Endocrine emergencies in adolescentsEndocrine emergencies in adolescents G. Chiumello, M.P.GuarneriG. Chiumello, M.P.Guarneri

Paediatric Department, Endocrine UnitVita –Salute San Raffaele University, Milan, ITALY

16561656 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 yrs3rd year of junior high school poor school performanceslarge familydisadvantaged socio-economic conditions

•Diabetes (onset 6 years of age) poor glycometabolic control

respiratory distressprogressive 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

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+

TREATMENT

• 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 yrsdiabetes 13 yrs duration poor glycometabolic control with frequent asymptomatic

hypoglycemiaHbA1c> 9%

arrived in Italy 1 year ago from Moroccounsatisfactory 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.

HyperthyroidismHyperthyroidism

Incidence 1:100.000/yr

0.1:100.000/yr (early childhood)

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

METHIMAZOLE / PROPYLTHIOURACIL (not available in Italy)

METHIMAZOLE PROPYLTHIOURACIL

Mechanism of action inhibition TPOinhibition TPO +

inhibition peripheral conversion T4/T3

Serum Half-lifeFreq. administration

4-6 hours every 12-24 hours

75 min. every 8 ore

Attack dose 0.5-1 mg/kgMax dose 30 mg/die

5-10 mg/kg

Time to normalization of thyroid function 4-6 weeks 4-6 weeks

SYMPTOMATIC THERAPY beta-blocker during the first 2 weeks of therapy children propranololadults atenolol

Thyrotoxic crisis

CausesCauses

surgery

status epilecticus

diabetes ketoacidosis

burns

sepsis

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 adrenergic activity (psychosis, extreme agitation, hyperexcitability) 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)

Acute adrenal insufficiency DEFECTS OF ADRENAL STEROIDOGENESIS

- congenital adrenal insufficiency- 21OHD- other enzyme defects

ADDISON D.

- autoimmune disease- genetic defects- adrenal hemorrhage- adrenoleukodystrophy

SECONDARY ADDISON D.

Panhypopituitarism

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 doctorsabout 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

Causes: Infections Surgery Severe stress Accidents and injuries Strenuous physical activity Therapeutic non-compliance

Clinical features: Anorexia Nausea Vomiting Abdominal pain Hypotension Dyselectrolitemia Hypoglycemia Fever Lethargy Shock

Acute adrenal crisis

GLUCOSALINE SOLUTIONGLUCOSALINE SOLUTION Glucose solution 5% with NaCl (10-5mEq/kg/die)Glucose solution 5% with NaCl (10-5mEq/kg/die) 120-150 ml/kg/die, half in first three hours120-150 ml/kg/die, half in first three hours

GLUCOCORTICOIDGLUCOCORTICOIDFlebocortid endovenous 2-3 mg/kg (bolus)Flebocortid endovenous 2-3 mg/kg (bolus)then 5mg/kg in three hours then 5mg/kg in three hours then 10mg/kg/diethen 10mg/kg/die

MINERALCORTICOIDMINERALCORTICOIDDeoxycorticosterone acetate i.m. 3 mg/dieDeoxycorticosterone acetate i.m. 3 mg/die

• 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%

PANCREATIC NEUROENDOCRINE TUMORSIN PEDIATRIC AGE

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)

Tumor Secreting Peptides Symptomatology

-Insulinoma (5-10%) Insulin, PP, VIP Hypoglycemia signs and symptoms -Glucagonoma (10%) Glucagone, PP Erythema

Calcitonin HyperglycemiaGloss/stomatitis

-Gastrinoma (25-40%) Gastrin, VIP, PP Zollinger Ellison Neurotensina Syndome

-VIPoma (5%) VIP Verner Morrison Syndrome

-Silent functional endocrine tumor (20%)

MAIN PANCREATIC NET AND ASSOCIATION TO MEN1

CLINICAL PRESENTATION

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, even while fasting, with faecal volume over 700 ml/die• Electrolytic alterations(ipokaliemia, acloridia)• Dyspepsia (inhibition of acid and peptic secretion )

Specific symptoms not always present: catch down growth, weight loss. Possible accidental diagnosis.

Confounding clinical features for multiple hormons.

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 rhythmCortisol 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