Transcript Emergenze endocrinologiche in adolescenza

Endocrine emergencies in adolescents
G. Chiumello, M.P.Guarneri
Paediatric Department, Endocrine Unit
Vita –Salute San Raffaele University, Milan, ITALY
1656 children (age 0-15 yrs)
affected by diabetes type 1
• DKA 19 %, severe DKA 4%
• DKA 30 %, severe DKA 8 %
less 2 yrs
Diabetes Care 2010
M.S. 14 yrs
 3rd year of junior high school  poor school performances
 large family
 disadvantaged socio-economic conditions
•Diabetes (onset 6 years of age)  poor glycometabolic control
respiratory distress
progressive worsening of general conditions
with state of consciousness alteration
EMERGENCY ROOM:
- pH 6,97 pCO2 17 HCO3 3,9 BEB -26,4
- glycemia 714 mg/dL
- Na+ 126mmol/L, K+ 5,7 mmol/L, creatinine 1,46 mg/dL
Intensive Care Unit
discontinuous insulin therapy during last 10-15
days and probably interruption of treatment in the last 24-48 hours
TREATMENT
I PERIOD: volume expansion / shock treatment (1-2 hours):
 10-20 ml/Kg saline solution 0,9%
II PERIOD: fluid replacement and maintenance (6 hours):
 Saline solution 0,9% + 40 mEq/L K+ (50% KCl + 50% KPO4)
III PERIOD: fluid replacement and maintenance (16-24 hours):
 Saline solution 0,45% + 40 mEq/L K+
• Gradual glycemia reduction
AFTER THE FIRST PERIOD
• e.v insulin (0,1 U/Kg/h) until DKA
resolution then switch to subcutaneous
insulin therapy
A.M. 18 yrs
 diabetes 13 yrs duration
 HbA1c> 10%
 poor glycometabolic control
 good social conditions
 optimal level of family care
During a relative’s acute illness, she voluntarily suspended the
administration of insulin for 48 hours
EMERGENCY ROOM: loss of consciousness
Serious DKA with oligoanuria and
hyperkalemia. Admitted to intensive
care unit
Psychological support
Persistence of poor glycometabolic control and onset of
eating disorders.
Found lifeless in bed  dead in bed syndrome
J.P.B. 17 yrs
 diabetes 13 yrs duration
 poor glycometabolic control with frequent asymptomatic
hypoglycemia
 HbA1c> 9%
 arrived in Italy 1 year ago from Morocco
 unsatisfactory familiar and personal compliance
After insulin injection, eveningwith friends, loss of
consciousness with generalized convulsions  glycemia 22
mg/dl
The following year, during another serious hypoglycemia,
involved in a traffic accident.
Hyperthyroidism
0.1:100.000/yr (early childhood)
Incidence  1:100.000/yr
3:100.000/yr (adolescence)
 initial symptoms can be mild: nervousness and anxiety, irritability, emotional
lability, fatigue, palpitations, tremors, insomnia, profuse sweating. Often drop in
school performance
variable thyroid size, usually symmetrical
increase with tense consistence
ophthalmic abnormalities less severe
than in adults, with staring eyes, puffiness
around the eyes, increased tear formation,
irritation and unusual sensitivity to light.
True exophthalmos is quite unusual
SYMPTOMATIC THERAPY  beta-blocker during the
first 2 weeks of therapy
children  propranolol
adults
 atenolol
METHIMAZOLE / PROPYLTHIOURACIL (not available in Italy)
METHIMAZOLE
PROPYLTHIOURACIL
Mechanism of action
inhibition TPO
inhibition TPO +
inhibition peripheral
conversion T4/T3
Serum Half-life
Freq. administration
4-6 hours
every 12-24 hours
75 min.
every 8 ore
Attack dose
0.5-1 mg/kg
Max dose 30 mg/die
5-10 mg/kg
Time to normalization
of thyroid function
4-6 weeks
4-6 weeks
Thyrotoxic crisis
Causes
surgery
sepsis
status epilecticus
diabetes ketoacidosis
burns
thyroxine overdose is not a cause of thyrotoxic crisis
METHIMAZOLO/PROPYLTHIOURACIL ev:
 block of thyroid hormones synthesis
LUGOL’S IODINE:
 oral or nasogastric administration
 inibition of FT4 / FT3 conversion
CORTISONICS:
 useful for their collateral inhibition of peripheral conversion of T4 to T3.
 Dexamethasone: 8-10mg/die in 3 administrations
 Hydrocortisone: 100-300mg/die in 3 administrations
BETA-BLOCKERS:
 if signs of marked
hyperexcitability)
adrenergic
activity
(psychosis,
extreme
PROPRANOLOL:
 0.1 mg/kg (up to 2mg) in 5-10 min ev
 2 mg/kg/die every 4-6 hours (max 6mg/kg/die)
agitation,
Acute adrenal insufficiency
DEFECTS OF ADRENAL STEROIDOGENESIS
- congenital adrenal insufficiency
- 21OHD
- other enzyme defects
ADDISON D.
-
SECONDARY ADDISON D.
