scholarly journals Familial Dysalbuminaemic Hyperthyroxinaemia and Other Causes of Euthyroid Hyperthyroxinaemia

1987 ◽  
Vol 80 (12) ◽  
pp. 750-752 ◽  
Author(s):  
C Farror ◽  
M L Wellby ◽  
C Beng

Clinical and biochemical studies on a family in which 3 members have familial dysalbuminaemic hyperthyroxinaemia (FDH) are presented. They were clinically euthyroid with elevated serum thyroxine (T4) and free T4 indices but normal free T4 by equilibrium dialysis and normal serum triiodothyronine (total and free). All thyroid function tests on the remaining family members were normal. The inheritance is consistent with autosomal dominance. Also presented are data on 4 unrelated patients with FDH and two patients with T4 autoantibodies. The methods for detecting FDH, T4 antibodies and other causes of euthyroid hyperthyroxinaemia are now freely available. Since these anomalies may be more common than previously supposed, clinical awareness of the conditions is necessary to protect patients from the consequences of incorrect diagnosis of thyrotoxicosis.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A587-A588
Author(s):  
Nicole Z Hernandez-Cordero ◽  
Yadiel Rivera-Nieves ◽  
Nicolle Canales-Ramos ◽  
Janet M Colon-Castellano ◽  
Alberto J Grana-Santini ◽  
...  

Abstract Background: A possible association between multiple sclerosis (MS) and dysregulation of hypothalamic-pituitary axis has been reported and its endocrine manifestations can be confused with many nonspecific symptomatology attributed to MS. We report such a case and present the improvement of symptoms independent of MS therapy. Clinical Case: Case of a 45 years-old female with history of type 2 diabetes mellitus, dyslipidemia, HTN, obesity class I and MS that was evaluated for follow up with complaints of fatigue, weakness, somnolence and memory problems. No menstrual disturbances with regular cycles. Denies weight changes, anorexia, nausea, vomiting or abdominal discomfort. Previous hormonal workup showed normal levels of cortisol, ACTH, prolactin and TSH. Nonetheless, on repeated hormonal profile due to nonspecific complaints, patient was found with normal TSH (2.65 mIU/mL, 0.3-3.0 mIU/mL) and low free T4 (0.65 ng/dL, 0.78-2.19 ng/dL). Repeated thyroid function tests by equilibrium dialysis showed a borderline low FT4 (0.8 ng/dL, 0.78-2.19 ng/dL), despite a persistently normal TSH (2.26 mIU/mL, 0.3-3.0 mIU/mL). Suspecting hypopituitarism, a complete hormonal workup revealed a low normal serum cortisol in early morning of 8.39 mcg/dL and ACTH of 16.7 pg/mL, normal prolactin of 10.5 ng/mL and a first IGF-1 evaluation of 68.9 ng/mL, which was low for female age range (98-261 ng/mL). Due to concerns for possible complications during an insulin tolerance test, a cosyntropin stimulation test was performed with adequate peak cortisol response at 30.5 mcg/dL. Most recent brain MRI without pituitary protocol was remarkable for multiple bilateral demyelinating plaques compatible with MS diagnosis that also involved the left thalamus, although no other area adjacent to the hypothalamus or pituitary gland was described. The patient was subsequently started on levothyroxine replacement to a goal of free T4 at the upper normal range, with overall improvement in symptoms and quality of life. Growth hormone status and gonadal axis to be reevaluated. This case emphasizes the importance of clinical judgement and reminds us that overlapping symptoms can lead to misdiagnosis, particularly in conditions with nonspecific symptomatology as MS. Conclusion: This is an unusual case of a patient with multiple sclerosis presenting with hypopituitarism suggesting the possibility of hypothalamic disturbance as the etiology. It has been proposed that demyelinating MS lesions in fiber bundles in and adjacent to the hypothalamus may compromise hypothalamic function. Mechanisms for fatigue in MS have been mostly associated with hyperactivity of HPA axis, not found in our patient. Hypothalamic dysfunction can be frequently overlooked due to overlapping symptoms with MS, despite being a treatable condition that can greatly improve quality of life in these patients.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Bilal Bashir ◽  
Moulinath Banerjee ◽  
Harnovdeep Singh Bharaj ◽  
Simmi Krishnan ◽  
Atir Khan ◽  
...  

