Thyroid Replacement Therapy Research Articles

Prevalence of Thyroid Function Abnormalities in Patients with Chronic Renal Failure under Regular Hemodialysis

Background: There are various changes in the thyroid gland and its function in end stage renal disease (ESRD). It is not surprising that impairment of kidney function leads to disturbed thyroid physiology. Objective: Is to detect thyroid function abnormalities in hemodialysis patients. Patients and Methods: 100 patients on maintenance hemodialysis (HD) were enrolled, they were excluded if they had the following criteria: history of thyroid disease, thyroid and parathyroid surgery, under interferon therapy, exposed to radiation, antithyroid drugs or thyroid replacement therapy, and those under 30 years. They were subjected to history taking, clinical examination and laboratory investigations including hepatitis C virological state, renal functions and thyroid functions. Results: 92% of patients had normal thyroid-stimulating hormone (TSH) levels, 8% had abnormal TSH levels. Regarding fT3 levels, 67 % had normal fT3 while 33 % had abnormal fT3, and only 11 patients had abnormal fT4. In respect to the thyroid hormone status, only one was hyperthyroid, 92% were in euthyroid status, 2% were clinically hypothyroid, 5% were subclinically hypothyroid, and 1% was hyperthyroid. There was significant negative correlation between TSH levels and dialysis duration, 8 patients having abnormal thyroid functions ere females, and 60% had HCV positive status. No significant associations were found between HCV infection and the thyroid hormones levels. However, HCV positive patients experienced lower levels of T4 and TSH. Conclusion: The average percentage of patients under regular hemodialysis with abnormal thyroid state is 8% with females having abnormal fT4 and TSH levels compared to males. TSH levels were inversely correlated with dialysis duration.

Self-Reported Allergy to Thyroid Replacement Therapy: A Multicenter Retrospective Chart Review

To determine patterns of adverse drug reactions (ADRs), including immediate drug hypersensitivity reactions (DHRs) and predictable ADRs, to thyroid replacement therapy (TRT). TRT is the treatment of choice for hypothyroidism. Levothyroxine (LT4) is among the most commonly prescribed medications in the United States, with over 70 million prescriptions annually. Documented immediate DHRs to TRT are rare, with only a few case reports. An 11-year (2008-2018) retrospective medical chart review of identified patients with self-reported allergy to TRT. ADRs to TRT were divided into immediate DHRs and predictable ADRs. A total of 466 patients were included in our study. We found an overall incidence of ADRs to TRT of 0.3%. Median age was 61.2 years; 85.8% were women, and 94.4% were Caucasian. The principal indication for TRT was autoimmune hypothyroidism (73.6%), followed by postsurgical hypothyroidism (17.4%) and subclinical hypothyroidism (6.7%). Predictable ADR manifestations to TRT were reported more commonly than DHR manifestations (57.5% vs. 42.5%, respectively). The most frequently reported of the former were palpitations (16.4%), nausea/vomiting (9.3%), and tremor (6.3%), while rash (23.8%), hives (9.5%), and pruritus (7.1%) were the most common regarding the latter. Fifty-six percent of the patients with an ADR to TRT tolerated an alternative TRT presentation. In our cohort, the majority of self-reported allergies to TRT were due to predictable ADRs rather than an immediate DHR. ADR = adverse drug reaction; DHR = drug hypersensitivity reaction; FDA = Food and Drug Administration; LT3 = liothyronine; LT4 = levothyroxine; SCAR = severe cutaneous adverse drug reaction; TRT = thyroid replacement therapy.

Annals for Educators - 2 June 2020

Annals for Educators - 2 June 2020

Huge Pulsatile Sternal Mass.

A 46-year-old woman presented with a huge, hard sternal mass with a one -year history. The size of the mass has been progressively increasing from an initial size of a table tennis ball. It was dull and aching in nature with a sensation of heaviness, which affected her daily life activities and made her seek medical attention. The mass was associated with skin discoloration and contact bleeding. There was no fever. Clinically, despite being hard and fixed, it tended to pulsate with bruit on auscultation [Figure 1]. She had a total thyroidectomy for a multinodular goiter 10 years prior, but defaulted follow-up soon after the surgery. She was on thyroid replacement therapy, but decided to stop taking it for the past two years due to a logistic issue.

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab

Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation.Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation. Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.

