Endocrine system

Endocrine system

 

KEY CONCEPTS IN THIS LECTURE

The major chemical regulators of the body are the internal secretions and their secreting cells, which are collectively known as the endocrine system.

Ordinarily the endocrine system of the newbom is adequately developed, but its functions are immature. For example, the posterior lobe of the pituitary gland produces limited quantities of antidiuretic hormone (ADH), or vasopressin, which inhibits diuresis. This renders the neonate highly susceptible to dehydration.

The effect of maternal sex hormones is particularly evident in the newbom because it causes a miniature puberty. The labia are hypertrophied, and the breasts may be engorged and secrete milk during the first few days of life. Female newborns sometimes have pseudomenstruation from the sudden drop in the levels of progesterone and estrogen.

The endocrine system is adequately developed at birth, but its functions are immature. The interrelatedness of all the endocrine organs has a major effect on the function of any one gland. The lack of homeostatic control because of various functional deficiencies renders the infant especially vulnerable to imbalances in fluid and electrolytes, glucose concentration, and aminoacid metabolism.

For example, corticotropin (ACTH) is produced in limited quantities during infancy. ACTH acts on the adrenal cortices to produce their hormones, particularly the glucocorticoids and aldosterone. Because the feedback mechanism between ACTH and the adrenal cortex is immature during infancy, there is much less tolerance for stressful conditions, which affect fluid and electrolytes and the metabolism of fats, proteins, and carbohydrates. In addition, although the islets of Langerhans produce insulin and glucagon during fetal life and early infancy, blood sugar levels tend to remain labile, particularly under conditions of stress.

The function of the endocrine system is:

–      to secrete intracellularly synthesized hormones into the circulation ,

–      to serve as pacemaker substances for metabolic processes,

–      together with the closely related but more rapidly reacting nervous system,

–      to serve to integrate the various physiologic functions of the organism in adjusting to external and internal environmental demands.

 Endocrine substances even in extremely small concentrations are effective in modifying metablism, behavior, and development.

The endocrine system consists of three components:

 (1) the cell, which sends a chemical message by means of a hormone;

 (2) the target cells, or end organs, which receive the chemical message;

 (3) the environment through which the chemical is transported (blood, lymph, extracellular fluids) from the site of synthesis to the sites of cellular action.

 Some hormones, such as acetylcholine, have specific local effects; others are secreted by specific endocrine glands and then transported by the fluids to create their effects on target tissues at locations distant from the secreting glands. Some of the general hormones, such as thyroid hormone and growth hormone, affect most cells of the body, whereas the effect of others, such as the tropic hormones, is chiefly restricted to some specific tissues.

 

 

1. The peripheral endocrine system involves the thyroid, adrenal, pancreas, parathyroid, and gonads.

2. The thyroid gland is composed of many follicles consisting of a secretory epihelium enclosing a gelatinous matrix. Thyroid hormones are unique in containing iodide, and they are synthesized and stored in the colloid of the follicle. Triiodotyronine (T3) and Thyroxine (T4) are the two active forms. Thyroid hormone regulates BMR and encourages protein synthesis, especially in combination with Testosterone. Thyroid gland function is stimulated by Thyroid Stimulating Hormone (TSH) from the anterior pituitary and regulation of the thyroid is achieved by hypothalamic-hypophyseal feedback.

3. The adrenal gland functions as two different glands, the adrenal cortex and the adrenal medulla. The cortex is under control of adrenocorticotropin (ACTH) from the anterior pituitary. The cortex releases two steroid, aldosterone (ion and water balance in the kidney) and cortisol (nutrient metabolism). Cortisol enhances glucose and glycogen synthesis at the expense of fats and protein. It acts as an anti-inflammatory and suppresses the immune system. It is regulated by hypothalamic-hypophyseal feedback. The adrenal medulla is stimulated by the sympathetic nervous system to release Epinephrine, E (and some Norepinephrine) during times of acute stress (=”fight or flight” response). E increases heart rate and blood pressure, causes vasocontriction of peripheral arterioles, vasodilation of the coronary arteries, and stimulates glycogen breakdown. The General Adaptation Syndrome (GAS) results from long term stimulation of the adrenal gland associated with chronic stress.

