1. Name:________________________________________________________________
Learning Objectives:
Discuss the aetiology, clinical manifestations, investigations & treatment of
Hyperparathyroidism
Tetany
General Medicine
Endocrinology
Parathyroid Diseases
Dr. J. Satish Kumar, MD, Department of Basic & Medical Sciences, AUST

2. Outline of calcium homeostasis showing interactions between parathyroid hormone (PTH), vitamin D and calcium.

3. Calcium control-mechanism

4. PTH-Intro
Parathyroid hormone (PTH) is a key controller of calcium metabolism, which interacts with vitamin D in kidney and bone.
Renal effects (steady state maintenance)
Inhibition of phosphate transport
Increased reabsorption of calcium
Stimulation of 25(OH)D-1alpha-hydroxylase
Bone effects (immediate control of blood Ca)
Causes calcium bone release within minutes
Chronic elevation increases bone remodeling and increased osteoclast-mediated bone resorption
Enhancing absorption of calcium from the small intestine:
Facilitating calcium absorption from the small intestine
PTH stimulates this process indirectly by stimulating production of the active form of vitamin D in the kidney.
Vitamin D induces synthesis of a calcium-binding protein in intestinal epithelial cells that facilitates efficient absorption of calcium into blood.

5. CLASSIFICATION OF DISEASES OF THE PARATHYROID GLANDS
Hormone excess
Primary hyperparathyroidism (adenoma, hyperplasia, occasionally carcinoma) Tertiary hyperparathyroidism
Secondary hyperparathyroidism
Hormone deficiency
Post-surgical Autoimmune Autosomal dominant hypoparathyroidism  
Hormone resistance
Pseudohypoparathyroidism Familial hypocalciuric hypercalcaemia  
Non-functioning tumours
Parathyroid carcinoma

6. CAUSES OF HYPERCALCAEMIA
With normal or elevated (i.e. inappropriate) PTH levels
Primary or tertiary hyperparathyroidism
Lithium-induced hyperparathyroidism
Familial hypocalciuric hypercalcaemia
With low (i.e. suppressed) PTH levels
Malignancy (e.g. lung, breast, renal, ovarian, colonic and thyroid carcinoma, lymphoma, multiple myeloma)
Elevated 1,25(OH)2 vitamin D (e.g. vitamin D intoxication, sarcoidosis, HIV)
Thyrotoxicosis
Paget's disease with immobilisation
Milk-alkali syndrome (Milk-alkali syndrome is caused by the ingestion of large amounts of calcium and absorbable alkali with resulting hypercalcemia.)
Thiazide diuretics
Glucocorticoid deficiency

7. Clinical assessment Symptoms and signs of hypercalcaemia
polyuria and polydipsia
renal colic
lethargy
anorexia
nausea
dyspepsia and peptic ulceration
constipation
depression
drowsiness and
impaired cognition

8. Patients with primary hyperparathyroidism may have a chronic, non-specific history.
‘Bones, stones and abdominal groans'.
50% primary hyperparathyroidism are asymptomatic.
Hypertension is common.
Parathyroid tumours are almost never palpable.
A family history of hypercalcaemia raises the possibility of FHH (Familial hypocalciuric hypercalcaemia) or MEN

9. Investigations Low plasma phosphate and elevated alkaline phosphatase
High plasma phosphate and alkaline phosphatase accompanied by renal impairment suggest tertiary hyperparathyroidism
Hypercalcaemia cause nephrocalcinosis and renal tubular impairment resulting in hyperuricaemia and hyperchloraemia.
The most discriminant investigation is the measurement of PTH using a specific immunoradiometric assay.
If PTH is normal or elevated and urinary calcium is elevated, then hyperparathyroidism is confirmed.

10. Management Primary hyperparathyroidism
strenuous attempts should be made to replace fluid deficits and lower the serum calcium concentration
Most patients do not require urgent treatment.
The only long-term therapy is surgery, with excision of a solitary parathyroid adenoma or debulking of hyperplastic glands.

11. TREATMENT OF SEVERE HYPERCALCAEMIA OF MALIGNANCY
Rehydration with normal saline
To replace as much as a 4-6 l deficit
May need monitoring with central venous pressure
Bisphosphonates
Causes a fall in calcium which is maximal at 2-3 days and lasts a few weeks
Additional rapid therapy may be required in very ill patients
Forced diuresis with saline and furosemide
Glucocorticoids
Calcitonin
Haemodialysis

12. Oral Manifestation of Primary HPT
Patients with primary HPT demonstrated:
1) increased incidence of tori
2) reduction in indices of cortical bone (lamina dura and gonial index)
3) a correlation between serum PTH levels and PDL width.
There are osseous alterations in the oral cavity associated with HPT.

13. Hypocalcemia
The presence of low serum calcium levels in the blood, usually taken as less than 2.1 mmol/L or 9 mg/dl
It is a type of electrolyte disturbance

14. Etiology Hypocalcemia may be associated with low PTH levels as seen in
hereditary hypoparathyroidism,
acquired hypoparathyroidism (surgical removal MCC of hypoparathyroidism), and
hypomagnesemia.
Hypocalcemia may be associated with high PTH levels when
the parathyroid hormone is ineffective;
in chronic renal failure, the hydroxylation of vitamin D is ineffective, calcium levels in the blood fall, and high PTH levels are produced in response to the low calcium, but fail to return calcium levels to normal.
Eating disorders
Excessive dietary magnesium, as with supplementation.
Prolonged use of medications/laxatives containing magnesium

15. Etiology Ineffective PTH Chronic renal failure Absent active vitamin D
Decreased dietary intake
Decreased sun exposure
Defective Vitamin D metabolism
Anticonvulsant therapy
Vitamin-D dependent rickets, type I
Ineffective active vitamin D
Intestinal malabsorption
Vitamin-D dependent rickets, type II

16. Hypocalcemia Spectrum of clinical manifestations
Few if any symptoms if the hypocalcemia is mild,
to life-threatening
seizures,
refractory heart failure, or
laryngospasm
Tetany, papilledema, and seizures may occur in patients who develop hypocalcemia acutely.
Ectodermal and dental changes, cataracts, basal ganglia calcification, and extrapyramidal disorders are features of chronic hypocalcemia. These last findings are most common in patients with hypoparathyroidism.

17. Tetany 
Acute hypocalcemia directly increases peripheral neuromuscular irritability.
As measured electromyographically, tetany consists of repetitive high-frequency discharges after a single stimulus.
Hyperexcitability of peripheral neurons is probably the most important pathophysiologic effect of hypocalcemia.

18. Clinical Features
Earliest symptom is Perioral tingling and parasthesia, 'pins and needles' sensation over the extremities of hands and feet.
Tetany, carpopedal spasm are seen.
Latent tetany
Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic)
Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)
Tendon reflexes are hyperactive
Life threatening complications
Laryngospasm
Cardiac arrhythmias
ECG changes include:
Prolonged QTc
Prolonged ST interval

19. Management
Two ampoules of intravenous calcium gluconate 10% is given slowly or if the hypocalcemia is severe, calcium chloride is given instead.
Maintenance doses of both calcium and vitamin-D (often as 1,25-(OH)2-D3, i.e. calcitriol) are often necessary to prevent further decline.