Endocrinology Test (Part 1)
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1) A patient is attending pre‐op clinic prior to elective excision of a Bartholin's cyst. The patient is well in themselves apart from feeling a bit tired. The nurse asks you to review them as the patients blood pressure is 88/58 and the bloods are as follows:
Na+ 133 mmol/l K+ 5.4 mmol/l Urea 8.5 mmol/l Creatinine 80 µmol/l You suspect adrenal insufficiency. What would the most appropriate next test be?
Explanation: According to NICE the first line tests for investigating suspected Addison's (adrenal insufficiency) are cortisol level and U&Es.
The cortisol level should be taken at 8‐9am. Caution needs to be applied to shift workers as they may have abnormal diurnal variation. When interpreting results:
Cortisol level <100 nanomol/L. Admit/Urgent Refer endocrine as adrenal insufficiency likely
Cortisol level 100 to 500 nanomol/L. Refer endocrine for Synacthen® test
Cortisol level is >500 nanomol/L. Addison's unlikely/excluded 24 hour urinary cortisol and dexamethasone suppression tests are useful if trying to diagnose cortisol excess i.e. Cushing's Syndrome. MRI may be appropriate at a later stage but isn't a first line investigation
2) What is the most common cause of premature menopause in the UK?
Explanation: Premature menopause is most commonly idiopathic
3) Where are ADH (vasopressin) and Oxytocin synthesised?
Explanation: Its important to read the question here. ADH and Vasopressin are synthesised in the Supraoptic and Periventricular nuclei of the hypothalamus. They are then stored and eventually released from the posterior pituitary
4) What is the leading cause of primary aldosteronism?
Explanation: Conn's Syndrome results from primary hyperaldosteronism. Aldosterone increases the reabsorption of sodium ions (and subsequently water) in exchange for potassium in the kidney. The result is increased blood volume and therefore increased blood pressure. Hypokalaemia may be present but is often within normal range. The main causes of primary hyperaldosteronism are adrenal hyperplasia (65%) and adrenal adenoma (30‐35%). Note some texts refer to primary aldosteronism as Conn's. Strictly speaking Conn's is primary aldosteronism due to adrenal adenoma Secondary hyperaldosteronism is due to increased renin production in conditions such as renal artery stenosis or a renin producing tumour.
5) Where are ADH (vasopressin) and Oxytocin synthesised?
Explanation: Calcitonin is produced by the Thyroid C‐cells (AKA parafollicular cells) Parathyroid Chief cells produce PTH
6) Which of the following inhibits prolactin?
Explanation: There are many stimulants of prolactin but few inhibitors. For the MRCOG be aware of dopamine and somatostatin as the main inhibitors. TRH, oxytocin, vasopressin and angiotensin II are all stimulators of Prolactin
7) Which of the following is true of nephrogenic diabetes insipidus?
Explanation: Diabetes Insipidus is due to a deficiency of AVP (also called ADH or simply PASS‐MRCOG |Endocrinology Vasopressin). This deficiency is either a real deficiency due to lack of production of ADH in the hypothalamus/posterior pituitary when it is termed central, cranial or neurological diabetes insipidus. In nephrogenic diabetes insipidous there are either normal or raised levels of ADH however the ADH receptors in the kidney are dysfunctional and therefore the ADH produced is ineffective. As a result of deficient ADH there is diuresis.
8) A patient with amenorrhoea is seen in clinic. History and examination reveal the patient runs 10‐20 miles every day and her BMI is 17.8. Which of the following is likely to explain her symptoms?
Explanation: World Health Organization (WHO) Group I ovulation disorder is due to hypothalamic pituitary failure. This is sometimes termed hypothalamic amenorrhoea or hypogonadotrophic hypogonadism. Women can improve frequency of ovulation, conception and an uncomplicated pregnancy by increasing their body weight (if BMI of <19) and/or moderating their exercise levels (if they undertake high levels of exercise). GnRH and LH may be administered in these patients. PCOS falls under type II ovulation disorders. WHO Group III ovulation disorder is due to ovarian failure.
9) What is the most common cause of endogenous Cushing's syndrome?
Explanation: The most common cause of Cushing's syndrome is steroid treatment. The most common endogenous cause is a Pituitary adenoma and this is referred to as Cushing's disease
10) What is the most common cause of premature menopause in the UK?
11) Which major hormone of pregnancy is produced by the placenta from 16‐hydroxydehydroepiandrosterone sulfate (16‐OH DHEAS)?
