Severe Hypothyroidism Research Articles

SUN-LB094 Massive Pericardial Effusion as an Initial Presentation of Hashimoto's Thyroiditis

Background: Pericardial effusion is a known complication of hypothyroidism and usually correlates with the severity and duration of the disease. However, massive pericardial effusion as the primary presenting manifestation of Hashimoto’s thyroiditis is extremely rare. Case: We present a 44-year-old female with a past history of diabetes mellitus who presented to the hospital with complaints of chest pain described as intermittent, sharp, non-radiating, 10/10 intensity ongoing for six days. On physical examination, she appeared lethargic with slow speech, cool dry puffy skin and muffled heart sounds on auscultation. EKG showed sinus rhythm and no significant ST-T wave changes and troponins trended negative. Initial lab-work was significant for a very high TSH of 86.4 (0.35-5.5 uIU/ml) and a low free T4 of 0.54 (0.61-1.12 ng/dl) with a normal free T3 and total T4. CBC, ESR and CRP were within normal limits. The patient did not endorse noticing any of the classical symptoms of hypothyroidism prior to this admission. Chest X-ray and Chest CT were concerning for a large pericardial effusion. Bedside echocardiogram revealed an ejection fraction of 30% and a massive pericardial effusion. No pericardial calcification or thickening was noted. Due to concern for tamponade physiology on echocardiogram, emergent pericardiocentesis was performed and 720 ml of straw-colored fluid was removed. Cardiac catheterization did not show any evidence of coronary artery disease and repeat echo showed trivial pericardial effusion with improvement in ejection fraction to 40-45%. The fluid analysis did not show evidence of mesothelial cells and cultures were negative. Serological markers for viral diseases (Coxsackie virus, EBV, Adenovirus), as well as immunological markers for rheumatoid arthritis (rheumatoid factor) and lupus (double-stranded DNA) were negative. Serum thyroid peroxidase (TPO) antibody was strongly positive: 877 IU/ml (<9IU/ml). Ruling out other common etiologies, pericardial effusion was attributed to severe hypothyroidism. The patient was treated with IV levothyroxine and IV hydrocortisone and her mental status improved over the course of her stay. Conclusion: Hypothyroidism should certainly be considered as a differential diagnosis in patients presenting with unexplained pericardial effusion. The mainstay of treatment for cases with mild to moderate effusions is thyroxine supplementation. Pericardiocentesis is only indicated in patients with massive effusion who are at risk of developing tamponade. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-590 Failure to Control Severe Hypothyroidism with L-Thyroxine Tablets Corrected by Switching to Oral Soft Gel Formulation

Background: Oral tablets of levothyroxine (L-T4) are the standard of care for the treatment of Hypothyroidism and are recommended by current professional guidelines. However, patients with malabsorption syndromes, intolerance to excipients or dyes in tablets, or the intake of certain medications or foods may not be adequately controlled on these tablets. The use of liquid soft gel capsules (Tirosint) has been reported to be of value in such circumstances. Case Report: A 29 year old woman underwent total thyroidectomy followed by 124.5 mCi 131I therapy at another facility for a right sided 3.7cm PTC with tall cell features. 12 ipsilateral central nodes were positive for cancer. Post therapy WBS was negative for evidence of distant metastases. She was placed onto branded L-T4 treatment but over the next 2 years, in spite of carefully documented adherence to her medication regimen, and with daily doses increasing from 0.1 to 0.3mg, TSH levels were unstable varying from 0.03 to 3.13μIU/ml and then 3 months later rose progressively further to 130μIU/ml. Her clinical Hypothyroidism became critical requiring emergent use of IV L-Thyroxine by her physicians who added L-T3 20μ/d to her L-T4 0.3mg but her TSH did not go below 98.54. She sought care at our institution. Issues of proper technique of medication administration were explained and emphasized with which the patient insisted she was fully compliant. Nevertheless, and in spite of a further increase in the daily L-T4 dose to 0.35mg, TSH remained excessive at 86.94. Treatment was then changed to Tirosint soft gel capsules alone starting at 0.3mg and then decreasing progressively to 0.2mg daily as her TSH reduced to 4.39 (6 months) and has remained in the range of 0.011 to 0.057 over the next 3 years. Other than Vitamin D and the temporary use of Depo-Provera, the patient denied the use of any other medications or supplements. Discussion: L-T4 tablets have long been the preferred and recommended treatment form for Hypothyroidism by professional societies. (1, 2) However, reports have appeared noting poor and inconstant response to this treatment in occasional patients such as those with malabsorption syndromes such as following bariatric surgery (3) or with gastroparesis (4), or with the concomitant intake of other medications such as proton pump inhibitors (5) or foods such as coffee (6). In such circumstances, it has been reported that use of liquid L-T4 or liquid soft gel capsules containing no excipients beyond glycerin and gelatin results in improved absorption of L-T4 with better and more stable control of thyroid biochemistry including TSH. (3, 4, 5, 6, 7) We present a case of a patient with Papillary Thyroid Cancer who, following total thyroidectomy and 131I therapy, had variable and inadequate TSH suppression with development of clinical unresponsiveness to standard branded L-T4 treatment. Switching therapy to a soft gel product has enabled stable control of TSH