Abstract Background: Raised free thyroxine (T4) with normal thyroid stimulating hormone (TSH) levels should be identified and interpreted with caution. Some of these conditions do not need treatment. We present three cases with similar biochemical abnormalities from three different causes. Case 1: A 62-year-old clinically asymptomatic lady was referred to us with Free T4 34.9 pmol/L (10.0 – 24.0 pmol/L), TSH 0.81 mU/L (0.2 – 5.0 mu/L) and negative TSH receptor antibodies (<0.9 IU/L). She was trialled on antithyroid drugs for 6 months. Her Free T4 stayed elevated between 29.0 – 35.0 pmol/L with normal TSH. We worked up for assay interference by running tests on two analysers, Roche Cobas e801 and Siemens ADIVA Centaur CP, both yielded similar results. Alpha1 glycoprotein subunits and SHBG were normal with clinical euthyroid status making TSHoma less likely. Serum protein electrophoresis did not detect any abnormal albumin. We were unable to perform equilibrium dialysis due to non-availability of facility at our centre. Due to strong clinical suspicion and family history of thyroid dysfunction that never needed a treatment, we tested her genetically for familial dysalbumineic hyperthyroxinemia (FDH) using mutation surveyor and fluorescent sequence analysis showed her to be heterozygous for c.725G>A ALB variant confirming diagnosis of FDH. Case 2: A 65-year-old clinically asymptomatic lady, was referred to us with Free T4 28.8 pmol/L (10.0 – 24.0 pmol/L) and TSH 2.50 mU/L (0.2 – 5.0 mu/L). Given inappropriately normal TSH levels, we repeated her TFTs using 3 different analysers, Roche cobas e801, Siemens ADIVA centaur CP and Abbot ARCHITECT i1000SR. Roche and Siemens assays yielded similar results, however Abbot assay showed normal thyroid function tests with TSH 1.01 mu/L (0.4-5.0 mu/L) and free T4 18.7pmol/L (9.0-19.0 pmol/L), confirming assay interference. As Siemens and Roche uses streptavidin-biotin immobilizing system while Abbot uses a magnetic bead-based capture system, the abnormal results could be due to biotin interference. Case 3: A 65-year-old lady, clinically asymptomatic was referred to us with Free T4 29.2 pmol/L (10.0 – 24.0 pmol/L) and TSH 1.59 mU/L (0.2 – 5.0 mu/L), 3 months after stopping amiodarone, which she took for 3 weeks for atrial fibrillation. This was thought to be due to amiodarone, owing to its long half-life of 58 days. We repeated thyroid function tests in 3 months from first clinical encounter i.e. 6 months after stopping amiodarone that showed Free T4 24.2pmol/L and TSH 2.30 mU/L and repeated further 3 months later that were normal, confirming amiodarone induced abnormal biochemical profile requiring no treatment. Conclusion: Hyperthyroxinaemia with normal TSH need to be interpreted with caution as illustrated above. Some of them do not need treatment and inappropriate interpretation can potentially cause anxiety for the patient and harm due to unnecessary treatment.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sabah Patel ◽  
Petra Krutilova ◽  
Janice L Gilden ◽  
Charles P Barsano

