Generation of a mouse model of thyroid storm and preliminary investigation of the therapeutic effects of ghrelin.

BACKGROUND: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, has limited therapeutic options. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. We aimed to develop a TS mouse model by administration of triiodothyronine and lipopolysaccharide, and then to examine the effects of ghrelin on this model. METHODS: We evaluated the use of serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. To establish the mouse model, preliminary experiments were conducted to determine the non-lethal doses of triiodothyronine and lipopolysaccharide when administered individually. As a TS model, C57BL/6 mice were administered with triiodothyronine 1.0 mg/kg (subcutaneously, once daily for seven consecutive days) and lipopolysaccharide 0.5 mg/kg (intraperitoneally, on day 7) to develop a lethal model with approximately 30% survival on day 8. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin 300 µg/kg on these parameters in TS model. RESULTS: Serum IL-6 was increased in patients with TS compared with those with Graves' disease as the diseased control (18.2 vs. 2.85 pg/mL, P < .05, n = 4 each). The dosage for the murine TS model was triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg. The TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin improved the survival rate to 66.7% (P < .01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. CONCLUSION: We established an animal model of TS that exhibits pathophysiological states similar to human TS with induction of serum IL-6 and other biomarkers by administration of T3 and LPS. The results suggest the potential effectiveness of ghrelin for TS in humans.

Therapeutic plasma exchange for control of thyroid storm.

Therapeutic plasma exchange (TPE) for thyroid storm has recently been upgraded to a category II indication after decades though its recommendation level still remains at Grade 2C according to the American Society for Apheresis (ASFA). In the absence of prospective randomized controlled trials due to the rarity of thyroid storm, retrospective data from case series continue to elevate the clinical evidence supporting TPE as a life-saving modality for complicated thyroid storm patients. We report three cases of life-threatening thyroid storm from Graves' disease rescued by TPE via rapid reduction in circulating thyroid hormones. Each patient underwent TPE when it was judged that other thyroid storm treatment options were futile or unsafe. The first patient received 4 cycles of TPE while the second patient received 9 cycles of TPE, and the third patient received 2 cycles of TPE with satisfactory clinical improvement. Plasma FT4 and TSH receptor antibody levels of the first case declined by 41.3% and >50% respectively right after the first round of TPE; plasma FT4 of the second patient dropped by up to 31.6% during the course of TPE; plasma FT4 and TSH receptor antibody of the third patient declined by 66% and 56.2% respectively after the first cycle of TPE. This demonstrates the safety, efficacy, and feasibility of TPE in thyroid storm especially when other therapeutic interventions are contraindicated. TPE operates via the elimination of serum proteins-bound thyroid hormones, thyroid autoantibodies, cytokines, and catecholamines in addition to increasing unsaturated binding sites for thyroid hormones.

Thyroid storm and warm autoimmune hemolytic anemia.

Graves' disease is often associated with other autoimmune disorders, including rare associations with autoimmune hemolytic anemia (AIHA). We describe a unique presentation of thyroid storm and warm AIHA diagnosed concurrently in a young female with hyperthyroidism. The patient presented with nausea, vomiting, diarrhea and altered mental status. Laboratory studies revealed hemoglobin 3.9g/dL, platelets 171×109L-1, haptoglobin <5mg/dL, reticulocytosis, and positive direct antiglobulin test (IgG, C3d, warm). Additional workup revealed serum thyroid stimulating hormone (TSH) <0.01µIU/mL and serum free-T4 (FT4) level 7.8ng/dL. Our patient was diagnosed with concurrent thyroid storm and warm AIHA. She was started on glucocorticoids to treat both warm AIHA and thyroid storm, as well as antithyroid medications, propranolol and folic acid. Due to profound anemia and hemodynamic instability, the patient was transfused two units of uncrossmatched packed red blood cells slowly and tolerated this well. She was discharged on methimazole as well as a prolonged prednisone taper, and achieved complete resolution of the thyrotoxicosis and anemia at one month. Hyperthyroidism can affect all three blood cell lineages of the hematopoietic system. Anemia can be seen in 10-20% of patients with thyrotoxicosis. Several autoimmune processes can lead to anemia in Graves' disease, including pernicious anemia, celiac disease, and warm AIHA. This case illustrates a rarely described presentation of a patient with Graves' disease presenting with concurrent thyroid storm and warm AIHA.

A case of thyroid storm with a markedly elevated level of circulating soluble interleukin-2 receptor complicated by multiple organ failure and disseminated intravascular coagulation syndrome.

