Download 15 Year-Old Boy with Weakness and Hyperpigmentation

15 Year‐Old Boy with Weakness and Hyperpigmentation
Matthew Wise, MD
Med‐Peds Endo
November 1, 2012
HPI
• 15 year old Caucasian boy
• Presented to ER with episode of “blacking out for 2 seconds” – while standing, waiting in line at school registration
• 8 months of progressive, diffuse muscle weakness, worsening sports/school performance, fatigue, nausea, occasional vomiting, abdominal discomfort, poor weight gain
• ER visits x3 for “dehydration” with IVF and release
• Recent craving for salty foods: french fries, pretzels
• 1.5 years of dark/tanned skin
Neurology evaluation
• Saw peds neurologist 1 month prior, noted proximal upper and lower ext muscle weakness
• Reviewed OSH ER records and noted elevated CK as high as 1247; noted OSH TFTs were nml
• Considered metabolic myopathies (mitochondrial, glycogen storage, FAO defects)
• Workup with CK, lactate, pyruvate, ammonia, acyl
carnitine, urine organic acids, plasma amino acids, EKG, EMG, consider muscle bx
• Of labs, only CK abnormal: 297 U/L (9‐185)
ROS
Endo: ‐ excess thirst/urination
Const: + subjective fever
Neuro: ‐ headaches, visual changes
Resp: + cough, sore throat x1wk
Rheum: ‐ joint pains
PMH
• Asthma (exercise‐induced)
• Eczema
Fam Hx
Meds
• Albuterol prn
Soc Hx
• Father 44y, pineal tumor dx age • High school sophomore
16, radiation, secondary cortical • Football player
tumor treated surgically
• Mother 42, hypothyroidism recently diagnosed
• Mat GM – hypothyroid since her 40’s, Rheumatoid arthritis
• Mat GGM – goiter
• Pat GM – thyroid disease
Physical Exam
Vitals 37.3 C, BP 113/59  89/44 with standing, HR 87, RR 13, O2 100% RA
Wt 58.7kg (60%ile), Ht 172.4cm (5’8”) (61%ile), BMI 19.7 (47%ile)
Gen: Awake, alert, NAD
Head/Face: non‐dysmorphic
ENT: mucosa dry
Neck: no thyromegaly, no acanthosis
Resp: clear bilaterally, unlabored
CV: RRR no m/r/g
Abd: Soft, scaphoid, non‐tender, no masses
GU: +palpable glandular breast tissue, mildly tender
Tanner IV pubic hair
Tanner III axillary hair
Testes 3.8‐4.5cm bilaterally, firm
Ext: warm, well perfused
Neuro: no objective muscle weakness
Derm: diffuse hyperpigmentation with less pigment on flexor surfaces and face where there is dry, rough skin; hyperpigmented macules on abdomen
Initial Evaluation/Mgmt
Started on IVF with D5 NS at near-maintenance 85 mL/hr (1300mL/m2/d)
Assessment and Recommendations
15 yo boy with progressive muscle weakness, fatigue, salt‐craving, orthostasis, hyperpigmentation and hyponatremia
Primary adrenal insufficiency: autoimmune
metabolic (adrenoleukodystrophy)
CAH (congenital adrenal hyperplasia)
adrenal hypoplasia
infiltrative disease
infectious/destructive
Test
Result
ACTH 2155 pg/mL
Cortisol
1.1
Na
123
Aldo
<4.0 ng/dL (<21)
Renin
32 ng/mL/hr (1.2‐2.4)
TSH
7 mcU/mL (0.3‐4.0)
Free T4
1.12 ng/dL (0.9‐1.7)
rT3
323 pg/mL (160‐353)
Workup
Test
Result
ACTH 2155 pg/mL
Cortisol
1.1
Na
123
Aldo
<4.0 ng/dL (<21)
Renin
32 ng/mL/hr (1.2‐2.4)
TSH
7 mcU/mL (0.3‐4.0)
Free T4
1.12 ng/dL (0.9‐1.7)
rT3
323 pg/mL (160‐353)
Adrenal Ab 244 U/mL (<1)
TPO Ab
+5120
Tg Ab
+160
Diagnosis:
autoimmune primary
adrenal insufficiency
with evidence of
autoimmune
hypothyroidism,
compensated;
consistent with
autoimmune
polyglandular syndrome
(APS)Type 2
Management
• Started hydrocortisone stress dose (2x physiologic) 20/10/10 for 2 days, then taper to physiologic at 10/5/5
• Started fludrocortisone 0.1mg daily
• Advised clinic f/u in 2 weeks, with repeat TFTs
• Na improved to 131 on day of discharge, pt already feeling significantly improved Clinical Questions
1) What are the phenotype components and cause of APS type 2?