Abstract Background: It is not uncommon to encounter patients whose thyroid function tests (TFTs) seem mutually inconsistent or inconsistent with a patient’s clinical status, At times, the simplest reconciliation of the findings invokes a rare disorder that we are hesitant to accept. In this case, a clinically euthyroid patient presents with elevated TSH and Free T4 (FT4) suggestive of a TSH-producing tumor or of Thyroid Hormone Resistance. Clinical Case: A 72 yr-old man with cardiomyopathy on amiodarone is admitted to the Medical Service for treatment of anasarca. He had no symptoms or signs of thyroid dysfunction and was not taking L-T4, amphetamines or propranolol. Findings on exam included normal VS, runs of atrial tachycardia, and edema from feet to scrotum. Thyroid exam was normal. Serum creatinine was 2.24 mg/dl (NL: 0.67-1.17). Bili was 2.7 mg/dl (NL: 0.67-1.17); AST and ALT were normal, Chest x-ray revealed cardiomegaly with clear lung fields. Thyroid ultrasound revealed a normal size gland containing a few sub-centimetric nodules. On Day 2 The serum FT4, by analog assay, was elevated at 1.66 ng/dl (NL: 0.76-1.46) and TSH was elevated at 9.06 mIU/L (NL: 0.35-3.74), Anti-peroxidase and anti-thyroglobulin antibodies were negative. The Medical Service’ diagnosis was “amiodarone-induced thyroiditis.” The amiodarone was discontinued and diuresis was induced with bumetanide, Endocrinology consultation was requested On Day 4 the FT4 and TSH were still elevated at 1.62 and 10.1, respectively. FT4 by dialysis was not elevated at 1.62 ng/dl (NL: 0.9-2.2). The FT3 was 2.34 pg/ml (NL: 2.18-3.98). On Day 5 Anti-thyroxine antibodies and Thyroid Stimulating Immunoglobulins (TSI) were negative. Paired TSH samples with and without neutralization of Human Anti-Mouse Antibodies (HAMA) were identical: both elevated at 8.30 mIU/L (NL: 0.4-4.50). Serum Iodine was markedly elevated at 2288 mcg/L (NL: 52-109). The FT4 levels by analog assay therefore appear to have been falsely elevated (as indicated by the dialysis assay) though not by recognized factors such as thyroxine antibodies, amphetamines or propranolol. Continued observation is necessary to further assess the transience of the post-admission TFTs. Conclusion: In patients admitted to Acute Medical or Psychiatric Services, most combinations of high or low TSH and FT4 have been reported as well other aberrations of “non-thyroidal illnesses.” In patients with conflicting TFTs at admission, especially those who are clinically euthyroid, it is generally better to allocate a few weeks for observation and monitoring than to immediately launch into searches for rare disorders. This is especially important when multiple potentially thyro-active clinical states exist, such as renal and hepatic compromise, amiodarone use, and highly elevated iodine levels.


2021 ◽  
pp. 64-70
Author(s):  
Mark Kong ◽  
Sarah La Porte

A 44-year-old man presented with an enlarged painful lower anterior neck lump with elevated serum concentrations of free thyroxine (T4) and tri-iodothyronine (T3), alongside the presence of antithyroid peroxidase antibodies. Prior to presentation, the patient was demonstrating recovery from a SARS-CoV-2 infection that required sedation, intubation, and invasive ventilation in the intensive care unit (ICU) for 11 days. Ultrasound examination of the thyroid demonstrated features of De Quervain’s (subacute) thyroiditis. This corresponded to the clinical picture, and continuous thyroid function tests were arranged. Emerging evidence throughout the SARS-CoV-2 pandemic describes the long-term sequelae of the infection, including developing atypical effects on the thyroid gland. This case report emphasises the association of painful subacute thyroiditis with post-viral infection and its manifestation during recovery from severe SARS-CoV-2, suggesting that follow-up thyroid function testing should be considered in patients discharged from the ICU who develop neck discomfort.


Author(s):  
Vasim Ismail Patel ◽  
Akshay B. K.

<p class="abstract"><strong>Background:</strong> The thyroid is an<strong> </strong>endocrine gland. It secretes two hormones thyroxine (T<sub>4</sub>), triiodothyronine (T<sub>3</sub>). Hypothyroidism is a common condition encountered by a clinician. Subclinical hypothyroidism (SCH) defined as normal free thyroxine (T4) and elevated thyroid stimulating hormone (TSH), is primarily a biochemical diagnosis with or without clinical symptoms. Studies have observed that TSH levels vary at different times in a day. In practice not much importance is given to the timing of the sample collection (pre-prandial or post-prandial sate). SCH is diagnosed depending on TSH value. So the condition may be under or over diagnosed based on a single value. So we conducted this study to determine whether timing of sample collection had any significant relationship in the determination of levels of thyroid hormones.</p><p class="abstract"><strong>Methods:</strong> The study was carried on 114 patients who visited ENT department, NMCH between July 2018 and June 2019. Group-1 consisted of 38 normal patients. Group-2 consisted of 36 hypothyroidism patients GROUP-3 consisted of 40 subclinical hypothyroidism patients. Thyroid function tests (TSH and free T4) were done in fasting state and 2 hours postprandially.  </p><p class="abstract"><strong>Results:</strong> TSH values were found to be significantly lowered after food in all the three groups. Free T4 values did not show any statistically significant alteration after food.</p><p class="abstract"><strong>Conclusions:</strong> There was a significant decline in TSH values postprandially. This might lead to inappropriate diagnosis and management of patients as cases of hypothyroidism, especially in cases of sub clinical hypothyroidism.</p>


