Title: PARATHYROID GLAND DISEASES
1PARATHYROID GLAND DISEASES
- Primary hyperparathyroidism
- Hypoparathyroidism
2Disorders 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 ).
3Disorders 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.
4Disorders 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
5Disorders 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.
6Disorders 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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8Disorders 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.
9P-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
10Hyperparathyroid 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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13Hyperparathyroid kidney disease
- Kidney stones (lt 15 of patients)
- Nephrocalcinosis
- Polidypsia, poliuria (loss of renal concentration
ability) - Gradual loss of renal function
14Other features of P-HPTH
- Lethargy, fatigue, depression, difficulty in
concentrating, personality changes - Frank psychosis
- Muscle weakness
- Hypertension
- Dyspepsia, nausea, constipation
- Chondrocalcinosis (pseudogout), gouty arthritis
15Stones 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
16Disorders 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
17Laboratory findings in P-HPTH
- ? total Cas (may be intermittent), ? Cau, ? Ps, ?
Pu - ? intactPTH (may be upper normal)
- hyperchloremic acidosis
- ? GFR
18Treatment 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)
19Surgery
- 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.
20- 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)
21Treatment of P-HPTH (II)
- Calcitonin
- Also inhibit osteoclast activity and prevent bone
resorption - Bisphosphonates
- They are given intravenously or orally to prevent
bone resorption.
22Treatment 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
23Treatment 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).
24Differential diagnosis
- Causes of hypercalcemia
- Primary hyperparathyroidism sporadic, associated
with MEN 1 or MEN 2a, familial, after renal
transplantation - Secondary, tertiary hyperparathyroidism
25Causes 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
26Causes of Hypercalcemia
Parathyroid - related
Vitamin D related
- Primary hyperparathyroidism
- Solitary adenomas
- Multiple endocrine neoplasia
- Lithium therapy
- Familial hypocalciuric hypercalcemia
- Vitamin D intoxication
- 1,25(OH)2D sarcoidosis and other granulomatous
diseases - Idiopathic hypercalcemia or infancy
27Differential Diagnosis
Causes of Hypercalcemia
Associated with high bone turnover
Malignancy - related
- Solid tumor with metastases(breast)
- Solid tumor with humoral mediation of
hypercalcemia (lung kidney) - Hematologic malignancies (multiple myeloma,
lymphoma, leukemia)
- Hyperthyroidism
- Immobilization
- Thiazides
- Vitamin A intoxication
- Assocated with Renal Failure
- Severe secondary hyperparathyroidism
- Aluminum intoxication
- Milk alkali syndrome
28hypoparathyroidism
29Clinical 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)
30Clinical 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
31Trousseau'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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33Chvostek'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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35diagnosis
- low Calcium
- high Phosphate
- low or undetectable intact PTH level
36Hypoparathyroidism 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
37Differential diagnosis
38Pseudohypoparathyroidism (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
39Causes 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
40- 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
41Treatment 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)
42IV 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
43IV 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?