BIOL 2200 Module 9: Endocrine Disorders

Organs in the endocrine system

• Hypothalamus

• Pituitary gland

• Thyroid gland

• Adrenal glands

• Pancreas

Which organ produces “releasing hormones” that target the anterior pituitary?

The hypothalamus produces “releasing hormones”

“Tropic hormones”

Hormones that target other tissues

Causes of endocrine disorders

1. Too much/little hormone

2. Hormone cannot bind/activate cell receptor

3. Disruption in effect of hormone binding to cel//receptor

What factors can affect delivery of hormone to target tissue?

• Poor blood supply

• Inadequate carrier proteins in plama (e.g. for aldosterone)

If antibodies bind to a cell receptor instead of hormone, how is function affected?

It acts as competitive inhibitors or mimics hormone action

Primary disorder

An issue with the target gland at the end of the cascade. Target tissue isn’t acting normally — e.g. thyroid → thyroxine

Secondary disorder

Issue with pituitary gland tropic hormone release. E.g. thyroid-stimulating hormone

Tertiary disorder

Issue with hormone production from hypothalamus, disrupting pituitary signaling. E.g. hypothalamus not working correctly

Most common hypothalamic dysfunction

Interruption of the pituitary stalk

Pituitary stalk

Vascular connection between the anterior pituitary and hypothalamus

Hypopituitarism

Decreased release of pituitary hormones. Typically caused from a problem within the pituitary gland, e.g. infarction

Panhypopituitarism

Deficiency in a few or all pituitary hormones

Hyperpituitarism

Excess production of pituitary hormones. Usually caused by an adenoma

Adenoma

Pituitary tumor

Gigantism

Oversecretion of growth hormone in childhood

Pituitary dwarfism

Undersecretion of growth hormone in childhood

Acromegaly

Oversecretion of growth hormone in adulthood

Diabetes insipidus

An inability to concentrate urine. Caused by dysfunctional ADH

Clinical manifestations of diabetes insipidus

Polyuria and thirst (from losing water)

What does high ADH cause?

Excess reabsorption of water, causing very concentrated urine

Ectopic production

Release of hormone-like substances by tumors

SIADH

Syndrome of Inappropriate AntiDiuretic Hormone secretion

Clinical manifestations of SIADH

Hyponatremia, anorexia, headache and fatigue

Thyrotoxicosis

Increased levels of thyroid hormones T3 and T4

Graves disease

Type II hypersensitivity because of autoantibodies that bind to the TSH receptor in the thyroid gland

Manifestations of hyperthyroidism

Increased sympathetic nervous system activity, higher metabolism, weight loss, exophthalmos

Exophthalmos

Bulging of eyes. E.g. in Grave’s disease

Why is TSH-secreting pituitary adenoma a secondary disorder?

Because it is an issue with the anterior pituitary (the adenoma)

Is Hyperthyroidism or Hypothyroidism more common?

Hypothyroidism is more common

Hashimoto disease

Where autoantibodies/autoreactive T lymphocytes attach the thyroid land

Myxedema

Fluid retention. E.g. from hypothyroidism

Steroid hormones produced by adrenal cortex

• Mineralcorticoids (aldosterone)

• Glucocorticoids (cortisol)

• Adrenal sex hormones (androgens)

Aldosterone

Helps regulate sodium, potassium, and water levels

Cortisol

Hormone with anti-inflammatory action that enhances protein breakdown, gluconeogenesis, and fat mobilization

How does cortisol act on epinephrine?

It enhances epinephrine’s action, helping maintain proper blood pressure

Cushing syndrome vs Cushing disease

Cushing syndrome has three forms, while Cushing disease is the secondary form

Cushing syndrome

Where adrenal glands produce too much glucocorticoid (cortisol)

Primary Cushing syndrome

Where the adrenal cortex is diseased, excreting excess cortisol

Secondary Cushing syndrome

Where hyperfunction of the anterior pituitary leads to excess cortisol production

Ectopic Cushing syndrome

Excess cortisol caused by excess corticosteroid drug use or a tumor secreting ACTH

Manifestations of Cushing syndrome

Weight gain, fat pad on back, muscle weakness, thinning extremities, osteoporosis!

