12.14 Adrenal Disorders Flashcards
Two types of body hair
Vellus hair
- Fine, non-pigmented hair that covers the body of children and adults.
- growth of vellus hair is not affected by hormones
Terminal hair
- Thick pigmented hairs found on the scalp, beard, armpits, and pubic area
- growth of terminal hairs is affected by hormones
Hirsutism
Def
Prevalence
Def
- excessive growth of thick dark hair in an androgen-dependent pattern (male-pattern) where hair growth in women is usually minimal absent (face, chest, and thighs)
- occurs as a result of increased androgen production, increased skin sensitivity to androgens, or both
Prevalence
- Affects 5-10% of women of women of reproductive age
Virilisation
Def
Features
Pathogenesis
Def
- when a female develops male sex characteristics
Features
- Deepening of the voice
- Facial hair (more pronounced)
- Increase in body hair
- Male-pattern baldness
- Clitoromegaly
Pathogenesis
- Increased Androgen Production:
• Ovary
• Adrenal glands
• Liver/Skin
• Idiopathic
- Decreased Sex Hormone Binding Globulin (SHBG) {more free androgens available}
- Target Tissue:
• Increased 5 a reductase
• Increased androgen receptors
Causes of Hirsutism without virilisation
Idiopathic
- Drugs e.g. glucocorticoids, epanutin, minoxidil
- Endocrinopathies:
• PCOS (Poly systic ovarion syndrome)
• Hypothyroidism
• Cushing’s
• Hyperprolactinemia
• Acromegaly
- Other e.g. menopause (physiological)
Idiopathic Hirsutism
- Common and often familial
- diagnosis of exclusion and thought to be related to disorders in peripheral androgen activity (skin)
- Onset occurs shortly after puberty with slow progression
- no other signs of virilisation, normal menstrual function and normal investigations
Causes of Hirsutism with virilisation
Ovarian
- Polycystic Ovary Syndrome
- Androgen producing ovarian tumours
Adrenal (Mixed adrenal cortex patterns = malignant)
- Adrenal Tumours e.g. Cushing’s, androgen producing (often rapidly progressing)
- Congenital Adrenal Hyperplasia (CAH) - 21 hydroxylase deficiency
- Late onset (NCCAH - non classical CAH)
Drugs
- Testosterone, Glucocorticoids, Anabolic steroids
Polycystic ovary syndrome
General
Pathophysiology
Diagnosis
- Most common endocrinopathy in women
- Prevalence 5-10 %
- Virilisation usually minimal
- Diagnosis: (pt should have 2/3)
• Clinical and/or biochemical hyperandrogenism
• Menstrual irregularity (oligo-anovulation)
• Polycystic ovaries - Increased LH:FSH
Pathophysiology
Increased GnRH pulse frequency
Hypersecretion of LH
⬇️
Stimulation of ovarian theca cell androgen production
- Pt don’t mensturate / ovulate
- inhibits expansion of follicular size and maturation leading to follicular arrest, PCOS morphology and anovulation
Diagnosis
- Presence of 12 or more follicles in the ovary measuring 2-9 mm in diameter, and/or increased ovarian volume (>10ml)
- Idiopathic (familial/genetic) hirsutism is the most common
- PCOS is the most common disease associated with hirsutism ± virilisation
- It is important to rule out other causes (<5%), since they may require attention in own right e.g. CAH, androgen producing adrenal tumours, Cushing’s etc.
What body areas does the Ferriman-Gallwey hirsutism scoring system use?