4. The pancreas regulates blood glucose by releasing two hormones that work in opposition. Following a meal, Insulin (hormone of “feasting”) lowers blood glucose and promotes its storage as glycogen or fat. Between meals, Glucagon (hormone of “fasting”) raises blood glucose by mobilizating energy reserves. A lack of sufficient insulin results in diabetes, either Type I (insuliot produced) or Type II (increased cellular resistance to insulin).

5. The parathyroid gland is embedded in the thyroid gland and regulates Ca++ metabolism. Parathyroid Hormone (PTH) increases plasma Ca++ by mobilizing bone Ca++ pools and by encouraging Ca++ absorption from the gut and Ca++ retention by the kidney. PTH release is stimulated directly by plasma Ca++ titer. Calcitonin, secreted by the D cells of the thyroid gland, opposes PTH action by decreasing plasma Ca++ when it is too high. Vitamin D, although not a hormone, encourages Ca++ absorption from the small intestine, following its activation by the kidney. 

LECTURE OBJECTIVES

1. Describe the structure and function of the major endocrine glands.<br>
2. Discuss the multiple systems which regulate hormone level.<br>
3. Identify diseases associated with disruption of endocrine function.

LECTURE OUTLINE

I. INTRODUCTION

 

   A. Comparison of central and peripheral endocrine glands

 

   B. Major peripheral endocrine glands (thyroid, adrenal, pancreas,

       parathyroid, and gonads)

 

II. THYROID GLAND

 

   A. Structure of the Thyroid

        1. Follicles enclose colloid

 

   B. Synthesis, Storage, Release, and Transport of Thyroid Hormone

        1. Synthesis in colloid on thyroglobulin       

            a. Roles of iodine and tyrosine in T3/T4 synthesis

        2. Storage on thyroglobulin

        3. Secretion of thyroid hormone

        4. Transport in blood

 

   C. Physiological Effects

        1. Increases BMR

        2. Accelerates protein synthesis in children

        3. Enhances sympathetic tone (sympathomimetic effect on heart, brown fat)

 

   D. Regulation of thyroid hormone

        1. Roles of TRH, TSH, stress, and cold in regulation

 

   E. Hypofunction and Hyperfunction

        1. Myxedema and Cretinism (in children)

        2. Grave’s disease

        3. Goiter

 

III. ADRENAL GLAND

 

   A. Structure

        1. Adrenal cortex and medulla

 

   B. Function of Cortex

        1. Aldosterone regulates Na+ retention

        2. Cortisol effects on cellular metabolism

            a. Enhances gluconeogenesis

            b. Anti-inflammatory action; suppresses immune response

        3. Dehydroepiandrosterone (DHEA)

            a. Adrenogenital syndrome in women

 

   C. Regulation of Adrenal Cortex

 

   D. Hypofunction and Hyperfunction

        1. Cushing’s Disease

            a. Symptoms and treatment

        2. Addison’s Disease

            a. Symptoms and treatment

 

   E. Functions of adrenal medulla–Role in acute stress

        1. Relationship to Sympathetic Nervous System

            a. Epinephrine has multiple effects

        2. “Fight or flight” response of W.B. Cannon

 

   F. General Adaptation Syndrome of H Seyle– Response to chronic stress

       1. Non-specific stressors elicit this syndrome

       2. Roles for Epinephrine, Cortisol, ACTH, and ADH

       3. Time course: Alarm, Resistance, and Exhaustion

 

IV. PANCREAS

 

  A. Structure

       1. Islet of Langerhans

           a. Beta cells secrete insulin

           b. Alpha cells secrete glucagon

 

  B. Insulin Function

      1. Insulin lowers blood glucose and promotes nutrient storage following a meal

      2. Direct regulation through plasma glucose

      3. Hypofunction:  Diabetes mellitus

          a. Distinctions between Type I and Type II diabetes

 

  C. Glucagon Function

      1. Role of glucagon between meals and during fasting

      2. Glucagon promotes catabolism of fuel stores

           a. Catabolism of fats, protein, and glycogen in liver cells

      3. Glucagon causes hyperglycemia in diabetics.

 

