Adrenal disorders 2

Adrenal Disorders - 2

Prof. Tariq Waseem

Prof. Tariq Waseem 104/15/2023

04/15/2023 Prof. Tariq Waseem 2

Mont NeboJordan

CASE SCENARIO

A 52 years old male was investigated for obesity of recent onset, polydipsia, and polyuria.

On examination, he had a B.P of 180/105mmhg and was obese, having purplish striae over the trunk and flanks.



Diagnosis?

Cushing’s Syndrome


Definition

A constellation of clinical abnormalities

due to chronic exposure to excess of

cortisol or related corticosteroid


Clinical Feature

Hypercotisolism

Lipid mobilization

Lipid catabolism

Lipid redistribution

Moon-face

buffalo hump

truncal obesity

Violaceous striae

Hepatic glucose production

Insulin resistance

Glucose intolerance

protein metabolism negative nitrogen balance

disruption of water and electrocytes metabolism

Proximal muscle weaknessDependent edema

Hypertension

Hypokalemic metabolic alkalosis


CLINICAL FEATURES OF GLUCOCORTICOID EXCESS

Frequency(%)

Weight gain 90“Moon facies” 75Hypertension 75

Violaceous striae 65Hirsutism 65Glucose intolerance 65Proximal muscle weakness 60Plethora 60Menstrual dysfunction 60Acne 40Easy bruising 40Osteopenia 40Dependent edema 40Hyperpigmentation 20Hypokalemic metabolic alkalosis 15




FIGURE . Multiple wide striae on the abdomen of a patient with Cushing's disease.


When stimulated by ACTH, the adrenal gland secretes cortisol and other steroid hormones. ACTH is produced by the pituitary gland and released into the petrosal venous sinuses in response to stimulation by corticotropin-releasing hormone (CRH) from the hypothalamus


Etiology and Pathophysiology

ACTH-dependent causes

ACTH-secreting pituitary tumor ( Cushing’ s disease )

Pituitary CRH-secreting neoplasm ( ectopic CRP syndrome )

Nonpituitary ACTH-secreting neoplasm ( ectopic ACTH syndrome )



ACTH-independent causes Adrenal adenoma

Adrenal carcinoma

Micronodular adrenal disease

McCune-Albright syndrome

Massive macronodular adrenal diease



Pseudo-cushing Syndrome

Factitious or surreptitious glucocorticoid administration


COMMON CAUSES OF ECTOPIC ACTH SECRETION

Small cell carcinoma of the lung 50%

Endocrine tumors of foregut origin 35%

Thymic carcinoid

Islet cell tumor

Medullary carcinoma thyroid

Bronchial carcinoid

Pheochromocytoma 5%

Ovarian tumors 2%


Diagnosis

Clinical manifestations

Lab findings

– Plasma cortisol and rhythm (RIA)

– Urinary free cortisol

17-hydroxycortisteriod

17-ketosteriods

– Plasma ACTHProf. Tariq Waseem 1704/15/2023

Suppression tests

Screening test

– 1mg DX P.O at midnight

– Plasma cortisol (PF) at 7-8 am next day

– PF suppressed: Normal

– PF NOT suppressed: Cushing’ s Syndrome


Suppression tests

Low dose DX suppression test

– DX 0.5 mg q6h P.O 2 days

– Urinary free cortisol decreased: Normal

– Urinary free cortisol NOT decreased:

Cushing’ s Syndrome


Suppression tests

Large dose DX suppression testD.X 2mg q6h P.O 2 days

Urinary free cortisol reduced 50%:

Cushing’s disease (Pituitary adenoma)

Urinary free cortisol NOT reduced 50%:

Adrenal tumor,

Carcinoma,

Eectopic ACTH SyndromeProf. Tariq Waseem 2004/15/2023

ACTH Stimulation test

ACTH 25u intravenously 8h2-5 fold increase in urinary free cortisol

in Cushing’ s diseasePlasma cortisol and urinary free cortisol

increase in half of adrenal adenoma patients

No response in adrenal carcinomaProf. Tariq Waseem 2104/15/2023

CRH stimulation test Etiology diagnose (especially for pituitary ACTH-

dependent or ectopic ACTH syndrome) A newer approach is to combine a CRH stimulation test

with a dexamethasone suppression test(4mg ). method :

1 µg / kg of CRH is administered intravenously.

ACTH and cortisol levels are measured before CRH injection and 15, 30, 45, 60, 90 and 120 minutes after injection.

