PARATHYROID GLAND DISEASES

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PARATHYROID GLAND DISEASES

• Primary hyperparathyroidism
• Hypoparathyroidism

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Disorders of the Parathyroid Glands

• Maintenance of calcium, phosphate and magnesium
  homeostasis is under the influence of two
  polypeptide hormones
• parathyroid hormone(PTH)
• and calcitonin (CT)
• as well as a sterol hormone
• -1,25 dihydroxy cholecalciferol (1,25 (OH)2D3 ).

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Disorders of the Parathyroid Glands

• These hormones regulate the flow of minerals in
  and out of the extracellular fluid compartments
  through their actions on intestine, kidneys, and
  bones.

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Disorders of the Parathyroid Glands

• The PTH acts directly on the bones and kidneys
  and indirectly on the intestine through its
  effect on the synthesis of 1,25 (OH)2D3. Its
  production is regulated by the concentration of
  serum ionized calcium.
• Lowering of the serum calcium levels will
  induce an increased rate of parathyroid hormone
  secretion

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Disorders of the Parathyroid Glands

• Calcitonin is released by the C cells
  (parafollicular cells in the thyroid gland) in
  response to small increases in plasma ionic
  calcium. It acts on the kidney and bones to
  restore the level of calcium to just below a
  normal set point which in turn inhibits secretion
  of the hormone.

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Disorders of the Parathyroid Glands

• Calcitonin is therefore the physiological
  antagonist of PTH. The two hormones act in
  concert to maintain normal concentration of
  calcium ion in the extracellular fluid.

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Disorders of the Parathyroid Function
Hyperparathyroidism

• Primary hyperparathyroidismis due to excessive
  production of PTH by one or more of
  hyperfunctioning parathyroid glands. This leads
  to hypercalcemia which fails to inhibit the gland
  activity in the normal manner.

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P-HPTH

• Common, usually asymptomatic disorder
• The incidence of the disease increases after the
  age of 50
• 2-4 fold commoner in females than in males
• Incidence approx. 42 per 100,000 inhibitants/year
• Single parathyroid adenoma 80,
• parathyroid hyperplasia 15
• parathyroid carcinoma 1-2

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Hyperparathyroid bone disease

• Osteitis fibrosa cystica (lt 10 of patients)
• Pain , pathologic fractures
• Cystic lesions containing fibrous tissue (brown
  tumours) or cyst fluid
• Subperiosteal resorption of cortical bone,
  salt-and-pepper appearance of the skull
• Secondary osteoporosis (loss of cortical bone)

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Hyperparathyroid kidney disease

• Kidney stones (lt 15 of patients)
• Nephrocalcinosis
• Polidypsia, poliuria (loss of renal concentration
  ability)
• Gradual loss of renal function

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Other features of P-HPTH

• Lethargy, fatigue, depression, difficulty in
  concentrating, personality changes
• Frank psychosis
• Muscle weakness
• Hypertension
• Dyspepsia, nausea, constipation
• Chondrocalcinosis (pseudogout), gouty arthritis

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Stones Renal stones Nephrocalcinosis
Polyuria Polydipsia Uraemia
Bones Osteitis fibrosa
subperiosteal resorption
osteoclastomas bone cysts Radiologic
osteoporosis Osteomalacia or rickets Arthrithis
Abdominal groans Constipation
Indigestion, nausea, vomiting
Peptic ulcer Pancreatitis
Psychic moans Lethargy, fatigue
Depression Memory loss
Psychoses paranoia Personality
change, neuroses Confusion, stupor,
coma
P-HPTH signs symptoms
Other Proximal muscle weakness Keratitis,
conjunctivitis Hypertension anemia
Itching
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Disorders of the Parathyroid Function
Clinical Features

• Now a days almost 90 of diagnosed cases in the
  developed countries are picked up by routine
  screening for calcium level using the new
  automated machines
• asymptomatic

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Laboratory findings in P-HPTH

• ? total Cas (may be intermittent), ? Cau, ? Ps, ?
  Pu
• ? intactPTH (may be upper normal)
• hyperchloremic acidosis
• ? GFR

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Treatment of P-HPTH

• The adenoma may be located throughout the neck or
  upper mediastinum
• The only localization study needed in a patients
  with hyperparathyroidism is to locate an
  experienced parathyroid surgeon
• Surgical parathyroidectomy ? cure rate over 95
  (adenoma excellent surgeon)
• Localization studies are very useful in
  reoperative parathyroid surgery neck ultrasound,
  99mTc-sestamibi scanning, CT, MRI (rarely
  angiography, venous sampling)

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Surgery

• Surgical treatment should be considered after
  diagnosis of primary hyperparthyroidism.
• During surgery the surgeon identifies all four
  parathyroid glands (using biopsy if necessary)
  followed by the removal of enlarged parathyroid
  or 3 ½ glands in multiple glandular disease.