Thyroid storm (TS) is a life-threatening endocrine emergency. However, the pathogenesis of TS is poorly understood. A 40-year-old man was admitted to a nearby hospital with body weight loss and jaundice. Five days after a contrasted abdominal computerized tomography (CT) scan, he exhibited high fever and disturbance of consciousness. He was diagnosed with TS originating from untreated Graves' disease and was transferred to the intensive care unit (ICU) of our hospital. The patient exhibited impaired consciousness (E4V1M4 in Glasgow coma scale), high fever (39.3°C), and atrial flutter with a pulse rate 162/min, and was complicated by heart failure, acute hepatic failure, and disseminated intravascular coagulation syndrome (DIC). His circulating level of soluble interleukin-2 receptor (sIL-2R), a serum marker of an activated immune response, was highly elevated (7,416 U/mL, reference range: 135-483). Multiple organ failure (MOF) and DIC were successfully managed by multimodality treatments using inorganized iodide, glucocorticoids, anti-thyroid drugs, beta-blockers, and diuretics as well as an anticoagulant agent and the transfusion of platelet concentrate and fresh frozen plasma. sIL-2R levels gradually decreased during the initial treatment, but were still above the reference range even after thyroidectomy. Mild elevations in serum levels of sIL-2R have previously been correlated with thyroid hormone levels in non-storm Graves' disease. The present study demonstrated, for the first time, that circulating sIL-2R levels could be markedly elevated in TS. The marked increase in sIL-2R levels was speculated to represent an inappropriate generalized immune response that plays an unknown role in the pathogenesis of TS.

Thyroid crisis mimicking clinically mild encephalitis/encephalopathy with a reversible splenial lesion: A pediatric case report.

BACKGROUND: Reversible lesions in the splenium of the corpus callosum (SCC) with viral infections are associated mainly with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We report a pediatric patient in thyroid crisis with reversible SCC lesions. CASE DESCRIPTION: We diagnosed a 9-year-old girl with thyroid crisis. She had presented with fever, tachycardia, and impaired consciousness. Magnetic resonance imaging revealed hyperintense signals in the splenium and genu of the corpus callosum and a white matter lesion of the left hemisphere in diffusion-weighted imaging. The initial, tentative diagnosis was clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We initiated intravenous methylprednisolone pulse therapy; thereafter, her level of consciousness rapidly improved. On admission, thyroid function studies revealed elevation of free thyroxine and a low level of thyroid stimulating hormone with thyroid-related autoantibodies. She was begun on thiamazole and was discharged without neurological sequelae. CONCLUSION: Thyroid crisis is similar to acute encephalitis or encephalopathy associated with viral infection, especially with MERS, because the clinical and radiological features resemble those of thyroid crisis; therefore, thyroid diseases should be considered as a possible cause of reversible lesions in the splenium of the corpus callosum.

Thyroid storm presenting as septic shock in the intensive care unit: A Case Series.

Thyroid storm is a rare endocrine emergency that rarely presents with septic shock. It occurs in thyrotoxic patients and is manifested by decompensation of multiple organs, triggered by severe stress. The diagnosis and response to treatment is made by Burch-Wartofsky point scale or Japanese thyroid association criteria due to lack of pathophysiology of thyroid storm. We reported series of patients that presented with altered sensorium, cough, fever, palpitation, shortness of breath and shock. Patient were treated initially for septic shock, later diagnosed as thyroid storm and was treated with oral carbimazole, propanolol and digoxin. From this, we want to emphasize that thyroid storm can have any presentation that should be kept in differential diagnosis of septic shock not responding to usual treatment; early diagnosis and treatment with oral medication can decrease morbidity and mortality in rural setting where intravenous form of antithyroid drug are not available for thyroid storm. Keywords: sepsis; septic shock; thyroid storm.

A case of atypical thyroid storm with hypoglycemia and lactic acidosis.

We describe herein a case of thyroid storm with hypoglycemia and lactic acidosis-a rare complication of thyroid storm. The patient was a 50-year-old Japanese woman who suffered cardiopulmonary arrest an hour after hospitalization. Analysis of a blood sample obtained before her cardiopulmonary arrest yielded surprising results: Her plasma glucose level was 14 mg/dL and her lactic acid concentration had increased to 6.238 mM. Thus, if atypical thyroid storm presents with normothermic hypoglycemia, and lactic acidosis, we believe it is necessary to consider a diagnosis of thyroid storm earlier, because this condition requires emergency treatment. Moreover, it is very important to apply standard principles in the treatment of atypical cases of thyroid storm.

Atypical presentation of thyroid storm: a diagnostic dilemma.

Thyroid storm (accelerated hyperthyroidism) is an uncommon life-threatening emergency. The diagnosis is difficult and at times delayed owing to atypical presentation. Early diagnosis is the key to its successful management. We came across a patient who had presentations of acute abdomen but later diagnosed in thyroid storm. Multiorgan involvement leads all resuscitative measures futile and prevented us to salvage the patient.