V. PARATHYROID GLAND

 

  A. Structure

       1. Found embedded in thyroid

 

  B. Function

      1. Parathyroid Hormone (PTH) regulates plasma Ca++

          a. Why regulate plasma Ca++?

          b. PTH regulates Ca++ via kidney reabsorption, instestinal

              absorption and active transport from the “bone pool”

 

  C. Regulation

      1. Direct regulation of PTH via plasma Ca++

      2. Calcitonin from thyroid acts in opposition to PTH

 

  D. Hypofunction and Hyperfunction.

      1. Hyperparathyroidism

 

  E. Vitamin D and calcium metabolism

      1. Sources of Vitamin D and its activation

      2. Vitamin D acts at small intestine to absorb Ca++

      3. PTH affects Vitamin D

      4. Vitamin D deficiency

          a. Rickets in children

 

 

Thyroid and Parathyroid Disorders.

I. Thyroid Disorders.

Thyroid Anatomy

The thyroid gland, a shield-like organ (sometimes it can be compared with butterfly shape) at the front of the neck, produces hormones that help regulate the body’s metabolism. It has two lobes, one on each side of the trachea, which are joined at the base by a bridge of thyroid tissue called the isthmus.

The gland’s blood supply comes from two paired major arteries entering its upper and lower poles. It is close to two other anatomic structures: the recurrent laryngeal nerves, which control the vocal cords, and the parathyroid glands, which adhere to the thyroid gland posteriorly, two on each side, and regulate the calcium level of the blood.

Thyroid gland has two kinds of cells that make hormones. Follicular cells make thyroid hormones (T₃ and T₄), which affects heart rate, body temperature, and energy level. C cells make calcitonin, a hormone that helps control the level of calcium in the blood.

Abridged classification of thyroid diseases

I. Diseases characterized by euthyroidism

A. Euthyroid goiter (goiter, struma)

1. Diffuse goiter

– Simple (the convertible terms are – colloid goiter, adolescent goiter, juvenile goiter, nontoxic goiter)

– Endemic (only in early stages it is euthyroid, then it becomes hypothyroid)

2. Nodular goiter

B. Tumors

1. Benign (single nodule)

2. Malignant

C. Thyroiditis

1. Acute thyroiditis

2. Subacute thyroiditis (De Quervain’s thyroiditis)

3. Chronic autoimmune thyroiditis or Hashimoto’s disease (only in early stages, then usually in children develops hypothyroidism).

4. Riedel’s thyroiditis

II. Diseases characterized by hyperthyroidism

1. Diffuse toxic goiter (the convertible terms are – thyrotoxicosis, Basedow-Graves’ disease)

2. Multinodular hyperthyroid goiter or Plummer’s disease

3. Autonomous nodule (hyperthyroid)

4. Excessive, exogenous thyroid hormones (thyrotoxicosis factitia and iatrogenic)

III. Diseases characterized by hypothyroidism

A. With thyroid gland hypofunction

1. Primary hypothyroidism

a. Acquired (iatrogenic (surgery, 131I therapy, external radiotherapy), chronic autoimmune thyroiditis (in the hypothyroid phase), Graves’ disease (end-stage), diffuse and nodular goiter, severe iodine deficiency

b. Neonatal congenital (ectopia, agenesis, inborn deficiencies of biosynthesis or action of thyroid hormone)

2. Secondary: hypothalamic-pituitary hypothyroidism (or central)

B. Without hypothyroidism

1. Generalized and peripheral resistance to thyroid hormones (receptor and postreceptor defects)

C. Transient hypothyroidism

 

Goiter.

A healthy thyroid is a little larger than a quarter or 25-kopics coin. It usually cannot be felt through the skin. A swollen lobe might look or feel like a lump in the front of the neck. A swollen thyroid is called a goiter. Definition. A goiter is an enlargement of the thyroid gland resulting from several different pathogenic mechanisms. The incidence of goiter increases with advancing age and is more common in girls at all ages. The presence of goiter does not correlate with thyroid function, i.e. patients may be euthyroid, hypothyroid or hyperthyroid, although most children are clinically euthyroid.