SAT-480 Myxedema Madness: A Rare Case of Severe Hypothyroidism Presenting as Psychosis

IntroductionMyxedema coma is a rare, life-threatening medical emergency resulting from uncontrolled hypothyroidism. Myxedema coma refers to the neurological sequelae of severe hypothyroidism, which classically manifests as depressed mental status. Rarely, myxedema coma can present with a hyperactive mental state and psychosis. We present an unusual case of a drug overdose secondary to myxedema coma-induced psychosis.Clinical CaseA 48 year old woman with a history of seizure disorder and hypothyroidism presented to the hospital after lamotrigine overdose. The patient’s spouse witnessed her ingest forty-five tablets of lamotrigine after an argument. The patient had no previous psychiatric diagnoses or suicide attempts. On examination, the patient was hemodynamically stable but was agitated, disoriented, and uncooperative. She had a normal neurologic exam and no peripheral edema. Her lamotrigine level was 25.4 ug/ml (2.5-15.0 ug/ml). The patient’s mental status did not improve with lamotrigine cessation. Psychiatry determined that the patient’s psychosis was not consistent with lamotrigine overdose. Given these recommendations, alternative causes of psychosis were considered. The patient’s husband stated she had not taken levothyroxine for over one year. Thyroid function tests revealed a thyroid stimulating hormone (TSH) of 299 mcIU/ml (0.35-5.50 mcIU/ml) with a free thyroxine (T4) level of 0.27 ng/dl (0.89-1.76 ng/gl). The patient was started on levothyroxine intravenously. After five doses of intravenous levothyroxine, her mental status improved to baseline and she was transitioned to oral levothyroxine. She denied that the lamotrigine ingestion was a suicide attempt. Based on the patient’s presentation and clinical course, we concluded that her overdose was due to severe hypothyroidism leading to myxedema madness.ConclusionSevere hypothyroidism with myxedema coma often presents with depressed mental status, which can manifest as progressive confusion, lethargy, and eventually coma. However, in the case of our patient, severe hypothyroidism presented as psychosis, a rare manifestation. Remarkably, the patient had no other obvious physical manifestations of severe hypothyroidism. Psychosis, though rare, has been seen in cases typically after thyroidectomy or in patients with previously undiagnosed Hashimoto’s thyroiditis. In this patient’s case, it is likely that her myxedema madness was precipitated by long-term nonadherence with her thyroid replacement therapy, as the patient had no prior psychiatric history. Additionally, her rapid reversal of symptoms after the administration of levothyroxine supports the diagnosis of hypothyroid-induced myxedema madness.

SAT-458 A Case of Cardiac Arrest Due to Hashimoto’s Thyroiditis Associated Cardiac Tamponade

Introduction: Myxedema coma is currently an uncommon medical emergency. We present a case of undiagnosed Hashimoto’s thyroiditis with myxedema coma and cardiac tamponade leading to cardiac arrest. Case Presentation: A 35 year-old man with no significant past medical history was brought to the emergency department after being found unresponsive. The patient was hypoglycemic (17 mg/dL), hypothermic (34°C), tachypneic (26/min), hypotensive (84/50 mmHg), and hypoxemic (90% on ambient air). Physical exam showed mild anasarca, jugular vein distention, clear lung sounds, and muffled heart sounds. Laboratory findings showed TSH 168.16 uIU/mL (0.45–5.33 uIU/mL), fT4 <0.25 ng/dL (0.58–1.64 ng/dL), fT3 1.33 pg/mL (2.5–3.9 pg/mL), cortisol 5.7 mcg/dL (3–16 mcg/dL). Chest x-ray demonstrated markedly enlarged, globular heart. ECG revealed sinus rhythm and low voltage of QRS complexes. Echocardiogram was significant for a very large pericardial effusion. Resuscitation was started with intravenous thyroxine and hydrocortisone, during which the patient was found to be in a cardiac arrest with pulseless electrical activity. CPR per ACLS protocol was initiated with return of spontaneous circulation. Clear fluid (2000 ml) was evacuated from the pericardial space. He was diagnosed with Hashimoto thyroiditis (thyroid peroxidase antibody level 355 IU/mL, normal <9 IU/mL). He recovered without neurological deficits and was discharged home with thyroid replacement therapy (levothyroxine 100 mcg). Discussion: Myxedema coma occurs as a complication of undiagnosed/untreated thyroid disease. It may be precipitated by an event such as infection, drug overdose, or myocardial infarction. The mainstay of treatment is T4 replacement along with supportive therapy, and glucocorticoids to counter possible underlying adrenal insufficiency. Massive pericardial effusion due to hypothyroidism, especially resulting in cardiac tamponade, is extremely rare. The incidence of pericardial effusion in patients with hypothyroidism has significantly decreased from 30–80% to 3–6%, due to early recognition of this common disorder. Our case highlights the importance of prompt recognition of hypothyroidism as a cause of cardiac tamponade, thus allowing rapid life-saving treatment. In patient populations with limited access to health care, it should be remembered that very late and potentially fatal complications of otherwise easily treatable conditions can occur. Awareness of this may help limit morbidity and mortality.

