Clinical Symptoms Of Hypothyroidism Research Articles

Prevalence of Subclinical Hypothyroidism in Patients with Recurrent Miscarriages

Background: Subclinical hypothyroidism poses a concealed threat to reproductive health. With evidence hinting at its prevalence in recurrent miscarriages, this study delves into unraveling the intricacies of this relationship for comprehensive understanding and improved clinical outcomes. Objective: To determine prevalence of subclinical hypothyroidism in patients with recurrent miscarriages. Study Design: Descriptive cross-sectional study. Settings: This study was conducted at the Department of Medicine, DHQ Teaching Hospital, KMU Institute of Medical Sciences, Kohat Pakistan. Duration: 6 months period from Jan-Jun, 2023. Methods: A total of 224 women meeting inclusion criteria were included in the study after taking informed written consent. Blood samples were taken as per standard hygiene protocol and send hospital lab for thyroid profile. Subclinical hypothyroidism was labeled when serum TSH level was ≥4.0 mIU/L and the patients didn’t have clinical symptoms of hypothyroidism. All the data was collected in a predesigned format and data analysis was done using SPSS 27.0. Results: Mean age of the patients in this study was 29.01±6.61 years wherein 58.0% (n=130) patients were in the age group of 18-30 years while remaining 42% (n=94) were in the age group of 31-40 years. As regards parity, 50.9% (n=114) patients were nulliparas, 28.1% (n=63) were primiparas and 21.0% (n=47) were multiparas. Mean BMI of the study sample was 24.87±3.7 kg/m2 wherein 52.7% (n=118) participants were normal weight, 37.9% (n=85) were overweight and only 9.4% (n=21) were obese. Previous number of miscarriages were almost same amount all the three groups as 3 miscarriages (33.5%), 4 miscarriages (35.7%) and 5 miscarriages (30.8%). Subclinical hypothyroidism was observed in 18.3% (n=41) patients. Frequency of mischarge was stratified on the basis of age, parity, BMI and previous number of miscarriage, it produced insignificant different for all the subgroups (p-value=0.05). Conclusion: In conclusion, our study highlights a consistent prevalence of subclinical hypothyroidism (18.3%) in women with recurrent miscarriage. This aligns with global findings, emphasizing the significance of thyroid dysfunction. These insights underscore the importance of routine thyroid screening in the management of recurrent miscarriage, guiding targeted interventions for improved reproductive outcomes.

Immune-Related Thyroid Adverse Events Predict Response to PD-1 Blockade in Patients with Melanoma.

Simple SummaryWe evaluated the immune-related thyroid adverse events (irTAEs) during anti-PD-1 therapy in terms of their influence on overall survival (OS) rates in melanoma. Based on data from 249 patients with metastatic melanoma and a normal thyroid stimulating hormone (TSH) at baseline, we found that during anti-PD-1 therapy, 95 patients had a TSH outside normal ranges (32 had clinical symptoms of hypothyroidism). The 3-year OS rates in patients with clinical hypothyroidism, abnormal but clinically not significant TSH, and euthyreosis were 56%, 43%, and 32%, respectively. After adjusting the Cox model for potential confounding variables, clinically significant hypothyroidism was an independent prognostic factor with HR 0.51 (95% CI 0.29–0.87).Antibodies against programmed cell death protein-1 or its ligand (PD-(L)1) are a standard of care in melanoma; however, this treatment may cause immune-related adverse events. The aim of this study was to evaluate the immune-related thyroid adverse events (irTAEs) during anti-PD-1 therapy and analyze their influence on the overall survival rates in melanoma. We included 249 patients with metastatic melanoma treated in our institution between 2014 and 2021; the median age was 62 years (range: 17–90); 58% were males, and 37% of patients had the BRAF mutation. We included patients with a normal TSH at baseline and followed up with measurement of TSH levels during immunotherapy. In our group, 95 patients had a TSH outside the normal range: 63 not clinically significant and 32 with clinical symptoms of hypothyroidism. The 3-year overall survival rate was related to the irTAEs of clinical hypothyroidism, abnormal clinically not significant TSH, and euthyreosis at 56%, 43%, and 32%, respectively (p = 0.002). After adjusting the Cox model for potential confounding variables, clinically significant hypothyroidism was an independent prognostic factor with HR 0.51 (95% CI 0.29–0.87). In conclusion, the patients who developed clinically significant hypothyroidism requiring replacement therapy with L-thyroxin were the group who benefitted most from anti-PD-1 treatment.

