Cushing’s Syndrome
Cushing’s syndrome refers to the clinical manifestations induced by, chronic exposure to excess corticosteroid.
Basically, Pituitary corticotrope adenomas account for 70% of patients with endogenous causes of Cushing’s syndrome.
However, it should be emphasized that iatrogenic hypercortisolism is the most common cause of cushingoid features.
1.Firstly, ACTH excess i.e.: –
- Cushing’s disease Ectopic ACTH secretion
- Carcinoma of lung (especially small cell)
- Carcinoid tumors of either thymus or lung
- Medullary carcinoma of thyroid
- Carcinoma of colon
- Pheochromocytoma
2.Secondly, Non-ACT dependent i.e.: –
- Primary unilateral adrenocortical tumors (either adenoma or carcinoma)
- McCune-Albright syndrome: Bilateral tumor (e.g. Gsα mutation)
- Primary pigmented nodular dysplasia
3. Thirdly, ACTH – independent i.e.: –
- Macronodular adrenal hyperplasia Spontaneous Cushing’s syndrome
Obesity, type 2 diabetes and poorly regulated blood glucose levels (blood sugar and hypertension)
- The taking of corticosteroid medications (long-term use)
- Pituitary gland tumours
- A primary adrenal gland disease or benign nodular enlargements of the adrenal glands
- An ectopic ACTH-secreting tumour.
The pathophysiology of Cushing’s syndrome is linked to hypercortisolism which can develop by excess ACTH secretion or excess cortisol secretion by adrenal glands. The underlying mechanisms are usually genetic mutations or overexpression of proteins.
- Excess ACTH secretion
- The excess ACTH secretion can be due to the pituitary adenoma or ectopic (non-pituitary) ACTH secretion. ACTH stimulates the adrenal cortex to release cortisol and is not regulated by the feedback mechanism.
- Pituitary adenoma: Various gene mutations are involved in the development of pituitary adenoma commonly USP8, MEN1, CDKIs, and CDKN1B/p27Kip1. Many proteins are also overexpressed like Brg1, HDAC2, TR4, PTTG, and EGFR. It is the most important cause of ACTH-dependent cushing’s syndrome and is also called cushing’s disease. It is considered that the corticotroph tumors are resistant to glucocorticoid negative feedback inhibition which results in the pathological adrenal cortisol secretion.
- Ectopic ACTH secretion: The molecular defects in the neuroendocrine tumors leading to ectopic ACTH secretion from gastroenteropancreatic tumors are largely unknown. Germline menin mutations or RET oncogene mutations in multiple endocrine neoplasias (MEN) may be responsible. Ectopic secretion of ACTH can be seen as a manifestation of the paraneoplastic syndrome in small cell lung carcinoma and carcinoid tumors(bronchial and thymus).
- The excess ACTH secretion can be due to the pituitary adenoma or ectopic (non-pituitary) ACTH secretion. ACTH stimulates the adrenal cortex to release cortisol and is not regulated by the feedback mechanism.
- Excess secretion of cortisol by adrenal gland
- Excess secretion of the cortisol by the adrenal gland is due to the adrenal causes independent of ACTH secretion.
- Benign Adrenocortical adenoma: Common defects leading to adrenocortical adenoma are mutations or activation of the cAMP-dependent or β-catenin signaling pathways and aberrant expression and function of various G-protein-coupled receptors (GPCR).
- Adrenal cortical carcinoma It is associated with germline TP53 mutations and MEN syndrome.
- Bilateral adrenal hyperplasia: It is associated with MEN1, familial adenomatous polyposis, and fumarate hydratase gene mutations. Several inactivating mutations of armadillo repeat containing 5 genes (ARMC5, chromosome 16p11.2) are also identified.
- Excess secretion of the cortisol by the adrenal gland is due to the adrenal causes independent of ACTH secretion.
There are two types of Cushing’s syndrome.
Exogenous Cushing’s syndrome
Exogenous Cushing’s syndrome is when the cause comes from something outside the body’s function.
It often results from long-term, high-dose usage of corticosteroid drugs, also known as glucocorticoids. These are similar to cortisol.
Examples include:
- prednisone
- dexamethasone
- methylprednisolone
People with rheumatoid arthritis, lupus, asthma, and recipients of an organ transplant may need high doses of these drugs.
Injectable corticosteroids, a treatment for joint pain, back pain and bursitis, can also lead to Cushing’s syndrome.
Steroid medications that do not appear to increase the risk of Cushing’s syndrome are:
- steroid creams, a treatment option for eczema
- inhaled steroids, a treatment for asthma
The National Institute of Diabetes and Digestive and Kidney Diseases Trusted Source (NIDDK) note that over 10 million people in the United States use glucocorticoid medications each year, but it remains unclear how many develop the symptoms of Cushing’s syndrome.
Endogenous Cushing’s syndrome
Endogenous Cushing’s syndrome is when the cause comes from inside the body, for example, when the adrenal glands produce too much cortisol.
