Week 128 - Gen Endocrinology

Question 1

What is Cushing’s Syndrome? (name the 3 types)

Answer 1

Cushing’s Disease - ↑ACTH, due to pituitary

ACTH dependent Cushing’s - ↑ACTH, due to ectopic production

non-ACTH dependent Cushing’s - ↑Cortisol, ↓ACTH, due to adrenal tumour

Question 2

What is Nelson’s disease

Answer 2

Increased pigmentation due to ↑ACTH

Associated with enlarging pituitary tumour

Question 3

What can the Dexamethasone Suppression Test show?

Answer 3

With:
Ectopic ACTH production - no change in Cortisol levels
Pituitary-dependent disease - ↓Cortisol

Question 4

What is Congenital Adrenal Hyperplasia?

Answer 4

Autosomal Recessive deficiency of 21 hydroxylase
Resulting in: ↓Cortisol, ↑ACTH

Diversion of steroid precursors occurs –> ↑17-hydroxyprogesterone and ↑testosterone levels

Clinical Features: sexual ambiguity, adrenal failure, hypotension, salt-losing state, primary amenorrhoea

Question 5

What is Primary Hypoadrenalism : Addison’s disease?

include clinical features and investigations

Answer 5

Autoimmune disease ( 21 hydroxylase = common antigen)

↓Cortisol, ↑CRH, ↑ACTH

Clinical Features: pigmentation, postural systolic hypotension (Na+ loss), fatigue, weight loss

Investigations: Tetracosactide (Synacthen) = confirms presence of hypoadrenalism

Management: hydrocortisone, fludrocortisone, education

Question 6

What is Conn’s Syndrome?

include investigations and treatment

Answer 6

Adrenal adenoma –> ↑aldosterone
↑Na+, ↓K+

Investigation: ↑aldosterone : renin ratio, CT scan, Adrenal Venous Sampling

Treatment: Laparoscopic adrenalectomy, low sodium diet, spironolactone

Question 7

What is Phaechromocytoma?

Answer 7

Adrenal Medulla tumour (sympathetic NS) secreting catecholamines

Clinical Features: Headaches, Sweating, Anxiety, Palpitations, Poorly controlled hypertension, weight loss, chest pain, nausea, vomiting

Investigations: Urinary catecholamines + metabolites, plasma catecholamines, clonidine suppression test, CT

Management: ↑salt diet, phenoxybenzamine (α-blockade), propranolol (β- blockade), laparoscopic adrenalectomy.

Question 8

What happens in Primary Hypogonadism (male)?

Answer 8

Testicular Failure
↓ Testosterone
↑FSH & LH

Question 9

What happens in Secondary Hypogonadism (male)?

Answer 9

Hypothalamic-pituitary Failure
↓ Testosterone
↓FSH & LH (or inappropriately low)

Question 10

What are the clinical features of androgen deficiency (hypogonadism-male)?

Answer 10

Small or absent testes
Gynacomastia
Infertility, sexual dysfunction
Small prostate
Reduced hair growth
Eunuchoid (if pubertal deficiency)

Question 11

What are the normal testicular sizes?

Answer 11

Pre-pubertal = 1 - 6 ml
Pubertal = 8 - 15 ml
Adult = 15 - 25 ml

Question 12

What investigations should be carried out for Androgen Deficiency?

Answer 12

Morning Testosterone x2

LH, FSH & seminal analysis x2

Question 13

Name the common causes of Primary Hypogonadism

Answer 13

Klinefelter's Syndrome
Surgical castration or trauma
Infections - orchitis
Drugs, alcohol, chemotherapy, radiotherapy
Chronic liver & kidney disease

Question 14

Name the common causes of Secondary Hypogonadism

Answer 14

Constitutional delayed puberty
Cushing's Syndrome
Drugs, opiates, anabolic steroids
Chronic disease, liver, kidney, HIV, diabetes
Obesity
Hypopituitarism
Hyperprolactinaemia

Question 15

What is Kallmann’s Syndrome?

Answer 15

Genetic syndrome resulting in suppressed gonadotrophins

In males: absent facial hair, poor musculature, gynaecomastia, infertility, eunochoid body proportions, ANOSMIA, COLOUR BLINDNESS

Question 16

What is Foetal Androgen Deficiency?

include clinical features

Answer 16

5-α reductase deficiency
Clinical Features: blind vagina, small clitoris, testis present (phenotypically female), bilateral inguinal hernia, primary amenorrhoea, ↑testosterone levels

Question 17

What is precocious puberty?

Answer 17

Oestogen secretion or cyclical ovarian activity before 7-8 years in girls
or
Androgen secretion & spermatogenesis before 9-10 years in boys

Question 18

What investigations would you carry out for precocious puberty?

Answer 18

LHRH/LH, FSH test, MRI pituitary, oestradiol, ovarian ultrasound, free T4, bone age

Question 19

What is Pseudoprecocious puberty?

Answer 19

Adrenal & gonadal disease, hCG-secreting tumours
–> premature epiphyseal fusion & short stature
Investigations: DHEAS, 17-α OH-progesterone, hCG

Question 20

What are the causes of primary amenorrhoea?

Answer 20

Primary ovarian failure (hypergonadotrophic hypogonadism)
Hypothalamic/pituitary failure
Excess sex steroid hormone production (CAH, adrenal tumours)
Turner’s Syndrome

Question 21

In what conditions will you find androgen excess?

