THYROID FUNCTION TESTS: A REVIEW

Thyroid function tests are one of the most common endocrine panels in general practice because a good understanding of when to order them, indications for treatment are important for the optimal treatment of thyroid dysfunction. Thyroid-stimulating hormone (TSH) should be the rst test to be performed on any patient with suspected thyroid dysfunction and in follow-up of individuals on treatment. It is useful as a rst-line test because even small changes in thyroid function are sufcient to cause a signicant increase in TSH secretion. Thyroxine levels may be assessed in a patient with hyperthyroidism, to determine the severity of hyperthyroxinemia. Antithyroid peroxidase measurements should be considered while evaluating patients with subclinical hypothyroidism and can facilitate the identication of autoimmune thyroiditis during the evaluation of nodular thyroid disease. The measurement of TSH receptor antibody must be considered when conrmation of Graves’ disease is needed and radioactive iodine uptake cannot be done.

Thyreotroop adenoom van de hypofyse: een zeldzame oorzaak van hyperthyreoïdie

TSH-secreting pituitary adenoma: a rare cause of hyperthyroidism Central hyperthyroidism is noted in a 35-year-old man with recurrent panic attacks. Thyroid-stimulating hormone-secreting pituitary adenoma (TSH-secreting adenoma) is found to be the underlying etiology. A pituitary adenomectomy is carried out, with regression of the symptoms and hyperthyroidism. TSH-secreting adenomas are rare and cause hyperthyroidism due to autonomous TSH secretion. In addition to hyperthyroidism, dysfunction of other pituitary axes and neurological problems due to local compression may also be present. Biochemically, TSH adenoma is characterized by elevated levels of thyroid hormones without suppression of the TSH concentration. After analytical interference has been ruled out, additional biochemical and radiological investigations are necessary in the differential diagnosis and to establish diagnostic certainty. Neurosurgical resection is the cornerstone of the treatment, although radiotherapy and somatostatin analogs may also be considered.

The Effect of Thyrotropin-Releasing Hormone and Antithyroid Drugs on Fetal Thyroid Function

A euthyroid pregnant woman will normally have a fetus that displays normal fetal development. However, studies have long demonstrated the role of T3 (Triiodothyronine), T4 (Thyroxine), and TSH (Thyroid Stimulating Hormone) and their degree of penetrability into the fetal circulation. Maternal thyrotropin-releasing hormone (TRH) crosses the placental site and, from mid-gestation onward, is able to promote fetal TSH secretion. Its origin is not only hypothalamic, as was believed until recently. The maternal pancreas, and other extraneural and extrahypothalamic organs, can produce TRH variants, which are transported through the placenta affecting, to a degree, fetal thyroid function. Antithyroid drugs (ATDs) also cross the placenta and, because of their therapeutic actions, can affect fetal thyroid development, leading in some cases to adverse outcomes. Furthermore, there are a number of TRH analogues that share the same properties as the endogenous hormone. Thus, in this narrative review, we highlight the interaction of all the above with fetal growth in uncomplicated pregnancies.

The spectrum of thyroid function tests during hospitalization for SARS COV-2 infection

Objective Alterations in thyroid function tests (TFTs) have been recorded during SARS-CoV-2 infection as associated to either a destructive thyroiditis or a non-thyroidal illness. Methods We studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units. Those with previous thyroid dysfunctions or taking interfering drugs were excluded. Differently from previous reports, TSH, FT3, FT4, thyroglobulin (Tg), anti-Tg autoantibodies (TgAb) were measured at baseline and every 3–7 days. C-reacting protein (CRP), cortisol and IL-6 were also assayed. Results The majority of patients had a normal TSH at admission, usually with normal FT4 and FT3. Low TSH levels were found either at admission or during hospitalization in 39% of patients, associated with low FT3 in half of the cases. FT4 and Tg levels were normal, and TgAb-negative. TSH and FT3 were invariably restored at the time of discharge in survivors, whereas were permanently low in most deceased cases, but only FT3 levels were predictors of mortality. Cortisol, CRP and IL-6 levels were higher in patients with low TSH and FT3 levels. Conclusions Almost half of our COVID-19 patients without interfering drugs had normal TFTs both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels, inversely correlated with CRP, cortisol and IL-6 and associated with normal Tg levels, is likely due to the cytokine storm induced by SARS-Cov-2 with a direct or mediated impact on TSH secretion and deiodinase activity, and likely not to a destructive thyroiditis.