SUN-581 An Unusual Presentation of Hypothyroidism

Introduction: Hashimoto’s thyroiditis (HT) rarely presents with clinical myopathy, with elevated muscle enzymes and acute kidney injury (AKI) due to rhabdomyolysis. A pilot study has suggested an increased prevalence of subclinical hypothyroidism in patients with unprovoked deep venous thrombosis (DVT). We report a case of HT presenting with asymmetric myopathy, AKI, and bilateral lower extremity DVTs, who responded well to thyroid hormone replacement. Case Description: A 58-year-old man with history of psoriasis presented with new erythematous plaques over the trunk and extremities for one month. He had episodic numbness and heaviness in the arms, thighs, and hands, especially when he held objects for sometime (e.g. steering wheel or holding a cell phone). He had difficulty in getting up from a sitting position. He also felt that his calves were swollen. He experienced stiffness in the hands. On examination, he had an asymmetric decrease in muscle power (4/5) in the proximal muscles of the upper and lower extremities. He had small circumscribed psoriatic plaques on the elbows, knees, and trunks. In addition, bilateral pitting edema was noted. Laboratory evaluation was remarkable for elevated creatinine phosphokinase 2310 IU/L, aldolase 15.6 U/L, elevated serum creatinine at 1.34 mg/dl, and elevated CRP at 9.5 mg/dl. Serological tests for connective tissue disease were all negative. Myositis associated and specific antibodies were negative. Electromyography was consistent with myopathic process with changes in numerous muscle groups bilaterally, most prominent in gluteus medius, lumbar, thoracic and cervical paraspinals. Nerve conduction study showed bilateral carpal tunnel syndrome. Three weeks later, his lower extremity swelling worsened. Ultrasound venous dopplers revealed bilateral DVT in the posterior tibial and peroneal veins. Thyroid function tests revealed elevated TSH (103.26 micro-IU/mL) and low free T4 (0.22 ng/dl). He has elevated thyroid peroxidase and thyroglobulin antibodies. He was hospitalized for management of unprovoked DVT and severe hypothyroidism secondary to HT. He was started on levothyroxine. Four weeks later, the myopathy resolved and muscle enzymes normalized. TSH improved to 35 micro-IU/ML. Discussion: HT presenting with clinical myopathy and DVT is extremely rare. Few features in this case raised the question of an alternative etiology for the myopathy – asymmetric proximal muscle involvement, acute to subacute course, and absence of myositis specific antibodies. In a pilot cross sectional study, increased prevalence of subclinical hypothyroidism was found in patients with unprovoked DVT, as noted in our case. This case highlights the atypical presentation of hypothyroidism due to HT. The identification of the hypothyroidism and initiation of thyroid hormone replacement improved the quality of life and physical function in our patient.

