Objective: Neutropenia can occur in untreated autoimmune hyperthyroidism (AIH) or in association with treatment with the anti-thyroid drug, methimazole (MMI). Starting MMI in children and adolescents with AIH and pre-existing neutropenia could thus be worrisome. The aim was to describe the prevalence of neutropenia in pediatric AIH, prior to antithyroid drug therapy and to assess the effect of antithyroid drugs on neutrophil count. Methods: Patients with AIH attending a pediatric endocrinology clinic were retrospectively reviewed. Absolute neutrophil count (ANC) data at presentation and during anti-thyroid treatment for up to 24 weeks was collected. AIH was defined as elevated free thyroxine (fT4) or free tri-iodothyronine (fT3), suppressed thyroid stimulating hormone, and positive thyroid autoantibodies. Neutropenia was defined as ANC <1500 cells/μL. Results: Thirty-one patients (71% female) were included with a median interquartile range (IQR) age of 14.71 (11.89-17.10) years. Neither fT4 nor fT3 levels correlated with ANC at presentation (r s =0.22, p=0.24 and r s =0.13, p=0.54, respectively). 26/31 (84%) had normal baseline ANC. None developed neutropenia with thionamides. 5/31 (16%) had baseline neutropenia (median ANC 1,200/μL; IQR 874-1200). Four of these five started MMI at diagnosis while one was started on propranolol only but MMI was started one week later. All five normalized ANC within 24 weeks. Conclusion: In this cohort, 16% of AIH patients had neutropenia at presentation, but this resolved in the short term and did not worsen with thionamides. Thionamides may be used with caution in these patients with close monitoring of blood counts.
Severe hypertriglyceridemia (HTG) (>885 mg/dl) can be caused by familial partial lipodystrophy Type 3 (FPLD 3), an autosomal dominant disorder caused by a loss of function of the peroxisome proliferator activated receptor gamma (PPARG), characterized by abnormal distribution of fat and metabolic derangements. 16 year old female (body mass index, BMI 23.5 kg/m 2 ) was hospitalized twice for pancreatitis (TG level >2200 mg/dl). She was managed with bowel rest, insulin infusion, and plasmapheresis. On a low fat 10 g daily diet and fenofibrate 160 mg daily her fasting TG had decreased to 411 mg/dL (range 0-149). Results: She had a normal leptin level.Panel testing of genes involved in triglyceride metabolism revealed a known pathogenic variant in PPARG gene (c.452A>G p.Tyr151Cys). A second variant detected in this gene, c.1003G>C (p.Val335Leu), is considered benign. HbA1C of 6.6% and two hours oral glucose tolerance test confirmed Type 2 diabetes (T2DM). We outline the earliest description of T2DM in an adolescent with a pathogenic variant of PPARG. PPARG related FLPD 3 should be considered in lean children presenting with severe HTG and insulin resistance and treatment with PPARy agonists Thiazolidinediones should be considered.
BACKGROUND: Autoimmune thyroiditis (AT) is a common cause of acquired hypothyroidism in children characterized by lymphocytic thyroid infiltration. Sometimes gradual thyroid failure occurs due to apoptosis of thyroid cells. It may occur via apoptotic cytokines, ligands and receptors, including T regulatory cells, tumor necrosis factors etc. AT can coexist with other organ specific autoimmune conditions. Rarely neurological autoimmunity due to glutamic acid decarboxylase (GAD) antigen may be associated with AT. In fact, up to 70% of patients with GAD 65 neuropathy may have other autoimmune disease (AT, type 1 diabetes, pernicious anemia). We present a case of AT that led to total destruction of the thyroid gland with coexisting neurological autoimmunity. CLINICAL CASE: A 7 yr old male presented with tiredness, heat intolerance and weight loss for 4 months, unsteady gait with frequent falls for 2 weeks. Exam showed tachycardia, firm thyromegaly and difficulty with tandem walking without other cerebellar signs. Labs showed undetectable TSH, elevated FT3, FT4 with positive thyroid antibodies, and negative for viral serology. MRI brain was normal and neurological symptoms resolved within few weeks. Thyroid ultrasound (TUS) showed hypervascularity and heterogenecity with right lobe volume (RLV) 2.8 cc, left lobe volume (LLV) 2.3cc with 0.9cm nodule. Thyroid scan showed increased uptake (52% and 61% at 4, 24 hrs). He required methimazole for 2.2 yrs. Five months later, at age 9.6 yrs he was hypothyroid and was started on Levothyroxine(LT4). TUS showed RLV 4.6cc, LLV 2.5cc and solid left nodule 1.2cm. FNA was consistent with AT. At age 14.4 yrs,TUS showed near complete involution of RL and isthmus with LLV 4.9cc and 0.6cm nodule and thyroid scan was negative for uptake. Repeat FNA reconfirmed AT. Due to progressive atrophic thyroiditis he had hyperthyrotropinemia with euthyroxinemia (TSH range 12–165, Normal FT4 1.15–1.73) requiring increasing dose of LT4 over nearly 7.6 yrs. At 14.8 yrs, he developed focal epilepsy treated with Levetiracetam and new-onset left fourth cranial nerve palsy. Autoimmune workup revealed extremely elevated GAD 65 antibodies in serum and cerebral spinal fluid, 1703 and 14.2 nmol/L respectively (N<0.02), confirming a diagnosis of GAD-65 central nervous system disease. He is currently receiving monthly IVIG. At 15.3 yrs, complete atrophy of RL with involuting LLV 2.4cc was noted. He remains euthyroid and seizure free on anti-epileptics with recovering cranial nerve palsy. CONCLUSION: This is an unusual and extreme form of atrophic thyroiditis leading to near total destruction of thyroid gland related to apoptosis with autoimmunity. GAD-65 CNS autoimmunity is important to be considered in children with AT presenting with seizures or focal neurological signs. Continued vigilance and follow up for the development of other autoimmune conditions is warranted.
Objectives Hashimoto’s thyroiditis (HT) is characterized by lymphocytic thyroid infiltration. Gradual thyroid failure can occur due to thyroid cell apoptosis. Rarely neurological autoimmunity due to glutamic acid decarboxylase (GAD) antigen can co exist with HT. Case presentation A seven-year-old male presented with tiredness, weight loss, frequent falls, tachycardia, firm thyromegaly, and abnormal gait. Biochemical markers and thyroid ultrasound (TUS) showed autoimmune hyperthyroidism. Methimazole (MMI) was started and continued for 2.2 years. MRI brain was normal and neurological symptoms resolved. At nine years, he became hypothyroid and levothyroxine (LT4) was started. Serial TUS showed progressive thyroid atrophy. At 14.8 years, he developed epilepsy and fourth cranial nerve palsy, and diagnosed with GAD-65 central nervous system disease. At 15.3 years, TUS showed complete atrophy of right lobe with involuting left lobe volume. Conclusions This is an unusual form of atrophic thyroiditis (AT) with coexisting neurological autoimmunity. GAD-65 CNS autoimmunity should be considered in children with AT presenting with neurological signs.
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