Iodide-induced goiter with or without hypothyroidism

Iodine, when given acutely in large doses, blocks the organic binding and coupling reactions. This effect or the Wolff-Chaikoff effect is normally transient, but prolonged administration of iodide may be associated with continued inhibition of hormone synthesis and development of goiter, with or without hypothyroidism (iodide myxedema).

Many patients with Graves’ disease, especially after treatment with radioiodine or surgery, or with Hashimoto’s disease are sensitive to blocking effect of iodide and develop hypothyroidism.

The fetal thyroid is similarly sensitive, and pregnant women should not ingest iodide in large amounts because of the danger of inducing hypothyroidism in the fetus.

Iodide in large doses is capable of inhibiting proteolysis of thyroglobulin and hormone release. Excess iodide may also induce thyrotoxicosis in susceptible individuals.

Manifestation of hypothyroidism in the adult:

Fatigue, lethargy, muscle weakness

Slowed intellectual and motor activity, decreased memory.

3. Bradycardia

Declined appetite

Cerebral ataxia

Constipation

Cold intolerance

Cool skin

Menorrhagia

Weight increases

Periorbital puffiness

H yperthyroidism (Thyrotoxicosis)

The most important of these disorders are those that lead to sustained overproduction of hormone by the thyroid gland itself. Sometimes, this hyperfunction results from excessive secretion of thyroid stimulating hormone by a pituitary tumor or as a result of resistance to thyroid hormone in the pituitary but not in peripheral tissues. Hyperthyroidism may result from excess present immunoglobulins TSIg (LATS), weak transport connection with blood proteins, intensive conversion of T4 to T3 in ‘target’ cells, the increase in the number of receptors T3, T4 in ‘target’ cells.

 Other causes are the action of nonphysiologic stimulator of extrapituitary origin, as in Graves’ disease and the development of one or more areas of autonomous hyperfunction within the gland itself.

Thyrotoxicosis may occur in subacute thyroiditis. In this disorder, an excess of performed hormone leaks from the gland owing to the presence of inflammatory disease.

Signs and symptoms of hyperthyroidism include:

- enlarged thyroid (goiter)

- nervousness, nervousness, difficulty concentrating due to accelerated cerebral function; excitability or nervousness caused by increased basal metabolic rate from T4; fine tremor, shaky handwriting, and clumsiness from increased activity in the spinal cord area that controls muscle tone; emotional instability

- heat intolerance and sweating warm, flushed skin, hyperthermia.

- heart systolic hypertension, tachycardia, full bounding pulse, wide pulse pressure, cardiomegaly, increased cardiac output and blood volume, paroxysmal supraventricular tachycardia and atrial fibrillation and occasional systolic murmur at the left sternal border

- increased respiratory rate, dyspnea on exertion and at rest, possibly due to cardiac decompensation and increased cellular oxygen use

- weight loss despite increased appetite; nausea and vomiting due to increased GI motility and peristalsis; increased defecation; soft stools or, in severe disease, diarrhea; liver enlargement (GI system)

- weakness, fatigue, and muscle atrophy;

- oligomenorrhea or amenorrhea, decreased fertility, increased incidence of spontaneous abortion (females),

- exophthalmos due to combined effects of accumulated mucopolysaccharides and fluids in the retro-orbital tissues, forcing the eyeball outward and lid retraction, thereby producing characteristic staring gaze; inflammation of conjunctivae, corneas, or eye muscles;

Complications

Possible complications include:

- muscle wasting

- visual loss or diplopia

- cardiac failure

- hypoparathyroidism after surgical removal of thyroid

- hypothyroidism after radioiodine treatment.

 

Parathyroid Glands

Primary hyperparathyroidism is one of the most common endocrine disorders, and it is an impotent cause of hypercalcemia.

In more than 95% of cases, the disorder is caused by sporadic parathyroid adenomas or sporadic hyperplasia.

Primary hyperparathyroidism presents in one of two ways:

1) It may be asymptomatic and be identified after a routine chemistry profile, or

2) patients may have the classics clinical manifestations of primary hyperparathyroidism.

Bone disease includes bone pain secondary to fractures of bones weakened by osteoporosis or osteitis fibrosa cystica.

Nephrolithiasis (renal stones) occurs in 20% of newly diagnosed patients, with attendant pain and obstructive uropathy. Chronic renal insufficiency and a variety of abnormalities in renal function are found, including polyuria and secondary polydipsia.

Gastrointestinal disturbances include constipation, nausea, peptic ulcers, pancreatitis, and gallstones.

Central nervous system alterations include depression, lethargy, and eventually seizures.

