Endocrine surgery · KIMS Secunderabad
Cushing's Syndrome — When Too Much Cortisol Damages the Body
Cushing's syndrome describes the clinical state of chronic cortisol excess — from any cause. Cortisol is the primary glucocorticoid hormone, produced by the adrenal cortex under stimulation from ACTH (adrenocorticotropic hormone) released by the pituitary. In normal physiology, cortisol regulates metabolism, immune function, and the stress response. Chronic cortisol excess disrupts virtually every metabolic system — causing the characteristic clinical features of Cushing's syndrome and substantially increasing the risks of diabetes, hypertension, cardiovascular disease, osteoporosis, and infections.
Cushing's syndrome is uncommon but frequently diagnosed late — the gradual weight gain, hypertension, and mood changes that characterise it are attributed to lifestyle and ageing for months to years before the diagnosis is considered. The most important initial distinction is between exogenous Cushing's (from prescribed steroids — by far the most common cause) and endogenous Cushing's (from the body's own excess cortisol production), and between ACTH-dependent and ACTH-independent endogenous disease.
Causes
Exogenous (iatrogenic) — prolonged steroid use
Prolonged steroid use (prednisolone, dexamethasone, inhaled or topical steroids in excess). ACTH status: Low ACTH. Frequency: Most common overall. Treatment: gradual steroid tapering under medical supervision — never stop abruptly.
Cushing's disease — ACTH-secreting pituitary adenoma
ACTH status: High ACTH. Frequency: 65–70% of endogenous cases. Treatment: transsphenoidal pituitary surgery (neurosurgery). Medical therapy (ketoconazole, metyrapone) while awaiting surgery.
Ectopic ACTH syndrome
ACTH from a non-pituitary tumour (small cell lung cancer, bronchial carcinoid, thymic carcinoid). ACTH status: High ACTH. Frequency: 10–15% of endogenous cases. Often severe and rapidly progressive. Treatment: resect the ACTH-secreting tumour; bilateral adrenalectomy if the source cannot be controlled.
Adrenal adenoma (cortisol-secreting)
ACTH status: Low ACTH. Frequency: 10–15% of endogenous cases. Treatment: laparoscopic or robotic adrenalectomy at KIMS — curative.
Adrenal carcinoma (ACC)
Rare but important — ACC may secrete cortisol. ACTH status: Low ACTH. Treatment: open adrenalectomy + mitotane.
Bilateral adrenal hyperplasia (macronodular or micronodular)
ACTH status: Low ACTH. Frequency: Rare. Treatment: bilateral adrenalectomy in severe cases.
Clinical features — the Cushing's phenotype
Central obesity — fat redistribution to the abdomen, face (moon face), and upper back (buffalo hump) with relative sparing of the extremities.
Skin changes — purple striae (stretch marks, typically above 1cm wide — distinguishing from physiological striae) on the abdomen, thighs, and breasts. Skin thinning and easy bruising. Poor wound healing.
Hypertension — cortisol activates mineralocorticoid receptors, causing sodium retention.
Diabetes mellitus or glucose intolerance — cortisol promotes gluconeogenesis and insulin resistance.
Proximal muscle weakness — difficulty rising from a chair, climbing stairs. Wasting of thigh and upper arm muscles.
Osteoporosis — cortisol inhibits bone formation and promotes bone resorption.
Psychiatric features — depression, anxiety, emotional lability, cognitive impairment.
Hypogonadism — cortisol suppresses GnRH, causing menstrual irregularity in women and reduced testosterone in men.
Immune suppression — increased susceptibility to infection, particularly fungal and opportunistic infections.
Diagnosis — confirming cortisol excess
24-hour urinary free cortisol (UFC)
Measures total cortisol output over 24 hours. Three-fold or more elevation above the upper limit of normal confirms hypercortisolism. Two collections required.
Late-night salivary cortisol
Cortisol normally reaches its lowest level between 11pm and midnight. In Cushing's syndrome, this nocturnal nadir is lost. Elevated late-night salivary cortisol on two occasions confirms the loss of circadian cortisol rhythm.