SAT-479 Atypical Presentation of Recurrent Cardiac Tamponade Following Pericardial Window in the Setting of Uncontrolled Hypothyroidism

INTRODUCTION:Classically, cardiac tamponade presents with hypotension, distant heart sounds and tachycardia (Beck’s triad). Pericardial window is considered effective treatment. Pericardial effusions are relatively common in hypothyroidism (3-6%) (1). Cardiac tamponade, however, is rarely seen in patients with hypothyroidism secondary to pericardial distensibility and the slow accumulation of fluid, allowing significant fluid accumulation without hemodynamic compromise (2).CLINICAL CASE:A 84 year-old female with history of post-surgical hypothyroidism (on levothyroxine 150 mcg) following total thyroidectomy for thyroid cancer, cardiac tamponade requiring pericardial window formation two years prior, presented for dyspnea on exertion and pedal edema for several days. She was tachypneic to 22/min with heart rate 47/min and blood pressure 92/62. Distant heart sounds were noted on exam.EKG demonstrated sinus bradycardia, low voltage QRS and T wave flattening. Further workup revealed TSH elevated to 44 uIU/mL (N:0.27–4.2 uIU/mL), free T4 0.17 ng/dl (N:0.93-1.7 ng/dl) and undetectable T3 (N: 80-100 ng/dl). Echocardiogram unexpectedly demonstrated a large circumferential pericardial effusion with diastolic collapse of the right atrial, right ventricular free wall, significant respiratory variations and interventricular dependence. These findings were consistent with cardiac tamponade physiology. She underwent a video assisted left thoracotomy pericardial window formation along with drainage of 400cc of yellow pericardial fluid. Fluid cytology and tissue histopathology were negative for malignancy. Her uncontrolled hypothyroidism was considered the cause for recurrence of cardiac tamponade and her levothyroxine dose was increased to 175 mcg. At two week follow up, she reported symptomatic improvement on the higher levothyroxine dose. Echocardiogram did not show reaccumulation of fluid.CONCLUSIONS:Sinus tachycardia is found in most patients with cardiac tamponade, except in hypothyroid patients (2). A high degree of suspicion is needed to diagnose cardiac tamponade in hypothyroidism, even in patients who have undergone presumed definitive therapy with a pericardial window in the past. The recent onset of pedal edema and low blood pressure were important indicators of impending cardiac compromise in our patient.Hypothyroid patients may be at higher risk of pericardial window failure compared to patients with cardiac tamponade of other etiologies, especially if thyroid replacement therapy is inadequate. The scientific literature is lacking in this regard and warrants further investigation.

SAT-484 Presyncope as Initial Presentation of Massive Pericardial Effusion with Tamponade in a Patient with Primary Hypothyroidism

