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1.  Prevalence, clinical and biochemical profile of subclinical hypothyroidism in normal population in Mumbai 
Background:
Subclinical Hypothyroidism (ScHt) affects 3–15% of the adult population. It's clinical and biochemical profile is not well defined, especially in Indian scenario. Our study aimed at screening normal population to define normative ranges of thyroid hormones and Serum thyroid stimulating hormone (S.TSH) and prevalence of ScHt and thyroid autoimmunity.
Materials and Methods:
Two-hundred thirty-seven normal subjects without family history of thyroid disease were evaluated for symptoms and laboratory tests for thyroid dysfunction and autoimmunity.
Results:
The thyroid function tests were as follows:
Euthyroid Group:
Mean values were: T3: 1.79 ± 0.42 ng/mL, T4: 10.23 ± 2.25 μg/dL, FT3: 1.88 ± 0.19 pg/mL, FT4: 1.12 ± 0.21 ng/dL, S.TSH: 2.22 ± 1.06 μlu/mL. 10.2% of euthyroid subjects had antimicrosomal antibodies (AMA) +ve (mean titer 1:918) and 23.6% were anti-thyroid peroxidase autoantibody (anti-TPO) +ve (mean titer 15.06 Au/mL). The euthyroid outlier range for S.TSH was 0.3–4.6 μlu/mL. The values were comparable in both the sexes. Those with S.TSH ≥ 5 μlu/mL were defined to have ScHt.
ScHt Group:
Prevalence of ScHt was 11.3% (M:F ratio 1:3.7). 74% belonged to 35–54 years age group and prevalence increased with age (post-menopausal females: prevalence 20%). S.TSH was 9.8 ± 7.22 μlu/mL, mean S.AMA was 1:5079 (40.7% positivity) and mean S.anti-TPO was 260 Au/mL (47.6% positivity). Majority were agoitrous (74%), and stage I goiter was seen in 26% of this population. Symptom score of 5–8 was seen in 55% ScHt subjects versus 35% normal subjects.
Conclusion:
Mean S.TSH in our population was 2.22 μlu/mL (euthyroid outliers: 0.3–4.6 μlu/mL); hence, S.TSH above 4.6 μlu/mL should be considered as abnormal. The prevalence of thyroid autoimmunity increases after age of 35 years. ScHt presents mainly in agoitrous form and with positive antibodies, suggesting autoimmunity as the cause.
doi:10.4103/2230-8210.111641
PMCID: PMC3712376  PMID: 23869302
Autoimmunity; normative ranges; prevalence; subclinical hypothyroidism
2.  Hyperthyroidism due to inappropriate TSH secretion with associated hyperprolactinaemia--a case report and review of the literature. 
Postgraduate Medical Journal  1984;60(703):328-335.
A patient with inappropriate thyrotrophin (TSH) secretion is described. She initially presented with classical hyperthyroidism during pregnancy, responded to propylthiouracil and, subsequently, had a normal delivery. Hyperthyroidism persisted and 7.5 months later a subtotal thyroidectomy was performed. After a further 16 months, mild symptoms of hyperthyroidism recurred. She again responded to propylthiouracil, but developed galactorrhoea. At that stage, it was noted that she had persistently elevated circulating TSH in the presence of elevated T4 and T3 levels. Her symptomatology was mild, although objective indices of thyroid activity, including pulse rate, BMR, sex hormone binding globulin and cholesterol, were indicative of hyperthyroidism. CT scan and tomography of the sella were normal. She had a markedly exaggerated TSH response to thyrotrophin releasing hormone (TRH). Basal TSH and responsiveness to TRH was suppressed by high dose dexamethasone. The TSH response to TRH was partially suppressed by exogenous T3, but there was no effect on basal TSH levels. TSH also decreased slightly with L-dopa and bromocriptine. Circulating TSH rose markedly during methimazole administration. TSH alpha and beta subunits were elevated and appropriate for the high TSH. In addition, both subunits increased following TRH. The patient had basal hyperprolactinaemia with an impaired prolactin (PRL) response to TRH and metoclopramide. PRL suppressed with L-dopa and bromocriptine. The remaining anterior pituitary function was intact. Most of the laboratory findings argue against the presence of a TSH producing pituitary tumour and the most likely cause for inappropriate TSH secretion in this patient is selective resistance of the thyrotroph to thyroid hormones. A mild element of peripheral resistance might also be present. The hyperprolactinaemia could be related to lactotroph resistance to thyroid hormone. The complexities of treatment in this patient are stressed. Therapy was initially attempted with low dose dexamethasone, but this had no effect. T3 treatment produced an exacerbation of her symptomatology and did not influence basal TSH, thyroid hormones, or 131I uptake. Bromocriptine administration for 11 months partially suppressed basal TSH without influencing T3 and there was an increase in T4. Methimazole did decrease her T4 and T3, but TSH and PRL rose to even greater levels. Her hyperthyroidism was eventually controlled with an ablative dose of 131I. Thyroid hormone will be given in an attempt to suppress her TSH.
PMCID: PMC2417872  PMID: 6429655
3.  Neonatal Thyroid Function in Seveso 25 Years after Maternal Exposure to Dioxin 
PLoS Medicine  2008;5(7):e161.
Background
Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy.
Methods and Findings
Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i) a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination), and 1,772 age-matched women from the surrounding noncontaminated area (reference); (ii) a biomarker study on 51 mother–child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH) was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 μU/ml (95% confidence interval [CI] 0.90–1.08) in the reference area (n = 533), 1.35 μU/ml (95% CI 1.22–1.49) in zone B (n = 425), and 1.66 μU/ml (95% CI 1.19–2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b-TSH > 5 μU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001). Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, β = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, β = 0.45, p = 0.005).