Adrenal cortical insufficiency

Where adrenal glands do not produce enough adrenal cortex hormones

Primary adrenal cortical insufficiency

Where the adrenal gland is destroyed. So no adrenal cortex hormones are produced. Known as Addison’s disease

Secondary adrenal cortical insufficiency

Decreased ACTH production caused by hypopituitarism

Manifestations of adrenal cortical insufficiency

Either asymptomatic, or symptoms os low aldosterone/low cortisol may develop (slowly)

Adrenal (Addisonian) crisis

Where shock occurs due to Addison’s disease

Who is at risk of Adrenal (Addisonian) crisis?

Individuals who do not respond to hormone replacement therapy, undergo extreme stress, or undergo gland thrombosis following severe infections

Pre-diabetes

Characterized by an imbalance between insulin availability and need. Can arise from insulin deficiency, impaired insulin release or insulin that is inactivated or detroyed

Effect of insulin

Stimulates expression of GLUT-4 glucose transporters in muscle and fat cell membranes, allowing glucose to enter

Type 1 diabetes

When the immune system destroys pancreatic beta cells. 5% to 10% of diabetes cases

How does Type 1 diabetes develop?

Autoantigens develop on beta cells → stimulate cellular and humoral immune responses → leads to T-cells destroying beta cells

Three P’s of Type 1 diabetes

Polyuria, Polydipsia, Polyphagia

Glycosuria

Glucose in the urine (excess glucose)

Diabetic ketoacidosis

Where the body lacks insulin to use sugar for energy, and breaks down fat too quickly (gluconeogenesis)

Type 2 diabetes

Impaired insulin utilization, leading to hyperglycemia. Typically starts as insulin resistance

Insulin resistance

Where the body stops responding effectively to insulin

In Type 2 diabetes, how does hyperinsulinemia become hypoinsulinemia?

Because of overproduction of insulin, which damages down the pancreas’s beta cells

How is insulin resistance related to obesity?

1. Adipokines → decreased insulin sensitivity

2. Intracellular cholesterol and triglyceride deposits → affects insulin signaling

3. Adipose tissue releasing inflammatory cytokines

How do inflammatory cytokines produced by adipose tissue induce insulin resistance?

These cytokines block cells from receiving insulin’s messages

How does Type 2 diabetes develop?

Insulin resistance leads to overproduction of insulin, tiring out beta cells

Metabolic syndrome

A cluster of conditions that increases the risk of developing type 2 diabetes

Gestational diabetes mellitus

First onset of glucose intolerence during pregnancy

Is hypoglycemia or hyperglycemia more dangerous?

Hypoglycemia is more dangerous because it can lead to starvation of brain cells

Somogyi affect

Alternating periods of hypoglycemia and hyperglycemia → low blood sugar overnight leads to high blood sugar in the morning (rebound)

Dawn phenomenon

Natural rise in blood glucose levels in the morning due to hormones

Hyperosmolar Hyperglycemic Syndrome (HHS)

Extreme glucose levels accompanying severe dehydration. Very deadly

Advanced Glycation End products (AGEs)

Chronic excess glucose leading to permanent binding of glucose inside and outside of cells (glycation)

Polyol pathway

Where tissues that don’t need insulin to import glucose can’t down-regulate uptake, converting it into sorbitol and causing cell swelling

Diabetes-induced hypoxia

Where glycation of hemoglobin leads to impaired oxygen release to tissue

Inappropriate protein kinase C (PKC) activation

Leads to vascular damage in retina, as it causes cell to mifire

Diabetic retinopathy

Where high blood sugar damages the retinal blood vessels

Diabetic nephropathy

Glomeruli damage caused by high blood sugar and fat level (glycation and loss of kidney function)

Diabetic neuropathy

Nerve damage caused by high blood sugar. May lead to gangrene

Macrovacular disorder

Disorder affecting the body’s tiny blood vessels. Increases risk of coronary artery disease, stroke, peripheral vascular disease