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• Surgery should be recommended if
• serum Ca is markedly elevated (above 2.8 mmol/l)
• if there has been a previous episode of
  life-threatening hypercalcemia
• if creatinine clearance is reduced below 70 of
  normal
• if a kidney stone is present
• if urinary calcium is markedly elevated (gt 400
  mg/24 h)
• if bone mass is substantially reduced (less than
  2 SD below normal for age, sex, and race)
• if the patient is young (under 50 years of age,
  particularly premenopausal women)

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Treatment of P-HPTH (II)

• Calcitonin
• Also inhibit osteoclast activity and prevent bone
  resorption
• Bisphosphonates
• They are given intravenously or orally to prevent
  bone resorption.

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Treatment of P-HPTH (II)

• Phosphate
• Oral phosphate can be used as an
  antihypercalcaemic agent and is commonly used as
  a temporary measure during diagnostic workup.
• Estrogen
• It also decrease bone resorption and can be given
  to postmenopausal women with primary
  hyperparathyroidism using medical therapy

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Treatment of P-HPTH (II)

• Management of hypercalcaemia rehydrating with
  saline, furosemide, calcitonin s.c. (4-8 IU/kg
  every 12 hrs.), bisphosponates (etidronate
  disodium, pamidronate disodium), glucocorticoids
  p.o. (in multiple myeloma, sarcoidosis,
  intoxication with vitamin D or A).

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Differential diagnosis

• Causes of hypercalcemia
• Primary hyperparathyroidism sporadic, associated
  with MEN 1 or MEN 2a, familial, after renal
  transplantation
• Secondary, tertiary hyperparathyroidism

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Causes of hypercalcemia

• Malignancies humoral hypercalcemia (caused by
  PTHrP, 1,25(OH)2D3, PTH), local osteolytic
  hypercalcemia
• Sarcoidosis
• Endocrinopathies thyrotoxicosis, adrenal
  insufficiency, pheochromocytoma, acromegaly
• Drug induced vitamin A, D intoxication,
  thiazides, lithium,milk-alkali syndrome,
  estrogens, androgens, tamoxifen
• Immobilization
• Acute renal failure

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Causes of Hypercalcemia
Parathyroid - related
Vitamin D related

• Primary hyperparathyroidism
• Solitary adenomas
• Multiple endocrine neoplasia
• Lithium therapy
• Familial hypocalciuric hypercalcemia

1. Vitamin D intoxication
2. 1,25(OH)2D sarcoidosis and other granulomatous
   diseases
3. Idiopathic hypercalcemia or infancy

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Differential Diagnosis
Causes of Hypercalcemia
Associated with high bone turnover
Malignancy - related

1. Solid tumor with metastases(breast)
2. Solid tumor with humoral mediation of
   hypercalcemia (lung kidney)
3. Hematologic malignancies (multiple myeloma,
   lymphoma, leukemia)

• Hyperthyroidism
• Immobilization
• Thiazides
• Vitamin A intoxication
• Assocated with Renal Failure
• Severe secondary hyperparathyroidism
• Aluminum intoxication
• Milk alkali syndrome

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hypoparathyroidism
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Clinical features of hypoparathyroidism (of
hypocalcemia)

• Neuromuscular manifestations
• overt tetany carpopedal spasm, painful
  laryngospasmus, blepharospasmus
• latent tetany Chvosteks sign, Trousseaus
  sign
• focal or generalized seizures, papilledema,
  confusion, organic brain syndrome, mental
  retardation in children,
• calcification of basal ganglia (skull X-ray, CT)

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Clinical features of hypoparathyroidism (of
hypocalcemia)