Conclusions
Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.
Andrea Baccarelli and colleagues show that maternal exposure to a dioxin following the industrial accident in Seveso, Italy in 1976 is associated with modified neonatal thyroid function even many years later.
Editors' Summary
Background.
The thyroid, a butterfly-shaped gland in the neck, controls the speed at which the human body converts food into the energy and chemicals needed for life. In healthy people, the thyroid makes and releases two hormones (chemical messengers that travel around the body and regulate the activity of specific cells) called thyroxine (T4) and triiodothyronine (T3). The release of T4 and T3 is controlled by thyroid secreting hormone (TSH), which is made by the pituitary gland in response to electrical messages from the brain. If the thyroid stops making enough T4 and T3, a condition called hypothyroidism (an underactive thyroid) develops. Adults with hypothyroidism put on weight, feel the cold, and are often tired; children with hypothyroidism may also have poor growth and mental development. Because even a small reduction in thyroid hormone levels increases TSH production by the pituitary, hypothyroidism is often diagnosed by measuring the amount of TSH in the blood; it is treated with daily doses of the synthetic thyroid hormone levothyroxine.
Why Was This Study Done?
Although hypothyroidism is most common in ageing women, newborn babies sometimes have hypothyroidism. If untreated, “neonatal” hyperthyroidism can cause severe mental and physical retardation so, in many countries, blood TSH levels are measured soon after birth. That way, levothyroxine treatment can be started before thyroid hormone deficiency permanently damages the baby's developing body and brain. But what causes neonatal hypothyroidism? Animal experiments (and some but not all studies in people) suggest that maternal exposure to toxic chemicals called dioxins may be one cause. Dioxins are byproducts of waste incineration that persist in the environment and that accumulate in people. In this study, the researchers investigate whether exposure to dioxin (this name refers to the most toxic of the dioxins—2,3,7,8-Tetrachlorodibenzo-p-dioxin) affects neonatal thyroid function by studying children born near Seveso, Italy between 1994 and 2005. An accident at a chemical factory in 1976 heavily contaminated the region around this town with dioxin and, even now, the local people have high amounts of dioxin in their bodies.
What Did the Researchers Do and Find?
The researchers identified 1,772 women of child-bearing age who were living very near the Seveso factory (the most highly contaminated area, zone A) or slightly further away where the contamination was less but still high (zone B) at the time of the accident or soon after. As controls, they selected 1,772 women living in the surrounding, noncontaminated (reference) area. Altogether, these women had 1,014 babies between 1994 and 2005. The babies born to the mothers living in the reference area had lower neonatal blood TSH levels on average than the babies born to mothers living in zone A; zone B babies had intermediate TSH levels. Zone A babies were 6.6. times more likely to have a TSH level of more than 5 μU/ml than the reference area babies (the threshold TSH level for further investigations is 10 μU/ml; the average TSH level among the reference area babies was 0.98 μU/ml). The researchers also examined the relationship between neonatal TSH measurements and maternal dioxin measurements at delivery (extrapolated from measurements made between 1992 and 1998) in 51 mother–baby pairs. Neonatal TSH levels were highest in the babies whose mothers had the highest blood dioxin levels.
What Do These Findings Mean?
These findings suggest that maternal dioxin exposure has a long-lasting, deleterious effect on neonatal thyroid function. Because the long-term progress of the children in this study was not examined, it is not known whether the increases in neonatal TSH measurements associated with dioxin exposure caused any developmental problems. However, in regions where there is a mild iodine deficiency (the only environmental exposure consistently associated with reduced human neonatal thyroid function), TSH levels are increased to a similar extent and there is evidence of reduced intellectual and physical development. Future investigations on the progress of this group of children should show whether the long-term legacy of the Seveso accident (and of the high environmental levels of dioxin elsewhere) includes any effects on children's growth and development.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050161.
The MedlinePlus encyclopedia provides information about hypothyroidism and neonatal hypothyroidism; MedlinePlus provides links to additional information on thyroid diseases (in English and Spanish)
The UK National Health Service Direct health encyclopedia provides information on hypothyroidism
The Nemours Foundation's KidsHealth site has information written for children about thyroid disorders
Toxtown, an interactive site from the US National Library of Science, provides information on environmental health concerns including exposure to dioxins (in English and Spanish)
More information about dioxins is provided by the US Environmental Protection Agency and by the US Food and Drug Administration
Wikipedia has a page on the Seveso disaster (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.0050161
PMCID: PMC2488197  PMID: 18666825
4.  Ectopic TSH-secreting pituitary tumor: a case report and review of prior cases 
BMC Cancer  2014;14:544.
Background
Ectopic TSH-secreting pituitary adenoma (TSH-oma) is a very unusual disorder. To date, there are only four cases reported. It is difficult to distinguish ectopic cases from both regular TSH-omas and resistance to thyroid hormone (RTH).
Case presentation
A newly identified case of ectopic TSH-oma arising from the nasal pharynx was described, and reports of four prior cases were reviewed. The patient was a 41-year-old male who developed what appeared to be typical hyperthyroidism and atrial fibrillation in 2009. Thyroid function tests showed elevated basal levels of free T3 (FT3, 24.08 pmol/L), free T4 (FT4, 75.73 pmol/L), and serum TSH (7.26 μIU/ml). Both TSH-oma and resistance to thyroid hormone syndrome were considered. TRH stimulating test was negative, whereas octreotide inhibition test showed a reduction in TSH by 30.8%. Furthermore, a large space-occupying lesion located at the nasopharynx was found by computed tomography and magnetic resonance imaging (MRI). A normal pituitary was visualized. Ectopic TSH-oma was preliminarily established. Using an endoscopic endonasal approach, the tumor was resected. Histological features and immunophenotypes were consistent with those of TSH-secreting tumor. The levels of both free thyroxine and TSH returned to normal ranges the day after surgery and remained within normal range for 48 months.