Author(s):  
Jayne A. Franklyn

Subclinical hypothyroidism is defined biochemically as the association of a raised serum thyroid-stimulating hormone (TSH) concentration with normal circulating concentrations of free thyroxine (T4) and free triiodothyronine (T3). The term subclinical hypothyroidism implies that patients should be asymptomatic, although symptoms are difficult to assess, especially in patients in whom thyroid function tests have been checked because of nonspecific complaints such as tiredness. An expert panel has recently classified individuals with subclinical hypothyroidism into two groups (1): (1) those with mildly elevated serum TSH (typically TSH in the range 4.5–10.0 mU/l) and (2) those with more marked TSH elevation (serum TSH >10.0 mU/l).


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Masayasu Iwabuchi

Abstract INTRODUCTION Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition is an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins. PCSK9, a serine protease that binds to the LDL receptor promoting its degradation, is an important regulator of LDL metabolism. In addition, LDL-cholesterol is also controlled by TSH and thyroid hormones via PCSK9. TSH has received increasing attention as being closely associated with increased LDL-cholesterol level and higher atherosclerotic risks. In vitro study, the effects of TSH on hepatic PCSK9 expression in HepG2 cells were reported (1). I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. This case highlights the involvement of thyroid function in PCSK9 Inhibitor therapy. CLINICAL CASE A 65-year-old man had a weight loss of 6 kg (13 lbs.) in 4 months, accompanied with fatigue. He had a past history of myocardial infarction and his LDL was 83 mg/dL by 2.5mg of rosuvastatin and heart rate was controlled by 10mg of carvedilol. Six months ago, he started a PCSK9 Inhibitor therapy with 140mg of evolocumab every 2 weeks for 6 weeks. He had no preceding viral illness and denied anterior neck pain or tenderness. His height was 1.53 m, weight 52.6 kg (115 lbs.), and body mass index (BMI) 22.46 kg/m2. His thyroid was not enlarged and non-tender without clear palpable thyroid nodules or neck lymph nodes. Hyperthyroidism was suspected and confirmed by thyroid function tests: TSH was less than 0.0005 μIU/mL (normal 0.35–4.94), and free T4 1.830 ng/dL (0.70–1.48). Graves’ disease was considered, and thyroid antibody tests performed. Thyroid peroxidase (TPO) antibody titer was less than 9 IU/mL (&lt;9), and TSI 141% (&lt;120%). To confirm the diagnosis of this hyperthyroid patient, Technetium-99m uptake and scan was done which showed uptake of 0.8% (0.5–7%). After careful observation for 2 months with 5mg of carvedilol, he turned asymptomatic and free T4 lowered to 1.480 ng/dL and TSH remained less than 0.0005 μIU/mL. CLINICAL LESSONS I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. There has been no report of hyperthyroidism induced by PCSK9 inhibitors. Immunological influence of anti-PCSK9 therapy on thyroid is unknown. In this case, the decrease of TSH due to hyperthyroidism was considered to reduce hepatic PCSK9 expression, leading to additive effect to PCSK9 inhibitor. PCSK9 inhibitors may modify the effects of hyperlipidemia treatment by causing changes in thyroid function. When using PCSK9 inhibitors, follow-up of thyroid function should be considered. This case highlights the involvement of thyroid function in PCSK9 inhibitor therapy. Reference (1) Gong, Y., Ma, Y., et al. Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression. Metabolism. 2017;76;32–41


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Robert P McEvoy ◽  
Anthony O’Riordan ◽  
Mark J Hannon

