16 7/12 year old Female with Down s Syndrome and Abnormal TFTs. Moina Uddin, D.O. Endorama 6/26/14
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1 16 7/12 year old Female with Down s Syndrome and Abnormal TFTs Moina Uddin, D.O. Endorama 6/26/14
2 Chief Complaint CC: 16 7/12 year old female with hx of Down's Syndrome and hypothyroidism admitted for epigastric abdominal pain x 3 weeks Endocrine concern: Abnormal TFTs (checked for history of hypothyroidism)
3 HPI Abdominal pain x 3 weeks intermittent pain, worsens with foods decreased appetite 11 pound weight loss in 2 weeks. Pepcid x 3 days No change in symptoms.
4 HPI Abdominal pain x 3 weeks CT abdomen/pelvis with PO contrast no acute abnormalities including a normal appendix Evaluation included Normal labs: CRP, ESR, ALT and Alk Phos, TFTs Abd. US non compressible appendix Peds Surg consult Repeat Abd CT Diagnosis: omental infarct
5 History of patient s hypothyroidism On levothyroxine since at least October, Started on 25 mcg once daily, then increased to 50 mcg in May, 2009 Followed by PCP. Visit with an endocrinologist at diagnosis She takes Levothyroxine daily at 0700 without any food (skips breakfast) and chews the tablet. The most recent TFTs prior to hospitalization: February 2013 FT4: 1.0 ( ) TSH: 3.05 ( mciu/l)
6 History Past Medical Hx: Hypothyroidism Down Syndrome Past Surgical Hx: Knee Surgery (b/l patellar dislocations: 2007, 2008) ENT Surgery: T&A Cardiac Surgery Birth Hx: Born at 39 weeks gestation, unremarkable. Family Hx: Grave s Disease: MGM (Non thyroid) Cancer: MGM Heart disease: MGM Diabetes: Multiple paternal relatives Social Hx: Lives at home with both parents, in Indiana. Has a 19 year old sister, healthy. Attends special school and gets As and Bs.
7 Review of Systems Constitutional: loss of appetite x 3 weeks due to abdominal pain, +fatigue, 11 lb wt loss over 2-3 weeks. No fever. No recent problems focusing at school. Endocrine: Hypothyroidism on levothyroxine, no polyuria, no polydipsia, no jitteriness, no anxiety. HENT: No congestion and rhinorrhea. Eyes: No visual disturbance. No proptosis Respiratory: No cough, No SOB Cardiovascular: No palpitations Gastrointestinal: + epigastric abdominal pain, No vomiting, + diarrhea after oral barium contrast, No constipation. Genitourinary: No dysuria. Menarche at age 14, regular periods lasting 5-7 days, heavier for the first 3-4 days. Musculoskeletal: No arthralgias. Skin: + dry skin since infancy, unchanged over time. + dry scalp also since infancy. Some intermittent hair-loss which seems more than usual at times, but never in clumps. + sweatiness. Neurological: + headaches, which mom attributes to sinusitis. Psychiatric/Behavioral: No anxiety, no agitation.
8 Physical Exam Temp: F, HR: 52-73, RR: 12-22, BP: ( )/(43-64) SpO2: 97 %-99 % Wt: 80 kg (>95 th %ile), Ht: cm (50-75 th %ile), BMI: 38.2 kg/m2 Constitutional: Appears well-developed and well-nourished. Active. No distress. No anxiety or diaphoresis. Down syndrome stigmata Mouth/Throat: Mucous membranes are moist, Oropharynx difficult to visualize Eyes: Conjunctivae and EOM are normal. No proptosis,+epicanthal folds but no eyelid swelling appreciated Neck: Neck supple. No adenopathy. No thyromegaly, no palpable thyroid masses Cardiovascular: Normal rate and regular rhythm. No murmur heard. Brisk capillary refill. Pulmonary/Chest: Effort normal. There is normal air entry. There are no wheezes. Breasts not examined, since patient was uncomfortable Abdominal: Soft, no distension. Some diffuse tenderness and patient resisted a thorough abdominal exam. Genitourinary: Deferred by patient Musculoskeletal: Normal range of motion. Difficult to appreciate edema due to body habitus. No tremor on outstretched arms Neurological: Alert. Exhibits normal muscle tone. Skin: Skin is warm. No rash noted. No acanthosis nigricans, no dry skin/scalp noted. Flesh colored striae noted on bilateral abdominal wall.
9 Labs CMP wnl. ft4: 3.33 ( ng/dl ) TSH: 0.05 ( mcu/ml ) TT3: 225 ( ng/dl )
10 Differential Diagnosis 1. Lab error 2. Over treatment 3. Endogenous hyperthyroidism
11 Plan Repeat TFTs Check Antibodies
12 Repeat TFTs TSH: 0.05 ( mcu/ml) T4: 11.6 ( mcg/dl) ft4: 2.91 ( ng/dl) TT3: 175 ( ng/dl) ft3: 534 ( pg/dl) Antibodies: Thyroglobulin Ab: >30 (<0.4 KU/mL) TSI: 6.3 (</=1.3) TPO: >30 (<0.4 KU/ml Ab TPO)
13 Diagnosis and Plan Autoimmune hyperthyroidism Plan: D/C Synthroid Repeat TFTs in 1 week Repeat TFTs 1 week later: TSH= ( ) FT4= 3.24 ( ) Methimazole initiated at 5 mg Qdaily
14 Clinical Questions 1) How common is Graves Disease after autoimmune hypothyroidism in the general population? 2) Is Graves Disease post hypothyroidism more common in Down s Syndrome? 3) What is the course of Graves Disease in Down Syndrome?
15 GRAVES DISEASE AFTER AUTOIMMUNE HYPOTHYROIDISM IN THE GENERAL POPULATION
16 GD in Children with Antecedent HT Retrospective study 109 children and adolescents with GD 20 boys Patients with Turner and Down Syndrome excluded Dx: TSH, ft4 and significantly + TRAB The retrospective diagnosis of HT: thyroid enlargement high titers of TPO ab and/or TG ab a hypoechogenic thyroid pattern 4 patients had well-documented antecedent HT
17 Wasniewska et.al. Frequency of Hashimoto s Thyroiditis Antecedents in the History of Children and Adolescents with Graves Disease. Horm Res Paediatr 2010;73:
18 Summary and Conclusions When compared with the remaining 105, the only relevant difference between the 2 groups was: TRAB in those without HT antecedent >> than the others (21.0 IU/l; range: IU/l vs. 12.5IU/l; range: 3 18 IU/l). Hypothyroidism Grave s Disease timeline ranged from 1.5 to 2.8 years Clinical course of GD not significantly different in 2 groups Report confirms the existence of a possible continuum between hypothyroidism and GD within the broad spectrum of AITD
19 Conversion of HT to GD: General Population Happens in a few weeks Theory: Alteration in the biological activity of TRAB from predominantly thyroid-blocking antibodies during the hypothyroid phase to thyroid-stimulating antibodies when GD manifests itself
20 GRAVES DISEASE AFTER HYPOTHYROIDISM IN DOWN SYNDROME
21 Aversa et.al. In Young Patients with Turner or Down Syndrome, Graves Disease Presentation Is Often Preceded by Hashimoto s Thyroiditis. Thyroid. 24 (4), 2014
22 Aversa et.al. In Young Patients with Turner or Down Syndrome, Graves Disease Presentation Is Often Preceded by Hashimoto s Thyroiditis. Thyroid. 24 (4), 2014
23 Conversion of HT to GD: Down Syndrome Takes longer than in the general population years vs years More likely 25.7 % vs. 3.7 % Detected more frequently because of close monitoring in this group?
24 COURSE OF GRAVES DISEASE IN DOWN SYNDROME
25 Alberto Goday-Arno et.al. Hyperthyroidism in a population with Down syndrome. Clinical Endocrinology (2009) 71,
26 Treatment of Graves Disease in DS population Treatment with carbimazole (pro-drug) was started in all patients at the time of diagnosis. Initial dose of 10 mg TID. Carbimazole withdrawal was attempted in all cases but no patient achieved remission longer than 6 months. Radioiodine considered If patients relapsed or after >24 months without carbimazole withdrawal.
27 Treatment of GD in DS population Definitive therapy with Iodine-131 was prescribed for all patients, except for those whose family refused it (2) Patients that underwent iodine treatment did not develop any side effects. No patient underwent surgery as definitive therapy
28 REFERENCES Aversa T, Lombardo F, Corrias A, Salerno M, De Luca F, and Wasniewska M. In Young Patients with Turner or Down Syndrome, Graves' Disease Presentation Is Often Preceded by Hashimoto's Thyroiditis. Thyroid. April 2014, 24(4): Goday-Arno, A., Cerda-Esteva, M., Flores-Le-Roux, J. A., Chillaron- Jordan, J. J., Corretger, J. M. and Cano-Pérez, J. F. (2009). Hyperthyroidism in a population with Down syndrome (DS). Clinical Endocrinology, 71: Wasniewska et.al. Frequency of Hashimoto s Thyroiditis Antecedents in the History of Children and Adolescents with Graves Disease. Horm Res Paediatr 2010;73:
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