Elevated thyroid-stimulating hormone is associated with poor sleep: a cross-sectional and longitudinal study

Purpose Poor sleep and the accompanying TSH (Thyroid Stimulating Hormone) elevation are not uncommon since TSH secretion is controlled by the circadian rhythm. However, the true relationship between poor sleep and TSH elevation is unclear, and hence we aimed to elucidate this association by cross-sectional and longitudinal studies. Methods Participants with isolated elevated and normal TSH concentration were recruited, and the Pittsburgh Sleep Quality Index (PQSI) was used to assess sleep status. The patients with isolated TSH elevation were followed up longitudinally, and TSH levels were remeasured when sleep status improved. Results The proportion of poor sleep and occasional poor sleep among subjects with isolated TSH elevation was significantly higher than that in subjects with normal TSH (70.24% vs. 49.58%, p = 0.001; 9.52% vs. 1.68%, p = 0.006), and the ratio of good sleep was obviously decreased in subjects with isolated TSH elevation than normal TSH (20.24% vs. 48.74%, p < 0.001). Patients with isolated TSH elevation had significantly higher PSQI scores in the subjective sleep quality, sleep latency, sleep duration, and habitual sleep efficiency dimensions than subjects with normal TSH (all p < 0.05). In the follow-up study, among patients with isolated TSH elevation at baseline, the ratio of TSH normalization in patients who slept better was significantly higher than that in patients who still slept poorly (85.42% vs. 6.45%, p < 0.001). Conclusion This study revealed isolated elevated TSH concentrations tends to normalize when sleep status improves, and we recommend that clinicians inquire about sleep status thoroughly and reexamine thyroid hormone levels when sleep status improves.

Suppression of thyrotropin secretion during roxadustat treatment for renal anemia in a patient undergoing hemodialysis

Background Inhibition of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) is a novel choice for the treatment of renal anemia, and an oral HIF-PH inhibitor roxadustat was approved for renal anemia. Roxadustat has high affinity to thyroid hormone receptor beta, which may affect thyroid hormone homeostasis. Case presentation We present here a patient undergoing hemodialysis with primary hypothyroidism receiving levothyroxine replacement, who showed decreased free thyroxine (FT4) and thyroid stimulating hormone (TSH) after starting roxadustat. Pituitary stimulation test revealed selective suppression of TSH secretion. Recovery of TSH and FT4 levels after stopping roxadustat suggested the suppression of TSH was reversible. Conclusions Physicians should pay special attention to thyroid hormone abnormalities in treatment with roxadustat.

An undiagnosed TSH-secreting pituitary macroadenoma found during pregnancy

Summary Thyroid stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is an uncommon cause of thyrotoxicosis, and is even rarer when found during pregnancy. Our patient presented with thyrotoxicosis accompanied by an inappropriately normal TSH level at 10 weeks of gestation during work-up of surgical termination of pregnancy (STOP). Subsequent investigations performed after STOP confirmed the presence of a TSH-secreting pituitary macroadenoma. She was initially treated with anti-thyroid drugs for biochemical control, followed by trans-sphenoidal surgery after STOP had been performed. Her thyroid function completely normalized after the trans-sphenoidal surgery. Our case illustrated the importance of recognizing the syndrome of inappropriate TSH secretion and highlighted several pregnancy-related aspects in the diagnosis and management of TSHoma during pregnancy. Learning points: This case report illustrates the need to raise awareness in recognizing the syndrome of inappropriate TSH secretion. Illustrate the different hormone tests available for reaching the diagnosis of TSH-secreting pituitary adenoma. Highlight the physiological changes in the thyroid status during pregnancy and the importance of using trimester-specific reference ranges for assessment of thyroid function during pregnancy. Describe the challenges in the management of TSH-secreting pituitary adenoma during pregnancy.

Central TSH Dysregulation in a Patient with Familial Non-Autoimmune Autosomal Dominant Hyperthyroidism Due to a Novel Thyroid-Stimulating Hormone Receptor Disease-Causing Variant

Background and Objectives. Familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) is a rare cause of childhood hyperthyroidism. It is caused by the thyroid-stimulating hormone receptor (TSHR) gene variants. So far, only around 40 families with FNAH have been reported. Patients with activating TSHR variants demonstrated the same classical signs and symptoms of hyperthyroidism as seen in patients with Graves’ disease. Since 2012, ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences. Case Presentation. We presented a young adult male patient with a novel heterozygous TSHR disease-causing variant p.Arg418Lys (c.1253G>A) in the exon 10, who presented with a mild but progressive FNAH, with a follow-up since infancy. Discussion. Constantly suppressed TSH, including during the euthyreosis in childhood and hypothyreosis after iodine ablation therapy, suggested central dysregulation of the TSH secretion.

