Disorders of Parathyroid Gland

BY:
DR. RAKESH
DR. KARTHIK
DR. SOUMYA
MODERATOR: DR. DEEPA MAM
Main regulators of calcium and phosphate
homeostasis in body

– PTH
– Vitamin D
– Calcitonin
Parathyroid hormone
Kidneys
• Increases calcium Re-absorption
• Inhibits phosphate Re-absorption
• Increases activity of 1 alpha-hydroxalase

Bone
• Stimulates bone Resorption
• Increases serum calcium levels

Intestine
• INDIRECT Effect through calcitriol
Hypoparathyroidism
Decrease in extracellular
calcium concentration

Detected by the membrane

bound CaSR

Releasing preformed PTH

into blood

Failure of the glands to

respond

HYPOPARATHYROIDISM
 Clinical Presentation
• Tetany---classic neuromuscular findings---sustained or
intermittent involuntary contractions

• Seizures
– short, lasting 1 minute or less, but repetitive initial
lack of a postictal phase

• Fatigue ,lethargic
• Signs of Rickets

• Stridor with partial occlusion

• Cyanosis with complete occlusion
• Bronchospasm can present as Wheezing
Clinical signs

– Chvostek sign
– Trousseau sign
Laboratory findings

• Shortened fourth and fifth metacarpals and

metatarsal (Pseudohypoparathyroidism)

• Prolongation of QT interval on electrocardiography

• Hypocalcemia, Hyperphosphatemia with Alkaline

phosphatase in the normal range

• Calcifications of the basal ganglia in longstanding

cases (generally >8 years) contribute to (cognitive)
dysfunction
Differential diagnosis
AHO:Albright hereditary osteodystrophy PHP :pseudohypoparathyroidis
Chromosomal Microdeletions
(22q11.2,10p15.3p14)

Hypoplastic or Absent parathyroid glands

DiGeorge syndrome

• Cardiac abnormality (commonly interrupted aortic arch,

truncus arteriosus and tetralogy of Fallot)

• Abnormal facies

• Thymic aplasia

• Cleft palate

• Hypocalcemia/Hypoparathyroidism
Congenital causes

• Barakat syndrome
– Deletion of the gene coding for GATA3
– the Triad of Hypoparathyroidism, Deafness, and Renal
dysplasia

• Sanjad-Sakati syndrome
– Mutations in the gene encoding TBCE
– Hypoparathyroidism ,Failure to thrive, Microcephaly,
and Marked intellectual disability

• Kenny-Caffey syndrome
– Normal intelligence
– Marked by thickened long bones at birth
Mitochondrial Cytopathies

• Kearns-sayre syndrome
• MELAS
• Should be considered in patients with unexplained symptoms

– Ophtalmoplegia
– Sensrineural hearing loss
– Cardiac function disturbances
– Tetany
– Gain-offunction mutations in the CaSR gene result
in Diminished parathyroid responsiveness to low
calcium concentrations

– Gene coding for PTH is mutated, resulting in a non-

functional or absent circulating product
Acquired causes

• Iatrogenic
• Non Iatrogenic
– Transient
– Infiltrative
– Destructive
Iatrogenic causes

• Intentional surgical removal-----for the

treatment of parathyroid hyperplasia

• Accidental destruction---during
Thyroidectomy or tumor resection

• Treatment of chronic anemia such as

Thalassemia with repeated blood transfusions -
---Iron overload---if concomitant iron
chelation therapy is not provided
Non-iatrogenic

Transient

• Maternal Hypercalcemia during pregnancy

• Abnormal concentrations of magnesium (both hypo-

and hypermagnesemia)

• Metals such as copper in patients with poorly

treated Wilson disease accumulate in the
parathyroid glands, causing loss of function
(reversible with treatment)
Infiltrative

– Neck tumors and granulomatous diseases may invade

the parathyroids
Destructive

Polyglandular autoimmune syndrome type I

• Dysfunctional product ofthe AIRE (autoimmune regulator)

gene

• Chronic mucocutaneous candidiasis (nails,mouth,intestine,

vagina)

• Adrenal failure
Treatment

• Calcium supplementation for documented

hypocalcemia

• Vitamin D supplementation with calcitriol

• Careful monitoring of serum calcium and

phosphorous during therapy

• Monitor urine calcium levels to avoid

hypercalciuria
Pseudo-Hypoparathyroidism (PHP)
 Pseudo-Hypoparathyroidism (PHP)

PTH is produced and released into the

circulation appropriately

fails to have calcemic effects

Genetic defect in hormone receptor

adenylate cyclase system
• Autosomal dominant

• The disorders can be categorized by their

(lack of) renal responsiveness to exogenously
administered PTH
Type IA

– Albright hereditary osteodystrophy.

