Transcript 10 Parathyroid Dirorders - King Saud University Medical Student

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Common Parathyroid Disorders in
Children
Dr Sarar Mohamed
FRCPCH (UK), MRCP (UK), CCST (Ire), CPT (Ire),
DCH (Ire), MD
Consultant Paediatric Endocrinologist & Metabolic Physician
Associate Professor of Pediatrics
King Saud University
Agenda
• Calcium homeostasis
• Causes of hypocalcaemia
• Rickets
• hypercalcaemia
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Key-players of calcium metabolism
• Calcium & Phosphates
• Parathyroid hormone (PTH).
• Cholecalciferol (Vit.D3) and Calcitriol (
active form of vit D and it produced by the kidney )
• Estrogen and other Sex hormones. ( in
adults only )
• Calcitonin.
PARATHYROID HORMONE
Function of PTH
1-raises the level of calcium in the blood
2-decreases levels of blood phosphate.
3-Partially antagonistic to calcitonin
PARATHYROID HORMONE
• Secreation stimulated by fall in serum Ca.
•
mobilize calcium from bone
• Increases renal reabsorption of ca
• decreases renal clearance of calcium
•  increase calcium absorption - intestine
Calcium homeostasis
Vitamin D
• Fat soluble ‘vitamin’
• Synthesised in skin
• Food sources include fish oils
NB : Calcitriol ( active form of vit
D and it produced by the kidney )
Vitamin D
The active hormone is
1,25(OH)2D3
It increases absorption
of calcium from gut.
It increases
reabsorption of ca
from kidney.
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Calcitonin
• It is a calcium lowering hormone
• Secreted by Thyroid C cells
Anti - PTH
Target Organs
Kidney
G.I.Tract
Bone
Dysfunction of parathyroid Gland - MCQ
1. Too little parathyroid hormone – hypoparahypothyroidism
causes low serum calcium and high phosphate
2. Too much parathyroid hormone– hyperparahyperthyroidism
causes high calcium and low phosphate.
Newborn Screening
Hyperparathyroidism
• Main symptom is hypercalcemia, and hypophosphatemia also
occurs but not always.
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Pseudohypoparathyroidism
‫مهم‬
• Normal or elevated PTH (intact pituitary function), the problem is
that end organ is resistant.
• Leading to decreased calcium and increased phosphate levels
with normal ALP.
• Clinical presentation: short stature, and obese.
• Radiology: x-ray shows short 4th metacarpal and delayed
development.
• Occur in End organ insensitivity  occur in obese childrens
Calcium profile
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To diagnose a metabolic bone disease
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calcium
Phosphate
Alkaline phosphatase
Parathyroid hormone
Vitamin D
Urinary calcium and phospherus
Newborn Screening
• Elevated ALP on calcium profile, think of rickets.
• For vitamin D deficiency, measure the 25 hydroxycholecalciferol (which is normally formed in the liver).
• Prolonged breast feeding without supplementation can lead to
nutritional deficiency in the infants.
Causes of hypocalcaemia
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Rickets
Hypopararthyroidism
Psuedohypopararthyroidism
Familial hypocalcaemia
Renal failure
Drugs: phenytoin
Maternal diabetes: newborn to diabetic mothers have decreased insulin,
hyperglycemia, and pancreatic atrophy. Insulin is required for PTH. This
condition subsides with time and patient is taken for counseling.
• Prematurity
• DiGoerge syndrome CATCH 22
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Cardiac abnormality (tertaolgy of Fallot).
Abnormal facies.
Thymus aplasia.
Cleft palate.
Hypoparathyroidism/hypocalceamia.
‫اوال‬: Rickets
• Reduced
mineralization
of bone matrix
due to calcium
deficiency.
Rickets results when the osteoid does not have mineral.
This can also happen quickly, depending on the severity of mineral
deficiency. In adolescents or adults it is called osteomalacia
because they are not growing bones.
Calcium deficiency/Vit D deficiency
Newborn Screening
• Commonest cause of vitamin D deficiency is decreased sun
exposure overall, but in infancy it is mainly from diet; therefore, if
patient is on breast milk switch to supplement.
• All types of rickets leads to decreased phosphate level except
renal rickets because of renal failure (renal osteodystrophy).
Etiology :
Deficiency of Vit. D
• Dietary lack of the vitamin  like in baby who is
breastfeeding dependant - MCQ ‫مهمه‬
• Insufficient ultraviolet skin exposure
• Malabsorption of fats and fat-soluble vitamins- A, D, E,
& K.
• Abnormal metabolism of vitamin D chronic renal
failure.
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Rickets: Non renal causes –
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Nutritional
Intestinal – malabsorption
Hepatobiliary
Metabolic – anticonvulsant therapy
Rickets of prematurity (happens in the first
weeks of life).
Renal causes
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Renal osteodystrophy: CRF
Familial hypophosphataemic rickets
Renal tubular acidosis
Fanconi syndrome (the loss of phosphate leads to rickets).
– Primary
– Secondary - cystinosis (abnormal accumulation of amino acid cystine,
autosomal recessive, commonest cause of Fanconi), Wilson’s disease,
Lowe’s syndrome (x-linked recessive), tyrosinemia.
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Vitamin D dependent type 1 rickets (Deficiency of 1-hydroxyvitamin-D25-hydrolase). ‫مهم‬
Vitamin D dependent type 2 rickets (End-organ insensitivity to
autogenous 1,25-dihydroxyvitamin D). Type 2 is associated with alopecia.
‫مهم‬
– Both are autosomal recessive.
Rickets: Effect at growth end plate
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Inadequate growth plate mineralization.
• Defective calcification in the interstitial regions.
• The growth plate increases in thickness.