Overnight 1mg dexamethasone suppression test (DST)
1mg dexamethasone given at midnight — morning cortisol should be suppressed below 50 nmol/L in normal individuals. Failure to suppress confirms autonomous cortisol production. High sensitivity (95%) for screening.
ACTH measurement
After confirming hypercortisolism, plasma ACTH distinguishes ACTH-dependent (high ACTH — pituitary or ectopic) from ACTH-independent (low/suppressed ACTH — adrenal adenoma, carcinoma, or bilateral hyperplasia) disease.
Adrenal CT / pituitary MRI
CT of the adrenals for ACTH-independent Cushing's (identifies the adrenal tumour). MRI of the pituitary for Cushing's disease (identifies the pituitary adenoma — often a microadenoma below 5mm requiring a specific protocol pituitary MRI with gadolinium).
Treatment — adrenal cause
When Cushing's syndrome is caused by a unilateral adrenal cortisol-secreting adenoma, laparoscopic or robotic adrenalectomy at KIMS is curative. The contralateral adrenal gland, suppressed by the excess cortisol, takes 6 to 18 months to recover normal function — during which time the patient requires hydrocortisone replacement therapy to avoid adrenal insufficiency. This cortisol taper is carefully managed by the KIMS team after surgery.
After adrenalectomy for Cushing's syndrome, patients must carry a steroid emergency card and know to double or triple their hydrocortisone dose during illness, surgery, or significant physical stress — adrenal insufficiency during these periods is life-threatening if not treated promptly.
Book a Cushing's Syndrome Assessment at KIMS
Frequently Asked Questions — Cushing's Syndrome
No — Cushing's disease is a specific cause of Cushing's syndrome. Cushing's syndrome is the general term for the clinical state of cortisol excess — from any cause (exogenous steroids, adrenal tumour, pituitary tumour, or ectopic ACTH). Cushing's disease specifically refers to Cushing's syndrome caused by an ACTH-secreting pituitary adenoma — the most common endogenous cause (65 to 70% of cases). The distinction matters because the treatment is different: Cushing's disease is treated by transsphenoidal pituitary surgery (neurosurgery), while adrenal Cushing's is treated by adrenalectomy.
Yes — exogenous Cushing's syndrome from prescribed steroids is the most common form of Cushing's syndrome overall, far more common than endogenous disease. Any systemic steroid (prednisolone, methylprednisolone, dexamethasone) taken at significant doses for more than a few weeks can cause Cushing's features. Even high-dose inhaled steroids (for asthma) or prolonged topical steroids absorbed through thin skin can contribute. The management is gradual steroid tapering — never abrupt cessation, which causes adrenal insufficiency because the hypothalamic-pituitary-adrenal axis has been suppressed.
Recovery from the surgery itself is rapid with robotic adrenalectomy — 1 to 2 nights in hospital, return to light activity within 1 to 2 weeks. However, recovery from the Cushing's state takes significantly longer. After removal of a unilateral cortisol-secreting adenoma, the suppressed contralateral adrenal gland takes 6 to 18 months to recover normal function. During this recovery period, hydrocortisone replacement therapy is required. The clinical features of Cushing's — weight, skin changes, muscle weakness, mood — gradually improve over 6 to 18 months as cortisol normalises. Bone density recovery continues for 2 to 3 years.
Yes — frequently. The gradual onset of weight gain, hypertension, diabetes, and mood changes is attributed to lifestyle and ageing in many patients for 2 to 5 years before Cushing's syndrome is considered. Clues that should prompt testing: hypertension and diabetes in a relatively young person without other risk factors, easy bruising and purple striae, proximal muscle weakness (difficulty rising from a chair), osteoporosis in a younger person, or any combination of the above. A single overnight 1mg dexamethasone suppression test performed at home (blood test the following morning) screens for Cushing's efficiently.
KIMS Secunderabad — Dr. Likhiteswer Pallagani (robotic adrenalectomy, 400+ cases), complete Cushing's workup (24h UFC, late-night salivary cortisol, 1mg DST, ACTH, CT adrenal), hydrocortisone replacement protocol, neurosurgery coordination for Cushing's disease. Da Vinci Xi AND X. NABH and NABL accredited. Call 040-4488-5000.