Human Endocrine Disorders

GR Sridhar, Endocrine and Diabetes Centre, Visakhapatnam-530002

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Along with the nervous system, the endocrine system forms the second communication channel between cells separated from one another in the body. Whereas neural signals transmit messages rapidly, endocrine signals or hormones, do so more slowly and in a sustained manner.

Clinical endocrinology is concerned with the function and dysfunction of a discrete group of endocrine glands. These glands are:

Hormones are not limited only to these organs or glands; in fact communication among nearly all organs takes place through hormones. Examples include atrial natriuretic peptide (heart and cardiovascular system), melatonin (pineal), renin (kidney), erythropoietin (kidney), cholecalciferol (skin) etc.

Disorders of the endocrine glands can manifest in the following ways:

Feed-back mechanism: Hormonal harmony is maintained by a system of check and balance. Stimulatory signals result in hormone formation and release into the circulation; the hormone in turn acts as a damper on the stimulatory signal so that homeostasis is maintained. Many layers of such control may exist, but the concept of feed-back is crucial in the endocrine system. Disorders can thereby result from abnormalities of either the stimulating centre, the responding centre, or changes in the responsivity of the target organs.

Hypothalamo-pituitary axis: The major coordination of various hormones occurs at the level of the hypothalamus, a tight collection of nerve bodies above the pituitary. Stimulatory and inhibitory signals arise from the hypothalamus and pass to the pituitary, which in turn releases hormones that act on the target organs (eg corticotropin releasing factor, adrenocorticotropic hormone, cortisol; growth hormone releasing hormone, growth hormone, gonadotropin releasing hormone, leuteinising hormone, estradiol/ testosterone etc).

Hormonal disorders:

Growth hormone excess. Growth hormone is produced by the anterior pituitary, and is necessary for adequate growth of children. Excessive production of growth hormone starting before growth is complete and ends of long bones are fused, results in gigantism. If it starts in adulthood, a condition called acromegaly occurs. The features of acromegaly are thick skin, increased sebum production, enlargement of extremities (acral enlargement), weakness, and muscle weakness; in addition the lower jaw is prominent. In gigantism the height is very much greater.

Growth hormone excess usually results from a tumour in the anterior pituitary, and is treated by surgical removal of the tumour. Surgery may be followed by radiation treatment to the tumour. Medical treatment with growth hormone inhibitory substances such as somatostatin analogues is also possible.

Hyperprolactinemia: Prolactin is a hormone secreted by the anterior pituitary. It is required for expression of milk from the breast. If prolactin levels are elevated, inappropriate secretion of milk occurs from the female breast. Menstruation may also cease. The common term used to describe this pattern is the galactorrhea-amenorrhea syndrome. Treatment is usually by means of a prolactin inhibitory agent called bromocriptine. If the tumour is large, surgery or radiotherapy may be necessary.

Growth hormone deficiency: When there is deficiency of growth hormone, the child fails to grow and is short, but could be otherwise normal, if other hormones are not deficient. Replacement of growth hormone, although very expensive, restores normal growth.

Combined pituitary hormone deficiency: Sometimes a combination of anterior pituitary hormones are deficient, in which case, the features depend on the combination of deficient hormones . Replacement with hormones secreted by the end organs is effective.

Disorders of posterior pituitary:

The posterior pituitary secretes two hormones: antidiuretic hormone (ADH) and oxytocin. ADH regulates the intake and excretion of water by the body.
When ADH secretion is inappropriately increased, fluid is retained and the concentration of sodium in the body is reduced.
When the hormone is deficient, diabetes insipid us results. In this condition, the body is unable to conserve water and large volumes of urine are excreted. Resultantly, thirst is profound. ADH can be replaced either by injection or nasal spray, to control the symptoms.

Disorders of thyroid

Hyperthyroidism: Excessive production of thyroid hormone results in a hastening of body processes: increased appetite, weight loss, frequency of motion, rapid beating of heart, shortness of breath, irritability, easy crying, tremor, weakness, separation of nails, hair loss, disturbances of reproductive function, prominence of eyes and changes in the skin. The size of the thyroid gland may be increased. All the features may not be present in each patient.

Excess hormone is normalised by

(a) Administration of drugs that reduces the secretion of excess thyroid hormones (eg carbimazine, propylthiouracil)

(b)Surgical removal of excess thyroid gland

(c) administration of radioactive iodine which destroys hyper functioning thyroid tissue.

Hypothyroidism: If on the other hand, the thyroid does not produce enough hormone as it should, the situation is reversed. There is loss of appetite, weight gain, constipation, slowness of thought, among other changes. In children poor growth is often present. In India, many children suffer from hypothyroidism due to inadequate iodine ingestion.
Hypothyroidism is treated with replacement of thyroid hormone.
Thyroiditis: Sometimes, the thyroid is inflamed and a condition called thyroiditis results.
Thyroid neoplasma: Tumours of the thyroid may be benign or malignant. The usual kind of thyroid malignancy is less dangerous than other malignancies elsewhere in the body. It is treated by surgery, usually followed by radiotherapy.

Disorders of parathyroids

The parathyroid glands secrete parathormone, which regulates the calcium balance in the body, along with vitamin D. Vitamin D is synthesized in the skin, liver and kidneys.
Hyperparathyroidism: When parathormone secretion is excessive, the serum calcium level increases, bones become brittle and weak, and stones may form in the kidneys. Surgical removal of the excess parathyroid glands is curative.
Hyperparathyroidism usually results either from a tumour of the gland, or hyperplasia of glands.
Hypoparathyroidism: Deficiency of parathormone results in hypoparathyroidism, in which serum calcium levels are low. The resultant condition manifests as tetany, in which the skeletal muscles are irritable and go into spasm. If the condition is long-standing, ectopic calcification may occur in the basal ganglia of the brain. Treatment consists of calcium supplementation, along with vitamin D.

