MINISTRY OF HEALTH PROTECTION OF UKRAINE
Vynnitsa national medical university named after M.I.Pyrogov
«CONFIRM»on methodical meeting of endocrinology department
A chief of endocrinology department, prof. Vlasenko M.V.
______“_31_”_august___ 2012 y
METHODOLOGICAL RECOMМENDATIONS
for independent work of students
by preparation for practical classes
Scientific discipline / Internal medicineМodule № 1 / Basis of Internal medicine
substantial module №1 / “Diagnostic, treatment and prophylactic basis of main endocrinology diseases”
Topic / Topic №14: Diseases of parathyroid gland. Hyperparathyroidism: etiology, pathogenesis, classification, clinics, differential diagnosis, treatment. Hypoparathyroidism: etiology, pathogenesis, classification, clinics, diagnostic, treatment.
Course / 4
Faculty / Medical № 1
Vynnitsa – 2012
METHODOLOGICAL RECOMМENDATIONS
for the students of 4-th course of medical faculty for preparation to the practical classes from endocrinology
1.Тopic №14: Diseases of parathyroid gland. Hyperparathyroidism: etiology, pathogenesis, classification, clinics, differential diagnosis, treatment. Hypoparathyroidism: etiology, pathogenesis, classification, clinics, diagnostic, treatment.
2. Relevance of topic: Parathyroid disorders are characterized by impairment of their function or structure. They occur rarely, but according to diffcult early diagnosis, consequences of wrong diagnosis and treatment, they are recommended to learn for students of higher medical school. Graduates of medical faculty of higher medical school commonly work as a general practice doctors, who must be able primary reveal endocrine pathology.
Hypoparathyroidism (a tendency to hypocalcemia, often associated with chronic tetany, resulting from hormone deficiency, characterized chemically by low serum calcium and high phosphorus levels) occurs permanently in 3 % of expartly performed thyroidectomies. Hypoparathyroidism is a generalized disorder resulting from excessive secretion of parathyroid hormone by one or more parathyroid glands and it is usually characterised by hypercalcemia, hypophosphatemia, and exessive bone resorption. It occurs with increased frequency in women and with aging.
Hyperparathyroidism (is characterized by hypercalcemia, associated with damaging of the bones, kidneys and gastrointestinal tract) occurs in 0,15 – 0,52 % of adults.
3. Aim of lesson:
- to know etiology, pathogenesis, main clinical manifestations, special features of parathyroid deseases
- to examine a patient with suspicion on parathyroid disease
- to carry out the diagnosis on a basis of clinical and laboratory fndings;
- to make up differential diagnosis and determine management;
- to give the frst aid in a case of hypoparathyroid crisis.
- to know phosphorus and calcium homeostasis.
- to know etiology, pathogenesis of hyper- and hypoparathyroidism.
- to know classifcation of hyper- and hypoparathyroidism.
- to know clinical presentation of these diseases.
- to know early diagnostics on a basis of laboratory and instrumental examination fndings.
- to know differential diagnostics between hyperparathyroidism and other diseases, incl. endocrine (thyrotoxicosis, acromegalia, pheochromocytoma, chronic adrenal insuffciency) and hypercalcinemic states.
- to know differential diagnostics between hypoparathyroidism and other causes of hypocalcinemia and convulsive syndrome.
- to know the treatment of hyper- and hypoparathyroidism, frst aid in a case of acute form of hypocalcinemic tetania.
4. References
4.1. Main literature
1. Endocrinology. Textbook/Study Guide for the Practical Classes. Ed. By Petro M. Bodnar: - Vinnytsya: Nova Knyha Publishers, 2008.-496 p.
2. Basіc & Clіnіcal Endocrіnology. Seventh edіtіon. Edіted by Francіs S. Greenspan, Davіd G. Gardner. – Mc Grew – Hіll Companіes, USA, 2004. – 976p.
