Levothyroxine Replacement Therapy Research Articles

#1246 The impact of severe nephrotic syndrome on thyroid function

Abstract Background and Aims Nephrotic syndrome (NS) is a clinical condition characterized by massive urinary loss of proteins, mostly albumin, but also hormones and their carrier proteins among others. The most frequently reported hormonal complication is thyroid dysfunction. The study aimed to assess the frequency of thyroid dysfunction in NS and its association with carrier protein levels and indicators of disease severity. Method A case-control study was conducted involving patients with newly diagnosed or relapsed severe NS, defined as proteinuria > 3.5 g/day and serum albumin ≤ 2.5 g/dL (NS group), and patients without proteinuria (control group). The evaluation included thyroid hormone profiles, serum levels of carrier proteins (prealbumin – PAB, and thyroid-binding globulin – TBG), and markers reflecting the course of NS. Results Forty-two nephrotic and 40 matched non-proteinuric patients were enrolled. The NS group comprised 67% males with a mean age of 49 years and an average proteinuria of 8.9 g/day (Table 1). The leading cause of NS was minimal change disease (22 patients), followed by membranous nephropathy (11 patients). The other causes included: amyloidosis (3 patients: AL – 2 cases, A – 1 case), focal segmental glomerulosclerosis (2 patients) and lupus nephritis (1 case). In 5 cases, no histological diagnosis was made. Thyroid dysfunction secondary to NS was observed in the majority of patients, occurring 18-times more frequently than in the control group (67% vs 10%, OR = 18, 95% CI: 5.3-60.7). Euthyroid sick syndrome was the most commonly seen in NS (15 cases, 36%), followed by overt (8 cases, 19%) and subclinical hypothyroidism (5 cases, 12%). According to the current guidelines, levothyroxine supplementation was required in 11 patients (26% of the NS group, 36% of those with thyroid dysfunction). Serum TSH correlated inversely with PAB (R = −0.63, p < 0.001), and positively with TBG (R = 0.39, p = 0.010), while no relationships were found between carrier proteins and free hormones (fT3 or fT4). The only indicator of NS severity related to thyroid function was serum albumin. It correlated, however, only with TSH (R = −0.41, p = 0.007), not with free hormones. Additionally, neither histological type, nor clinical course of NS distinguished between euthyroidism, euthyroid sick syndrome, or hypothyroidism (Table 2). Conclusion Thyroid dysfunction is a common complication of severe NS. Although euthyroid sick syndrome predominates, the proportion of patients with hypothyroidism who may potentially require levothyroxine replacement therapy remains substantial.

The effect of low-level laser therapy on the oxidative stress level and quality of life in patients with Hashimoto’s thyroiditis

This study aimed to examine the effects of low-level laser therapy (LLLT) combined with levothyroxine replacement therapy on thyroid function, oxidative stress (OS), and quality of life in patients with Hashimoto’s thyroiditis (HT). Forty-six patients diagnosed with HT were randomized to receive active LLLT (n = 23) and sham LLLT (n = 23) twice a week for three weeks. Clinical and laboratory evaluations of the participants were performed before treatment and three months after treatment. Biochemical parameters were taken from the patient file requested by the physician as a routine examination. Malondialdehyde and nitricoxide indicating oxidant stress and superoxide dismutase, catalase, and glutathione, which indicate antioxidant capacity, were used in OS evaluation. The Oxidative Stress Index was calculated by measuring the Total Antioxidant Status and the Total Oxidant Status. At the end of our study, a significant improvement in oxidant and antioxidant biomarker levels showing OS and quality of life was observed in the treatment groups (p < 0.05). There was no change in thyroid function and autoimmunity at the end of the treatment between the two groups (p > 0.05). Improvements in glutathione levels and quality of life were significantly higher in the active treatment group than in the sham-controlled group. LLLT was found to be more effective on OS and quality of life in patients with HT than in patients in the sham-controlled group. It was concluded that LLLT is a safe and effective method that can be used in the treatment of patients with HT.

Body composition changes in patients with differentiated thyroid cancer after iodine-131 treatment and short-term levothyroxine replacement and suppression therapy.