Conclusions
Although exceedingly rare, ectopic TSH-oma should be considered for patients with inappropriate secretion of TSH with hyperthyroidism and pituitary tumor undetectable by computed tomography and MRI. To our knowledge, this is the first case followed up more than 4 years. The characteristics and successful interventions summarized in this report provide a guideline for clinicians.
doi:10.1186/1471-2407-14-544
PMCID: PMC4125694  PMID: 25069990
Ectopic TSH-secreting pituitary adenoma; Resistance to thyroid hormone (RTH); TRH stimulating test; Octreotide inhibition test; Hyperthyroidism
5.  A Case of simultaneous occurrence of Marine – Lenhart syndrome and a papillary thyroid microcarcinoma 
Background
Marine-Lenhart syndrome is defined as the co-occurrence of Graves’ disease and functional nodules. The vast majority of autonomous adenomas are benign, whereas functional thyroid carcinomas are considered to be rare. Here, we describe a case of simultaneous occurrence of Marine-Lenhart syndrome and a papillary microcarcinoma embedded in a functional nodule.
Case presentation
A 55 year-old, caucasian man presented with overt hyperthyroidism (thyrotropin (TSH) <0.01 μIU/L; free thyroxine (FT4) 3.03 ng/dL), negative thyroid peroxidase and thyroglobulin autoantibodies, but elevated thyroid stimulating hormone receptor antibodies (TSH-RAb 2.6 IU/L). Ultrasound showed a highly vascularized hypoechoic nodule (1.1 × 0.9 × 2 cm) in the right lobe, which projected onto a hot area detected in the 99mtechnetium thyroid nuclear scan. Overall uptake was increased (4.29%), while the left lobe showed lower tracer uptake with no visible background-activity, supporting the notion that both Graves’ disease and a toxic adenoma were present. After normal thyroid function was reinstalled with methimazole, the patient underwent thyroidectomy. Histological work up revealed a unifocal papillary microcarcinoma (9 mm, pT1a, R0), positively tested for the BRAF V600E mutation, embedded into the hyperfunctional nodular goiter.
Conclusions
Neither the finding of an autonomously functioning thyroid nodule nor the presence of Graves’ disease rule out papillary thyroid carcinoma.
doi:10.1186/1472-6823-13-16
PMCID: PMC3654942  PMID: 23657056
Toxic adenoma; Graves’ disease; Marine-Lenhart syndrome; Papillary carcinoma; Hyperthyroidism
6.  Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years 
Introduction:
Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up.
Patients and Methods:
A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (low Free thyroxine [FT4] and increased thyroid-stimulating hormone [TSH] levels >5 μIU/ml); subclinical hypothyroidism (normal FT4, TSH between 5 μIU/ml and 10 μIU/ml) and central (secondary) hypothyroidism (low FT4 and normal or decreased TSH).
Results:
A total of 48 patients (22 males and 26 females) completed a 12 year-period of follow-up. During this period, hypothyroidism was diagnosed in 17/48 (35%) of patients. There was no significant difference in the prevalence in males 7/22 (32%) versus females 10/26 (38%). Sixteen of the patients had hypothyroidism after the age of 10 years (94%). The prevalence of overt hypothyroidism had risen from 0% at the age of 7 years to 35% at the age of 18 years. None of the patients had high anti-thyroperoxidase antibody titers. Out of 17 patients, 13 patients with hypothyroidism had normal or low TSH level (not appropriately elevated) indicative of defective hypothalamic pituitary response to low FT4 (central hypothyroidism). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4). The general trend of FT4 level showed progressive decrease over the 12 years, whereas, TSH levels did not show a corresponding increase. These data suggested defective hypothalamic pituitary thyroid axis involving both TSH and FT4 sretion in patients with thalassemia major over time. There was a significant negative correlation between serum ferritin and FT4 (r = −0.39, P = 0.007), but no correlation was found between ferritin and TSH.
Conclusions:
Worsening of thyroid function was observed in 35% of the studied thalassemic patients by the age of 18 years. The lack of proper increase of TSH in response to the low circulating levels of FT4 in 13/17 (76%) of these patients indicates a relatively high incidence of defective pituitary thyrotrophic function in these patients.
doi:10.4103/2230-8210.122635
PMCID: PMC3872691  PMID: 24381890
Ferritin; free thyroxine; growth; hypothyroidism; prevalence; thalassemia; thyroid stimulating hormone
7.  What affects functional ovarian reserve, thyroid function or thyroid autoimmunity? 
Background
Thyroid dysfunction is the most common autoimmune endocrine disorder in women of reproductive age, and is associated with menstrual irregularities, anovulation and infertility. Whether it is thyroid function or thyroid autoimmunity that affects functional ovarian reserve (FOR, i.e., the small growing ovarian follicle pool) reflected in anti-Müllerian hormone (AMH) has, however, remained under dispute.
Methods
We investigated in 225 infertile women whether thyroid function, after adjustment for thyroid autoimmunity, affects FOR within what is considered normal thyroid function (TSH, 0.4–4.5μIU/mL) by assessing AMH levels in reference to TSH levels, stratified for TSH < or ≥3.0μIU/mL. Thyroid autoimmunity was defined by presence of anti-thyroid peroxidase, −thyroglobulin and/or -thyroid receptor antibodies.