• The columns of cartilage cells are disorganized.
• Hereditary type is associated with short stature.
Rickets
Rickets
• Cupping of the epiphyses.
• Bones incapable of withstanding mechanical stresses and lead
to bowing deformities.
• Eventual length of the long bones is diminished (short stature).
Age of presentation
• VITAMIN D DEFICIENCY RICKETS (nutritional)
– 6 to 18 months (first 2 years of life).
• NON NUTRITIONAL RICKETS
– Beyond this age group.
• VITAMIN D DEPENDENT RICKETS
– Presents early in life.
Skeletal manifestations of Rickets
• Craniotaes (depression when pressing
on the skull  ping ball sign)
• Delayed closure of anterior fontanelle
• Frontal and parietal bossing
• Delayed eruption of primary teeth
• Chest for rickets Rosary (increase in
size of costo-chondoral junction)
Skeletal manifestations
EXTREMITIES –
 Enlargement of long bones around wrists
and ankles due to increased size of distal
bones (radius and ulna)
 Bow legs, knock knees
 Green stick fractures
Extra – skeletal manifestations
 SEIZURES AND TETANY –
Secondary to hypocalcaemia
 HYPOTONIA AND DELAYED MOTOR DEVELOPMENT
In rickets developing during infancy.
Investigations
• BASIC INVESTIGATIONS TO CONFIRM RICKETS
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Low or normal serum Ca
Low phosphorus (very early on in the disease may be normal)
High alkaline phosphatase
X rays of ends of long bones at knees or wrists
– Shows Widening, fraying, cupping of the distal ends of shaft.
• Vit D level low
• Parathyroid hormone high is secondary due to hypocalcemia ‫مهم‬
Newborn Screening
Rickets
• Radiology changes :
Show : Widening + cupping + decrease
Mineralization
Genu valgus
Wrist cupping
Tri radiate pelvis
Looser’s zones
Wrist widening
Wide metaphysis
Vitamin D Resistant Rickets ( X linked hypocalcemia )
• In the renal tubular disorders, rickets develops in
the presence of normal intestinal function and are
not cured by normal doses of vitamin D.
• Resistant or refractory rickets.
• Commonest is x-linked hypophosphatemic rickets
• Short stature and late presentation. ‫مهمه‬
• Vitamin D is normal but the pathology is in the
kidney because it can not absorb phosphate
Defective final conversion of Vit. D in to active form or End
organ insensitivity.
Newborn Screening
• Rickets is a clinical diagnosis, whereas vitamin D
deficiency is a biochemical one.
Vitamin D Resistant Rickets
Vitamin D Resistant Rickets
Newborn Screening
Inherited rickets ‫اعرفها كاسماء فقط وكلها تم‬
‫تفصيلها سابقا‬
• 1- hypophotemic rickets :
PHEX , FGF23 , DMP1
• 2- vit D dependant rickets :
Type 1 : CYP27B1 gene
Type 2 : VDR gene  present with alopecia
• 3- 25 hydroxylase deficincy
CYP2R1
Treatment of Rickets
• Vitamin D supplement
– Nutritional (commonest) we give vitamin
D3.
– Resistant rickets is treated by the active
form of vitamin D.
• Type and dose depends on underlying
cause of Rickets
Causes of hypercalcaemia
• Hyperparathyroidism
• Vitamin D intoxicity
• William syndrome
• Familial hypocalcuric hypercalcaemia: calcium is not excreted.
• malignancy
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• Full term 1 year old boy who
presented with afebrile tonic clonic
convulsions. He has no chronic
illnesses or medication. On
examination he has no apparent
dysmorphic features and his vital
signs were normal.
a. Describe an abnormality.
b. List two important investigations to
confirm your diagnosis.
c. What is the most likely diagnosis?
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Full term 1 year old boy who presented with afebrile
tonic clonic convulsions. He has no chronic illnesses or
medication. On examination he has no apparent
dysmorphic features and his vital signs were normal.
a. Describe an abnormality.
b. List two other important investigations to confirm your
diagnosis.
Answer:
a. Bowing of legs
b. 1. Serum calcium level, serum
alkaline phosphatase, 25 Vitamin D
level, hand x-ray
2. Possible diagnosis is nutritional
Vitamin D deficiency due to the age of
the baby.
Data interpretation
. An
obese 2 year old girl was found to be hypocalcemic
and did not respond to vitamin D.These results were
found. Plasma Calcuim 1.2 mmol/L , Plasma
phosphate 2.8mmol/L ( N- 0.8-1.4)
Alkaline Phosphatase 300 1u/L
Urea 4mmol/L
Magnesium 0.7 mmol/L
Parathyroid hormone 20mg/ml ( n <1)
What is the most likely diagnosis?
Psudohyperparathyrodism
what may radiological exams of hand reveal? Shorting
of the 4th metacarbal bone ‫عالمه مميزه‬
Newborn Screening
• This is a case of pseudohypoparathyroidism. What makes it
more likely is that the ALP, urea is normal (excluding both renal
and non-renal causes of rickets) and only calcium is low with
high PTH.
• An 8 ½ yr old girl followed by the
Endocrine Clinic was apparently well
until three years ago when she started
to have muscle pains and difficulty in
getting out of bed in the morning.
a. Describe two abnormalities.
b. Give the most likely diagnosis.
• An 8 ½ yr old girl followed by the
Endocrine Clinic was apparently well
until three years ago when she started
to have muscle pains and difficulty in
getting out of bed in the morning.
a. Describe two abnormalities.
b. Give the most likely diagnosis.
Answer:
a. Short stature bony deformity in the form
of bowing of legs
b. X-Linked Hypophosphatemic Rickets