Transcript Approach to common endocrine disorders

Approach to common
endocrine disorders
Dr Amir Babiker
MBBS, FRCPCH (UK), CCT (UK),
Msc Endocrinology and Diabetes - Queen
Mary University, London (UK)
Consultant Paediatric Endocrinologist, KKUH
and Assistant Professor, KSU (KSA)
Growth and Puberty
disorders
IS SHE SHORT?
SHORT STATURE
• Standing height > 2SD
below the mean (< 2.5
percentile) for gender
and chronological age.
• Investigation of children
<-2SDS identifies
pathology in 14%
• Investigation of children
<-3SDS identifies
pathology in 58%
• Compare the child’s
height with that of a
larger population of a
similar background and
mid-parental target
height.
Key points
• Short stature is defined as standing height or recumbent
length more than 2 standard deviations (SD) below the
mean value for chronologic age.
• Height (growth) velocity (cm/year) is another key
auxological parameter in the assessment of a child for
short stature.
• Height of a child must always be defined in the context of
genetic potential conferred by parental heights.
• Short stature must not be confused with failure to thrive.
Genetic factors
are also
important
GROWTH VELOCITY
• Most important
aspect of growth
evaluation
• Change in standing
Ht over:
• Infants: 4 mo
• Children: 6mo
• Normal (cm/yr)
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1y: 25
2y: 12
3y: 8
Then until puberty:
4-7 cm
REGULATION OF POSTNATAL GROWTH
• Infancy:
– Nutrition
– GH/IGF-I
• Childhood:
– GH/IGF-I
– Thyroxine
• Pubertal:
– GH/IGF-I
– Sex steroids
SS CAUSES
• Non-pathogenic
– Constitutional Delay of Growth and Puberty
– Familial short stature
• Nutritional
• Intra-Uterine Growth Restriction & Genetic disorders
– Syndromic e.g Silver-Russell syndrome
– Non-syndromic
• Systemic disorders and medications related
– Cardiovascular disease e.g. congenital heart disease
– Renal e.g. chronic renal failure, RTA
– Respiratory e.g. cystic fibrosis, asthma
– Gastrointestinal disease e.g. IBD
– Neurological e.g. brain tumour
– Psychosocial e.g. anorexia nervosa, child abuse
• Endocrine disorders
CDGP VS FAMILIAL SS
SS Causes: Endocrine causes
GH-related causes
• Growth hormone (GH) deficiency: isolated or combined with
other pituitary hormone deficiencies
• GH insensitivity
Hypothyroidism
Glucocorticoid excess
• Cushing syndrome
• Poorly managed congenital adrenal hyperplasia
• Exogenous corticosteroid administration
Pseudohypoparathyroidism
IS SHE SHORT?
EVALUATION OF SHORT STATURE
Prenatal history, including maternal infection, consumption of
alcohol or drugs, and smoking
Pattern of growth (height and weight), including birth weight
and length in relation to gestational age
Family history, including parental heights and age of onset of
puberty of parents and first-degree relatives
Profile of patient’s pubertal development, including age of
onset of breast development and menarche, testicular and
penile enlargement, pubic hair, and body odor
Nutrition
Evaluation of short stature
Evidence of systemic disease (gastrointestinal, cardiac,
pulmonary, renal)
Drug administration (steroids, methylphenidate)
Psychosocial milieu
Neurologic symptoms, especially headache, visual
disturbance
Physical Examination
Accurate measurements of height, weight, head
circumference, arm span, and upper and lower body segments
Assessment of nutritional state and fat distribution
Abnormal pigmentation of the skin
Dysmorphic features
Sexual maturity rating (Tanner staging)
Neurological examination including fundoscopy and visual field
tests
Examination of the thyroid gland
Target height of the child
BOYS:
[Father’s ht (cm)+ (mother’s Ht (cm)+ 13)]
2
GIRLS:
[(Father’s ht (cm) -13) + mother’s Ht(cm)]
2
Inches: change 13 for 5’’
BASELINE INVESTIGATIONS FOR
SHORT STATURE
• Full blood count, ESR
• Creatinine, urea, electrolytes
• Calcium, phosphate, liver function tests
• Ferritin, endomysial antibodies
• Karyotype (in girls)
• T4, TSH
• Skeletal survey in dysmorphic children
• Bone age X-ray (this is NOT a diagnostic investigation)
Further investigations
•Low levels of IGF-1 and IGFBP3 are suggestive of GH
deficiency
•Provocative GH stimulation test (insulin, arginine,
clonidine, glucagon, L-dopa) is the accepted method
for confirming the diagnosis of GH deficiency.
