1. PARATHYROID GLAND DISEASES
Primary hyperparathyroidism
Hypoparathyroidism

3. 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

5. 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%

6. 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

8. P-HPTH signs & symptoms
„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 Indigestion, nausea, vomiting Peptic ulcer Pancreatitis
P-HPTH signs & symptoms
„Psychic moans”
Lethargy, fatigue Depression Memory loss Psychoses – paranoia Personality change, neuroses Confusion, stupor, coma
Other
Proximal muscle weakness Keratitis, conjunctivitis Hypertension Itching

9. 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)

12. Hyperparathyroid kidney disease
Kidney stones (< 15% of patients)
Nephrocalcinosis
Polidypsia, poliuria (loss of renal concentration ability)
Gradual loss of renal function

13. 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

14. Laboratory findings in P-HPTH
 total Cas (may be intermittent),  Cau,  Ps,  Pu
 intactPTH (may be upper normal)
hyperchloremic acidosis
 GFR
Cas mmol/l, Cau < 4 mg/kg/24 h (<250 mg/24 h in women, < 300 mg/24 h in men)
Ps mg% ( mmol/l), Pu mg/24 h

15. 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)

16. 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).

17. 1990 NIH Consensus Development Conference
Surgery should be recommended if:
serum Ca is markedly elevated (above 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 (> 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)

18. 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

19. 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

22. 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

23. 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

24. Treatment of hypocalcemia
Acute hypocalcemia: calcium chloride or gluconate i.v. (up to mg/24 h), oral calcium and vitamin D should be started (caution: digitalis treatment, stridor)
Chronic hypocalcemia: objective: normalisation of serum calcium and phospate
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)