Obesity Management Hypercortisolism (Cushing's syndrome)

Obesity Management Hypercortisolism (Cushing's syndrome)

Cushing's syndrome describes the signs and symptoms associated with prolonged exposure to inappropriately high levels of the hormone cortisol. This can be caused by taking glucocorticoid drugs, or diseases that result in excess cortiso, adrenocorticotropi hormone (ACTH, or CRH levels.

Cushing's disease refers to a pituitary-dependent cause of Cushing's syndrome: a tumor (adenoma) in the pituitary gland produces large amounts of ACTH, causing the adrenal glands to produce elevated levels of cortisol. It is the most common non-iatrogenic cause of Cushing's syndrome, responsible for 70% of cases excluding glucocorticoid related cases. An easy way to distinguish Cushing's syndrome from Cushing's disease is that the measured ACTH levels are lower in the former. The decrease in ACTH is due to increased negative feedback of cortisol on the hypothalamus and anterior pituitary.

-:In summary:-

01. Rapid weight gain

02. Moodiness, irritability, or depression

03. Muscle and bone weakness

04. Memory and attention dysfunction

05. Osteoporosis

06. Diabetes mellitus

07. Hypertension

08. Immune suppression

09. Sleep disturbances

10. Menstrual disorders such as amenorrhea in women and decreased fertility in men

11. Hirsutism

12. Hair loss.

13. Hypercholesterolemia.

Signs and symptoms :-

01. Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). Common signs include the growth of fat pads along the collarbone, on the back of the neck or "buffalo hump" and on the face "moon facies". Other symptoms include hyperhidrosis(excess sweating), telangiectasia (dilation of capillaries), thinning of the skin (which causes easy bruising and dryness, particularly the hands) and other mucous membranes, purple or red striae (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth), baldness and/or extremely dry and brittle hair. In rare cases, Cushing's can cause hypocalcaemia. The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, inhibited aromatase, reduced libido, impotence in men, amenorrhoea/oligomenorrhe  and infertility in women due to elevations in androgens. Studies have also shown that the resultant amenorrhea is due to hypercortisolism, which feeds back onto the hypothalamus resulting in decreased levels of GnRH release.

02. Cognitive conditions, including memory and attention dysfunctions, as well as depression are commonly associated with elevated cortisol and may be early indicators of exogenous or endogenous Cushing's. Patients frequently suffer various psychological disturbances, ranging from euphoria to psychosis. Depression and anxiety are also common. Other striking and distressing skin changes that may appear in Cushing's syndrome include facial acne, susceptibility to superficial dermatophyte and malassezia infections, and the characteristic purplish, atrophic striae on the abdomen

03. Other signs include polyuria (and accompanying polydipsia), persistent hypertension (due to cortisol's enhancement of epinephrine’s vasoconstrictive effect) and insulin resistance (especially common in ectopic ACTH production), leading to hyperglycemia (high blood sugar) and insulin resistance which can lead to diabetes mellitus. Insulin resistance is accompanied by skin changes such as acanthosis nigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cortisol can also exhibit mineralcorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion). Furthermore, excessive cortisol may lead to gastrointestinal disturbances, opportunistic infections and impaired wound healing related to cortisol's suppression of the immune and inflammatory responses. Osteoporosis is also an issue in Cushing's syndrome since osteoblast activity is inhibited. Additionally, Cushing's syndrome may cause sore and aching joints, particularly in the hip, shoulders, and lower back.

04. Cushing’s syndrome includes all the causes of increased cortisol leading to the diseased state. Cushing’s disease is a specific type of Cushing’s syndrome caused by a pituitary tumor leading to excessive production of ACTH (Adrenocorticotropic hormone). Excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol, producing the disease state. Cushing's disease 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). A variant of Cushing's disease can be caused by ectopic, i.e. extra-pituitary, ACTH production from for example a small cell lung cancer. When Cushing's syndrome is caused by an increase of cortisol at the level of the adrenal glands (via an adenoma or hyperplasia), negative feedback ultimately reduces ACTH production in the pituitary. In these cases, ACTH levels remain low and no hyperpigmentation develops. While all Cushing’s disease is Cushing’s syndrome, not all Cushing’s syndrome is Cushing’s disease.

Causes Exogenous vs. endogenous:- 

The most common cause of Cushing's syndrome is exogenous  administration of glucocorticoids prescribed by a health care practitioner to treat other diseases (called iatrogenic Cushing's syndrome). This can be an effect of corticosteroid treatment of a variety of disorders such as asthma and rheumatoid arthritis  or in immunosuppression after an organ transplant. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Although rare, Cushing's syndrome can also be due to the use of medroxyprogesterone. In this form of Cushing's, the adrenal glands atrophy due to lack of stimulation by ACTH, since glucocorticoids downregulate production of ACTH. Cushing syndrome in childhood usually results from use of glucocorticoid medication

Pseudo-Cushing's syndrome :-

Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone, leading to Pseudo-Cushing's syndrome. Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated. However, the total free cortisol, which is the active hormone in the body, as measured by a 24 hour urine collection for urinary free cortisol, is normal

Diagnosis:- 

When Cushing's syndrome is suspected, either a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offer equal detection rates. Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, cortisol levels >50nmol/L (1.81 µg/dL) would be indicative of Cushing's syndrome because there is an ectopic source of cortisol or ACTH (such as adrenal adenoma) that is not inhibited by the dexamethasone. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which may be equally sensitive, as late night levels of salivary cortisol are high in Cushingoid patients. Other pituitary hormone levels may need to be ascertained. Performing a physical examination to determine any visual field defect may be necessary if a pituitary lesion is suspected, which may compress the optic chiasm causing typical bitemporal hemianopia.

Cushing’s Syndrome :- 

C - Central obesity, Clavical fat pads, Collagen fiber weakness, Comedones (acne).

U - Urinary free cortisol and glucose increase.

S - Striae, Suppressed immunity.

H - Hypercortisolism, Hypertension, Hyperglycemia, Hypercholesterolemia, Hirsutism, Hypernatremia, Hypokalemia.

I - Iatrogenic (Increased administration of corticosteroids).

N - Noniatrogenic (Neoplasms).

G - Glucose intolerance, Growth retardation.

Treatments ;-

Pl Referred to client immediately to  Respected Endocrinologist & Touch with Dr. Always.