Sunday, 3 January 2010

Cushing's Syndrome in Pregnancy

Excellent Powerpoint on Cushing's syndrome


(i)adrenal adenoma-disproportionately more common in pregnancy(40-50% Vs 17-19%)

(iii)ectopic ACTH

Clinical features

(I) Weight gain
(II) Hypertension
(III)Glucose intolerance
(IV)Purple striae

The above features aren't uncommon in pregnancy.

(V)Proximal myopathy

Changes in normal pregnancy

raised (i)total cortisol (ii)free cortisol levels (iii) urinary cortisol (iv) cortisol binding globulin

Corticotropin releasing hormone is secreted by placenta.

How does Cushing's Syndrome affects pregnancy?

(I) In untreated Cushing's syndrome hypothalamic pituitary axis is suppressed,so the patients tend to infertile.

(II) most common complications are hypertension & diabetes

(III) less frequent complications are osteoporosis,delayed wound healing and psychiatric complications

(IV) fetal complications -miscarriage,prematurity,intrauterine growth restriction & still births.

Maternal cortisol can cross the placenta.

(i)Increased rate of miscarriage
(ii)Premature delivery
(iii)Still birth


Tests used for diagnosis

Pregnancy specific ranges should be examined

(i) 24 hour urinary free cortisol-Higher cutoff need to be used in pregnancy.

(ii)midnight serum cortisol -Physiological nocturnal drop is the serum cortisol level is also observed Cushing's syndrome.Higher cut off values should be used.

(iii)dexamethasone suppression test-

2 types of test

(A)overnight dexamethasone suppression test-1mg dexamethasone given at 23.00 hrs and serum cortisol is measured at 9am

(B)48 hour dexamethasone suppression test 0.5 mg given

6 hourly(9.00,15.00,21.00,3.00 hrs).Serum cortisol measured 9.00 at

the start & end of test.

The suppression effect on cortisol by dexamethasone is diminished in normal pregnancy.

So the usefulness of dexamethasone suppression is limited in pregnancy.

Once the Cushing's syndrome is confirmed, further tests done find the aeitiology.

If ACTH level is low adrenal imaging with MRI is useful.However adrenal' incidentaloma'(non secreting adrenal tumors can be found in 2-1% of abdominal CT's.It is important to correlate the CT findings to clinical & biochemical findings.

If ACTH level is elevated,high dose dexamethasone suppression test helps in differentiating between pituitary source vs ectopic ACTH.MRI of head or MRI of chest & abdomen can be arranged accordingly.

High dose of dexamethasone suppress cortisol in Cushing's disease but the suppression fails in adrenal adenoma & ectopic ACTH secretion.

ACTH measurement-ACTH level reduced in adrenal adenoma.

CRH (corticotropin releasing hormone) stimulation test-Pituitary tumors would show rise in cortisol but adrenal adenoma & Ectopic ACTH wouldn't.


Multidisciplinary approach involving Obstetrician,Endocrinologist,Anaesthetist and Surgeon is important.

It's important to control the blood pressure and diabetes mellitus.

Definitive treatment options depend on aeitiology.
(I) Adrenal adenoma-Adrenalectomy
(II)Cushing's disease-Transsphenoidal treatment,Medical treatment or adrenalectomy.

adrenalectomy in Pitutary adenoma could lead to Nelson syndrome

(III)Ectopic ACTH-resection of the source.

medical treatment can be used but generally surgery is the preferred.

Medical treatment options


(II)ketoconozole-This crosses the placenta,so there is a theoretical risk of inhibition of fetal adrenal cortex. Ketaconozole is also teratogenic in animal studies.

(III)metyrapone-can cause severe hypertension.

Medical treatment isn't currently recommended due to potential adverse side effects on fetus.

Post natal

(I) lactation is discouraged because

(a)there is possibility permanent galactorrhoea.

(b)drugs may be secreted into breast milk(ex.cyproheptadine)

(II) Neonate should be reviewed for potential intrauterine suppression of hypothalmic pituitary adrenal axis suppression.

(i) Cushing's syndrome in pregnancy: an overview.Vilar L, Freitas Mda C, Lima LH, Lyra R, Kater CE.
Arq Bras Endocrinol Metabol. 2007 Nov;51(8):1293-302.

(ii)Cushing syndrome in pregnancy .Deborah J. Cook, MD, FRCPC,Robert H. Riddell, MD, FRCPath,John D. Booth, MD, FRCPC. CMAJ, VOL. 141, NOVEMBER 15, 1989,pp1059-1061

(3)Nelson-Piercy C. Handbook of obstetric medicine. Taylor & Francis; 2002.

(4)Swiet MD. Medical disorders in obstetric practice. Wiley-Blackwell; 2002.

(5)Pituitary and adrenal disorders complicating pregnancy:Chandraharan, Edwin; Arulkumaran, Sabaratnam
Current Opinion in Obstetrics and Gynecology:April 2003 - Volume 15 - Issue 2 - pp 101-107