Chapter 18: Alterations of Hormonal regulation

Hormonal alterations may be due to:

1) Too much hormone
2) Too little hormone
3) Faulure of target cell to response to hormone (clinically this situation is similar to "too little hormone")

Primary endocrine disorder

result from intrinsic defects within the hormone-secreting gland
- Primary hyposecretion = low target gland hormone, high pituitary hormone
- Primary hypersecretion = high target gland hormone, low pituitary hormone

Secondary disorders

result from abnormal pituitary secretion of tropic signals.

Growth Hormone Disorders

1) Increase protein synthesis in most tissues of the body
2) Increase liver glycogenolysis (producing hyperglycemia)
3) Increase fat utilization in most tissues of the body due to increased fat mobilization
4) Stimulate increased muscle and skeletal growt

Growth hormone deficiency during childhood

Pituitary dwarfism

GH deficiency in adults

Cause: traumatic head injuries or resection of pituitary tumors
Sign and symptom:
- Decreased lean body mass
- Hypercholesterolemia
- Decreased bone density

GH excess in childhood

Pituitary gigantism
- Die early due to cardiovascular disease

GH excess in adults

Acromegaly since epiphyseal plate closure at puberty

Physical features of acromegaly includes:

1) A protruding jaw
2) Increased bone density
3) Increased growth of soft tissues (nose and ears)
4) Large hands and feet

The cause of acromegaly is

Usually a benign tumor of the pituitary gland (therefore, the only known risk factor for acromegaly is prior history of a pituitary tumor)

Clinical manifestation of Acromegaly:

1) Enlarged tongues
2) Edema
3) Increase in size and function of sebaceous glands and sweat glands
4) Coarse skin and body hair

GH Hypersecretion and Type 2 Diabetes mellitus

Inhibition of glucose uptake => Hyperglycemia => Hyperinsulinemia => Insulin resistance

Treatment of acromegaly

1) Surgical removal of the GH-secreting adenoma
2) Octreotide, a synthetic somatostatin analog, is very effective at suppresing production of GH and lower GH levels

Octreotide

Synthetic somatostatin to lower GH levels

SIADH

Syndrome of Inappropriate ADH secretion
=> ADH is continually released + Water retention + Hyponatremia

Diagnosis of SIADH includes:

Serum hypoosmolality, Hyponatremia
Urine hyperosmolality
Urine Na+ excretion matches intake

Level of Na+ in SIADH

130-136 mEq/L mild symptoms
120-130 Moderate
<115 is severe

Symptoms of SIADH

1) GI symptoms occur early in the disease and include:
- Nausea
- Anorexia
- Vomitting
2) Neuropsychiatric symptoms:
- Headaches
- Blurred vision
- Lethargy
- Apathy
- Disorientation
- Irritability
- Seizures

Treatment of SIADH

1) Correction the underlying causal problems
2) Fluid restriction to 600-800 mL/day
3) Administration of Hypertonic Saline combined with furosemide (diuretic) therapy

Drugs and SIADH

No drugs to stop ADH release but there are drugs to make renal tubules resistant to ADH (Demaclocycline)

Critical point in treatment of hyponatremia

Don't do too rapidly or it will develops central pontine myelinolysis (damage the myelin sheath)

Diabetes Insipidus

Large diuresis of very dilute urine due to deficiency of ADH (urine cannot be concentrated and free water is lost, causing hyperosmolality)

4 types of diabetes insipidus

1) Neurogenic: inability to produce and release ADH
2) Nephrogenic: kidneys inability to respond to ADH
3) Gestagenic is lack of ADH that develops during pregnancy
4) Primary polydipsia: ADH is suppressed by excessive fluid intake:
a) Dipsogenic polydipsi

Clinical manifestations of diabetes insipidus

Polyuria
Nocturia
Thirst
Polydipsia
Low urine specific gravity
Low urine osmolality
High-normal plasma osmolality

Untreated diabetes insipidus can produce :

Hypovolemia (decreases CO)
hyperosmolality
circulatory collapse
loss of consciousness (decreased CO causes this)
CNS damage.

Primary vs Secondary Hypothyroid disease

Primary: High TSH (more common)
Secondary: Low TSH

Myxedema

Facial swelling due to hypothyroidism
Can cause myxedema coma (60% mortality)

Goiter

Can be in both hyperthyroidism and hypothyroidism

Clinical manifestations of hypothyroidism

Low BMR
Cold intolerance
Lethargy
Tiredness
Constipation

Cretinism

In infants and children due to lack of thyroid hormone (congenital hypothyroidism)
- However, it can also develop later if there is a lack of iodine in the diet of the thyroid is diseased or surgically removed.