Presyncope as initial presentation of massive pericardial effusion with tamponade in a patient with primary hypothyroidism Background: Hypothyroidism is an endocrinologic disorder that affects multiple systems ranging from cardiovascular, central nervous system, musculoskeletal, etc. One of the possible cardiovascular complications of hypothyroidism is pericardial effusion which is only rarely associated with tamponade. In this case report we have a 49 years old woman who presented with impending pericardial tamponade secondary to chronic primary hypothyroidism. Clinical case: A 49 years old woman with history of hypothyroidism presented to the hospital on account of headache, dizziness with presyncope episode, generalized weakness and shortness of breath for 7 days, physical exam showed normal vital signs, distant heart sounds, laboratory tests showed TSH:29.5 uIU/mL (normal range 0.270- 0.4200 uIU/mL), fT4: <0.1ng/dL (normal range 0.9–1.8 ng/dL), fT3: 1.68 pg/mL (normal range 1.80–4.60 pg/mL. Electrocardiogram showed low voltage QRS, chest CT showed large pericardial effusion with findings suggestive of right heart failure, Echocardiogram showed left ventricular dysfunction and large pericardial effusion. The patient was taken to the operating room for emergent pericardial window creation with pericardiectomy and was admitted to the Cardiac Care Unit for management of tamponade status post pericardial window. Levothyroxine 150 mcg, Liothyronine 25 mcg and Hydrocortisone 50 mg were started, the steroid was discontinued after adrenal insufficiency was ruled out. The pericardial drain was removed after 8 days and repeated tests showed TSH: 13.1 uIU/mL, fT3: 3.37 pg/mL, fT4: 0.5 ng/dL, studies of pericardial fluid only showed polymorphonuclear cells. The patient’s symptoms resolved and she was discharged on Levothyroxine 150 mcg and Liothyronine 25 mcg. During follow up visits the thyroid function tests were normal, Liothyronine was discontinued and a repeated Echocardiogram showed normal systolic function. Conclusions: Pericardial effusion can be found in 3–30% of patients with hypothyroidism but only in very rare cases (less than 3%) is associated with cardiac tamponade and occurs when there is a severe underlying condition like myxedema coma or prolonged untreated hypothyroidism (1). It is important not to miss that dizziness and presyncope in a patient with hypothyroidism may be a manifestation of cardiac tamponade. Once the diagnosis of hypothyroidism is made it is imperative to start treatment early as untreated hypothyroidism can cause severe cardiovascular complications but even when such are present, they can be reversible with thyroid replacement therapy. Reference: (1) Kahaly, G. and Dillmann, W. (2005). Thyroid Hormone Action in the Heart. Available at: https://academic.oup.com/edrv/article/26/5/704/2355198 [Accessed July 12 2019].

SUN-LB2 Undescended Testicle and Short Stature as Manifestation of Pituitary Stalk Interruption Syndrome a Report From Saudi Arabia

BackgroundPituitary stalk interruption syndrome (PSIS) is a congenital disease with isolated growth hormone deficiency or multiple anterior pituitary hormone deficiencies. Here, the authors report a case of PSIS from Saudi Arabia.Clinical CaseA 16 year old Saudi boy presented to the endocrine clinic with short stature and undescended testis, status post bilateral orchidopexy. He was delivered by caesarean section because of breech presentation and birth asphyxia. Investigation revealed underdeveloped secondary sexual characteristics with decreased facial and pubic hair growth. The patient height was 134 cm whereas the bone age was 9 - 11 years. Pelvis examination showed a scrotum with bilateral 1 mL testes and the stretch penile length was 3 cm.The patient laboratory investigations showed hemoglobin level of 13 g/dL, serum sodium 140 mmol/L, serum potassium 4.1 mmol/L, serum chloride 102 mmol/L, calcium 9.1 mg/dL, random blood sugar 110 mg/dL and albumin 3.8 mg/dL. A pituitary hormone profile showed hypopituitarism with thyroid, and adrenal sparing. The patient free T4 was 17.3 pmol/L (9-25 pmol/L) and synacthen test revealed a morning baseline cortisol level of 6.5 µg/dL (normal = 4.3-22.4 ug/dL) with adrenocorticotrophic hormone of 9.8 pmol/L (1.1 - 13.2 pmol/L). Insulin-like growth factor 1 level 50 ng/dL (normal = 193.0 - 731.0 ug/L), follicle-stimulating hormone 0.35 µIU/mL (normal, 0.0-10.0), and leutinizing hormone 0.4 µIU/mL (normal = 1.2-7.8). The patient’s morning testosterone level showed 8 ng/dL (normal = 280-800 ng/dL) and prolactin 116 mIU/L (normal = 86 - 324 mIU/L). There were no symptom suggestive of posterior pituitary involvement like polyuria and polydipsia as urine and serum osmolality. The MRI examination showed no pituitary gland identified in the sella turcica and no clear pituitary stalk. A T1 hyperintense focus with post-contrast enhancement was identified posterior to the optic chiasma representing an ectopic posterior pituitary gland. The growth hormone and testosterone therapy were added to medical therapy of the patients and no thyroid or hydrocortisone replacement therapy was given. Conclusion: Despite the fact that this is a rare disorder, it should always be kept in the differential diagnosis of a patient presenting with short stature. Patients with this disease have an excellent opportunity to reach normal height if they present before the joining of epiphyses.