– Lack of adequate expression of the a subunit of
the G-protein that is responsible for PTH signal
transduction

Type IB

– The Biochemical profile is the same

– No phenotype correlation.
Clinical Presentation

• Attributable to
Hypocalcemia
• Short, stocky build
• Round face
•Brachydactyly with
dimpling of dorsum of
hand

•Short wide
phalanges

•Short 2nd
metacarpal and
metatarsal
• Thickening of calvaria

• Subcutaneous calcium deposits and

metaplastic bone formation

• Calcification of basal ganglia and lenticular

catarcts
Diagnosis

– Hypocalcemia

– Phosphorous and Alkaline phosphatase

elevated

– Confirmation: lack of response to

exogenously admnistered PTH

– Definitive diagnosis: Demonstaration of

mutated G protein
Treatment

• Calcitriol together with an oral source of

• Calcium

Careful follow-up assessment

• Blood and Urine calcium concentrations to

monitor for hypercalcemia/hypercalciuria
complications
 Pseudo-pseudo
Hypoparathyroidism
Pseudo-pseudo hypoparathyroidism

– Phenotypically similar but metabolically dissimilar

– Usual anatomic stigmata of PHP

– Members of same family

– But serum calcium and phosphorous are normal

– PTH slightly elevated

– Transition from normocalcemia to hypercalcemia

may occur with age
Hyper-Parathyroidism
 TYPE OF
HYPERPARATHYROIDISM DIFFERENTIAL DIAGNOSIS

Primary Parathyroid adenoma

Parathyroid hyperplasia

Secondary Vitamin D deficiency

1-a-hydroxylase deficiency
Chronic kidney disease
Malabsorption
Hereditary vitamin D-resistant rickets
Malnutrition
Medications affecting vitamin-D
metabolism

Tertiary Renal failure

Primary hyperparathyroidism

• Serum calcium and PTH concentrations are

concomitantly high

• Causes
• Parathyroid hyperplasia/adenoma
• Parathyroid carcinoma
 Primary Hyperparathyroidism

Symptoms

• Abdominal pain, Constipation

• Nausea and Vomiting

• Flank pain, Hematuria , Polyuria

• Fatigue, Depression, and Hypertension-related headache

• Changes in mentation progressing to stupor and coma

Clinical Signs

• Weakness, Loss of reflexes

• Bradycardia

• Band keratopathy

• Bone disease
– generalized demineralization and subperiosteal resorption
– With prolonged disease, cysts with a hemorrhagic
component, known as brown tumors, on radiography
Genetic syndromes associated with primary
hyperparathyroidism

• Multiple endocrine neoplasia (MEN-1)

• MEN 2-A

• Hyperparathyroidism Jaw-Tumor syndrome

MEN-1

• Pituitary tumors, Insulinomas, Gastrinomas

• mutations in the MENIN gene (tumor suppressor

gene)

• presents in the second to third decade, although it

has been described in the first decade

• Treatment is Surgical removal

MEN-2A

– Medullary thyroid carcinoma

– Pheochromocytoma
– Parathyroid adenoma
Jaw-tumor syndrome

– Autosomal dominant

– has a higher risk for both parathyroid carcinoma and

adenoma

– Fibro-osseous jaw tumors

– May also have Polycystic kidney disease ,Renal

hemartomas, Wilms tumor

– Treatment : Surgical removal

Secondary hyperparathyroidism

• Appropriately elevated PTH values in response to

low calcium concentrations

• Causes:
– Vitamin D deficiency
– 1-a-hydroxylase deficiency
– Chronic kidney disease
– Malabsorption
– Hereditary vitamin D-resistant rickets
– Malnutrition
– Medications affecting vitamin-D metabolism
Biochemical evaluation

– Total and ionized calcium, electrolytes

– Renal and liver function tests

– Serum phosphate, 25-hydroxyvitamin D,

1,25Di-hydroxyvitamin D

– Magnesium

– Urine calcium and creatinine

Treatment

• Calcium-vitamin D supplementation

• Administration of calcitriol---depending on
the cause
Tertiary hyperparathyroidism
• Occurs in the setting of secondary
hyperparathyroidism leading to parathyroid
hyperplasia and subsequent autonomous PTH secretion
• Elevated serum calcium & normal PTH (the history in
this case is what differentiates the two entities)

• Causes: Chronic kidney disease

• Treatment may involve parathyroidectomy or, in some

cases, calcimimetics
TYPE OF CALCIUM PHOSPHORUS CALCITRIOL ALKALINE URINE
HYPERPARAT PHOSPHATA CALCIUM/CR
HYROIDISM SE EATININE
RATIO