SAT-619 Myxedema Coma: A Modern Day Rarity

Background: Myxedema coma is a rare, but severe form of hypothyroidism with a high mortality rate. Case: An eighty-nine-year-old female with a history of hypothyroidism and hypertension presented from a nursing home with lethargy, bradycardia, and hypothermia. She was oriented to self only, minimally verbal requiring assistance for activities of daily life at baseline. Medications included cardizem, lisinopril, and levothyroxine 150 mcg at stable doses for a year. Physical examination was significant for hypothermia (35.4°C) and bradycardia (heart rate of 40); the patient was obtunded. Initial labs were significant for AKI, hyperkalemia, and transaminitis. Echo showed an EF of 60% with impaired LV relaxation. A temporary pacemaker was placed and the patient was started on an isoproterenol drip. TSH was drawn due to the history of hypothyroidism and was elevated at 270 (0.5-5 mU/L). Serum cortisol was drawn and a dose of hydrocortisone 100 mg was given intravenously followed by an IV dose of levothyroxine 100 mcg and liothyronine 20 µg. Serum cortisol level was high at 54.2 µg/dl (0.4-22.6 µg/dl). Her mental status improved the following day, bradycardia resolved and the isoproterenol drip was stopped. She was started on IV levothyroxine 50mcg daily. Subsequently, hyperkalemia and transaminitis resolved, but her renal function continued to deteriorate. Due to her poor baseline functional status, her spouse decided against dialysis and the patient was transitioned to inpatient hospice. Discussion: Myxedema coma is defined as severe hypothyroidism leading to decreased mental status, hypothermia and other symptoms related to slowing of function in multiple organs. Nowadays, due to the wide availability of TSH assays that are performed routinely, hypothyroidism is detected and treated early and rarely leads to myxedema coma. However, it can present itself in hypothyroid patients with poor compliance and comorbid conditions. Since it is associated with a high mortality rate, treatment should be initiated without waiting for lab results. Glucocorticoids are given until the possibility of co-existing adrenal insufficiency has been excluded. A dose of IV T₃ and T₄ is administered followed by maintenance IV T₄ daily until the patient is able to take PO.T₃ is continued until clinical improvement and stabilization of the patient. Clinical and biochemical improvement is usually seen within a week. Despite treatment, it has a 30-50% mortality rate. Conclusion: Myxedema coma is a rare endocrine emergency with a high mortality rate that requires a high index of suspicion and warrants early treatment.

OR10-1 Regulation of Glucocorticoid Metabolism: A Novel Function for Thyroid Hormones?

Glucocorticoid hormone metabolism and action are regulated by the 11-beta hydroxysteroid dehydrogenase (11βHSD) isozymes: the 11βHSD2, mostly expressed in the distal nephron, converts cortisol [F] into cortisone [E] in humans or corticosterone [B] into 11-dehydrocorticosterone [A] in rodents (11-dehydro derivatives being inactive compounds), and the 11βHSD1, ubiquitously expressed but abundant in the liver, catalyzes the opposite reaction. Under pathophysiological conditions of severe hypothyroidism, altered glucocorticoid metabolism has been observed, with decreased [F] to [E] conversion1,2. However, direct functional relationship between these two hormonal pathways has never been demonstrated to date. Using bioinformatics analyses, we identified five thyroid hormone response elements in the promoter region of the murine hsd11b2 gene. Therefore, we aimed at investigating whether thyroid hormones (T3) directly regulate expression and/or activity of the 11βHSD2 enzyme. We used three complementary models: human and mouse translational studies and molecular analyses in HEK293T cells and in fully differentiated KC3AC1 cortical collecting duct cells. Children and adults in hypo- or hyperthyroidism status were first compared either to age- and sex-matched euthyroid controls, or to themselves after reaching a euthyroid status. The urinary [E]/[F] ratio measured by LC-MS/MS method, was used as an index of renal 11βHSD2 activity. Interestingly, a 60% decrease in the [E]/[F] ratio was observed in hypothyroid patients, corroborating our hypothesis (p<0.05). Next, a mouse model of hyperthyroidism, generated by administrating T3 in drinking water, led to a significant 10% increase in renal 11βHSD2 mRNA and protein levels compared to wild type mice (n=10, p<0.05). Furthermore, we demonstrated in HEK293T cells that T3 transactivates the mouse hsd11b2 promoter cloned upstream the luciferase reporter gene via the Thyroid Receptor α1(TRα1). Finally, we showed that T3 exposure induces a 50% increase in 11βHSD2 mRNA levels in KC3AC1 cells, in a dose-dependent and time-dependent manner (as early as 6 h) (p<0.01). This induction was abrogated by Actinomycin D or DRB, two inhibitors of transcription, underlining a transcriptional regulatory mechanism. In addition, 11βHSD2 enzymatic activity, quantified by the [F] to [E] conversion ratio measured by LC-MS/MS in cell supernatants, increased significantly by 20% (p<0.05) after 24 h exposure to 100 nM T3. ChIP experiments further demonstrated a T3-dependent specific recruitment of the TRα1 onto the hsd11b2 promoter region. Altogether, our findings constitute the first demonstration that thyroid hormones directly regulate expression and activity of the renal 11βHSD2 enzyme, thereby controlling glucocorticoid metabolism and action.

