hyperthyroidism, hypothyroidism, thyrotoxicosis and adrenal gland dysfunction Flashcards
what’s the funciton of the thyroid gland?
The thyroid gland secretes three hormones: thyroxine (T4), triiodothyronine (T3), and calcitonin.8,10,11 Thyrox- ine and triiodothyronine collectively, they are termed thyoid hormone. Thyroid hormone in uences the growth and maturation of tissues, cell respiration, and total energy expenditure. This hormone is involved in the turnover of essentially all substances, vitamins, and hormones.8,10,11
Most thyroid actions (metabolic and developmental) are mediated through activity of nuclear receptors that are tissue site–speci c.8 Thyroid receptors work by alter- ing gene expression in response to changes in thyroid hormone concentrations (mostly T3). This alteration in gene transcription pro le is believed to account for most of the observed physiologic effects of thyroid hor- mones, although there are also actions of thyroid hor- mones that do not involve transcription.11 Thyroid hormone increases oxygen consumption, thermogenesis, and expression of the low-density lipoprotein (LDL) receptor, resulting in accelerated LDL cholesterol degra- dation. In myocardium, T3 increases myocyte contrac- tility and relaxation by altering myosin heavy chain and sarcoplasmic reticulum adenosine triphosphatase (ATPase). In the cardiac conducting system, T3 increases the heart rate by altering sinoatrial node depolarization and repolarization. Other physiologic effects of thyroid hormone include increased mental alertness, ventilatory drive, gastrointestinal motility, and bone turnover. During fetal development, thyroid hormone plays a criti- cal role in brain development and skeletal maturation.1
Calcitonin is involved, along with parathyroid hormone and vitamin D, in regulating serum calcium and phosphorus levels and skeletal remodeling. (This hormone and its actions are considered further in Chapter 12.)8,10,11
what is the etiology, pathophysiology, and complications of thyrotoxicosis (hyperthyroidism)?
The term thyrotoxicosis refers to an excess of T4 and T3 in the bloodstream. This excess may be the result of production by ectopic thyroid tissue, multinodular goiter, or thyroid adenoma or may be associated with subacute thyroiditis (painful and painless), ingestion of thyroid hormone (thyrotoxicosis factitia) or of foodstuffs con- taining thyroid hormone, or pituitary disease involving the anterior portion of the gland (see Table 16-1). In this section, the signs and symptoms, laboratory tests, treat- ment, and dental considerations for the patient with Graves’ disease are considered in detail; this disease serves as a model for other conditions that can result in similar clinical manifestations. Of note, multinodular goiter, ectopic thyroid tissue, and neoplastic causes of hyperthyroidism are rare compared with toxic goiter.1,8,12
Graves’ disease is an autoimmune disease in which thyroid-stimulating immunoglobulins bind to and acti- vate thyrotrophic receptors, causing the gland to grow and stimulating the thyroid follicles to increase the synthesis of thyroid hormone.1,8,12 The chief risk factors for Graves’ disease are genetic mutations (i.e., in susceptibility genes for CD40, cytotoxic T lymphocyte antigen [CTLA-4], thyroglobulin, TSH receptor, and PTPN2212) and female gender, in part because of modu- lation of the autoimmune response by estrogen. This disorder is much more common in women (with a male- to-female ratio of 10 : 1) and may manifest during puberty or pregnancy, or at menopause (see Figure 16-3). Genetic predisposition along with emotional stress such as severe fright or separation from loved ones has been reported to be associated with its onset. The disease may occur in a cyclic pattern and may then “burn itself out” or con- tinue in an active state.1,8,12
how is feedback done and how are T4 and T3 in the bloodstream?
Under normal conditions, thyrotropin-releasing hormone (TRH) is released by the hypothalamus in response to external stimuli (e.g., stress, illness, metabolic demand, low levels of T3 and, to a lesser extent, T4). TRH stimu- lates the pituitary to release thyroid-stimulating hormone (TSH), which causes the thyroid gland to secrete T4 and T3. T4 and T3 also have a direct in uence on the pituitary. High levels turn off the release of TSH, and low levels turn it on. In the blood, T4 and T3 are almost entirely bound to plasma proteins.7,8,11,17
what is thyroid storm/thyrotoxicosis crisis?