SUN-281 Pituitary Hyperplasia Secondary to Uncontrolled Primary Hypothyroidism

Background: There are several recognized causes of hyperplasia of the pituitary gland. These may present as sellar masses and be misdiagnosed as pituitary adenomas. Pituitary hyperplasia can occur in the presence of long standing primary hypothyroidism due to the loss of negative feedback caused by decreased secretion of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland, leading to excessive thyrotropin releasing hormone (TRH) production by the hypothalamus causing Thyrotroph pituitary hyperplasia Clinical case: 51 y/o female with a past medical history that includes anxiety & depression, obesity, pre-diabetes and uncontrolled hypothyroidism due to Hashimoto’s, presented to the Endocrinology clinic for recent diagnosis of pituitary macroadenoma. Patient reported tiredness, decrease energy, myalgias, weight gain, abnormal menstrual periods and frontal headaches. On physical exam, she had a body mass index of 37.39kg/m2, blood pressure of 130/85mmHg, heart rate of 91 bpm. There was no thyromegaly noted on exam. No abdominal striae was noted. Overall, exam was unremarkable. Her neurological exam was normal and there were no obvious visual field deficits. Initial laboratory tests revealed a thyroid stimulating hormone (TSH) >150 uIU/mL (0.46–4.7 uIU/mL), free T4 0.3 ng/dL (0.7–1.3 ng/dL) and positive TPO antibodies. Other endocrine work up including ACTH, cortisol, prolactin, FSH, LH and IGF-1, were normal. An MRI of the pituitary revealed a heterogeneous enhancing mass replacing the pituitary gland in the sella that measured 16 x 17 x 11 mm. She was evaluated by Neurosurgery, for presumed diagnosis of pituitary macroadenoma. However, prompt recognition of uncontrolled primary hypothyroidism causing pituitary hyperplasia lead to medical management, first. She was started on weight based (1.6mcg/kg/day) levothyroxine at 175 mcg per day. Six weeks after thyroid replacement therapy laboratory evaluation showed improvement in thyroid function test with a TSH of 0.8mIU/mL, free T4 2.8ng/dL and total T3 307ng/dL. A repeat MRI of the pituitary showed decrease in size of the pituitary gland measuring 15 x 4 x 10 mm. Conclusion: This case illustrates the importance of early recognition of uncontrolled primary hypothyroidism during the evaluation of a pituitary mass. Complete regression of this pituitary gland abnormality can be achieved with thyroid hormone replacement avoiding the irreversible consequences of inappropriate pituitary surgery.

A Bull in a Pill Shop: Alpha-Gal Allergy Complicating Treatment Options for Postprocedural Hypothyroidism

The galactose-alpha-1,3-galactose (alpha-gal) allergy, an IgE-mediated response to nonprimate meat, has a singular pathogenesis linked to tick bites and a delayed allergic presentation, which makes it especially cumbersome to diagnose and manage. As a large array of enteral medications contain ingredients derived from meat byproducts, this can affect the care of alpha-gal patients across multiple medical disciplines. Our objective is to present a patient with an alpha-gal allergy, which can complicate hypothyroidism treatment selection. In this case of difficulty tailoring thyroid replacement therapy secondary to the alpha-gal allergy, the diagnostic studies included IgE immunoassays for alpha-gal as well as thyroid function tests. A 45-year-old woman with postoperative hypothyroidism and a history of an alpha-gal allergy (diagnosed after an anaphylactic reaction to beef) could not be immediately started on any common thyroid hormone replacement formulation because of our concern regarding the possible presence of nonprimate mammalian meat byproduct components in the thyroid hormone medication. After consulting allergy and immunology specialists and compounding pharmacists and contacting multiple drug companies in an effort to confirm the nature of the inactive ingredients in their thyroid hormone products, she was prescribed a plant-based compounded levothyroxine preparation with good clinical results. This case emphasizes the importance of recognizing various risk factors and common drugs which may be associated with the alpha-gal allergy. It is not known how to best tailor enteral medications for patients with an alpha-gal allergy. Further research and pharmaceutical attention to this allergy are needed.

Влияние пролактина на иммунные характеристики у женщин с аутоиммунным тиреоидитом