Panhypopituitarism
autoimmune disease
genetic defects
adrenal hemorrhage
adrenoleukodystrophy
P.G. 17 yrs
ICS
 Holidays in Egypt with friends
 Fails to inform friends about his underlying disease
 Acute gastroenteritis with severe evolution and fever
 Admitted after 36 hours of symptoms in intensive care unit
 loss of consciousness,
 severe hypotension
 dyselectrolitemia
Parents, alerted by friends, informed local doctors
about son’s disease (ICS)
Diagnosis:Acute adrenal insufficiency in ICS
Adequate therapy
 Replacement therapy:
 Glucocorticoid (hydrocortisone)
 Mineralcorticoid (deoxycorticosterone)
 Absolute need of:
 good therapeutic compliance
 therapeutic management
Acute adrenal crisis
 Causes:
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Infections
Surgery
Severe stress
Accidents and injuries
Strenuous physical activity
Therapeutic non-compliance
 Clinical features:
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Anorexia
Nausea
Vomiting
Abdominal pain
Hypotension
Dyselectrolitemia
Hypoglycemia
Fever
Lethargy
Shock
GLUCOSALINE SOLUTION
Glucose solution 5% with NaCl (10-5mEq/kg/die)
120-150 ml/kg/die, half in first three hours
GLUCOCORTICOID
Flebocortid endovenous 2-3 mg/kg (bolus)
then 5mg/kg in three hours
then 10mg/kg/die
MINERALCORTICOID
Deoxycorticosterone acetate i.m. 3 mg/die
PANCREATIC NEUROENDOCRINE TUMORS
IN PEDIATRIC AGE
• Prevalence in children: 0.005-0.007 per 100,000 (M:F = 9:10)
• 32,8 % of pancreatic tumors
• Unusual before 10 years (1.2%). Average age at diagnosis>40 years
• More aggressive in children
• Survival rate at 15 years: 50%
J. Pediatric Surgery 2008
87% accidentally found
Sugical choice:
distal pancreatectomy /
DCP
CLINICAL PRESENTATION
• Accidental ultrasound/radiologic diagnosis (lesions < 1 cm)
•
Clinical syndromes related to endocrine mediators peptides production (sometimes
accidentally discovered at blood tests)
MAIN PANCREATIC NET AND ASSOCIATION TO MEN1
Tumor
Secreting Peptides
Symptomatology
-Insulinoma (5-10%)
Insulin, PP, VIP
Hypoglycemia signs and
symptoms
-Glucagonoma (10%)
Glucagone, PP
Calcitonin
Erythema
Hyperglycemia
Gloss/stomatitis
-Gastrinoma (25-40%)
Gastrin, VIP, PP
Neurotensina
Zollinger Ellison
Syndome
-VIPoma (5%)
VIP
Verner Morrison Syndrome
-Silent functional endocrine tumor (20%)
CLINICAL PRESENTATION
Specific symptoms not always present: catch down growth, weight loss.
Possible accidental diagnosis.
Confounding clinical features for multiple hormons.
GLUCAGONOMA
•necrolytic migrant erythema (70%)
•hyperglycemia (83%)
•glossitis and stomatitis (34%)
•weight loss (66%)
•thromboembolic disease (30%)
•occasionally, but not always present, nausea and vomiting
ZOLLINGER ELLISON SYNDROME
• Multiple peptic ulcers prone to perforation
•Diarrhea
•Identification of tumor
•Weight loss
VERNER MORRISON SYNDROME
•Pancreatic cholera: non continues diarrhea,
fasting, with faecal volume over 700 ml/die
• Electrolytic alterations(ipokaliemia, acloridia)
even
• Dyspepsia (inhibition of acid and peptic secretion )
while
DIAGNOSTIC PROBLEMS
• multiple hormonal involvement
• MIXED TUMOR: neuroendocrine and neoplastic exocrine tumors
• possible changes in tumor secretion (spontaneous or treatment-induced)
A.O. 9 yrs
Catch down growth
 GH: Clonidine 29.3 ng/ml,
GRF + Arginine > 35 ng/ml
IGF1 50-90° p.le
•TSH 6.6 mcu/ml; FT4 1.08 ng/dl.
•Thyroid Ultrasound: image suggestive of chronic
mild diffuse thyroiditis.
•Bone age = statural age
 Hypothalamic-pituitary RM: normal
Persistence velocity rate ≈ - 2SDS
• TSH: 9.36…6.28; FT4: 1.45…1.12
• Eutirox 1,4 mcg/kg/die TSH normalization
• urinary cortisol 24h: 122...125…240 mcg/24h.
(v.n. 25 – 75), ACTH: normal (34.4 pg/ml)
Hypercortisolism Hypothesis: dexamethasone
suppression test at low doses: adequate inhibition
of cortisol and ACTH
T
Hypercortisolism Hypothesis?
Suppression test at low doses (Dexamethasone 0,5 mg x 4/die for 2 days)
Cortisol 3 mcg/dl (v.n. < 1,4)  Cushing syndrome  admission to our Department
Absence of circadian rhythm
Cortisol  12 p.m. (242…162 ng/ml v.n. <44)
Urinary and salivary cortisol: 
Dexamethasone Test: appropriate cortisol and ACTH inhibition
FUNCTIONAL HYPERCORTICISM
Abdomen ultrasound: adenoma 5x4x4,5 cm (pancreatic tale)
TAC e RM: NEUROENDOCRINE TUMOR
Markers: Glucagon +++ 
Glucagonoma
Laparotomic partial pancreatectomy