROC) curve method, and the cut-off points for various sensitivity and specificity were calculated. RESULTS: The mean basal is highly correlated to peak cortisol response in the ACTH test (r = 0.7724, p < 0.0001). Iatrogenic Cushing's syndrome, caused by ingestion of herbs with illegal steroid additives, was the most common cause (60%) of adrenal insufficiency in the 52 patients with subnormal result. A mean basal morning serum cortisol of > or = 300 nmol/L excluded the possibility of adrenal insufficiency, and a level of < 110 nmol/L suggested adrenal insufficiency. A mean basal cortisol level of > or = 234 nmol/L predicted a normal cortisol response in the ACTH test with optimal sensitivity (80.6%) and specificity (91.4%). CONCLUSIONS: The mean morning cortisol level is a cost-effective screening test in predicting the results of the ACTH test. A mean morning cortisol level > or = 300 nmol/L in suspicious cases of adrenal insufficiency which are not due to acute central etiologies excludes the possibility of subnormal cortisol response to ACTH; whereas a level < 110 nmol/L is likely to have subnormal cortisol response to ACTH. The short ACTH test or insulin tolerance test should be performed in patients with a morning cortisol level 300 nmol/L or with clinical symptoms highly suggestive of adrenal insufficiency.

A reappraisal of the ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of Cushing's syndrome: a comparison with the standard high-dose dexamethasone suppression test.

BACKGROUND: We evaluated the diagnostic efficacy of the ovine corticotropin-releasing hormone (oCRH) stimulation test in the differential diagnosis of Cushing's syndrome and compared it with the standard high-dose dexamethasone suppression test. METHODS: Twelve healthy volunteers and 30 with Cushing's syndrome (12 Cushing's disease and 18 adrenal Cushing's syndrome) were enrolled. Plasma ACTH and cortisol levels were measured before and after an intravenous bolus of 100 microg oCRH. Plasma and urinary free cortisol were determined after standard 2-day high-dose dexamethasone suppression. RESULTS: Basal cortisol in 12 patients with Cushing's disease and 18 with adrenal Cushing's syndrome were higher than the control group (21.4 +/- 0.1 microg/dl vs. 22.3 +/- 0.5 microg/dl vs. 9.1 +/- 1.5 microg/dl; p < 0.01). In Cushing's disease, basal plasma ACTH value was significantly higher than those with adrenal disease (61.1 +/- 1.4 pg/ml vs. 6.2 +/- 4.5 pg/ml; p < 0.01). After oCRH, plasma ACTH and cortisol significantly increased, with a mean of 2.0 +/- 0.2-fold (range 1.0-2.4) and 1.6 +/- 0.1-fold (range 1.1-2.1), respectively over the basal values in patients with Cushing's disease, and 11 (90%) attained a significant ACTH (1.5-fold) or cortisol (1.2-fold) response. All except 2 (89%) with adrenal Cushing's showed no apparent change in response to oCRH. Dexamethsone suppressed urinary free cortisol by 90% in 8 (67%) with Cushing's disease, but all (100%) with adrenal Cushing's syndrome were resistant. No patient with Cushing's disease was refractory to oCRH and dexamethasone, while none with adrenal Cushing's syndrome was responsive to both. Combination of both tests could achieved a specificity of 100% for Cushing's disease and adrenal Cushing's, when these 2 tests gave concomitant positive or negative results, respectively. CONCLUSIONS: The oCRH test is a reliable examination in the differential diagnosis of Cushing's syndrome and is comparable to the high-dose dexamethasone test. A highest discrimination could be achieved when both are used.