Download Prezentacja programu PowerPoint

PARATHYROID GLAND DISEASES
Primary hyperparathyroidism
Hypoparathyroidism
Causes of hypercalcemia

Primary hyperparathyroidism: sporadic, associated
with MEN 1 or MEN 2a, familial, after renal
transplantation
 Secondary, tertiary hyperparathyroidism
 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
P-HPTH

Common, usually asymptomatic disorder
 2-3fold commoner in females than in males
 Incidence approx. 42 per 100,000
inhibitants/year
 Single parathyroid adenoma – ca. 80%,
parathyroid hyperplasia – ca. 15%,
parathyroid carcinoma – 1-2%
Defense mechanism against
hypercalcemia
Hypercalcaemia  supression of PTH secretion
 bone resorption
 renal production of 1,25(OH)2D3
 calcium resorption from intestine
 urinary calcium loss
„Stones”
„Bones”
Renal stones
Nephrocalcinosis
Polyuria
Polydipsia
Uraemia
Osteitis fibrosa with:
subperiosteal resorption
- osteoclastomas
- bone cysts
Radiologic „osteoporosis”
Osteomalacia or rickets
Arthrithis
„Abdominal groans”
Constipation
Indigestion, nausea,
vomiting
Peptic ulcer
Pancreatitis
P-HPTH
signs
& symptoms
Other
Proximal muscle weakness
Keratitis, conjunctivitis
Hypertension
Itching
„Psychic moans”
Lethargy, fatigue
Depression
Memory loss
Psychoses – paranoia
Personality change,
neuroses
Confusion, stupor, coma
Hyperparathyroid bone disease






Osteitis fibrosa cystica (< 10% of patients)
Pain , pathologic fractures
 AlP
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)
Hyperparathyroid kidney disease
Kidney stones (< 15% of patients)
 Nephrocalcinosis
 Polidypsia, poliuria (loss of renal
concentration ability)
 Gradual loss of renal function

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

Laboratory findings in P-HPTH
 total Cas (may be intermittent),  Cau,  Ps,
 Pu
  intactPTH (may be upper normal)
 hyperchloremic acidosis
  GFR

Cas 2.25-2.75 mmol/l, Cau < 4 mg/kg/24 h (<250
mg/24 h in women, < 300 mg/24 h in men)
Ps 3.0-4.5 mg% (1.0-1.5 mmol/l), Pu 400-1400
mg/24 h
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, 99mTcsestamibi scanning, CT, MRI (rarely angiography,
venous sampling)

Treatment of P-HPTH (II)

No definitive therapy for hyperparathyroidism
 Estrogen replacement therapy in
postmenopausal women
 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).
1990 NIH Consensus Development Conference
Surgery should be recommended if:
1)
2)
3)
4)
5)
6)
7)
serum Ca is markedly elevated (above 2.8-3.0
mmol/l)
if there has been a previous episode of lifethreatening hypercalcemia
if creatinine clearance is reduced below 70%
of normal
if a kidney stone is present
if urinary calcium is markedly elevated (> 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)
Causes of hypocalcemia

Hypoparathyroidism: surgical, idiopathic, neonatal,
familial, postradiation, infiltrative
 Resistance to PTH action:
pseudohypoparathyroidism, renal insufficiency,
medications that block osteoclastic bone resorption
(calcitonin, bisphosphonates)
 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
Clinical features of hypocalcemia




Neuromuscular manifestations:
overt tetany: carpopedal spasm, painful;
laryngospasmus, blepharospasmus
latent tetany: Chvostek’s sign, Trousseau’s sign
focal or generalized seizures, papilledema,
confusion, organic brain syndrome, mental
retardation in children,
calcification of basal ganglia (skull X-ray, CT)
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
Hypoparathyroidism






Surgical, autoimmune, idiopathic, familial
 Cas,  Ps, low or undetectable intact PTH level
Surgical – ensues 1-2 days postoperatively,
transient in 50% of cases
Autoimmune – most commonly associated with
Addison’s 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
Pseudohypoparathyroidism (PHP)

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.
Albright’s hereditary osteodystrophy

(short stature, a round face, short neck,
brachydactyly, subcutaneous ossifications)
PHP 1B – no characteristic somatic phenotype
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[OH]D3), calcitriol (1,25[OH]2D3), low
phosphate diet (no milk)