3. Harrison‘s Endocrinology. Edited J.Larry Jameson. Mc Grew – Hill, USA,2006. – 563p.
4. Endocrinology. 6th edition by Mac Hadley, Jon E. Levine Benjamin Cummings.2006. – 608p.
5. Oxford Handbook of Endocrinology and Diabetes. Edited by Helen E. Turner, John A. H. Wass. Oxford, University press,2006. – 1005p.
4.2. Additional literature
6. Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New York: WC Graw-Hill Book, 1985. - P. 232-236. Pediatric Endocrinology. 5th edition. – 2006. – 536p.
7. Thyroid Disordes (Aclevelend Clinic Guide) by Mario Skugor, Jesse Bryant Wilder Clevelend Press,2006. – 224p.
Basic Level.
Students must know:
1. Anatomy and physiology of parathyroid glands.
2. Main functions of сalcitonin and parathyroid hormone.
3. Biological effects of calcium on organism.
4. Laboratory and instrumental methods which can be used in patients with diseases of parathyroid glands.
Students should be able to:
1. Examine patient.
2. Interpritate data of laboratory and instrumental methods of examination.
Students’ Independent Study Program.
You should prepare for the practical class using the existing text books and lectures. Special attention should be paid to the following:
1. Anatomy, physiology of parathyroid glands.
2. Regulation of calcium-phosphorus homeostasis.
3. Hypoparathyroidism: etiology and pathogenesis.
4. Classification of hypoparathyroidism.
5. What are the main diagnostic criteria of hypoparathyroidism?
6. Early diagnostics on a basis of laboratory and instrumental examination fndings.
7. Differential diagnostics between hypoparathyroidism and other causes of hypocalcinemia and convulsive syndrome.
8. What does treatment of hypoparathyroidism include?
9. What are the main causes and signs of hypocalcemic crisis?
10. What does emergency treatment of hypocalcemic crisis include?
11. Hyperparathyroidism: etiology and pathogenesis.
12. Classification of hyperparathyroidism.
13. What are the main diagnostic criteria of hyperparathyroidism?
14. Differential diagnostics between hyperparathyroidism and other diseases, incl. endocrine (thyrotoxicosis, acromegalia, pheochromocytoma, chronic adrenal insuffciency) and hypercalcinemic states.
15. What does treatment of hyperparathyroidism include?
16. What are the main causes and signs of hypercalcemic crisis?
17. What does emergency treatment of hypercalcemic crisis include?
Short content of the theme.
Normal serum calcium (Ca) levels range between 2, 25 – 2,75 mmol/l (8.8 – 10.4 mg/100 ml. Approximately 40 % of the total blood Ca is bound to serum proteins while the remaining 50 % is ultrafilterable and includes ionized Ca plus Ca comlexed with phosphate and citrate. The ionized Ca fraction (about 50 % of the total blood Ca) is influenced by pH changes. Acidosis is associated with decreased protein - binding and increased ionized Ca and alkalosis with a fall of ionized Ca due to increased protein – binding. These pH – induced changes in ionized Ca occur independently of any change in total blood Ca concentration. In the laboratory determination of serum Ca, only total serum Ca is usually measured.
Maintenance of the blood Ca level is partially dependent upon dietary Ca intake (0,5 – 1,0 gm/day), gastro-intestinal absorption of Ca, and renal Ca excretion. The major factor preserving the constancy of blood Ca concentration is the bone Ca reservoir. About 99 % of body Ca is in bone, of which 1 % is freely exchangeable with ECF.
Parathyroid hormone (PTH) is secreted by the parathyroid glands. PTH and vitamin D are the principle regulators of Ca and phosphorus (P) homeostasis; their metabolic actions are interrelated. PTH promotes renal formation of the active metabolite of vitamin D. Conversely, with a deficiency of the vitamin or any resistance to its action, some of the effects of the hormone are blunted.
The most important actions of PTH are:
1) increasing the rate of bone resorption with mobilization of Ca and P from bone;
2) increasing intestinal absorption of Ca (mediated by an action on the metabolism of vitamin D);
3) stimulation of Ca resorption in the distal tubule of the kidney;
4) decreasing renal tubular reabsorption of phosphate (PO4).