The purposes of this study were to assess the changes in body composition in patients who underwent thyroidectomy due to differentiated thyroid cancer (DTC) after radioactive iodine therapy (RAI) and short-term levothyroxine (LT4) supplementation and to explore the correlations between body composition distribution and corresponding blood indices. Fifty-seven thyroidectomized DTC patients were included. Serum was tested for several biochemical indices of thyroid function, lipids, and bone metabolism, and body composition parameters were measured via dual-energy X-ray absorptiometry before and 4-6 weeks after RAI and LT4 supplementation. The body composition of DTC patients changed after RAI. Fat mass in all parts of the body decreased (range of relative change (RRC) -12.97--2.80%). Bone mineral content (BMC) increased throughout the body (relative change (RC) 12.12%), head (RC 36.23%), pelvis (RC 9.00%), and legs (RC 3.15%). Similarly, bone mineral density (BMD) increased in different regions (RRC 3.60-26.43%), except for the arms. Notably, lean mass in the arms (RC 4.30%) and legs (RC 3.67%) increased, while that in the head decreased (RC -2.75%), while total lean mass did not change at 4-6 weeks after LT4 supplementation. Furthermore, changes in fat distribution in the android region were related to the changes in total cholesterol (r = -0.390) and low-density lipoprotein cholesterol (r = -0.354), and changes in the BMC and BMD of the lumbar spine were positively associated with the changes in calcitonin (r = 0.302 and 0.325, respectively). After RAI and short-term LT4 supplementation in DTC patients, body composition rapidly and positively changed and was characterized by decreased fat mass and increased BMC and BMD.

To compare the efficacy and safety of 5 days a week levothyroxine versus daily replacement therapy in hypothyroid patients: An experience from a tertiary care center in Central India

Introduction: Hypothyroidism is a common endocrine disorder and associated with several complications if not diagnosed and managed. Levothyroxine (LT4) replacement therapy is the treatment of choice. Levothyroxine has a long half-life of 6–7 days and hence can be given intermittently keeping the weekly dose the same. Aim: The aim of the study was to compare the efficacy and safety of 5 days a week levothyroxine versus daily replacement therapy in patients with hypothyroidism and to identify the patient’s satisfaction level at the end of the trial. Methods: This was a prospective cohort study in which patients diagnosed with hypothyroidism and having stable thyroid function in the last 6 months with a minimum of two normal thyroid profile reports on the same LT4 dose were shifted 5 days a week LT4 (keeping the total weekly dose the same) after informed consent. Then, patients were followed up at regular intervals, and biochemical analysis of thyroid profile was done at 12 and 24 weeks or Si Opus Sit (SOS)according to clinical judgment. Results: One hundred and fifty patients with hypothyroidism were included in the study with a male-to-female ratio of 4:21. The mean age of our patients was 40.6 ± 8.58 years. The mean duration of hypothyroidism was 5.9 ± 3.01 years. The mean thyroid-stimulating hormone, T4, and T3 at baseline were 3.22 + 0.91 μIU/mL, 8.71 + 1.91 μg/dL, and 0.93 + 0.04 ng/mL, and at 12 weeks and 24 weeks were 3.62 ± 0.82 μIU/mL, 8.01 ± 2.01 μg/dL, and 1.2 ± 0.05 ng/mL and 3.33 ± 0.79 μIU/mL, 8.36 ± 1.99 μg/dL, and 0.88 ± 0.03 ng/mL, respectively. One hundred and twenty-seven patients did not require any dose adjustment. There was no significant difference in thyroid profile. Conclusion: Five days a week levothyroxine replacement regimen is noninferior to daily levothyroxine replacement regimen in treating patients with hypothyroidism and can be conveniently prescribed. Furthermore, 5 days regimen increased the compliance and satisfaction level in patients with hypothyroidism.

Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma.

Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

Prior Anti-Angiogenic TKI-Based Treatment as Potential Predisposing Factor to Nivolumab-Mediated Recurrent Thyroid Disorder Adverse Events in mRCC Patients: A Case Series.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) have revolutionized the management of many types of solid tumors, including metastatic renal cell carcinoma (mRCC). Both sequential and combinatorial therapeutic strategies utilizing anti-PD-1 monoclonal antibodies (mAbs) and anti-angiogenic tyrosine kinase inhibitors (TKIs) have demonstrated to improve the survival of patients with mRCC as compared to standard therapies. On the other hand, both ICIs and TKIs are well known to potentially cause thyroid disorder adverse events (TDAEs). However, in the context of sequential therapeutic strategy, it is not clear whether prior anti-angiogenic TKI may increase the risk and/or the severity of ICI-related TDAEs. In this work, by describing and analyzing a case series of mRCC patients treated sequentially with prior TKIs and then with ICIs, we investigated the role of prior anti-angiogenic TKI-based treatment as a potential predisposing factor to anti-PD-1-mediated recurrent TDAEs, as well as its potential impact on the clinical characteristics of nivolumab-mediated recurrent TDAEs. Fifty mRCC patients were included in the analysis. TKI-mediated TDAEs were reported in ten out of fifty patients. TKI-mediated TDAEs were characterized by hypothyroidism in all ten patients. Specifically, 40%, 40% and 20% of patients presented grade 1, 2 and 3 hypothyroidisms, respectively. Following tumor progression and during anti-PD-1 nivolumab treatment, five out of ten patients developed anti-PD-1 nivolumab-mediated recurrent TDAEs. Anti-PD-1 nivolumab-mediated recurrent TDAEs were characterized by an early transient phase of thyrotoxicosis and a late phase of hypothyroidism in all five patients. The TDAEs were grade 1 and 2 in four and one patients, respectively. Prior anti-angiogenic TKI did not modify the clinical characteristics of nivolumab-mediated recurrent TDAEs. However, all five patients required an increased dosage of levothyroxine replacement therapy. In conclusion, our work suggests that prior anti-angiogenic TKI-based treatment significantly increases the risk of ICI-mediated recurrent TDAEs in patients with mRCC without modifying their clinical characteristics. The most relevant effect for these patients is the need to increase the dosage of lifelong levothyroxine replacement therapy.

SAT624 Neurosarcoidosis Presenting With Panhypopituitarism

Abstract Disclosure: E.M. Niedzialkowska: None. T. Blazin: None. K. Strubchevska: None. M. Kozyk: None. N. Saini: None. Introduction: Neurosarcoidosis is estimated to occur in approximately 5-15% patients with sarcoidosis. Pituitary involvement may be present in up to 5% of those cases and can manifest as hypothalamus, adenohypophysis dysfunction or arginine vasopressin deficiency (AVP-D) in isolated fashion or variedly combined. Clinical case: 32 year old male presented with chief complaint of worsening bilateral lower extremity weakness, urinary incontinence, polyuria and polydipsia. 9 months prior to admission the patient was diagnosed with neurosarcoidosis. At that time brain MRI showed diffuse leptomeningeal enhancement, chest CT showed hilar lymphadenopathy, lumbar puncture with CSF analysis showed protein 227 mg/dl (N&amp;lt;38), ACE 6 U/l (N &amp;lt;2.5), WBC 10 (N&amp;lt;5) with 88% lymphocytes. Hilar lymph node biopsy was consistent with non-caseating granuloma. The patient was diagnosed with neurosarcoidosis and started on prednisone and methotrexate. The patient was referred to our institution for further evaluation. On examination gait ataxia and gynecomastia were noted. Laboratory results showed urine specific gravity of 1.001, LH 0.4 mIU/ml (N 0.6-1.2), FSH 1.1 mIU/ml (N 1-12), ACTH &amp;lt;5 pg/ml (N 6-46), cortisol 2.1 ug/dl (N 2.9-19.4), prolactin 10.5 ng/ml (N 2-18), total testosterone 4 ng/dl (N 240-1080), free testosterone 0.1 ng/dl (N 4.8-19), TSH 0.58 uIU/ml (N 0.4-4.5), free ft3 1.5 pg/ml (N 1.7-3.7), free ft4 0.6 ng/dl (N 0.7-1.5), IGF-1 52 ng/ml (N 71-234), Copeptin proAVP of &amp;lt;2.8 pmol/l( N&amp;gt;13.2), urine osmolality of 72 mOsmol/kg, blood osmolality of 297 mOsmol/kg (N &amp;lt;295), vit D 25-OH 9 ng/ml (N 30-100), vit D 1,25-OH 57.3 pg/ml (N 19.9-79.3). MRI of the spine showed extensive nodular enhancement of the leptomeninges of the cervical, thoracic spine and lumbar cauda equina nerve roots. Brain MRI was positive for numerous small nodular enhancement involving leptomeninges and pituitary stalk. The patient was started on desmopressin with significant improvement of symptoms and increase in urine osmolality to 709 mOsmol/kg. Due to risk of hypercalcemia and normal vit D 1,25-OH vitamin D supplementation was not initiated. For neurosarcoidosis the patient was started on pulse dose methylprednisolone and infliximab infusion. Upon discharge he was transitioned to oral hydrocortisone and started on levothyroxine and testosterone replacement therapy. Conclusion: We present a case of pituitary neurosarcoidosis presenting with AVP-D, secondary hypothyroidism, secondary adrenal insufficiency, hypogonadism and growth hormone deficiency. Panhypopituitarism with complete anterior and posterior pituitary dysfunction is extremely rare and might be found in up to 13% cases of pituitary sarcoidosis. The diagnosis should be considered in patients with sarcoidosis and endocrine dysfunctions. Presentation: Saturday, June 17, 2023