A rise in the cortisol value of 20 percent or more above basal level or a rise in the ACTH value of at least 50 percent above basal level is considered evidence for an ACTH-dependent lesionProf. Tariq Waseem 2204/15/2023

Metyrapone Test

Etiology diagnose (especially for pituitary or adrenal)

– Metyrapone 2-3g (30mg/kg) P.O at midnight

– Urinary 17-OHCS, Plasma ACTH,11-deoxycortisol

more above basal level : Cushing’s disease

(Pituitary adenoma)

– No response in adrenal carcinoma , tumor, ectopic

ACTH Syndrome


Imaging diagnosis

Pituitary CT has a sensitivity of about 50% for identifying microadenomas

MRI has increased sensitivity but is not 100% predictive


Imaging diagnosis

If diagnostic doubt need bilateral inferior petrosal sinus sampling for ACTH


Imaging diagnosis


Adrenal ultrasonography---first choiceAbdominal CT will allow identification of adrenal pathology

Imaging diagnosis

Somatostatin scintigraphy to identify sites of ectopic hormone production



Etiological diagnosis Cushing’ s disease:

Adrenal adenoma:

Adrenal carcinoma:

Ectopic ACTH Syndrome:

Chronic, moderate clinical features can be suppressed by large dose test

Shorter course , mild features can NOT be suppressed by large dose test

Acute onset, progressive course, hyperandrogenic effect predominate, palpable mass, low ACTH

Appear suddenly, progress rapidly, not typical manifestation of Cushing’s syndrome, hyperpigmentation, hypokalemia, high ACTH


Differential diagnosis Simple obesity

– General obesity, long history, over nourished– Narrow and short striae– Urinary free cortisol can be suppressed by screening ( overnight )

test and/or low-dose DX suppression test– Normal diurnal rhythm, almost normal plasma cortisol

Type 2 DM– Normal plasma cortisol and rhythm– Once blood glucose controlled, urinary free cortisol turns to normal

Alcoholic Cushingnoid Syndrome– No drinking for one week, plasma cortisol and urinary free cortisol

become normal

Depression – Lack of clinical manifestation of Cushing’s SyndromeProf. Tariq Waseem 3004/15/2023

Treatment Cushing’s disease

– Transsphenoidal microadenomectomy– Pituitary radiation– Bilateral total adrenolectomy– Drugs

Adrenal adenoma and carcinoma– Surgical removal– Drugs ( mitotane, metyrapone, ketoconazole ) for

nonresectable or metastatic carcinoma Ectopic ACTH Syndrome

– Surgical removal of the ectopic tumor– Chemotherapy, radiotherapy– Drugs ( mitotane, metyrapone, ketoconazloe )


MANAGEMENT

CUSHING’s DISEASE :

Surgical treatment :Trans –sphenoidal surgery for elective

removal of pituitary adenoma


CONTINUED

BILATERAL ADRENALECTOMY :If bilateral adrenalectomy is done for

pituitary adenoma dependant cushings syndrome it may lead to excessive growth of the adenoma due to lack of negative feed back provided by raised cortisol this may lead to nelson’s syndrome


NELSON ‘s SYNDROME

Aggressive pituitary macroadenoma and very high ACTH levels causing pigmentation

Nelson ‘s syndrome can be prevented by pituitary irradiation


ADRENAL TUMOURS

ADRENAL ADENOMA :Laproscopic removal

ADRENAL CARCINOMA :Resection and irradiation of the

carcinoma followed by cytotoxic chemotherapy


ECTOPIC ACTH SYNDROME

Localized tumours causing this syndrome should be removed for example bronchial carcinoid


Medical therapy of Cushing’ s Disease

Purpose

– Correct metabolic abnormalities before

attempted surgical cure

– Palliate surgically noncurable disease

– Achieve remission in patients for whom

surgery is unlikely to achieve satisfactory

long term results


Steroidogenic inhibition– Mitotane ( OP’-DDD – Metyrapone – Aminoglutethimide – Ketoconazole

Neuromodulatory treatment– Bromocriptine – Cyproheptadin– Valproic acid – Octreotide

– Glucocorticoid receptor antagonist– RU486



CASE SCENARIO No.2

A 34 years old female presented to the opd with the complains of increasing body weight over the past few months along with complains of headache over past 1 month

On examination she is found to be hypertensive ,and some black velvety discoloration was noticed around her neck and also in her armpits.


DIAGNOSIS

?


CASE SCENARIO No.3

A 36 years old female was referred with oligomenhorrea and hirsitism and weight gain. She has also noticed excessive hair on her face,arms and legs. She has been on Hakim medication for Asthma.

On examinaion she has excessive acne and facial hair.

Her BP is 160/100 mmhg.Prof. Tariq Waseem 4204/15/2023


DIAGNOSIS

?



Dead SeaJordan

Health & Medicine

Adrenal disorders 2