Endocrinology (2) Flashcards
Define multiple endocrine neoplasia
An autosomal dominant inherited syndrome characterised by tumours of the endocrine organs.
Summarise the aetiology of multiple endocrine neoplasia
Genetically inherited autosomal dominant
MEN1 gene mutation - mutation of tumour supressor gene
Causes MEN type 1
RET gene mutation - mutation of proto-oncogene
Causes MEN type 2A and 2B
MEN 1: Parathyroid adenoma Pituitary adenoma Pancreatic cancer - most often gastrinoma Facial angiofibromas and collagenomas
MEN 2A:
Thyroid medullary cancer
Phaeochromocytoma
Parathyroid adenoma
MEN 2B: Thyroid medullary cancer Phaechromocytoma Multiple neuromas Marfanoid habitus
Summarise the epidemiology of multiple endocrine neoplasia
Very rare
MEN 1 diagnosis usually made in 4th decade of life, however tumours develop in teenage years
What are the presenting symptoms and signs on physical examination of multiple endocrine neoplasia?
MEN1: Parathyroid adenoma - hypercalcaemia Abdominal pain and tenderness Constipation Confusion Symptoms of nephrolithiasis - loin to groin pain
Pancreatic gastrinoma - Zollinger-Ellison syndrome: Abdominal pain Dysphagia Gastro-oesophageal reflux Vomiting
Pancreatic insulinoma - hypoglycaemia - dizziness, hunger
Pancreatic glucagonoma - hyperglycaemia
Prolactinoma - galactorrhoea, gynaecomastia, amenorrhoea, headaches, bilateral hemianopia
Hypersomtatotrophinaemia - acromegaly, headaches, bilateral hemianopia
MEN 2A:
Thyroid medullary cancer - hoarseness, coughing, trouble swallowing, sweating, hypertension, pruritic skin lesions, lump in the neck, diarrhoea, palpable thyroid nodules
Phaeochromocytoma - hypertension, sweating, tremor, tachycardia, palpitations, headaches
Parathyroid adenoma
MEN 2B: Thyroid medullary cancer Phaechromocytoma Multiple neuroma Marfanoid habitus - long limbs, long fingers, high arched palate
What are the appropriate investigations for multiple endocrine neoplasia?
MEN 1: Hormone hypersecretion blood tests - PTH, gastrin, insulin, glucagon, prolactin, GH, IGF-1 Serum calcium DNA testing for genetic abnormality MRI head to look for pituitary adenoma
MEN 2:
24hr urine metanephrines for phaechromocytoma
MRI/CT adrenals
Serum calcitonin - elevated in Medullary thyroid cancer
FNA of thyroid nodules
Thyroid ultrasound
Parathyroid adenoma - elevated calcium and PTH
Define primary hyperaldosteronism
Increased autonomous production of aldosterone by the adrenal glands due to a problem with the adrenals, resulting in suppression of plasma renin activity.
Summarise the aetiology of primary hyperaldosteronism
Conn’s syndrome - adrenal adenoma secreting aldosterone (most common - 70%)
Adrenal carcinoma - RARE
Adrenal cortex hyperplasia - 30% of cases
Familial hyperaldosteronism - dominant inheritance,
Idiopathic
Summarise the epidemiology of primary hyperaldosteronism
1-2% of hypertensive patients
Conn’s syndrome is more common in WOMEN and YOUNG patients
Bilateral adrenal hyperplasia is more common in MEN and presents at an older age
What are the presenting symptoms of primary hyperaldosteronism?
Usually asymptomatic and found incidentally on bloods
Hypertension symptoms:
Headaches
Flushing
Hypokalaemia symptoms: Polydipsia and polyuria (due to nephrogenic DI) Nocturia Constipation Weakness Fatigue Numbness Tingling Tetany
What are the signs on physical examination of primary hyperaldosteronism?
Hypertension
Complications of hypertension eg hypertensive retinopathy
What are the appropriate investigations for pulmonary hyperaldosteronism?
Serum aldosterone - high
Serum renin - low
Serum potassium - may be hypokalaemic
Serum sodium - may be hypernatraemic
Serum magnesium - may be hypomagnesiumaemic
Urine potassium - high
Aldosterone:renin activity ratio: elevated
CT adrenals - may show adrenal adenoma or carcinoma
Genetic testing for familial hyperaldosteronism
Confirmatory Tests
Salt Loading: failure of aldosterone suppression following salt load confirms Conn’s
Postural Test: Measure plasma aldosterone, renin activity and cortisol when patient lies down at 8am, and measure again after 4 hours of the patient being upright.
Aldosterone-producing adenoma: aldosterone secretion decreases between 8am and noon
Bilateral adrenal hyperplasia: adrenals respond causing increase renin leading to increased aldosterone
What is the management of primary hyperaldosteronism?
Bilateral Adrenal Hyperplasia:
Spironolactone (aldosterone receptor antagonist)
Eplerenone if spironolactone side-effects are intolerable
Amiloride (potassium-sparing diuretic)
Monitor serum K+, creatinine and BP
ACE inhibitors and CCBs may also be added
Aldosterone Producing Adenomas: Adrenalectomy
Adrenal Carcinoma: Surgery and post-operative mitotane (antineoplastic)
What are the possible complications of primary hyperaldosteronism?
Hypokalaemia Metabolic alkalosis Hypertension Stroke MI AF Heart failure Impaired renal function Complications of hypertension
Summarise the prognosis of primary hyperaldosteronism
Surgery may cure the hypertension or make the hypertension easier to manage
Hypertension improved by management in all forms
Define osteoporosis
A metabolic bone disorder characterised by a decrease in bone mineral density and altered bone architecture, resulting in increased bone fragility and susceptibility to fracture. Bone mineralisation is normal
Summarise the aetiology of osteoporosis
Mainly post-menopausal or senile osteoporosis
Secondarily seen with drugs or systemic conditions
Other causes:
Low oestrogen eg postmenopausal leading to loss of bone matrix
Age related - osteoblast senescense
Iatrogenic - glucocorticoids, heparin, L-thyroxine
Malignancy – myeloma, metastatic carcinoma
Rheumatological – rheumatoid arthritis, ankylosing spondylitis
Gastrointestinal – malabsorption, liver disease, anorexia
Hypogonadism (in young men and women) – sex hormones inhibit bone resorption
Endocrine - Cushing’s, hyperthyroidism, primary hyperthyroidism
What are the risk factors of osteoporosis?
Post-menopause Age Family history Low BMI Low calcium intake/serum calcium Smoking Lack of physical exercise Low exposure to sunlight Alcohol abuse Late menarche Early menopause Hypogonadism Glucocorticoid use
Summarise the epidemiology of osteoporosis
Predominently white post-menopausal women
Can affect any sex, age and ethnicity
In the UK, osteoporosis causes fractures in 50% of women and 20% of men aged >50 years
What are the presenting symptoms of osteoporosis
Asymptomatic until a pathologic fracture occurs
Most often vertebral fracture which results in back pain, height loss and hunched posture
Can also have distal radius and femoral neck fractures often in post-menopausal
What are the signs on physical examination of osteoporosis?
There are often no signs until complications develop
When vertebral fractures occur:
Tenderness on percussion
Thoracic kyphosis (due to multiple vertebral fractures)
Neck of femur fracture:
Severe pain when hip flexed and externally rotated
What are the appropriate investigations for osteoporosis?
DEXA Scan - compares bone density to that of normal individual to develop t-score. T score compares to healthy 25 year old female at peak bone mass.
T score -1 is normal
Quantitative ultrasound/CT scan/x-ray of the heel to detect reduced bone mineral density
X-rays to diagnose fractures
Biochemical markers of bone resorption and formation (urinary deoxypyridinoline)
Serum albumin - may be decreased
Serum alkaline phosphatase - normal, osteomalacia if raised
Serum calcium - normal. If low, osteomalacia. If high, hyperparathyroidism.
Serum creatinine, phosphate, vitamin D
Thyroid function tests and serum parathyroid hormone
Define polycystic ovarian syndrome
A condition characterised by 2 of the three:
Hyperandrogenism
Oligo/anovulation
Polycystic ovaries on USS
It also shows oligo/amenorrhoea, hirsuitism, obesity, insulin resistance and can be associated with diabetes mellitus and dyslipidaemia.
Summarise the aetiology of polycystic ovarian syndrome
Increased secretion of LH by the anterior pituitary gland
Aetiology is unknown
Environmental factors
Genetic variants
Hyperinsulinaemia results in increased ovarian androgen synthesis and reduced hepatic sex hormone binding globulin (SHBG) synthesis - causes increase in free androgens (which gives rise to the symptoms)
Summarise the epidemiology of polycystic ovarian syndrome
Most common endocrine disorder of females of reproductive age
Accounts for 80-90% of causes of hyperandrogenism in women
Affects 6-8% of women
Most common cause of infertility in women
What are the presenting symptoms of polycystic ovarian syndrome?
Symptoms of hyperandrogenism:
Acne on face, back, chest
Hisutism - facial hair on chin, upper lip chest and back
Male pattern hair loss
Obesity
Oligomenorrhoea or amenorrhoea
Dysfunctional uterine bleeding
Infertility
What are the signs on physical examination of polycystic ovarian syndrome?
Hirsutism Acne Obesity Male pattern hair loss Ancanthosis nigricans - dark velvety thickened, hyperpigmented patches in creases on neck, groin, underarm - sign of insulin resistance
What are the appropriate investigations for polycystic ovarian syndrome?
Bloods: LH - elevated LH:FSH - elevated >3:1 Elevated androgens - testosterone, androstenedione, DHEA Low FSH and sex hormone binding globulin
USS pelvis - may show follicles on ovaries and increase in ovarian volume
Rule out: Hyperprolactinaemia Hypo/hyperthyroidism Cushing’s syndrome Congenital adrenal hyperplasia (check 17OH-progesterone levels)
Look for impaired glucose tolerance/T2DM: Fasting blood glucose, HbA1c
Fasting lipid profile