Mona Lisa is euthyroid: a modern-day diagnosis.

Making any medical diagnosis of an individual appearing in an old painting is risky. Throughout history, the famous painting of the Mona Lisa by Leonardo da Vinci has challenged many scientists and physicians to scrutinize this striking and enigmatic female image for the purpose of potentially explaining the woman "behind the smile" and offering a medical diagnosis of her state of health. A recent proposal was that she suffered from severe hypothyroidism and that her asymmetric smile was due to psychomotor retardation. Today, in the twenty-first century, can Mona Lisa get "a second opinion?"

A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma.

SummaryImmune checkpoint inhibitors (ICIs) have revolutionised cancer therapy and improved outcomes for patients with advanced disease. Pembrolizumab, a monoclonal antibody that acts as a programmed cell death 1 (PD-1(PDCD1)) inhibitor, has been approved for the treatment of advanced melanoma and other solid tumours. Immune-related adverse events (irAEs) including endocrinopathies have been well described with this and other PD-1 inhibitors. While hypothyroidism and hyperthyroidism, and less commonly hypophysitis, are the most common endocrinopathies occurring in patients treated with pembrolizumab, the incidence of type 1 diabetes mellitus (T1DM) was low in clinical trials. We report a case of pembrolizumab-induced primary hypothyroidism and T1DM presenting with severe diabetic ketoacidosis (DKA). A 52-year-old male patient was treated with pembrolizumab for metastatic melanoma. He presented to the emergency department with a 1-day history of nausea and vomiting 2 weeks after his seventh dose of pembrolizumab, having complained of polyuria and polydipsia for 2 months before presentation. He had been diagnosed with thyroid peroxidase (TPO) antibody-negative hypothyroidism, requiring thyroxine replacement, shortly after his fifth dose. Testing revealed a severe DKA (pH: 6.99, glucose: 38.6 mmol/L, capillary ketones: 4.9 and anion gap: 34.7). He was treated in the intensive care unit as per the institutional protocol, and subsequently transitioned to subcutaneous basal-bolus insulin. After his diabetes and thyroid stabilised, pembrolizumab was recommenced to treat his advanced melanoma given his excellent response. This case highlights the importance of blood glucose monitoring as an integral part of cancer treatment protocols composed of pembrolizumab and other ICIs.Learning points:The incidence of T1DM with pembrolizumab treatment is being increasingly recognised and reported, and DKA is a common initial presentation.Physicians should counsel patients about this potential irAE and educate them about the symptoms of hyperglycaemia and DKA.The ESMO guidelines recommend regular monitoring of blood glucose in patients treated with ICIs, a recommendation needs to be incorporated into cancer treatment protocols for pembrolizumab and other ICIs in order to detect hyperglycaemia early and prevent DKA.

Myxedema coma precipitated by diabetic ketoacidosis after total thyroidectomy: a case report