Clinical insights of pregnancy management, adrenal insufficiency as a possible cause of elevated TSH: a pilot study of case series

BackgroundThe upper limit for thyroid-stimulating hormone has been strictly defined for pregnancy management, at which point levothyroxine replacement therapy will been initiated. However, it is essential to exclude adrenal insufficiency, including subclinical adrenal insufficiency, when initiating levothyroxine replacement therapy. However, in pregnancy management, it has rarely reported the incidence, clinical course, and characteristics of adrenal insufficiency as a possible cause of elevated thyroid-stimulating hormone.MethodsThis case series study included pregnant patients undergoing thyroid-stimulating hormone management in a single-center diabetes endocrinology department between 2017 and 2020. The primary study outcome was the incidence of newly diagnosed adrenal insufficiency. We reported the clinical course and assessed the adrenal insufficiency characteristics at baseline and delivery and compared them with those of hypothyroidism.ResultFifteen pregnant women were included for thyroid-stimulating hormone management; and nine were below the basal serum cortisol level, and four were newly diagnosed as having adrenal insufficiency (26.7%) with the endocrinological stimulation test. Among them, two cases exhibited nausea and hypoglycemic symptoms after the start of levothyroxine replacement therapy. In cases of adrenal insufficiency, the patients were successfully treated with appropriate steroid coverage.ConclusionsIn the management of elevated thyroid-stimulating hormone levels during pregnancy, the frequency of adrenal insufficiency suspecting hypothyroidism may be higher than expected; therefore, we must be careful about starting levothyroxine replacement therapy for hypothyroidism. These clinical insights can have a significant impact on the pregnancy outcomes.

Effects of levothyroxine replacement therapy on insulin resistance in patients with untreated primary hypothyroidism

ObjectivesThis study investigated the effects of levothyroxine replacement therapy on insulin resistance, lipid profile, and thyroid function in patients with untreated primary hypothyroidism. 105 patients with hypothyroidism with indication for levothyroxine replacement were enrolled in the present study. Insulin, fasting blood glucose and lipid profile were assessed at the beginning of diagnosis and three months after levothyroxine replacement. Insulin resistance was calculated by hemostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI).ResultsOur data revealed a significant reduction in body mass index (27.18 ± 4.27 versus 26.81 ± 4.18 kg/m2, p = 0.028), cholesterol (199.79 ± 37.61 versus 178.10 ± 32.25 mg/dl, p < 0.001), triglyceride (160.41 ± 71.86 versus 146 ± 61.11 mg/dl, p = 0.012), low density lipoprotein-cholesterol (123.54 ± 30.7 versus 107.08 ± 26.98 mg/dl, p < 0.001), fasting insulin (8.91 ± 3.92 versus 8.05 ± 2.65 mIU/l, p < 0.001), and thyroid stimulating hormone (47.47 ± 3.4 versus 2.22 ± 1.84 µIU/ml, p < 0.001) levels before and after drug intervention. However, no statistical differences were observed in HOMA-IR, QUICKI, and high density lipoprotein-cholesterol. In conclusion, in patients with untreated primary hypothyroidism, levothyroxine replacement therapy based on HOMA-IR and QUICKI did not improve insulin resistance; however, lipid profile was significantly improved following levothyroxine administration.Trial registrationThis study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20130610013612N10 on the date 2019-09-02.