Results
Mean age of studied women was 38.4 ± 5.0 years; their mean AMH was 1.3 ± 2.0 ng/mL and mean TSH 1.8 ± 0.9 μIU/mL. Thyroid autoimmunity was present in 11.1 % of patients. Women with TSH <3.0μIU/mL presented with significantly higher AMH compared to those with TSH ≥3.0μIU/Ml (P = 0.03). This difference remained significant after adjustment for thyroid autoimmunity as well as age (P = 0.02).
Conclusions
Even after adjustment for thyroid autoimmunity and age, TSH <3.0μIU/mL in euthyroid infertility patients is associated with significantly better FOR (higher AMH) than TSH ≥3.0μIU/mL. This observation suggests a direct beneficial effect of lower TSH levels on follicular recruitment, and warrants investigations of thyroxin supplementation in infertile women with TSH levels ≥3.0μIU/mL in attempts to improve FOR.
doi:10.1186/s12958-016-0162-0
PMCID: PMC4862175  PMID: 27165095
Thyroid stimulating hormone (TSH); Infertility; Ovarian reserve; Thyroid function; Thyroid autoimmunity; Anti-Müllerian hormone (AMH)
8.  Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population 
Journal of Korean Medical Science  2013;28(11):1622-1626.
Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 µIU/mL, free T4 < 1.09 ng/dL and Anti-TPO Ab > 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH.
doi:10.3346/jkms.2013.28.11.1622
PMCID: PMC3835504  PMID: 24265525
Subclinical Hypothyroidism; Natural History; Hypothyroidism
9.  The impact of thyroid function and thyroid autoimmunity on embryo quality in women with low functional ovarian reserve: a case-control study 
Background
Women with hyper-and hypothyroidism are at increased risk for infertility and adverse pregnancy outcomes. Whether in women considered euthyroid thyroid function (TSH values) and thyroid autoimmunity (thyroid antibodies) influence in vitro fertilization (IVF) cycle outcome has, however, remained controversial. Any such effect should be easily visible in women with low functional ovarian reserve (LFOR) and thus small oocyte and embryo numbers.
Methods
We evaluated the relationship between TSH levels and embryo quality in euthyroid women with LFOR undergoing IVF. Mean age for the study population was 39.9 ± 4.6 years. Embryo quality was assessed in 431 embryos from 98 first IVF cycles according to TSH levels (with cut-off 2.5μIU/mL), and to presence versus absence of thyroid autoantibodies.
Results
Mean Anti Mullerian hormone (AMH) was 0.8 ± 0.8 ng/mL and mean TSH was 1.8 ± 0.9 μIU/mL. Comparable embryo quality was observed in women with TSH ≤ and >2.5μIU/mL. TPO antibodies significantly affected embryo quality in women with low-normal TSH levels (P = 0.045). In women with high-normal TSH levels, increasing TSH had a negative impact on embryo quality (P = 0.027). A trend towards impaired embryo quality with TPO antibodies was also observed in these patients (p = 0.057).
Conclusions
TPO antibodies affect embryo quality in euthyroid women with low-normal TSH ≤2.5 μIU/mL. In women with high-normal TSH levels, increasing TSH levels, and possibly TPO antibodies, appear to impair embryo quality. These results suggest that the negative impact of thyroid autoimmunity becomes apparent, once thyroid hormone function is optimized.
doi:10.1186/s12958-015-0041-0
PMCID: PMC4443631  PMID: 25975563
Diminished Ovarian Reserve (DOR); Embryo quality; Euthyroid; In Vitro Fertilization (IVF); Low Functional Ovarian Reserve (LFOR); Thyroid autoimmunity; Thyroid Stimulating Hormone (TSH)
10.  Validation of a Decision Rule for Selective TSH Screening in Atrial Fibrillation 
Introduction
Atrial fibrillation (AF) is the most common cardiac dysrhythmia. Current guidelines recommend obtaining thyroid-stimulating hormone (TSH) levels in all patients presenting with AF. Our aim was to investigate the utility of TSH levels for emergency department (ED) patients with a final diagnosis of AF while externally validating and potentially refining a clinical decision rule that recommends obtaining TSH levels only in patients with previous stroke, hypertension, or thyroid disease.
Methods
We conducted a retrospective, cross-sectional study of consecutive patients who presented to an ED from January 2011 to March 2014 with a final ED diagnosis of AF. Charts were reviewed for historical features and TSH level. We assessed the sensitivity and specificity of the previously derived clinical decision rule.
Results
Of the 1,964 patients who were eligible, 1,458 (74%) had a TSH level available for analysis. The overall prevalence of a low TSH (<0.3μIU/mL) was 2% (n=36). Elevated TSH levels (>5μIU/mL) were identified in 11% (n=159). The clinical decision rule had a sensitivity of 88.9% (95% CI [73.0–96.4]) and a specificity of 27.5% (95% CI [25.2–29.9]) for identifying a low TSH. When analyzed for its ability to identify any abnormal TSH values (high or low TSH), the sensitivity and specificity were 74.4% (95% CI [67.5–80.2]) and 27.3% (95% CI [24.9–29.9]), respectively.
Conclusion
Low TSH in patients presenting to the ED with a final diagnosis of AF is rare (2%). The sensitivity of a clinical decision rule including a history of thyroid disease, hypertension, or stroke for identifying low TSH levels in patients presenting to the ED with a final diagnosis of atrial fibrillation was lower than originally reported (88.9% vs. 93%). When elevated TSH levels were included as an outcome, the sensitivity was reduced to 74.4%. We recommend that emergency medicine providers not routinely order TSH levels for all patients with a primary diagnosis of AF. Instead, these investigations can be limited to patients with new onset AF or those with a history of thyroid disease with no known TSH level within three months.
doi:10.5811/westjem.2014.11.23490
PMCID: PMC4307717  PMID: 25671041
11.  Metabolic Clearance and Production Rates of Human Thyrotropin 
Journal of Clinical Investigation  1974;53(3):895-903.