SAT-493 A Case of Profound Hypothyroidism Secondary to Immune Check Point Inhibitors

Background: The discovery of immune check-point inhibitors (ICI) revolutionized cancer treatment. CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies have been approved in recent years. However, the advantageous clinical outcomes can also be associated with potentially severe immune related adverse effects (irAEs) such as hypophysitis, thyroiditis, type 1 diabetes mellitus, and adrenal insufficiency [1]. We report to highlight the importance of awareness of irAEs and collaboration of endocrinology and oncology specialties in managing oncology patients with ICI in an underserved community hospital in Brooklyn, NY.Clinical case: 62 years old woman with unremarkable thyroid history presented with chronic mid-chest pain and dysphagia in 2016 found to have a mass in middle third of esophagus. Biopsies revealed invasive squamous cell carcinoma (T3N0). She underwent radiotherapy and esophagectomy.On 1/2018, surveillance imaging detected a new tracheobronchial angle lymph node, which was confirmed as hypermetabolic and likely malignant by PET scan. Patient received additional 5 cycles of radiotherapy followed with 5 cycles of chemotherapy with Oxaliplatin and Capecitabine. Since post-chemotherapy PET scan showed local recurrence, patient was started on PD1 inhibitor, Pembrolizumab 200 mg Q3 week. After 3 doses patient developed cold intolerance, weight gain and low mood. Her TSH was 173 uIU/ml (0.27-0.42), FT4 <0.1 ng/dL (0.9-1.8) and referred to endocrine clinic. Repeat TSH was 190 uIU/ml, FT4 0.2 ng/dL, TPOAbs 619 IU/ml (<35) and TSI<0.1 IU/L (<0.55). Adrenal insufficiency was ruled out and started on levothyroxine 50 mcg in the morning, increased to 75 mcg. After 2 months of levothyroxine use, TSH was 11.8 uIU/ml and FT4 1.3. Pembrolizumab therapy is restarted shortly after.Conclusion: National Comprehensive Cancer Network guideline for management of immunotherapy related toxicities recommends routine monitoring of TSH and FT4 at baseline and every 4-6 weeks during immunotherapy, follow up every 12 weeks and TPO antibodies if TSH is high. This patient’s clinical symptoms of hypothyroidism might be confused by nonspecific symptoms of underlying malignancy. Combination radiotherapy and immunotherapy place this patient at higher risk of developing hypothyroidism. This case showed the successful collaboration of endocrinology and oncology team in giving vulnerable patient an optimized care with good clinical outcome.

Hypothyroidism in Clinical Practice

Hypothyroidism in Clinical Practice

Patients on levothyroxine replacement in the community: association between hypothyroidism symptoms, co-morbidities and their quality of life.

Patients may be symptomatic, resulting in lower quality of life (QOL), despite L-thyroxine (LT4) therapy for hypothyroidism or having normal thyroid function. We hypothesized that their clinical symptoms of hypothyroidism and co-morbidities were associated with QOL. The study aimed to determine the association between the hypothyroid-related symptoms of Asian patients on LT4 treatment, their co-morbidities and their QOL. A questionnaire survey was conducted from November 2015 to July 2016 on consecutive multi-ethnic Asian patients on LT4 treatment for their hypothyroidism in a public primary care clinic in Singapore. Data on their demography, clinical symptoms, morbidity status, QOL scores based on the EQ5D instrument and thyroid function tests were computed and analysed, including logistic regression analysis to identify factors associated with lower QOL. Complete data of 226 Asian patients (79.0% women; 74.2% Chinese, 10.0% Malay, 13.1% Indian and 2.6% other minority groups; median age 57 years; 27.5% had previous thyroid surgery) were analysed. Their QOL was not associated with their socio-demographic profiles, clinical parameters and latest thyroid-stimulating hormone and free thyroxine levels. Patients reporting weight gain, dry or coarse skin, leg swelling, feeling weak and carpal tunnel syndrome had significantly lower QOL; 53.6% of them with any single symptom had lower QOL. More patients had lower QOL if they had two or more symptoms and multiple medical conditions. In Asian patients with hypothyroidism, weight gain, feeling tired, feeling weak, having dry or coarse skin, leg swelling and increased number of co-morbidities and symptoms were significantly associated with poorer QOL.