Результаты могут быть использованы для совершенствования патогенетической терапии аутоиммунного тиреоидита. Цель — установление особенностей иммунного статуса у женщин с аутоиммунным тиреоидитом (АИТ) в зависимости от уровней пролактина (ПРЛ). Материал и методы. Обследованы 90 женщин с АИТ и субкомпенсированным гипотиреозом: исследованы базальные уровни ПРЛ, тиреотропного гормона (ТТГ), свободного тироксина (свТ4). В подгруппах с гипер- и нормопролактинемией (ГПРЛ, НПРЛ) изучены иммунофенотип лимфоцитов (CD3, CD4, CD8, CD16, CD22), уровень антитиреоидных антител к тиреоглобулину (АтТГ) и тиреопероксидазе (АтТПО). Результаты. ГПРЛ имела место в 35,5% случаев, ее наличие сопровождалось более выраженным гипотиреозом (р&lt;0,05 для повышения уровня ТТГ и р&lt;0,05 для снижения концентрации свТ4) по сравнению с группой с НПРЛ. Все исследованные показатели клеточного иммунитета, а также АтТПО в группе с ГПРЛ были достоверно выше, чем у пациенток с НПРЛ. Установлены достоверные ассоциативные связи между показателями ПРЛ и клеточного иммунитета, а также АтТПО. Выводы. Наличие гиперпролактинемии у пациенток с АИТ провоцирует снижение эффективности заместительной терапии гипотиреоза. Гиперпролактинемия может расцениваться как стимулятор иммунопатогенетического звена аутоиммунного тиреоидита. Повышенные уровни пролактина ассоциируются с повышением уровней Т-, В-лимфоцитов, натуральных киллеров и провоцируют усиление выработки антитиреоидных антител.

Two distinct clinical patterns of checkpoint inhibitor-induced thyroid dysfunction

IntroductionImmune checkpoint inhibitors can lead to thyroid dysfunction. However, the understanding of the clinical phenotype of ICI-induced thyroid dysfunction in the real-world population is limited. The purpose of this study was to characterise the clinical patterns of dysfunction and evaluate the demographic, biochemical and immunological features associated with this patient cohort.Materials and methodsTo characterise the longitudinal clinical course of thyroid dysfunction in patients from a single, UK regional cancer centre, a retrospective review of patients was conducted. Inclusion criteria included all patients treated with antiPD-1 checkpoint inhibitors (ICI), either as monotherapy (pembrolizumab/nivolumab) or in combination with a CTLA-4 inhibitor (ipilimumab). Patterns of toxicity were evaluated together with assessment of antibody titres.ResultsOver 16 months, thyroid dysfunction was seen in 13/90 and 3/13 patients treated with anti-PD1 monotherapy and in combination with ipilimumab, respectively. Patients either developed hyperthyroidism followed by hypothyroidism (12/16) or de novo hypothyroidism (4/16). Most patients were female (n = 11). All patients required thyroid replacement therapy. There was no relationship between clinical pattern of dysfunction and the presence of thyroid autoantibodies.ConclusionsThere are two distinct patterns of thyroid dysfunction in ICI-treated patients. Patients with thyroiditis develop subsequent hypothyroidism in the vast majority of cases. The potential benefit from steroids or other therapy to manage the hyperthyroid phase remains unclear. Early detection of these patients through appropriate monitoring will improve clinical management and early hormone replacement, reducing the symptomatic burden of hypothyroidism.

Thyroïdites : où en est-on en 2019 ?

Thyroiditis is a frequent and mostly benign disease that can sometimes disrupt the thyroid balance. Their diagnosis, as well as their aetiology, is a necessary step in the management of the patients. Painful thyroiditis includes acute thyroiditis of infectious origin and subacute thyroiditis. The first one can be treated by antibiotics or antifungals depending on the germ found. The second one will be treated with non-steroidal anti-inflammatory drugs or corticosteroids. In cases of Hashimoto's thyroiditis with overt hypothyroidism, replacement therapy with L-thyroxine will be adapted to the TSH level. As amiodarone treatment provides dysthyroidism, the thyroid status should be monitored regularly. Hypothyroidism will be treated using thyroid replacement therapy. Hyperthyroidism imposes a stop of amiodarone when it is possible. Treatment with synthetic antithyroid drugs (propyl-thio-uracil) or corticosteroids could be used whether there is an underlying thyroid disease or not. Immunotherapies with anti-PD-1/PDL1 or anti-CTLA-4 can also provide dysthyroidism. A monitoring of the thyroid assessment needs to be done in these patients, even if there are no clinical signs, which are not very specific in this context. The treatment of hypothyroidism will be based on thyroid replacement therapy according to the TSH level and the presence or absence of anti-TPO antibodies. Treatment of symptomatic hyperthyroidism may involve a prescription of beta-blockers, or synthetic antithyroid drugs in case of positive anti-TSH receptor antibodies. In all cases, it is desirable to contact an endocrinologist to confirm the diagnosis hypothesis and to decide on a suitable treatment.