FDA-Approved indications for growth
hormone therapy
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GHD
PWS
SGA/IUGR
Turner syndrome
Noonan syndrome
ISS
Chronic renal insufficiency
AIDS wasting
Adult GHD
SHOX deficiency
Side effects of GH therapy
•Hypothyroidism
•Edema and sodium retention
•Benign intracranial hypertension
•Insulin resistance
•Slipped capital femoral epiphysis
•Scoliosis
•Gynecomastia
•???Development of cancers
TALL STATURE: CAUSES
ABNORMAL PUBERTY
OVERVIEW
• Physiology of normal puberty
• Pubertal assessment
• Early puberty:
• Causes
• Diagnosis
• management
• Delayed puberty:
• Causes
• Diagnosis
• management
TIMING OF PUBERTY
INCOMPLETE PUBERTY
• Premature thelarche
• Premature Adrenarche
• Premature menarche
CAUSES OF CPP
• Idiopathic (F>>M)
• Organic CNS disruption:
• Tumours of the hypothalamic-pituitary region
• Post head injury / meningitis
• Neurofibromatosis
• Williams syndrome
• Prematurity / Cerebral Palsy
• Hydrocephalus
• Post cranial surgery or radiotherapy
• Hypothyroidism
• Priming
PRECOCIOUS PSEUDOPUBERTY IN
FEMALES
Isosexual (feminizing) conditions
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McCune – Albright syndrome
Autonomous ovarian cyst
Ovarian tumors
Feminizing adrenocortical tumor
Exogenous estrogens
Heterosexual (masculinizing)
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Congenital adrenal hyperplasia
Adrenal tumor
Ovarian tumor
Glucocorticoid receptor defect
Exogenous androgens.
PRECOCIOUS PSEUDOPUBERTY IN
MALES
Isosexual
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Congenital adrenal hyperplasia
Adrenocortical tumor
Leydig cell tumor
Familial male precocious puberty
HCG secreting tumor
Teratoma
Heterosexual
• Feminizing adrenocortical tumor
• Exogenous estrogens
CAUSES OF PSEUDO-PRECOCIOUS PUBERTY
Sex steroids from the adrenal:
• Congenital adrenal hyperplasia
• Adrenal tumour
• Premature adrenarche (<8-9 yr)
• Cushing’s Syndrome
Sex steroids from the gonad:
• Ovarian tumour, cysts
• McCune-Albright Syndrome
• Testotoxicosis
• HCG – secreting (germ cell) tumours
Exposure to exogenous steroids
ASSESSMENT
History, Family history
Physical examination:
•Cutaneous lesions e.g neurofibromatosis,
McCune Albright syndrome
• CNS examination - Fundi
Auxology:
Pubertal staging (Tanner) + size of testes
Height, weight, MPH, growth velocity
Bone age
INVESTIGATIONS
Endocrine tests:
• Testosterone / oestradiol
• LH / FSH
• Adrenal androgens (DHEA-S, androstenedione)
• 17 –OH progesterone ± synacthen test
• β HCG
• GnRH test (central or pseudo-precocious)
Radiology:
• Pelvic ultrasound
• MRI hypothalamic – pituitary region
DNA analysis:
• For known genetic disorders (testotoxicosis, McCune Albright Syndrome)
THE GOALS OF TREATMENT FOR CPP
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Improvement of adult height
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Prevention of social and psychological problems.