Explanation: The placenta produces Estriol from 16‐OH DHEAS. Estriol is the major oestrogen (estrogen) of pregnancy and the placenta is the primary site of production. Pregnenolone is synthesised by the placenta from cholesterol and this is converted to dehydroepiandrosterone (DHEA) in the fetal adrenal gland
12) You are called to assist in an initially midwife led delivery. Upon delivering a female baby you notice the baby has partial fusion of the labioscrotal folds. You suspect congenital adrenal hyperplasia. Which of the following is the most common enzyme deficiency?
Explanation: Congenital Adrenal Hyperplasia (CAH) refers to a group of autosomal recessive disorders that result in deficiencies of enzymes involved in mediating the production of cortisol, aldosterone or both. These result in excessive or deficient steroid hormone production 90% of cases are due to 21‐hydroxylase deficiency as a result of abnormal CYP21A genes. This results in androgen excess and mineralocorticoid deficiency. 5% of cases are due to 11‐hydroxylase deficiency
13) What percentage of pregnancies are affected by hypothyroidism (including subclinical hypothyroidism)?
Explanation: Hypothyroidism (including subclinical hypothyroidism) is present in 2.5% of pregnancies. Interestingly thyroid peroxidase antibodies are present in 10% of women at 14 weeks of gestation . Only 1‐3 per 1,000 pregnancies are complicated by overt hypothyroidism
14) The ovaries produce androgen and progesterone. What is the common precursor for both of these hormones?
Explanation: Cholesterol is the common precursor for progesterone and androgen production
15) You see a 32 year old women in clinic who mentions she has been sweating and has frequent headaches. On examination you note her blood pressure is 195/105 and pulse rate is 110. You suspect pheochromocytoma. Pheochromocytoma accounts for what percentage of cases of hypertension?
Explanation: . The rate of pheochromocytoma is quoted at around 1 in 54,000 pregnancies 20% are familial The maternal mortality rate is 2% to 4% if diagnosed in the antenatal period, rising to 14% to 25% if it is diagnosed intrapartum or postpartum
Which of the following hormones stimulate ductal morphogenesis during pregnancy hPL ‐ Human Placental Lactogen GH ‐ Growth Hormone
Explanation: Ductal Morphogenesis is stimulated by Oestrogen and Growth Hormone. Alveolar morphogenesis is under control of Progesterone, Prolactin and hPL.
17) Prognathism and macroglossia are features of which of the following?
Explanation: These are features of excess growth hormone i.e. Acromegaly. Down's and Cri du chat typically cause Micrognathia (small jaw)
18) Whilst reviewing a 34 year old patient with amenorrhoea in clinic they tell you they have gained over 10kg in weight in the past 8 weeks and have noticed worsening acne. Routine bloods taken that morning show a random glucose 11.1mmol/l, normal thyroid function tests and negative pregnancy test. BP is 168/96 mmHg. You suspect Cushing's. What would the most appropriate investigation be to conform the diagnosis?
Explanation: In Cushing's syndrome there is excess cortisol. Causes are broadly divided into 2 types: ACTH dependent disease: excess ACTH from the pituitary (Cushing's disease), ectopic ACTH‐producing tumours or excess ACTH administration. Non‐ACTH‐dependent: adrenal adenomas, adrenal carcinomas, excess glucocorticoid administration. The recommended diagnostic tests for the presence of Cushing's syndrome are 24‐hour urinary free cortisol, 1 mg overnight dexamethasone suppression test and late‐night salivary cortisol. There are several other tests that may also be performed to find the cause. ACTH and cortisol
19) You are called to see a 22 year old primigravida women who is 10 weeks pregnant, has severe vomiting and is unable to keep fluids down. You suspect hyperemesis gravidarum. What is the underlying cause?
Explanation: Increased circulating HCG is thought to cause HG
20) The zona glomerulosa produces which of the following hormones?
Explanation: The Zona Glomerulosa produces Aldosterone.
21) Human Chorionic Gonadotrophin (HCG) is structurally similar to which of the following hormones?
Explanation: Although hormone similarities may not seem clinically relevant it is something the RCOG can ask about in the part 1. In this case there are 3 other hormones (TSH,FSH and LH) that are structurally similar to HCG and could be used as an answer
22) You are asked to review a patient with known adrenal insufficiency. Which of the following causes of adrenal insufficiency would you NOT expect hyper pigmentation to be a clinical feature of?
Explanation: Autoimmune adrenalitis, adrenal dysgenesis and Waterhouse Friderichsen syndrome are all causes of primary adrenal insufficiency. In Primary adrenal insufficiency the brain produces more ACTH in response to low steroid hormone levels. ACTH gets cleaved into MSH (melanocyte‐stimulating hormone) which causes hyper pigmentation i.e. High ACTH = High MSH = hyper pigmentation. In secondary and tertiary adrenal insufficiency there is low ACTH and low adrenal steroid hormone production as a result.