Disorders of pancreas

The pancreas secretes insulin, glucagon, pancreatic polypeptide and a variety of other hormones that regulate the energy metabolism. Insulin maintains the levels of glucose in the body within a narrow range.

Diabetes mellitus: Diabetes mellitus results when there is a mismatch between the availability of insulin and its requirement. Absolute insulin deficiency usually occurs in children, producing insulin dependent diabetes mellitus. Whereas in adults, the insulin deficiency is relative, and the condition is called non insulin dependent diabetes mellitus.

The classical complaints are increased appetite and thirst, weight loss, passage of large urine volume. In adults, such typical symptoms may not be present. Diabetes mellitus is diagnosed by documenting elevated levels of glucose in the blood.

Treatment of diabetes consists of a regular schedule of diet, exercise and if necessary, the use of drugs. There are two kinds of drugs: one is insulin, or the hormone secreted by the body. It is usually given into the subcutaneous tissue. The second kind of medicines that are commonly used, especially in adults are agents taken orally, which either stimulate the pancreas to produce more insulin, improve the action of insulin, or alter the absorption of food from the gut. Oral agents should not be used when there is insulin deficiency in children.

Diabetes is a common disorder, and has been called a disease of complications. A lot of work is being done to understand the pathogenesis of the complications, and the ways to prevent them.

Future options in treatment could be transplantation of pancreatic islet cells, or introduction of insulin gene which takes over the work of the pancreas.

Insulinoma: This is the reverse of diabetes mellitus, where excess amount of insulin is secreted, resulting in low blood glucose levels. It is managed by ingesting frequent meals, or removal of the pancreatic tumour producing the excess insulin, or finally by giving medicines that reduce the production of inappropriate amount of insulin.

Disorders of the adrenal glands

The adrenal glands are paired organs in the abdomen, situated over the upper pole of the kidneys. Each gland consists of two zones: an outer cortex and an inner medulla. The cortex secretes glucocorticoids, mineralocorticoids and weak androgens. Corticosteroids raise blood glucose. They are the fight or flight hormones. Mineralocorticoids act on the kidneys to regulate sodium excretion by the body.

Hyperadrenocorticolism: Excess production of cortisol may be as a result of a tumour of ACTH secreting cells in the pituitary, or in the adrenal cortex itself. The condition is called Cushings syndrome. Patients with this condition gain weight, have muscle and bone weakness, have puffiness of face, and thin bruised. Women may have menstrual abnormalities and excess body hair. However the condition commonly results from use of glucocorticoids exogenously.

Treatment consists of stopping the drugs, if they are taken from outside (iatrogenic Cushings syndrome), or removal of the tumour (in the pituitary or adrenal cortex). Radiation therapy or drugs may be sometimes necessary.

Addisons disease: When adequate adrenal cortical hormones are not produced, adrenal deficiency results. Patients with this condition are weak, lose weight, have poor appetite, vomiting, gastrointestinal disturbances, low blood pressure and darkening of skin pigmentation.

Treatment is by replacing the glucocorticoid hormone.

Primary hyperaldosteronism (Con n's syndrome). A rare cause of secondary hypertension, Con n's syndrome results from inappropriate secretion of the mineralocorticoid, usually from an adrenal tumour. Surgical removal is curative.

Pheochromocytoma: When a tumour develops in the adrenal medulla, which secretes catecholamines, hypertension is a characteristic feature. Again, surgery is curative.

Disorders of male reproductive glands

Testes in males is responsible for secretion of the male hormone, testosterone, and for the production of spermatozoa, which are the male germ cells.

Hypogonadism and infertility: Deficiency in male sex hormone results in delayed or absent development of secondary sexual characters. Treatment is by replacing deficient hormone, testosterone. Adequate sexual development and function is possible. If hypogonadism is a result of pituitary gonadotropins, replacement of gonadotropins can lead to both normal sex development and spermatogenesis. The latter is not possible if testicular damage is the cause for gonadal deficiency.

Precocious sexual development: Rarely, the hypothalamo-pituitary gonadal axis is activated well before the age of usual puberty. Sexual changes occur in children. Treatment is removal of the cause (eg a tumour of the hypothalamus), or administration of medicines that block the secretion of gonadotropins (gonadotropin releasing hormone analogues).

Disorders of female reproductive glands Hypogonadism: Analogous to the male, the female gonads (ovaries) secrete female sex hormones and produce ova or germ cells. Deficiency and treatment are similar in men (although replacement is of female sex hormones, estrogen and progesterone).

Precocious puberty in girls is similar to that in boys (but development is usually that of women), and is treated in the same way.

Separation techniques and quantiation in endocrinology:
Although concepts of duct less secretions or hormones were first identified more than 100 years ago, endocrinology really took off when methods to quantify infinitismally small quantities of hormones, and separation techniques were evolved. The past 30 years have seen an explosion of knowledge, after the development of radioimmunoassay technique. In this, an unknown sample is added to a mixture of known amount of radio labelled antigen and antibody. The concentration of the unknown substances can be inferred from the proportion of bound and unbound fraction.

Other labels such as enzymes, luminescence substances and magnetic compounds are also being used to assay hormones.

Advances in genetic engineering has revolutionised the study of chemical signals in the body. Dissection of the genes and the polymerase chain reaction (PCR) have opened the flood gates to extensive knowledge of the endocrine system.

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