Treatment of Pseudopuberty – by treating the cause (e.g adrenal
tumour or CAH)
DELAYED PUBERTY/PUBERTAL FAILURE
1. Central (Hypogonadotrophic Hypogonadism) Physiological
central delay and true GnRH /gonadotrophin deficiency
2. Peripheral (Hypergonadotrophic Hypogonadism) Primary
gonadal failure
HYPOGONADOTROPHIC
HYPOGONADISM
Constitutional delay of puberty
• Chronic illness / systemic disease
• Malnutrition (including anorexia nervosa, Dieting, overexercise)
• Hypothyroidism
Impaired H-P axis:
• Tumours H-P axis
• Congenital: SOD, Genetic defects
• Acquired : CNS Radiotherapy / trauma
HYPERGONADOTROPHIC HYPOGONADISM:
GIRLS
• Gonadal dysgenesis / Turner’s syndrome
• Autoimmune ovarian failure
• Gonadal failure following chemotherapy or
abdominal irradiation
• Toxic damage (iron overload)
• Intersex disorders including CAIS
• PCO
Hypergonadotrophic hypogonadism: Boys
• Testicular damage: cryptoorchidism, orchidopexy
torsion etc.
• Bilateral anorchia
• Syndromes: Noonans’s, P-W S, L-M-B-B S
• Gonadal dysgenesis: Klinefelter’s syndrome, other XY
aneuploidy, XO / XY
• Gonadal failure following chemotherapy or testicular
irradiation
ASSESSMENT
INVESTIGATIONS
TREATMENT OF DELAY/FAILURE
THYROID DISORDERS
THYROID GLAND
• Thyroid gland is composed of over a million cluster of
follicles
• Follicles are spherical & consists of epithelial cells
surrounding a central mass (colloid)
• Thyroglobulin is a storage room
• Two main hormones:
– Tetraiodothyronine (Thyroxin) = T4
– Triiodothyronine = T3
Production of Thyroid Hormones
NIS (Na+/I- Sympoter)
TPO
t1/2 = 5-7d
t1/2 = < 24 hrs
Effects of thyroid hormones
•Foetal brain & skeletal maturation
• Increase in basal metabolic rate
• Inotropic & chronotropic effects on heart
• Increases sensitivity to catecholamines
• Stimulates gut motility
• Increase bone turnover
• Increase in serum glucose
• Decrease in serum cholesterol
• Conversion of carotene to vitamin A
• Play role in thermal regulation
Thyroid disorders: Aetiology
• Congenital
• Acquired
– Primary
– Secondary
– Tertiary
Congenital hypothyroidism
• Agenesis (No goiter) or dysgenesis (aplasia,
hypoplasia, ectopic gland) are the commonest
causes…..85%
• Dyshormonogenesis (10%) and a goiter will be
present. Pendred syndrome with sensorineural
deafness is the commonest (often euthyroid).
• Transplacental maternal TSH receptor blocking
Abs (TRBAb) account for 5% of cases.
• Pituitary failure and maternal ingestion of
goitrogens are other causes
Congenital hypothyroidism
• One of the most common treatable causes of
Mental retardation
•
CH Screening is the most cost effective program
• Almost all affected Newborns have no S/S at
birth
• Congenital Anomalies increased by
10%(cardiac)
•
It is permanent in more than 90% of the cases
•
The earlier diagnosis the better IQ
A. Delayed epiphyseal appearance
B. epiphyseal dysgensis
Signs of congenital hypothyroidism
31% prolonged jaundice
• 23% umbilical hernia
• 21% constipation
• 21% macroglossia
• 19% feeding problems
• 16% hypotonia
• 16% hoarse cry
• 13% large posterior fontanelle
• 10% dry skin
• 5% hypothermia
• 2% goiter
• 40% delayed bone age
•
Management of congenital
hypothyroidism
• Documentation
– Free T4, TSH
• Thyroid scan, ultrasound (optional)
• Treatment (normal size full term)
– start L-thyroxin at 10-15 mcg/Kg daily
– Monitor TSH every 2-3 months during first 2
years of life.
