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

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

Calcium control-mechanism

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.

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

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

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

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

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.

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.

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

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.

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

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

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

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.

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.

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

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.