- beard
- lip
- chest
- stomach
- pubic area
- arms
- legs
- upper back
- lower back
Other abnormalities associated with excessive levels of androgens
- Cardiovascular disease, dyslipidaemia, glucose intolerance insulin resistance and hypertension
- Acanthosis nigricans, a marker for insulin resistance, may also be present
- Pelvic mass (ovarian) adrenal tumour
Menopause
Def
Perimenopause
Associated diseases
Def
- natural phenomenon which occurs in all women when their finite number of ovarian follicles are depleted
- defined by 12 months of amenorrhea after the final menstrual period
- Oestrogen and progesterone hormone levels fall
- Luteinising hormone (LH) and follicle stimulating hormone (FSH) increase in response to a fall in ostrogen and progesterone
Perimenopause
- Menopausal transition
• begins with variation in menstrual cycle length and an elevated serum FSH concentration and ends with the final menstrual period
- Perimenopause means “around the menopause”
Associated diseases
Cardiovascular disease
- Coronary artery disease, stroke, PVD
- Osteoporosis
- Alzheimer’s disease
- Urogenital atrophy
Primary vs. Secondary hypoadrenalism
PRIMARY HYPOADRENALISM (ADDISON’S DISEASE)
- HIGH ACTH = hyperpigmentation
- deficient adrenal production of steroids in adrenal cortex due to destruction or dysfunction of adrenal cortex
- All adrenal cortex hormones deficient ⬇️⬇️
• Glucocorticoids
• Mineralocorticoids
• Sex steroids
SECONDARY HYPOADRENALISM
- LOW ACTH
- Only glucocorticoid deficient
- deficient adrenal glucocorticoid production due to deficient pituitary ACTH secretion
Secondary Hypoadrenalism causes
- Hypopituitarism (various causes - refer to lecture)
- Isolated ACTH deficiency
- Autoimmune
- Genetic defects (POMC gene mutations/ Cleavage enzyme defects/ TPIT gene mutations)
- Familial CBG deficiency
- Traumatic brain injury
- Drugs (high dose progesterones, opiates)
Tertiary hypoadrenalism
- Chronic high dose glucocorticoid use
- After cure for Cushing’s disease
- Any process involving hypothalamus and decreased secretion of CRH
Addison’s disease
General
Causes
Presentation
Associated features
- primary
- adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex.
- disease only occurs when 90% of dysfunc occurs
Causes
- autoimmune (isolated; polyglandular syndrome)
- infections (TB, fungal, HIV, CMV, Syphilis)
- Haemorrhage / infarction (meningococcus, pseudomonas, thrombotic conditions)
Clinical presentation
- Patients usually present with features of both glucocorticoid and mineralocorticoid deficiency.
- The predominant symptoms vary depending on the duration of disease.
- Patients may present with clinical features of chronic Addison disease or in acute Addisonian crisis precipitated by stress factors such as infection, trauma, surgery, vomiting, diarrhea, or noncompliance with replacement steroids.
Associated features
- evidence of ACTH excess (MSH, Hyperpigmentation)
- evidence of other autoimmune diseases (Vitiligo; Diabetes mellitus; Hypothyroid etc.)
Primary vs Secondary hypoadrenalism
PRIMARY HYPOADRENALISM
- Hyperpigmentation
- Dehydration and hypotension
- Hyperkalaemia
- Hyponatraemia dueto aldosterone deficiency
- Hypoglycaemia
- High renin
- Low aldosterone and DHEAS
- Gl symptoms
- Signs of other polyglandular syndrome
** CENTRAL /Secondary HYPOADRENALISM**
- No hyperpigmentation
- No mineralocorticoid deficiency
- No hyperkalaemia
- Hyponatraemia (require cortisol for free water excretion)
- Normal or low renin
- Normal aldosterone and DHEAS
- GI symptoms uncommon
- Hypoglycaemia
- Other signs of central cause e.g. panhypopituitarism or compressive effects (visual fields etc.)
Acute adrenal crisis
Causes
Precipitating events
Causes
- acute illness in pt with underlying chronic adrenal insufficiency
Primary causes:
- Auto-immune
- TB of adrenals
- Metastatic malignancy to adrenals
-NB: Acute destruction of the adrenals can also occur with bleeding in the adrenals
- Sepsis
- DIC
- Complication of anticoagulant therapy
Secondary:
- pituitary or hypothalamic disease
Precipitating factors
- pt know with Addisons but don’t take meds
- certain drugs that increase steroid metabolism
