Thyroid testing paradigm switch from thyrotropin to thyroid hormones—Future directions and opportunities in clinical medicine and research

Purpose Recently published papers have demonstrated that particularly in untreated individuals, clinical parameters more often associate with thyroid hormone, particularly free thyroxine (FT4), levels than with thyrotropin (TSH) levels. Clinical and research assessments of the thyroid state of peripheral tissues would therefore be more precise if they were based on FT4 levels rather than on TSH levels. In this paper we describe implications of, and opportunities provided by, this discovery. Conclusions The FT4 level may be the best single test of thyroid function. The addition of free triiodothyronine (FT3) and TSH levels would further enhance test sensitivity and distinguish primary from secondary thyroid dysfunction respectively. There are opportunities to reconsider testing algorithms. Additional potential thyroidology research subjects include the peripheral differences between circulating FT4 and FT3 action, and outcomes in patients on thyroid replacement therapy in terms of thyroid hormone levels. Previously performed negative studies of therapy for subclinical thyroid dysfunction could be repeated using thyroid hormone levels rather than TSH levels for subject selection and the monitoring of treatment. Studies of outcomes in older individuals with treatment of high normal FT4 levels, and pregnant women with borderline high or low FT4 levels would appear to be the most likely to show positive results. There are fresh indications to critically re-analyse the physiological rationale for the current preference for TSH levels in the assessment of the thyroid state of the peripheral tissues. There may be opportunities to apply these research principles to analogous parameters in other endocrine systems.

When Your Thyroid Causes Muscle Paralysis

Background: Periodic paralysis represents a spectrum of disorders characterized by ion channel dysfunction, mainly Na-K-ATPase channels. Thyrotoxic periodic paralysis (TTP) is defined by the presence of hypokalemia and diffuse muscular paralysis in a pre-existing hyperthyroid state. Diagnosis can be challenging, especially in cases of undiagnosed hyperthyroidism due to the non-specific presentation of this illness. We present a case of a young male who presented with recurrent, spontaneous paralysis found to have Graves’ disease. Clinical Case: A 38-year-old Asian male presented with sudden onset diffuse weakness, numbness, and tingling. The weakness was so severe that he could barely walk more than a few steps. However, his symptoms resolved in less than 24 hours without any intervention. Five months later, the patient experienced a recurrent episode of this similar constellation of diffuse muscle weakness and paresthesia. The patient was taken to a nearby hospital, where he was provided with intravenous fluid resuscitation. Initial laboratory workup was notable for hypokalemia to 1.4 mmol/L (n: 3.6 - 5.3 mmol/L), hypophosphatemia to 0.6 mmol/L (n: 2.4 – 4.8 mmol/L), and elevated creatinine kinase to 807 U/L (n: 22 – 198 U/L). Additionally, TSH was <0.001 mU/L (n: 0.45 – 4.5 mU/L) along with free T4 3.4 ng/dL (n: 0.80 – 1.70 ng/dL. The patient denied any other symptoms or a family history of similar symptoms. Lumbar puncture and brain/spine MRIs were unremarkable. Symptoms gradually improved throughout hospitalization with fluid and electrolyte repletion. Hyperthyroidism was treated with methimazole 5mg twice daily, later changed to PTU 50mg every eight hours due to recurrent headaches. Thyroid uptake scan showed diffuse bilateral uptake to 39.11% at 4 hours and 61.8% at 24 hours. Follow up labs revealed: TSH 0.3 mU/L, free T4 1.44 ng/dL, free T3 3.5 pg/mL (n: 2.3 – 4.1 pg/mL). Patient denied recurrent episodes of weakness or paresthesia. Definitive hyperthyroidism treatment with RAI was planned. Conclusions: The prevalence of TPP is higher in Asian males compared to other ethnic groups. TPP manifests as a sporadic onset of muscle weakness ranging from mild weakness to flaccid paralysis. It has been described that thyroid hormone itself augments the activity of the Na-K-ATPase channel and increases its responsiveness to beta-adrenergic stimulation. In addition, hyperthyroidism is associated with insulin resistance leading to hyperinsulinemia. Both beta-agonism and insulin promote potassium to be driven into cells resulting in hypokalemia. As such, activities which increase beta adrenergic stimulation, like stress and exercise, and promote the secretion of insulin, such as heavy carbohydrate intake, are well described triggers of TPP. Treatment revolves around acutely treating hypokalemia followed by preventing subsequent attacks via regulation of the altered thyroid state.

Influence of sodium selenite on immunological indexes of tuberculosis patients with diabetes mellitus and autoimmune thyroiditis

In 60 tuberculosis patients with diabetes mellitus and autoimmune thyroiditis serum level of selenium, thyroid state and immunological indexes were studied. Low level of selenium, subclinical hypothyroidism and weaken immunological response toward tuberculosis were diagnosed. Prescribing of selenite sodium with 200 ц daily during 2 months normalized serum level of selenium, restored thyroid function and improved immunological response. Inclusion of selenite sodium in complex therapy of tuberculosis patients with diabetes mellitus and autoimmune thyroiditis after examination of serum level of selenium and thyroid state is recommended.