23) You see a 32 year old women in clinic who mentions she has been sweating and has frequent headaches. On examination you note her blood pressure is 195/105 and pulse rate is 110. You suspect pheochromocytoma. Pheochromocytoma incidence in pregnancy is approximately?
Explanation: Pheochromocytoma is rare accounting for around 0.1% of cases of hypertension. The rate of pheochromocytoma is quoted at around 1 in 54,000 pregnancies 20% are familial
24) Which of the following inhibit Glucagon?
Explanation: Raised urea, somatostatin and fatty and/or keto‐acids are the main inhibitors to be aware of. Insulin is the other obvious inhibitor
25) Human placental lactogen (hPL) is structurally similar to which of the following hormones?
Explanation: Although hormone similarities may not seem clinically relevant it is something the RCOG can ask about in the part 1. This question may have used GH or Prolactin in place of hPL as all 3 are structurally similar. PASS‐MRCOG |Endocrinology GH consists of 191 amino acids and a molecular weight of 22,124 daltons. hPL consists of 191 amino acid and has a molecular weight of 22,125 daltons Prolactin has different forms. The smallest and most biologically active consists of 198 amino acids and weighs around 22KDa
26) You review a patients notes to see they are consistently hypertensive with average BP of 160/105. The U&Es are also abnormal with a borderline low potassium of 3.2 mmol/l. You suspect Conn's syndrome. Which of the following would be the most appropriate next test?:
Explanation: Remember Conn's is a condition of raised Aldosterone (with subsequent effects on the aldosterone‐renin‐angiotensin system). Catecholamines and cortisol tests are not useful in diagnosing this. High aldosterone‐to‐renin ratio is useful in looking for Conn's (primary hyperaldosteronism) and would be an appropriate next test. The diagnosis is made via one of the following: Saline suppression test Ambulatory salt loading test Fludrocortisone suppression test If primary hyperaldosteronism is confirmed biochemically then adrenal CT or MRI is typically performed to find the cause.
27) Which of the following is NOT a recognised cause of hyperprolactinaemia?
Explanation: Hypothyroidism is a recognised cause of raised prolactin. In fact it is the most common cause.
28) In the non‐pregnant state which of the following hormones is secreted by the corpus luteum?
Explanation: The Corpus Luteum is a temporary endocrine structure that secretes two steroid hormones: Progesterone (17a Hydroxyprogesterone) Estradiol The corpus luteum also secretes Inhibin A. In the menstrual cycle if fertilisation doesn't occur the corpus luteum stops secreting progesterone and degenerates into a corpus albicans. If fertilisation occurs hCG signals the corpus to continue progesterone production and it is then termed the corpus luteum graviditatis
29) Where is Angiotensin II produced?
Explanation: Angiotensin I is converted to Angiotensin II by ACE in the lung
30) What is the appropriate response to increased calcitonin production
Explanation: Calcitonin is released from the thyroid C‐cells in response to a raised serum calcium. Its actions are mostly antagonistic to PTH i.e. Inhibits calcium absorption by the intestines Inhibits osteoclast resorption of bone Stimulates osteoblast activity in bone to sequester calcium Inhibits renal tubule resorption of calcium. Increases urinary calcium excretion Note calcitonin inhibits phosphate reabsorption in the kidney causing lowering of serum phosphate (PTH also lowers phosphate)
31) Which of the following statements regarding progesterone production in the ovary is true?
Explanation: Its important to understand the endocrine function of the ovary. In each menstrual cycle the corpus luteum develops from an ovarian follicle. The follicular theca and granulosa cells are luteinized into theca lutein (or small luteal) and granulosa lutein (or large luteal) cells respectively. These form the corpus luteum in the ovary. Large luteal cells produce the majority of progesterone but both types of luteal cells produce progesterone. Progesterone is synthesized form cholesterol.
32) Which of the following is responsible for the formation of Angiotensin I from Angiotensinogen
Explanation: Renin cleaves the peptide bond on Angiotensinogen forming Angiotensin I
33) Cortisol is produced where?
Explanation: Below is a summary of hormone production sites
34) You see a 42 year old women in clinic who mentions she has been sweating and has frequent headaches. On examination you note her blood pressure is 195/105 and pulse rate is 110. You suspect pheochromocytoma. Which of the following conditions is NOT associated with higher risk of pheochromocytoma?
Explanation: The conditions associated with increased risk of pheochromocytoma are: MEN type 2 Paraganglioma syndromes types 1,3 and 4 VHL Neurofibromatosis type 1
35) At ovulation the surge in LH causes rupture of the mature oocyte via action on what?
