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) 2 D 3 , 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) 2 D 3  calcium resorption from intestine  urinary calcium loss

„Stones”

Renal stones Nephrocalcinosis Polyuria Polydipsia Uraemia

„Bones”

Osteitis fibrosa with: subperiosteal resorption - osteoclastomas - bone cysts Radiologic „osteoporosis” Osteomalacia or rickets Arthrithis

„Abdominal groans”

Constipation

„Psychic moans”

Peptic ulcer Pancreatitis

& symptoms

Lethargy, fatigue Depression Memory loss

Other

Psychoses – paranoia Personality change, Proximal muscle weakness neuroses Keratitis, conjunctivitis Confusion, stupor, coma Hypertension Itching

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 Ca s (may be intermittent),  P u intactPTH (may be upper normal) Ca u ,  P s ,   hyperchloremic acidosis  GFR Ca s 2.25-2.75 mmol/l, Ca u < 4 mg/kg/24 h (<250 mg/24 h in women, < 300 mg/24 h in men) P s 3.0-4.5 mg% (1.0-1.5 mmol/l), P u mg/24 h 400-1400

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, 99m Tc sestamibi 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) serum Ca is markedly elevated (above 2.8-3.0 mmol/l) if there has been a previous episode of life threatening hypercalcemia 3) 4) 5) 6) 7) 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) 2 D 3 :

vitamin D deficiency, hereditary vitamin D-dependent rickets, type 1 (1  -hydroxylase deficiency)

Resistance to produce 1,25(OH) 2 D 3 :

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  Ca s ,  P s , low or undetectable intact PTH level

Surgical

– ensues 1-2 days postoperatively, transient in 50% of cases

Autoimmune

syndrome) – most commonly associated with Addison’s disease and mucocutaneous candidiasis (type I polyglandular autoimmune

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 D 3 , active metabolites: alfacalcidol (1  [OH]D 3 ), calcitriol (1  ,25[OH] 2 D 3 ), low phosphate diet (no milk)