Metabolic clearance (MCR) and production rates (PR) of human thyrotropin (hTSH) were determined by the constant infusion to equilibrium method 57 times in 55 patients. 16 control patients had a mean hTSH MCR of 50.7 ml/min. The mean hTSH MCR was significantly (P < 0.02) higher in 19 euthyroid men (51.6 ml/min) than in 12 euthyroid women (43.0 ml/min), but this apparent sex difference disappeared when the MCR were corrected for surface area, 25.8 (men) versus 25.2 ml/min per m2 (women). Hypothyroid patients had significantly (P < 0.005) lower hTSH MCR (30.9 ml/min), and hyperthyroid patients had significantly (P < 0.05) higher hTSH MCR (60.9 ml/min) than controls. The hTSH MCR in patients with “decreased thyroid reserve” (40.9 ml/min), hyperfunctioning thyroid nodule (53.8 ml/min), and “empty sella syndrome” (46.6 ml/min) were not significantly different from controls. The mean hTSH PR in controls (104.3 mU/day) was significantly (P < 0.005) different from that in patients with “decreased thyroid reserve” (956 mU/day), hypothyroidism (4,440 mU/day), hyperthyroidism (< 43.9 mU/day) and a hyperfunctioning thyroid nodule (< 38.7 mU/day). In primary hypothyroidism intravenous triiodothyronine therapy (50 μg/day) for 10 days decreased the hTSH PR (from 4,244 to 2,461 mU/day) before changes in the hTSH MCR (from 33.1 to 33.7 mU/day) were observed.
These studies have demonstrated that changes in the serum concentration of hTSH are mainly due to altered pituitary hTSH secretion with only a minor contribution from the change in hTSH MCR.
PMCID: PMC333072  PMID: 4812446
12.  Level of Thyroid-Stimulating Hormone (TSH) in Patients with Acute Schizophrenia, Unipolar Depression or Bipolar Disorder 
Neurochemical Research  2014;39(7):1245-1253.
The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1 %; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9–22.3 % for schizophrenia, 13.9–26.0 % for unipolar depression, 10.8–27.6 % for bipolar disorder, 12.2–28.5 % for bipolar depression, and 11.4–24.5 % for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = − 0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = − 0.21, p < 0.001), unipolar depression (r = − 0.23, p < 0.001), bipolar depression (r = − 0.25, p = 0.002) and bipolar disorder (r = − 0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.
doi:10.1007/s11064-014-1305-3
PMCID: PMC4103998  PMID: 24723220
Thyroid-stimulating hormone; Schizophrenia; Depression; Bipolar disorder
13.  Thyroid Function in Heart Failure and Impact on Mortality 
JACC. Heart failure  2013;1(1):48-55.
Objectives
The aim of this study was to investigate whether patients with systolic heart failure (HF) and abnormal thyroid function are at increased risk for death.
Background
Thyroid hormone homeostasis is vital to the optimal functioning of the cardiovascular system, but an independent prognostic effect of thyroid abnormalities in patients with HF has not been established.
Methods
In SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), which randomized patients with ischemic or nonischemic HF to placebo or amiodarone or implantable cardioverter-defibrillator therapy, thyroid-stimulating hormone (TSH) was measured at baseline and at 6-month intervals throughout the 5-year study.
Results
Of 2,225 patients, the majority (87%) had normal TSH levels (0.3 to 5.0 μU/ml) at baseline, 12% had values suggestive of hypothyroidism, and 1% had values consistent with hyperthyroidism. Compared with euthyroid patients, those hypothyroid at baseline were older and included more women and Caucasians (all p values <0.05). Over the median follow-up period of 45.5 months, among patients euthyroid at baseline, 89 developed abnormally low TSH levels, and 341 developed abnormally high values. Patients randomized to amiodarone (median dose 300 mg) had an elevated risk for developing abnormal TSH levels compared with implantable cardioverter-defibrillator therapy or placebo (p < 0.0001). Patients with baseline or new-onset abnormal thyroid function had a higher mortality than those with normal thyroid function, even after controlling for other known mortality predictors (hazard ratio: 1.58; 95% confidence interval: 1.29 to 1.94; p < 0.0001 for hypothyroid; hazard ratio: 1.85; 95% confidence interval: 1.21 to 2.83; p = 0.0048 for hyperthyroid). Implantable cardioverter-defibrillator benefit did not vary with thyroid function.
Conclusions
Abnormal thyroid function in patients with symptomatic HF and ejection fractions ≤35% is associated with significantly increased risk for death, even after controlling for known mortality predictors. (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609)
doi:10.1016/j.jchf.2012.10.004
PMCID: PMC3803999  PMID: 24159562
amiodarone; heart failure; ICD; thyroid disease
14.  Suppression of Pituitary TSH Secretion in the Patient with a Hyperfunctioning Thyroid Nodule 
Journal of Clinical Investigation  1973;52(11):2783-2792.
10 patients with a single hyperfunctioning thyroid nodule each were studied for pituitary thyrotropin (TSH) suppression. They were judged to be euthyroid on clinical grounds. The total thyroxine (T4D), free thyroxine (FT4), total triiodothyronine (T3D), and free triiodothyronine (FT3) were normal in most of the patients. Incorporation of 131I into the hyperfunctioning thyroid nodules was not suppressed by the administration of physiological doses of T3. Basal serum TSH concentrations were undetectable (<0.5 - 1.0 μU/ml) in all patients. The metabolic clearance of TSH in one patient before and after excision of the thyroid nodule was unchanged (40 vs. 42 ml/min) whereas the calculated production rate was undetectable before the operation (<29 mU/day) and normal after (103 mU/day). These data, in one patient, suggest that the undetectable concentration of TSH in these patients is a result of suppressed TSH secretion rather than accelerated TSH clearance.