These actions account for most of the important clinical manifestations of PTH excess or deficiency.
(Calcitonin is synthesized in the C cells of the thyroid gland. The major regulator of calcitonin secretion is the serum Ca concentration. In contrast to their effect on PTH, hypercalcemia stimulates and hypocalcemia suppresses calcitonin secretion. A number of gastrointestinal hormones including gastrin, glucagon, and cholecystokinin are pharmacologic secretegogues for calcitonin, but gastrin is the most potent.
Physiologic actions:
- inhibiting osteoclastic bone resorption;
- decreasing renal tubular calcium reabsorption and others.)
HYPOPARATHYROIDISM
it is a disease resulting from PTH deficiency, characterized chemically by low serum calcium and high serum phosphorus levels, often associated with chronic tetany.
(Pseudohypoparathyroidism is a congenital condition in which there is tissue resistance to the effects of parathyroid hormone. It presents with skeletal abnormalities, elevated levels of serum parathyroid hormone and normal serum calcium.)
Etiology.
1) accidental removal of or damage to several parathyroid glands during thyroidectomy (2 %);
2) radioactive iodine therapy of the hyperthyroidism or X-ray therapy of the neck organs;
3) it is also occurs as a part of a genetic syndrome of type I (hypoparathyroidism, Addison’s disease, mucucutaneous candidiasis);
4) congenital deficiency (DiGeorge syndrome), agenesis or aplasia of parathyroid glands;
5) hemorrhages, infarctions, infections of the glands;
6) severe hypomagnesemia;
7) autoimmune processes.
Classification.
1. Congenital hypoparathyroidism (aplasia of parathyroid glands).
2. Idiopathic hypoparathyroidism (autoimmune): isolated or type I autoimmune polyglandular syndrome.
3. Post operative hypoparathyroidism.
4. Secondary hypoparathyroidism due to:
- irradiation; X-ray therapy; treatment of the thyroid gland by radioactive iodine;
- infectious damaging of the glands;
- hemochromatosis, granulomatous disease of parathyroids;
- disturbances of the innervation or vascularization.
Due to duration:
1. Manifest hypoparathyroidism (acute and chronic).
2. Latent hypoparathyroidism.
Clinical presentation.
Patients may be asymptomatic
1. The most characteristic syndrome is tetany, resulting from severe hypocalcemia or a reduction in the serum ionized Ca fraction without marked hypocalcemia (e.g., in respiratory or metabolic alkalosis). Tetany is characterized by: 1) sensory symptoms consisting of paresthesias of the lips, tongue, fingers and feet: 2) carpopedal spasm (the hands incarpal spasm adopt a characteristic position, the metacarpophalangeal joints are flexed, the interphalangeal joints of fingers & thumb are extended and there is opposition of the thumb), which may be prolonged or painful; 3) generalized muscle aching; 4) spasm of facial musculature; 5) laryngeal stridor. Tetany may be overt (spontaneous symptoms) or latent. In latent tetany the neuromuscular instability frequently is brought out by provocative tests. Trousseau’s sign is carpopedal spasm caused by reduction of the blood supply to the hand when a tourniquet or blood pressure cuff above systolic pressure is applied to the forearm for 3 min. Chvostek’s sign is contraction of the facial muscles, elicited by a light tapping of the facial nerve. Erba’s sign is dyspnea which develops after hyperventilation.
2. Changes of other organs and systems.
1. The clinical manifestations of hypocalcemia may be primarily neurologic. Slowly developing, insidious hypocalcemia may produce mild, diffuse encephalopathy and thus should be suspected in any patient with unexplained dementia, depression, or psychosis.
2. Trophic changes:
- papilledema occasionally may be present and cataracts may develop after prolonged hypocalcemia:
- changes of the skin and hair.
3. Respiratory system:
- dyspnea;
- laryngospasm.