BackgroundMyxedema coma is profound decompensated hypothyroidism usually precipitated by stressors, and its occurrence in association with total thyroidectomy or metabolic disorders, such as diabetic ketoacidosis, is unusual.Case presentationA 43-year-old Asian man with history of total thyroidectomy who was scheduled for a second radioactive iodine therapy presented to our hospital with decreased mental status and hyperglycemia. He had a history of thyroid cancer but did not have diabetes mellitus. He was in a hypothermic state and had a Glasgow Coma Scale score of 10 out of 15 at presentation; arterial blood gas analysis revealed a state of metabolic acidosis and laboratory findings suggested hyperglycemia with glycosuria, ketoacidosis, and severe hypothyroidism. A thyroid function test showed thyroid-stimulating hormone of 34.126 uIU/mL, free thyroxine of 1.02 ng/dL, and triiodothyronine of 1.04 ng/mL. The glycated hemoglobin of this patient was checked due to hyperglycemia and the value of glycated hemoglobin was 16.5% which met the criteria for a diagnosis of diabetes. After treatment for myxedema with liothyronine 5 mcg two times per day and levothyroxine 175 mcg once daily via a nasogastric tube and diabetic ketoacidosis with intravenously administered fluid and insulin, his clinical condition rapidly improved including mental status, hyperglycemia, and acidosis. During the hospitalization, a workup for diabetes mellitus was performed and the results suggested that a diagnosis of type 2 diabetes mellitus would be appropriate.ConclusionsThis case demonstrated that diabetic ketoacidosis not only could be a potential contributor to myxedema coma but also mask typical clinical features, making diagnosis more difficult. Considering the possibility of an increasing number of potential patients with hypothyroidism developed after thyroidectomy, constant vigilance is required for a better clinical outcome, including early recognition and management in critical care in advance for unusual diabetic ketoacidosis which could precipitate decompensated hypothyroidism.

A CASE OF AMIODARONE-INDUCED HYPOTHYROIDISM COMPLICATED BY TORSADES DE POINTES

Amiodarone is a class III antiarrhythmic drug that is commonly used for management of tachyarrhythmias. Amiodarone-induced hypothyroidism is a well-established side effect; however severe hypothyroidism presenting with torsades de pointes (TdP) is an underappreciated complication. A 69-year-old

A CURIOUS CASE OF THE DILATED HEART: A CASE OF REVERSIBLE DILATED CARDIOMYOPATHY DUE TO SEVERE HYPOTHYROIDISM CAUSED BY HASHIMOTO THYROIDITIS

Dilated cardiomyopathy has varied etiology. Here we present a case of severe hypothyroidism presenting as reversible dilated cardiomyopathy. 64 yo African American female was referred to us for consideration for advanced heart failure therapies. She was in her usual state of health until 4 months

Adrenal Steroids in Female Hypothyroid Neonates: Unraveling an Association Between Thyroid Hormones and Adrenal Remodeling.

The adrenal gland undergoes substantial remodeling during the neonatal period, an essential developmental process that remains incompletely understood. With respect to control over the remodeling process and, specifically, the role of thyroid hormones (THs), no human studies have been published. The effects of both hypo- and hyperthyroidism have only been evaluated in adults, focusing on the mature adrenal. Recent studies have identified expression of the TH receptor β1 in the mouse adrenal X-zone and have demonstrated that TH administration could alter the postnatal adrenal remodeling process. To address whether THs influence adrenal steroid profiles and adrenal remodeling during the neonatal period. We compared the adrenal steroid profile of a naturally occurring prototype, female neonates with severe congenital hypothyroidism (CH) (n = 22, upon diagnosis of CH), with that of euthyroid neonates (n = 20). Significantly higher levels of adrenal steroids (17-OH-progesterone, dehydroepiandrosterone sulfate, Δ4-androstenedione, and testosterone) were measured in neonates with severe CH compared with euthyroid neonates and returned to within normal range after euthyroid state had been established on l-thyroxine replacement therapy, whereas cortisol levels did not differ. TSH values in the CH group were positively correlated with circulating adrenal steroids, whereas free T4 levels were negatively correlated with circulating adrenal steroids. The hormonal profile of female neonates with severe CH suggests a more active adrenal fetal zone compared with control subjects. These data indirectly associate THs with the adrenal remodeling and maturation process in humans. Based on our results, we suggest that severe hypothyroidism decelerates the involution of the adrenal fetal zone that normally occurs postnatally.

Combination therapy of propranolol, levothyroxine, and liothyronine was effective in a case of severe consumptive hypothyroidism associated with infantile hepatic hemangioma.

