Chapter 32 Disorders of Endocrine Function Essentials of Pathophysiology Chapter 32 Disorders of Endocrine Function

Pre lecture quiz true/false Hypopituitarism is characterized by a decreased secretion of pituitary hormones. Hypothyroidism is evidenced by an increased metabolic rate, restlessness, irritability, tachycardia, diarrhea, and heat intolerance. Primary adrenal insufficiency, or Addison disease, is caused by destruction of the adrenal gland. Moon facies, buffalo hump, obesity, amenorrhea, and increased facial hair are manifestations of Cushing syndrome. Addison disease is a temporary condition.

Pre lecture quiz Acromegaly Cushing Graves growth puberty In children, _____________ hormone deficiency interferes with linear bone growth, resulting in short stature or dwarfism. When growth hormone excess occurs in adulthood or after the epiphyses of the long bones have fused, the condition is referred to as ______________. Precocious ______________ is the early activation of the hypothalamic-pituitary-gonadal axis, resulting in the development of appropriate sexual characteristics and fertility. ______________ disease is a state of hyperthyroidism that is often accompanied by goiter and exophthalmos. ______________ syndrome refers to the manifestations of excess cortisol. Acromegaly Cushing Graves growth puberty

Hypothalamus- Pituitary Axis Releasing hormones from hypothalamus tell the pituitary what to release into the blood Trophic hormones from the pituitary tell specific peripheral glands to grow and produce their hormones Releasing Hormones Trophic Hormones

Hormone Disorders Tertiary: abnormality in stimulation from the hypothalamus Secondary: abnormality in stimulation from the pituitary Primary: abnormality in the gland

Pituitary Hormones Growth ACTH FSH TSH hormone and LH stimulates adrenal stimulate thyroid cortex gonads

Question Which hormone(s) stimulate the ovaries and testes? GH FSH and LH TSH ACTH and GH

Answer FSH and LH Rationale: Gonads are sex organs (ovaries and testes). These organs are stimulated by follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

The Hypothalamus Controls Growth Hormone Release GH secretion stimulated by: Hypoglycemia, fasting, starvation Stress GH inhibited by: Increased glucose levels, free fatty acid release, and obesity Cortisol Hypothalamus Next Slide GHIH GHRH Somatostatin stimulates inhibits Anterior pituitary Growth hormone

Growth Hormone Sitimulated BY ? Hypoglycemia, fasting, starvation, Stress ?? It would seem that adequate energy supply would be needed for Growth ? A baseline level of GH exists during normal nutrition mildly stimulated by Deep Sleep, Exercise, and Protein Consumption. GH stimulates IGF-1 During fasting etc. and increased release of GH occurs due to a decrease in GHIH. This produces a protective effect preventing muscle wasting by stimulating lipolysis and FFA metabolism maintaing blood glucose for the CNS Without GH significantly more muscle wasting occurs

Functions of Growth Hormone Promotes Growth Inhibits Insulin

Growth Hormone Deficiency Idiopathic GH deficiency Lacks hypothalamic GHRH Pituitary tumors, agenesis of the pituitary Cannot produce GH Laron-type dwarfism Hereditary defect in IGF production

In childhood: gigantism In adulthood: acromegaly Growth Hormone Excess In childhood: gigantism In adulthood: acromegaly

Question Tell whether the following statement is true or false. GH deficiency may result in dwarfism.

Answer True Rationale: Laron-type dwarfism is caused by a genetic inability to produce normal amounts of GH. Not True. Normal GH abnormal IGF

The Hypothalamus Controls Gonadal Hormone Release Excessive GnRH secretion can be stimulated by: Hypothalamic tumors Pituitary tumors Giving high levels of GnRH causes the pituitary to become less responsive and reduces the effects of abnormal GnRH secretion hypothalamus GnRH stimulates anterior pituitary FSH LH production of gametes and gonadal hormones

Thyroid Control Thyroid releases T3 and T4 Both are carried by binding proteins T3 stimulates metabolism T4 is inactive until converted into T3 in the tissues Both exert negative feedback on the hypothalamus Why?

Thyroid Insufficiency Due to Lack of I T3 and T4 are not made There is no negative feedback to the hypothalamus TRH and TSH continue to be made If it is able, the thyroid will grow in response to the TSH

Thyroid Imbalances Hypothyroidism Congenital Acquired Hashimoto thyroiditis Thyroidectomy Hyperthyroidism (thyrotoxicosis) Graves disease Thyroid tumors

Question Tell whether the following statement is true or false. Simple goiter is caused by increased production of thyroid hormone.

Answer False Rationale: Simple goiter is the result of iodine (I) insufficiency. Since I is necessary in order to produce thyroid hormone, a deficiency results in low serum levels of T3 /T4. This causes TSH to stimulate the thyroid gland to make more hormone (which it cannot do because it needs I). The cells of the thyroid gland hypertrophy in an effort to function (make thyroid hormone).

Major Adrenal Cortical Hormones Cortisol What can cause Cortisol Stimulation? Hypothalamus releases ?? Causes the Anterior Pituitary to release ?? Causes the adrenal cortex to release ??

Major Adrenal Cortical Hormones Hypothalamus Corticotropin-releasing hormone (CRH) Negative Anterior pituitary feedback Negative Adrenal corticotrophic feedback hormone (ACTH) Adrenal cortex Cortisol Testosterone Aldosterone

Actions of Cortisol cortisol Increases catabolism plasma immune/ proteins inflammatory increased systems suppressed muscle breakdown SNS response increased free fatty acids blood glucose increased increased

Adrenal Cortical Disorders Adrenal cortical insufficiency: inability to make all three hormones Primary adrenal cortical insufficiency (Addison disease) Secondary adrenal cortical insufficiency Acute adrenal crisis Excessive adrenal secretion Glucocorticoid hormone excess (Cushing syndrome) Hyperaldosteronism Congenital adrenal hyperplasia Decreased cortisol synthesis; other hormones may be increased or decreased

Clinical Manifestations of Addison Disease (chronic adrenal insufficiency) Author: Add text?

Clinical Manifestations of Cushing Syndrome (high levels of cortisol in the blood)

Scenario Three men have adrenal problems. One has hypoaldosteronism, one has an inability to make cortisol, and one has an inability to make testosterone. Question: Which of them is most likely to develop: Hypotension? High CRH levels? Hypoglycemia? Hypervirilization? Decreased libido? Hyperkalemia?

Scenario Two women have benign pituitary tumors. One woman has lost weight and complains of being hot all the time; she presents as thin and nervous, with tachycardia and exophthalmos The second woman has gained weight in her abdomen and presents with a round face and thin arms and legs with stretch marks; she says that at her last checkup her doctor told her she was prediabetic Question: What hormones are being secreted by the pituitary tumors in these patients? Why?