4. Cardiovascular system:
- pain in the region of the heart like angina;
- the ECG typically shows prolongation of the Q – T.
5. Gastrointestinal tract:
- spastic constipation or diarrhea.
Laboratory findings.
1. The level of total Ca < 2,2 mmol/l, ionized Ca , 1,0 mmol/l.
2. High serum PO4.
3. Low or absent urinary Ca.
Differential diagnosis
have to be made with other causes of hypocalcemia:
1) increased phosphate (chronic renal failure; phosphate therapy);
2) drugs (calcitonin; diphosphanates);
3) acute pancreatitis; citrated blood in massive transfusion;
4) pseudohypoparathyroidism (resistance to PTH);
5) deficiency or resistance to vitamin D;
and tetany:
1) infectious diseases (tetanus);
2) alkalosis (repeated vomiting of gastric juice; hyperventilation).
Treatment of Acute severe hypocalcemic tetany.
1. It is treated initially with IV infusion of Ca salts. 10 – 50 ml of 10 % solution of Ca gluconate or Ca chloride may be given IV over 15 – 30 min, but the effect lasts for only a few hours. (side effects: thrombophlebitis, IM injection can cause local necrosis).
2. Magnesium repletion.
3. Parathyroidin 1 – 2 ml IM 2 times a day.
4. Sedative preparations and spasmolitics.
Treatment of chronic hypocalcemia:
1. Diet with increased quantity of calcium and vitamin D.
2. Preparations of Ca and vitamin D, which have to be given orally (Calcium-D3 nicomed, Calcemin).
3. Surgery (transplantation of a special bone into the muscles of the abdomen or back. The efficacy is about 8 – 12 month).
HYPERPARATHYROIDISM.
It is a generalized disorder resulting from excessive secretion of parathyroid hormone by one or more parathyroid glands; it is usually characterized by hypercalcemia, hypophosphatemia, and abnormal bone metabolism.
Classification due to etiology.
1. Primary (due to parathyroid glands):
- adenoma of a single gland (80 %), multiple adenomata (5 %);
- hyperplasia of parathyroid glands (15 %);
- carcinoma of a gland (< 5 %);
- associated with syndromes of familial endocrine neoplasia (MEN-types I and II).
2. Secondary (due to increased physiological demand of hormone in response to low serum Ca in chronic renal failure, malabsorption, rickets and osteomalacia):
- renal;
- intestinal;
- vitamin D insufficiency.
3. Tertiary (due to development of parathyroid tumor against a background of prolonged secondary hyperparathyroidism).
Classifcation of Hyperparathyroidism
I. Primary hyperparathyroidism
1. Solitary adenoma (80 %), multiple adenomas (5 %).
2. Hyperplasia of parathyroid glands (15 %).
3. Parathyroid carcinoma (<5 %).
4. Primary hyperparathyroidism at multiple endocrine neoplasia types 1 and 2 syndrome (MEN-1 and MEN-2).
II. Secondary hyperparathyroidism
1. Renal secondary hyperparathyroidism.
2. Secondary hyperparathyroidism with normal renal function:
a) malabsorption syndrome with calcium absorption disorder;
b) hepatic pathology: cirrhosis (formation of 25-[OH]-D3 from cholecalciferol disorder), cholestasis (resorption of calciferol disorder).
2. Vitamin D defcit (insuffcient sunlight exposure).
III. Tertiary hyperparathyroidism
Clinical forms of hyperparathyroidism.
1. Bone:
- osteoporosis;
- osteodystrofya.
2. Visceropatic:
- dyspeptic;
- gastrointestinal;
- nephrotic;
- pancreatic.
3. Mixed:
- myopathy;
- mixed damaging of organs and systems
Clinical presentation.
Many patients with mild hypercalcemia are asymptomatic, and the condition is discovered accidentally during routine laboratory screening.
Onset is usually gradual with bone pain or swelling, rarely sudden with fracture or renal colic.