In eight patients, basal serum TSH concentrations failed to increase after the intravenous administration of 200 μg of thyrotropin-releasing hormone (TRH); minimal increases in serum TSH concentrations were observed in two patients. The suppression of TSH was evident despite “normal” concentrations of circulating thyroid hormones. The observation that normal serum concentrations of T4D, FT4, T3D, and FT3 may be associated with undetectable basal serum TSH concentrations and suppressed TSH response to TRH was also found in four hypothyroid patients given increasing doses of L-thyroxine and sequential TRH stimulation tests.
Images
PMCID: PMC302546  PMID: 4201265
15.  Patterns of thyroid hormone levels in pediatric medullary thyroid carcinoma patients on vandetanib therapy 
Background
Tyrosine kinase inhibitors (TKIs) have been associated with elevated TSH as a drug class effect. Prior studies of vandetanib in adults with medullary thyroid carcinoma (MTC) described an increase in levothyroxine (LT) requirement. We studied TSH, free T4, and LT dosing in children and adolescents enrolled in the phase I/II trial of vandetanib for medullary thyroid cancer (MTC)
Methods
Data from 13 patients with multiple endocrine neoplasia type 2B (MEN 2B) and MTC were analyzed [6 M, 7 F, median age 13.0 y (9.1-17.3)] Eleven patients (85%) had undergone prior thyroidectomy and all received single-drug therapy with vandetanib for > 6 months. Confirmed compliance with vandetanib (67–150 mg/m2/day) and LT was a necessary inclusion criterion.
Results
While on vandetanib treatment, all 11 athyerotic patients exhibited significantly increased TSH levels. The baseline TSH level was 4.37 mclU/ml (0.08 - 23.30); in comparison, the first peak TSH concentration on vandetanib was 15.70 mclU/ml (12.50 - 137.00, p = 0.0010). The median time to reach the initial peak of elevated TSH was 1.8 months (0.3 - 9.3). Free T4 levels remained within the normal reference range. An increase from a baseline LT dose of 91 mcg/m2/day (±24) to 116 mcg/m2/day (±24) was required in order to resume normative TSH levels (p = 0.00005), equal to an increase of 36.6% (±16.56) in the dosage of LT in mcg/day. For the 2 patients with intact thyroid glands, free T4 and TSH remained normal over a combined 6 patient years of follow up.
Conclusions
In our cohort of pediatric MTC patients, athyreotic patients with preexisting hypothyroidism developed increased TSH and reduced free T4 during the first few months of treatment with vandetanib, necessitating an increase in LT dosage. Additional patients with normal thyroid function before treatment and intact glands (n = 2) maintained normal thyroid function tests during treatment. Elevated TSH in athyreotic patients may be due to an indirect effect of vandetanib on the metabolism of thyroid hormone, or to altered TSH sensitivity at the pituitary. Proper recognition and management of abnormal thyroid hormone levels is critical in growing children on TKIs.
Trial registration
ClinicalTrials.gov Identifier: NCT00514046
doi:10.1186/1687-9856-2015-3
PMCID: PMC4429462  PMID: 25972901
Multiple Endocrine Neoplasia type 2 B (MEN2B); Medullary thyroid carcinoma (MTC); Tyrosine kinase inhibitor (TKIs); Vandetanib
16.  Percutaneous Ethanol Sclerotherapy of Symptomatic Nodules Is Effective and Safe in Pregnant Women: A Study of 13 Patients with an Average Follow-Up of 6.8 Years 
Background. Because of the increased risk of surgery, thyroid nodules causing compression signs and/or hyperthyroidism are concerning during pregnancy. Patients and Methods. Six patients with nontoxic cystic, four with nontoxic solid, and three with overt hyperthyroidism caused by toxic nodules were treated with percutaneous ethanol injection therapy (PEI). An average of 0.68 mL ethanol per 1 mL nodule volume was administered. Mean number of PEI treatments for patients was 2.9. Success was defined as the shrinkage of the nodule by more than 50% of the pretreatment volume (V0) and the normalization of TSH and FT4 levels. The average V0 was 15.3 mL. Short-term success was measured prior to labor, whereas long-term success was determined during the final follow-up (an average of 6.8 years). Results. The pressure symptoms decreased in all but one patient after PEI and did not worsen until delivery. The PEI was successful in 11 (85%) and 7 (54%) patients at short-term and long-term follow-up, respectively. Three patients underwent repeat PEI which was successful in 2 patients. Conclusions. PEI is a safe tool and seems to have good short-term results in treating selected symptomatic pregnant patients. Long-term success may require repeat PEI.
doi:10.1155/2015/765950
PMCID: PMC4677206  PMID: 26697066
17.  Comparison of Therapeutic Efficacy and Clinical Parameters Between Recombinant Human Thyroid Stimulating Hormone and Thyroid Hormone Withdrawal in High-Dose Radioiodine Treatment with Differentiated Thyroid Cancer 
Purpose
High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer.
Methods
We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups.
Results
The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change of body mass index was 0.4 (±0.7) kg/m2 in the THW group and was decreased by −0.6 (±0.6) kg/m2 in the rh-TSH group.