Acquired hypothyroidism
• More common than hyperthyroidism
• 99% is primary (< 1% due to TSH deficiency)
• Hashimoto’s
– most common thyroid problem (4% of population)
– most common cause in iodine-replete areas
– chronic lymphocytic thyroiditis
– Associated with TPO antibodies (90%), less commonly Tg
antibodies
• Iatrogenic Hypothyroidism from radioactive iodine
therapy
Symptoms
Symptoms
– General Slowing Down
– Lethargy/somnolence
– Depression
– Modest Weight Gain
– Cold Intolerance
– Hoarseness
– Dry skin
– Constipation (↓ peristaltic activity)
– General Aches/Pains
– Arthralgias or myalgias (worsened by cold temps)
– Brittle Hair
– Menstrual irregularities
– Excessive bleeding
– Failure of ovulation
– ↓ Libido
Examination
• Dry, pale, course skin with yellowish tinge
• Periorbital edema
• Puffy face and extremities
• Sinus Bradycardia
• Diastolic HTN
• ↓ Body temperature
• Delayed relaxation of reflexes
• Megacolon (↓ peristaltic activity)
• Pericardial/ pleural effusions
• Congestive heart failure
• Non-pitting edema
• Hoarse voice
• Myopathy
Diagnosis
Congenital hypothyroidism
• Thyroid hormone level
• TSH
• Thyroid scan
• Maternal investigations: TFT and Abs
Acquired Hypothyroidism
• TSH
• fT4
• Thyroid antibodies
• Thyroid ultrasound
• TSH: low in secondary hypothyroidism -high in primary hypothyroidism
• TRH test: to differentiate between secondary & Tertiary hypothyroidism
Hyperthyroidism (Thyrotoxicosis)
Definition
• Excessive secretion of T3 & T4
• Affects metabolic processes in all body
organs
• Hyperthyroidism is 4-10 times more
prevalent in women
Graves’ Disease
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Most common cause of hyperthyroidism
Goiter, proptosis
TSH-R antibody (stimulating) = TRAB
40-70% relapse after 2 years of treatment
HYPERTHYROIDISM S&S
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Heat intolerance
Hyperactivity, irritability
Weight loss (normal to increased appetite)
Diarrhea
Tremor, Palpitations
Diaphoresis (sweating)
Lid retraction & Lid Lag (thyroid stare)
Proptosis
Menstrual irregularity
Goiter
Tachycardia
A 15 years old female with classic
Graves disease
DIAGNOSIS
• TSH level usually < 0.05 µu / ml
• 95 % of cases, high FT4 & FT3
• In 5% high FT3 with normal T4 (T3 Thyrotoxicosis)
• Thyroid receptor (TRAB) are usually elevated at diagnosis
• Antibodies against thyroglobulin, peroxidase or both are
present in the majority of patients
TREATMENT
Medical:
• Beta-blockers
• Carbimazole or Methimazole
• PTU (propylthiouracil)
Other modalities (definitive treatment)
• Radioactive iodine
• surgery
ADRENAL
DISORDERS
BASIC ANATOMY OF THE HUMAN
ADRENAL GLAND
Length: 4 – 6 cm; Width: 2 – 3 cm.