Abstract The population attending the Medical Assessment Unit at our hospital comprises patients attending electively for investigation and acutely unwell patients presenting for unscheduled care. The standard panel of blood tests taken on arrival includes thyroid function tests (TFTs, i.e. TSH and free-T4), despite a recent review questioning the clinical utility of this practice [1]. We performed a retrospective audit to determine what proportion of our patients had abnormal thyroid function on presentation, and whether these abnormal test results were being followed up. Using the iSoft Clinical Manager software, a list was generated of all patients who attended the hospital between January 2018 and June 2018 inclusive. For each attendance, we recorded the date, medical record number, patient age, gender, and TFT result. Abnormal TFT results were classified as overt or subclinical hyper- or hypothyroid, or non-thyroid illness syndrome (NTIS), based on their admission TSH and free-T4. We then examined the hospital and primary care records of patients with abnormal TFTs to determine if they had ongoing thyroid follow up post discharge. In total, 2,298 patients attended over the 6-month study period. The mean patient age was 67.2 years, and 49% were female. Thyroid function tests were ordered on the day of attendance for 1,688 patients (73%). Of these, 181 results (11%) were abnormal: 20 overt hyperthyroid (11%), 72 subclinical hyperthyroid (40%), 12 overt hypothyroid (7%), 35 subclinical hypothyroid (19%), and 42 NTIS (23%). Twenty of these patients died within 3 months of the abnormal TFT result (4 overt hyperthyroid, 3 subclinical hyperthyroid, 3 overt hypothyroid, 6 subclinical hypothyroid, and 4 NTIS). Of the remaining 161 patients, 74 (46%) had not been followed up within 3 months (4 overt hyperthyroid, 34 subclinical hyperthyroid, 3 overt hypothyroid, 15 subclinical hypothyroid, and 18 NTIS). The low percentage of abnormal TFTs (11%) in this audit is in keeping with similar studies where thyroid function testing was performed on unselected hospital populations [1]. Subclinical hyperthyroidism was by far the most common abnormality found. A high percentage of abnormal tests (46%) were not followed up, with poor compliance with thyroid management guidelines [2]. Future work will investigate adoption of an ‘opt-in’ order system [3] and electronic alerts to flag abnormal results for follow-up. [1] Premawardhana LD. Thyroid testing in acutely ill patients may be an expensive distraction. Biochemia medica. 2017; 27(2): 300-307. [2] Ross DS et al. 2016 American Thyroid Association Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016 Oct; 26(10):1343-1421. [3] Leis B et al. Altering standard admission order sets to promote clinical laboratory stewardship: a cohort quality improvement study. BMJ Qual Saf. 2019; 28(10): 846-52.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A940-A941
Author(s):  
Nyembezi Dhliwayo ◽  
Rana Wajahat ◽  
Andriy Havrylyan ◽  
Alvia Moid ◽  
Walid Khayr ◽  
...  

Abstract There is considerable evidence that some Borrelial (Lyme spirochetal) proteins share significant antigenic properties with several thyroid-related proteins (e.g. TSH receptor, thyroglobulin, thyroid peroxidase) and can induce thyroid autoimmunity, sometimes associated with Hashimoto’s thyroiditis and perhaps also a “destructive thyroiditis” such as “silent” thyroiditis or “Hashitoxicosis.” As an acute illness, Lyme disease may also constitute a “non-thyroidal illness” capable of perturbing thyroid function tests without causing thyroid dysfunction. We report a 22-year old woman admitted with an acute paranoid schizophrenia, thyroid function tests consistent with autoimmunity, transient thyrotoxicosis (tachycardia, lid-lag, brisk DTR’s) and a greatly reduced radioiodine uptake. The thyroid was not palpably enlarged, nodular or tender. On screening assay, reactivity was demonstrated to 4 of 13 Borrelial proteins. Anti-Lyme IgM but not IgG, antibodies, were positive. This was consistent with recent Lyme disease infection. Serum TSH (NL: 0.358-3.74 mcU/ml), Free T4 (NL: 0.76-1.46 ng/dl), and Free T3 (NL: 2.18-3.98 pg/ml) were, respectively: Day1: 0.087 mcU/ml (suppressed), 1.52 ng/dl (slightly elevated), 2.07 pg/ml (slightly reduced); Day2: 0.148 (suppressed), 1.18 (normal), no FT3; Day4: 0.827 (normal), no FT4 or FT3; Day5: 1.66 (normal), 0.89 (normal), 1.77 (low). Anti-Tg and Anti-Peroxidase antibodies were both moderately elevated. Thyroid Stimulating Immunoglobulins were not elevated. The radioactive iodine uptake on Day4 was 2.8% (NL: 15-30% at 24 hr). Thyroid ultrasonogram was normal. An attractive explanation is that Lyme disease triggered a “destructive thyroiditis,” perhaps but not necessarily mediated by thyroid autoimmunity. This would account for the brief interval of thyrotoxicosis accompanied by a very low radioiodine uptake. Alternatively, Lyme disease, as an acute process, would expectedly be capable of eliciting the thyroid function abnormalities of “non-thyroidal illnesses” in general, as would acute psychosis, well-known to often resemble Graves’ disease at admission.


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