• Cardiac effects prolongation of QT interval,
  congestive heart failure
• Ophtalmologic effects subcapsular cataract
• Dermatologic effects dry and flaky skin, brittle
  nails, impetigo herpetiformis, pustular psoriasis

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Trousseau's sign
the induction of carpopedal spasm by inflation of
a sphygmomanometer above systolic blood pressure
for 3 minutes adduction of the thumb, flexion of
the metacarpophalangeal joints, extension of the
interphalangeal joints, and flexion of the
wrist.
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Chvostek's sign

• Chvostek's sign is contraction of the ipsilateral
  facial muscles elicited by tapping the facial
  nerve just anterior to the ear
• The response ranges from twitching of the lip to
  spasm of all facial muscles and depends upon the
  severity of the hypocalcemia
• occurs in about 10 percent of normal subjects
• Although Trousseau's sign is more specific than
  Chvostek's sign, both may be negative in patients
  with hypocalcemia

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diagnosis

• low Calcium
• high Phosphate
• low or undetectable intact PTH level

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Hypoparathyroidism causes

• Surgical, autoimmune, idiopathic, neonatal,
  familial, postradiation, infiltrative
• Surgical ensues 1-2 days postoperatively,
  transient in 50 of cases
• Autoimmune most commonly associated with
  Addisons disease and mucocutaneous candidiasis
  (type I polyglandular autoimmune syndrome)
• Idiopathic an isolated form, age of onset 2-10
  years, commoner in females
• Familial due to activating mutation of the
  parathyroid calcium receptor gene

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Differential diagnosis
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Pseudohypoparathyroidism (PHP)

• Resistance to PTH action
• A heritable disorder of target-organ
  unresponsineness to PTH (Ellsworth-Howard test
  lack of an increase in urinary cAMP after
  administration of exogenous PTH)
• Hypocalcemia and hyperphosphatemia, but elevated
  PTH level and a markedly blunted response to PTH
  administration
• 2 distinct forms
• PHP 1A characteristic somatic phenotype, i.e.
  Albrights hereditary osteodystrophy (short
  stature, a round face, short neck, brachydactyly,
  subcutaneous ossifications)
• PHP 1B no characteristic somatic phenotype

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Causes of hypocalcemia

• Failure to produce 1,25(OH)2D3 vitamin D
  deficiency, hereditary vitamin D-dependent
  rickets, type 1 (1?-hydroxylase deficiency)
• Resistance to produce 1,25(OH)2D3 hereditary
  vitamin D-dependent rickets, type 2 (defective
  VDR)
• Acute complexation or deposition of calcium
  acute hyperphosphatemia (crush injury, rapid
  tumour lysis, excessive enteral and parenteral
  phosphate administration), acute pancreatitis,
  citrated blood transfusion, hungry bones syndrome

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• Dietary deficiency of vitamin D or calcium
• Decreased intestinal absorption of vitamin D or
  calcium due to primary small bowel disease, short
  bowel syndrome, and post-gastrectomy syndrome.
• Drugs that cause rickets or osteomalacia such as
  phenytoin, phenobarbital, cholestyramine, and
  laxative.
• Severe hypomagnesemia
• Chronic renal failure

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Treatment of hypocalcemia

• Acute hypocalcemia calcium chloride or gluconate
  i.v. (up to 400-1000 mg/24 h), oral calcium and
  vitamin D should be started (caution digitalis
  treatment, stridor)
• Chronic hypocalcemia objective normalisation of
  serum calcium and phospate
• 1.0-2.0 g of elemental calcium p.o. per day,
  vitamin D3, active metabolites alfacalcidol
  (1?OHD3), calcitriol (1?,25OH2D3), low
  phosphate diet (no milk)

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IV calcium

• Symptomatic patients
• Ca lt 2 mmol/L
• 10 ml of 10 calcium gluconate in 50 ml of normal
  saline given over 10 min with ECG monitoring
• Repeat above treatment until symptoms free
• Treat hypomagnessemia if present with IV
  magnesium sulfate

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IV calcium

• Start IV infusion of 100 ml (10 ampoules) of 10
  calcium gluconate in 1L of NS 0.9 or D5 at a
  rate of 50 to 100 ml/hr
• Adjust the rate to normalize calcium
• Start oral calcium and potent vitamin D
• Treatment with PTH?