Hyperthyroidism in Takotsubo syndrome: prevalence, clinical features and long-term outcomes

Background Takotsubo syndrome (TTS) is an increasingly recognized form of transient left ventricular dysfunction, often completely reversible. The exact pathogenesis is not fully understood, but central role of adrenergic dysfunction has been widely accepted. A possible link between hyperthyroidism and TTS has been hypothesized, since thyroid and adrenergic systems are in closely connection. Nevertheless, clinical study to define the association between hyperthyroidism and TTS is still lacking. Purpose This study aimed to assess prevalence, clinical features and long-term outcomes of hyperthyroidism at presentation in TTS patients. Methods Overall, 590 TTS patients from 23 centers were included in this prospective registry. Thyroid profile was available for 314 patients at time of TTS admission. Patients in hypothyroid state (n=32) according to TSH value were excluded. The remaining 282 patients were divided in normal thyroid state and hyperthyroid state according to TSH value, respectively 240 (85%) and 42 (15%) patients. Results The median age was 73±10 and the female rate was 93%. TTS related to physical trigger was mostly detected in hyperthyroidism patients (52% vs 30%, respectively in hyperthyroid state and normal thyroid state; p=0.005); while, TTS related to emotional trigger was less common (19%, vs 38%, respectively in hyperthyroid state and normal thyroid state; p=0.016). In TTS unprovoked by a stress factor, there was no statistical difference in thyroid state (29% vs 31%, respectively in hyperthyroid state and normal thyroid state; p=0.690). Follow-up rate was 95% and follow-up length was 41±36 months. At long-term follow-up, mortality rate was 39% and 20% in hyperthyroidism and normal thyroid state, respectively (p=0.008; Figure 1) and adverse event rates (the composite of all-cause death, myocardial infarction and stroke) were 39% and 24% in hyperthyroid state and normal thyroid state, respectively (p=0.034). At multivariable analysis, hyperthyroidism resulted as a strong predictor of mortality (OR 3.82, 95% CI: 1.71–8.50; p=0.001) and of adverse event rates (OR 2.18, 95% CI: 1.19–3.98; p=0.011). Conclusion Hyperthyroidism at presentation is relatively common in TTS patients and associated with physical triggers and unfavorable long-term prognosis. Figure 1. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

Prevalence of Hypothyroidism among Dialysis Patients in Palestine: A Cross-Sectional Study

Introduction. The kidney affects the thyroid gland causing various derangements in its function whenever the kidney is impaired, even with a minor imperfection in its job, and this makes dialysis patients more prone to thyroid disorders with subsequent increase in mortality and morbidity. This study aims to assess the prevalence of thyroid disease (hypo- and hyperthyroidism) among dialysis patients and their associated factors. Methods. This cross-sectional study was conducted in the dialysis unit of An-Najah National University Hospital. 209 dialysis patients (60% were male, 57.6 ± 14.5 years, mean age) meeting our inclusion criteria were tested for thyrotropin (TSH) and free thyroxine (FT4) in addition to routine laboratory tests. Findings. The prevalence of hypothyroidism was assessed as 16.3% (95% CI = 11.29% to 21.3%), overt hypothyroidism was 9.1%, and subclinical hypothyroidism was 7.2%. Subclinical hyperthyroidism prevalence was 1%, and no overt hyperthyroidism cases were reported. We observed no significant association between thyroid state and age, gender, duration of dialysis, or weight. Discussion. Hypothyroidism (both subclinical and overt type) is commonly seen in dialysis patients, and its symptoms are ordinary complains even in euthyroid dialysis patients, and this warrants screening programs and more studies on the efficacy of thyroid hormone supplements.

Renal insufficiency in overt hypothyroidism

Hypothyroidism is a common endocrine disorder worldwide. In hypothyroidism, there is altered regulation of renal hemodynamics and basal metabolic rate. This hospital-based case-control study was done to evaluate the changes in uric acid level in hypothyroid subjects. This study includes 25 hypothyroid cases with age and sex-matched controls. Serum total thyroid profile was estimated by ChemiluminiscenceImmunoassay (CLIA) and uric acid by the Uricase method in fully automated Vitros 5600. The mean uric acid level is increased in hypothyroid. Triiodothyronine(T3)&Thyroxine(T4)levelof hypothyroid patients showed a significant negative correlation with uric acid with 'r' values of 0.45 and 0.51, respectively. A positive correlation was observed between Thyroid-stimulating hormone (TSH) and uric acid (p=0.22) in hypothyroid subjects. The raise in uric acid is hypothyroid subjects is due to hemodynamic changes like reduction in renal plasma flow and disordered thyroid state affects purine metabolism, leading to hyperuricemia and gout. Hence, these parameters should be monitored regularly in hypothyroid patients.