PURPOSE: Obesity is a well-known risk factor for central precocious puberty (CPP). Recently, elevated thyroid stimulating hormone (TSH) was reported in obese youth. However, few data regarding the relationship between CPP and TSH are available. The aim of this study was to evaluate thyroid function in girls with CPP and the relationship between CPP and serum TSH concentration. METHODS: This was a retrospective cross-sectional study. A total of 1,247 girls aged between 6.0 and 8.9 years who had undergone a gonadotropin-releasing hormone (GnRH) stimulation test to determine the presence of puberty were studied. Subjects were classified into CPP (n=554) and non-CPP (n=693) groups according to the results of the GnRH stimulation test. Characteristics and laboratory data of the CPP and non-CPP groups were compared and correlations between those characteristics and laboratory data and TSH concentration were evaluated. Serum TSH concentration in the CPP group was higher than that of the non-CPP group (3.19±1.55 mIU/L vs. 2.58±1.34 mIU/L, P<0.001). RESULTS: Serum free thyroxine (fT4) concentration in the CPP group was notably lower than that of the non-CPP group (1.38±0.14 ng/dL vs. 1.44±0.18 ng/dL, P<0.001). Across all subjects, 149 girls (11.9%) had hyperthyrotropinemia. The prevalence of hyperthyrotropinemia was higher in the CPP group compared to the non-CPP group (15.7% vs. 8.9%, P<0.001). TSH concentrations were positively correlated with age, height, weight, BMI, bone age, bone age advance, insulin-like growth factor 1 (IGF-1), IGF-1 standard deviation score, basal luteinizing hormone (LH), peak LH and basal follicle-stimulation hormone. TSH concentrations were negatively correlated with fT4. Multiple linear regression analysis showed that age (β=0.548, P<0.001) and peak LH (β=0.019, P=0.008) were independently associated with serum TSH concentration. CONCLUSIONS: Hyperthyrotropinemia in girls with CPP tends to be associated with pubertal LH elevation. In conclusion, pubertal onset may be associated with thyroid function.
Adolescent ; Cross-Sectional Studies ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Insulin-Like Growth Factor I ; Linear Models ; Luteinizing Hormone ; Obesity ; Prevalence ; Puberty ; Puberty, Precocious ; Retrospective Studies ; Risk Factors ; Thyroid Gland ; Thyrotropin ; Thyroxine

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.
Animals ; Diethylhexyl Phthalate* ; Female ; Humans ; Hyperplasia ; Male ; Parathyroid Hormone ; Plastics ; Rats* ; RNA, Messenger ; Thyroglobulin ; Thyroid Gland* ; Thyrotropin-Releasing Hormone ; Weaning

With the generalized use of highly sensitive thyroid stimulating hormone (TSH) and free thyroid hormone assays, most thyroid function tests (TFTs) are straightforward to interpret and confirm the clinical impressions of thyroid diseases. However, in some patients, TFT results can be perplexing because the clinical picture is not compatible with the tests or because TSH and free T4 are discordant with each other. Optimizing the interpretation of TFTs requires a complete knowledge of thyroid hormone homeostasis, an understanding of the range of tests available to the clinician, and the ability to interpret biochemical abnormalities in the context of the patient's clinical thyroid status. The common etiologic factors causing puzzling TFT results include intercurrent illness (sick euthyroid syndrome), drugs, alteration in normal physiology (pregnancy), hypothalamic-pituitary diseases, rare genetic disorders, and assay interference. Sick euthyroid syndrome is the most common cause of TFT abnormalities encountered in the hospital. In hypothalamic-pituitary diseases, TSH levels are unreliable. Therefore, it is not uncommon to see marginally high TSH levels in central hypothyroidism. Drugs may be the culprit of TFT abnormalities through various mechanisms. Patients with inappropriate TSH levels need a differential diagnosis between TSH-secreting pituitary adenoma and resistance to thyroid hormone. Sellar magnetic resonance imaging, serum α-subunit levels, serum sex hormone-binding globulin levels, a thyrotropin-releasing hormone stimulation test, trial of somatostatin analogues, and TR-β sequencing are helpful for the diagnosis, but it may be challenging. TFTs should be interpreted based on the clinical context of the patient, not just the numbers and reference ranges of the tests, to avoid various pitfalls of TFTs and unnecessary costly evaluations and therapies.
Diagnosis ; Diagnosis, Differential ; Diagnostic Errors ; Euthyroid Sick Syndromes ; Homeostasis ; Humans ; Hyperthyroidism ; Hypothyroidism ; Magnetic Resonance Imaging ; Physiology ; Pituitary Neoplasms ; Rare Diseases ; Reference Values ; Sex Hormone-Binding Globulin ; Somatostatin ; Thyroid Diseases ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin ; Thyrotropin-Releasing Hormone

Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group. The mRNA expression of miR-124 and the mRNA and protein expression of pyridoxal kinase (PDXK) were detected by quantitative real-time polymerase chain reaction and western blotting. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale. Brdu, neuron-specific enolase (NSE), neurofilament (NF) and microtubule-associated protein 2 (MAP2) were detected using immunohistochemistry. The expression levels of thyrotropin-releasing hormone (TRH), prostacyclin (PGI2) and gangliosides (GM) were measured using an enzyme-linked immunosorbent assay. PDXK was identified as the target gene of miR-124. The overexpressed miR-124 group exhibited higher miR-124 expression than the SCI, NC and si-PDXK groups. Compared with the SCI and NC groups, the PDXK expression was downregulated in the overexpressed miR-124 and si-PDXK groups, and the BBB scores were significantly increased 7, 21 and 35 days after transplantation. The double-labeled positive cell densities (Brdu+NSE/NF/MAP2) and the expression levels of TRH, PGI2 and GM in the overexpressed miR-124 group were significantly higher than those in the NC and SCI groups. These results indicated that miR-124 targeted PDXK to accelerate the differentiation of BMSCs into neurocytes and promote SCI repair.
Animals ; Blotting, Western ; Bone Marrow* ; Bromodeoxyuridine ; Cell Count ; Enzyme-Linked Immunosorbent Assay ; Epoprostenol ; Gangliosides ; Immunohistochemistry ; Intermediate Filaments ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stromal Cells* ; Microtubule-Associated Proteins ; Phosphopyruvate Hydratase ; Pyridoxal Kinase ; Rats* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Spinal Cord Injuries* ; Spinal Cord* ; Thyrotropin-Releasing Hormone

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.
Adrenal Insufficiency/diagnosis/etiology ; Adult ; Brain/diagnostic imaging ; Depression/etiology ; Female ; Hepatolenticular Degeneration/*complications ; Humans ; Hypopituitarism/complications/*diagnosis/drug therapy ; Hypothyroidism/diagnosis/etiology ; Liver Cirrhosis/complications/diagnostic imaging ; Magnetic Resonance Imaging ; Steroids/therapeutic use ; Thyrotropin-Releasing Hormone/therapeutic use

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.
Adrenal Insufficiency/diagnosis/etiology ; Adult ; Brain/diagnostic imaging ; Depression/etiology ; Female ; Hepatolenticular Degeneration/*complications ; Humans ; Hypopituitarism/complications/*diagnosis/drug therapy ; Hypothyroidism/diagnosis/etiology ; Liver Cirrhosis/complications/diagnostic imaging ; Magnetic Resonance Imaging ; Steroids/therapeutic use ; Thyrotropin-Releasing Hormone/therapeutic use

A thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, with an incidence of one case per million. Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the axial skeleton. Extra-articular manifestations, such as anterior uveitis, may also be prominent features in AS but little is known about the association between AS and thyroid diseases including TSH-secreting pituitary adenomas. We present a case study of a 26-year-old male AS patient who was diagnosed with a TSH-secreting pituitary adenoma using a thyrotropin releasing hormone stimulation test, measurement of the TSH alpha-subunit, and magnetic resonance imaging, and subsequently treated with a transsphenoidal tumor resection.
Adult ; Humans ; Hyperthyroidism ; Incidence ; Magnetic Resonance Imaging ; Male ; Pituitary Neoplasms* ; Rheumatic Diseases ; Skeleton ; Spondylitis, Ankylosing* ; Thyroid Diseases ; Thyrotropin* ; Thyrotropin-Releasing Hormone ; Uveitis, Anterior