 

A. Simple goiter (the convertible terms are – colloid goiter, adolescent goiter, juvenile goiter, nontoxic goiter) is an acquired enlargement of the thyroid gland with normal function that is not caused by an inflammatory process or a tumor. At least 25 % of all children with thyroid enlargement have a simple goiter. The gland tends to be symmetric, smooth and of normal texture. For diagnosis we need normal function tests, negative thyroid antibodies, normal radioactive iodine (RAI) scan (not usually indicated).

Treatment. Thyroxin is usually not recommended when the gland is cosmetically insignificant. No other treatment is recommending except periodic reassessment.

B. Endemic goiter occurs predominantly in iodine-deficient areas. An accurate test for diagnosing iodine deficiency exists. Extreme deficiency occurs when daily urine contains less then 25 mg of iodine; moderate deficiency occurs when it is 25-50 mg and an adequate intake is reflected by an excretion of 100-200 mg/day.

Laboratory findings. The thyroxin (T₄) level is slightly low, triodthyronin (T₃) level is normal or mildly high and thyroid-stimulating hormone (TSH) level is elevated, but these patients are clinically euthyroid.

Treatment. We use iodine. And here I have to mention Lugol’s solution developed by French physician Dr. Jean Lugol in the 1820-s. His solution mixed iodine (5 %) with potassium iodide (10 %) and 85 % water. Dr. Lugol’s solution killed germs and was used with success in treating infections and many other conditions. This solution in the recommended 2 drops dosage contains 12,5 mg. of iodine for daily intake for profilaxis of hypothyroidism in endemic regions. For the treatment of iodine-depending hypothyroidism doctors recommends taking 50 mg of Iodoral (four 12.5 mg. tablets), Lugol’s solution (8 drops) or Triodide (8 drops) daily for 3 months as a loading dose. Then this dose should be gradually reduced to the 12.5 mg. maintenance dosage under the supervision of a knowledgeable health care professional. Sometimes is necessary to use thyroxine, which either interrupts the cycle, leading to a decrease in TSH secretion and regression of the goiter.

C. Diffuse toxic goiter (the convertible terms are – thyrotoxicosis, Basedow-Graves disease) is the most common cause of hyperthyroidism. The clinical symptoms are:

·                     Increased nervousness, irritability

·                     Muscle tremor

·                     Tachycardia, hypertension

·                     Warm and moist skin

·                     Weight loss

·                     Wide-eyed stare

·                     Fatigue, feeling exhausted

Patients with frequently develop eye symptoms that can lead to serious eye problems if not diagnosed and treated promptly. The combination of an overactive thyroid gland and related eye problems is also known medically as Graves’ ophthalmopathy. Although the exact cause of Graves’ ophthalmopathy is not known, it is believed that the body’s immune system attacks the tissues located within the socket of the eye (orbit) such as the eye muscles, the lachrymal (tear) gland, and the protective cushion of fat surrounding the eyes. Furthermore, there is increased stimulation of the nerves that hold the lid open (lid retraction) giving rise to the common staring appearance of patients with hyperthyroidism. Due to the body’s immune system attacking the tissues within the orbit, there is an inflammatory reaction that causes symptoms ranging from dryness of the eye, to marked discomfort, eye pain, double vision, and in severe cases, to loss of vision, which can be permanent. The eyelid retraction, combined with the bulging forward of the eyes, leads to inability to close the eyes fully. The front surface of the eye (cornea) then becomes extremely dry, and can become ulcerated and infected, leading to loss of sight. 

Laboratory findings. Serum T₃ and T₄ are increased. Serum TSH, measured by the sensitive methods, is undetectable or subnormal.

Treatment. We use antithiroid agents (methimazole (Tapazole), propylthiouracil (PTU) mercasolil). The beginning dose of mercasolil is not less then 30 mg daily, gradually it becomes lower. Beta-adrenergic blockers (propranolol), sometimes corticosteroids and sedatives are necessary to use also.