Low TSH Is Associated With Frailty in an Older Veteran Population Independent of Other Thyroid Function Tests

Low TSH is associated with frailty in the older adult. We studied whether low TSH is an independent marker of frailty or is an indicator of subclinical hyperthyroidism, which in turn predicts frailty. Of outpatient veterans seen between January 2005 and December 2016, we identified 100 patients aged ≥60 years with two low TSH (<0.5 µIU/ml) and one fT3 measurement and 50 matched controls (TSH 0.5–5.0 µIU/ml). We used a deficit accumulation approach to create a frailty index (FI). The higher the FI, the more likely (p<0.001) that patients had expired. Patients with low (0.31 ± 0.11 µIU/mL) versus normal (1.84 ± 0.84 µIU/mL) TSH had higher mean FI compared to controls (0.25 ± 0.12 vs. 0.15 ± 0.07, p < .001). Low TSH was significantly associated with frailty ( p < .001), independent of age. However, lower TSH was not associated with higher fT3 or fT4 levels. There was a nonsignificant inverse association of fT3 levels with FI ( p = .13), which disappeared when adjusted for age. Similar to prior studies, low TSH was associated with frailty. However, neither fT3 nor fT4 predicted low TSH or FI, suggesting that the association of low TSH with frailty is not due to subclinical hyperthyroidism, but perhaps to effects of comorbidities on TSH secretion.

Adenoma hipofisário secretor de TSH: uma revisão sistemática / TSH-secreting pituitary adenoma: a systematic review

Introdução: Os adenomas hipofisários são tumores caracterizados pela proliferação de células adeno-hipofisárias produtoras de hormônios tróficos. Dentre eles, os adenomas hipofisários produtores de TSH (TSHomas), neoplasias benignas pouco frequentes, que correspondem a menos do que 3% dos adenomas hipofisários. Método: Pesquisamos os termos TSHomas, tireotropinomas e adenomas pituitários secretores de TSH nas bases Pubmed, Lilacs e Scielo. Incluímos artigos publicados entre 2010 e 2020, sendo excluídos relatos de casos, artigos indisponíveis e que não tratavam sobre o tema. Resultados e discussão: Os TSHomas são tumores fibrosos, monoclonais, com incidência entre 0,015 a 0,03 casos/100.000 habitantes, que se manifestam por hipertireoidismo e sintomas causados por efeito de massa. São diagnosticados diante da elevação de TSH juntamente a hormônios tireoidianos, na presença de alterações neurorradiológicas. O tratamento de primeira escolha consiste na neurocirurgia transesfenoidal, sendo os análogos de somatostatina e a radioterapia alternativas para o manejo de pacientes em que a intervenção cirúrgica é desaconselhada. Conclusão: Os TSHomas são raros, contudo, precisam ser investigados diante da secreção inadequada de TSH.Palavras chave: Adenoma, Hormônios tireoidianos, Neoplasias hipofisárias, Síndrome da secreção inadequada de TSH, Hipertireoidismo centralABSTRACTIntroduction: Pituitary adenomas are tumors characterized by the proliferation of adenohypophysis cells that produce trophic hormones. Among them, TSH-producing pituitary adenomas (TSHomas), uncommon benign neoplasms, whichcorrespond to less than 3% of pituitary adenomas. Method: We searched for the terms TSHomas, thyrotropinomas and pituitary adenomas secreting TSH in the Pubmed, Lilacs and Scielo databases. We included articles published between 2010 and 2020, excluding case reports, articles that were unavailable and did not deal with the topic. Results and discussion: TSHomas are fibrous, monoclonal tumors, with an incidence of 0.015 to 0.03 cases / 100,000 inhabitants, which are manifested by hyperthyroidism and symptoms caused by a mass effect. They are diagnosed with elevated TSH along with thyroid hormones, in the presence of neuroradiological changes. The first-choice treatment consists of transsphenoidal neurosurgery, with somatostatin analogs and radiotherapy being alternatives for the management of patients in whom surgical intervention is not recommended. Conclusion: TSHomas are rare, however, they need to be investigated due to inadequate TSH secretion.Keywords: Adenoma, Thyroid hormones, Pituitary neoplasms, Inappropriate TSH secretion syndrome, Central hypothyroidism