Primary High Low High/Normal High High

Secondary Normal/Low Low High/Normal High Low

Tertiary High Low High/Normal High High

• VITAMIN D
SOURCES

- 90% synthesised in skin via UVB light exposure

Cholecalciferol (vitD3 = inactive)
- 10% from food – Ergocalciferol (vit D2= inactive)
 DIETARY SOURCES
 Fatty fish, like tuna, mackerel, and
salmon.
Cod liver oil
Foods fortified with vitamin D, like some
dairy products, orange juice, soy milk,
and cereals.
Beef liver.
Cheese.
 Egg yolks

RICH EST S O U R C E - FISH LIVER OIL

CH EA P E ST S O U R C E - SUNL IGH T
 DAILY REQUIRMENT

 Children & adults –400IU(10µg/day)

 Pregnancy and lactation –

400IU(10µg/day)

 Over 70years- 800IU (20µg/day)

1 m i c r ogra m of v i t a m i n D = 40 I nt er na ti onal
Units
VITAMIN D–ACTIONS OF CALCITRIOL

Increases the Mineralization of Increased

intestinal absorption bone at low doses reabsorption of
of calcium and calcium and
phosphate Mobilization of phosphorus
by increased calcium from bone at Decreased
synthesis of calcium high doses excretion of calcium
binding protein and phosphorus
(calbinding D28k)
 VITAMIN D DEFICIENCY

VITAMIN D STATUS- 25(OH)D LEVEL ( ng / ml)

 Nor m al l e ve l of v i t a m i n D - > 30
 Vitamin D i ns uf f i ci ency -- 21-29
 Vitamin D d e f i c i en c y -- < 20
 S e v e re d e fic ien c y -- <10
 RISK FACTORS FOR VITAMIN D DEFICIENCY
 Elderly Individuals older t h a n 65 years
D a r k skin
No s u n exposure
Strict vegan diet
Obesity
Nursing home residents
P a t i e n t s on medications t h a t
induce P-450 enzyme activity.
Individuals with kidney disease (CRF)
 Individuals with low bone m a s s or osteoporosis
 Individuals with nonvertebral or hip fractures
Individuals with history of falls
VITAMIN D RELATED DISEASE

- RICKETS seen in children

-OSTEOMALACIA In Adults
OSTEOMALACIA
- O ste omal ac i a
is softening of the bones caused
by defective bone mineralization secondary to
hypocalcemia, hypophosphatemia & vitamin D
deficiency.
Even in the presence of normal calcium and
phosphate levels, chronic acidosis and drugs
such as bisphosphonates (etidronate ) &
phosphate-binding antacids can lead to
osteomalacia.
Demineralization occurs mainly in spine,
pelvis & lower extremities.
 I t m a n i f e s t s with bone pain,severe malaise, proximal
muscle weakness & waddling gait.
Radiologically- Pseudofracture- Looser’s
o
Zones of decalcification along t h e course o
r
of major arteries.
Biochemical changes -
Decreased s e r u m calcium or phosphorus.
Decreased s e r u m 25-hydroxyvitamin D .
Increased S e r u m ALP & PTH.
T r e a t m e n t - Vit D deficiency corrected by 60000 IU
once weekly for 4-6 wk. f/b once a month.
 TREATMENT: VITAMIN D
DEFICIENCY
 Depends on underlying disorder & severity of the
condition.
 Vitamin D should always be repleted in conjunction with
calcium supplementation since most of the consequences
of vitamin D deficiency are a result of impaired mineral
ion homeostasis.
 In patients in whom 1α-hydroxylation is impaired,

metabolites t h a t do not require this activation step are

the t r e atme nt of choice. They include 1,25(OH) 2 D3
[calcitriol , 0.25–0.5 g/d] and 1α-hydroxyvitamin D2 ( 2.5-
5 g/d).
 TREATMENT: VITAMIN D DEFICIENCY..

 •If the pathway required for activation of

vitamin D is intact, severe vitamin D
deficiency can be treated with initially
50,000 IU of Vit D weekly for 3–12 weeks,
followed by maintenance therapy (800 IU
daily).
• Calcium supplementation should include 1.5–2 g/d
of elemental calcium. Normocalcemia is usually
observed within one week of the institution of
therapy, although increases in PTH and alkaline
phosphatase levels may persist for three to six
months.
Prevention of Vitamin D Defeciency

• Sensible sun Exposure – 5-30 Minutes of exposure of arms and legs

between 10am and 3pm twice a week is often adequate
• To prevent vitamin D deficiency, the American academy of
pediatrics (AAP) recommends that infants and children receive at
least 400 IU per day from diet and supplements.
• All pregnant & lactating mother should take 400IU vitamin D
supplements daily
• Evidence shows that vitamin D supplementation of atleast 700 to
800 IU per day reduces fracture and fall rates in adults
• Fortification of flood with Vitamin D such as milk, butter
chapatiflour, maida, cereals etc.
Thank you