Thyroid storm induced by trauma due to spear fishing-gun trident impaction in the neck.

A rare case of thyroid storm induced by thyroid gland injury because of penetrating neck trauma is reported. The injury was because of a spear fishing-gun trident impaction in the neck. The diagnosis of thyroid gland injury was suspected by preoperative clinical examination and established during neck exploration in the theatre. The gland injury led to thyroid storm owing to the rupture of acini and liberation of T4 into the bloodstream. Withdrawal of the impacted trident along with subtotal thyroid lobectomy and repair of soft tissue damage in addition to supported treatments, which corrected the hyperthyroid state, led to uneventful recovery.

Thyroid Storm Precipitated by Diabetic Ketoacidosis and Influenza A: A Case Report and Literature Review.

A 46-year-old woman with a history of Graves' disease presented with the chief complaints of appetite loss, weight loss, fatigue, nausea, and sweating. She was diagnosed with diabetic ketoacidosis (DKA), thyroid storm, and influenza A. She was treated with an intravenous insulin drip, intravenous fluid therapy, intravenous hydrocortisone, oral potassium iodine, and oral methimazole. As methimazole-induced neutropenia was suspected, the patient underwent thyroidectomy. It is important to maintain awareness that thyroid storm and DKA can coexist. Furthermore, even patients who have relatively preserved insulin secretion can develop DKA if thyroid storm and infection develop simultaneously.

Thyrotoxicosis and thyroid storm.

Thyroid storm represents the extreme manifestation of thyrotoxicosis as a true endocrine emergency. Although Grave's disease is the most common underlying disorder in thyroid storm, there is usually a precipitating event or condition that transform the patient into life-threatening thyrotoxicosis. Treatment of thyroid storm involves decreasing new hormone synthesis, inhibiting the release of thyroid hormone, and blocking the peripheral effects of thyroid hormone. This multidrug, therapeutic approach uses thionamides, iodine, beta-adrenergic receptor antagonists, corticosteroids in certain circumstances, and supportive therapy. Certain conditions may warrant the use of alternative therapy with cholestyramine, lithium carbonate, or potassium perchlorate. After the critical illness of thyroid storm subsides, definitive treatment of the underlying thyrotoxicosis can be planned.

T4-throid storm in pernicious anemia.

A 32-year-old woman first had thyrotoxicosis and severe pernicious anemia (PA) in 1975. The initial serum thyroxine (T4) level, 14.5 microgram/dL, rose to 29.2 microgram/dL, with no other therapy except cyanocobalamin injection and blood tranfusions. She again had thyroid storm and PA in 1978. The serum T4 level was only slightly elevated, but the triiodothyronine (T3) level was normal. She received therapy for both diseases and recovered. Four months later, with a normal hematocrit reading, thyrotoxicosis recurred, with noticeable elevation of T4 and T3. These data suggest that first, thyroid storm can occur with excess T4 only, and its occurrence does not depend on the degree of thyroid hormone elevation; and second, thyroid hormone level may be depressed in severe PA, and a normal T3 level should not rule out thyrotoxicosis in this condition.

Severe starvation hypoglycemia and congestive heart failure induced by thyroid crisis, with accidentally induced severe liver dysfunction and disseminated intravascular coagulation.

A 69-year-old woman caught a cold resulting in nausea, vomiting, diarrhea and severe anorexia. Then she suffered progressively from dyspnea and leg edema, and finally became delirious. On admission severe hypoglycemia, hypothermia, marked tachycardia, generalized edema, mild jaundice and cachexy were noted. EKG showed atrial fibrillation. A chest X-ray, chest CT and echocardiography showed congestive heart failure. Therapeutic use of diuretics induced shock leading to serious liver dysfunction and disseminated intravascular coagulation. However, combined therapy by intravenous glucose, digitalis, diuretics, anti-fibrinolytic drug and hydrocortisone were effective. Addition of antithyroid therapy brought a further favorable outcome.

Thyroid storm caused by a chinese herb contaminated with thyroid hormones.

BACKGROUND: We report a case of thyroid storm caused by consuming a Chinese herb contaminated with thyroid hormones. CASE REPORT: A 70-year-old man presented to an emergency department after 2 days of nausea, vomiting, and weakness. Three days previously, he had started taking Cordyceps powder and "Flower Man Sang Hung" as recommended by his Chinese physician. Following admission, the patient deteriorated and was eventually diagnosed with thyroid storm complicated by rapid atrial fibrillation requiring cardioversion, intubation, and intensive care admission. The analysis of the Chinese herb "Flower Man Sang Hung" was positive for levothyroxine. The patient was extubated 11 days after admission and discharged to a rehabilitation centre after 17 days of hospitalization. The Chinese medicine physician was informed of the events. CONCLUSIONS: Herbal products can be the source of illness, medication interactions, and contamination. Awareness should be raised among Chinese medicine physicians, allopathic physicians, and their patients. Clinicians should also have a low threshold of suspicion to seek laboratory analysis of suspect substances when the cause of the clinical presentation is unclear.