Neuromuscular abnormalities include complaints of weakness and fatigue.

Cardiac manifestations include aortic and mitral valve calcifications (or both).

Secondary hyperparathyroidism occurs due to increased parathyroid hormone elaboration secondary to a disease elsewhere in the body. Hypocalcaemia stimulates compensatory hyperplasia of the parathyroid glands and causes secondary hyperparathyroidism.

Etiology.

1. Chronic renal insufficiency resulting in retention of phosphate and impaired intestinal absorption of calcium.

2. Vitamin D deficiency and consequent rickets and osteomalacia may cause parathyroid hyperfunction.

3. Intestinal malabsorption syndromes causing deficiency of calcium and vitamin D.

 Clinical features.

1. mild hypocalcaemia;

2. signs and symptoms of the disease which caused secondary hyperparathyroidism;

3. renal osteodystrophy (osteomalacia, osteoporosis and osteosclerosis);

4. soft tissue calcification.

Tertiary hyperparathyroidism is a complication of secondary hyperparathyroidism in which the hyperfunction persists in spite of removal of the cause of secondary hyperplasia. Possibly, a hyperplastic nodule in the parathyroid gland develops which becomes partially autonomous and continues to secrete large quantities of parathyroid hormone without regard to the needs of the body.

Hypoparathyroidism

Hypoparathyroidism is far less common then is hyperparathyroidism.

Hypoparathyroidism is of 2 types - primary hypoparathyroidism and pseudohypoparathyroidism. 

Primary Hypoparathyroidism.

Primary hypoparathyroidism is caused by disease of the parathyroid glands. Most common causes of primary hypoparathyroidism are:

1. surgical procedures involving thyroid, parathyroid, or radical neck dissection for cancer;

2. idiopathic hypoparathyroidism of autoimmune origin in children;

3. may occur as sporadic or familial cases;

4. congenital absence of all glands, such as thymic aplasia. 

Clinical Features. The main biochemical dysfunctions in primary hypoparathyroidism are hypocalcaemia, hyperphosphataemia and hypocalciuria. The clinical manifestations of these abnormalities are:

1. Increased neuromuscular irritability and tetany.

2. Calcification of the lens and cataract formation.

3. Abnormalities in cardiac conduction.

4. Disorders of the CNS due to intracranial calcification.

5. Abnormalities of the teeth.

6. Ocular disease results in calcification of the lens leading to cataract formation.

7. Mental status changes can include emotional instability, anxiety and depression, confusional states, hallucinations, and frank psychosis.

.

Pseudohypoparathyroidism.  Resistance of the organs to normal or elevated levels of PTH occurs of pseudohypoparathyroidism,

 It is a rare inherited condition with an autosomal dominant character. The patients are generally females and are characterised by signs and symptoms of hypoparathyroidism and other clinical features like short stature, flat nose, round face and multiple exostoses. Since renal tubules cannot adequately respond to parathyroid hormone, there is hypercalciuria, hypocalcaemia and hyperphosphataemia. Hypocalcaemia results, leading to secondary parathyroid hyperfunction, unanticipated elevated serum PTH levels.

Diabetes Mellitus

Diabetes mellitus is a chronic clinical syndrome characterised by hyperglycaemia due to deficiency or defective response of insulin. It is estimated that approximately 3% of population suffers from diabetes mellitus. The most common and important forms of diabetes mellitus arise from primary disorders jf the islet cell-insulin signaling system. These can be divided into two common variants type I and type II.

Type I diabetes, also called insulin-depended diabetes mellitus (IDDP) and referred to as juvenile-onset diabetes (10%). Type II diabetes (80 – 90%) also called non-insulin-depended diabetes mellitus (NIDDM).

Type I diabetes mellitus, is caused by absolute deficiency of insulin resulting from reduction in В cell mass. There are 3 mutually-interlinked mechanisms: genetic susceptibility, autoimmunity, and certain environmental factors.

I. Genetic susceptibility. Diabetes mellitus runs in families has been known for years.

II. Autoimmunity. Type I diabetes is believed to be an autoimmune disease that results in specific immunologic destruction of В cells of islet of Langerhans.

III.Environmental factors. Epidemiologic studies in type I diabetes have revealed involvement of certain environmental factors in its pathogenesis. These factors are certain viruses, chemicals and common environmental toxins.

 Type II diabetes mellitus diabetes is further of 2 subtypes-obese and non-obese.

The basic metabolic defect in this type of diabetes is unable the peripheral tissues to respond to insulin (insulin resistance).