Explanation: The luteinizing hormone (LH) surge during ovulation causes: Increases cAMP resulting in increased progesterone and PGF2 production PGF2 causes contraction of theca externa smooth muscle cells resulting in rupture of the mature oocyte
36) Delayed puberty in girls is defined as?
Explanation: In girls the absence of breast development in girls beyond 13 years old defines delayed puberty. In both girls and boys delayed puberty is most commonly down to constitutional delay
37) In girls what is the first sign of puberty?
Explanation: Puberty is often classed into 5 stages using the Tanner classification. Breast development typically begins between 10 and 11. The breast bud hs typically developed by a mean age of 11.2 years and is considered stage 2. Peak growth velocity, axillary hair growth and acne are Stage 3 (mean age 12.4 to 13.2) Menarche is stage 4 (mean age 13.3)
38) Where is Renin produced?
Explanation: Renin is secreted by the afferent arterioles of the kidney from specialized cells called granular cells of the juxtaglomerular apparatus
39) The zona glomerulosa produces which of the following hormones?
Explanation: Oxytocin stimulates the milk ejection reflex (let‐down) in response to suckling. Galactopoiesis is maintained via the action of Prolactin. Alveolar gland proliferation and differentiation occurs under the actions of Oestragens, Progesterone, HPL and prolactin. Prolactin stimulates Lactogenesis when not inhibited
Which of the following hormones are required for alveolar morphogenesis during pregnancy hPL ‐ Human Placental Lactogen GH ‐ Growth Hormone
Explanation: Ductal Morphogenesis is stimulated by Oestrogen and Growth Hormone. Alveolar morphogenesis is under control of Progesterone, Prolactin and hPL
41) Polycystic ovarian syndrome is classed as?
Explanation: There are 3 types of ovulation disorder: WHO type I hypo‐gonadotropic, hypo‐estrogenic, (15%) WHO type II normo‐gonadotropic, normo‐estrogenic, (80%) WHO type III hyper‐gonadotropic, hypo‐estrogenic (5%) PCOS is type 2
42) In relation to ovulation when does the LH surge occur?
Explanation: LH surges 24‐36 hours before ovulation
43) What is the most common cause of hypothyroidism worldwide?
Explanation: In the UK and most developed countries 90% of cases of hypothyroidism are autoimmune or iatrogenic. Worldwide however Iodine deficiency is the most common cause
44) Which of the following is the most common cause of hyperthyroidism and is typically characterised by a small to moderate diffuse firm goitre?
Explanation: Grave's disease is the most common cause of hyperthyroidism and has an autoimmune basis. It is mediated by B and T lymphocytes
45) Aromatase is key to Estradiol production in the ovaries. Which of the following statements is true?
Explanation: It is important to have a good understanding of the two main cell types of the ovaries. The theca cells produce androgen in the form of androstenedione.The theca cells are not able to convert androgen to estradiol themselves. The produced androgen is therefore taken up by granulosa cells.
46) A 15 year old girl is being investigated for primary amenorrhoea. She has normal FSH,LH and E2 levels on hormone profiling and normal secondary sexual characteristics. An ultrasound shows no uterus. What is the likely diagnosis?
Explanation: There are 2 conditions with a congenital absence of the uterus: Mullerian Agenesis AKA Rokitansky‐Kuster‐Hauser syndrome CAIS AKA Testicular Feminisation Syndrome Of the two Mullerian Agenesis is more common (1 in 5000) compared to CAIS (1 in 40,000 live births) CAIS patients will have low E2 typically. Genetically they are Karyotype 46XY Mullerian agenesis patients are karyotype 46 XX.
47) Chromaffin cells produce which of the following hormones?
Explanation: Chromaffin cells are located in the adrenal medulla and they secrete adrenalin, Noradrenalin and Dopamine
A patient is referred to the fertility clinic by her GP. Whilst you are explaining her blood results the patient admits she has been using the combined oral contraceptive pill intermittently but had told her GP she hadn't had any contraception in the past 12 months.Which of the following accurately reflects the effects of the COCP on a patients hormone profile?
FSH ‐ follicle stimulating hormone LH ‐ luteinizing hormone E2 ‐ Oestradiol (estradiol) AMH ‐ anti‐mullerian hormone
Explanation: Both biochemical and ultrasound markers can be used to measure ovarian reserve. COCP's have been shown to effect both of these.
50) Thyroid Stimulating Hormone (TSH) is structurally similar to which of the following hormones?
Explanation: Although hormone similarities may not seem clinically relevant it is something the RCOG can ask about in the part 1. In this case there are 3 other hormones (HCG,FSH and LH) that are structurally similar to TSH and could be used as an answer.
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