Sexual function and depressive symptoms in young women with hypothyroidism receiving levothyroxine/liothyronine combination therapy: a pilot study

Objective Even mild hypothyroidism in pre-menopausal women is accompanied by impaired sexual functioning. The study was aimed at comparing the effect of levothyroxine, administered alone or in combination with liothyronine, on sexual function and depressive symptoms in pre-menopausal women treated because of hypothyroidism.Methods This quasi-randomized, single-blind study included 39 young women receiving levothyroxine treatment who, despite thyrotropin and thyroid hormone levels within normal limits, still experienced clinical symptoms of hypothyroidism. These patients were divided into two groups: group A (n = 20) continued levothyroxine treatment, while group B (n = 19) received levothyroxine/liothyronine combination therapy. At the beginning of the study, and 6 months later, all participants of the study filled in questionnaires evaluating female sexual functioning (Female Sexual Function Index; FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition; BDI-II).Results The study was completed by 37 women. Baseline sexual functioning and depressive symptoms did not differ between the study groups. Neither the total FSFI score nor the domain scores changed throughout the study in women who continued levothyroxine treatment. Compared to levothyroxine administered alone, levothyroxine/liothyronine combination therapy increased scores for two domains: sexual desire and arousal, tended to increase the total FSFI score, as well as tended to decrease the overall BDI-II score. The effect of the combination therapy on sexual function correlated with a treatment-induced increase in serum levels of free triiodothyronine and testosterone.Conclusions The obtained results suggest that levothyroxine administered together with liothyronine is superior to levothyroxine administered alone in affecting female sexual functioning.

Hypothyroidism - A New View On An Old Disease

Hypothyroidism is a common disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. Underactivity of thyroid is usually primary, from disease of thyroid, but may be secondary to hypothalamic-pituitary disease (reduced TSH drive). Untreated hypothyroidism can cause a number of health problems, such as obesity, hypertension, dyslipidaemia, infertility. The prevalence increases with age, and is higher in females than in males. Autoimmune thyroid disease is the most common aetiology of hypothyroidism. Clinical symptoms of hypothyroidism are nonspecific and may be subtle, especially in older persons. TSH and FT4 measurement are the laboratory examinations necessary for the diagnosis of hypothyroidism as well as the differential diagnosis between primary (clinical or subclinical) and secondary one. In the majority of patients, alleviation of symptoms can be accomplished through oral administration of synthetic levothyroxine, and most patients will require lifelong therapy.KYAMC Journal Vol. 7, No.-1, Jul 2016, Page 707-713

P200 – 2741: Autoimmune thyroiditis presenting as a cerebral vein thrombosis in a child: A case report

Objective Cerebral vein thrombosis (CVT) is a multifactorial condition that many systemic ilnesses constitute the risk factors. Mostly, hyperthyroidism has been associated with CVT in case reports, and increased levels of factor VIII and von Willebrand factor have been proposed as the possible link in this association. On the other hand, only a few study showing the relation of autoimmune thyroiditis and CVT in adults but there is no study or reports regarding the children. To our knowledge, this is the first case report of autoimmoune thyroiditis presenting as CVT in a child. Methods The patient was 11 years old girl, presenting with headache and right hemiplegia. CVT was diagnosed with MRI and MR venography. Subclinic hypothyroidism was diagnosed in the acute phase of CVT. She had an autoimmune thyroiditis but no diffuse goiter. No other risk factors for CVT was detected. She was treated with anticoagulation and thyroid replacement therapy with excellent clinical outcome. Results The relation between autoimmune thyroiditis and CVT in this patient should emphasize importance of hypothroidism in pediatric population as causing cerebrovascular pathology. Several hemostatic and fibrinolytic parameters have been demonstrated to be impaired in hypothyroidism suggesting a possible role of this disease in CVT pathogenesis. Beside, indirect evidence also supports possible endothelial dysfunction and venous stasis in hypothyroidism, further emphasizing the physiopathological relation between the two conditions. More research is needed to establish a possible causal role of hypothyroidism on CVT. Conclusion We strongly suggest that thyroid function should be screened in pediatric patients presenting with CVT even if there is no clinical symptoms of hypothyroidism.

Pharmacists provide care

Pharmacists provide care

Hashimoto’s Thyroiditis in children and adolescents: at presentation and during long-term follow up

Results The mean age of the patients at the time of diagnosis was 10.9 ± 2.3 years and female/male ratio was 49/8. The complaint at the time of hospital presentation was goiter in 66.7% of the patients. Other reasons for referral were clinical symptoms of hypothyroidism (7.1%) and findings on work-up for an unrelated problem (24.6%) or for high-risk groups (1.8%). At baseline, 49.1% (n=28) of the patients were euthyroid, whereas 31.6% (n=18) had subclinical hypothyroidism, 10.5% (n=6) of subjects were evaluated as hypothyroid. Out of 57 patients, 5 were diagnosed with hashitoxicosis. Five of the 28 subjects, who were initially euthyroid developed subclinical or overt hypothyroidism during the follow-up period and were started on thyroid medication.