Answer 21

PCOS
Non-classical adrenal hyperplasia (CAH)
Ovarian tumours
Adrenal tumours
Drugs

Question 22

What are the clinical features of PCOS?

include investigations

Answer 22

ovulatory dysfunction –> ↑testosterone ↓SHBG
hirsuitism, acne
insulin resistance
raised LH/FSH ratio
?raised prolactin
Investigations: LH:FSH ratio, testosterone, prolactin, T4 & TSH, 17-α OH-progesterone, ovarian ultrasound.

Question 23

What cells secrete PTH?

Answer 23

Chief cells

Question 24

What is the effect of PTH?

Answer 24

↑ [Ca] plasma
↓ [PO4] plasma
Enhances renal tubular reabsorption; osteoclast bone resorption; ↑25(OH)vitD –> 1,25(OH)vitD

Question 25

What is the effect of calcitonin?

Answer 25

↓ [Ca] plasma | ↓ [PO4] plasma

Question 26

What is the effect of vitamin D?

Answer 26

↑ [Ca] plasma | ↑ [PO4] plasma

Question 27

What are the main causes of Hypercalcaemia?

Answer 27

Primary hyperparathyroidism | Malignancy

Question 28

What are the causes of Primary Hypeparathyroidism? (include symptoms)

Answer 28

Adenoma, hyperplasia, carcinoma Can be familial: MEN type 1, 2a Generally asymptomatic, but may present with renal stones, musculoskeletal, GI or neuro problems

Question 29

What are the causes of Secondary Hypeparathyroidism?

Answer 29

compensatory, elevated PTH level secondary to hypocalcaemia with parathyroid gland hyperplasia

Question 30

What are the causes of Tertiary Hypeparathyroidism?

Answer 30

Autonomous secretion of PTH following long term hypocalcaemia

Question 31

Treatment of Hyperparathyroidism?

Answer 31

``` ?Tumour ablation i.v. fluids Diuretics Bisphosphonates Glucocorticoids Calcitonin ```

Question 32

What are the causes of Hypocalcaemia?

Answer 32

Hypoparathyroidism Impaired PTH secretion Target organ resistance Vitamin D-related disorders (diet, liver/kidney malfunction)

Question 33

What is the Clinical Presentation of Hypocalcaemia?

Answer 33

Chvostek's sign (angle of jaw) Trousseau's sign (BP cuff) ECG abnormalities, prolonged QT Laryngeal spasm, tetany, paraethesia

Question 34

What is the treatment for Hypocalcaemia?

Answer 34

i.v. Calcium infusion ?magnesium infusion oral (Ca, vitD, magnesium)

Question 35

What are the causes of Hypocalcaemia?

Answer 35

``` Post surgical Post radioactive iodine Polyendocrine deficiency syndromes Hypomagnaesaemia (e.g. PPI use) Metastases, haemochromotosis, chemotherapy, PTH resistance ```

Question 36

What is Pseudo Hypoparathyroidism (PHP)?

Answer 36

Deficient Gα activity in renal tubules, erythrocytes, platelets, lymphoblasts -> Hormone resistance (TSH, FSH, LH) Investigation: ↓plasma cAMP Albright's Hereditary Osteodystrophy - cluster of symptoms (short stature, round face, short metacarpals (4), subcutaneous calcification)

Question 37

In the development of pituitary gland, what two segments come together in week 11 to form the pituitary gland?

Answer 37

Ectoderm & the hypophyseal diverticulum (Rathke's pouch) AND Neuroectoderm and the neurohypophyseal diverticulum (infudibulum)

Question 38

Name the hormones secreted by posterior pituitary

Answer 38

Oxytocin, Vasopressin (ADH)

Question 39

Where does the thyroid gland develop from?

Answer 39

Foramen caecum (part of developing tongue)

Question 40

What duct may persist and cause problems after the thyroid gland descends?

Answer 40

The thyroglossal duct may persist and appear as a midline cyst

Question 41

Describe the development of the parathyroid gland

Answer 41

Ultimobrachial body arises from 4th pharyngeal pouch (neural crest) become C cells (parafollicular cells) that make calcitonin. Inferior parathyroid glands come from 3rd pharyngeal pouch Superior parathyroid glands come from 4th pharyngeal pouch

Question 42

What are neurohormones?

Answer 42

Released from synapses and travel via bloodstream

Question 43

Name some PEPTIDE hormones

Answer 43

GH, Prolactin, Insulin, ACTH, LH, FSH

Question 44

Name some STEROID hormones

Answer 44

Cortisol, Aldosterone, Testosterone, Oestrogen

Question 45

Name some AMINO ACID hormones

Answer 45

Thyroxine, Adrenaline, Noradrenaline

Question 46

Name some Lipid hormones

Answer 46

Prostacyclin, Prostaglandins, Thromboxanes, Leukotrienes

Question 47

Name some hormones secreted by the thymus

Answer 47

Thymosin, Thymopoietin, Thymulin

Question 48

What hormones are derived from Tyrosine?

Answer 48

Thyroid hormones, Catecholamines

Question 49

How is testosterone modified in different tissues?

Answer 49

testosterone (5α reductase) -> skin,external genitalia -> dihydrotestosterone testosterone (aromatase) -> bone,brain -> estradiol

Question 50

What is the effect of T3 & T4?

Answer 50

Breakdown of carbohydrates and fats, synthesise proteins | Hormones made by follicular cells and carried in the blood bound to TBG

Question 51

What are the effects of Cortisol?

Answer 51

↑ amino acids in blood, ↑gluconeogenesis, ↑use of fat