Adrenocorticotropic Hormone Insufficiency

Osteoporosis

Inhibits Vitamin D absorption-> inhibit calcium absorption-> Osteoporosis

(Cushing Syndrome)

Anti inflammatory effect

Immunosuppression

Catabolism and anti anabolic effects

– Supraphysiologic amounts:

(Cushing Syndrome)

Decrease muscle mass, peripheral fats, weakness and thinning of the skin

inhibits macrophage, and antigen presenting cells

Immunosuppression:

suppresses inflammatory cytokines, chemokines and inflammatory mediators

Anti inflammatory effect:

Insomnia and euphoria

Nervous system:

– Initial:

depression

Nervous system:

Chronic:

Large doses: Inc. Intracranial pressure

(pseudotumor cerebi)

buffalo humps

Facial, nuchal and supraclavicular fats

For fetal lung formation and production of

pulmonary surfactants

Effects on infant

Primary adrenal insufficiency (Addison disease)

Most often involves the destruction of all

regions of the adrenal cortex. There are

deficiencies of cortisol, aldosterone, and

the various androgens, and levels of CRH

and ACTH increase in a compensatory

manner.

Autoimmune dysfunction

Responsible for 80% to 90% of cases in

developed countries, whereas

tuberculosis is the predominant cause in

developing countries

Secondary adrenal insufficiency

from exogenous corticosteroid use, leading

to suppression of the hypothalamic-pituitary-

adrenal axis

– decreased ACTH release, resulting in

impaired androgen and cortisol production

Mirtazapine and progestins (eg,

medroxyprogesterone acetate, megestrol

acetate)

induce secondary adrenal insufficiency.

Secondary disease typically presents with normal

mineralocorticoid concentrations.

Congenital adrenal hyperplasia

Defect in 11b hydroxylase

Defect in 17 a hydroxylase

Adrenocortical hypo and hyperfunction

Hypogonadism

Defect in 17 a hydroxylase

Hypogonadism

Increase 11 deoxy corticosterone

– Inc. BP and hypokalemia

Decrease aldosterone production

• Hypertension with o without hypokalemic alkalosis

Defect in 11b hydroxylase:

Congenital adrenal hyperplasia

Defect in 21b hydroxylase

Congenital adrenal hyperplasia

Defect in 21b hydroxylase: dec. cortisol synthesis,

increased androgen production

• Virilization

– Development in male pattern hair growth and physical traits

Short cosyntropin stimulation test

assess patients with suspected hypocortisolism

– increase to a cortisol level of 18 mcg/dL or more (500 nmol/L)

400 to 2000 pg/mL (88 to 440 pmol/L)

Plasma ACTH levels

• Primary insufficiency

normal to low (5–50 pg/mL [1.1–11 pmol/L])

Plasma ACTH levels

Secondary insufficiency

– Weakness

– Fatigue

– Weightloss

– Hypotension

– Hyperpigmentation

– Inability to maintain blood glucose level during fasting

Addison’s disease

Waterhouse-Friderichsen Syndrome

adrenal gland failure due to

bleeding into the adrenal

glands, commonly caused by

severe bacterial infection.

Typically, it is caused

by Neisseria meningitidis

Neisseria meningitidis

Waterhouse-Friderichsen

Syndrome

adrenal gland failure due to

bleeding into the adrenal

glands, commonly caused by

severe bacterial infection.

Typically, it is caused

by

Waterhouse-Friderichsen

Syndrome

Rapidly progressive

hypotension leading to

shock

Waterhouse-Friderichsen

Syndrome

Disseminated intravascular

coagulation (DIC)

Waterhouse-Friderichsen

Syndrome

Rapidly developing

adrenocortical insufficiency

associated with massive

bilateral adrenal

haemorrhage

20-30 mg hydrocortisone daily with increased amounts during stress

– Synthetic glucocorticoids that are long acting W/O salt retaining activity SHOULD NOT BE GIVEN

Treatment

• Primary adrenal insufficiency:

– Immediate treatment

– Parenteral (IV) hydrocortisone sodium succinate or phosphate 100mg IV Q8H until stable

– Reduce dose gradually to achieve maintenance dose within 5 days

– Salt retaining hormone is resumed when the total hydrocortisone dosage has been reduced to 50mg/da

Treatment

• Acute adrenocortical insufficiency

Ceftriaxone

– Hydrocortisone: sometimes for reversal of

adrenal insufficiency

– Amputation

– Reconstructive surgery

– Tissue grafting

Treatment:

• Waterhouse-Friderichsen Syndrome

Inform patients of treatment

complications, expected outcomes,

proper medication administration and

adherence, and possible side effects

• Patients with adrenal insufficiency

should carry a card or wear a bracelet

or necklace that contains information

about their condition.

Non pharmacologic Treatment

Endogenous Cushing Syndrome

Chronic prolonged exposure to high level

of cortisol

Endogenous Cushing Syndrome

Endogenous glucocorticoid

overproduction hypercorticolism may be

dependent or independent of ACTH

Endogenous Cushing Syndrome

Caused by low negative feedback to

pituitary corticotropic cells from a high

level of serum cortisol

Endogenous Cushing Syndrome

Elevated ACTH levels may be due to anterior pituitary tumor

Osilodrostat

beta hydroxylase inhibitor

Pasireotide

Somatostatin analogs

Metyrapone, ketoconazole, etomidate

Adrenal Steroid inhibitor

Mifepristone

Glucocorticoid receptor antagonist

Mitotane

Adrenolytic agents

adrenalectomy

Surgical removal of the tumor

Dexamethasone suppression test
• MRI of the pituitary

Diagnosis

Fatigue

– Depression

– Visual field defect and blurring of vision

Neuro

Adrenal crisis

Emergency situation

– May be due to patients on steroids who

suddenly stopped taking the medication

Endogenous Cushing Syndrome

Chronic prolonged exposure to high level

of cortisol

Endogenous Cushing Syndrome

Endogenous glucocorticoid

overproduction hypercorticolism may be

dependent or independent of ACTH

Endogenous Cushing Syndrome

Caused by low negative feedback to

pituitary corticotropic cells from a high

level of serum cortisol

Endogenous Cushing Syndrome

Elevated ACTH levels may be due to

anterior pituitary tumor

Probenazole

Most potent topical corticosteroid

– Ceftriaxone

– Hydrocortisone: sometimes for reversal of adrenal insufficiency

– Amputation

– Reconstructive surgery

– Tissue grafting

Treatment:

• Waterhouse-Friderichsen Syndrome

– Immediate treatment

– Parenteral (IV) hydrocortisone sodium

succinate or phosphate 100mg IV Q8H

until stable

– Reduce dose gradually to achieve

maintenance dose within 5 days

– Salt retaining hormone is resumed when

the total hydrocortisone dosage has been

reduced to 50mg/day

Treatment

• Acute adrenocortical insufficiency

20-30 mg hydrocortisone daily with

increased amounts during stress

– Synthetic glucocorticoids that are long

acting W/O salt retaining activity SHOULD

NOT BE GIVEN

Treatment

• Primary adrenal insufficiency: