18 yo F w/chiari malformation (s/p decompression), pseudotumor (s/p shunt) w/worsening hypotension. Jess Hwang 9/12/13
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1 18 yo F w/chiari malformation (s/p decompression), pseudotumor (s/p shunt) w/worsening hypotension Jess Hwang 9/12/13
2 HPI Admitted 7/2013 Adm for HA, nausea/vomiting. Ophtho exam: no optic disc swelling, VF normal. LP shunt revision performed. HA are mainly frontal but in the last 2 years have also been located in the occipital region. Worse in AM, with stormy weather, when bearing down, with sitting up for >2h Has been on dilaudid q4h chronically at home. Started on Methadone on 7/17.
3 Headache history Age 4 Chiari surgery (synthetic patch graft) 4/2011 Cleveland Clinic for HA LP opening pressure 27.5 cm improved symptoms after drainage and starting diamox 4/2012 Chiari decompression (replacement w/autograft) 5/2012 readm with HA, nausea/vomiting with worsening photophobia. She requeted an LP opening pressure 23 cm H2O. Started on Diamox. 6/2012 Ophtho- disc edema orbital pseudotumor 6/2012 Lumbar drain placed removed 7/2012 LP shunt insertion, revised in 1/2013.
4 HPI Intermittent episodes of acute word-finding difficulties, blurry vision after being upright for a while. BP range 80/50-100/50 since admission. Often requiring IVF for maintenance. Diagnosed with POTS a few years ago and has been on Florinef 0.1 mg BID. 8/5 consult for hypotension, hypocortisolemia
5 Endocrine ROS LMP was a 3 days before consultation. +menorrhahgia No galactorrhea, no peripheral vision problems No polyuria, no polydypsia +constipation, +nausea +fatigue, +dizziness, +depression Has been on 2% hydrocortisone cream BID for 2 wks for PICC line irritation
6 More history PMH Chiari type 1 (s/p decompression 1999) Migraine (since 8 yo) Platelet abnormality Menometrorrhagia MTHFR mutation (heterozygous) Postural orthostatic tachycardic syndrome (POTS)- (since 14 yo)- sees cards in OH Premature 36 wks Seizures Reflux- sees GI in OH, has had multiple EGDs and has required PPI BID FHx Mother- hypothyroidism No known pituitary/adrenal problems SHx Senior in highschool Lives with mom/dad/sister 4.5 hours away in Michigan
7 Home meds Prozac 25 mg daily Nexium 40 mg BID Flexeril 10 mg daily prn Zofran 8 mg q8h prn Desmopressin 2 sprays q12h (prn menorrhagia) Topamax 125 mg BID Valium Vitamin E daily CoQ mg BID Thiamine 100 mg BID Miralax Pericolace Dilaudid Florinef 0.1 mg BID Midodrine 5 mg BID Propanolol LA 60 mg daily Pyridostigmine 60 mg 5x/d Adderall daily Riboflavin 200 mg BID Selenium 50 mcg daily L-carnitine 330 mg BID Lipoic acid 100 mg daily
8 Physical Exam Vitals: 36.2, HR 84, RR 14, BP 105/62, O2 sat 100 RA (+orthostatic vitals) Gen: chronically ill appearing HEENT: PERRL. EOMI. VF grossly normal on confrontation. Extreme pallor. Neck: no thyromegaly or nodules. Heart: RRR. Resp: no distress. CTAB. GI: soft, NT/ND. Ext: no edema. Neuro: A+Ox3, napping before and after exam. Psych: flat affect
9 Labs OH vit D 16 Iron 19 mcg/dl (RR ) TIBC 429 mcg/dl (RR ) % saturation 4.4 (14-50) Ferritin 6 ng/ml (RR ) CRP 4 mg/l (RR <5) Pregnancy test neg MCV 73
10 8/3 8AM cortisol 0.5 Endo work-up Cosyntropin stim 8AM 30 min 60 min ACTH 9.9 Cortisol < 0.4 Cortisol 4.7 Cortisol 6.9 Prolactin ng/ml (RR ) IGF1 249 ng/ml (RR ) FSH 2.9/LH 3.2/Estradiol 28 (day 5 of her cycleearly follicular phase) TSH 1.31 FT4 0.74, TT3 121, rt3 134 ( ), Tg Ab +/TPO Ab + 7/4 6:30AM cortisol = 6.8 Adrenal Ab neg 7/4 TSH 0.41, FT4 1.10
11 Steroid history 4/23-5/2/2012 High-dose decadron/taper 6 months ago recalls taking a few doses of Prednisone for?pneumonia Hydrocortisone 2% cream BID during this admission for PICC line irritation
12 Other tests 3/2013 CSF WBC 10 (Lymph 89%, Mono 11%), protein 47 (RR 15-45), glu 62 (50-70) 7/3/2013 CSF WBC 2 (Lymph 86%), protein 58, glucose 71 Pelvic US: normal uterus, endometrium. Normal ovaries.
13 Non specific heterogeneous enhancement of pituitary gland without defined pituitary masses. Pituitary gland appears somewhat prominent which maybe normal for patient s age. Stalk is thickened and appears mildly nodular.
14 DDx of Thickened Pituitary Stalk Neoplasms of the stalk- craniopharyngioma, germ cell tumor, metastatic disease (lymphoma), Langerhans histiocytosis Inflammatory: lymphocytic hypophysitis, sarcoidosis, histiocytosis, hypophysitis (lymphocytic, granulomatous, necrotizing) Infection: bacterial, viral, fungal Chronic opioid use (per our radiologists) Byrne TN. MGH Neuroendocrine Clinical Center Bulletin. Spring 2008;14(1):1-3.
15 Biopsy+ lymphocytic hypophysitis
16 Clinical Questions Epidemiology/Presentation/Management of lymphocytic hypophysitis (LH) Presumptive diagnosis of LH without biopsy Natural history of LH
17 Epidemiology of LH Prevalence = 5 per million As of 2008, there are 500 patients described M:F ratio ranges from 4-6:1 Peak incidence is 4 th decade of life In 211 women with LH between years of age, LH presented during late pregnancy or early post-partum in 69% Caturegli P. Autoimmun Rev 2008 Sept;7(8):
18 Typical presentation of LH Categories of symptoms 58% Headache, visual disturbances 44% Hypopituitarism 31% Polyuria/polydypsia 18% Hyperprolactinemia Caturegli P. Autoimmun Rev 2008 Sept;7(8):
19 Typical presentation of LH N = 145. Multiple hormone deficiencies are found in 75% Molitch ME. Lymphocytic Hypophysitis. Horm Res 2007;68(5):
20 Work-up Definitive diagnosis = biopsy Biopsy is only considered if alternative treatments with significant adverse effects (high-dose steroids, immunosuppressive agents, pituitary radiation) are being considered. Antigen-specific antibody assays are not sensitive/specific, nor are they readily available
21 MRI findings Generally the gland is symmetrically enlarged Intense/homogeneous post-gad enhancement Loss of posterior pituitary bright spot Dura adjacent to the mass shows marked contrast enhancement dural tail Thickened but undisplaced stalk Molitch ME. Lymphocytic Hypophysitis. Horm Res 2007;68(5):
22 Medical Management of LH High-dose steroids Variable response Other immunosuppressive agents: azathioprine, methotrexate Supportive management= hormone replacement
23 Medical Management of LH N = 44 cases, follow-up only available in 37 patients Pituitary size reduced in 84% Anterior pituitary function improved in 45% Posterior pituitary function improved in 41% Lupi I. J Endocrinol. Invest. 2011;34:e245-e252.
24 Presumptive clinical diagnosis History of gestational/post-partum hypopituitarism (esp if no hypotension) Contrast-enhancing sellar mass with typical features Pattern of pituitary hormone deficiency (ACTH > TSH > FSH/LH) vs adenomas (GH > LH/FSH > ACTH = TSH) Relatively rapid development of hypopituitarism Pattern of symptoms out of proportion to MRI findings Molitch ME. Lymphocytic Hypophysitis. Horm Res 2007;68(5):
25 Natural history of LH Aim: define course of hypophysitis Cohort: 33 F mice (18 immunized with pituitary proteins, 15 controls) Results: immunized mice showed significant expansion of pituitary volume during early phase. Volume decreased gradually in 78% cases and reached empty sella values by day 300. Lupi I. Endocrinology 2011;152(11):
26 18 post-immunization mice Non immunized mice
27 Back to our patient Repeat Prolactin ng/ml (RR ) Dilution: no hook effect Discharged home on: HC 40/20 taper after 1 week to 20/10 LT4 50 mcg daily rechecking labs in a month Iron, Vitamin D replacement Plan for repeat MRI pituitary Will also check celiac, vit B12, folic acid, immunoglobulin levels Follow-up with NUS, Endo
28 Take Home Points Presumptive clinical diagnosis includes symptoms, pattern of hormone deficiency, MRI findings. Possible improvement in hypopituitarism reportedly 40-50% with high dose steroids MRI improvement is 80% with high dose steroids but this could be the natural course of disease
29 References Caturegli P. Pituitary autoimmunity: 30 years later. Autoimmun Rev 2008 Sept;7(8): Byrne TN. Etiology of Thickened Pituitary Stalks. MGH Neuroendocrine Clinical Center Bulletin. Spring 2008;14(1):1-3. Thodou E. Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings. JCEM 1995;90: Molitch ME. Lymphocytic Hypophysitis. Horm Res 2007;68(5): Unluhizarci K. Distinct Radiological and Clinical Appearance of Lymphocytic Hypophysitis. JCEM 2001;86(5): Howlett TA. How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsy? Clin Endo 2010;73: Glezer A. Pituitary Autoimmune Disease: Nuances in Clinical Presentation. Endocrine 2012;42: Lupi I. From Pituitary Expansion to Empty Sella: Disease Progression in a Mouse Model of Autoimmune Hypophysitis. Endocrinology 2011;152(11):
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