.Infantile hepatic hemangioma (IHH) can be accompanied by consumptive hypothyroidism. We report the case of a 4-mo-old boy who showed massive hepatomegaly, peripheral coldness, lethargy, and failure to thrive. An enhanced computed tomography scans demonstrated multiple hemangiomas in both lobes of the liver, and a thyroid function tests showed severe hypothyroidism: TSH 561.5 µIU/mL, free triiodothyronine (fT3) 1.0 pg/mL, and free thyroxine (fT4) < 0.7 ng/dL. IHH gradually regressed following propranolol treatment and fT4 increased to a low normal level (1.0 ng/dL) by high dose replacement of levothyroxine, while fT3 remained very low (< 1.0 pg/mL), even following high doses of levothyroxine; fT3 eventually normalized following the administration of liothyronine. We suggest that treatment strategies should be individualized based on thyroid function, and that the combination therapy of propranolol for anti-tumor treatment and levothyroxine and liothyronine for respective thyroid hormone replacement is effective, particularly in cases of severe consumptive hypothyroidism due to multiple IHHs.

Severe hypothyroidism-associated acute renal failure – A case series from North India and review of literature

Background: Several cases of complete or partially reversible renal failure have been reported in association with severe hypothyroidism, which have responded to thyroxine replacement. However, its risk factors, pathology, pathophysiology, and time of recovery remain unclear. Aim: We report our experience with 31 cases of renal failure in association with severe hypothyroidism, from a goiter-endemic belt in North India, along with a review of existing literature. Materials and Methods: We retrieved cases presenting to our centre, from August 2013 to April 2018 and collected information regarding clinical presentation, laboratory parameters including renal and thyroid function tests, creating kinase, urinary findings and follow-up data pertaining to time and extent of renal function recovery. In three cases, renal biopsies were also done, and these were reviewed by a pathologist. Results: In our study, females slightly outnumber males. More than one-third of patients were known hypothyroid and had defaulted on medications. The severity of serum thyroid-stimulating hormone and CK elevation were not associated with the severity of renal failure or its extent or time of recovery. Older age, coexistence of diabetes mellitus and/or hypertension, higher serum creatinine at presentation, and urinary abnormalities (proteinuria and/or active sediments) correlated significantly with lack of complete renal recovery. All the three biopsies revealed significant tubulointerstitial fibrosis. Conclusions: Thyroid function tests should be performed in the evaluation of unexplained renal failure, even in cases with underlying chronic kidney disease. It is also an important preventable cause of renal failure in known hypothyroid patients.

White matter microstructural abnormalities in children with severe congenital hypothyroidism.

This study assessed white matter microstructural integrity and behavioral correlates for children with severe congenital hypothyroidism (CH) who were identified and treated early following newborn screening. Eighteen children with severe CH and 21 healthy controls underwent a battery of behavioral measures of hearing, language and communication, along with diffusion MR imaging. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. Microscopic diffusion anisotropy mapping based on the Spherical Mean Technique was also used to evaluate biologically specific metrics. Compared with age-matched controls, children with severe CH had poorer hearing and communication skills, albeit generally within normal limits. Children with severe CH had fractional anisotropy that was significantly lower in the cerebellum, bilateral thalami and right temporal lobe, and radial diffusivity that was significantly higher in the cerebellum and bilateral thalami. Microscopic fractional anisotropy and intra-neurite volume fraction were also significantly decreased, and transverse microscopic diffusivity was significantly increased, in the CH group in areas including the cerebellum, thalamus, occipital lobe, and corpus callosum, and in the white matter adjacent to sensorimotor cortex, particularly in the left hemisphere. Significant and widespread correlations were observed between behavioral measures and measures of white matter microstructural integrity in children with CH. The results indicate that children with severe CH who are identified through newborn screening may have significant brain white matter microstructural abnormalities despite early treatment.

Thyroid Symptomatology across the Spectrum of Hypothyroidism and Impact of Levothyroxine Supplementation in Patients with Severe Primary Hypothyroidism.