Congenital Hypothyroidism among Newborns and its Association with Maternal Biosocial Factors in Rajshahi Medical College Hospital

Congenital hypothyroidism is the commonest preventable cause of mental retardation. It is more prevalent in endemic goiter regions like Bangladesh. This study was done to assess the congenital hypothyroidism in neonates (age 4 to 28 days) admitted in Rajshahi Medical College Hospital. It was a cross sectional descriptive study conducted at pediatric department of Rajshahi Medical College Hospital from July 2016 to June 2018. After taking written consent from each mother/guardian, 3 ml venous blood was collected and sent to the laboratory of Institute of Nuclear Medicine and Allied Sciences, Rajshahi to estimate serum TSH/ serum TSH and T4 level. Total 500 samples were collected in two years of study period. All information was put in the data collection sheet and was analyzed through standard statistical method by using SPSS version 16.0. Serum level of TSH ≥ 20 μIU/ml was considered as congenital hypothyroidism. Serum level increased but bellow 20μIU/ml were recalled to repeat serum TSH level within 2 to 6 weeks of age. Among 500,321(64.2%) male and 179 (35.8%) female, Among 500 study population, 199 and 135 came from Rajshahi and Chapai Nawabganj district respectively. Total 7 mothers were hypothyroid and on thyroid replacement therapy. TSH level above 20 μIU/ml was found in 5 neonates, 11 to 20 μIU/ml in 7 neonates. After repeat TSH testing one infant had serum TSH level above 20 μIU/ml. Finally total 6 infants were diagnosed as having congenital hypothyroidism. Thus frequency of congenital hypothyroidism was 1.2%. Congenital hypothyroidism in Rajshahi region is very high in relation to global incidence. Although this is not the actual picture of our country but this figure is alarming. Therefore neonatal screening program should be started as soon as possible to reduce the number of mentally retarded child. Maternal obesity and thyroidal status have significant association with neonatal TSH level.&#x0D; TAJ 2019; 32(2): 36-42

Effect of hypothyroidism on cognitive status: Evidence from stroop task

Background: Very less work has been done in the past to assess cognition in hypothyroid patients using classical color-word Stroop task. The Stroop color-word task is a well-recognized tool which estimates cognitive inhibition. Stroop task is based on the fact that reading words and identifying color of written words are two different information and they process with a common response channel but with different speeds. The aim of this study was to assess the cognitive inhibition process in drug-naive hypothyroid patients and their comparison with the same patients after the attainment of euthyroid status and also with euthyroid controls using classical color-word Stroop task. Materials and Methods: Thirty drug-naive newly diagnosed hypothyroid patients were study cases who underwent Stroop task once before initiating treatment and then after the attainment of euthyroid state. We performed the same test in euthyroid controls twice at an interval of 3 months for comparison purpose. Correlation analysis was also done for hypothyroidism and cognition. Results: The reaction time of Stroop task was decreased in all the three conditions of each block, i.e., neutral, incongruent, and congruent conditions after the attainment of euthyroid state, and the finding confirms posttreatment modulation of the attention processes in hypothyroid patients. Reaction time of Stroop task in hypothyroid patients was positively correlated with the serum thyroid-stimulating hormone levels. Processing of color identification was suppressed than reading words in hypothyroid patients as evidenced by increased reaction time of Stroop task. This increase in reaction time can be reversed by earlier identification of drug-naive hypothyroid cases so that they can get timely treatment to restore their cognitive status. Conclusions: Stroop task scores are reduced in overt hypothyroid patients, but improve after thyroid replacement therapy.

Poremećaji kardiovaskularne funkcije i ehokardiografskih parametara srca u manifestnom i subkliničkom hipotireoidizmu

Decreased thyroid function leads to changes in cardiovascular hemodynamics, changes in myocardial contractility and accelerated atherosclerosis. Peripheral circulation in hypothyroidism is characterized by increased vascular resistance and prolonged circulatory duration. Endothelial dysfunction that occurs in hypothyroid patients predisposes to the development of atherosclerosis, and increases arterial stiffness. The influence of subclinical hypothyroidism on the cardiovascular system is manifested through systolic and diastolic cardiac function, myocardial anatomy and effort endurance. Subclinical hypothyroidism in acute myocardial infarction increases cardiac mortality 3.6-fold and 2.3-fold overall mortality. Overt hypothyroidism is characterized by hypercholesterolemia, significantly elevated LDL cholesterol and apolipoprotein B. Subclinical hypothyroidism is associated with a small increase in LDL cholesterol, a decrease in HDL cholesterol, increasing the risk of developing atherosclerosis and coronary artery disease. Isovolumic relaxation time (IVRT) is significantly prolonged in hypothyroid patients, which indicates impaired passive relaxation of the left ventricle. Global right ventricular strain and right ventricular free wall strain are reduced in hypothyroid patients compared to healthy subjects. These changes are completely reversible after the application of thyroid replacement therapy and mostly after 6 months of L-thyroxine administration.

