Dr Rubab Khalid: Adrenal Disease and Pregnancy

This blogpost is about the Adrenal Disease and Pregnancy. The points have been taken from a TOG article which was published in October 2021. The article covers this topic quite comprehensively. It is recommended to read the original article for complete understanding of this important exam topic. I hope you find this post helpful.

To download the original article: Click Here

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Introduction

Adrenal disease in pregnancy is rare
Challenging to diagnose
Associated with ↑ adverse outcomes for both mother & fetus
Timely diagnosis & MDT involvement are essential to manage these high risk pregnancies

Major Adrenal Disorders

Primary Adrenocortical Insufficiency (Addisons’s Disease)
Cushing’s Syndrome
Primary Aldosteronism (PA)
Congenital Hyperplasia (CAH)
Pheochromocytoma & Paraganglioma (PPGL)

Primary Adrenocortical Insufficiency (Addisons’s Disease)

Adrenal insufficiency (AI) classified → primary, secondary & tertiary

Primary Insufficiency in Pregnancy

Uncommon 1 in 3000 to 5.5 in 100 000 pregnancies
Results due to adrenocortical disease
Both Glucocorticoid (GC) & Mineralocorticoid (MC) deficiency
70-90% due to autoimmune atrophy of adrenal gland

Secondary Insufficiency associated with ACTH secretion disorders mainly cortisol deficiency

Tertiary Insufficiency associated with CRH secretion disorders mainly cortisol deficiency

Cortisol during pregnancy

↑ Levels Both free & total cortisol
Peaks at 26th weeks
Diurnal rhythmic variation is maintained

Ref: TOG

Diagnosis

Females with Primary AI → lower fertility rates
Most diagnosed before pregnancy & are already on GC & MC
Challenging to diagnose for the 1st time in pregnancy as overlap of physiological symptoms of pregnancy
Highly Suggestive Features → hyperpigmentation on mucous membranes, extensor surfaces & non exposed regions

Short Synacthen stimulation Test

Non-pregnant → diagnosis likely if morning cortisol <140 nmol/L along with ↑ ACTH
Pregnant → this cut-off not reliable as most women have values >555 nmol/L in 2nd /3rd tri
Offer treatment if indeterminate SST & retest after delivery

Salivary free cortisol

In pregnancy → consistent, generalisable & rationale measure of adrenal function

Noninvasive Can be done in OPD

Radiological imaging → not routine defer until after delivery

Management

Joint team of obstetricians & endocrinologist
Replacement regimens same like non-pregnant

Hydrocortisone (HC) Preferred MC

Short acting does not cross placenta typical dose 15-25 mg in 2-3 divided doses

Fludrocortisone for MC replacement dose 0.05 mg - 1 mg/day

Prednisolone for GC replacement 3-5mg OD in those with poor compliance

If symptoms worsen (postural hypotension /fatigue) after 24 wks → ↑ the doses of GC ± fludrocortisone
HC has MC effect (40 mg = 0.1 mg fludrocortisone)
No need to ↑ fludrocortisone
Prednisolone does not have MC effect so dose may ↑ by 20-30%

Acute Adrenal Insufficiency

Rare, life-threatening emergency
Keep high index of suspicion
May occur

in patients with primary/secondary AI specially if severe hyperemesis
from sudden bilateral adrenal necrosis
in woman being treated with steroids during stressful time e.g. labour, illness when demands increase

Sudden withdrawal of therapeutic doses may precipitate
If use ≥ 5-20 mg prednisolone per day for 3 wks→ must give IV HC Intrapartum @50-100 mg 8 hrly for 24 hrs
To reduce morbidity & mortality → prompt evaluation & concurrent treatment needed
IV access, Blood samples for ACTH, cortisol, glucose & serum electrolytes
T/m with IV saline + IV HC 2-3 litres of 0.9% saline or 5% dextrose in 0.9% saline given quickly for patients in shock
Fluid rate adjusted according to urine output & volume status
HC 100 mg 6-8 hrly or in a continuous infusion
Recovery usually quick within 24 hrs
Parental HC to be tapered off over 1-3 days
Carefully investigate & treat the precipitating cause

Ref: TOG

Sick day rules & Stress dose

Sick day rule → a set of measures aimed to prevent occurrence of adrenal crisis
Triggers during pregnancy could be hyperemesis, infections, delivery and surgery
Educate & train woman + birth partner
Women with AI having hyperemesis should be given IV HC & fluid resuscitation
Stress doses of GC to be given during labour & delivery

Ref: TOG

Pregnancy Outcomes & Breastfeeding

Encourage vaginal delivery
CS only for obstetric reasons
Assess for VTE risk & provide prophylaxis
Generally good outcome for mother for fetus ↑ risk of FGR
↑ maternal morbidity in untreated / suboptimal replacement therapy
HC & prednisolone excreted in breast milk in very low quantity — unlikely to harm baby

Cushing’s Syndrome

Characterised by ↑ cortisol levels ± ↑ androgens
Rare for untreated woman to be pregnant
Timely diagnosis, early treatment and individualised care in MDT is critical for optimised pregnancy outcomes

Aetiology

60% due to adrenal adenoma & 70% pituitary-dependent

Unlike to have menstrual abnormalities in adrenal adenomas
Spontaneous pregnancy unlikely due to ↑ androgens produced by adrenal hyperplasia / adrenal carcinoma

Pregnancy-specific Cushing’s syndrome → onset occurring during pregnancy or within 12 months of delivery/miscarriage

Diagnosis

Timely diagnosis during pregnancy — unique challenge as overlap of physiological features of pregnancy
Differentiating clinical features— proximal myopathy, easy bruising, osteopenia/osteoporosis-induced fractures, hirsutism, early onset of HTN & red or purple striae (instead of pale)

Diagnostic tools

Preliminary screening test → midnight plasma cortisol levels
Reliable confirmatory tests → salivary cortisol at night + urinary free cortisol (UFC)

Values >3 times the upper limit of normal are diagnostic
Thresholds 1st tri <6.9 2nd tri <7.2 3rd tri <9.1

High dose (8 mg) dexamethasone suppression test —diagnostic in pregnancy

No cortisol suppression after high dose + normal to low ACTH = Adrenal Cushing's
Cortisol suppression + high ACTH = pituitary - dependent Cushing’s

MRI — useful in suspected pituitary lesions as well as adrenal masses better than USG for imaging to adrenals
CRH testing— no role in pregnancy

Management

If treated & complete remission → not much effect on pregnancy
Untreated / poorly treated/ diagnosed during pregnancy → significant adverse effects on mother & fetus
Fetus is relatively shielded from maternal hypercortisolism (as cortisol covered to biologically inactive form by placental enzyme)
Pregnancy to be managed by MDT including obstetrician s, endocrinologists, anaesthetist, neurologists and surgeons
Holistic approach
If diagnosed during pregnancy → early treatment is key

Surgical treatment — 1st line option

Laparoscopic unilateral adrenalectomy & trans-sphenoidal surgery —associated with good outcomes from 2nd tri onwards
In refractory case → bilateral adrenalectomy
Surgically treated (in remission) to be managed as having AI & should be given HC supplements

Medical treatment — 2nd line option

Metyrapone → most widely used reduces cortisol by inhibiting conversion of 11-hydroxycortisol to cortisol ↑ risk of hypertension need careful monitoring
Cabergoline → an alternative in pituitary-dependent Cushing’s
Do not use → Ketoconazole / Mitotone as associated with risk of teratogenicity
Equally important to have optimal treatment of HTN, glycemic control & vigilance for PTL
Encourage vaginal delivery
Ensure followup in endocrinology service