Cushing’s disease is an example of this.
Similar symptoms can also result from adrenal gland tumors or from a benign or malignant tumor in the pancreas, thyroid, thymus gland, or lung.
Body compartment/system | Signs and symptoms
|
Body fat – | Weight gain, central obesity, rounded face, fat pad on back of neck (in other words, “buffalo hump”) |
Skin – | Facial plethora, thin also brittle skin, easy bruising, broad also purple stretch marks, acne, hirsutism |
Bone – | Osteopenia, osteoporosis (especially, vertebral fractures), decreased linear growth in children |
Muscle – | Weakness, proximal myopathy(prominent atrophy of gluteal also upper leg muscles) either with difficulty climbing stairs or getting up from a chair |
Cardiovascular system – | Hypertension, hypokalemia, edema, additionally atherosclerosis |
Metabolism – | Glucose intolerance/diabetes, dyslipidemia |
Reproductive system – | Decreased libido, in women amenorrhea (due to cortisol-mediated inhibition of gonadotropin release) |
Central nervous system – | Irritability, emotional lability, depression, sometimes cognitive defects; occasionally, in severe cases, paranoid psychosis |
Blood and immune system – | Increased susceptibility to infections, increased white blood cell count, eosinopenia, hypercoagulation with increased risk of deep vein thrombosis also pulmonary embolism. |
Physical examination of patients with Cushing’s syndrome is as follows:
Appearance of the patient
- Patients with Cushing’s syndrome are usually overweight.
Vital signs
- Hypertension, due to cortisol’s enhancement of epinephrine’s vasoconstrictive effect.
Head
- Moon-face is a medical sign where the face swells up into a rounded shape. It is often associated with Cushing’s syndrome, which has led to it being known as Cushingoid facies (“Cushings-like face”), or steroid treatment, which has led to the name steroid facies.
Skin
- Hyperpigmentation – this is due to melanocyte stimulating hormone (MSH) production, as a byproduct of ACTH synthesis from Proopiomelanocortin (POMC)
- Telangiectasia (dilation of capillaries)
- Thinning of the skin (which causes easy bruising)
- Purple or red striae (the weight gain in Cushing’s 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)
Hirsutism (facial male-pattern hair growth)
Eye
- Bitemporal hemianopsia – pituitary lesion may cause compression of the optic chiasm.
Neck
- Growth of fat pads along the collar bone and on the back of the neck (known as lipodystrophy).
- Full blood count
- Urea and electrolytes – Hypokalaemia occurs with severe cortisol excess.
- Liver function test
- Bone profile
- Fasting glucose, lipids and glycosylated haemoglobin – Cardiovascular risk is greatly increased in Cushing’s syndrome. Annual risk assessment is therefore mandatory.
- Thyroid stimulating hormone
- Urinary free cortisol
- Low dose dexamethasone suppression test
- Hydroxyprogesterone
- Testosterone, androstenedione, dehydroepiandrosterone, sex hormone binding globulin
- Luteinising hormone, follicle stimulating hormone
- High dose dexamethasone suppression test
- In general, These tests may include increased 24-h urinary free cortisol excretion in three separate collections, failure to appropriately suppress morning cortisol after overnight exposure to dexamethasone, also evidence of loss of diurnal cortisol secretion with high levels at midnight, the time of the physiologically lowest secretion.
- Tests indicating cortisol overproduction i.e.-
- 24-hour urinary cortisol excretion
- Overnight dexamethasone suppression test
- Low-dose dexamethasone suppression test
- High-dose dexamethasone suppression test
- Corticotrophin-releasing hormone test
- There are no specific methods for prevention of Cushing’s disease.
- Awareness of the symptoms associated with this disease is found to be the most crucial element in order to identify and treat the problem in early stages.
- The treatment depends on the cause of the problem.
- Corticosteroid medications which have caused this syndrome are usually decreased under some medical supervision, while pituitary or adrenal tumor requires surgery.
- To enhance your recovery from this disease, doctors advise sensible eating, using nutritious and wholesome food, with plenty of calcium and vitamin D.
- Take care of your body and soothe aches and pains you might have, but increase your activities slowly.
- Monitor your mental health and if you happen to notice any signs of depression, don’t hesitate to consult your doctor.
- Your brain may also need some exercise, so engage in math problems or crosswords to recover and improve its function.
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Homeopathic Medicines for Cushing’s Syndrome
The homeopathic remedies (medicines) given below indicate the therapeutic affinity but this is not a complete and definite guide to the homeopathy treatment of this condition. The symptoms listed against each homeopathic remedy may not be directly related to this disease because in homeopathy general symptoms and constitutional indications also taken into account for selecting a remedy, potency and repetition of dose by Homeopathic doctor.
So, here we describe homeopathic medicine only for reference and education purpose. Do not take medicines without consulting registered homeopathic doctor (BHMS or M.D. Homeopath).