In mild cases, treatment of thyroid eye disease is mainly supportive. Artificial tears in a form of drops are applied during the day, and ointment is administered in the evening before sleeping. If the eyes do not shut fully due to lid retraction, they are taped shut after applying lubricating ointment. In more severe cases where there is marked swelling of the tissues in the socket of the eye, steroid medications (prednisone) are given to control the inflammation and even operation is necessary sometimes. In thyreotoxic crisis, which can appear as the complication of Graves disease, it’s necessary to prescribe hydrocortisone (100-200 mg) with physiological saline and 5% glucose solution intravenously.

The effective therapy of hyperthyroidism for young children or women of childbearing age is sub-total thyroidectomy. Recurrent laryngeal nerve damage, causing hoarseness and possible difficulty breathing, occurs in one to two percent of all thyroid operations.

The risk of permanent damage to the parathyroid glands following complete removal of the thyroid is between five and 10 percent, and this damage requires the patient to take calcium supplements for life. The body needs only one-half of one parathyroid gland to maintain a normal calcium blood level, so the loss of several centimetres of parathyroid is usually well tolerated.

Hypothyroidism

Definition. Hypothyroidism is the condition resulting from a lack of the effects of thyroid hormone on body tissues. Because thyroid hormone affects growth and development and regulates many cellular processes, the absence or deficiency of thyroid hormone has many detrimental consequences.

Clinical features. Patients  with hypothyroidism may complain of:

·                     Fatigue or lack of energy

·                     Mental slowing

·                     Bradycardia

·                     Weight gain

·                     Hypothermia

·                     Dry skin and hair, edemas

·                     Constipation

Laboratory findings. Because of the sensitivity of the serum TSH level as an indicator of primery hypothyroidism, serum TSH may be the best method to screen for the disorder. Its range is elevated usually, with the exception of central hypothyroidism. Serum T₃ and T₄ are low as a rule but their ranges may be normal or subnormal too.

Therapy.  The most adequate is the therapy of replacement: synthetic thyroxin (T4) and T₃-T₄ combination. When someone is first started on thyroid hormone the initial dose is carefully selected based on information such as a person’s weight, age, and other medical conditions. The dose will theeed to be adjusted by

a physician to keep the thyroid functioormal. The physician will make

sure the thyroid hormone dose is correct by performing a physical

examination and checking TSH levels. There are several brand names of thyroid hormone available. Although these all contain the same synthetic thyroxin (T4), there are different inert ingredients in each of the brand names.

PRODUCT:

Unithroid®

L-Thyroxin

Levo-T®

Levoxyl®

Novothyrox®

Synthroid®

Levothroid®

Levolet®

Also we use vitamins, neurotropic drug, therapeutic physical training, speech therapist.

Thyroiditis

A. Hashimoto thyroiditis (chronic thyroiditis, autoimmune thyroiditis)

Etiology. Hashimoto thyroiditis is an organ-specific autoimmune disorder. The basic defect underlying this disease is not entirely clear, although current evidence suggests an abnormality in suppressor T lymphocytes that allows helper T lymphocytes to interact with specific antigens directed against the thyroid cell. A genetic predisposition is also suggested.

Clinical features. Physical examination usually discloses a symmetrically enlarged, very firm goiter; a pebbly or knobby consistency is common.

Laboratory findings. Approximately 80 % of patients with Hashimoto thyroiditis have normal circulating T₃, T₄ and TSH levels at the time of diagnosis. Antithyroglobulin antibodies and antithyroperoxidase antibodies are measurable in more than 85 % of patients with Hashimoto thyroiditis.

Treatment. Thyroid hormone in full replacement dosages is the treatment of choice. The aim is to decrease the goiter, especially in patients with significant enlargement goiter, which causes the symptoms of dysphagia or other discomfort. When there is a rapidly enlarging goiter we use glucocorticoids. Surgery is indicated only if significant pressure symptoms occur.

B. Acute thyroiditis

Etiology. This rare disorder is usually due to a bacterial pathogen, most commonly Staphylococcus hemolitica, Streptococcus hemolitica, Streptococcus pneumoniae or anaerobic streptococcal organisms.

Clinical features. Fever, chills and other systemic signs or symptoms of abscess formation are present. Anterior neck pain and swelling are usual, with pain occasionally radiating to the ear or mandible. The physical examination suggests the presence of an abscess, with erythema of the skin, marked tenderness to palpation and at times fluctuance.

