Patho: Endocrine Disorders

What causes the tan appearance in Addison's disease?

reduced cortisol causes an elevation in ACTH. As precursor molecule for ACTH also contains melanocyte-stimulating hormone (MSH). As more ACTH is formed, so is more MSH, which in turn activates melanocytes leading to a tanned appearance.

What does the adrenal cortex secrete?

secretes corticosteroids, also called glucocorticoids (cortisol), androgens (testosterone), and mineralocorticoids (aldosterone)

What does the adrenal medulla secrete?

secretes epinephrine and norepinephrine

Anterior Pituitary secretes what hormones?

-ACTH -TSH -FSH -LH -Prolactin

What hormones are secreted by the posterior pituitary?

-ADH -Oxytocin

Panhypopituitarism

A rare disorder, is the complete loss of all the pituitary hormones.

Mary presents in your office with the unusual complaint of being "more tan" than expected based on her self-report sun exposure. Follow up questions reveal that Mary has been experiencing severe fatigue, dizziness upon standing, and an overall feeling that "something is wrong." You examine Mary and order blood tests. The test results show the following abnormalities: low cortisol, low aldosterone, elevated ACTH, low blood glucose, low serum sodium, elevated serum potassium, normal calcium, normal PTH. Mary is taking no medications. Which of the following conditions is most likely based on Mary's laboratory results? Based on Mary's laboratory results, which form of adrenal insufficiency does Mary have?

Adrenal insufficiency: Mary's laboratory results indicate normal PTH and calcium levels, so issues with the parathyroid gland can be ruled out. Low cortisol and elevated ACTH levels are associated with adrenal insufficiency. Elevated cortisol is a sign of adrenal excess. Primary adrenal insufficiency: Mary's condition is a result of a problem in the adrenal glands not being able to produce cortisol. The adrenal glands are receiving a signal from the anterior pituitary, shown by the elevated ACTH; however, the glands are incapable of responding to this signal. A tertiary condition is a problem in the hypothalamus, and Mary's problem is located within the adrenal glands.

Addison's Disease

Adrenal insufficiency: This condition causes a lack of cortisol, which is often caused by autoimmune destruction of the adrenal gland. Symptoms: Weakness; Easy fatigue Hypotension Inability to concentrate Emotional lability Anorexia; Nausea; Vomiting Hypoglycemia Electrolyte imbalances Tanned appearance In women, there is loss of pubic and axillary hair and amenorrhea.

What are the effects of high cortisol levels?

Block the action of insulin which results in glucose intolerance and hyperglycemia. Inhibits bone formation and accelerates bone reabsorption... osteopenia and osteoporosis. Suppresses the inflammation and the formation of antibodies and inhibits white blood cells... immunosuppression. Elevates blood pressure... hypertension

Diabetes Insipidus (DI)

Categories of disease: 1- Central DI : cause: lack of secretion of ADH (post pit) 2- Nephrogenic DI when the kidney fails to respond to ADH Pathophysiology of DI: The nephron does not perform antidiuresis, meaning that the nephron does not reabsorb water from the tubule fluid. Urine output, causing polyuria and highly dilute urine. The bloodstream loses water, which concentrates its sodium content, causing hypernatremia and dehydration S/S: Frequent dilute urination (Increased UO) Thirst & Dehydration Confusion & Disorientation Myoclonus Seizures Coma

What is upregulation of endocrine receptors?

Conversely, upregulation of receptors is an increase in the number of receptors and their sensitivity. The most common reason for upregulation is a reduction in the receptor stimulation by hormones.

Cushing's Syndrome; Hyperadrenalism

Cushing's syndrome, also called hyperadrenalism or hypercorticolism, is an endocrine disorder caused by high levels of cortisol in the blood. There are two terms: Cushing's syndrome and Cushing's disease. Cushing's disease refers to a tumor of the pituitary gland that produces large amounts of ACTH, resulting in excessive cortisol production. Cushing's syndrome is hyperadrenalism that is caused by a hyperactive adrenal gland that secretes excessive cortisol. CUSHING'S SYNDROME is MORE COMMON. S/S: Weight gain Redistribution of body fat to the face, trunk, and abdomen Rose-colored, puffy face called "moon facies" Extra subcutaneous fat in the cervicothoracic area called "buffalo hump" Increase in the waist-to-hip circumference ratio, with apple-shaped fat distribution Increased subcutaneous fat deposits, particularly in the abdomen, lead to purple stretch marks called striae. Easy bruising and poor wound healing Women demonstrate hirsutism, male pattern hair growth.