Objective:This study aimed to determine the clinical and biochemical profile of patients with severe primary hypothyroidism (SPH) (TSH ≥40 μIU/ml) as compared to milder forms of hypothyroidism and document improvement in hypothyroidism symptoms in SPH.Methods:Thyroid symptomatology and biochemistry were evaluated in SPH, non-severe overt primary hypothyroidism (NSOPH; TSH <40 μIU/ml), subclinical hypothyroidism (ScH) and healthy controls. A total of 598 consecutive patients of hypothyroidism were screened of which 461 patients' data were analyzed (91 SPH, 130 NSOPH and 240 ScH). Thyroid symptomatology was re-evaluated at 12 weeks follow-up in SPH following restoration of euthyroidism with levothyroxine.Results:The median (interquartile range) age of patients was 35 (28-42) years with 91.6% female. The commonly noted symptomatology were shortness of breath (93.4%) and fatigueability (91.2%) in SPH, fatigueability (68.46%) and limbs swelling (43.07%) in NSOPH, and fatigueability (56.67%) and shortness of breath (32.92%) in ScH. All symptomatology were significantly higher in SPH. Delayed tendon reflex, carpel tunnel syndrome and meno-metrorrhagia were exclusive in SPH. Occurrence of menstrual irregularities was 73.62%, 28.46% and 16.25% in SPH, NSOPH and ScH, respectively. SPH patients had significantly higher cholesterol and triglycerides. There was significant improvement in symptomatology, reduction in body weight (−2.11 kg), improvement in hemoglobin (+0.64 g/L) with fall in total cholesterol (−18.96%), LDL-cholesterol (−23.46%) and triglycerides (−13.53%) following euthyroidism restoration in subjects with SPH. Common residual symptoms were fatigue (10%), poor memory (8%) and menstrual irregularities (6%).Conclusion:Thyroid symptomatology differs significantly across spectrum of hypothyroidism, being significantly worse in SPH. Euthyroidism restoration is associated with reversal of majority of thyroid symptomatology.

Severe hyponatremia as a presenting sign of panhypopituitarism due to non-functioning pituitary adenoma: a case report

ABSTRACT BACKGROUND: Hyponatremia is a commonest electrolyte imbalance which is defined as \&amp;quot;serum sodium level less than 135mEq/L\&amp;quot;. It is seen especially in elderly patients presenting in emergency department of hospitals. There are wide range of differentials in hyponatremic patients but it can be the initial sign of pituitary disease specifically in old age population. Diagnosis can often be challenging because symptoms can be attributed to normal aging process and high index of clinical suspicion is necessary. CASE PRESENTATION: Here we present the case of 61-year old female presented in our facility with history of vomiting, drowsiness and fatigue for 2 days before admission. On investigating, her CBC, LFT\&amp;apos;s, RFT\&amp;apos;s and urine R/E were within normal limits. Serum electrolytes showed hyponatremia. CXR was also normal. As patient was not in fluid overload, so our differentials based on euvolumic hyponatremia included syndrome of inappropriate anti-diuretic hormone secretion(SIADH), severe hypothyroidism or glucocorticoid insufficiency. Urine osmolarity was not in range of SIADH. Serum cortisol was normal. FSH, LH, estrogen and progesterone were low although these should be high as patient was post-menopausal. Prolactin was normal. MRI brain with contrast showed supra and intrasellar mass consistent with pituitary macroadenoma. Depending on presentation and investigations, Non-functioning pituitary adenoma(NFPA) presenting with panhypopituitarism complicated by hyponatremia was the final diagnosis. CONCLUSION: Our case highlights the importance of diagnosing NFPA in elderly patients who present with hyponatemia which can often be challenging and should not be delayed as this is life-saving, hence targeted treatment should be started as soon as possible.

Hypothyrodisim: A new aspects of old disease

Objective: To present relevant and updated information on the status of hypothyroidism in the pediatric population (newborn infants to adolescents). Sources: Original and review articles and books containing relevant updated data. Summary of the findings: This review addressed data on the etiopathogeny of hypothyroidism and on the importance of screening for congenital hypothyroidism to assure early diagnosis and treatment of the newborn. We point out the difficulties experienced in the handling of subclinical hypothyroidism; we also address the importance of diagnosing autoimmune Hashimoto’s thyroiditis, the high incidence of the disease among adolescents, mainly females, and the occurrence of a severe neurological condition, Hashimoto’s encephalopathy. We indicate situations in which severe hypothyroidism may lead to puberty disorders (precocious or delayed puberty) and describe the importance of transcription factors in thyroid embryogenesis. Diagnostic and therapeutic criteria are also addressed. Conclusion: Thyroid hormones are necessary for normal growth and development since fetal life. Insufficient production or inadequate activity on the cellular or molecular level lead to hypothyroidism. These hormones are necessary for the development of the brain in the fetus and in the newborn infant. Neonatologists and pediatricians deal with child development issues in their practice, and many of these issues start during intrauterine life. Currently, with neonatal screening, neonatologists and pediatricians can prevent irreversible damage through early treatment. They should also be alert for dysfunctions such as subclinical hypothyroidism and Hashimoto’s thyroiditis, which may provoke damage not only to growth, but also to the neurological and psychological development of these children and adolescents, thyroid hormones, thyropathies, thyroid failure, pediatric hypothyroidism, thyroid deficiency.