Serum triiodothyronine concentration in thyroid storm.

Serum triiodothyronine levels were elevated in 6 patients with thyroid storm (769 plus or minus 181 ng/100 ml) but the values observed were not significantly different from those found in uncomplicated thyrotoxicosis (752 plus or minus 282 ng/100 ml). This observation suggests that the pathogenesis of thyroid storm resides in mechanisms other than a simple increase in serum triiodothyronine concentration.

Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration.

Thyroid hormone is one of several factors that modulate the level of sex hormone-binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal subjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P less than 0.0001). Mean SHBG levels in the patients with GRTH [37.6 +/- 16.2 (+/- SD) nmol/L] were not significantly different from those in the normal subjects (35.1 +/- 19.3 nmol/L) or hypothyroid patients (26.3 +/- 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 +/- 19.2 nmol/L; P less than 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 micrograms daily to 7 normal subjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (delta SHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (non-resistant subjects). After administration of 50 micrograms T3 daily, the mean delta SHBG level was decreased [-2.9 +/- 5.3 (+/- SD) nmol/L] in the resistant patients and increased (4.0 +/- 4.9 nmol/L; P less than 0.005) in the nonresistant subjects. After administration of 100 micrograms T3 daily, the mean delta SHBG was -4.5 +/- 6.8 nmol/L in the resistant patients and 8.6 +/- 5.1 nmol/L (P less than 0.0001) in the nonresistant subjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant subject.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyroid storm presenting as multiple organ dysfunction syndrome.

Thyroid storm is a rare disorder characterized by hypertension, hyperthermia, and multiple systems involvement. Early recognition and treatment of thyroid storm are essential in reducing morbidity and mortality from this disorder. We present the case of a patient with an atypical (normothermic, normotensive) presentation of thyroid storm, accompanied by multiple organ dysfunction syndrome, including lactic acidosis and liver dysfunction, both of which are very rare complications. This case highlights both the multiple organ systems that can be involved in thyroid storm and the importance of recognizing atypical presentations of thyroid storm.

Case report: pseudoephedrine-associated thyroid storm: thyroid hormone-catecholamine interactions.

Thyroid storm is an increasingly rare, life-threatening manifestation of thyrotoxicosis that can be precipitated by many physiologic stressors. The exact mechanism by which thyrotoxicosis decompensates into thyroid storm in certain individuals is unknown. These individuals may have an enhanced cellular sensitivity to either catecholamines or thyroid hormone. Serum levels of catecholamines are usually low or normal in thyrotoxic individuals. Ingestion of sympathomimetic drugs in thyrotoxic individuals may precipitate thyroid storm. This article presents an unusual case of Graves' disease that decompensated into thyroid storm after the ingestion of an over-the-counter cold medication containing pseudoephedrine.

[Iodine-induced hyperthyroidism in urology caused by using roentgen contrast media. Risks and prevention]. / Jodinduzierte Hyperthyreose in der Urologie durch Anwendung von Röntgenkontrastmittel. Risiko und Prävention.

The presence of functionally autonomous portions of the thyroid is a precondition for the occurrence of iodine-induced hyperthyroidism after the administration of i.v. contrast media, in the form either of latent immunogenic hyperthyroidism (Basedow's disease) or of localized or diffuse autonomy. The normal thyroid can compensate an iodine excess in multiple ways. In the malfunctioning thyroid, however, autoregulation mechanisms may fail, resulting in complicated forms of hyperthyroidism. In Germany autonomy-correlated hyperthyroidism occurs much more often than in other countries in which sufficient alimentary iodine is present. Especially in elderly patients with long-standing nodular goitres, there is an elevated risk of iodine-induced hyperthyroidism arising from thyroidal autonomy. These cases may differ from those seen in younger patients. An existing hyperthyroidism may worsen dramatically after administration of contrast media. To prevent an iodine-induced thyrotoxic crisis, contrast media should only be given to patients with latent of manifest hyperthyroidism when vital indications are present, and then only after thyrostatics have been administered. To evaluate the morphology of the renal collecting system and ureter in these cases a retrograde rather than an intravenous pyelography should be performed. When this is combined with determination of serum creatinine and creatinine clearance, functional and morphological evaluation, respectively, of the upper urinary tract are possible.