Secondary disorder

Dysfunction caused by abnormal pituitary activity

Tertiary disorder

Dysfunction caused by hypothalamic cause

Primary disorder

Dysfunction caused by the endocrine gland itself

Syndrome of Inappropriate ADH (SIADH)

Excess ADH=excessive water reabsorption at nephron into blood Hypervolemia & Conc urine Dilutional hyponatremia SIADH CAUSES: Brain injury Brain surgery Cancer: paraneoplastic secretion of ADH

Hyperthyroidism

Excessive secretion of T3 and T4. Graves' disease is the most common cause, an autoimmune stimulation of the thyroid gland (also called thyrotoxicosis). Other causes include thyroid adenoma, excessive pituitary TSH secretion, subacute thyroiditis, toxic multinodular goiter, excessive iodine ingestion, and excessive thyroid hormone replacement.

Thyroid hypofunction

Hashimoto's thyroiditis, an autoimmune condition, is the most common form of thyroid hypofunction. Because thyroid hormones affect the nervous system, lack of sufficient hormones may result in slow reflexes. Primary forms of hypothyroidism are due to problems within the thyroid gland itself. In this case, TSH, the signal from the anterior pituitary, is elevated, while T3 and T4 levels remain low. High levels of thyroid hormone represent hyperfunction, no hypofunction. Graves' disease is an example of thyroid hyperfunction. Cretinism is a specific form of thyroid hypofunction which occurs in infants.

Lee, age 45, recently received a phone call from his physician who was concerned about some laboratory values obtained at a recent appointment, specifically extremely elevated serum calcium levels.

Hyperparathyroidism: Parathyroid hormone, secreted by the parathyroid glands, elevates serum calcium levels. His elevated calcium levels are due to hyperparathyroidism. The adrenal glands do not regulate serum calcium levels.

What do patients experience during adrenal mineralocorticoid deficiency?

In the absence of aldosterone, there is loss of sodium and water with retention of potassium. Patients experience hyponatremia, hyperkalemia, and dehydration.

What does the pineal gland secrete?

Melatonin

Thyrotoxic Crisis (Thyroid Storm)

Overwhelming release of thyroid hormones that exerts an intense stimulus on the metabolism. This is a life-threatening condition most commonly precipitated by surgery, trauma, or infection.

Hypopituitarism

P: Hypopituitarism (pituitary insufficiency), is the hyposecretion of one or more of the pituitary hormones, in turn, target gland hormone production is then decreased. Normally low levels of target gland hormone feedback to the pituitary gland increases tropic hormone production. However, in hypopituitarism, the pituitary gland is dysfunctional and the response is absent or inadequate. pituitary adenoma is the most common cause of hypopituitarism. It is a benign, epithelial neoplasm that can compress pituitary tissue or interfere with the delivery of hypothalamic hormones to the pituitary gland. S/S: The most serious concerns are Adrenal insufficiency, Hypothyroidism, and Diabetes Insipidus (DI) (DI = lack of ADH). Neonate & infant: Dwarfism, developmental delay, various visual and neurological symptoms, seizure disorder, and congenital malformations. Adults: Adrenal Insufficiency: Weakness, weight loss, hypotension Hypothyroidism: Weight gain, sluggishness, and depression

Sheehan's syndrome

P: Pituitary ischemia and infarction that develops after childbirth due to severe hemorrhage. Creates a deficiency of ACTH, TSH, FSH, LH, ADH, and PRL, which results in adrenal insufficiency, hypothyroidism, amenorrhea, diabetes, and inadequate lactation.

Hypothyroidism

P: There is a lack of t3 and t4 hormones released by the thyroid gland. Effects: Raises cholesterol; hyperlipidemia Raises carotene levels (yellows skin) Decreases filtration by kidney Can cause hoarse voice Causes anemia S/S: In child: cretinism In adults: sluggishness, weight gain, sensitivity to cold, constipation, depression

hormone hyperfunction

occurs when there is an excessive amount of hormone secreted by the gland.

Hyperpituitarism

Pituitary adenoma is the most common cause of hyperpituitarism, which can produce excess ACTH, TSH, or growth hormone (GH). Excessive GH: Children: Gigantism: greater than 7 feet tall, large hands and feet, coarse facial features, hypogonadism, diabetes, and other endocrine problems Adults: Acromegaly: excessive growth of jaw, hands, feet, enlarged tongue and organ enlargement, causing metabolic disorders

At his follow-up examination, Lee's laboratory values revealed elevated serum PTH, elevated serum calcium, and reduced serum phosphorus. What form of hyperparathyroidism does Lee exhibit?

Primary hyperparathyroidism: Primary hyperparathyroidism is a disorder in the parathyroid glands themselves. The laboratory values indicate disruption of normal parathyroid function, as elevated serum calcium usually negatively feedback to the parathyroid glands, suppressing PTH release. In this instance, the parathyroid glands are no longer responding as expected to the calcium signal. Secondary hyperparathyroidism is elevated PTH levels as a result of some other organ, not the parathyroid glands, experiencing dysfunction. For example, if the kidneys are unable to reabsorb calcium, PTH levels remain elevated.

What is downregulation of endocrine receptors?

Prolonged, excessive stimulation of an endocrine gland often results in receptor insensitivity and may decrease its number of receptors in a process known as a downregulation of receptors.