The evaluation of function and the ultrasonographic picture of thyroid in children treated for medulloblastoma

Medulloblastoma (MB) is one of the most frequent and sensitive to radiation aggressive brain tumor in children. Abnormalities of the thyroid function are common complications of head and neck irradiation for childhood cancer. The aim of this study was to assess thyroid function in children treated for medulloblastoma according to the treatment protocol phase. Twenty-three children with MB were enrolled to this study. All patients underwent chemotherapy and radiotherapy to the whole craniospinal axis and boost with the conformal therapy restricted to the tumor bed to a total dose of 54 Gy. Thyroid function was evaluated based on thyroid-stimulating hormone (TSH), free thyroxine (fT4) levels controlled before MB treatment, directly after irradiation and at the end of the treatment protocol. Ultrasonography has been used to detect parenchymal abnormalities. All patients presented normal thyroid hormone range before chemotherapy. Hypothyroidism was found in 12 patients in the course of treatment, in 2 patients hormone deficits diagnosed directly after irradiation, in 10 patients such condition was observed at the end of the whole therapy. All of these patients needed thyroid hormone substitution. None of them presented clinical symptoms of hypothyroidism. Ultrasound-detected abnormalities have been found in 20 patients. It is crucial to monitor the functions of the thyroid gland in children treated for medulloblastoma because of the high risk of hypothyroidism resulting from the treatment. The change in the echogenicity of the thyroid gland may be an early marker for a dysfunction of this organ in children treated for medulloblastoma.

Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up

Objective:To investigate the clinical manifestations of autoimmune thyroiditis (AIT) leading to referral in children and adolescents, in addition to disease course and long-term outcome.Design:Chart review.Setting:Major tertiary hospital.Patients:114 children/adolescents (92 female,...

Dramatic interaction between levothyroxine and lopinavir/ritonavir in a HIV-infected patient

Dramatic interaction between levothyroxine and lopinavir/ritonavir in a HIV-infected patient

TSH-Controlled L-Thyroxine Therapy Reduces Cholesterol Levels and Clinical Symptoms in Subclinical Hypothyroidism: A Double Blind, Placebo-Controlled Trial (Basel Thyroid Study)

This study evaluated the effect of physiological, TSH-guided, l-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 ± 0.8 mIU/liter) were randomly assigned to receive l-thyroxine or placebo for 48 wk. Individual l-thyroxine replacement (mean dose, 85.5 ± 4.3 μg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 ± 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the l-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [−0.24 mmol/liter, 3.8% (P = 0.015) and −0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological l-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9–31% can be estimated from the observed improvement in low density lipoprotein cholesterol.

Selenium Deficiency and Thyroid Function in Acute Renal Failure

The lethality of acute renal failure exceeds 50% due to multiorgan dysfunction. In such critically ill patients a reduction of thyroid hormone concentrations without clinical symptoms or laboratory evidence of hypothyroidism frequently occurs. Selenium has recently been shown to play a major role in thyroid hormone metabolism. The aim of this study was to investigate the possible influence of selenium on thyroid hormone metabolism in acute renal failure. Changes in thyroid metabolism were related to the severity of multiorgan failure and to the clinical course. Thyroxine (T4), tri-iodothyronine (T3), free-T4, free-T3, thyrotropin (TSH), serum creatinine, and plasma selenium concentrations in 28 patients (mean age 60 ± 13) with acute renal failure and multiple-organ dysfunction syndrome were determined initially, and every 3 days after hospital admission. The plasma selenium concentration was found to be reduced compared to normal controls (32 ± 14 vs. 70–120 μg/L). T4 (56 ± 15 nmol/L, normal range 64–148), T3 (1.31 ± 0.38 nmol/L, normal range 1.42–2.46), free-T3 (3.1 ± 1.0 pmol/L, normal range 4.7–9.0), and free-T4 (10.8 ± 4.0 pmol/L, normal range 10.3–25.8) values were low in 50–70% of the patients at the time of presentation. Plasma TSH concentrations were within the normal range (0.59 ± 0.79 mU/L, normal range 0.25–3.1), and no clinical symptoms of hypothyroidism were observed. T4 concentration was higher in patients who survived acute renal failure compared to nonsurvivors (62 ± 22 vs. 51 ± 16 nmol/L, p < 0.05). Plasma selenium concentration was lower in patients with a severe organ dysfunction syndrome (36 ± 10 vs. 29 ± 19 μg/L) and correlated with the number of organ failures in these patients (r = –0.247, p < 0.05). T4 and free-T4 values paralleled decreasing selenium concentrations (r = 0.35, p < 0.05). Thyroid hormone levels were reduced in patients with acute renal failure without an increase in TSH. An increase in T4 concentrations became apparent during treatment and may be related to a favorable outcome in acute renal failure. Thyroid hormone concentrations paralleled plasma selenium levels, indicating a possible influence of selenium on thyroid function in acute renal failure.