Fetal Sinus Bradycardia Is Associated with Congenital Hypothyroidism: An Infant with Ectopic Thyroid Tissue.

Hypothyroidism is rarely included in the differential diagnosis for fetal sinus bradycardia. We report an infant with congenital hypothyroidism caused by ectopic thyroid tissue, who showed antenatal bradycardia. The baseline fetal heart rate was 100-110 bpm at 30 weeks of gestation, and fetal echocardiography revealed sinus bradycardia but no cardiac anomalies. Maternal thyroid function was normal (thyroid-stimulating hormone [TSH] 2.03 μIU/ml, free T3 2.65 pg/ml, and free T4 0.99 ng/dl) when measured at 31 weeks of gestation. Her serum anti SS-A and SS-B antibodies, anti-thyroglobulin, and microsomal antibodies were negative. A male infant without cardiac anomalies was delivered at 35 weeks and 4 days of gestation and admitted for prematurity and respiratory distress syndrome. The infant's heart rate was 70-110 bpm (normal: 120-160 bpm) on admission. On 8 days of age, thyroid function tests revealed that the infant had severe hypothyroidism (TSH 903.3 μIU/ml, free T3 1.05 pg/ml, and free T4 0.26 ng/dl). The prolonged jaundice assumed to be due to hypothyroidism. Oral levothyroxine sodium hydrate (10 μg/kg/day) was immediately started on day 8. After the treatment, the heart rate was gradually increased to 130-140 bpm as the infant's thyroid function was improved (TSH 79.8 μIU/ml, free T3 2.95 pg/dl, and free T4 1.66 ng/dl on day 22). The infant was diagnosed ectopic thyroid tissue because of the high thyroglobulin level (85.9 μg/l). In conclusion, congenital hypothyroidism should be included in the differential diagnosis in cases of fetal bradycardia without cardiac anomalies or maternal autoimmune diseases.

An exonic splicing enhancer mutation in DUOX2 causes aberrant alternative splicing and severe congenital hypothyroidism in Bama pigs.

ABSTRACTPigs share many similarities with humans in terms of anatomy, physiology and genetics, and have long been recognized as important experimental animals in biomedical research. Using an N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we previously identified a large number of pig mutants, which could be further established as human disease models. However, the identification of causative mutations in large animals with great heterogeneity remains a challenging endeavor. Here, we select one pig mutant, showing congenital nude skin and thyroid deficiency in a recessive inheritance pattern. We were able to efficiently map the causative mutation using family-based genome-wide association studies combined with whole-exome sequencing and a small sample size. A loss-of-function variant (c.1226 A>G) that resulted in a highly conserved amino acid substitution (D409G) was identified in the DUOX2 gene. This mutation, located within an exonic splicing enhancer motif, caused aberrant splicing of DUOX2 transcripts and resulted in lower H2O2 production, which might cause a severe defect in thyroid hormone production. Our findings suggest that exome sequencing is an efficient way to map causative mutations and that DUOX2D409G/D409G mutant pigs could be a potential large animal model for human congenital hypothyroidism.

Cardiac tamponade combined with pleural and peritoneal effusions, as the presenting manifestation of primary hypothyroidism

We present a rare case of cardiac tamponade as the initial presentation of primary hypothyroidism. A 38-year-old woman presented with shortness of breath and fatigue for 2 months. She had cardiomegaly on chest X-ray, and transthoracic echocardiogram showed evidence of cardiac tamponade. Urgent pericardiocentesis was performed; the pericardial fluid was exudative with negative cultures and cytology. She was also found to have pleural effusions and ascites. Laboratory tests revealed severe hypothyroidism, and thyroxine replacement therapy was started. The case highlights that the diagnosis of hypothyroidism should not be overlooked during the evaluation of patients with pericardial effusions.