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Medicine 101 Endocrinology Module Cortisol Physiology(review)

Topic – Cushing’s Syndrome Lecturer- Sasanga Rathnayake

Medicine 101 Endocrinology Module Cushing’s Syndrome Lecture content • •

Etiology & Pathophysiology Clinical correlate

• •

Investigations Management

Etiology& Pathophysiology • Exogenous – Chronic corticosteroid intake • Endogenous o ACTH-dependent  Cushing’s Disease  Ectopic ACTH secreting tumor o ACTH-independent  Adrenal adenomas  Adrenal carcinomas  Macro-nodular Adrenocortical Hyperplasia  Primary Pigment Nodular Adrenocortical Disease Clinical Correlates

Topic – Cushing’s Syndrome Lecturer- Sasanga Rathnayake

Medicine 101 Endocrinology Module Investigations 1. Investigations to establish Cushing’s syndrome • 24 hr urinary free cortisol • ONDST LDDST • Multiple Late-night salivary cortisol- to assess circadian rhythm 2. Investigations to determine underlying cause. • Plasma ACTH • High Dose ACTH suppression test • Inferior Petrosal sinus sampling • Imaging o Pituitary adenoma

o CT Chest -ACTH Ectopic

Topic – Cushing’s Syndrome Lecturer- Sasanga Rathnayake

Medicine 101 Endocrinology Module o Adrenocortical Adenoma

o Adrenocortical carcinomas

o AIMAH

Topic – Cushing’s Syndrome Lecturer- Sasanga Rathnayake

Medicine 101 Endocrinology Module o PPNAD

Management • Medical (limited use) o Metyrapone and Ketoconazole • Surgical (Main stay of Rx) o Cushing’s Disease  Trans Sphenoidal Approach- ACTH secreting pituitary adenomas

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External Pituitary irradiation

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Medical therapy- bromocriptine, cabergoline & cyproheptadine B/L adrenalectomy

ACTH Ectopic  Should be removed, if possible, most of the time mainstay of Rx is chemoradiation.  

o

Symptomatic control with Ketoconazole and Metyrapone B/L adrenalectomy may be considered,

ACTH-independent  

B/L or U/L adrenalectomy depending on the cause. Complication of B/L adrenalectomy -Nelson’s syndrome

Topic – Cushing’s Syndrome Lecturer- Sasanga Rathnayake

Medicine 101 Endocrinology Module 1. A 45-year-old man is diagnosed with Cushing’s disease. He undergoes a bilateral adrenalectomy and recovers well from the operation. One year later, he complains of a constant dull headache, peripheral visual disturbances and increasing pigmentation of the skin creases of both hands. The most likely diagnosis is: a) Ectopic ACTH secreting tumor b) Prolactinoma c) Nelson syndrome d) Addison’s disease e) Side effects from iatrogenic steroid intake 2. A28-year-old woman has noticed a change in her appearance; most notably her clothes do not fit properly and are especially tight around the waist. Her face appears flushed and more rounded than usual, despite exercising regularly and eating healthily her weight has steadily increased over the last 3 weeks. On visiting her GP, he notices her blood pressure has increased since her last visit and she has bruises on her arm. She is especially worried about a brain tumor. The most appropriate investigation would be: a. Low-dose dexamethasone test b. High-dose dexamethasone test c. Urinary catecholamines d. Computed tomography (CT) scan e. Urinary free cortisol measurement

3. Most reliable test for confirmation of pituitary ACTH secreting adenomas is a. 24-hour urine free cortisol b. Bilateral inferior petrosal sinus ACTH sampling c.

Overnight 1 mg dexamethasone suppression test

d. Basal plasma ACTH levels e. Late night salivary cortisol test 4. Which of the following is likely to be the most common cause for Cushing’s syndrome? a.

Pituitary corticotrope adenoma

b. Chronic asthmatic c. Ectopic tumor ACTH production d. Cortisol producing adrenal adenoma e. AIMAH

Sources 1. Kumar and Clark Clinical Medicine 10th edition. 2. Davidson’s Principle and Practice of Medicine 23rd edition 3. Harrison’s Manual of Medicine 19th edition 4. https://www.ncbi.nlm.nih.gov/books/NBK470218/Cushing’s Syndrome stat pearls

Topic – Cushing’s Syndrome Lecturer- Sasanga Rathnayake

Medicine 101 Endocrinology Module Case Study Mrs. A. a 35-year-old woman who presents to her GP complaining of a dull but persistent backpain, blurred and dimmed vision , menstrual abnormalities, both an excessive thirst and appetite. She also feels very depressed and does not have much energy and has stopped performing all the activities that she had previously enjoyed (Evening walks, shopping for new clothes) She is married, has a son and daughter and has been in relatively good health throughout her life. Her father is a cancer survivor of childhood leukemia, and her mother has a history of rheumatoid arthritis and lung cancer. The patient smokes and consumes alcohol in moderation at social functions only. She is not taking any medications other than a daily multivitamin tablet and celecoxib (as needed) for the back pain. O/E •

Significant facial hair growth with fullness of the face

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Skin shows localized areas of hyperpigmentation, thinning with bruising at the elbow crease

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Prominent muscle weakness in the right and left lower extremities

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CVS and RS – unremarkable

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Abdomen – Blue purple striae with marked increase of the waist hip circumference.

Investigations •

Hb – 14.4 g/dl

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N - 8.5 x 10 ^9/l

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L – 1.1 x 10^9/l

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M – 0.5 x 10^9/l

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E- 0.4 x 10^9/l

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S. Sodium-145 meq/l

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S. Potassium - 3.1 meq/l

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S. Chloride – 106 meq/l

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Arterial pH – 7.47

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UFC - 190 ug/24h

1. List the abnormalities in the investigation panel (5) 2. What is the most likely diagnosis for presenting symptoms (10) 3. What further investigations would you order to confirm your diagnosis in question 2 (15) 4. Outline the Mx for this patient (20)

Topic – Cushing’s Syndrome Lecturer- Sasanga Rathnayake...