Long term steroids suppress the endocrine system (hypothalamus, pituitary & adrenals) in their production of the bodies own steroids.

Thus the body needs time to start producing steroids on its own before removing all exogenous steroids. 

Vasopressin (Anti-diuretic hormone)

Oxytocin

Lactogenic hormone (Prolactin)

Growth hormone

ACTH

Thyroid-stimulating hormone

Follicle stimulating hormone

Luteinizing hormone

Vasopressin acts on the kidney to promote resorption of water into the blood stream

Untested fun fact that might help you remember it's action:

Caffeine and alcohol suppress vasopressin secretion, hence why you gotta pee more when you consume them. 

Pituitary Tumours

(Adenomas)

Hyperprolactinemia

Cushing's Disease (ACTH)

Acromegaly (GH)

CN III, IV & VI 

Maxillary Branch of V

Ophthalmic Branch of V

They are likely to be involved because they are all in the cavernous sinus. 

1. Surgery-transphenoidal if small enough

2. Radiotherapy

3. Pharmacologic therapy

If the body senses low levels of thyroid hormone the hypothalamus will secrete thyroid releasing hormone. 

The pituitary gland will, in response, release not only thyroid stimulating hormone but also prolactin. 

This becomes a cycle since enough thyroid hormone is never produced and so the pituitary will continue to be stimulated and secrete TSH and Prolactin. 

Amenorrhea

Galactorrhea (milk secretion)

Loss of libido

Visual field defects

Headaches

What sort of drug action could be used to treat hyperprolactinemia?

Give an example of such a drug

Dopamine agonist-not only affects production but may decrease the size of the tumour.

Bromocriptine

Cabergoline

Your 27 yo pt Henry comes in complaining of recent changes that have occurred in his body over the last year. He feels like his tongue is large, his voice has changed, his limbs seem bigger and he experiences terrible headaches. 

He also says he has high blood sugar levels. 

What do you suspect could be the issue?

Somatostatin analogues

Can only use Dopamine agonists to decrease the size of the tumour

2 drugs: Octreotide and Lanreotide

What are they used to treat?

Cortisol

Corticosterone

Vasopressin

 ('presses' on the vessels)

A small ACTH producing tumour in the pituitary

It does not respond to the hypothalamus telling the pituitary to reduce production of ACTH. 

Overstimulation of the adrenal glands causes hyperplasia

Low ACTH

High cortisol

in the plasma

A neoplasm

(benign adenoma or malignant carcinoma)

in the adrenal cortex produces cortisol.

Independent of signals from the pituitary to reduce production. 

A neoplasm in some random place that produces ACTH

Most often are small cell carcinomas of the lung

Hypertension

Weight gain

Fatty moon face buffalo hump weakling comes into your office for an eye exam.

He doesn't turn out to be very bright so you decide to give him a nickname to help him remember what 'disorder' he has, what should it be?

'Cushy' of course

Because he has a somewhat advanced case of Cushing's syndrome

Glucocorticoids interrupt the breakdown of glucose. 

Thus the pt experiences high levels of glucose in the blood. 

Their disorder causes the catabolism of proteins- this includes collagen.

If collagen is broken down it will affect the skin

The excess of steroids in Cushing's syndrome suppresses the immune system.

Neutrophils circulate but all other signals are turned off, inhibiting the neutrophils from recognizing what to attack. 

1. Dexamethasone Suppression Test

2. Impaired glucose tolerance

3. MRI w/ contrast

Adrenal insufficiency

Often occurs after an adrenalectomy 

Primary-a lesion cause the overproduction of aldosterone

Secondary-A condition causes the release of aldosterone as a by product. 

Heart failure causes lowered blood pressure.

The body will respond by telling the kidney to release renin and a consequent cascade occurs that results in oversecretion of aldosterone. 

Anorexia

Nausea & vomiting

diarrhea

Weight loss

GI disturbances

Hypotension

Hyperpigmentation 

Weakness/Fatigability

Headache

Sweating

Palpitations

Pheochromocytoma

They are called this because they do so many things 10% of the time

eg. 10 %are malignant, 10% are in children, 10% are bilateral etc.

T/F

Mumsi has a goiter, it is MOST likely that she has an overactive thyroid.

False

Most goiters are associated with hypothyroidism.

There is only so much TBG in the body, thus excess thyroid hormone means there will be lots of unbound T3 and T4 .

Thyroid hormone that is not bound by TBG upregulates carb metabolism, lipid catabolism and protein synthesis, thus the overall metaboilc rate is increased.

1. Thyroid hyperplasia due to Graves'

2. Ingestion of too much Thyroid hormone

3. Hyperfunctional, multinodular goiter

4. Hyperfunctional thyroid tumour

5. Pituitary tumour (most rare)

Antibodies are developed against the TSH receptors. 

They bind to the TSH receptor sites in the thyroid and cause overstimulation.

High T3/T4

Low TSH

Exophthalmos

EOM weakness

Diplopia

Lid retraction

Lid edema

Keratitis

Compressive optic neuropathy

Medication

Surgery

Radioactive iodine treatment

Beta-blockers

they help to 'calm' the system down, lower the HR, BP, tremor etc. 

Drugs like Methimazole inhibit the oxidation of iodine.

This decreases the amount of iodine that is available for thyroid hormone synthesis and therefore decreases thyroid hormone levels. 