Weight : 3 – 5 g each
VASCULAR SUPPLY OF THE
ADRENAL
One of the most vascular tissues
 Arterial supply: Superior, Middle and Inferior
adrenal arteries
 Venous drainage:
› Right adrenal vein Inferior Vena cava
› Left adrenal vein Left Renal Vein
 Lymphatic drainage: Para-aortic lymph nodes
Without cortisol, we could not live
Cortisol functions:
• help the body respond to stress
• helps maintain blood pressure and
cardiovascular function
• helps slow the immune system's
inflammatory response
• helps balance the effects of insulin in
breaking down sugar for energy
• helps regulate the metabolism of
proteins, carbohydrates, and fats
• helps maintain proper arousal and
sense of well-being
• Pituitary gland, (at base of brain)
makes ACTH that drives the adrenal
gland
• production of glucocorticoids
ADRENAL DYSFUNCTION
Decrease function
Increase function
• Adrenal insufficiency
• Low cortisol, aldestrone
• Low Androgens
Eg Addison disease
• Cushing syndrome
High Cortisol
• Hyperaldosteronism
High aldosterone
• Pheochromocytoma
High
catecholamine
.
ADRENAL INSUFFICIENCY
• Primary or secondary
• Congenital or Acquired (for each)
• Symptoms
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Weight loss
Anorexia
Weakness
Fever
Depression
Nausea / abdo pain
Myalgia
Confusion
MANAGEMENT
• Resuscitation
• IV fluids (0.9% Nacl)
• IV hydrocortisone
• Continue with sick day rules
AMBIGUOUS GENETALIA
CUSHING SYNDROME
CALCIUM METABOLISM
AND ITS DISORDERS
OUTLINES
• Calcium metabolism
• Calcium disorders (↓Ca, ↑Ca)
• Parathyroid disorders
• Vitamin D disorders
• Rickets
BONES
CELLS
PHYSIOLOGICAL IMPORTANCE OF
CALCIUM
• Calcium salts in bone provide structural integrity of
the skeleton
• Calcium ions in extracellular and cellular fluids is
essential to normal function of a host of biochemical
processes
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Neuoromuscular excitability
Blood coagulation
Hormonal secretion
Enzymatic regulation
CALCIUM HOMEOSTASIS
• While PTH and vitamin D act to increase plasma Ca++--
• Calcitonin causes a decrease in plasma Ca++.
CALCIUM HOMEOSTASIS
ANATOMY AND FEEDBACK INHIBITION
CAUSES OF HYPOCALCEMIA
Hypo
parathyroid
Postoperative
Non parathyroid
PTH Resistance
Vitamin D
deficiency
Pseudohypoparathyroidism
Idiopathic
Malabsorption
hypomagnesaemia
Post radiation
Liver disease
Congenital
Kidney disease
Vitamin D
resistance
PSUEDOPSEUDOHYPOPARATHYROIDIS
M
Similar clinical features
but normal biochemistry
(PTH, Ca and PO4)
RICKETS
Reduced mineralization of bone matrix due to calcium
deficiency.
Commonest cause is Vit D3 deficiency:
• Dietary lack of the vitamin
• Insufficient ultraviolet skin exposure
• Malabsorption of fats and fat-soluble vitamins- A, D, E, & K.
• Abnormal metabolism of vitamin D
• Chronic renal failure.
TYPES OF RICKETS
• Nutritional
• Vitamin D deficient
• Vitamin D dependant type I
• Vitamin D dependant type II (Vit D resistant)
• Hypophosphataemic
OTHER CONDITIONS THAT CAN CAUSE
RICKETS
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Medications
Antacids
Anticonvulsants
Corticosteroids
Loop diuretics
Malignancy
Prematurity
CLINICAL FEATURES
 Skeletal deformities
 Features of hypocalcaemia ( eg. Apathetic, poor
feeding, tetany and seizures)
 Hypotonia and delayed motor development
INVESTIGATIONS
Bone profile
• calcium
• Phosphate
• Alkaline phosphatase
• Parathyroid hormone
• Vitamin D (25 OH VitD +/- 1,25 (OH)2 Vit D)
• Urinary calcium and phospherus
X- rays
TREATMENT
• Vitamin D supplement or
• Vitamin D analogues (one alpha, calcitriol)
Dose and type depends on the underline cause of Rickets
• Calcium
• Phosphate
THE EFFECT OF TREATMENT
Before
After
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