Week 128 - Gen Endocrinology Flashcards
What is Cushing’s Syndrome? (name the 3 types)
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
What is Nelson’s disease
Increased pigmentation due to ↑ACTH
Associated with enlarging pituitary tumour
What can the Dexamethasone Suppression Test show?
With:
Ectopic ACTH production - no change in Cortisol levels
Pituitary-dependent disease - ↓Cortisol
What is Congenital Adrenal Hyperplasia?
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
What is Primary Hypoadrenalism : Addison’s disease?
include clinical features and investigations
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
What is Conn’s Syndrome?
include investigations and treatment
Adrenal adenoma –> ↑aldosterone
↑Na+, ↓K+
Investigation: ↑aldosterone : renin ratio, CT scan, Adrenal Venous Sampling
Treatment: Laparoscopic adrenalectomy, low sodium diet, spironolactone
What is Phaechromocytoma?
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.
What happens in Primary Hypogonadism (male)?
Testicular Failure
↓ Testosterone
↑FSH & LH
What happens in Secondary Hypogonadism (male)?
Hypothalamic-pituitary Failure
↓ Testosterone
↓FSH & LH (or inappropriately low)
What are the clinical features of androgen deficiency (hypogonadism-male)?
Small or absent testes Gynacomastia Infertility, sexual dysfunction Small prostate Reduced hair growth Eunuchoid (if pubertal deficiency)
What are the normal testicular sizes?
Pre-pubertal = 1 - 6 ml Pubertal = 8 - 15 ml Adult = 15 - 25 ml
What investigations should be carried out for Androgen Deficiency?
Morning Testosterone x2
LH, FSH & seminal analysis x2
Name the common causes of Primary Hypogonadism
Klinefelter's Syndrome Surgical castration or trauma Infections - orchitis Drugs, alcohol, chemotherapy, radiotherapy Chronic liver & kidney disease
Name the common causes of Secondary Hypogonadism
Constitutional delayed puberty Cushing's Syndrome Drugs, opiates, anabolic steroids Chronic disease, liver, kidney, HIV, diabetes Obesity Hypopituitarism Hyperprolactinaemia
What is Kallmann’s Syndrome?
Genetic syndrome resulting in suppressed gonadotrophins
In males: absent facial hair, poor musculature, gynaecomastia, infertility, eunochoid body proportions, ANOSMIA, COLOUR BLINDNESS
What is Foetal Androgen Deficiency?
include clinical features
5-α reductase deficiency
Clinical Features: blind vagina, small clitoris, testis present (phenotypically female), bilateral inguinal hernia, primary amenorrhoea, ↑testosterone levels
What is precocious puberty?
Oestogen secretion or cyclical ovarian activity before 7-8 years in girls
or
Androgen secretion & spermatogenesis before 9-10 years in boys
What investigations would you carry out for precocious puberty?
LHRH/LH, FSH test, MRI pituitary, oestradiol, ovarian ultrasound, free T4, bone age
What is Pseudoprecocious puberty?
Adrenal & gonadal disease, hCG-secreting tumours
–> premature epiphyseal fusion & short stature
Investigations: DHEAS, 17-α OH-progesterone, hCG
What are the causes of primary amenorrhoea?
Primary ovarian failure (hypergonadotrophic hypogonadism)
Hypothalamic/pituitary failure
Excess sex steroid hormone production (CAH, adrenal tumours)
Turner’s Syndrome
In what conditions will you find androgen excess?
PCOS Non-classical adrenal hyperplasia (CAH) Ovarian tumours Adrenal tumours Drugs
What are the clinical features of PCOS?
include investigations
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.
What cells secrete PTH?
Chief cells
What is the effect of PTH?
↑ [Ca] plasma
↓ [PO4] plasma
Enhances renal tubular reabsorption; osteoclast bone resorption; ↑25(OH)vitD –> 1,25(OH)vitD
What is the effect of calcitonin?
↓ [Ca] plasma
↓ [PO4] plasma
What is the effect of vitamin D?
↑ [Ca] plasma
↑ [PO4] plasma
What are the main causes of Hypercalcaemia?
Primary hyperparathyroidism
Malignancy
What are the causes of Primary Hypeparathyroidism? (include symptoms)
Adenoma, hyperplasia, carcinoma
Can be familial: MEN type 1, 2a
Generally asymptomatic, but may present with renal stones, musculoskeletal, GI or neuro problems
What are the causes of Secondary Hypeparathyroidism?
compensatory, elevated PTH level secondary to hypocalcaemia with parathyroid gland hyperplasia
What are the causes of Tertiary Hypeparathyroidism?
Autonomous secretion of PTH following long term hypocalcaemia
Treatment of Hyperparathyroidism?
?Tumour ablation i.v. fluids Diuretics Bisphosphonates Glucocorticoids Calcitonin
What are the causes of Hypocalcaemia?
Hypoparathyroidism
Impaired PTH secretion
Target organ resistance
Vitamin D-related disorders (diet, liver/kidney malfunction)
What is the Clinical Presentation of Hypocalcaemia?
Chvostek’s sign (angle of jaw)
Trousseau’s sign (BP cuff)
ECG abnormalities, prolonged QT
Laryngeal spasm, tetany, paraethesia
What is the treatment for Hypocalcaemia?
i.v. Calcium infusion
?magnesium infusion
oral (Ca, vitD, magnesium)
What are the causes of Hypocalcaemia?
Post surgical Post radioactive iodine Polyendocrine deficiency syndromes Hypomagnaesaemia (e.g. PPI use) Metastases, haemochromotosis, chemotherapy, PTH resistance
What is Pseudo Hypoparathyroidism (PHP)?
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)
In the development of pituitary gland, what two segments come together in week 11 to form the pituitary gland?
Ectoderm & the hypophyseal diverticulum (Rathke’s pouch) AND Neuroectoderm and the neurohypophyseal diverticulum (infudibulum)
Name the hormones secreted by posterior pituitary
Oxytocin, Vasopressin (ADH)
Where does the thyroid gland develop from?
Foramen caecum (part of developing tongue)
What duct may persist and cause problems after the thyroid gland descends?
The thyroglossal duct may persist and appear as a midline cyst
Describe the development of the parathyroid gland
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
What are neurohormones?
Released from synapses and travel via bloodstream
Name some PEPTIDE hormones
GH, Prolactin, Insulin, ACTH, LH, FSH
Name some STEROID hormones
Cortisol, Aldosterone, Testosterone, Oestrogen
Name some AMINO ACID hormones
Thyroxine, Adrenaline, Noradrenaline
Name some Lipid hormones
Prostacyclin, Prostaglandins, Thromboxanes, Leukotrienes
Name some hormones secreted by the thymus
Thymosin, Thymopoietin, Thymulin
What hormones are derived from Tyrosine?
Thyroid hormones, Catecholamines
How is testosterone modified in different tissues?
testosterone (5α reductase) -> skin,external genitalia -> dihydrotestosterone
testosterone (aromatase) -> bone,brain -> estradiol
What is the effect of T3 & T4?
Breakdown of carbohydrates and fats, synthesise proteins
Hormones made by follicular cells and carried in the blood bound to TBG
What are the effects of Cortisol?
↑ amino acids in blood, ↑gluconeogenesis, ↑use of fat