Neurodevelopmental Outcome of Infants with Transient Hypothyroxinemia of Prematurity in a Newborn Intensive Care Unit

The aim of this study was to evaluate neurological development of infants with transient premature hypothyroxinemia (THOP). This prospective study included newborns who were born between 28-36 weeks of gestation (GW) and were admitted to the neonatal intensive care unit. Newborns exposed to maternal thyroid disease, or with severe intracranial problems, and congenital anomalies were excluded. Infants with THOP were the study group and those without THOP formed the control group. The study group was subdivided into those receiving levothyroxine replacement (5 μg/kg/day) and those who were untreated. Neonatal demographics, and morbidities, including respiratory distress syndrome, bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) were evaluated. The Ages and Stages Questionnaire (ASQ) and ASQ:Social-Emotional (ASQ:SE) developmental screening tests were administered to the entire study population at the corrected age of two years. Seventy infants were included in this study, 40 of whom had THOP. The mean GW was 34.4±3.8 weeks in the study group and 37.2±2.3 weeks in controls (p=0.69). Mean overall birth weight was 1640±428 g. Levothyroxine replacement was started in 12/40 infants (30%). The groups were similar in terms of demographic characteristics. Rates of BPD and ROP were higher in the treated group (p=0.01). ASQ and ASQ:SE results did not differ between groups (p=0.75), nor did these scores differ between infants with THOP who did or did not receive levothyroxine (p=0.14). Although levothyroxine replacement therapy was associated with increased rates of BPD and ROP, this treatment did not appear to improve long-term neurological outcomes in this small group of infants with THOP. Prospective controlled studies with much larger sample sizes are needed to clarify the role of levothyroxine replacement in THOP.

The pleiotropic effects of levothyroxine replacement therapy in patients with subclinical hypothyroidism and hypertension

Background. According to epidemiological studies, the prevalence of subclinical hypothyroidism is about 6 % and it depends on age, gender, region of residence and, at the same time, significantly exceeds the frequency of primary hypothyroidism. Within one year, 5 % of cases of subclinical hypothyroidism turn into the manifested form. Delayed diagnosis of the disease increases the risk of serious complications. It is still controversial whether subclinical hypothyroidism affects blood pressure because of conflicting results in published studies. Thus, the aim of this study was to assess the effects of levothyroxine replacement therapy in patients with subclinical hypothyroidism and hypertension on lipid metabolism, functional state of the endothelium and cognition. Materials and methods. Thirty-one patients with subclinical hypothyroidism and stage 2 hypertension participa­ted in the study, among them 12 (38.71 %) men and 19 (61.29 %) women. The average age of participants was 63.19 ± 1.93 years. The study examined lipid profile, functional state of the endothelium, and cognitive functions based on the results of the Montreal Cognitive Assessment before and after 3 months of additional administration of the levothyroxine replacement thera­py at a dose 25–50 µg daily. Results. The lipid analysis revealed a significant decrease in total cholesterol for 10.08 % (5.54 ± 0.17 mmol/L against 6.23 ± 0.25 mmol/L, Р &lt; 0.05), low-density lipoprotein choleste­rol for 24.5 % (3.39 ± 0.17 mmol/L against 4.49 ± 0.27 mmol/L, Р &lt; 0.01), triglycerides for 19.42 % (1.66 ± 0.11 mmol/L against 2.06 ± 0.16 mmol/L, Р &lt; 0.05) compared to those at baseline. At the same time, patients with subclinical hypothyroidism and hypertension showed a reliable decrease in atherogenic dyslipidemias, 64.52 against 74.19 %. We also observed a reliable improvement of the functional state of the endothelium: the mean value of the endothelium-dependent vasodilation of the brachial artery increased for 11 % (6.56 ± 0.10 % against 5.91 ± 0.05 %, Р &lt; 0.001). The results of the neuropsychological testing showed a reliable improvement of the cognitive functions among examined patients: the average score on the Montreal Cognitive Assessment raised from 23.77 ± 0.60 at baseline to 26.65 ± 0.47 after three months of taking levothyro­xine, Р &lt; 0.001. Conclusions. Levothyroxine replacement therapy in patients with subclinical hypothyroidism and hypertension was followed by a normalization of lipid profile and a decrease in atherogenic dyslipidemias, an improvement of the functional state of the endothelium and state of cognition.