Absence of circulating adrenal autoantibodies in adult-onset X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a frequent cause of adrenal insufficiency in young-adult patients with Addison's disease. As the contribution of an autoimmune process in the destruction of steroid cells in ALD is unclear, the aim of the present study was to evaluate the occurrence of adrenal-, thyroid- and islet-specific and non organ-specific autoantibodies in adult ALD patients. In all 5 patients, Addison's disease was the first manifestation of ALD. None of the ALD patients were positive for adrenal cortex autoantibodies in an indirect immunofluorescence assay, or for 21-hydroxylase autoantibodies in a radiobinding assay with recombinant human antigen. Similarly, we found neither non-organ specific autoantibodies (such as anti-nuclear, anti-ribosomal, anti-mitochondria, anti-smooth-muscle, anti-liver/kidney microsomal or anti-reticulin autoantibodies), nor islet-cell antibodies or glutamic acid decarboxylase (GAD65 or GAD67) autoantibodies, nor thyroglobulin autoantibodies in the sera of the 5 ALD patients. Two out of five patients were positive for thyroid microsomal autoantibodies. One of the two latter thyroid antibody-positive patients had clinical symptoms of hypothyroidism, and the other presented high levels of circulating TSH but no clinical signs or symptoms of hypothyroidism. Our study demonstrates that adult ALD is not immediately associated with the presence of adrenal autoantibodies and suggests that adrenal insufficiency is not mediated by an autoimmune process in adult ALD patients.

Hypothyroidism Associated With Aminoglutethimide in Patients With Prostate Cancer

The administration of aminoglutethimide and hydrocortisone is a second-line hormonal maneuver commonly prescribed for the treatment of metastatic prostate cancer. We determine the incidence of aminoglutethimide-induced primary hypothyroidism in an elderly population who have prostate cancer. Prospective evaluation. Twenty-nine men with stage D2 prostate cancer who were treated at the National Cancer Institute, Bethesda, Md, in 1992. Clinical and biochemical evidence of hypothyroidism (thyrotropin levels greater than 10 mU/L) was noted in nine of 29 patients treated following the initiation of aminoglutethimide (250 mg four times daily). The elevation in thyrotropin and the clinical symptoms of hypothyroidism were reversed by the administration of levothyroxine (n = 4). Hypothyroidism should be included in the differential diagnosis of lethargy in elderly patients who are receiving aminoglutethimide for prostate cancer. Furthermore, patients who are receiving this agent at a dosage of 1000 mg/d or greater should have their serum thyrotropin levels monitored, and replacement therapy with levothyroxine should be initiated when abnormally elevated levels are noted.

Reversible Hypothyroidism in Growth Hormone-Deficient Children Treated with Human Growth Hormone

Six children with human growth hormone (hGH) deficiency became hypothyroid during the course of their therapy with hGH. This was accompanied by a decreasing growth rate, clinical symptoms of hypothyroidism and decreased serum T4 concentrations. Three of the 6 patients returned to the euthyroid state, both clinically and biochemically, with cessation of hGH therapy, and reinstitution of hGH precipitated hypothyroidism again in 2 of the three. The patients who remained hypothyroid have evidence of multiple pituitary trophic hormone deficiencies while those who reverted to euthyroidism appear to have isolated hGH deficiency. Evaluation of thyroid function while on hGH showed low T4, free T4 and T3 concentrations. The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent or markedly blunted in 4 of 6 patients while receiving long-term hGH therapy but was normal or exaggerated in all patients when tested before or after only 5 days of hGH therapy. These data indicate that exogenous hGH results in an inhibition of the TSH response to TRH. The mechanism of this inhibition is unclear, but we postulate that it may be mediated by somatostatin secretion in response to pulse doses of hGH.