Medicine for Cushing’s Syndrome:
Calcarea carbonica:
- Fair, fat, flabby and perspiring also cold, damp and sour. Additionally, Apprehensive.
- Craving for indigestible things – chalk, coal, peanuts.; also, for eggs, salt also sweets. Milk disagrees.
- Ravenous hunger. Besides this, Repugnance to hot food. Wants cold drinks.
- All in all, Loss of appetite when overworked. Palpitation. Weakness. Worse – especially; at night, after eating.
Fucous vesiculosus:
- Especially indicated medicine “For obesity and non – toxic goiter.”
- Furthermore, Digestion is furthered and flatulence is diminished, Obstinate constipation.
- Forehead feels as if compressed by iron ring.
- Lastly, Thyroid enlargement in obese subjects.
Graphites:
- Generally, Stout, fair complexion with tendency to skin affections also constipation, fat, chilly and costive.
- Moreover, Tendency to obesity. Aversion to meat. Besides this, Sweets nauseate.
- Hot drinks disagree. Additionally, Burning in stomach causing hunger.
- Worse – warmth, night, during also after menstruation. On the other hand, Better – dark, from wrapping up.
Mercurious:
- Good medicine for Cushing’s Syndrome
- Bruised pain in small of back, especially when sitting. Tearing pain in coccyx, better pressing on abdomen.
- Extremities – Weakness of limbs, bone-pain alsonin limbs, worse night.
- Patient very sensitive to cold. Additionally, Oily perspiration.
- Trembling extremities, especially hands, paralysis agitans. Specifically, Lacerating pains in joints.
- Cold, clammy sweat on legs at night. Lastly, Dropsical swelling of feet also legs.
Phosphorus:
- Back- Burning in back; especially, pain as if broken, heat between the shoulder blades, Weak spine.
- Extremities- Weakness and trembling from every exertion.
- Can scarcely hold anything with hands. Tibia inflamed also becomes necrosed.
- Arms, hands become numb. All in all, Can lie only right side, joints suddenly give way.
Thyroidinum:
- Specifically indicated medicine for Cushing’s Syndrome
- Most importantly, Thyroid exercises a general regulating influence over the mechanism of the organs of nutrition, growth and development.
- Another key point is that, Thyroid weakness causes decided craving for large amounts of sweets.
- At last, Excessive obesity. Best with pale patients. Weak; tachycardia; Palpitation from least exertion.
Silicea:
- Back Weak spine, very susceptible to draughts on back. Additionally, Pain in coccyx, diseases of bones of spine.
Capsicum:
- Lax fiber, weak; diminished vital heat. Generally, Fat, indolent, opposed to physical exertion.
- General uncleanliness of body. Especially in Homesickness.
- Worse – while eating, from heat. Whereas; Better – open air, uncovering, draughts.
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- Reducing sodium intake
- Increasing calcium and vitamin D intake
- Reducing cholesterol
- Controlling blood sugar
- Reducing or eliminating alcohol and tobacco
[1] Medicine Golwala
[2] ABC Manual Of Materia Medica And Therapeutics (Therap Part) By Clarke G. H.
[3] https://www.healthline.com/health/cushings-syndrome#:~:text=Cushing%20syndrome%20can%20lead%20to,high%20blood%20pressure%20(hypertension).
[4]What risk factors are associated with Cushing’s syndrome? (mymed.com)
[5]Cushing’s syndrome pathophysiology – wikidoc
[6]Cushing’s syndrome: Causes, symptoms, types, and diagnosis (medicalnewstoday.com)
[7]Cushing’s syndrome diagnosis – investigation (endobible.com)
[8]Prevention of cushing’s disease | Healthy Living articles | Well Being center | SteadyHealth.com
What is Cushing’s Syndrome
Cushing’s syndrome refers to the clinical manifestations induced by, chronic exposure to excess corticosteroid.
Homeopathic Medicines used by Homeopathic Doctors in treatment of Cushing’s Syndrome
- Calcarea carbonica
- Fucous vesiculosus
- Graphites
- Mercurious
- Phosphorus
- Thyroidinum
- Silicea
- Capsicum
What are the symptoms of Cushing’s Syndrome
- Weight gain
- Central obesity
- Rounded face, fat pad on back of neck (in other words, “buffalo hump”)
- Facial plethora
- Thin also brittle skin
- Osteopenia, Osteoporosis
- Weakness
- Proximal myopathy
- Hypertension
- Hypokalemia
- Edema
- Atherosclerosis
- Irritability, Motional lability, also Depression
What are the causes of Cushing’s Syndrome
- Ectopic ACTH secretion
- Carcinoma of lung
- Carcinoid tumors of either thymus or lung
- Medullary carcinoma of thyroid
- Carcinoma of colon
- Pheochromocytoma
- adenoma
- McCune-Albright syndrome
- Primary pigmented nodular dysplasia
- Macronodular adrenal hyperplasia