Neurodevelopmental Outcome of Preterm Infants with Hypothyroidism

Background: Hypothyroidism is one of the most common causes of preventable intellectual disability and is common in preterm infants. Some studies have reported that developmental delay is still high in these patients despite appropriate treatment. Objectives: This study aimed to investigate the short-term neurodevelopmental outcome of preterm infants with thyroid dysfunction. Methods: This cohort study included 50 preterm infants with thyroid dysfunction requiring levothyroxine treatment (case group) and 50 age- and sex-matched healthy preterm infants with normal thyroid tests (control group). The patients were followed, and Ages and Stages Questionnaires (ASQ) (including five domains) were filled out at 6 and 12 months to evaluate the short-term neurodevelopmental outcome. Results: There was no statistically significant difference in gestational age, sex, and birth weight between the two groups (P-values = 0.648, 0.756, and 0.866, respectively). A total number of 4 (8%) and 7 (14%) of the case group and 1 (2.85%) and 2 (5.71%) of the control group had a possible neurodevelopmental delay based on the low score in at least one domain of ASQ at 6 and 12 months of age (P-values = 0.321 and 0.222, respectively). Treated hypothyroidism was not significantly associated with higher impaired neurodevelopmental outcomes (P-value = 0.236, Odd Ratio: 2.686, 95% CI: 0.523 - 13.787). Conclusions: In this study, the risk of neurodevelopmental impairment in preterm infants with hypothyroidism was similar to that of healthy preterm infants. Thus, these findings may confirm the adequacy of levothyroxine replacement therapy in preventing neurodevelopmental delay.

SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients

Background and purposePrimary hypothyroidism due to abnormality in the thyroid gland is the most common endocrine disease The recommended starting dose of levothyroxine replacement therapy is 1.6 µg/kg. This dose however is not optimal for every patient and dose adjustments are frequently done. Genetic polymorphisms in the absorption and metabolism pathway of levothyroxine are likely to influence its dose requirements. This study aimed to study the influence of genetic polymorphisms on levothyroxine replacement requirements.MethodsThis was a cross-sectional study. Participants were recruited through a private nutrition clinic and through announcements distributed in the University of Petra in Amman, Jordan between September 2020 and February 2021. Hypothyroid patients had already been on stable doses of levothyroxine for the previous 3 months. A questionnaire was distributed to collect demographic and clinical information and a blood sample was taken for DNA extraction and clinical biochemistry analysis. rs11249460, rs2235544, rs225014, rs225015, rs3806596, rs11185644, rs4588, rs602662 were analyzed using Applied Biosystems TaqMan™ SNP Genotyping Assays on Rotor-Gene® Q and rs3064744 by direct sequencing. SPSS and Excel were used to perform analysis.Results76 patients were studied. The equation we calculated to find predicted daily dose of levothyroxine (mcg/kg) is 3.22+ (0.348 for CT genotype of rs11185644, 0 for other genotypes) + 0.027*disease duration (years) − 0.014*age (years) − 0.434*T3 (pmol/L) levels+ (0.296 for CC genotype of rs2235544, 0 for other genotypes).ConclusionSNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 affect dose requirement in hypothyroid patients and if confirmed in larger trials they can be used to individualize thyroxine starting doses.