Conclusions
Consistent with previous studies, the rates of complete ablation between the THW and rh-TSH groups were not significantly different. The clinical parameters, as we mentioned above, were elevated for THW group but were irrelevant for the rh-TSH group. The findings favor HD-RIT after rh-TSH, especially for patients with chronic liver and kidney disease.
doi:10.1007/s13139-014-0308-y
PMCID: PMC4463877  PMID: 26085856
Thyroid cancer; High-dose radioiodine therapy; Recombinant human TSH; Thyroid hormone withdrawal; Complete ablation rate; Liver function; Kidney function
18.  Variable Thyrotropin Response to Thyrotropin-releasing Hormone after Small Decreases in Plasma Free Thyroid Hormone Concentrations in Patients with Nonthyroidal Diseases 
Journal of Clinical Investigation  1980;66(3):451-456.
Although a normal serum thyrotropin (TSH) concentration is generally considered to be the most important finding to support the clinical impression of euthyroidism in patients with nonthyroidal diseases and decreased serum triiodothyronine (T3), the regulation of TSH secretion in sick patients has not been studied previously. Accordingly, we studied the regulation of TSH secretion in 23 patients with nonthyroidal diseases; 15 of the patients had decreased serum T3. TSH regulation was studied by measuring the TSH response to injected thyrotropin-releasing hormone (TRH) before and after effecting a small decrease in serum thyroxine (T4) and/or T3 concentrations by iodide treatment, 262 mg daily for 10 d. Iodide treatment significantly decreased (> 10%) the free T4 index (FT4-I) and/or free T3 index (FT3-I) in all patients. FT4-I values were correlated (0.611, P < 0.001), with free T4 concentration determined by equilibrium dialysis. Despite decreased FT4-I and/or FT3-I after iodide treatment in all patients, the TSH response to TRH after iodide treatment was augmented in only 8 of 15 patients who had decreased serum T3 (group 1) and in only 5 of 8 patients who had a normal serum T3. Mean base-line TSH concentration was increased significantly (P < 0.05) from 0.9±0.1 to 1.5±0.3 μU/ml in group 1 only. Comparison of the mean TSH response to TRH showed that there was no significant difference between groups 1 and 2. Moreover, no significant difference in thyroidal parameters was observed between patients who had augmented TSH response to TRH after iodides and those who had either similar or decreased TSH response irrespective of the initial serum T3. These studies show that an augmented TSH response to TRH in response to a small reduction in serum T4 and T3 concentration occurred in only 57% of the entire group of patients with nonthyroidal diseases and that the presence or absence of a normal TSH response to this stimulus did not seem to be related to the base-line serum T3 concentration. Because an increase in serum TSH in response to decreased serum T4 and T3 did not occur in about one-half of patients with nonthyroidal diseases, normal serum TSH may not be a reliable index of the euthyroid state in these patients.
PMCID: PMC371672  PMID: 6772675
19.  Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L 
Obstetrics & Gynecology Science  2014;57(6):507-512.
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 µg 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.
doi:10.5468/ogs.2014.57.6.507
PMCID: PMC4245345  PMID: 25469340
Infertility; Ovulatory disorder; Subclinical hypothyroidism; Thyrotropin-releasing hormone stimulating test
20.  Endogenous Thyrotropin and Triiodothyronine Concentrations in Individuals with Thyroid Cancer 
Thyroid  2008;18(9):943-952.
Background
Thyroid hormone suppression therapy is associated with decreased recurrence rates and improved survival in patients with differentiated thyroid cancer. Recently higher baseline thyrotropin (TSH) levels have been found to be associated with a postoperative diagnosis of differentiated thyroid cancer. Our objective was to confirm whether preoperative TSH levels were higher in patients who were diagnosed with differentiated thyroid cancer after undergoing thyroidectomy, compared with patients who were found to have benign disease. We also sought to determine whether thyroid hormone levels were lower in the patients with malignancy.
Methods
The study was a retrospective analysis of a prospective study. The study setting was the General Clinical Research Center of an Academic Medical Center. Participants were 50 euthyroid patients undergoing thyroidectomy. Thyroxine, triiodothyronine (T3), and TSH levels were documented in patients prior to their scheduled thyroidectomy. Following thyroidectomy, patients were divided into those with a histologic diagnosis of either differentiated thyroid cancer or benign disease. Preoperative thyroid profiles were correlated with patients' postoperative diagnoses.
Results
All patients had a normal serum TSH concentration preoperatively. One-third of the group was diagnosed with thyroid cancer as a result of their thyroidectomy. These patients had a higher serum TSH level (mean = 1.50 mIU/L, CI 1.22–1.78 mIU/L) than patients with benign disease (mean = 1.01 mIU/mL, CI 0.84–1.18 mIU/L). There was a greater risk of having thyroid cancer in patients with TSH levels in the upper three quartiles of TSH values, compared with patients with TSH concentrations in the lowest quartile of TSH values (odd ratio = 8.7, CI 2.2–33.7). Patients with a thyroid cancer diagnosis also had lower T3 concentrations measured by liquid chromatography tandem mass spectrometry (mean = 112.6 ng/dL, CI 103.8–121.4 ng/dL) than did patients with a benign diagnosis (mean 129.9 ng/dL, CI 121.4–138.4 ng/dL).
Conclusion
These data confirm that higher TSH concentrations, even within the normal range, are associated with a subsequent diagnosis of thyroid cancer in individuals with thyroid abnormalities. This further supports the hypothesis that TSH stimulates the growth or development of thyroid malignancy during its early or preclinical phase. We also show for the first time that patients with thyroid cancer also have lower T3 levels than patients with benign disease.
doi:10.1089/thy.2008.0061
PMCID: PMC2879493  PMID: 18788918
21.  Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect—Results of an Observational Study 
Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3–11.8) to 2 (1.3–3) (p < 0.01) and fT3 decreased from 3.85 (3.5–4.78) to 3.45 (3.3–3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%–6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones.
doi:10.1155/2016/2541912
PMCID: PMC4756131  PMID: 26955394
22.  Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH". 