Had Lee been experiencing primary hypothyroidism, instead of primary hyperparathyroidism, what laboratory results would you expect?

Reduced PTH, reduced calcium, elevated phosphorus: Hypoparathyroidism indicates reduced, not elevated, PTH levels. As PTH increases serum calcium levels, a reduction in PTH results in lower than normal calcium levels. Phosphorus levels are often opposite calcium levels. As calcium levels decline, phosphorus levels increase.

Hormone resistance

Such as diabetes

Excess antidiuretic hormone is associated with which of the following conditions?

Syndrome of inappropriate antidiuretic hormone

Diagnosis of Cushing's syndrome is...

The Dexamethasone suppression test

Graves' Disease (Hyperthyroidism)

Thyroid-stimulating antibodies bind to and activate thyrotropin receptors within the thyroid gland, causing the gland to enlarge and continually synthesize thyroid hormones. Signs/Symptoms: Nervousness; Weight loss; Sensitivity to heat Insomnia; Atrial fibrillation Gland is usually enlarged and palpable. An audible bruit may be heard because of high glandular blood flow. Exophthalmos (eyes)

Anterior Pituitary hypofunction

The anterior pituitary secretes tropic hormones, so any hypofunction of the anterior pituitary causes a reduction in one or more of these hormones. Traumatic brain injury may damage the anterior pituitary, causing a reduced performance of the gland. Sheehan's syndrome is a specific example of anterior pituitary hypofunction resulting from ischemia to the gland during childbirth. Pituitary adenomas, which may compromise function of one of more cell types of the anterior pituitary, may also result in hypofunction. Polyuria is associated with abnormalities of the posterior pituitary and cretinism is a due to hypofunction of the thyroid gland.

Posterior Pituitary Hypofunction

The posterior pituitary releases the hormones ADH and oxytocin. Central diabetes insipidus is a condition in which ADH is not produced at sufficient levels or the kidneys are unable to respond to ADH. Inadequate ADH results in polyuria and dilution of the urine, decreasing urine osmolarity.

Hypoparathyroidism

The symptoms associated with hypoparathyroidism are the result of insufficient PTH secretion and the resultant hypocalcemia. Symptoms of hyperparathyroidism are caused by excessive secretion of PTH with resulting hyper-calcemia and bone breakdown S/S; Muscle cramps Irritability Tetany Convulsion *Hypocalcemia causes a carpal spasm known as Trousseau's sign and facial muscle twitch called Chvostek's sign.Muscle weakness Poor concentration Neuropathies Hypertension Kidney stones Metabolic acidosis Osteopenia Pathological fractures Constipation Depression, confusion, or subtle cognitive deficits

Thyroid Hyperfunction

Thyrotoxicosis is an elevation in thyroid hormones. Thyroid hormones, T3 and T4, increase metabolic rate, which may cause an individual to be warm and intolerant to heat. The heart and nervous system are sensitive to thyroid hormones, so elevation of these hormones may cause elevated heart rate and tremors. Secondary thyroid hyperfunction is due to an elevation in the anterior pituitary hormone, TSH, stimulating overproduction of thyroid hormone. Thus, TSH, T3, and T4 are all elevated in secondary forms of hyperfunction. Hashimoto's thyroiditis is associated with hypofunction of the thyroid gland. Central diabetes insipidus is a condition of the posterior pituitary

Anterior Pituitary Hyperfunction

Tropic hormones are produced by the anterior pituitary, so hyperfunction of this gland causes an elevation in one or more of these hormones. Elevated tropic hormones will in turn increase end organ activity. Prolactinomas are the most common form of anterior pituitary hyperfunction. Changes in plasma osmolarity are associated with the posterior, not anterior, pituitary. Weight gain is common in hypothyroidism.

Prolonged Corticosteroid Use

When patients are administered prolonged corticosteroid treatment beyond 4 to 5 weeks, there is negative feedback suppression of CRH and ACTH. As a result, the adrenal gland can downregulate its receptors and undergo glandular atrophy. With atrophy, there is a decreased ability to secrete natural cortisol. The patient will then develop symptoms of adrenal insufficiency; in the case of high stress, surgery, or infection, the patient may develop adrenal crisis.

Posterior Pituitary hyperfunction

When the poster pituitary demonstrates increased function, excess water reabsorption may result due to elevated ADH levels. Such elevations in ADH occur in the disease syndrome of inappropriate antidiuretic hormone, SIADH. Additional fluid volume in the body will dilute particles in the plasma, reducing plasma osmolarity. Myxedema and exophthalmos are associated with thyroid, not posterior pituitary disorders. Prolactinomas are a condition of the anterior pituitary.

Empty sella syndrome

a condition caused by compression of the pituitary gland by brain tissue herniation ( ICP, radiation or trauma).

Hormone hypofunction

occurs when there is an inadequate amount of hormone secreted by the gland.