Uncommon clinical features of juvenile primary hypothyroidism

This case study presents an 18-year-old boy with severe short stature and distinct physical features, including facial abnormalities, skeletal deformities, and intellectual impairment. Further investigations revealed hypothyroidism, autoimmune thyroiditis, and delayed bone age. Treatment with levothyroxine replacement therapy was initiated. The study highlights the importance of detection and management of hypothyroidism in individuals with short stature and associated features.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

The impact of lockdown on thyroid hormone metabolism in patients on levothyroxine replacement therapy residing in Adjara

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1406483: Thyroid Hormone Resistance Diagnostic and Therapeutic Challenges

Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity to thyroid hormone (TH). We present the challenges in diagnosing and treating a 24-year-old male who presented with a mixed picture of hypothyroidism and hyperthyroidism with elevated TSH, upper normal free T4, and elevated free T3 and was found to have a mutation in the THRβ gene. A 24-year-old male was referred for a second opinion of post-ablative hypothyroidism with elevated TSH, elevated free T3, and suspicion of pituitary microadenoma. He complained of fatigue, weight gain, tremors heat cold intolerance. Family history is Graves’ disease in his mother's status post partial thyroidectomy due to a salivary tumor. Initially, in 2020, he was diagnosed with negative antibody Grave’s disease. Labs were TSH 0.86 mIU/L, free T4 1.99 ng/dl (0.89-1.76), and free T3 4.66 pg/ml (2.3-4.2). A thyroid ultrasound showed mild thyromegaly. A thyroid uptake scan showed 24-hour thyroid uptake of 36.7%. Thyroid antibodies including thyroglobulin, TPO, thyroid receptor, and thyroid stimulating immunoglobulin were negative. He was treated with radioactive iodine ablation (I-131). Afterward, His TSH increased gradually along with free T3. Free T4 was normal. The patient remained symptomatic, and he was not on any thyroid replacement therapy. A repeat thyroid uptake scan showed an increase uptake of 36% at 24 hrs. During our evaluation, a repeat TSH 54.05 mIU/l, free T4 1.3 ng/dl, free T3 4.3 pg/ml, and T3 by equilibrium dialysis 4.0. A repeat magnetic resonance imaging of the head showed no definitive focal enhancing lesion. Pituitary axis hormones were normal, and the alpha subunit was 0.73 (high); however, the alpha-glycoprotein subunit /TSH molar ratio 0.135 sex hormone binding globulin 5.8 nmol/l (low), macro TSH was not detected. These findings raised suspicion for THRB mutation; hence genetic studies were obtained. PCR amplification of THRB gene exons 10, 9, and 8, followed by gene sequencing, showed a heterozygous missense mutation C >G located at exon 10. The mutation caused a change in thyroid hormone receptor beta protein amino acid 453 proline to an alanine, P453A Initially, he was started on levothyroxine 25 mg PO daily but soon after, it was stopped due to palpitations; a beta blocker was started along with liothyronine 5 mg every other day and levothyroxine 50 mg every other day. The patient tolerated the regimen with significant improvement in his symptoms. RTH is rather uncommon; it is important to be able to recognize the syndrome to avoid unnecessary invasive treatment. There is no specific therapy currently available to fully correct the TRβ defect. The goal of treatment is based on the patient's symptoms and clinical picture instead of aiming to normalize thyroid hormone levels. Thyroidectomy and radioactive iodine ablation result in lifelong levothyroxine replacement therapy and RTHβ persistently high serum TSH. Levothyroxine therapy is challenging, and supraphysiologic doses are often needed to maintain serum TSH in the lowest tolerable level.

Adult Thyroid Outcomes of Congenital Hypothyroidism.

Background: More than 40 years have passed since the introduction of newborn screening (NBS) for congenital hypothyroidism (CH), and many early diagnosed patients have reached adulthood. Their thyroid morphology and function have been little studied. This cross-sectional, observational study was conducted to characterize the thyroid morphology and function of adult CH patients diagnosed in the framework of NBS for CH. Methods: A total of 103 adult CH patients born after 1979 were enrolled at Ito Hospital, Tokyo, Japan, and were classified into Goiter, Normal gland, and Dysgenesis groups based on ultrasonographic findings. For 60 patients, genetic analysis was performed. Thyroid function test results and the proportion of patients with thyroid nodules were compared among the three groups and between 56 female CH patients and 168 non-CH women matched for thyrotropin levels. Results: A significantly low serum free triiodothyronine/free thyroxine ratio (0.22) was observed in the Dysgenesis group. Thyroid nodules were detected in 14.3% (8/56) of female CH patients, more frequently than in non-CH women. Thyroid nodules were detected most frequently in the Goiter group (71%, 10/14). Genetic defects were identified in 89% (8/9) of patients belonging to the Goiter group, including thyroglobulin defect (33%, 3/9), thyroid peroxidase defect (33%, 3/9), and dual oxidase 2 defect (22%, 2/9). Conclusions: Our results suggest that adults with thyroid dysgenesis on levothyroxine replacement therapy have relative triiodothyronine deficiency. Most adults with goitrous CH have genetic dyshormonogenesis. They are at high risk of developing thyroid nodules. Our findings support the current guideline recommendation that CH patients with dyshormonogenesis should undergo periodic thyroid ultrasonography.