Journal of Clinical Investigation  1975;56(3):633-642.
An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed.
PMCID: PMC301911  PMID: 1159077
23.  Screening Strategies for Thyroid Disorders in the First and Second Trimester of Pregnancy in China 
PLoS ONE  2014;9(6):e99611.
Background
Thyroid dysfunction during pregnancy is associated with multiple adverse outcomes, but whether all women should be screened for thyroid disorders during pregnancy remains controversial.
Objective
To evaluate the effectiveness of the targeted high risk case-finding approach for identifying women with thyroid dysfunction during the first and second trimesters of pregnancy.
Methods
Levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOAb) were measured in 3882 Chinese women during the first and second trimester of pregnancy. All tested women were divided into the high risk or non-high risk groups, based on their history, findings from physical examination, or other clinical features suggestive of a thyroid disorder. Diagnosis of thyroid disorders was made according to the standard trimester-specific reference intervals. The prevalence of thyroid disorders in each group was determined, and the feasibility of a screening approach focusing exclusively on high risk women was evaluated to estimate the ability of finding women with thyroid dysfunction.
Results
The prevalence of overt hypothyroidism or hyperthyroidism in the high risk group was higher than in the non-high risk group during the first trimester (0.8% vs 0, χ2 = 7.10, p = 0.008; 1.6% vs 0.2%, χ2 = 7.02, p = 0.008, respectively). The prevalence of hypothyroxinemia or TPOAb positivity was significantly higher in the high risk group than in the non-high risk group during the second trimester (1.3% vs 0.5%, χ2 = 4.49, p = 0.034; 11.6% vs 8.4%, χ2 = 6.396, p = 0.011, respectively). The total prevalence of hypothyroidism or hyperthyroidism and the prevalence of subclinical hypothyroidism or hyperthyroidism were not statistically different between the high risk and non-high risk groups, for either the first or second trimester.
Conclusion
The high risk screening strategy failed to detect the majority of pregnant women with thyroid disorders. Therefore, we recommend universal screening of sTSH, FT4, and TPOAb during the first trimester and second trimester of pregnancy.
doi:10.1371/journal.pone.0099611
PMCID: PMC4055732  PMID: 24925135
24.  Management of Subclinical Hyperthyroidism 
The ideal approach for adequate management of subclinical hyperthyroidism (low levels of thyroid-stimulating hormone [TSH] and normal thyroid hormone level) is a matter of intense debate among endocrinologists. The prevalence of low serum TSH levels ranges between 0.5% in children and 15% in the elderly population. Mild subclinical hyperthyroidism is more common than severe subclinical hyperthyroidism. Transient suppression of TSH secretion may occur because of several reasons; thus, corroboration of results from different assessments is essential in such cases. During differential diagnosis of hyperthyroidism, pituitary or hypothalamic disease, euthyroid sick syndrome, and drug-mediated suppression of TSH must be ruled out. A low plasma TSH value is also typically seen in the first trimester of gestation. Factitial or iatrogenic TSH inhibition caused by excessive intake of levothyroxine should be excluded by checking the patient’s medication history. If these nonthyroidal causes are ruled out during differential diagnosis, either transient or long-term endogenous thyroid hormone excess, usually caused by Graves’ disease or nodular goiter, should be considered as the cause of low circulating TSH levels.
We recommend the following 6-step process for the assessment and treatment of this common hormonal disorder: 1) confirmation, 2) evaluation of severity, 3) investigation of the cause, 4) assessment of potential complications, 5) evaluation of the necessity of treatment, and 6) if necessary, selection of the most appropriate treatment.
In conclusion, management of subclinical hyperthyroidism merits careful monitoring through regular assessment of thyroid function. Treatment is mandatory in older patients (> 65 years) or in presence of comorbidities (such as osteoporosis and atrial fibrillation).
doi:10.5812/ijem.3447
PMCID: PMC3693616  PMID: 23843809
Hyperthyroidism; Disease Management; Therapeutics; Graves’ Disease
25.  Limited adequacy of thyroid cancer patient follow-up at a Canadian tertiary care centre 
Canadian Journal of Surgery  2013;56(6):385-392.
Background
We sought to evaluate the adequacy of follow-up of thyroid cancer patients at a Canadian centre.
Methods
We mailed a survey to the family physicians of thyroid cancer patients and analyzed the findings relative to follow-up guidelines published by the American Thyroid Association (ATA). Statistical significance between early and late follow-up patterns was analyzed using the χ2 test.
Results
Our survey response rate was 56.2% (91 of 162). The time from operation ranged from 1.24–7.13 (mean 3.96) years, and 87.9% of patients had undergone a physical exam within the previous year. Only 37.4% and 14% of patients had a serum thyroglobulin measurement within 6 and between 6 and 12 months before the survey, respectively. Thyroid simulating hormone (TSH) levels were measured within the prior 6 months in 67% of patients and between 6 and 12 months in 13.2%. The TSH levels were suppressed (< 0.1 μIU/L) in 24.2% of patients, 0.1–2 μIU/L in 44% and greater than 2 μIU/L in 17.6%. Ultrasonography was the most common imaging test performed.
Conclusion
There is significant variation in the follow-up patterns of patients with thyroid cancer, and there is considerable deviation from current ATA guidelines.
doi:10.1503/cjs.018112
PMCID: PMC3859780  PMID: 24284145

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