Methimazole

Propylthiouracil is an older option. 

<20% of pts experience remission with this method

The drugs have side effects such as:

-Rash

-Agranulocytosis

-Hepatitis

There is a risk that the thyroid will no longer produce enough-->hypothyroidism

Also damage to the laryngeal nerve is a risk

The hypothalamus and pituitary secrete normally but the thyroid just does not respond in primary hypothyroidism.

Thus there will be high levels of TRH and TSH but low levels of T4/T3

Low levels of both TSH and T3/T4

(TRH levels may or may not be low, depending on whether the problem is with the hypothalamus or the pituitary)

Eeyore of course.

Perhaps Tigger is Hyperthyroid.....

Hypothyroidism that develops in infancy and early child due to a lack of iodine in the diet. This can refer to either the child's diet/metabolism or the diet of the pregnant mother.

Results in impaired skeletal and CNS development

Multiple Nodules vs. Solitary nodules

Which finding is more likely to be neoplastic?

Hot vs. Cold nodules

Which is more likely to be benign?

Young vs. old pts 

Nodules on which patients are more likely to be neoplastic?

Nodules on

Males vs. Females

Which is more likely to neoplastic?

"Painful bones, renal stones, abdominal groans and psychic moans'

Which disorder?

Associated with hypoparathyroidism

Tapping on the facial nerve in front of the ear causes contraction of the facial muscles and upper lip, due to low calcium levels

Metabolic Syndrome

aka Insulin-resistance syndrome

Education/diet/exercise

Control of BP, FPG and smoking cessation

What type of Diabetes Mellitus is a slow progressive form of DM 1 that is sometimes misdiagnosed as DM2.

Patients affected by this tend to be nonobese and >35yo

PPARs=Peroxisome Proliferator-Activated Receptors

They control the entry of sugar and fat into cells

 Currently a big area of Diabetes research

1. Decreased number of insulin receptors on cells

2. Decreased insulin activity after binding to cells

3. Decreased PPAR activity

Reduced/impaired insulin secretion also contributes to high blood glucose levels as well as tissue resistance.

This impairment is possibly due to the hypothalamus becoming desensitized to high glucose levels. 

DM 1.5 or DM3 or Double Diabetes

Sometimes incorrectly referred to as LADA

Pts with Maturity-Onset Diabetes of the Young can be easily controlled with low dose insulin, diet or oral agents.

They may have to eventually go on higher doses of insulin

Developing Gestational Diabetes is a risk for all women, not just women who are overweight. 

These pts may require insulin until after the baby is born. 

If the body does not have insulin it can not use glucose for metabolism. 

Instead the body will use glycogen in the liver for fuel and eventually will metabolize free fatty acids to ketones.

Too many ketones-->ketonemia, ketouria and ketoacidosis

The body's high glucose levels make it easier for microorganisms to grow.

WBC activity is decreased

Diagnosing Diabetes

In terms of a 'casual plasma glucose' levels, what amount would be diagnostic of Diabetes?

A level of >200 mg/dL 

Diagnosing Diabetes:

What are the Fasting plasma glucose levels diagnostic of Diabetes?

1. Renal Failure

2. Myocardial infarction

Microalbuminuria-protein in the urine.

Kidney must be damaged if it is spilling protein into the urine. 

Diabetes causes accelerated atherosclerosis and decreased NO activity in the endothelium which results in thinner blood vessels. 

These complications lead to major risk of macrovascular disease

Diminished blood flow to the extremities can be seen by:

1. Leg pain relieved by rest

2. Cold feet/low pulse

3. Nocturnal leg pain relieved by dangling legs/walking

4. Loss of hair on foot/toes

Cataracts

Retinopathy

Glaucoma

AGE=Advanced Glycosylated End-products

Form when glucose levels in the blood are so high that lots of the proteins get glycated

There is increased Thromboxane A2 synthesis, which stimulates platelet adhesion.

Aspirin counteracts this process. 

Increased:

-Endothelial proliferation

-Angiogenesis

-Vascular permeability

1. Possible Hypoglycemia

2. Has to be injected

3. May cause weight gain

They have a longer duration of action than the others (24 hr control)

Also, they are more painful when injected than the others. 

NPH=Neutral Protamine Hagedorn

It is a mix of regular insulin with protamine zinc insulins. It causes the insulin to be bound to zinc.

This makes it so the insulin is absorbed more slowly and thus is longer acting

It is a synthetic Amylin analog.

Amylin is a substance that is normally secreted with insulin, it slows gastric emptying. 

It is given to DM1 and DM2 patients who need better control

Incretins are proteins in the body that promote a sense of satiety and also promote the release of insulin from the pancreas. 

GLp-1 is an Incretin

Gliptins are Dipeptidyl peptidase-4 inhibitors

ie. Gliptins block the enzymes that degrade Incretins.

This in turn stimulates the pancreas to secrete more insulin and causes decreased hepatic glucose production

Metformin is the #1 Biguanide

Also have Glucovance and Avandamet (which have metformin in them)

Meglitinide stimulates the release of insulin from functioning beta cells, but only in the presence of glucose. 

Once the glucose is depleted the drug is no longer active. 

Primary Hyperaldosteronism due to an aldosterone secreting adrenal adenoma

This is the most common form of Primary hyperaldosteronism