BACKGROUND/AIMS: There are limited therapeutic options available for irritable bowel syndrome with diarrhea (IBS-D). We tested the effects of Atractylodes japonica rhizome, a perennial plant native to North Asia, on both upper and lower gastrointestinal (GI) motility in guinea pigs. METHODS: The extract of A. japonica rhizome was administered orally at different doses to test its effects on upper GI motility as determined from charcoal transit in native guinea pigs and in guinea pigs pretreated with thyrotropin-releasing hormone or mustard oil. Regarding its effect on lower GI motility, the removed guinea pig colon was suspended in a chamber containing Krebs-Henseleit solution and the transit time of artificial feces was measured with various dilutions of the extract. As for in vivo assay, weight and number of fecal pellets expelled were determined under the same drug preparation used in upper GI motility experiment. RESULTS: The extract of A. japonica rhizome had no significant effect on upper GI motility in either normal or altered physiological states. However, the extract increased colonic transit time in the in vitro model. In the fecal expulsion study, the cumulative weight and number of pellets did not differ significantly between the control group and groups treated with the extracts. In the animals pretreated in vivo with thyrotropin-releasing hormone, however, the weight and number of fecal pellets were significantly decreased in animals treated with 300 mg/kg and 600 mg/kg doses of extract. CONCLUSIONS: Our findings suggest that the extract of A. japonica rhizome can be a potential agent for IBS-D.
Animals ; Asia, Northern ; Atractylodes* ; Charcoal ; Colon ; Diarrhea ; Drug Compounding ; Feces ; Gastrointestinal Motility* ; Guinea Pigs* ; Irritable Bowel Syndrome ; Mustard Plant ; Plants ; Rhizome* ; Thyrotropin-Releasing Hormone

Congenital central hypothyroidism (C-CH) is a rare disease in which thyroid hormone deficiency is caused by insufficient thyrotropin (TSH) stimulation of a normally-located thyroid gland. Most patients with C-CH have low free thyroxine levels and inappropriately low or normal TSH levels, although a few have slightly elevated TSH levels. Autosomal recessive TSH deficiency and thyrotropin-releasing hormone receptor-inactivating mutations are known to be genetic causes of C-CH presenting in the absence of other syndromes. Recently, deficiency of the immunoglobulin superfamily member 1 (IGSF1) has also been demonstrated to cause C-CH. IGSF1 is a plasma membrane glycoprotein highly expressed in the pituitary. Its physiological role in humans remains unknown. IGSF1 deficiency causes TSH deficiency, leading to hypothyroidism. In addition, approximately 60% of patients also suffer a prolactin deficiency. Moreover, macroorchidism and delayed puberty are characteristic features. Thus, although the precise pathophysiology of IGSF1 deficiency is not established, IGSF1 is considered to be a new factor controlling growth and puberty in children.
Adolescent ; Cell Membrane ; Child ; Glycoproteins ; Humans ; Hypothyroidism* ; Immunoglobulins ; Infant, Newborn ; Neonatal Screening* ; Prolactin ; Puberty ; Puberty, Delayed ; Rare Diseases ; Thyroid Gland ; Thyrotropin ; Thyrotropin-Releasing Hormone ; Thyroxine

OBJECTIVE: To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. METHODS: This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 microg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). RESULTS: The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). CONCLUSION: TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH.
Anovulation ; Female ; Humans ; Hypothyroidism* ; Infertility ; Infertility, Male ; Injections, Intravenous ; Male ; Polycystic Ovary Syndrome ; Prevalence ; Thyrotropin* ; Thyrotropin-Releasing Hormone*