Though much less is known about the mechanisms involved in the pathogenesis of type П diabetes, a number of factors have been implicated.

I. Obesity (Obese type II diabetes). Obesity is a common finding in type II diabetes. There is impaired insulin sensitivity of peripheral tissues such as muscle and fat cells to the action of insulin in obese individuals (insulin resistance).

II. Insulin receptor defect (Non-obese type II diabetes). In such individuals, the increased insulin resistance of peripheral tissues is due to either decrease in the number of insulin receptors or there is post-receptor defect.

 Type II diabetes is a complex multifactorial disease involving 'deranged insulin secretion' and 'insulin resistance', with possible genetic defects, obesity sand fault in the insulin receptors.

Pathologic changes in islets have been demonstrated in both types of diabetes, though the changes are more distinctive in type I diabetes.

Clinical Features.

Type I diabetes usually manifests at early age, generally below the age of 40. Characteristically, the plasma insulin levels are low and patients respond to exogenous insulin therapy. The onset of symptoms is generally abrupt with polyuria, polydipsia and polyphagia. The patients are not obese but have generally progressive loss of weight. These patients are prone to develop metabolic complications such as ketoacidosis and hypoglycaemic episodes.

Type II diabetes. This form of diabetes generally manifests in middle life or beyond, usually above the age of 40. The onset of symptoms in type II diabetes is slow and insidious. Generally, the patient is asymptomatic when the diagnosis is made on the basis of glucosuria or hyperglycaemia during physical examination. The patients are frequently obese and may present with polyuria, polydipsia, unexplained weakness and loss of weight. In contrast to type I diabetes, plasma insulin levels in type II diabetes are normal-to-high, though they are lower relative to the plasma glucose level i.e. there is relative insulin deficiency. Metabolic complications such as ketoacidosis are infrequent.

As a consequence of hyperglycaemia of diabetes, every tissue and organ of the body undergoes biochemical and structural alterations, which account for the major complications in diabetics.

Both types of diabetes mellitus may develop complications, which are broadly divided into 2 major groups:

I. Acute metabolic complications include:

- ketoacidosis - is almost exclu­sively a complication of type I diabetes. It can develop in patients with severe insulin deficiency combined with glucagon excess.

- hyperosmolar nonketotic coma, is usually a complication of type II diabetes. It is caused by severe dehydration resulting from sustained hyperglycaemic diuresis. The loss of glucose in urine is so intense that the patient is unable to drink sufficient water to maintain urinary fluid loss. The usual clinical features of ketoacidosis are absent but prominent central nervous signs are present. Blood sugar is extremely high and plasma osmolality is high. Thrombotic and bleeding complications are frequent due to high viscosity of blood. The mortality rate in hyperosmolar nonketotic coma is high.

- hypoglycaemia. Hypoglycaemic episode may develop in-patients with type I diabetes. It may result from excessive administration of insulin, missing a meal, or due to stress. Hypoglycaemic episodes are harmful as they produce permanent brain damage, or may result in worsening of diabetic control and rebound hyperglycaemia.

II. Late systemic complications:

These are atherosclerosis, diabetic microangiopathy, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy and infections.

Renal Complications

There are a variety of complications involving the kidney. Both nodular and diffuse glomerulosclerosis can lead to chronic renal failure. Diabetics are prone to infections, particularly pyelonephritis. Both bacterial and fungal infections can occur.

Ocular Complications

The eyes can be affected in several ways by diabetes mellitus. Diabetic retinopathy is one of the leading causes for irreversible blindness. This retinopathy can occur with either type I or type II diabetes mellitus, usually a decade or so after the onset of diabetes. Most persons with type I diabetes and many of those with type II diabetes develop some background (non-proliferative) retinopathy. Proliferative retinopathy is more ominous and is more likely to occur when diabetes mellitus is poorly controlled.

Cataracts are more common in diabetics. This predilection for development of cataracts is felt to result from hyperglycemia leading to accumulation of sorbitol that results in osmotic damage to the crystalline lens.

Persons with diabetes mellitus, either type I or type II, have early and accelerated atherosclerosis. The most serious complications of this are atherosclerotic heart disease, cerebrovascular disease, and renal disease. The most common cause of death with diabetes mellitus is myocardial infarction.

Peripheral vascular disease is a particular problem with diabetes mellitus and is made worse through the development of diabetic neuropathy, leading to propensity for injury.

 

CONTROL QUESTIONS

1. Two types of organization of the endocrine system.

2. Primary, Secondary, and Tertiary Disorders of endocrine system.

3. Causes of hypofunction of an endocrine gland.

4. The pituitary gland disorders.