2) How does APS type 2 commonly first present?
3) What is the recommended screening program?
APS type 2 (PGA type 2, PAS type 2)
1:20,000
CTLA-4
Eisenbarth 2004 NEJM 350
APS type 2
• APS2a: adrenal insufficiency
+ AITD or DM1
may have vitiligo, pernicious anemia, or other
• APS2b: AITD
without adrenal insufficiency
+ DM1, myasthenia gravis, vitiligo
pernicious anemia, primary hypogonadism, alopecia, hypophysitis
APS type 2 Phenotypes
Dittmar 2003 JCEM 88(7)
Screening/Diagnostic Approach
Disease
Evaluation
Frequency
Addison’s
ACTH, cortisol, Annual
lytes, aldo, DHEA‐S, Abs at diagnosis
21‐OH Ab
Alopecia
Physical exam
Annual
Autoimmune Thyroid Disease
TFTs, TPO/Tg Abs
Annual
Celiac Disease
tTG, IgA
Annual
Pernicious Anemia
Antiparietal cell Ab, q5 years
CBC, B12
Primary Hypogonadism
LH, FSH, Testosterone or E2
DM1
A1c, fasting glucose Annual
GAD65, IA‐2, IAA
Abs at dx and q3‐5y
Annual
Endotext 2012
Follow‐up with our Patient
• Returned to endo clinic 3 weeks after diagnosis
• All presenting symptoms improved significantly
• Screening tests:
Thyroid: TSH 2.2 uU/mL, fT4 1.2 ng/dL
Hypogonadism: LH 3.3, FSH 2.0, Ttest 368 ng/dL
DM: A1C 5.4%, IA‐2 ‐, GAD65 ‐, IAA ‐
Celiac: tTG 2 (<20)
Pernicious anemia: parietal Ab <25 (<25) Hgb 12.9 (MCV 84)
Alopecia: not on PE
Take Home
• Symptomatic hypotension is a common presentation of Addison’s which should be suspected with progressive weakness, fatigue, weight loss, hyperpigmentation or other autoimmune disease
• APS type 2a is characterized by Adrenal insufficiency, typically with DM1 and/or AITD; and/or other autoimmune conditions
• Clinical suspicion for other autoimmune conditions should be high in our patients with DM1 or AITD, with targeted screening considered
References
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Dittmar, M (2003). Polyglandular Autoimmune Syndromes: Immunogenetics and Long‐Term Follow‐Up. Journal of Clinical Endocrinology & Metabolism, 88(7), 2983‐2992. doi:10.1210/jc.2002‐021845
Eisenbarth, G., & Gottlieb, P (2004). Autoimmune polyendocrine syndromes. New England Journal of Medicine. Retrieved from http://www.nejm.org/doi/full/10.1056/nejmra030158
Betterle, C., Pra, C., Mantero, F., & Zanchetta, R (2002). Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease …. Endocrine Reviews. Retrieved from http://edrv.endojournals.org/content/23/3/327.short
Majeroni, B., & Patel, P (2007). Autoimmune polyglandular syndrome, type II. Am Fam Physician. Retrieved from http://www.sepeap.org/secciones/documentos/pdf/poliglandular_II.pdf
Endotext section on polyglandular diseases: accessed Oct 19, 2012: http://www.endotext.org/pediatrics/pediatrics6/pediatricsframe6.htm