The subclinical hypothyroid state might predict 30-day readmission in patients admitted with acute heart failure syndrome and reduced left ventricular ejection fraction.

Introduction:Thyroid hormone (TH) has an essential role on the functional capability of cardiac muscle with its gene modulation and induction of vasodilatory effects. There is considerable evidence to suggest the role of TH in patients with acute coronary syndrome, but less is known about its prognostic role in heart failure (HF) patients. We aim to evaluate the association between subclinical hypothyroid state (SCHS) and event rates including 30-day all-cause and HF readmission in patients with an index hospitalization for acute HF syndrome (AHFS).Methodology:A retrospective chart review analysis of 2335 patients admitted with the diagnosis of AHFS between 1 January 2007 and 31 December 2017 was conducted. SCHS was defined as thyroid-stimulating hormone (TSH) level >4.50 mIU/L with a normal thyroxine (T4) level. Patients with pre-existing thyroid disease or receiving thyroid replacement therapy were excluded. HF with preserved ejection fraction (HFpEF) was defined as left ventricular ejection fraction (LVEF) >40% and HF with reduced ejection fraction (HFrEF) was defined as having LVEF ⩽40%. Percentage of 30-day, 3-month and 6-month all-cause readmission and mortality rates were calculated in both cohorts of AHFS (HFpEF and HFrEF) with and without SCHS.Results:The mean age of the 2335 AHFS population was 65 (±14.8) years. Of the 2335 patients admitted with AHFS, 1228 (52.6%) patients were found to have HFrEF and 1107 (47.4%) with HFpEF. There were 170 (7.3%) patients with AHFS found to have SCHS. There were more males than females (54% versus 46%). The percentage of hospital readmission within 30 days was higher for patients with SCHS compared with those without SCHS in the HFrEF group (42% versus 30%, p = 0.001). Hospital readmission within 30 days for patients with SCHS compared with those without SCHS in the HFpEF group did not differ (36.5% versus 31%, p = 0.47). Additionally, all-cause mortality was higher among patients with SCHS compared with patients without SCHS in the HFrEF group (18.7% versus 7.0%, p < 0.001). All-cause mortality was found similar in both arms of the HFpEF group (9.5% versus 7.7%, p = 0.73).Conclusion:During an index hospital admission for AHFS, SCHS was an independent predictor of readmission in 30 days in patients with HFrEF but not in patients with HFpEF. Additionally, it was related to adverse outcome such as all-cause mortality in HFrEF patients but not in HFpEF patients. Further studies regarding the concept of tissue thyroid and the potential for a therapeutic target are warranted.

Lithium-associated hypothyroidism and potential for reversibility after lithium discontinuation: Findings from the LiSIE retrospective cohort study.

Background:The association between lithium and thyroid dysfunction has long been known. However, it remains unknown if lithium-associated hypothyroidism is reversible once lithium treatment has been stopped.Aims:To determine whether lithium-associated hypothyroidism was reversible in patients who subsequently discontinued lithium.Methods:A retrospective cohort study in the Swedish region of Norrbotten into the effects and side- effects of lithium treatment and other drugs for relapse prevention (Lithium – Study into Effects and Side Effects). For this particular study, we reviewed medical records between 1997 and 2015 of patients with lithium-associated hypothyroidism who had discontinued lithium.Results:Of 1340 patients screened, 90 were included. Of these, 27% had overt hypothyroidism at the start of thyroid replacement therapy. The mean delay from starting lithium to starting thyroid replacement therapy was 2.3 years (SD 4.7). In total, 50% of patients received thyroid replacement therapy within 10 months of starting lithium. Of 85 patients available for follow-up, 41% stopped thyroid replacement therapy after lithium discontinuation. Only six patients reinstated thyroid replacement therapy subsequently. Of these, only one had overt hypothyroidism.Conclusions:Lithium-associated hypothyroidism seems reversible in most patients once lithium has been discontinued. In such cases, thyroid replacement therapy discontinuation could be attempted much more often than currently done. Based on the limited evidence of our study, we can expect hypothyroidism to recur early after thyroid replacement therapy discontinuation, if at all.