Cushing’s Syndrome

Monica Majillo, Ruilian Ma, Karl Lorenzo, Meei-Shyuan Liao

OBJECTIVES

Discuss the function of cortisol

Analyze the synthesis of cortisol

Describe the HPA axis

Analyze the effects of cortisol on different organs

Define Cushing’s Syndrome

Explain clinical manifestations of Cushing’s Syndrome

LAYERS OF THE
ADRENAL GLAND
CORTISOL aka HYDROCORTISONE

A steroid hormone

Main glucocorticoid

Functions:

Stress response

Regulating metabolism

Inflammatory response

Immune function
SYNTHESIS OF CORTISOL
Hypothalamo-Pituitary-Adrenal Axis
Cortisol’s effect on the following organs

ADIPOSE TISSUE - increases amount of free fatty acid

BONE - decreases osteoblastic activity

SKELETAL MUSCLE - degrades contractile proteins to free amino acids

LIVER - increase in gluconeogenesis

PANCREAS - increases glucagon levels

 4. Enumerate the manifestations of Cushing’s Syndrome and identify which were seen in the
patient

---fat redistribution
---skin
---osteoporosis
---hypertension
---hyperglycemia
---Erectile dysfunction
---polyuria
---myopathy
---hypokalemia and alkalosis
5. Explain the clinical manifestations seen in the patient:

1. effect of cortisol on fat metabolism

(1) Lipogenesis: Causes some fat deposition on the central portions of the body →central obesity
---Only the central parts are affected
---pendulous abdomen
---Moon facies
--- Buffallo Hump
(2) Lipolysis: Due to fat mobilization from the extremities coupled by amino acid mobilization
---Thin extremities
5. Explain the clinical manifestations seen in the patient:

2. effects on skin and connective tissue

➢ Collagen synthesis ↓(thinning of the skin and walls of the capillaries)

---Proteins are also metabolized, in that the patient will have a stretch mark.

---The amino acids in the collagen are actually lost resulting to very

fragile connective tissue and formation of stria

➢ Leads to Intracutaneous hemorrhage

5. Explain the clinical manifestations seen in the patient:

---Cushing's syndrome due to excess ACTH may also result in hyperpigmentation.

---This is due to melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis

from pro-opiomelanocortin (POMC).
5. Explain the clinical manifestations seen in the patient:

Female-pattern hair loss:

(1) Female balding in Cushing's syndrome results from androgen hypersecretion that
occurs in ACTH-dependent forms (i.e., pituitary or ectopic ACTH tumors)
(2) Androgenetic alopecia, often referred to as female-pattern hair loss (FPHL), is a
nonscarring form of hair loss in which the growth (anagen) phase of hair follicles
is shortened resulting in follicular miniaturization
 Discuss diagnostics for Cushing’s Syndrome

1. Screening tests
(1) ↑ free cortisol on 24-hr urinalysis.
(2) ↑ late night salivary cortisol.
(3) No suppression with overnight low-dose (1 mg) dexamethasone
test
2. Establish the Cause of Hypercortisolism:
- ACTH testing is the best initial test to determine the cause (source) or location of
hypercortisolism
Discuss diagnostics for Cushing’s Syndrome
 Discuss treatment and rationale for Cushing’s Syndrome

---Surgically remove the source of the

hypercortisolism.

---Transsphenoidal surgery is done for pituitary

sources

--- laparoscopic removal is done for adrenal sources.

Discuss treatment and rationale for Cushing’s Syndrome

--- If surgery is not successful, use pasireotide,

which is a somatostatin analog. ---Pasireotide
controls unresectable pituitary ACTH
overproduction.

--- Unresectable adrenal tumors are treated

with ketoconazole or metyrapone
5. Explain the clinical manifestations seen in the patient:

a. Easy bruising after minimal injury:

b. Facial plethora
c. Female-pattern hair loss
d. Hyperpigmentation
e. Purple (violaceous) striae: Because in the skin, there are connective tissues there and when there is
degradation of proteins, collagen will weaken

f. Truncal, facial, and nuchal adiposity :