Cretinism can cause:

Retardation of physical and mental development
1) Growth is stunted
2) Skin is thick, flabby, and waxy in color
3) Nose is flattenned
4) Abdomen protrudes
5) Generally slowness of movement and speech

Graves disease

Autoimmune type II hypersensitivity reaction that targets the thyroid gland and causes overproduction of thyroid hormones
(85% if all cases of hyperthyroidism is because of grave disease)

Thyroid storm

Life threatening. Excessive amounts of thyroid hormones being acutely released into the circulation

Thyroid storm is charactered by:

1) Tachycardia
2) Hypertension
3) High temperature
4) Cardiac dysrhythmias and CHF

hyperparathyroidism

High serum Ca++ decreases neuromuscular excitability, leading to muscle and bone weakness. High serum Ca++ also can lead to cardiac arrhythmias and renal calculi.
Treatment is to remove the abnormal gland

hypoparathyroidism

low serum Ca++ levels, which increases neuromuscular excitability, leading to tetany and seizures
Treatment: Ca supplement

Alteration of glucorticoids (Cortisol)

Cortisol helps maintain BP and CV function, suppresses the immune system inflammatory response, stimulates gluconeogenesis, increases protein breakdown, and increases mobilization of FFA.
==> Anti-insulin

Alteration of mineralocorticoids (Aldosterone)

Aldosterone helps maintain blood pressure and water and salt balance in the body by helping the kidney retain Na+ & excrete K+ .

Sex Steroid (Androgens)

Minor role in the development and maintenance of secondary sex characteristics
- Exception is in children with congenital adrenal hyperplasia

Primary vs Secondary Adrenocortical insufficiency:

Primary: increased ACTH => ADDISON DISEASE
Secondary: low ACTH (more common)

Addison disease:

Primary adrenocortical insufficiency
- Weight loss
- Salt wasting
- Volume depletion
- Low blood pressure (due to volume depletion)
- Hypoglycemia (due to decreased cortisol)
- Hyperkalemia (due to decreased aldosterone)
- Weakness
- Fatigue
HYPERPIGMENTA

Vitiligo

Pigmentatiom disappears from a patch of skin

Cushing disease

Excessive cortisol production due to pituitary hyperstimulation of the adrenal cortex (STEROID IS THE MOST COMMON CAUSE OF CUSHING DISEASE)

Clinical manifestation of Cushing disease:

Moon face
Cervical fat pad
Central obesity
Thin extremities
Weight gain
Thin skin
Striae
Hypertension
Hyperglycemia
Brusing

Hyperaldosteroneism

Conn syndrome:
- Hypervolemia
- Hypertension
- Hypokalemia (muscle aches, fatigue, mild weakness)

Congenital adrenal hyperplasia

In the newborn, congenital adrenal hyperplasia is a life-threatening condition because of inadequate circulating cortisol.
Virilization in female
Enlarged penis and hyperpigmented scrotum in male

A diagnosis of diabetes mellitus is based on:

1) An elevated fasting plasma glucose concentration > or = 126 mg/dL
or
2) An increased 2-hr plasma glucose during 75-g glucose tolerance testing > 200 mg/mL

3 "P"s in signs and symptoms for diabetes:

1) Polyuria
2) Polydipsia (excessive or abnormal thirst)
3) Polyphagia (excessive appetite or eating)
Also: weight loss and fatique

Type 1 Vs Type 2 Diabetes

Type 1: Absolute insulin deficiency (beta) cells in pancreas are destroyed. (glucagon must also present)
Type 2: Insulin resistance with an insulin secretory deficit

2 forms of Type 1:

1) Immune-mediated: beta cell destruction that occurs as a result of an autoimmune attack on the pancreatic beta cell
2) Idiopathic: destruction without evidence of autoimmune markers.

Hypoglycemia level:

45-60 mg/dL

Diabetic Ketoacidosis

300 - 750 mg/dL
Develops when there is a deficiency of insulin (therefore, won't see in type 2)
Hepatic glucose production increases and peripheral glucose usage decreases
Fat is mobilized and ketogenesis is stimulated
ADOLESCENCE

HHNKS

600 - 4800 mg/dL
Hyperosmolar hyperglycemic nonketonic syndrome
- SImilar to Diabetic Ketoacidosis but less common since there is sufficient insulin present to prevent lipolysis and protein catabolism.

Chronic complication:

1) Neuropathies: sensory
2) Microvascular disease: Microangiopathy (thickening of capillary basement membrane due to hypoxia and ischemia); Retinopathy blind; Nephropathy (glomerulosclerosis)
3) Macrovascular disease: Brain (stroke), Heart (damage vessle)