CHAPTER 32

DISORDERS OF ENDOCRINE FUNCTION

Essentials of Pathophysiology

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.

T

F

T

T

F

PRE LECTURE QUIZ 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

Primary: abnormality in the gland

Secondary: abnormality in stimulation from the pituitary

Tertiary: abnormality in stimulation from the hypothalamus

HORMONE DISORDERS

PITUITARY HORMONES

Growth hormone

FSH and LH

ACTHTSH

stimulate gonads

stimulates thyroid

stimulates adrenal cortex

QUESTION

Which hormone(s) stimulate the ovaries and testes?

a. GHb. FSH and LHc. TSHd. ACTH and GH

ANSWER

b. FSH and LHRationale: 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

GHRH stimulates

Somatostatin inhibits

Hypothalamus

Anterior pituitary

Growth hormone

GHIHNext

Slide

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

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

TrueRationale: 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

GnRH stimulates

hypothalamus

anterior pituitary

FSH

production of gametes and gonadal hormones

LH

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

º Hashimoto thyroiditis

º 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

FalseRationale: 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

Negative feedback

Negative feedback

Hypothalamus

Corticotropin-releasing hormone (CRH)

Anterior pituitary

Adrenal corticotrophic hormone (ACTH)

Adrenal cortex

Cortisol AldosteroneTestosterone

ACTIONS OF CORTISOL

cortisol

Increases catabolism

blood glucoseincreased

muscle breakdown

plasma proteins

increased

free fatty acids

increased

SNS responseincreased

immune/inflammatory

systemssuppressed

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)

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?