The effects of calcitonin on quality of life in hypothyroid patients – A pilot study

IntroductionHypothyroidism is a very common endocrine disorder routinely treated with levothyroxine replacement therapy. Despite treatment to biochemical euthyroidism, some individuals continue to have hypothyroidism-related symptoms. Many individuals with hypothyroidism also have low levels of calcitonin. Our aim was to evaluate the effects of calcitonin treatment on quality of life in hypothyroid individuals treated with levothyroxine. MethodsAdult, hypothyroid individuals were treated with nasal calcitonin spray, 200 international units daily for 6 weeks. Participants completed a modified City of Hope Quality of Life questionnaire prior to initiating calcitonin and after completing 6 weeks of therapy. Perception of quality-of-life benefit with calcitonin was also assessed. ResultsImprovements in quality-of-life scores with calcitonin treatment from 184.77 to 148.44 (p = 0.342) were not statistically significant. Also, only one individual perceived any benefit with calcitonin therapy. ConclusionTreatment with nasal calcitonin spray in individuals with hypothyroidism on levothyroxine replacement therapy did not result in quality-of-life benefit.

Acute adrenal crisis precipitated by thyroid storm in a patient with undiagnosed autoimmune polyglandular syndrome type 2.

Autoimmune polyglandular syndrome (APS) type 2 is characterized by the presence of Addison's disease (AD) along with autoimmune thyroid disease and/or type 1 diabetes. APS type 2 is known as Schmidt's syndrome when autoimmune adrenal insufficiency is associated with chronic lymphocytic thyroiditis. We report a very rare case of a 28-year-old female patient who had Schmidt's syndrome revealed by a thyroid storm (TS) concomitant with an acute adrenal crisis. The onset of AD resulted in a surgical emergency. The patient presented with cardiogenic shock and an acute abdomen. The precipitation factor was Hashitoxicosis presented as TS. This life-threatening condition was successfully reversed with aggressive medical therapy based on antithyroid drugs and intravenous glucocorticoids. This hyperthyroid phase lasted for a period of 8 months. The patient eventually developed hypothyroidism, suggesting that Hashimoto's thyroiditis was the most likely diagnosis. She was started on levothyroxine replacement therapy and remained euthyroid on levothyroxine. The case we describe had several diagnostic pitfalls that are discussed both at the start as well as during the evolution. Autoimmune diseases can appear concomitantly or succeed each other over time. The clinician must be vigilant to detect these diseases in time in order to avoid a misdiagnosis of a life-threatening emergency such as adrenal insufficiency or thyroid storm. Thyroid storm is an uncommon but life-threatening manifestation of hyperthyroidism. Diagnosis is dependent on clinical symptoms, and no specific laboratory tests are available. Glucocorticoids should be used in the treatment of thyroid storm because they have an inhibitory effect on peripheral conversion of T4 to T3. In patients who have severe thyrotoxicosis, especially in conjunction with hypotension, treatment with glucocorticoids has become standard practice because of the possibility of relative adrenal insufficiency or the possibility of undiagnosed Addison's disease. The differential diagnosis of hyperthyroidism can be challenging. Graves' disease can be discussed in view of the severity of the clinical presentation and the prolonged duration of the hyperthyroid phase. Hashitoxicosis is the initial hyperthyroid phase in chronic autoimmune thyroiditis. The hyperthyroid phase is always followed by definitive resolution, with persistent euthyroidism and no hyperthyroid relapses. Synthetic antithyroid drugs may be prescribed during the hyperthyroid phase of Hashimoto thyroiditis if the clinical presentation is severe and the duration of the hyperthyroid phase is prolonged.