Kristen Dillard, M.D. Endorama December 6, 2012
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1 Kristen Dillard, M.D. Endorama December 6, 2012
2 12 7/12 yo girl with h/o Cushing s disease presented to OSH with concern for CVA Consumed ½plate of food the night before, had raisins and diet soda on the way to school Acute speech slurring progressing to left sided weakness, left hemianopsia She was conscious throughout the event though responded inappropriately to commands Initial vitals: HR 70 BP 101/52 BMP: Glu 70 Na 141 K 3.4 CT scan negative Transferred to Comer PICU
3 Comer PICU Initial vitals HR 52 BP 106/55 BMP: Glu /3.6/109/23/9/0.5 Ca 9.1 Sedated with dexmedetomidine for MRI/MRA fingerstick BG 46 mg/dl D10W bolus repeat BG 44 D10 0.9NS (GIR 3.4 mg/kg/min), BG remained Cortisol was < 0.4 Hydrocortisone considered but not given, BP stable All symptoms resolved once awakened from sedation
4 Presented at age 11 5/12 yrs with progressive weight gain, growth attenuation and cessation of pubertal development at 8.5 yrs Elevated urinary free cortisols diagnosed with Cushing s disease by CRH stimulation 11 months prior ACTH at 30 min Cortisol at 30 min 59 at 120 min 8 months prior had transsphenoidal left hemihypophysectomy Pathology: ACTH secreting adenoma
5 Transient central diabetes insipidus POD 1 Na , d/c home on DDAVP 100 mcg qhs Resolved within 4 weeks Dexamethasone taper then transitioned to physiologic hydrocortisone POD 1 AM cortisol month post op: ACTH 6.8, cortisol < 0.4, HC weaning begun 5 months post op: ACTH 6.1, cortisol 2.1 on HC ~3 mg/m2/day HC wean completed 3 weeks prior to presentation Diagnosed with central hypothyroidism 6 months post op, began LT4 88 mcg daily Decreased to 44 mcg daily ~ 2 months later
6 PMH Birth history normal ACTH secreting pituitary adenoma Central hypothyroidism PSH Double hernia repair as an infant Transsphenoidal left hemihypophysectomy Meds LT4 44 mcg daily FH Mother 68 inches, menarche at 12 Father 73 inches, nl pubertal development T2DM, paternal lineage No growth or pubertal disorders in family SH Lives with parents, only child, excellent student in 7 th grade, very active and social
7 Constitutional: + Poor appetite, weight loss ~30 lb since surgery, heat intolerance on warm days and with strenuous exercise HENT: Negative for congestion and rhinorrhea. Respiratory: Negative for cough and shortness of breath. Cardiovascular: Bradycardia, now resolved Gastrointestinal: Negative for abdominal pain. Musculoskeletal: Negative for arthralgia or weakness. Skin: Negative for color change. Neurological: Dysarthria and weakness resolved, + infrequent headaches x 4 months, no h/o seizures and syncope. Psychiatric/Behavioral: moody Endocrine: breast development and pubic hair at age 8.5 years with little progression since, has grown taller in past 6 months
8 HR 65 RR 22 BP 103/48 Wt 41 kg (35 th %) Constitutional: Sleeping but responds to commands Mouth/Throat: Mucous membranes are moist. Eyes: Conjunctivae are normal. Cardiovascular: Normal rate and regular rhythm. Pulses are palpable. No murmur heard. Pulmonary/Chest: Effort normal and breath sounds normal. Tanner 3 breasts Abdominal: Soft. She exhibits no distension. There is no hepatosplenomegaly. There is no tenderness. Genitourinary: Tanner 3 pubic hair Musculoskeletal: She exhibits no edema. Neurological: She exhibits normal muscle tone. CN grossly intact Skin: Skin is warm. Capillary refill takes less than 3 seconds. No striae, very mild acanthosis nigricans, IV lines in place on upper extremities
9 MRI/MRA negative Neurology Hemiplegic migraine vs hypoglycemia induced seizure secondary to adrenal insufficiency with recent steroid cessation Endo? Secondary to central adrenal insufficiency, however Usual state of health good, growing per parents report Short overnight fast with no documented hypoglycemia by serum Symptoms resolved without glucocorticoids Unable to determine whether symptoms resolved with dextrose Stress of event could have triggered hypoglycemia No hyponatremia Unlikely iatrogenic adrenal suppression given long wean Hypothyroidism was treated
10 TSH 0.01 Free T T4 9.8 T3 194 ACTH 7.8 Cortisol <0.4 DHEA SO4 <15 Clarification of ROS Poor appetite due abdominal pain and nausea x 4 5 mo Actually has frequent H/As x 4 months
11 ACTH stimulation (0.8 mcg) Likely central adrenal insufficiency with probable hypopitiutarism Could draw conclusions about primary insufficiency EEG Neurology Evaluation Post ictal slowing over right parietal region consistent with seizure likely provoked by hypoglycemia MRI from 6 months prior Periventricular heterotopic migratory defect Predisposition to seizures Hypoglycemia provoked seizure vs seizure provoked stress leading to hypoglycemia due to adrenal insufficiency
12 D/C home with 1 week 2x maintenance HC divided BID then physiologic No hypoglycemia/seizure recurrence Increased energy and mood 2.5 lb weight gain over 2 months Follow up scheduled with Dr. Brian Bordini for hypopituitary evaluation
13 Recovery of GH and TSH secretion for uncomplicated TSS in children is 4 12 months Magiakou MA 1994 JCEM Stratakis CA 1997 J Pediatr Recovery of HPAA is dependent on CRH secretion not the pituitary corticotrophs in uncomplicated TTS ACTH 250 mcg stimulation is preferred test Gomez MT et al 1993 JCEM
14 Lodish M, Dunn SV, et al. JCEM 2012
15 JCEM 2012
16 Associated: Lower UFC with partial recovery Not associated: Gender Age Disease length 12 am cortisol or UFC at dx Lodish M, Dunn SV, et al. JCEM 2012
17 Cortisol mcg/dl Peak stimulated level at 6 months: Sensitivity 70 80% Specificity 64 73% Lodish M, Dunn SV, et al. JCEM 2012
18 Lodish M, Dunn SV, Sinaii N, Keil MF, Stratakis CA 2012 Recovery of the hypothalamic pituitary adrenal axis in children and adolescents after surgical cure of Cushing s disease. J Clin Endrocrinol Metab 97: Magiakou MA, Mastorakos G, Gomez MT, Rose SR, Chrousos GP Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing s disease before and after surgical cure. J Clin Endrocrinol Metab 78: Stratakis CA, Mastorakos G, Magiakou MA, Papavassiliou E, Oldfield EH, Chrousos GP 1997 Thyroid function in children with Cushing s disease before and after transsphenoidal surgery. J Pediatr 131: Gomez MT, Magiakou MA, Mastorakos G, Chrousos GP The pituitary corticotroph is not the rate limiting step in the postoperative recovery of the hypothalamic pituitary adrenal axis in patients with Cushing syndrome. J Clin Endrocrinol Metab 77:
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