Classically 6-18 hours postoperatively. Signs:
• Pyrexia, sweating, dehydration, hypoglycaemia, ketosis
• Tachycardia, arrythmias, cardiac failure; occ. hypotension
• Nausea, vomiting, diarrhoea, abdominal pain
• Restlessness, confusion, delerium.
• Severe hypotension and coma can occur
• Reactions appear to be associated with adrenal cortical insufficiency (low cortisol levels)
Tx.
large doses of antithyroid drugs (200mg PTU), propranolol (to antagonize adrenergic component), hydrocortisone (100-300mg to combad adrenal cortical insufficiency), dexamethasone (2mg orally q6h to inhibit release of hormone from the gland and peripheral conversion of T4 to T3), IV glucose solution, vit B complex, wet packs, fans and ice packs.
what about hypothyroidism?
The causes of hypothyroidism can be divided into four main categories (see Table 16-1): primary atrophic, sec- ondary, transient, and generalized resistance to thyroid hormone. Up to 95% of cases of hypothyroidism are caused by primary and goitrous hypothyroidism. Acquired impairment of thyroid function affects about 2% of adult women and about 0.1% to 0.2% of adult men in North America.1,7,8,13 Hypothyroidism may be congenital or acquired. Permanent hypothyroidism occurs about once in every 4000 live births in the United States. Transient hypothyroidism occurs in 1% to 2% of newborns. Most infants with permanent congenital hypothyroidism have thyroid dysgenesis—that is, ectopic, hypoplastic, or thyroid agenesis. The acquired form may follow thyroid gland or pituitary gland failure and commonly is due to irradiation of the thyroid gland (radioactive iodine), sur- gical removal, and excessive antithyroid drug therapy. However, some occur with no identi able cause.1,7,8,13
Subclinical hypothyroidism is a prevalent condition that is characterized by elevated serum TSH concentra- tion and normal serum FT4 and T3.13
what is adrenal insufficiency ?
Primary adrenocortical insuf ciency is caused by pro- gressive destruction of the adrenal cortex, usually because of autoimmune disease, chronic infectious disease (tuber- culosis, human immunode ciency virus [HIV] infection, cytomegalovirus infection, and fungal infection) or malignancy. The condition also may result from hemor- rhage, sepsis, adrenalectomy, drugs, or genetic mutations (e.g., familial glucocorticoid de ciency).14-16
Secondary adrenocortical insuf ciency is a far more common problem and may be caused by structural lesions of the hypothalamus or pituitary gland (e.g., tumor), administration of exogenous corticosteroids, or less commonly, administration of speci c drugs (e.g., desferrioxamine in the treatment of thalassemia) or a critical illness (burns, trauma, systemic infection).17 Sup- pression of the HPA axis by exogenous or endogenous glucocorticoids is the most common cause of secondary
adrenal insuf ciency. The secretion of cortisol is directly dependent on the level of circulating ACTH. As plasma cortisol level increases, the production of ACTH decreases by virtue of negative feedback to the pituitary and the hypothalamus. With the administration of cor- ticosteroids, the feedback system senses the elevated plasma steroid levels and inhibits ACTH production, which in turn suppresses adrenal production of cortisol (see Figure 15-3). The result is partial adrenal insuf - ciency. The production of aldosterone, because it is ACTH-independent, is not appreciably affected.
what’s the pathophysiology behind adrenocortical insufficiency?
The major hormones of the adrenal cortex are cortisol and aldosterone. Addison’s disease is caused by the lack of these compounds. Lack of cortisol results in impaired metabolism of glucose, fat, and protein, as well as hypo- tension, increased ACTH secretion, impaired uid excre- tion, excessive pigmentation, and an inability to tolerate stress. The relationship between corticosteroids and response to stress involves the maintenance of vascular reactivity to vasoactive agents and the maintenance of normal blood pressure and cardiac output. Aldosterone de ciency results in an inability to conserve sodium and eliminate potassium and hydrogen ions, leading to hypo- volemia, hyperkalemia, and acidosis.1,2
Chronic excessive use of glucocorticoids can result in clinical features mimicking those of Cushing’s disease. This collection of clinical features of glucocorticoid excess is known as Cushing’s syndrome. This condition results from high levels of cortisol altering the proteins, carbohydrate and fat metabolism, the effects of insulin and vasculature homeostasis.