Laboratory findings. Leukocytosis with a left shift is usually present. Patients are euthyroid usually.

Treatment. Parenteral antibiotics should be administrated according to the specific pathogen identified. If fluctuance is present, incision and drainage might be required.

II. Parathyroid Disorders.

Hypoparathyroidism. Etiology. The causes of parathyroid failure and resistance to parathyroid hormone (PTH) are absence or genetic defect in PTH biosynthesis, autoimmune destruction of parathyroid gland, reduced PTH secretion and resistance to PTH as a consequence of hypomagnesemia.

Clinical features. There may be tetany, convulsive syndrome (titanic more typical), karpopedal spasm, paresthesiae, muscle weakness, tiredness, Trousseau and Hvostek symptoms, cataract; hair, nails and skin affection, growth failure, hypocalcemia, hyperphosphatemia.

A. Idiopathic hypoparathyroidism is a rare form of hypoparathyroidism. Several varieties of the disorder exist, both as sporadic and familiar condition. This disorder occurs as part of type I autoimmune polyglandular syndrome, as isolated idiopatic hypoparathyroidism, as part of Kearns-Sayre syndrome or due to congenital aplasia or dysgenesis of the parathyroids. The diagnosis of idiopatic hypoparathyroidism is generally one of exclusion. Demonstration of low to absent levels of PTH in the presence of hypocalcemia, frequently with hyperphosphatemia and with no evidence for magnesium depletion, strongly supports this diagnosis.

B. Surgical hypoparathyroidism. Surgical damage to or removal of parathyroid tissue accounts for the majority of cases of loss of parathyroid function.

Treatment. The aim of the hypoparathyroidism therapy is the correction of hypocalcemia. Although mild hypocalcemia might not require therapy, any neonate with a serum calcium level below 7,5 mg/dl (Ca²⁺ less then 2,8 mg/dl) or an older child with a serum calcium level less then 8-8,5 mg/dl should be treated to prevent tetany and other symptoms.

ü     Acute. In acute symptomatic hypocalcemia intravenous therapy is required. It should be used 20-50 mg/kg /day of elemental calcium. When a central line is available, the calcium gluconate can be diluted with saline or dextrose infusion fluids and given continuosly.

ü     Chronic. In the absence of tetany, seizures and severe degrees of hypocalcemia, oral therapy will suffice. A dosage of 50 mg/kg/day of elemental calcium is generally prescribed. Chronic hypocalcemia, exept in the mildest cases, is treated by the administration of vitamin D or its metabolites. Also the terapy of replacement by parathyroidin is used.

Hyperparathyroidism. Etiology. The main causes of the hyperparathyroidism are: primery congenital PTH hyperproduction, hyperplasia of hyperparathyroid glands, chronic renal diseases, Fankoni syndrome and malignant processes in hyperparathyroid glands.

Clinical features. Patients with hyperparathyroidism may suffer from “renal stones, painful bones, abdominal groans, psychic moans and fatigue overtones”. Symptoms often include polydipsia, polyuria, nocturia, constipation, increases fatigue, weakness and musculosceletal aches and pains.

Laboratory tests. For diagnostic of hyperparathyroidism if patient have hypercalcemia are usefull:

General tests (serum):                               Other tests:

ü     Calcium, phosphorus                     – Urinalisis    

ü     Parathyroid hormone                     – 24-hour urinary calcium

ü     Chloride                                         – Chest radiograph

ü     Alcaline phosphatase, pH              – Intravenous pyelogram

ü     Protein electrophoresis

ü     Uric acid

ü     Creatinine, hematocrit

Specialized tests:

ü     Hydrocortisone suppression test

ü     1,25-Dihydroxyvitamin D

ü     Tubular resorption of phosphorus

Treatment. There is a general agreement that patients with symptomatic hyperparathyroidism and all patients with a serum calcium level 1 mg/dl above the upper limits of normal should be treated by parathyroidectomy. Operative treatment, however is not urgent and in all patients the diagnosis must be certain.

 The patients with hypercalcemic crisis should be treated with vigorous hydration. Calcium antagonists, calcitrinum, glucocorticoids and hemodialysis are applied if nessesary.